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25.1: Prelude to Animal Nutrition and the Digestive System - Biology


All living organisms need nutrients to survive. While plants can obtain the molecules required for cellular function through the process of photosynthesis, most animals obtain their nutrients by the consumption of other organisms. At the cellular level, the biological molecules necessary for animal function are amino acids, lipid molecules, nucleotides, and simple sugars. However, the food consumed consists of protein, fat, and complex carbohydrates. Animals must convert these macromolecules into the simple molecules required for maintaining cellular functions, such as assembling new molecules, cells, and tissues. The conversion of the food consumed to the nutrients required is a multi-step process involving digestion and absorption. During digestion, food particles are broken down to smaller components, and later, they are absorbed by the body.

One of the challenges in human nutrition is maintaining a balance between food intake, storage, and energy expenditure. For example, eating too much food while not expending much energy leads to obesity, which in turn will increase the risk of developing illnesses such as type-2 diabetes and cardiovascular disease. The recent rise in obesity and related diseases makes understanding the role of diet and nutrition in maintaining good health all the more important.


FATTY ACID CONTENT AND CHEMICAL COMPOSITION OF FRESHWATER MICROALGAE 1

We thank S. Tengblad for expert help performing the GLC analyses of the FA, and L. Merino and J. Johansson for the other chemical analyses as well as evaluation and quantification of the FA chromatograms. We also thank Y. Olsen, SINTEF, Trondheim, Norway for making parallel analyses of some samples. The amino acids were analyzed by the Department of Biochemistry, BMC, Uppsala. This work was supported by Sven and Dagmar Salén's Foundation.

ABSTRACT

Fatty acid (FA), total lipid, protein, amino acid, carbon, nitrogen, and phosphorus content was analyzed in 24 samples of freshwater microalgae. The samples originated from batch, continuous, or mass cultures in various growth phases and from net samples from lakewater. FA were analyzed quantitatively by using an internal standard in a GLC system and expressed as mg·g −1 dry weight (DW). The FA of one group of blue-greens (e.g. Oscillatoria and Microcystis) were similar to those of the greens with higher amounts of 18C acids of the ω3 type compared to the ω6 type, whereas the other group (e.g. Anabaena and Spirulina) contained mostly ω6 acids. The flagellates, a taxonomically diverse group, were characterized by high amounts of long-chained (20–22 C) polyunsaturated FA (PUFA), particularly of the ω3 type. The ω3/ω6 ratio appears to be highest in algae in the exponential growth phase. The increased lipid content in stressed algae was mostly due to increased saturated fatty acids and ω6 acids, whereas the valuable ω3 acids were unchanged or even decreased.

Amino acid composition (% of total amino acids) did not vary much betaken species, but when analyzed quantitatively (mg-g −1 DW), varied considerably between species and within species in different growth phases. The nitrogen and phosphorus contents were variable in all three algal groups. The relationship between PUFA and phosphorus content differed among the algal groups. The data suggest that PUFA in the phospholipids consist mostly ω3 acids.


Board CBSE
Class XII
Subject Biology
Sample Paper Set Paper 1
Category CBSE Sample Papers

Students who are going to appear for CBSE Class 12 Examinations are advised to practice the CBSE sample papers given here which is designed as per the latest Syllabus and marking scheme as prescribed by the CBSE is given here. Paper 1 of Solved CBSE Sample Paper for Class 12 Biology is given below with free PDF download solutions.

Time: 3 Hours
Maximum Marks: 100

General Instructions:

  • There are total 26 questions and five sections in the question paper. All questions are compulsory.
  • Section A contains question number 1 to 5, Very Short Answer Type Questions of one mark each.
  • Section B contains question number 6 to 10, Short Answer Type Questions of two marks each.
  • Section C contains question number 11 to 22, Short Answer Type Questions of three marks each.
  • Section D contains question number 23, Value Based Question of four mark.
  • Section E contains question number 24 to 26, Long Answer Type Questions of five marks each.
  • There is no overall choice in the question paper, however, an internal choice is provided in one question of two marks, one question of three marks and all three questions of five marks. An examiner is to attempt any one of the question out of the two given in the question paper with the same question number.
  • No. of printed pages are three.

Question 1.
Apple is eaten as a raw fruit all over the world. But still known to be a false fruit. State the reason behind this fact.

Question 3.
Estimate the way to predict the age of any fossil or a rock.

Question 4.
In what ways phenomenon of animal breeding is proved to be a successful event for livestock these days?

Question 5.
Under what conditions would a particular stage in the process of succession returns back to an earlier stage?

Question 6.
Archaeologists believe that there is some connecting link between the birds and reptiles i.e. ‘Birds have somewhere been evolved from reptiles’. Give evidences what Palaeontology provides in support of the above statement.

Question 7.
State the criteria used for determining a biodiversity hotspot.

Question 8.
What does a mass of cells released by sponges is called? Give one example where this helps in reproduction.
OR
Diagrammatically represent the process of multiple fission in Plasmodium.

Question 9.
Indian government had established the GEAC under rules 1989 to make all decisions on its own. Expand the term GEAC and also state the objectives behind setting this committee.

Question 10.
Differentiate between the process of development of a male and female gametophyte in plants.

Question 11.
One of the child of a couple was born with a blood group ‘O’. If the same father having blood group ‘A’ and mother having blood group ‘B’, were crossed then predict out the possible genotypes of both parents and other off springs produced.

Question 12.
At the time of Independence, the population of India was 350 million, which exploded to over 1 billion by May 2000. List any two reasons for this rise in population and any two steps taken by the government to check this population explosion.

Question 13.
Draw a neat and a well labelled diagram of the longitudinal section of a maize grain featuring the structure of a well matured embryo.

Question 14.
Design the cross proposed by Mendel to prove that the gametes does not show the blending of the two characters in the F2 generation with the help of a checker box, defining the law responsible for this fact.

Question 15.
Some college students were caught partying with their friends at an illegal place. Police asked victims to call their parents as the students were taking drugs and were not in the condition to go back home. Observe the condition and answer the following questions that follows

  1. What are the reasons of attraction of children towards the drugs these days?
  2. State different modes of consumption of such drugs. ‘
  3. Name the organ of the body which can be affected by even little consumption of these drugs.

Question 16.
Give reasons for the following statements.

  1. Neutrophils and macrophages are called soldiers and scavengers of animal body.
  2. One should avoid driving after consuming alcohol.
  3. Persistent use of corticosteroids is harmful for human body.
  1. Mutations are said to be beneficial for plant breeding. Taking an example, justify the statement.
  2. Discuss briefly the technology that made us self sufficient in food production.

Question 17.
What is single cell protein? What is the significance of such a protein?

Question 18.
A bacterium Bacillus thuringiensis produces a toxic protein called cry protein which is proved to be lethal to certain insects but not the bacterium itself. Explain how this happens.

Question 19.
Study the linking of DNA fragment shown below.

(1) Name ‘A’ DNA and ‘B’ DNA.
(2) Name the restriction enzyme that recognises this palindrome.
(3) Name the enzyme that can join these two DNA fragments.

Question 20.
What will be the fate of following structures in an angiospermic plant after fertilisation? Ovary wall, ovule, zygote, outer integument, inner integument and primary endosperm nucleus. 3 Q21. Ritesh went to his cousin’s place on hills, where he found very large plants. He got surprised because he was remembering the place to be exactly same which he had visited some years before. He asked his cousin about such a rapid change of plantation of that area. Being his cousin how will you satisfy Ritesh?

Question 22.
Illustrating the design of a bioreactor, highlight the difference between a flask in your laboratory and a bioreactor which allows cells to grow in a continuous culture system?

Question 23.
Undue human activities have accelerated the rate of extinction of species from the earth. Due to which our biological wealth is declining day by day. Being a good citizen of a country like India, Ankit is concerned about the issue and its long term effects.

  1. Give some known examples of species which have led to the recent extinction.
  2. List the major effects of loss of biodiversity.
  3. State different causes of loss of biodiversity.

Question 24.
Hershey and Chase through their experimentations proved that DNA acts as the genetic material in most living things including humans, plants, bacteria, etc. Explain experimentally with the help of a diagram. OR
Sketch out a labelled and schematic structure of a transcription unit explaining the function of each part of the unit involved in the process of transcription.

Question 25.
(1) State some major causes for air pollution.
(2) Mention the reason for converting the diesel buses of Delhi to run on CNG in the year 2002.
(3) Draw the labelled diagram of electrostatic precipitator that is used to remove fine particles from a flowing gas using the force of an induced change.
OR
(1) An ecological succession is known to be a sequential, gradual and predictable changein the species composition in over a period of time. Define the terms given in regard of occurrence of succession in an ecology.
(a) Pioneer species
(b) Sere
(c) Ecological succession
(d) Climax community
(2) State the use of biodiversity in modem agriculture.

Question 26.
Typhoid and pneumonia are the bacterial diseases that infects human beings. Discuss the causative agent, symptom and the way in which an infection enters the human body?
OR
Antibodies are produced by B-lymphocytes in response to pathogens. Explain in detail the types and roles of antibodies.

Answer 1.
Apple develops from the thalamus instead of ovary as in case of other fruits. Therefore, it is called a false fruit.

Answer 2.
Heterogenous RNA is a precursor RNA transcribed by RNA polymerase that contains both exons and intoms.

Answer 3.
Absolute dating method involving carbon (C 14 ) dating technique, Uranium-lead technique and potassium-argon
technique are used in determining age of a fossil or a rock.

Answer 4.
Animal breeding mainly aims at increasing the yield of animals and improving the desirable qualities of the produce.

Answer 5.
The process of succession returns back to their earlier stages either by natural or human induced disturbances like fire, deforestation, etc.

Answer 6.
The evidence that birds have evolved from reptiles provided by fossil Archaeopteryx are:
(1) It has beak and wings like that of a bird,
(2) It has teeth and scales similar to a reptile.

Answer 7.
The determination of a biodiversity hotspot were used by considering
(1) Number of endemic species which are not found anywhere else.
(2) Degree of threat which is measured in terms of habitat loss.

Answer 8.
Gemmule is a reproductive structure, which on germination gives rise to a new individual, e.g. reproduction in sponges occurs by the formation of gemmule.
OR

Answer 9.
GEAC stands for Genetic Engineering Approval Committee.
Its main objectives are:
(1) To examine the validity of genetically modified organisms. .
(2) Inspection for the safety of introducing genetically modified organisms for public services.

Male Gametophyte Female Gametophyte
(1) It develops by the process called micro­sporangium. It develops by the process of megasporo- genesis.
(2) It is known as the process of formation of microspores insporogenous tissue due to meiosis. It is known as the process of formation of megaspores in megaspore mother cell due to meiosis.
(3) Microspore leads to the development of a male gametophyte. Megaspore leads to the formation of a female gametophyte.

Answer 11.
The child bom with blood group ‘O’ has homozygous recessive alleles.Both the parents are heterozygous, i.e., genotype of father is I A i and mother is I B i for giving birth to a child with blood group ‘O’.

The possible genotypes of other offsprings will be ‘AB’, and ‘B’.

Answer 12.
Two reasons for increase in population are:
(1) A rapid decline in death rate, Maternal Mortality Rate (MMR) and Infant Mortality Rate (IMR).
(2) Increase in number of people in reproducible age.
Two steps taken to check the population explosion are:
(1) Statutory raising of marriageable age of the females to 18 years and that of males to 21 years.
(2) Incentives given to the couples with small families.

Answer 13.

Answer 14.
This can be easily proved by the cross given below between a homozygous tall plant (TT) which is dominant and a hemizygous dwarf plant (tt) as per the law of segregation which do not show any blending.

Answer 15.
(1) Reasons for attraction of children towards drugs are:

  • Curiosity and need of adventure, excitement and experiment.
  • To avoid unsupportive family structure.
  • Social pressure
  • To avoid stress, depression and frustration.

(2) The drugs such as cannabinoids are often mixed with tobacco and smoked. Bhang, another form of drug is even taken orally as an ingredient of a drink or food.
(3) Brain and Nervous system of human beings are often affected by these drugs.

  1. Neutrophils and macrophages are called soldiers and scavengers of animal body as they dispose off microbes and dead cells by feeding on them.
  2. One should avoid driving after consuming alcohol as its consumption causes blurred vision,slow response, impaired judgement and reduced coordination of limbs.
  3. Use of corticosteroids causes osteoporosis (disease of bones, in which bones become weak and more likely to break), therefore its persistent use should be avoided.
  1. Mutations in plants through diverse means leads to desirable characters development.
    Example Resistance to yellow mosaic virus in lady finger (Abeimoschus esculentus) was transferred from a wild species and resulted in a new variety of a escultentus known as Parthani Kranti.
  2. Plant breeding technology used in the green revolution has made us self sufficient in food production, which has eventually helped in the development of high yielding and disease-resistant varieties of wheat, rice, maize, etc.

Answer 17.
Single protein is a biomass obtained from microorganisms which can be treated or processed in food industry.

Significance of single cell protein:

  1. Its production reduces pollution as it uses organic wastes and industrial effluents.
  2. It provides a protein-rich diet.
  3. It takes off the pressure from agriculture system by fulfilling the demand of protein for human diet.

Answer 18.
1. The Bt toxin exists as inactive protoxin, which gets converted into its active form once an insect ingest it.
2. After entering the body of an insect it gets converted into an active toxin due to the alkaline pH of its gut which solublises the crystals. This activated toxin then binds to the surface of the midgut epithelial cells creating pores that causes swelling and lysis of the cells and eventually causes the death of an insect.
3. This protein has benefited the humans by producing bollworms and com borer-resistant crop of cotton and com.

  1. A is vector/plasmid DNA and B is a foreign DNA.
  2. EcoRI is the restriction enzyme that recognises this palindrome.
  3. DNA ligase helps in joining these two DNA fragments.

Answer 20.
Following structures of an angiospermic plant after fertilisation will result into
Ovary wall – Pericarp
Ovule – Seed
Zygote – Embryo
Outer integument – Testa
Inner integument – Tegmen
Primary endosperm nucleus – Endosperm

Answer 21.
Ritesh’s cousin explained him that, such a change had occurred in that area due to a process of succession of rocks. As during early period, lichens were the pioneer species on a bare rock, which had secreted organic acids and had dissolved and corroded the rock surface.
This has produced depression and releases out minerals that were being required for the proper growth of the lichens.
The lichens hold the fine particles of the rock along with the sand particles that were being brought up by the wind to initiate the soil formation. This thus, paves way for the next community i.e. bryophytes following various serai communities. Finally, the forests had became the climax community which remains stable as long as the environment remains unchanged.

Answer 22.

Bioreactor differs from a laboratory flask in a way that the bioreactor refers to any manufactured or engineered device or a system that supports a biologically active environment. In this a chemical process is carried out to involve organisms to get biological active substances derived from such organisms. The process in bioreactor can be either aerobic or anaerobic in nature. The flask used in laboratory is for making solutions, holding, containing, collecting or sometimes measuring chemicals, samples, solutions, etc. for the chemical reactions or other process such as mixing, heating, cooling, dissolving, boiling precipitation or some analysis i.e. it does not allow the growth of microbes in it.

Answer 23.
(1) Some examples of recent extinction are Dodo (Mauritius), Quagga (Africa), Thylacine (Australia), Steller’s sea cow (Russia) and three sub-species of tiger (Bali, Javan, Caspian)
(2) Some major effects of loss of biodiversity are :

(3) Causes of loss of biodiversity are:

Answer 24.
Alfred Hershey and Martha Chase carried out experiment to find out that DNA acts as a genetic material in many living things. They carried this experiments with the viruses that infect bacteria and performed this experiment with E. coli and T2 bacteriophage to predict out whether it was protein or DNA from the virus that had entered into the bacteria. For this they took two separate media for growing these bacteriosphages.
(1) One medium contained radioactive phosphorus and’the other medium contained radioactive sulphur.

(2) The growth of viruses in the presence of radioactive phosphorus ( 35 P) contained DNA (but not radioactive protein). This is because DNA contains phosphorus. In the same way viruses grown in the presence of radioactive sulphur ( 35 S) contained radioactive protein (but not radioactive DNA). This is because DNA does not contain sulphur.
(3) These radioactive viruses (bacterio-phages) were then allowed to attach to a bacteria (E. coli).
(4) They observed that the bacteria that were infected with virus containing radioactive DNA were radioactive whereas, bacteria infected with the virus containing p
rotein were not radioactive. This indicates that only DNA and not the protein coat entered the cell. Thus, the genetic material was DNA and not protein that passed from virus to bacteria

OR
Function of each part of the unit involved:

(1) A Promotor: It is a DNA sequence that provides binding site for RNA polymerase. It also defines the template and coding strands.

(2) Structural gene: It produces mRNA (transcription) which in turn, synthesises polypeptide on ribosome translation.

(3) A Terminator: It defines the end of transcription.

Answer 25.
(1) Causes for Air Pollution: Smoke emanating from thermal power plants and automobiles, smelters and other industries which release particulate and gaseous air pollutants together with harmless gases such as nitrogen and oxygen.

(2) All buses were converted to run on CNG by the end of2002 in Delhi, as CNG is cleaner. It bums more efficiently than petrol or diesel in the automobiles and very little of its unbumt. It is also known to be cheaper than petrol or diesel and cannot be siphoned off by thieves and adultered like petrol or diesel.

OR
(1)
(a) Pioneer Species: The species invading a bare area.
(b) Sere: The entire sequence of communities that successfully changes in a given area.
(c) Ecological Succession: The gradual and fairly predictable change in the species composition of a given area.
(d) Climax Community: The composition and structure of community constantly change in response to the changing environment conditions. These changes lead finally to a community that is near equilibrium with the environment.

(2) Use of Biodiversity in Modern Agriculture: Agrochemicals cause pollution of soil and water but are too expensive for the farmers. Genetic modification has made the crops more tolerant to abiotic stresses like cold, heat, drought, salinity, etc. It has also reduced the dependence of crops on chemical pesticides as they are pest resistant.


World Food and Nutrition Study: Enhancement of Food Production for the United States : a Report of the Board on Agriculture and Renewable Resources, Commission on Natural Resources, National Research Council, Prepared for the NRC Study on World Food and (1975)

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SECTION III: PRODUCTION OF FOOD AND FEED CROPS INTRODUCTION The world's food supply begins with crops harvested from the land. However, the basic requirements and research needs for crops grown for human consumption are similar to those for feed, fiber, and fuel. Plants are a renewable resource and an increase in productivity will benefit food, feed, and biomass uses. But plants require, and may compete for, the nonrenewable resources of land, water, energy, fertilizer, and chemicals. Many plants (e.g., feed grains and grain legumes) can be routed as either food for man or feed for livestock. Others, such as the grasses and forages, are useful only to livestock. Biomass production of plants is already widely used for fiber and may again be more extensively used for fuels. The significance of food and feed crops is that they provide, directly or indirectly, about 90 percent of the world's food supply. Chief among the major food crops are rice, wheat, maize, sorghum, millet, barley, rye, oats, soybeans, field beans, chick peas, pigeon peas, peanuts, cassava, sweet potatoes, potatoes, sugar beets, sugarcane, coconuts, and bananas. A variety of fruits and vegetables, processed and fresh, adds personal enrichment and pleasure in eating and provides essential dietary nutrients. Hay and pastures (grazing crops) provide most of the feed units for cattle and sheep. Current rates of population growth and changes in dietary habits will double the need for these crops during the final quarter of the twentieth century. Our forests and tree plantations provide fiber, as do some feed and food crops. New fast-growing, high-yielding crops will have to be developed for biomass production of fuel, as well as food and feed. Crop production is a central issue. Global production of grain must be increased at the rate of 25 million metric tons per year just to keep pace with population increases and rising demands. Fuel production will become critical as we exhaust our oil and gas reserves. Chemists, microbiologists, and engineers will have to convert massive amounts of organic plant material to basic chemicals for industry and fuel. Nature did this slowly in the past from plants. Now man will have to do it quickly as he increasingly uses plants for food, feed, fiber, and fuel. There are major uncertainties involving future agricultural needs, including adequacy of land, water, -117-

energy, fertilizer, and pesticide resources. There are environmental, social, political, legal, and economic constraints, and numerous disincentives in agricultural food production. Weather and changing climatic patterns continue to play a predominant but unpredictable role in dictating the selection of crops tolerant to change. A national program for greater food production and improved nutrition must focus on the major food and feed crops. Research investments are needed to maximize or optimize the production of food crops per unit of time, with the least expenditure or commitment of land, water, fuel, and fertilizer. The two most important processes that use solar energy are photosynthesis and biological nitrogen fixation research on these processes can be expected to lead to greater production of carbohydrates, proteins, fiber, and energy. -119-

CHAPTER 14 PHOTOSYNTHETIC PRODUCTIVITY RECOMMENDATIONS 1: Efficiency of the Photosynthetic Process. The impressive yield increases of the past 25 years have come from a combination of new varieties, high rates of fertilization, high plant populations, disease resistance, and control of insects and weeds. Further significant yield increases will require greater photosynthetic efficiency. Therefore, need is great to expand research on the factors which control the photosynthetic process, especially in four areas: (1) control by source-sink relationships (2) control of photorespiration (3) control of plant senescence and (4) carbon dioxide enrichment and other improvements of field techniques for crop production. 2: Use of the Seasonal Potential. In much of the U.S. there is a waste of potential photosynthetic production because the photosynthetic system in the crops grown is poorly adapted to either warm or cool weather or length of growing seasons whereas other species may have their most rapid growth during those times. The potential needs to be evaluated for developing crop varieties which can produce rapidly in both cool and warm weather and in variable growing seasons. Planting designs and multiple cropping should be developed to capture maximum solar energy. INTRODUCTION It is estimated that world food production must double by the year 2000. Adoption of currently available agricultural technology could alter yields in the agriculturally developing nations by a significant amount but for yields to double in the U.S. or other developed countries, which produce much of the total and all of exportable food, will require a marked increase in photosyn- thetic productivity over the levels achieved in current agricultural practice. We often hear faith expressed in the ingenuity of American agriculture. Many knowledgeable people suggest, on the basis of past performance, that the percentage gains in -119-

crop yields over the past 25 years will be repeated in the 25 years ahead. Such projections need careful analysis. One of the better examples of success in agriculture is the yield increase that has occurred in corn production in the U.S. In 1950, average yields were 57 bushels per acre (bu/A). The estimated yield for 1975 is 93 bu/A. That impressive increase has been due to new disease resistant varieties which are responsive to narrow row spacing and high fertility as now practiced. Extremely effective chemicals for controlling weeds are now almost universally in use. This combination of variety, spacing, high fertility, and freedom from weeds has resulted in the current high yields. It is that technology which could contribute to yield increases in the agriculturally developing countries. Could corn yields be increased in the U.S. by the year 2000? With the high price of grain and the removal of acreage controls, all crop land readily and presently available is being farmed. Increases in crop acreage will come slowly and at considerable cost. Thus, about the only possibility for exploitation of further yield increases on our most highly productive land is to develop higher yielding varieties. Where can the varietal input to yield come from in a crop such as corn? Considerable progress has been made in recent years by developing varieties which put more of the photosynthetic yield into grain. Today, about one half of the total plant weight at corn harvest is grain, the remainder being stalks, leaves, and roots. The roots, stalks, and leaves are absolutely essential to the plant. Possibly this proportion can be somewhat further reduced, but in order for grain yield of corn to double, an increase in the photosynthetic yield of the crop also must be attained. Thus, the future of the world's food supply may lie squarely at the door of photosynthesis and its partitioning into the harvested part. What has been the history of photosynthetic yields while these remarkable successes in grain yield have been obtained in corn? They have increased, but the startling fact is that the biochemical capacity of corn for photosynthesis has not changed at all. The photosynthetic yield increase has been achieved by more dense plantings, earlier plantings, later harvests, steadily increasing rates of fertilizer application, and the relative freedom of the crop from pests and disease. While we are faced with need in the future to drastically alter the capacity of crop varieties for photosynthesis, we have made no progress in increasing the efficiency of the process in the past 25 years, and we are nearing the limit of exploitation through technology. To make further progress we must improve the photosynthetic process itself, yet we have currently only a token research effort on photosynthetic productivity. -120-

The photosynthetic yield of an acre is derived from the photosynthetic rate per unit area and time of individual leaves multiplied by the area of those leaves contained on an acre (the leaf area index or LAI) and the length of time the system functions. The entire system is driven by solar energy. Although the preceding statements seem obvious, each of these points becomes important when we consider potential research on photosynthesis. EFFICIENCY OF THE PHOTOSYNTHETIC PROCESS Rationale As indicated above, the biochemical efficiency of the photosynthetic process in major crops has not changed in the last 25 years. Yet great differences in efficiency exist between crops. In the warmth of midsummer, corn and sorghum and sugarcane are highly efficient, greatly surpassing such summer crops as soybeans or potatoes. In cool spring weather, however, photosynthesis in wheat, barley, or rye greatly surpasses that in the warm season crops. In the past decade it has been discovered that corn, sugarcane, and some other crops have photosynthetic systems that consist of a sequence of biochemical events strikingly different from that which occurs in wheat or barley. The enzymes involved have high optimum temperatures and function very effectively in high temperatures and intense sunlight. The relationship with season is not clearcut, however soybeans do best in warm weather, although they possess the same biochemical system for photosynthesis as wheat or barley. Since striking differences exist among crop species in efficiency or photosynthesis and in the adaptability of the photosynthetic enzyme systems to seasons, the potential to alter the photosynthetic process in ways useful to man seems great indeed. Yet progress has been nil in breeding crop varieties which have superior photosynthetic yield capacity. The photosynthetic rate in crop species has proven to be highly variable in time and subject to enormous environmental influence. Progress in vital areas is unlikely until the factors that control photosynthesis are understood. Implementa tion Research on factors that control photosynthesis is sorely needed in four different areas. -121-

1. Control by source-sink relationships New growth or the development of fruit or grain enhances leaf photosynthetic rates. On the other hand, ample photosynthesis is necessary to produce the potential for a large fruit or grain yield. The signals that pass between leaves and other organs which tell the leaf to increase or decrease its photosynthesis are not understood. The factors that control the fate of photosynthate—whether it goes to storage in grain or fruit, becomes part of the plant structure as new leaves or roots, or is respired, wastefully or to provide plant energy—are largely unknown. It is critical that research efforts be greatly expanded in this area. 2. Control of photorespiration In plants such as wheat or soybeans the enzyme responsible for fixing carbon dioxide and forming carbohydrates can also react with oxygen. When this happens, carbohydrates are destroyed—not produced—and as far as is known, wastefully so. When this destruction of carbohydrates occurs, the process is called photo- respiration. Corn, sugarcane, and several other highly productive crop species have evolved a photosynthetic system which protects its carboxylating enzyme from photo- respiration. It is estimated that the photosynthetic yield of wheat, rice, soybeans, and many other crops could be increased by up to 100 percent if a genetic or chemical inhibition of photorespiration could be attained. Research on this topic needs much more emphasis than it is now getting. 3. Control of senescence The photosynthetic capacity of all the grain crops (including soybeans and other legumes) decreases precipitously during the grain-filling period, exactly at the time when the need for photosynthesis is greatest. It appears that, in selecting crops for uniform ripening so that they are amenable to machine harvesting, varieties of many crops have been developed which are now limited in their yield because their photosynthetic factories close down too soon. We must understand the control mechanisms within plants that tell it to mature and die. The potential seems great to markedly alter yields simply by keeping the photosynthetic factor going for a longer period of time. This area also needs research effort. -122-

4. Carbon Dioxide Enrichment The carbon dioxide concentration available to plant foliage is the most important variable determining the rate of photosynthesis. For example, a sixfold increase in N

fixation for soybeans has been achieved by a threefold increase in atmospheric carbon dioxide (Evans 1975). Experimental and commercial results confirm that major growth increases, often exceeding 100 percent, can occur with increases in the carbon dioxide concentrations in the atmosphere. Heretofore, textbooks on crop fertilization, with few exceptions, have ignored carbon dioxide as a plant nutrient from which growth responses may be derived. This blind spot in management for food producing systems needs serious reappraisal. Although the knowledge of carbon dioxide benefit by crops grown in greenhouses has been known for half a century, and was put to use to a limited extent during World War II in Germany, it has not been pursued as a researchable means of maximizing the productivity of field food crops. Massive supplies of carbon dioxide are dumped into the atmosphere and could potentially be used for enhancing crop production. There are also large geological resources of carbon dioxide adjacent to major food producing areas in Texas and the Mississippi Delta. USE OF THE SEASONAL POTENTIAL Rationale Since photosynthetic yield is a product of rate and time, one obvious way to increase biomass production is to increase the proportion of the time that a crop occupies the soil. The practice of multiple cropping which is practiced intensively in some subtropical areas has the potential for much wider application in the world. If varieties of summer crops could be developed which had a cool season capability for photosynthesis, plantings could be earlier and seasons extended on many millions of acres. Research in this area is almost nonexistent in temperate climates. Yet crops such as winter wheat or rye are capable of producing tons of biomass per acre each spring before corn is even planted in the Corn Belt. Obviously, such crops do not mature grain before corn is planted, but the point to be made is that large amounts of solar energy go unharnessed because the summer crops lack a cool season photosynthetic capacity. The potential needs to be evaluated for using the seasons more fully. -123-

CHAPTER 15 BIOLOGICAL NITROGEN FIXATION RECOMMENDATIONS 1: Research Teams in Nitrogen Fixation. Research teams should be established for the purpose of conducting coordinated efforts toward obtaining in-depth knowledge of the nitrogen fixation process and its application in production of food, feed, and fiber control of soil erosion and maintenance of ecological balance. 2: Rhizobial Technical Center. A rhizobial center should be established to provide leadership and expertise in the technology essential to effective legume inoculation. INTRODUCTION The major portion of all nitrogen required for the production of food, fiber, and other plant products is derived from the atmospheric reservoir through biological nitrogen fixation and industrial chemical fixation. The biological fixation process is indirectly dependent upon solar energy that is stored by plants in products of photo- synthesis. Organisms capable of using atmospheric nitrogen ordinarily are not dependent upon another source, but those lacking this capability require nitrogen from fertilizer or from soil reserves. The chemical synthesis of compounds of nitrogen and their distribution for fertilizer require enormous quanti- ties of hydrogen from natural gas plus additional energy expenditure to maintain the temperature and pressure for synthesis and to transport the products to their destination. In 1972, 465 billion cubic feet of natural gas or 2 percent of all the natural gas used in that year was consumed for the production of anhydrous ammonia. New methods have revealed that biological nitrogen fixation is more widespread than originally imagined. In the U.S. alone, the quantity of nitrogen fixed by agri- cultural and nonagricultural species has been estimated to exceed 23 million U.S. tons annually (Evans 1975). In addition to agricultural legumes, biological nitrogen fixa- tion also is of major importance in forests, woodlands, arid regions, and in fresh water and marine habitats where the -124-

quantity fixed per year may approach that fixed annually by agricultural legumes. Since nitrogen is the major plant nutrient limiting the production of food, fiber, and other products for an expanding population, it is essential to exert maximum effort to increase the supply of a usable form of this element by both biological and chemical means. An increased supply of biologically fixed nitrogen may be accomplished without excessive use of our energy resources. Furthermore, biological nitrogen fixation takes place in the fields, forests, and other environments where it is used. Transportation is not a major factor, and most importantly the capital investment for the construction of factories for nitrogen fixation is unnecessary. Expansion of biological nitrogen fixation capabilities in the agriculturally developing countries is now being and should continue to be vigorously encouraged. RESEARCH TEAMS IN NITROGEN FIXATION Rationale During the past 30 years, agriculturists have used relatively inexpensive fertilizer nitrogen for their crops, and research on such practical problems as legume ino- culation, rhizobium strain effectiveness, and use of legume cover and green manure crops has declined. Responsibility for the manufacture, testing, and maintenance of the quality of rhizobium inoculants has been delegated to commercial manufacturers. Many of our well known experts in rhizobium bacteriology have retired, and the supply of well-trained young scientists in the field is at a low level. During the past two years the price of fertilizer nitrogen has more than quadrupled, and the current cost to farmers of nitrogen as anhydrous ammonia is $250 per ton. Fossil fuels represent 50 percent of the current cost of ammonia manufacture, and fossil fuels are becoming scarce and more expensive. While there has been a declining interest in the more applied areas of biological nitrogen fixation, research on the detailed biochemical properties of the nitrogen-fixing complex and related enzymes has proceeded at a rapid rate, and new methodology for the investigation of broad aspects of the process is now available. The acetylene reduction technique for measuring nitrogenase activity and relatively new methods for transferring nitrogen-fixing genes from one bacterium to another, for example, provide an opportunity for some major advances in the field. These opportunities include: (a) the improvement of nitrogen fixation by leguminous crop plants, (b) extension of the nitrogen-fixing capability to additional plants, (c) discovery of new and use of existing nitrogen-fixing organisms in nature, and (d) discovery of new chemical mechanisms of nitrogen fixation -125-

based on the chemical process that occurs in nitrogen-fixing microorganisms or on the development of the chemistry of nitrogen fixation under mild conditions (of temperature and pressure) by homogenous catalysts. In order to take advantage of these opportunities, training programs in some areas need to be encouraged and interdisciplinary research teams need to be organized. A rhizobium technical center is needed as a service to research workers in this and other countries, to manufacturers of inoculants, and to farmers. Implementation Federal and state agencies already have a substantial investment in facilities and personnel now conducting research in several aspects of nitrogen fixation. Therefore, research teams of 10 to 12 scientists should be organized by supplementation, where possible, of staff and facilities that are already in operation in laboratories and field stations with strengths in areas such as microbial genetics. In some areas new teams will need to be organized while in others, additional staff appointments and/or additional facilities could create dynamic research units. Success will require coordination of efforts by several agencies such as CSRS, ARS, USAID, and NSF. 1. Teams Assigned to Forage and Grain Legumes A team consisting of agronomists, soil scientists, plant nutritionists, bacteriologists, bacterial geneticists, plant geneticists, plant physiologists, biochemists, and extension specialists (the number to be determined by the need) should be located in each particular region of the country where grain and forage legumes are of major importance. The primary goal of each group should be to develop new and/or use existing bacterial strains and host cultivars and the most efficient agronomic practices for the production of maximum quantity of high quality food and feed. Since many of our legume cultivars have been developed in areas where high populations of indigenous rhizobia of unknown effectiveness were present, plant geneticists, bac- teriologists, and agronomists must reevaluate efficiency of nitrogen fixation by leguminous crops in order to determine whether or not the most effective combinations of rhizobium strains and leguminous hosts are being used. Also they must determine the factors that influence the survival and competitiveness of rhizobium strains in different environments and whether present inoculation techniques are adequate to insure that applied inoculum is capable of com- peting with existing populations of indigenous rhizobia. Plant physiologists, plant nutritionists, and biochemists, -126-

for example, should contribute to the team effort to enhance nitrogen-fixing capability by identification of those physiological, nutritional, and environmental factors that limit the process and by a search for methods for the alleviation of limitations. These endeavors will include the identification of the products of photosynthesis that are transferred to nodules as sources of energy for the support of nitrogen fixation and the definition of environmental and physiological conditions that limit nodule photosynthate supply under both laboratory and field conditions. Also the metabolic systems that participate in the transfer of products of nitrogen fixation out of nodules and the control mechanisms that influence the nitrogen- fixing process and closely related processes need to be characterized. The biochemical basis for the specificity of the infection of legumes by rhizobium species and strains needs to be understood. The information obtained may then be used in attaining the primary goal listed under Recommendation 1. 2. Teams for Grain and Forage Grasses A team located in the subtropical region of the U.S. should be organized to determine the magnitude and potential importance of biological nitrogen fixation on the roots of grasses and other species of agricultural importance. This team should include plant geneticists, microbiologists, agronomists, and plant physiologists who should direct their efforts toward such goals as determination of the magnitude of nitrogen fixation on the roots of corn, sugar cane, and subtropical forage grasses. Microorganisms responsible for fixation should be identified, compatibility of grass cultivars and bacterial strains should be tested, and the optimum environmental and other conditions for nitrogen fixation on or within grass roots should be defined. These investigations are particularly pertinent since Dobereiner in Brazil (Evans 1975) recently has described associations of bacteria on roots of Paspalurn notatum and Digitaria decumbens that are claimed to fix nitrogen at rates up to 100 kg of N per year. Measurements of field increases, however, have not been reported. Nitrogen fixation is known to occur on roots of grasses in temperate zones, but rates reported are relatively low. 3. Teams for Forests, Woodlands, Aquatic, and other Habitats Research teams consisting of phycologists, microbiologists, physiologists, mycologists, ecologists, foresters, and statisticians should be organized for the purpose of evaluating in quantative terms the contribution -127-

of fixed nitrogen to our non-arable lands, forests, aquatic, and other environments by the variety of non-leguminous nitrogen-fixing systems that are now known to exist. This is necessary in order to evaluate their contribution to food, feed, and fiber production and their role in controlling soil erosion and maintaining of ecological balance. Some of these systems include: free-living blue- green algae nitrogen-fixing bacteria associations of nitrogen-fixing bacteria with roots of herbaceous species and with fungi in rotting wood associations of blue-green algae with fungi, liverworts, mosses, and ferns and symbiotic associations between unidentified microorganisms and woody species, such as Alnus, Ceanothus, Purshia, Mvrica, and Dryas. If the basic biological characteristics of these nitrogen-fixing systems were understood, intelligent management and therefore maximum use of them could be made. A major objective, for example, would be to obtain pure cultures in laboratory media of the nitrogen- fixing endophytes of Alnus, Ceanothus, Myrica, Purshia, Dryas, and Comptonia. None of the endophytes in nodules of nitrogen-fixing woody species can be cultured at present, and as a consequence, methods for preparation of inocula that could be used to increase the extent of nodulation of these species have not been perfected. Also a search should be made for new naturally occurring nitrogen-fixing systems that are closely associated with plants. 4. Basic Genetics Teams Teams should be organized for the purpose of using genetic and cell-fusion techniques in extension of the range, extent, and usefulness of biological nitrogen-fixing capability. For example, genetic techniques should be employed to attempt to transfer nitrogen-fixing genes into additional bacteria of economic importance and to enhance biological nitrogen-fixing capability of organisms already known to fix nitrogen, by genetically altering control mechanisms that influence nitrogenase synthesis. Efforts should be directed toward the development of mutant strains of rhizobium with advantageous alterations in their specificity toward hosts. As a long-term objective this team also should attempt to incorporate nitrogen-fixing capability into tissues of crop plants, such as corn, wheat, or sorghum, and to develop strains of nitrogen-fixing bacteria with a capability of invading or associating themselves with roots of grass species and establishing effective nitrogen-fixing associations. -128-

5. Basic Biochemical and Chemical Research Teams Research teams should be organized for the purpose of continued improvement of understanding of the chemistry and biochemistry of biological nitrogen fixation by elucidation of detailed chemical changes that take place during the reduction of nitrogen gas to ammonia by nitrogenase and by chemical model systems. This objective requires collaboration of physical chemists, inorganic chemists with expertise in metal complexes, protein chemists, and enzymologists who are familiar with the detailed properties of nitrogenase. In addition to providing a basic understanding of the biological nitrogen-fixing process, this research offers the possiblity for discovery of new chemical mechanisms of reducing nitrogen. 6. Nitrogen Fixation in Conjunction with the Micro- biological Degradation of Waste Carbohydrates A team consisting of microbiologists, microbial geneticists, physiologists, biochemists, and engineers should be organized for the purpose of increasing the availability of fixed nitrogen by utilization of the energy in waste materials, such as corn stalks, grass straws, and wood products as substrates for the support of microorganisms, including those capable of nitrogen fixation. Precedent for this research already has been provided by the discovery of large populations of nitrogen-fixing bacteria in the decaying heartwood of forest trees (Evans 1975). The economic feasibility of these principles in the use of cellulose and other components of waste materials needs to be evaluated. The magnitude of operations could range from those designed to use large-scale industrial and farm by- products to small compost units for home gardens. RHIZOBIAL TECHNICAL CENTER Functions of a rhizobial technical center should include: (a) acquisition and storage of a world collection of rhizobia to insure the availability of a valuable collection of diverse types of rhizobia to researchers in this country and other countries (b) collection of new rhizobial isolates to enable improved strain selection (c) evaluation of rhizobial accessions (d) training of technologists to work on the many aspects of selection, production, testing, and distribution of rhizobia and (e) aid to the responsible government agency in the control of the quality of commercial inoculants. This center would provide technical service to the research teams listed above (1 through 5) and also services concerned with the use of microorganisms for the inoculation of non-leguminous species -129-

if justification for this is provided by current and future research. -130-

CHAPTER 16 CROP IMPROVEMENT RECOMMENDATIONS 1: Plant Genetic Resource Management. An immediate program of systematic assembly, maintenance, evaluation, and use of plant genetic resources should be undertaken, including the development of improved techniques for exploiting plant genetic resources. 2: In Vitro Techniques. Studies should be supported on technology for genetic transfer in plants through in vitro techniques for crop improvement, with emphasis at centers where interdisciplinary teams already exist or can be formed. 3: Chemical Control. Efficient and practical methods for the chemical control of plant growth should be developed. 4: Micronutrient Elements. The possibility that food and feed crops require additional micronutrient elements should be investigated. 5: Protein Quality and Quantity and Nutritional Availability. Research should be intensified on the genetic improvement of protein quality and quantity in cereals and cereal legumes, and on the biological verification of the nutritional value of the modified protein. 6: Protein from Oilseeds. Research should be intensified on increasing the protein in oilseeds by improving gossypol-free varieties of cotton, on yields and changes in types of fatty acids in sunflower, and on new varieties of soybeans to increase their range and yield. -131-

PLANT GENETIC RESOURCE MANAGEMENT Rationale The important food crops grown in the U.S. originated outside the U.S. and have been imported. The genetic lines of these crops are becoming increasingly uniform. An important aspect in maintaining the genetic variability upon which man depends for future breeding programs is the preservation of a maximal range of genetic stocks. It will be important to provide adequate steps for preserving genetic materials. The Agricultural Research Policy Advisory Committee (ARPAC) of the Agricultural Research Service (ARS/USDA) has recommended a genetic resources board to devise a national plan and program of genetic resource management. It is important that such a plan be implemented in order that germ plasm from centers of diversity will not be lost. Crop productivity at the genetic level is limited by the genetically-controlled growth responses to environmental resources and stresses. Sufficient information is available to support the expectation of high sustained yields if the physiologic genetic processes regulating the vigor of plant growth could be understood and brought under agronomic control. Most frequently, specific useful characters or combina- tions of characters occur in only a small fraction of a population of basic stocks or endemic strains of a species. Ways need to be found to simplify and expedite the identifi- cation of characteristics useful for meeting given objec- tives. Environmental stresses on crop plants are a fact of life that must be faced as we seek knowledge and develop technology for meeting our basic needs for sustenance. The genetic approach is ecologically nonpolluting and energy conserving. Sustained, debilitating drought may occur again over major parts of our most important crop production areas. Air pollution is limiting crop production in some areas (Benedict et al. 1973). Widespread culture of genetically similar varieties may result in greater losses from environmental stresses than would otherwise be the case, particularly if the varieties have not been selected for stress tolerance. Rather than add chemicals to change the soil to fit the plant, it now appears wiser in some uses to change the plant to fit the soil. Selecting or breeding plants more tolerant to salinity is a case in point. Better understanding must be sought of (a) differences among strains and varieties in their ability to withstand stresses, and (b) the alternatives that are available for continuing to produce adequate supplies of food, feed, and fiber in situations of extreme environmental stress. We need to strengthen current efforts to transfer genetic material from one species (or genus) to another by means of conventional crossing procedures. Dramatic examples of successful transfer can be cited: leaf rust -132-

resistance from wild Aegilops species into wheat and golden nematode resistance from wild Solanum species into potatoes. Related wild species of our crop plants represent a source of genetic material that has hardly been tapped. IN VITRO TECHNIQUES Rationale Great strides have been made in what is being called the "new botany," that is, the production of new types of plants without recourse to sexual reproduction by using the in vitro techniques of cell and tissue culture. The approaches afforded by these recent advances have great potential for plant breeders. New techniques are now feasible because of the progress made in plant cell culture during the past decade (Chellef and Carlson 1974). These include: (1) meristem culture for the propagation of plants difficult to multiply and to free infected plants of viral, bacterial, and/or fungal contaminants (2) embryo culture for growth of plants which naturally abort before or soon after germination (because of incompatibility with maternal tissue or because of the production of toxic materials by the maternal tissue) and (3) the long time storage under liquid nitrogen of germplasm of vegetatively propagated plants, such as fruit trees, shrubs, and potatoes. In addition, there are techniques which can be used at the cellular level for the manipulation of plant systems including: (1) exploitation of spontaneous variation in cell and tissue culture, polyploidy, aneuploidy, and chromosomal mosaics (2) induced mutations (3) induced polyploidy (particularly doubling of chromosomes through the use of the alkaloid colchicine) (1) haploids (individuals with only one set of chromosomes in the vegetative state, a condition in higher plants usually reserved for sex cells) plants from pollen or from anthers (5) fusion of protoplasts produced from vegetative cells (6) transformation (to change the heritage of one strain by introducing the chemical carrier of heredity from another strain) and (7) efficient selection and screening procedures to recover desired cell or plant types from large populations. New plants have already been obtained using these approaches. Success has been achieved in obtaining mutants resistant to several diseases and to environmental stresses. Fusion of protoplasts from vegetative cells from different species of Nicotiana to produce a hybrid plant has been demonstrated. The hybrids are similar to those produced by sexual methods, demonstrating that the approach is theoretically sound. Transformation in higher plants is in infancy, but some investigators believe this approach to be the most effective because it should allow more directed change with better control and definition of the desired modification. -133-

The most effective use of these new techniques will be realized when selection can be coupled with directed change. Support is needed for studies of selection methods at the cellular level. The agricultural implications appear to be significant: possibilities include not only new plants not possible through the sexual process, but also higher yielding lines, increased disease resistance, and even production of desirable products in more than one part of the plant. CHEMICAL CONTROL Rationale Compounds that control crop maturity could have an important economic impact in the foreseeable future. These chemicals can increase yields by effecting metabolism, preventing losses due to failure to achieve maturity or to the delay of the timing of maturity, limiting fruit set, and delaying fruit drop. An excellent example of the positive results achieved in the recent past is the use of chemical ripening compounds in sugarcane resulting in a 10 to 15 percent increase in yield of the economic product, in this case sucrose (Nickell 1974). There is every reason to believe that changes in cultural practices to adjust to this new approach will give additional yield increases. Similarly, the use of a naturally occurring growth stimulant nearly doubles both yield and sugar content of seedless grapes (Weaver 1972). The success in sugarcane and grapes strongly suggests the desirability of studying other systems in increasing metabolic products in the vegetative stage of crop production, and it is not unrealistic to propose inaugurating similar approaches to sexually produced crops. Recent studies have shown that the inhibition (or delay) of senescence in small grains substantially increases yield (Weaver 1972). It has also been found that legume nodules cease fixing nitrogen and start to disintegrate when their carbohydrate supply decreases from the shoot. In addition to these direct effects on yield increases, there are other indirect ways to improve yields or to pre- vent losses. One is to delay or speed up the flowering time in crops, such as cotton, so that there are no developing young fruit to serve as hosts for the insect pests. Another is to control the germination, growth, and development of plant vegetation to synchronize with the rainfall distribution pattern for semi-arid areas. A combination of chemical control over plant growth with development of new plants through in vitro techniques may enhance the potential of both approaches to crop improvement. Development of specific chemicals to adjust the physiological mechanisms of new plants should be moved -134-

ahead concurrently and with close liaison among the researchers involved in both activities. MICRONUTRIENT ELEMENTS Rationale The first step in meeting the mineral nutrient requirements of man and animals is the absorption of the required minerals by plants growing on soil. In many instances, the concentrations and ratios of the minerals in the plant are not those most desirable in human and animal diets. The problem is most critical with some of the so- called "trace elements"—iron, zinc, selenium, copper, iodine, cobalt, and others. Recognition and correction of some mineral deficiencies in animals that stem from deficiency in soils and are reflected in plant composition have increased food production and permitted animal agriculture to expand into new areas (Allaway 1975). But mineral deficiencies in humans and animals still persist as evidenced by widespread iron deficiency or by the recently established zinc deficiency in people. Correction of these deficiencies by direct supplementation of people and animals has met with mixed success in the developed countries and will face additional difficulties in developing countries where food technology is not advanced. In addition, the people of many developing countries must depend primarily on direct consumption of plants to meet calorie requirements, without the animal acting as an intermediate collector of essential minerals and a barrier to the transfer of toxic minerals and antimetabolites. Several elements—silicon, chromium, vanadium, nickel, and others—have recently been added to the list of those essential or probably essential, for man and animals, but relatively little is known about how these elements move through food chains. Other elements will undoubtably be added to the list of those essential for plants or animals. It is now appropriate to try to improve plants as sources of dietary trace elements for people and animals, to identify and correct malfunctions of the trace element food chain that are unique to certain geographic regions, and to develop plants that will be better sources of minerals than any of those grown up to now. The research should include efforts to control the concentration of minerals in food and feed crops plus efforts to improve the digestibility and nutritional value of minerals in plants. -135-

Implementation Nutritional researchers should attempt to control movement of essential and toxic minerals from soils to plants to animals. The approach should include studies of the chemistry of these elements in soils directed toward development of soil tests that can be used to predict the concentration of specific elements in the edible parts of plants, and to predict how this concentration will change under different fertilizer additions or soil management practices. The processes of uptake and translocation of these elements in plants should be investigated along with the factors affecting the chemical combinations of these elements in the plant. Plant breeders should be assigned to develop food and feed crops that are adapted to specific trace element environments or may be efficient accumulators of different minerals. The work of these scientists should be supplemented by nutritionists who investigate the digestibility and nutritional function of elements contained in different plants and who establish plant composition goals based on human and animal requirements for different elements, or on critical concentrations to prevent toxicity from others. PROTEIN QUALITY AND QUANTITY AND NUTRITIONAL AVAILABILITY Rationale In a world in which animal protein will become increasingly costly, plant proteins will have to provide a greater share of the protein intake of people everywhere. This requires that plant proteins be of adequate nutritional value when ingested in diets of adequate caloric value. In classic cases, particular amino acids have been shown to be nutritionally limiting, and genetic mutants have been found which alter their levels in seeds. The different cereals of economic importance all have one characteristic in common— they are low in the essential amino acid, lysine. Because of the lack of adequate lysine, cereal proteins are inferior nutritionally to the proteins found in milk, meat, eggs, and grain legumes. With the discovery 10 years ago that the maize mutant opaque-2 had nearly twice as much lysine as ordinary maize, scientists realized that cereal grain proteins could be im- proved in quality by genetic manipulation. The recent discovery of high lysine mutants of barley and sorghum raises the hope that all cereals of economic importance may eventually be improved in protein quality by genetic selection. Grain legumes, including dry beans, dry peas, pigeon peas, chick peas, and mung beans, have high protein contents and are rich sources of protein to large segments of the -136-

world's population. These proteins in general supplement those in cereal grains because they are relatively high in lysine content, with the result that when the edible legumes are consumed in conjunction with the cereal grains, a far better balanced protein diet is attained. A greater research effort is needed to improve the protein quality and quantity in food legumes. Other plant protein sources are not fully exploited. For example, mutant types of pumpkins are known which contain seeds without a seed coat. These seeds contain over 30 percent protein and over 40 percent oil content. The quality of both oil and protein surpasses that from peanuts and soybeans. Cucurbits such as pumpkins require less water per unit of production and are adapted to arid areas. Plant selection programs which ignore grain yield or amino acid balance and are directed solely at protein content of cereals and grain legumes could be counterproductive. Increased protein content at the expense of an essential amino acid bearing fraction may lower the overall biological value of the protein. In like manner the digestibility of the protein and its availability when used in the normal dietary pattern is an equally important consideration in product improvement but overall yield of calories and balanced protein is the most important objective. The biological value of a protein is the ultimate mea- sure of its worth in human and animal diets. Protein is often not fully available, and the reasons for this are in most cases not understood. The evaluation of protein availability in these systems must be an integral part of any plant breeding program designed to affect protein quality and/or quantity. To date, biological evaluations have been limited largely to the testing of products from a research program at a time they were nearing commercial production. Biological testing capabilities in the early stages of a breeding and selection program must receive renewed attention. Implementation Successful genetic modification of protein quality and/or quantity can be maximized by interactions between the disciplines of plant genetics, biochemistry, human and animal physiology, human and animal nutrition, and agronomic production when members of each disciplinary area are aware of and appreciate problems of the interacting group. Progress in the successful development of nutritionally superior varieties of basic food crops could be accelerated. Integrated research in this area can be developed by the establishment of funded core projects which can, in turn, fund research in supporting project areas with each project area participating in the evaluation of the overall project. -137-

Biological as contrasted to chemical evaluation of plant products used for food is a necessary step in any im- provement program. The digestive process can be affected by composition, quantity, and competitive interactions with the various components of the heterogenous food source. While the quality of the human diet is the ultimate factor to be evaluated, animal experimentation must provide the bulk of the information. Plant breeding improvements in nutritional quality are difficult to detect unless they are associated with an easily detected chemical change. Because of the quantities of materials required for early testing of plant materials, nutritional data from existing animal systems are too costly to collect. Rapid, low feed requiring animal systems need to be developed to support and verify plant modification studies. PROTEIN FROM OILSEEDS Rationale The potential protein supply for human use from present production of oilseeds is high. However, only a small fraction of these proteins is now consumed directly by humans. The major oilseeds in terms of total protein are soybeans, cottonseed, and peanuts. Other oilseed plants include sunflower, safflower, rapeseed, sesame, olive oil, palm oil, and copra. Cottonseed oil accounts for about 10 percent of the world's edible vegetable oil production. Cottonseed meal is a largely untapped source of protein for humans it currently goes into livestock feeds. Gossypol, a phenolic pigment that is toxic to man and some animals, is a problem in both cottonseed oil and meal. Techniques for removal of gossypol and the development of gossypol-free varieties of cotton will increase the usefulness of cottonseed oil and meal. Sunflower seed has become the world's second most im- portant source of edible vegetable oil and must rank high in any priority list for research attention. Sunflowers have a large unexplored genetic variability, which will allow breeders the chance to breed for particular climatic zones and environments. Soybean oil accounts for one-fifth of total edible veg- etable oil production, while soybean meal accounts for ap- proximately one-haIf of total world oilseed meal production. The meal in terms of amino acid balance is of the best of the vegetable protein family. Even so, soy protein is deficient in sulfur amino acids. A modest improvement in the concentration of methionine and cystine in soybeans would enhance the value of these proteins, minimize the amount of protein that must be eaten in order to meet essential amino acid requirements, and decrease the -138-

potential hazards of overconsumption of total protein. Its use is primarily for feed of livestock and poultry. Any significant breakthrough to increase production could profoundly affect the food and feed industry of this country and the world. Implementation Processing technology needs to be implemented which would provide for greater and more flexible use of the by- products of oilseeds. These efforts should be coordinated with plant breeding and selection which would provide not only the maximum yield of oil but would also contain the lowest possible levels of undesirable, naturally occurring constituents. -139-

CHAPTER 17 FORAGE AND RANGELAND IMPROVEMENT, HARVEST AND PROCESSING TECHNOLOGY RECOMMENDATIONS 1: Genetic Improvement. Research should be intensified on the genetic understanding as well as the genetic improvement of forage yield, quality, adaptability, and pest resistance of important forage and range species. 2: Germplasm and Seeding Technology. Germplasm and seeding technology should be developed to improve rangeland productivity. 3: Production Systems. Forage and livestock systems should be developed that utilize the full potentials of forage, range, and livestock management capabilities to meet most economically the various nutritional requirements of animals for various physiological functions. 4: Harvest and Processing Technology. Harvest and processing technology should be developed that (1) in- creases the efficiency of use of labor and/or energy (2) minimizes losses of biologically fixed nutrients (3) is independent of weather hazards and (4) increases forage output quantity and quality. GENETIC IMPROVEMENT Rationale Forages (harvested forages, pastures, rangelands, silages, and crop residues) are major crops in terms of total value of production and acreage. Some 245 million hectares in the U.S. are used for silage, hay, or grazing. More than 50 percent of all feed units (corn equivalent) consumed by all U.S. livestock are derived from forages. Beef cattle and dairy cattle obtain about 73 and 63 percent, respectively, of their feed units from range and forages, while sheep obtain about 89 percent from these sources (Hodgson 1968). In most other countries of the world, ruminant livestock is even more heavily dependent on range and forages—in some countries almost completely so. -140-

In recent years, there has been a rapid increase in the world's demand for the meat and milk of ruminant livestock. Correspondingly, the numbers of such animals have increased dramatically to supply those demands. Plentiful, cheap grain supplies were used to partially sustain animal population increases but, in the U.S., that population increased to more than our grasslands could support. Projections are that world demand for meat and milk will continue to grow. Increasing prices have reduced the amounts of grain available for feeding cattle in the U.S., and the same situation prevails to a degree in other countries. Such pressures may well continue into the future with only occasional fluctuations. Thus, the high dependency of ruminant animals on range and forages, the increasing demand for the meat and milk of these animals, and the current and projected reduced avail- ability of cereal grains to feed them all point clearly to the urgent need to increase the capacity of forage lands throughout the world. There is a need for higher levels of productivity and better quality of forage crops. Current animal populations will experience a sharp de- cline unless this increased range and forage capacity is achieved. while the animal population reduction is occurring, meat supplies will be plentiful and consumer prices relatively cheap. But after the reduction has run its course, meat and milk supplies are likely to be reduced to levels below needs and in a market of scarcity, consumer prices will escalate substantially with consequential serious impacts on the nutrition of major segments of our population. There are two principal methods of forage and range improvement: (1) genetic improvement and (2) seeding improved species into permanent grasslands. The breeding and genetic effort on forage and range species is generally low. There is no effort on some species of major importance on others the effort may be only a very few scientist man years—well below the necessary critical mass required for reasonable progress. On few, if any, is the effort adequate to approach capturing the potential of the species. Only limited basic genetic information (considered so essential for grain crops) is available for any forage species. While it should not be construed that other potentials for improvement are not present or of considerable magnitude, the potential for genetic improvement of forage and range species is great and centers around four main thrusts. 1. Increasing the genetic potential for yield of herbage will be a basic component in increasing total production. Selection criteria for herbage yield are different from those for seed yield and not well understood. The perennial and polyploid nature of many forage and range species complicates the selection process. -141-

2. Improving the quality of forage and range has potential for increasing performance per animal on high forage rations. Opportunities exist in such areas as (a) improving dry matter digestibility, (b) increasing animal intake potential by increasing palatability, (c) reducing lignin and silicon content, and (d) eliminating or reducing antimetabolites in some species. The potential from such efforts is indicated by one example. An improved cultivar of bermudagrass with about 10 percent increased digestibility produced a 30 percent increase in weight gain of grazing animals (Burton et al. 1967). Considerable research is needed to develop methodologies and genetic data for use in breeding for improved yield and quality. 3. Forages usually are grown on inferior sites and with a lower order of environmental control than are most annual cultivated crops. This requires a wide adaptability potential in useful cultivars and a large number of cultivars. Forage crop improvement efforts must accommodate these needs. H. Pest resistance also offers great potential for success because of the large number of pests that attack the wide range of forage and range species and cause serious losses. In addition, perennial plants provide a year-round host for many pests and can make pest impact more debilitating. GERMPLASM AND SEEDING TECHNOLOGY Rationale Overuse of many of the world's grasslands has resulted in deterioration of plant cover and productivity. Restoration of much of this important resource will require or be enhanced by improved seeding or superior natural forage and range species. The beneficial results could come rapidly, but the task is immense and should proceed without delay on the most responsive sites wherever ownership, social, or political constraints permit. PRODUCTION SYSTEMS Rationale Of particular importance is the definition and application of optimum improvement and management strategies for permanent grasslands that will permit increased animal production while preventing deterioration of the resource or, in many cases, even improving it. Such activities should receive high priority for prompt and sizeable attention. -142-

A wealth of forage and grazing management technology is available. Yet, certain cultural and use refinements will be needed as better cultivars are available and as dependence on herbage increases. Special emphasis is needed now to capitalize on the potential of innovative forage and range and livestock management practices to develop highly sophisticated production systems. These potentials should match herbage availability and quality on a year-round basis to the nutritional needs of animals for the various physiological functions of maintenance, reproduction, growth, and milk production. Similarly, there is opportunity to develop and apply animal management strategies to better use forage and range potential in different environments, types of production systems, and so on. HARVEST AND PROCESSING TECHNOLOGY Rationale Large volumes of forages are harvested annually in humid or irrigated areas of the world. Harvest practices are generally labor and energy intensive, time consuming, and in humid areas subject to physical and chemical crop losses during the harvest process. It has been estimated that annual protein losses in harvesting the U.S. alfalfa crop may be equivalent to half the yearly protein intake requirement of the U.S. human population. Losses of soluble carbohydrates are also large. Such losses mean high risk potential for harvested forages with resultant decreases in production inputs and thus lower than potential yields. Harvest technologies are needed that: (1) minimize time, labor, and energy inputs (2) reduce losses of biologically fixed proteins, carbohydrates, and other nutritional factors (3) are resistant to stresses from weather and (d) increase the quantity and quality of forage output. One approach that offers great potential but which re- quires more research and development is that of mechanical removal of water from the harvested forage. The process not only promises to accomplish the above aims, but also produces, from the expressed juices, a low fiber, high protein product of exceptional biological value that can be used as feed for certain high producing ruminants or monogastric animals or as a valuable new source of protein for humans. This concept offers great promise for simplification in technology and scale and, for that reason, for rapid adaptation to many developing nations. -143-

SELECTED REFERENCES Allaway, W.H. (1975) The Effect of Soils and Fertilizers on Human and Animal Nutrition. Washington, D.C.: USDA Agricultural Information Bulletin 378. Benedict, H.M., C.J. Miller, and J.S. Smith (1973) Assessment of Economic Impact of Air Pollutants on Vegetation in the United States: 1969 and 1971. Palo Alto: Stanford Research Institute. Burns, R.C. and R.W.F. Hardy (1973) Nitrogen Fixation in Higher Plants. Berlin: Springer-Verlag. Burton, G.W., R.H. Hart, and R.D. Lowery. (1967) Improving Forage Quality in Bermuda Grass by Breeding. Crop Science 7:329-332. Chellef, R.S. and P.S. Carlson (1974) Ann. Rev. Genetics 8:267-278. CIMMYT (1972) Purdue International Symposium on Protein Quality in Maize, High Quality Protein Maize. El Batan, Mexico. Evans, H.J., ed. (1974) Proceedings of a Workshop, "Enhancing Biological Nitrogen Fixation." National Science Foundation, Division of Biological and Medical Sciences. Washington, D.C.: National Science Foundation. Heimer, D., C. Thomas, and P.S. Carlson (1975) Personal communication. Harvard University and Michigan State University. Also, R. Mengher and H. Boyer (19"?5) Personal communication. University of California, San Francisco. Hodgson, H.J. (1968) Importance of Forages in Livestock Production in the United States Forages: Economics/Quality. Amer. Soc. of Agronomy Spec. Pub. 13. National Academy of Sciences (1972) Genetic Vulnerability of Major Crops. Washington, D.C.: National Academy of Sciences National Academy of Sciences (in press) Genetic Improvement of Seed Proteins. Washington, D.C.: National Academy of Sciences. Nickell, L.G. (1974) Plant Growth Regulators in Sugar Cane. Bulletin, Plant Growth Regulators, Vol. 2. Pimentel, D., L.E. Kurd, A.C. Bellotti, M.J. Forster, I.N. Oka, O.D. Sholes, and R.J. Whitman (1973) Food Production and the Energy Crisis. Science 182: 443-448 Sprague, H.B. (1975) The Contributions of Legumes to Continuously Productive Agricultural Systems for the Tropics and Subtropics. Technical Series Bulletin 12, Office of Agriculture, Technical Assistance Bureau. Washington, D.C.: USAID, Stone, J.F., ed. (1974) Plant modification for more efficient water use. Agric. Meteorology 14 1/2. U.S. Department of Agriculture (1974a) Opportunities to Increase Red Meat Production from Ranges ot the United -144-

States, Prepared by USDA Inter-Agency Work Group on Range Production. U.S. Department of Agriculture (1974b) Agricultural Prices, Pr (4-74). USDA-SRS Agricultural Prices, Pr 1 (9-74) . Statistical Reporting Service. Washington, D.C.: U.S. Government Printing Office,. Weaver, R.J. (1972) Plant Growth Substances in Agriculture. San Francisco: W.H. Freeman and Co. Zelitch, I. (1971) Photosynthesis, Photorespiration, and Plant Productivity. New York: Academic Press. -145-

SECTION IV LIVESTOCK, POULTRY, AND FISH PRODUCTION INTRODUCTION Animal products comprise significant portions of the food supply in the U.S., supplying two-thirds of the protein consumed, one-third of the energy, one-half of the fat, four-fifths of the calcium, nearly two-thirds of the phosphorus, and significant quantities of essential min- erals, micronutrients, and vitamins. The amino acid composition of animal proteins is of high biological value to man. In some countries, animal products supply much smaller proportions of the diet in others, the dependency on animal products, especially fish, is much greater than in the U.S. Further, a high proportion of people prefer to eat animal products. The production, processing, transportation, and marketing of these products provides employment for a large segment of the population of the U.S. Thus, the viability of the livestock industry is of significant economic importance to the country. Ruminants can convert cellulosic or concentrated feeds to food, while monogastrics require concentrated feeds for the most part. For most of man's history, and even today in much of the world, domesticated animals have consumed feedstuffs not usable by man—fibrous plant materials and the wastes. In recent times a few countries, including the U.S., have achieved the capacity to produce cereal grains, especially maize and sorghum, in quantities in excess of food needs. Livestock has played a significant role as a residual user of surplus feeds. Prices have been low enough to make such grains important animal feeds, and animal productivity has increased. But within the past few years world demand for all grains, both as food and feed (together with changes in world market structures), have resulted in price increases. As a result, a new look is being taken at the use of grain, improved forages, crop residues and by- products as ration constituents. A large part of the earth's land surface can only infrequently produce cultivated crops directly usable by man, but it can produce high cellulose plant material that can be converted economically to food only by animals. Other land, that could regularly produce food crops, finds its greatest economic value in producing forages. Also, most plant food crops produce large volumes of cellulosic residues usable by ruminant animals. Rangelands are one of the world's greatest untapped sources of feed for livestock, -146-

and improved rangeland management could greatly enhance food production. (See Chapter 17, Forage and Rangeland Improvement, Harvest and Processing Technology.) The world livestock population exceeds the human popu- lation by two to three times. The number of ruminants (cattle, buffalo, sheep, goats, and camels) alone approximates the human population of 3.5 billion, and there are about 0.6 billion swine and 5.3 billion poultry. Livestock constitutes a storehouse of food available to man, reducing his vulnerability to periods of poor crop production. It is important to emphasize that increasing livestock productivity is dependent upon improving the total food production system.

CHAPTER 18 REPRODUCTIVE EFFICIENCY RECOMMENDATIONS 1: Reproductive Diseases. Research is needed on reducing losses and controlling diseases during gestation or incubation. 2: Number and Sex of Progeny. Studies are needed on increasing the number of progeny per breeding female as well as on the sex control of the progeny. 3: Genetically Superior Animals. Research is needed on increasing the reproductive capacity of selected genetically superior mammalian animals and on estrus synchronization of females for insemination. REPRODUCTIVE DISEASES Rationale The first step is to control diseases causing abortion in mammals, hatching failure in poultry, and male or female sterility. Much of the technology to detect such diseases and substances that cause abortions or infertility and to control them within economic levels is available, but much basic research is still necessary to gain sufficient understanding for their control. The second step is management for reproduction and providing breeding females with essential nutrients. For example, it is well documented that in some areas of the tropics, provision of the minimum essential levels of the phosphorus in supplemental feed to cattle on deficient pastures has raised the calving levels. Constraints on the reproductive efficiency of animals result from improper breeding management, infections, toxic diseases, and nutritive deficiencies. Procedures should be developed for early and rapid diagnosis of incipient infertility, and for the determination of the etiology, incidence, and control of diseases, toxins, and deficiencies which induce male or female infertility and cause abortion or stillbirth, or the birth of defective offspring. Infectious diseases include brucellosis, vibriosis, -148-

leptospirosis, foot and mouth disease, and many others toxins involved include the mycotoxins of moldy feed. Many nutritive deficiencies affect reproduction, of which insufficient phosphorus intake, for example, is well known. Some control measures are already known and others should be developed for all of these. NUMBER AND SEX OF PROGENY Rationale Techniques for increasing the number of progeny produced by each female reduce the cost of maintaining the breeding herd or flock, but technical skills and materials required may not decrease the basic cost of each progeny. Thus, economic studies are needed. Areas of research should include: (a) increasing the number of young produced from each gestation: for example, increasing litter size in swine, the incidence of twinning in cattle, and of twins and triplets in sheep and goats amd (b) shortening the gestation interval by terminating gestation at optimum periods and still allowing satisfactory offspring survival: the objective is to increase the number of gestations per lifetime of each female. For some purposes control of the sex of the progeny would be economically and genetically advantageous. Conflicting results are reported for the techniques employed, but much more research is necessary to make the process feasible. GENETICALLY SUPERIOR ANIMALS Rationale Studies are needed on how to rapidly increase the number of genetically superior animals by (a) hormone treatments to induce multiple ovulation, (b) artificial fertilization, (c) removal of embryos to "incubator females" for gestation, and (d) reduction of periods of reproductive quiescence in genetically superior females. Artificial insemination, which is a long established and viable technique for increasing the number of progeny from genetically superior males, is an expensive technical service. The costs could be reduced in this procedure and in management of parturition and of resulting newborn if optimum numbers of females at each farm unit could be bred in one short interval. -149-

CHAPTER 19 IMPROVED EFFICIENCY OF LIVESTOCK PRODUCTION RECOMMENDATIONS 1: Genetic Improvement. Research is needed on genetic selection of animals with desirable production traits including rapid growth, efficient feed conversion, high production per animal, and disease resistance. 2: Nutrition Efficiency. Research on nutrition efficiency should be carried out on nutritional requirements, use of nonprotein nitrogen, rumen bypass, greater use of forage, and unconventional feedstuffs. 3: Disease Prevention and Control. Research should be increased on disease prevention and control, such as systems to reduce prevalence of disease, detection and elimination of carriers, nature of defense mechanisms, and drugs and chemicals for control of diseases. GENETIC IMPROVEMENT Rationale Artificial insemination in dairy cattle has permitted highly effective selection on males (from one male per five to twenty females, to one male per three thousand or more females). This, coupled with precise mathematical studies of records of related females, has permitted marked improvement in milk production (doubling of the average milk yield of American dairy cattle in five generations) and reduction of the national breeding herd from about 25 million to about 11 million milk cows. For poultry the time required to produce a broiler has been reduced from 14 weeks to 8 weeks, with feed efficiency being increased twofold (U kg feed/kg broiler to 2 kg feed/kg broiler). Crossbreeding has wide potential applicability for improving production. Crossing of widely divergent lines often leads to increased survival and vigorous growth of the progeny and increased feed efficiency, which results in increased production of human food from a fixed breeding population. But to achieve this, an investment is required in a scientifically oriented system of providing the necessary inputs to manage, feed, and garner the harvest -150-

from the improved progeny. It is also necessary to maintain breeding herds with resistance to disease, parasites, and stresses of climate and environment. The necessary steps involve: (a) description of the characteristics desired (b) measurements of such characteristics in a standard manner, to reduce variation due to environment (c) determination of the heritability of the desired characteristic (d) generation of means for rigorous selection for the characteristics and (e) implementation of the operation on a broad scale. NUTRITION EFFICIENCY Rationale Quantitation of nutrient requirements is a complex area of research, because of the variety of factors that influence requirements, the criteria for nutritive adequacy, and the variability within and among animal species. Continued changes in breeding, management, and introduction of new feedstuffs and methods of feed processing bring with them new factors or introduce extreme situations that influence nutrient metabolism and requirements hence, there is a continuing need for reevaluation. For example, deliberate alteration of the gene pool of a meat-producing animal species to attain greater production and more desirable carcass characteristics may influence specific nutrient requirements in as yet unknown ways. This fact is well recognized in poultry, in which strain differences are known to influence arginine, zinc, manganese, and riboflavin requirements. What is the extent of variation in specific requirements within other animal species? Is it feasible to employ selection techniques to develop strains with lower nutrient requirements? Many problem areas where research should be implemented were identified by the NRC Committee on Animal Nutrition (NAS 1974) . Four of the most important are discussed below. 1. Define Nutritional Requirements for Optimal Production and Optimal Use of Feedstuffs In our knowledge of nutritional requirements of animals there are many gaps that must be eliminated before optimal use of feedstuffs and optimal animal production can occur. -151-

2. Improve Use of Nonprotein Nitrogen (NPN) Sources Ruminants, through their ruminal microorganisms, can use NPN compounds to synthesize body proteins and convert these proteins to milk, meat, and fiber. Basic research on the biochemistry and physiology of NPN use is needed to improve the efficiency of NPN use by ruminants, and to a lesser extent, by non-ruminants. 3. Develop Rumen Bypass Technology to Improve Amino Acid Use This is an area of research that could increase the efficiency of feed use by ruminants. Preliminary studies indicate that certain amino acids may benefit ruminants, particularly at high levels of productivity, if they are treated so that they bypass the rumen (preventing bacterial degradation) and become available in the fourth stomach and lower intestinal tract. 4. Develop Systems for Greater Forage Use Ruminants can digest fibrous feeds which humans do not eat and cannot digest. Most of the forage ruminants consume is grown in land areas where the best and sometimes only use of them is in forage production. Approximately one-half of the land area in the U.S. produces forage. Therefore, ruminants are important in converting inedible forage into animal protein. As grains and other feeds are increasingly consumed directly by humans, more forages and unconventional feedstuffs will be used in the rations of all animals. Research is needed to develop rations, as well as management and production programs, which make use of different forages at varying levels of intake. Special emphasis should be given to the following: (a) Develop improved forage preservation methods and delivery systems. Development of organic acids by bacterial breakdown of carbohydrates is a classic method of feed preservation. Direct addition of organic acids is being used to preserve forages, offering possibilities for eliminating molds and for increasing the feeding value of forages. Other additives and treatments have also been used to decrease ensiling losses and to improve silage quality. Improved methods of ensiling, dehydration, and other methods of handling forages will increase their feeding value and use and decrease nutrient losses. (b) Improve crop residue utilization by chemical, physical, or other treatments. The feeding value of high fiber crop residues (e.g., straws, corn stalks, and low quality forages) can be increased by chemical treatments, -152-

such as the process developed in Germany involving the use of sodium hydroxide. These treatments would increase the digestibility of cellulose, hemicellulose, and other nutrients, thereby enhancing their value. Physical treatments, such as pelleting, are especially helpful in in- creasing the palatability, intake, and feeding value of low quality, high fiber feeds. DISEASE PREVENTION AND CONTROL Rationale Diseases retard maturity, decrease feed efficiency, increase overhead costs, and result in wastage from condemnation. This results in the loss of at least one out of every ten animals each year in the U.S. An unanticipated temporary impact of the highly effective control of one disease of poultry, Marek's disease, with the introduction of a vaccine was the depression of the market price caused by rapid overproduction resulting from increased survival. This situation has developed into decreased costs of poultry production to the benefit of both producer and consumer. Many of the discoveries of methods for controlling diseases of livestock and poultry have been applied to the control of disease in humans. Implementation Research emphasis should be given to the following areas: A. Eradicable Diseases Some preventable diseases have been eradicated in many nations, but they remain as primary constraints on livestock productivity in many agriculturally developing countries. Consequently, they have led to the imposition of quarantines that seriously restrict international commerce. A report by the American Veterinary Medical Council (AVMC) in 1974 showed that systems that were successful in ridding the U.S. of foot and mouth disease, babesiosis (Texas cattle fever), vesicular exanthema, and exotic Newcastle disease, and in reducing brucellosis, tuberculosis, screwworm, and hog cholera to rare infections can be applied to developing nations. To protect the U.S. against reestablishment of these plagues, to assist other nations in eliminating these diseases, and to make possible the eradication of other infections enzootic to the U.S., three research objectives should be satisfied: -153-

1. identification of diseases and their epide- miologies 2. creation of systems that reduce the prevalence of disease to a level that makes eradication feasible, such as the development of effective vaccines and methods of environmental management and 3. development of methods that will detect and eliminate carriers and vectors of disease so that effective quarantine can be established and maintained. Before the usefulness of a method can be fully evaluated, the findings from the fundamental studies required to achieve the three research objectives must be applied to specific diseases in specific hosts, first under controlled conditions and later with field conditions under adequate supervision. The primary criterion for selection of subjects for ap- plied research should be the identification of a specific disease for an official control program. The establishment of an official program should be made only after the above research objectives have been satisfied. B. Diseases with Complex Etiology The major unsolved disease problems in intensively reared livestock are the result of interaction of one or more pathogens with the stressor effects of environment or crowding on host animals. In this group we find many of the neonatal diseases, all of the diseases associated with animal transport, and many of those found in large dense populations. Fundamental research is needed on: (1) the nature and inheritance of innate defense mechanisms of livestock and poultry species, (2) methods of effectively stimulating specific immunity, and (3) the contributions of environmental and behavioral stressors on the susceptibility of animals to disease. This research will require federal funds not now available for staff and materials, and for sophisticated and expensive environmental facilities, such as high temperature and controlled humidity chambers. Applied research is needed on neonatal diseases of swine and cattle and on respiratory and enteric diseases of swine, cattle, and poultry. C. Diseases Controllable by Drugs and Chemicals Diseases in this group, caused by parasites and certain bacteria, contribute in a major way to the loss of efficiency in feed conversion and to lesions that are a significant cause of condemnation. Drugs and chemicals, while often effective, are expensive if used at high levels and may leave undesirable residues in meat, milk, or eggs if -154-

improperly used. Research is needed that will: (a) reduce the requirement for high level use of chemotherapeutic substances by developing management systems that reduce the exposure to parasites (b) breed for increased resistance of the animal to parasites and (c) develop drug regimes that will provide adequate protection against parasitism without leaving drug residues. The second of these objectives would require the systematic study of the potential for breeding animals for disease resistance. It may necessitate the assembly, preservation, and inventory of gene pools of food animal species for factors that determine resistance to disease. The long-term costs of controlling disease in terms of labor, drugs, and food safety justify serious consideration of breeding for animals resistant to disease. -155-

CHAPTER 20 PRODUCT QUALITY AND CONSUMER ACCEPTABILITY RECOMMENDATIONS 1: Human Health. More emphasis should be placed on studies on the effect of animal products on human health. 2: Fat in Beef and Pork. Feeding, management, and production programs should be developed for decreasing excess, trimmable fat in beef and pork. 3: Safety in Foods. Criteria should be developed for determining biological safety in foods. HUMAN HEALTH Rationale Much is still to be learned about the relationship of animal products, saturated fats, and cholesterol to heart disease. It is still unclear whether dietary changes, such as substituting unsaturated fats for saturated fats, can significantly reduce cardiovascular problems. Feeding diets high in saturated fatty acids to experimental animals over a long period of time indicates that serious problems may develop. It has been demonstrated that the linoleic acid (unsaturated) content of milk, eggs, and body fat can be increased by dietary control of farm animals. But before this is recommended to the farmer it should first be demonstrated that it is advantageous to human health to do so. Moreover, scientists need to determine whether animal products containing unsaturated fats will be accepted by the public as readily as those with saturated fats. Studies are needed on the effects of feeding products at varying levels and for varying periods of time to experimental animals, and on the application of these to human health. -156-

FAT IN BEEF AND PORK Rationale Much of the beef and pork produced in the U.S. is fatter than the consumer wants. Thus, grain and other energy feeds are being wasted by overfinishing cattle and swi ne. Approximately 20 percent of excess fat is trimmed in choice beef carcasses. In 1973, the resultant waste amounted to a $1.15 billion loss which was ultimately absorbed by the consumer (NAS/in press). Similarly, nearly 90 percent of the barrows and gilts marketed in the U.S. have more separable fat than lean in their carcasses, leaving only 10 percent to grade USDA number 1—the only grade with more lean than fat. Similarly, the waste fat content of the approximately 14 billion pounds of carcass pork produced annually in the U.S. could be reduced by 5 percent. An increase in the lean and decrease in the waste fat by 5 percent would result in a saving of .5 billion per year in lower feed costs. SAFETY IN FOODS Rationale As new feed additives, animal wastes, by-product feeds, and alternative feed sources are used, the possibility of harmful residues occurring in animal products needs to be guarded against. Research is required on procedures that could safely salvage for human consumption animal protein that would otherwise be destroyed to eradicate animal diseases. It is recommended that more adequate methods be devel- oped for determining the biological safety of foods for human consumption. A concept of biological zero should be established with regard to residues in food. This would be defined as the level which a panel of competent scientists, after examining adequate data, would determine as having no harmful effect on humans. -157-

CHAPTER 21 FISH PRODUCTION RECOMMENDATIONS 1: Wild Stocks. A research program should be implemented to increase food production from wild stocks of fish, including the increased harvest and efficiency of underutilized species. The creation of a national fisheries management regime should also be undertaken. 2: Aquaculture. Support should be given to the development of technological and scientific bases for aguaculture, and pilot plants and culture systems should be developed in conjunction with industry. WILD STOCKS Rationale Concern that society has generally failed to conserve and allocate fisheries resources in an effective manner under existing institutions (both domestic and international) reflects a lack of centralized policy for fisheries management in the U.S. and a lack of coordinated, effective management. In the U.S. this is a consequence of historical practice whereby the states were given responsibility for and authority over fisheries management out to the limit of territorial waters, while the federal government had no authority except where international fisheries were involved. The fragmentation of authority and management and the general lack of cooperation among states for the regulation of fish stocks that cross state borders have made it difficult to implement workable management programs within state waters. It has also been a tradition in this country that resources of marine fish are available to all, with the result that no limit could be placed on the number of boats allowed to engage in a fishery. The outcome has been exploitation and overcapitalization, in many cases seriously damaging the stocks biologically and wasting labor and financial resources. Other natural resources have not faced this handicap in the U.S., nor is this practice common to many of the other principal fishing nations. It will be necessary to alter the system eventually, and an opportunity -158-

is offered to make the change now when the U.S. is being obliged by international events, including the Law of the Sea Conference, to make significant changes in its national fishery policies. In the field of international fisheries conservation, the U.S. has relied on international commissions and bilateral agreements to control fishing and to protect stocks. To varying degrees, none of these arrangements has been fully satisfactory, principally because insufficient authority has been given to the management bodies. As a consequence, some international fisheries stocks have been damaged—in some cases perhaps irreparably. Implementation There are three ways to increase the production of pro- tein from wild stocks: (1) use species not being used, or only partially used (2) develop more efficient systems of recovery of protein in harvesting and processing and (3) develop effective management. These three ways are discussed below. 1. Underutilized Species The present world catch of marine fish and shellfish is about 60 million metric tons per year, according to data supplied by the Food and Agriculture Organization (FAO). FAO estimates of the potential world catch of conventional species are from 100 to 115 million metric tons. If unconventional species such as krill and lantern fish are included, the potential is much larger. In U.S. coastal waters the current annual harvest by U.S. and foreign fleets is 5.5 million metric tons, from statistics provided by the U.S. National Marine Fisheries Service (NMFS). NMFS estimates that this could be increased to at least 8.6 million metric tons. 2. More Efficient Recovery Greater use of fish could be achieved through more efficient recovery from current harvests. For example, flesh-separating machines which squeeze the flesh from the skin and bones of fish and pass it through perforations on stainless steel plates may increase the useable yield by as much as 40 to 50 percent. Fully automated mechanized methods would also maximize cost effectiveness. Information dissemination and research can help to greatly reduce the present waste of fish protein through spoilage. Preservation techniques should be taught to fishermen and others in the coastal communities. -159-

Other gains can be achieved through increased human consumption of fish now used for industrial products (principally fish meal) and through the use of species that are discarded at sea by developing new products, such as minced fish, and alternative methods of shipboard preservation. 3. Effective Management Better management is required to prevent the overfishing or the economic extinction of traditional stocks of fish. Sometime in 1976, the U.S. will probably assume some form of extended jurisdiction over the coastal fisheries resources out to 200 nautical miles from its shores. This will give us the first opportunity in our history to create coordinated and effective conservation measures in both domestic and international fisheries. The enormously increased areas over which the U.S. will exercise exclusive fisheries jurisdiction (approximately 2,222,000 square nautical miles of continental shelf and the overlying water) contain the largest fisheries resources of any nation in the world. This area has an annual potential production of at least 8.6 million metric tons of fish for food and recreation, more than 10 percent of the current world production. Other coastal nations will be offered the opportunity to apply conservation management to large areas of ocean off their coasts. The U.S. is thus obligated to reexamine its national policy because for the first time it would be responsible for managing the fisheries resources within a 12 to 200 mile zone. This obligation is a consequence of events that have taken place in this country and around the world in recent years altering domestic and foreign attitudes toward the rights to fisheries resources and their conservation. Many other countries will also be reexamining their fisheries management policies. AQUACULTURE Rationale World aquaculture production is 6 million metric tons (8.6 percent of seafood supplies). In the past five years production from aquaculture worldwide has doubled, and the proportion it produces may be as much as 10 percent of the world's aquatic-derived foods. In the U.S. the 1973 production of fish was 2,136,000 metric tons, of which 73,000 metric tons were produced by aquaculture total U.S. consumption of fisheries products is about 3.2 million metric tons. Thus, aquaculture produces about 3.4 percent of U.S. production and a little over 2 percent of the -160-

supply. Because of the existence of very extensive areas of suitable aquatic habitat and the availability of proven technologies for several species, the potential exists for significant increases in fish production by culture, especially in the estuarine and marine environments. Although aquaculture has been slow in developing, fish farming on a small scale has existed for a long time and the desirability of expanding its scope and production has been recognized, both by those engaged in the culture of such species as oysters, catfish, and trout, and by those attempting to develop industries for shrimp, mussels, and their products. In recent years in particular, there has been high interest in aquaculture and increased activity, during which government, academic, and industrial groups have engaged in aquaculture research and development. In many cases results were encouraging, but in others they fell short of expectations. Moreover, many of the problems, some of which had seemed near solution, proved intractable, often for economic reasons. Aquaculture development in the U.S. has therefore stagnated. While biological and technological information and culture methods are available to increase production of salmon, trout, catfish, oysters, and some species of clams, development of viable aquaculture of most other species will require research to provide adequate biological and technological bases and to develop and test culture systems on a pilot scale. Only then will private capital be attracted that will lead to the establishment of an industry. Much of this research, because of its nature and cost, should be performed by the government or by other research groups with government funds. Expanded aquaculture also requires unpolluted coastal or estuarine areas or supplies of high quality fresh water, but other users also want these limited resources. Where such problems cannot be resolved, closed systems will need to be developed, thereby releasing aquaculture from dependence on natural water supplies and expensive waterfront property. Urgent research areas on fish culture include: (a) Research on methods of increasing supplies of seed (eggs and larvae). This research should include reproductive physiology to develop the ability to induce maturation and spawning in captivity and for the development and maintenance of brood stocks. This is also a necessary prelude to genetic modification and selective breeding. (b) Research on nutrition of cultured animals including larval stages, and on the development of inexpensive and nutritionally effective feeds. (c) Research on disease control of hatchery fish and shellfish production. With the high density populations that result from intensive culture, disease incidence and severity increase markedly. Information on disease -161-

prevention and control is presently insufficient for cultured species. (d) Research on the nature of institutional and related constraints on aquaculture development and on methods of technology transfer. Implementation The federal government has an essential role to play in encouraging expansion of aquaculture. Private aquaculture in the U.S. is based primarily on systems developed and research conducted or sponsored by the federal government. Commercial salmon and trout culture became possible following government research and development for public hatchery programs, which solved problems such as nutrition and disease control. In 195**, l.U million pounds of trout were produced in private fish farms in 1973, production was about 60 million pounds. Techniques for commercial rearing of salmon, recently developed in government programs, has started a new industry and about 10 companies are engaged in commercial salmon farming. In recent years the oyster culture industry has been strengthened by research in government laboratories on hatchery production of young. The importance of the federal government role in aquaculture is greater now than it will be in future years, since much basic and essential information is currently lacking and the industry is small. The appropriate role of the government now would appear to be to conduct long-term research, much of which is highly technical, requiring spe- cialized equipment and the multidisciplinary approach of highly trained scientists, engineers, and economists. These kinds of expertise are unavailable to industry at the present stage of aquaculture development. Later, when a larger and better organized industry exists, it can assume much of the government's responsibility. -162-

SELECTED REFERENCES Alverson, D.L. (1975) Opportunities to Increase Food Production from the World's Ocean. Marine Technology Society Journal 9(5): 33-40. Anonymous (1975) Fisheries Management Under Extended Jurisdiction: A Study of Principles and Policies. Staff Report to the Associate Administrator for Marine Resources National Oceanic and Atmospheric Administration. pp. 1-75. AVMA Council on Research (1974) Justification for Veterinary Animal Health Research, Am. J. Vet. Res. 35: pp. 875- 887. Bardach, J.E., J.H. Ryther, and W.O. McLarney (1972) Aquaculture. Wiley-Interscience, New York. pp. 868. Cole, H.H., G.H. Fass, R.J. Gerrits, H.D. Hafs, W.H. Hale, R.L. Preston, L.C. Ulberg (1975) On the safety of estrogenic hormone residues in edible animal products. BioScience, 25 (1): 19-25. January. Council for Agricultural Science and Technology (1974) Report 31, Zero Concept in Air, Water and Food Legislation, August 12. Council for Agricultural Science and Technology (1975) Ruminants As Food Producers - Now and for The Future. Council for Agricultural Science and Technology Special Publication, No. 4, March. Cunha, T.J. (1974) Role of Ruminant Production in Increasing Animal Foods in Latin America. Proc. International Conference on Nutrition and Agriculture and Economic Development in the Tropics. Guatemala City. December 2-6. Edwards, R. and R.H. Hennemitt (1975) Maximum Yield: Assessment and Attainment. Oceanus, 18 (2) . Guthrie, H.D., D.M. Henricks and D.L. Handlin (1974) Plasma hormone levels and fertility in pigs induced to superovulate with PMSG. J. Reprod. Fert. 41. 361. Idyll, C.P. (1975) The Sea Against Hunger: Harvesting the Oceans to Feed a Hungry World. New York: Thomas Y. Crowell Company. Idyll, C.P. (1973) Marine Aquaculture: Problems and Prospects. Journal Fisheries Research Board of Canada. 30(12) pt. 2: pp. 2178-2183. Inskeep, E.K. (1973) Potential uses of prostaglandins in control of reproduction cycles of domestic animals. J. Anim. Sci. 36, 1149. Kiddy, C.A. and H.D. Hafs (1971) Sex Ratio at Birth- Prospects for Control. Am. Soc. of Anim. Sci. Maurer, F.D. (1975) Livestock, a World Food Resource Threatened by Disease. J. Am. Vet. Med. Assn. 166:920-923. National Academy of Sciences (1973) Animal Disease Eradication: Evaluating Programs. Proceedings of a National Academy of Sciences' Workshop, University of -163-

Wisconsin-Madison, Wisconsin, April 12-13, 1973. Washington, D.C.: National Academy of Sciences. National Academy of Sciences (1974a) A Nationwide System for Animal Health Surveillance. Committee on Animal Health. Washington, D.C.: National Academy of Sciences, National Academy of Sciences (1974b) Research Needs in Animal Nutrition. Committee on Animal Nutrition. Washington, D.C.: National Academy of Sciences. National Academy of Sciences (in press) Changing the Fat Content and Composition of Animal Products. Board on Agriculture & Renewable Resources and Food & Nutrition Board, National Research Council. Washington, D.C.: National Academy of Sciences. Pillay, T.V.R. (1973) The Role of Aquaculture in Fishery Development and Management. Journal Fisheries Research Board of Canada. 30(12) pt. 2: pp. 2202-2217. Rowson, L.E.A., R.A.S. Lawson, and R.M. Moor (1971) Production of twins in cattle by egg transfer. J. Reprod. Fert. 25, 261. Rowson, L.E.A., R.A.S. Lawson, R.M. Moor, and A.A. Baker (1972) Egg transfer in the cost: Synchronization requirements. J. Reprod. Fert. 28, p. 427. Rowson, L.E.A., R.M. Moor, and R.A.S. Lawson (1969) Fertility following egg transfer in the cow effect of method, medium, and synchronization of oestrus. J. Reprod. Fert. 18, 517. Salisbury, G.W., N.L. VanDemark and J.R. Lodge (in press) Reproductive physiology and artificial insemination of cattle. 2nd Edition. San Francisco: W.H. Freeman and Co. Salisbury, G.W., R.H. Hart, and J.R. Lodge (in press) The fertile life of spermatozoa. Perspectives in Biology and Medicine. Saulmon, E.E. (1973) A New World of Animal Health Program Financing. Proc. 77th Ann. Meeting. U.S. Animal Health Assoc., St. Louis, Missouri, October 14-19. Smith, L.E. Jr., G.D. Sitton, and C.K. Vincent (1973) Limited injections of follicle stimulating hormone for multiple births in beef cattle. J. Anim. Sci. 37, 523. U.S. Department of Agriculture (1974) Protecting American Agriculture - Inspection and Quarantine of Imported Plants and Animals. Agric. Econ. Report 266:1-58. Wa shington, D.C. U.S. Department of Agriculture (1975) Meat Research, ARS progress report. USDA Agriculture Information Bulletin, 375:1-83. Washington, D.C. -164-

SECTION V: FOOD SCIENCE AND TECHNOLOGY INTRODUCTION Primitive man had to forage for food in his natural en- vironment, feasting in times of plenty and starving in lean times. Gradually he learned the technology of food preservation and improved his ability to save plentiful foods for later use in time of shortage. In developed countries, food science and technology have done much to relieve the impact of hunger and malnutrition, but many developing countries do not enjoy such benefits. There the seasons still alternate from wet to dry or cold to warm, bringing the same stresses on man's food supply as in pre- historic times. The major goals of the food system other than food pro- duction can be listed as follows: 1. to maximize the availability of high quality, safe, nutritious foods at the least cost to consumers 2. to improve the efficiency and dependability of food delivery systems 3. to reduce food losses in distribution and storage 4. to reduce resources needed in protection, storage, and distribution of food and 5. to determine the comparative advantages of food production and distribution systems to minimize total inputs and maximize total outputs. Because of consumer concerns and government actions, food processors must be concerned, not only with the production of wholesome, safe foods, but also with pollution aspects of their process, with nutritional value, and with shelf life of the product. Pollution concerns not just industrial waste, but packaging as well and its effect on eventual solid waste disposal. Connected to this is the ecological problem of power and water use. Processing and preservation technology is aimed at storage stability of foodstuffs including packaging. The major issues involved are the safety of the food supply from pathogens, the maintenance of quality (i.e., no chemical or microbial decay), the prevention of losses from insects, and the maintenance of nutritional value. The primary principles of processing include the destruction of harmful microorganisms by sterilization, pasteurization, or blanching separation processes, such as membrane processes, extraction and immobilized enzymes environmental, temperature, and gaseous atmospheric control chemical preservatives, fermentation, and/or alkali -165-

preservatives and additives and control of water- dehydration, intermediate moisture foods, and freezing. The prime generic function of a commercially viable package is protection of the contents. Considerations in packaging research are energy and resource conservation needs, such as prevention of loss of foodstuff, quantity of packaging material, energy to create packaging material, and disposal or secondary use of used packaging materials. Other considerations include consumer acceptance, cost to the consumer, and the relationship of packaging technology to a large system of processing and preserving foods. Flexible pouches and thin-walled drawn containers with heat sealed lids for heat stabilized foods are being developed and show promise. They eliminate refrigeration costs of material compare favorably with metal cans and their weight is about 10 percent that of cans empty- container storage needs are fewer and in the opinion of many food technologists, the products surpass frozen and canned foods. However, pouch output is slow and labor intensive, capital investment is high, and pouched products containing meat or poultry have not received USDA approval. The evaluation of new potential sources of food is particularly important in future development. Some important critieria are: increased growth potential, greater biological value in human nutrition, freedom from vicissitudes of weather, higher yields per unit area, utility in food formulation, and economy. -166-

CHAPTER 22 LOSSES IN THE FOOD SYSTEM RECOMMENDATIONS 1: Losses of Raw Product. Research must be increased to reduce losses during harvest or slaughter, handling, and storage of raw product. 2: Losses of Prepared Product. Research must be increased to minimize losses due to stress in packaging, storage, transportation, and distribution of processed foods. LOSSES OF RAW PRODUCT Rationale Rapid and large increases in available food supplies can be achieved by reducing losses incurred during harvest, slaughter, handling, and storage of the raw product. In addition, an effective reduction in losses and consequently an increase in yields represents a major conservation in energy. Inherent in the increased availability is also the potential for enhanced nutrient availability and consumer acceptability of the product. Implementation To reduce losses during harvest, slaughter, handling, and storage of the raw product, the following are recommended as major steps: 1. improve harvesting, slaughter, and handling systems 2. expand knowledge of postharvest and postslaughter physiology 3. increase knowledge of microbiological growth and control of toxicity 4. improve pest control and 5. evaluate the significance of the chemical activity of water in storage. -167-

LOSSES OF PREPARED PRODUCT Rationale The segments of packaging, storage, transportation, and distribution compose another area of our food system in which significant increases in availability of food supplies can be achieved through reductions in loss. Stress, the major cause of these losses, consists of primary and secondary factors which in most instances are additive. Stress, which occurs in each segment of this area, is usually initiated by mechanical or environmental effects (primary factors) which then induce chemical, biochemical, and biological effects (secondary factors). For example, mechanical stress can result in broken grain, bruised fruits and vegetables, or ruptured packages. Mechanical stress breaks down the protective barrier, be it natural or artificial, and allows chemical or biochemical reactions or microbial and pest invasion to destroy nutrients and consequently lower quality and acceptability. Environmental stress, such as significant changes in temperature, light, or atmospheric conditions, can induce chemical and biochemical reactions (e.g., enzymatic or nonenzymatic brownings) which destroy the quality of the product with or without permeating the protective barriers. Environmental stress can also produce physical, chemical, and physiological changes which create optimum conditions for loss due to microbiological proliferation and development of toxins. In addition, stress in one segment of the packaging, storage, transportation, and distribution area may induce loss in another segment. Stress, therefore, must be critically evaluated in a total system, ranging from harvest to consumption. In this way, the purpose of increased availability of supplies through reductions in loss can be achieved with a minimum of effort in each segment. -168-

CHAPTER 23 FOOD PRESERVATION AND PROCESSING RECOMMENDATIONS 1: Food Composition and Chemistry. Research must be expanded to increase our fundamental knowledge of food composition and chemistry. 2: Food Composition and Quality Assurance. Research and development are needed on rapid and quantitative methods of detection of food components and hazards associated with foods and their toxicological significance. FOOD COMPOSITION AND CHEMISTRY Rationale The development of the technology of food preservation and processing has evolved slowly. Significant improvement in the efficiency of current operations and the safety and quality of products cannot be achieved without a significant increase in our knowledge of food composition and chemistry, and without attention to types of waste and proper use of waste within the total farm-to-processor system. This knowledge base is also essential to the further development of food fabrication processing, i.e., the conversion of food components—carbohydrates, lipids, proteins, vitamins, and minerals—into products for the consumer. The process may become essential in meeting the world's need for food. But only with the processor's adequate knowledge of the composition and chemistry involved can the quality and safety of the products be assured for the consumer. Implementation Primary emphasis for research on food composition and chemistry should be placed on the following areas: 1. knowledge of the native structure and composition of plant and animal materials and the physical-chemical interactions of food components -169-

2. knowledge of the effects of preservation and processing on the nutrients and physical-chemical interactions of food components and 3. ways to minimize generation of waste and maximize use of waste. FOOD COMPOSITION AND QUALITY ASSURANCE Rationale Food composition and quality assurance are tangible terms which can be measured and related to set standards for various foods. Food safety is an abstract term and cannot be measured: it is the absence of hazard. The most fundamental problem in the area of food safety is that of quantifying hazards associated with foods. The critical problem area lies in determining, in a raw or processed food, the presence and extent of hazard which is either naturally present in the food or a by-product of processing. The second major problem in the area of food safety is that of establishing permissible levels of hazardous substances on the basis of scientifically defensible criteria. Extrapolation of toxicological, teratological, and/or oncological data from animals to humans is subject to debate. Exposure to zero levels of carcinogenic or toxic substances is scientifically untenable, thus scientific criteria for these substances must be established. There are six major classes of hazard in foods: (1) food borne diseases of microbiological origin (2) malnutrition (3) environmental contaminants (U) naturally occurring toxicants in foods (5) pesticide residues and (6) food additives. Hazards 1, 3, 4, 5, and 6 can occur with a high rate of fre- quency therefore, rapid, quantitative methods of detecting these hazards and their toxicological significance are needed, and their development should be given priority. Food composition and quality assurance of raw and processed foods are dependent on measuring the constituents of foods and their nutritional value chemically or microbiologically. The most important need in this area is the development of rapid, quantitative methods for the determination of protein, fat, carbohydrate, moisture content, water activity, vitamin and mineral content, dietary fiber, protein quality, heavy and trace mineral content, and the presence of intentional or unintentional food additives. It is also important to support research which will de- termine the biological availability of the nutrients in raw and processed foods, as well as identification of processing -170-

conditions which affect their biological availability during processing, distribution, and storage. Finally, such an encompassing research effort will create a problem unless computer technology (both hardware and software) is developed to provide analytical systems to collate, calculate, interpret, and evaluate the research data. Implementation The feasibility of developing a program to measure composition, quality assurance, and safety of our food supply from harvest or slaughter through consumer use is dependent upon three major points: (1) development of a useful computer storage and retrieval system for current and future scientific data (2) federal support of research on food science and human nutrition in governmental agencies and universities and (3) communication of this information to the public. This program will require a sizeable commitment of federal dollars. -171-

CHAPTER 24 DISTRIBUTION AND TRANSPORTATION RECOMMENDATIONS 1: The Packaging System. Research and development is urgently needed on standardization of our packaging system to improve handling in distribution. 2: National Transportation Plan. Research is needed for the development of a more detailed national transportation plan as it affects agriculture. THE PACKAGING SYSTEM Rationale The cost of distributing food and food products represents about half of the total cost of most food products. Many of the inefficiencies in materials handling can be traced to an industry pattern in which product variety was deliberately created to appeal to special buyers. More than 1,400 different container sizes are used by the fruit and vegetable industry alone. Apples are now packaged in 40 different shapes and sizes, none of which will fit the standard grocery shipping pallet. The lack of standardization in packaging is a serious obstacle to efficient materials handling and distribution. In certain instances, however, for the convenience of the consumer the packaging of the same product in a size that is enough for two servings, for one serving, or for a family of six, may serve a valuable purpose. Ideally, goods should be packed in cartons of standard dimensions that fit on a single-sized pallet, which in turn fits into standardized containers, railroad cars, and trailers. Implementation There should be a complete review of the possible sizes and shapes of all the various containers, packages, pallets, and transportation vehicles to determine the changes that would optimize distribution economics. The benefits and disadvantages of each pattern of standardization need to be -172-

carefully weighed. Industry participation in this endeavor is essential. NATIONAL TRANSPORTATION PLAN Rationale Transportation is a limiting factor in every part of our food system. Agriculture is pursued where the land is productive, but this productivity has no necessary relationship to the location of the ultimate consumer. The food system, therefore, is more dependent on transportation than most other parts of our economy. The rural railroad network has disintegrated as railroads have abandoned tracks that were not profitable. The rural highway system has not been improved sufficiently to take the heavy loads that were previously handled by rail. The problem is aggravated by transportation regula- tions, such as "tariffs" that define a set of conditions under which a shipper can ship goods, and the rates that will apply to those shipments. This allows only a portion of this already inadequate transportation system to be used in moving goods into the rural communities. From a long-range viewpoint, the food system cannot ignore the greater fuel efficiencies of moving foods by water and rail rather than by truck. We need to develop a transportation system that optimizes the flow of goods with a minimal expenditure of petroleum. This will require coordination of the regulatory powers of various agencies toward the common goal of a more efficient system. In the near future, however, improvements must be effected within this transportation system as it now exists. Such improvements will, of necessity, be made within one mode of transportation at a time. In view of the overall transportation plan, any action that is taken to increase the efficiency of railroads must be coordinated with corresponding necessary ICC regulations concerning changes in our truck system to realize the greatest overall gain in transportation efficiency (Miles 1974) . Implementation To design a more detailed national transportation plan as it affects agriculture, it is essential to know what commodities are being moved, in what quantities, between what points, and at what cost. It is important to know the relationship of the flow of agricultural products to the flow of other types of commodities and the way in which this interaction relates to the aggregate capacity of barge, rail, and truck transportation. -173-


CONGRUENCE AND CONTROVERSY: Toward a Higher-Level Phylogeny of Diptera

AbstractThe order Diptera (true flies) is one of the most species-rich and ecologically diverse clades of insects. The order probably arose in the Permian, and the main lineages of flies were present in the Triassic. A novel recent proposal suggests that Strepsiptera are the sister-order to Diptera. Within Diptera, evidence is convincing for the monophyly of Culicomorpha, Blephariceromorpha, and Tipulomorpha but weak for the monophyly of the other basal infraorders and for the relationships among them. The lower Diptera (Nematocera) is paraphyletic with respect to Brachycera, and morphological evidence suggests the sister-group of Brachycera lies in the Psychodomorpha. Recent analyses suggest Tipulomorpha are closer to the base of Brachycera than to the base of Diptera. Brachycera are undoubtedly monophyletic, but relationships between the basal lineages of this group are poorly understood. The monophyly of Stratiomyomorpha, Xylophagomorpha, Tabanomorpha, and Muscomorpha is well supported. Eremoneura, and its constituent clades Empidoidea and Cyclorrhapha, are monophyletic. The sister-group of Eremoneura is likely to be part or all of Asiloidea. Several viewpoints on the homology of the male genitalia of eremoneuran flies are discussed. Phylogenetic analyses suggest that lower Cyclorrhapha (Aschiza) are paraphyletic however, schizophoran monophyly is well supported. The monophyly of Acalyptratae is not well-founded and the relationships between acalyptrate superfamilies remain obscure. Recent advances document the monophyly of the families of Calyptratae and the relationships among them. Areas critical to future advances in understanding dipteran phylogeny include the relationships among the basal infraorders of Diptera and Brachycera and the relationships between the superfamilies of acalyptrates. Progress in dipteran phylogenetics will accelerate with the exploration of novel data sources and the formulation of hypotheses in an explicitly quantitative framework.


Why Amish Are Immune to Allergies and Asthma

God&rsquos Word surely is the answer to all of life&rsquos problems. Psalm 119:104-105:

104 Through thy precepts I get understanding: therefore I hate every false way.

105 Thy word is a lamp unto my feet, and a light unto my path.

When once reviewing various archaeological discoveries, I came across an ancient foot lamp. The user would light this lamp and it would extend out from the body by about 5&rsquo&mdashjust above ground level. By the use of this contraption, one could safely walk on a starless night. The Word of God is a lamp unto our feet, but, as the foot lamp of old, it must lead in order to deliver the needed results. The Bible speaks of man&rsquos condition prior to salvation in Matthew 4:16:

The people which sat in darkness saw great light and to them which sat in the region and shadow of death light is sprung up.

Have you seen the Light? John 1:6-9:

6 There was a man sent from God, whose name was John.

7 The same came for a witness, to bear witness of the Light, that all men through him might believe.

8 He was not that Light, but was sent to bear witness of that Light.

9 That was the true Light, which lighteth every man that cometh into the world.

Have you been born again? Are you ready for the eternal Light that will eliminate all your darkness, the Light that will satisfy all your needs? Today is your day of salvation. Click onto &ldquoFurther With Jesus&rdquo for childlike instructions and immediate entry into the Kingdom of God. NOW FOR TODAY&rsquoS SUBJECT.

GOD SAID, Leviticus 25:2-4, 20-22:

2 Speak unto the children of Israel, and say unto them, When ye come into the land which I give you, then shall the land keep a sabbath unto the LORD.

3 Six years thou shalt sow thy field, and six years thou shalt prune thy vineyard, and gather in the fruit thereof

4 But in the seventh year shall be a sabbath of rest unto the land, a sabbath for the LORD: thou shalt neither sow thy field, nor prune thy vineyard.

20 And if ye shall say, What shall we eat the seventh year? behold, we shall not sow, nor gather in our increase:

21 Then I will command my blessing upon you in the sixth year, and it shall bring forth fruit for three years.

22 And ye shall sow the eighth year, and eat yet of old fruit until the ninth year until her fruits come in ye shall eat of the old store.

GOD SAID, Leviticus 25: 11-12:

11 A jubilee shall that fiftieth year be unto you: ye shall not sow, neither reap that which groweth of itself in it, nor gather the grapes in it of thy vine undressed.

12 For it is the jubilee it shall be holy unto you: ye shall eat the increase thereof out of the field.

GOD SAID, Galatians 6:7:

Be not deceived God is not mocked: for whatsoever a man soweth, that shall he also reap.

MAN SAID: Our science has mastered agriculture. We can chemically control the pests of the field and our genetically modified products will fill the earth with plenty.

Now THE RECORD. The Bible was authored by God and penned by His holy men. Its narrative is historically accurate, the miraculous accounts fully certified, and inherent within His commandments are a blessing or a curse. Because God&rsquos commandments are true and righteous altogether, obeying them yields the blessing of doing the right thing disobeying results in the curse of doing the wrong thing. It really is just that simple. The results of man continually rejecting the direction of the Creator are negative and even deadly. Those looking for proof need look no further.

The first five books of the Bible&mdashknown as the Torah or Pentateuch&mdashwere given by God to Moses. The examples and commandments pronounced by God in these books were given for the purpose of building a holy nation full of good fruits and contentment. The laws and directives were national in nature. Every Israelite was obliged to obey. For the purpose of this feature, GodSaidManSaid has placed the commandments in five categories:

  1. Myriad of laws that ensure the underwriting of the expense of government, that alleviate guilt and stress, regulate social conduct, and establish a national rhythm and identity.
  2. The strict commandment to bury in the ground all human waste&mdashnot to flush it into the waterways, treated and untreated, as is commonly done today.
  3. God&rsquos dietary laws concerning what not to eat or even touch, and what to eat, such as clean meats purged of blood and fat, and raw milk, raw honey, olive oil, and more.
  4. God&rsquos law of the quarantine for running issues of any nature, even the common cold. Contagious issues were separated from the general population for seven days outside the camp until the individual was pronounced clean by a priest.
  5. God&rsquos commandment to give the land its Sabbath, as well as the commandment of the Jubilee every 50 years, where two Sabbaths of the land were back-to-back.

These national laws were designed to build a powerful and happy people.

It should make good sense that obeying the instructions of the Manufacturer of life would be the right thing to do, but man has found a &ldquobetter&rdquo way. This feature will air several different pieces of information which seem slightly unrelated, but a closer look will reveal their commonality. First, several preparatory paragraphs from the GodSaidManSaid feature, &ldquoThe Dirt You Eat&rdquo follow:

  • Beans, snap green à 34%
  • Broccoli à 53%
  • Carrots à 27%
  • Peaches à 44%
  • Strawberries à 33%
  • Tomatoes à 62%

The following excerpts are from The Healthy Home Economist, November 13, 2014. The headline reads, &ldquoThe Real Reason Wheat is Toxic (it&rsquos not the gluten).&rdquo

  • Gastrointestinal disorders
  • Obesity
  • Diabetes
  • Heart Disease
  • Depression
  • Autism
  • Infertility
  • Cancer
  • Multiple Sclerosis
  • Alzheimer&rsquos disease and the list goes on and on.

RealFarmacy.com published the following under the heading, &ldquoScientists Reveal Why Amish Children are Immune to Allergies & Asthma:&rdquo

Studies in Sweden have determined that kids raised on dairy farms are considerably more resistant to allergies than those who live elsewhere, including nearby rural areas without non-dairy farms. This wasn&rsquot the only study displaying this phenomena.

Allergies and asthma have been on the rise in the West over the past few decades, especially among younger children. In addition to vaccinations and our immersion into chemicals that permeate a fetus from mothers&rsquo exposure to them, there has been conjecture that our obsession for cleanliness is a contributing factor.

The argument posits that exposure to dirt and its natural microbes helps an immune system develop in a young child, so playing in the dirt is a good thing. This theory is known as the &ldquohygiene hypothesis,&rdquo where too much hygiene or cleanliness for babies and toddlers disables development of a mature immune system.

Recently, researchers conducted an epidemiological study at the University of Gothenburg, located in Sweden&rsquos second largest city, Gothenburg. They monitored children&rsquos health from birth to age three in a large nearby rural district. Around half of them lived on dairy farms while the rest did not.

Those who lived on dairy farms tended to be allergy-free, while the others were 10 times more prone to developing allergies. (http://sahlgrenska.gu.se)

These farms were all smaller traditional farms. Besides breathing in or absorbing microbes from poop [animal dung] and earth in the immediate air, the kids drank or used raw milk. More importantly, so did their moms. The researchers mentioned the prevalent raw milk evidence briefly but tap-danced around it.

After Swiss Amish were studied with similar results as other traditional European farm studies, the researchers seemed stuck on what differentiated these types of farms from others.

But an American researcher followed up with Indiana (USA) Amish study to find similar results, higher immunity to disease, asthma, and allergies. The Amish tend to use raw milk from humanely-treated, grass-fed cows while avoiding or minimizing toxic chemicals on their crops.

You won&rsquot find higher immunity on factory farm dairies and large monoculture farms that indulge in excessive amounts of toxic pesticides, herbicides, and chemical fertilizers.

As a matter of fact, more and more children on or even near those farms are experiencing autistic spectrum disorders or autoimmune diseases beyond asthma or allergies. [End of quote]

Disregard for God&rsquos given ecological protocols generate debilitating results such as the rejection of a national law to give the land its Sabbath. Today&rsquos research has not even addressed the biological benefit of eating the preserved old fruit of the land during and following the Sabbath of the land. The Word of God is the foundation of all truth. Build your life here.

GOD SAID, Leviticus 25:2-4:

2 Speak unto the children of Israel, and say unto them, When ye come into the land which I give you, then shall the land keep a sabbath unto the LORD.

3 Six years thou shalt sow thy field, and six years thou shalt prune thy vineyard, and gather in the fruit thereof

4 But in the seventh year shall be a sabbath of rest unto the land, a sabbath for the LORD: thou shalt neither sow thy field, nor prune thy vineyard.

GOD SAID, Leviticus 25: 11-12:

11 A jubilee shall that fiftieth year be unto you: ye shall not sow, neither reap that which groweth of itself in it, nor gather the grapes in it of thy vine undressed.

12 For it is the jubilee it shall be holy unto you: ye shall eat the increase thereof out of the field.

GOD SAID, Galatians 6:7:

Be not deceived God is not mocked: for whatsoever a man soweth, that shall he also reap.

MAN SAID: Our science has mastered agriculture. We can chemically control the pests of the field and our genetically modified products will fill the earth with plenty.

Authorized King James Version

Louis, PF, &ldquoScientists Reveal Why Amish Children are Immune to Allergies & Asthma,&rdquo RealFarmacy.com

Sarah, &ldquoThe Real Reason Wheat is Toxic (it&rsquos not the gluten&rdquo, TheHealthyHomeEconomist.com


Featured Publications of FOEDRC Members

Wolf RM, Liu TYA, Thomas C, Prichett L, Zimmer Galler I, Smith K, Abramoff MD, Channa R. The SEE Study: Safety, Efficacy, and Equity of Implementing Autonomous Artificial Intelligence for Diagnosing Diabetic Retinopathy in Youth. Diabetes Care. 2021 Jan 21:dc201671. doi: 10.2337/dc20-1671. Epub ahead of print. PMID: 33479160.

Ferhaan Ahmad, MD, PhD:

Pereira NL, Ahmad F, Byku M, Cummins NW, Morris AA, Owens A, Tuteja S, Cresci S. COVID-19: Understanding Inter-Individual Variability and Implications for Precision Medicine. Mayo Clin Proc. 2021 Feb96(2):446-463. doi: 10.1016/j.mayocp.2020.11.024. Epub 2020 Dec 3. PMID: 33549263 PMCID: PMC7713605.

James Ankrum, PhD:

Burand AJ Jr, Di L, Boland LK, Boyt DT, Schrodt MV, Santillan DA, Ankrum JA. Aggregation of Human Mesenchymal Stromal Cells Eliminates Their Ability to Suppress Human T Cells. Front Immunol. 2020 Feb 2511:143. doi: 10.3389/fimmu.2020.00143. PMID: 32158443 PMCID: PMC7052295.

Mark Arnold, PhD:

Ye M, Arnold MA. Selectivity and Sensitivity of Near-Infrared Spectroscopic Sensing of β-Hydroxybutyrate, Glucose, and Urea in Ternary Aqueous Solutions. Anal Chem. 2021 Apr 693(13):5586-5595. doi: 10.1021/acs.analchem.1c00300. Epub 2021 Mar 24. PMID: 33760590.

Wei Bao, MD, PhD:

  • Jin Q, Shi N, Aroke D, Lee DH, Joseph JJ, Donneyong M, Conwell DL, Hart PA, Zhang X, Clinton SK, Cruz-Monserrate Z, Brasky TM, Jackson R, Tinker LF, Liu S, Phillips LS, Shadyab AH, Nassir R, Bao W, Tabung FK. Insulinemic and Inflammatory Dietary Patterns Show Enhanced Predictive Potential for Type 2 Diabetes Risk in Postmenopausal Women. Diabetes Care. 2021 Jan 8:dc202216. doi: 10.2337/dc20-2216. Epub ahead of print. PMID: 33419931.
  • Tang J, Chen R, Yu Y, Bao W, Tiemeier H, Rodney A, Zhu X, Li M, Huang D, Zhao Q. Associations of pre-pregnancy impaired fasting glucose and body mass index among pregnant women without pre-existing diabetes with offspring being large for gestational age and preterm birth: a cohort study in China. BMJ Open Diabetes Res Care. 2021 Feb9(1):e001641. doi: 10.1136/bmjdrc-2020-001641. PMID: 33568359.
  • Jasper EA, Cho H, Breheny PJ, Bao W, Dagle JM, Ryckman KK. Perinatal determinants of growth trajectories in children born preterm. PLoS One. 2021 Jan 2816(1):e0245387. doi: 10.1371/journal.pone.0245387. PMID: 33507964 PMCID: PMC7842887.
  • Tang J, Zhu X, Chen Y, Huang D, Tiemeier H, Chen R, Bao W, Zhao Q. Association of maternal pre-pregnancy low or increased body mass index with adverse pregnancy outcomes. Sci Rep. 2021 Feb 1511(1):3831. doi: 10.1038/s41598-021-82064-z. PMID: 33589654 PMCID: PMC7884680.
  • Zheng X, Yang D, Luo S, Yan J, Guo X, Yang H, Bao W, Groop L, Dornhorst A, Weng J CARNATION Study Group. Association of Implementation of a Comprehensive Preconception-to-Pregnancy Management Plan With Pregnancy Outcomes Among Chinese Pregnant Women With Type 1 Diabetes: The CARNATION Study. Diabetes Care. 2021 Feb 24:dc202692. doi: 10.2337/dc20-2692. Epub ahead of print. PMID: 33627365.
  • Liu B, Du Y, Wu Y, Snetselaar LG, Wallace RB, Bao W. Trends in obesity and adiposity measures by race or ethnicity among adults in the United States 2011-18: population based study. BMJ. 2021 Mar 16372:n365. doi: 10.1136/bmj.n365. PMID: 33727242.
  • Sun Y, Liu B, Snetselaar LG, Wallace RB, Shadyab AH, Kroenke CH, Haring B, Howard BV, Shikany JM, Valdiviezo C, Bao W. Association of Major Dietary Protein Sources With All-Cause and Cause-Specific Mortality: Prospective Cohort Study. J Am Heart Assoc. 2021 Feb10(5):e015553. doi: 10.1161/JAHA.119.015553. Epub 2021 Feb 24. PMID: 33624505.
  • Trim A, Hankinson SE, Liu S, Shadyab AH, Meliker J, Bao W, Luo J, Liu B, Manson JE, Tinker L, Bigelow C, Reeves KW. Biomarkers of phthalates and inflammation: Findings from a subgroup of Women's Health Initiative participants. Int J Hyg Environ Health. 2021 Apr 1234:113743. doi: 10.1016/j.ijheh.2021.113743. Epub ahead of print. PMID: 33813346.

Melissa Bates, PhD:

Vasilyev M, Berschel MR, Tomasson MH, Bates ML. Viewpoint: Time to stop treating the heart as a single organ? Exp Physiol. 2021 Mar 17. doi: 10.1113/EP089497. Epub ahead of print. PMID: 33728739.

Christopher Benson, MD:

Khataei T, Romig-Martin SA, Harding AMS, Radley JJ, Benson CJ. Comparison of murine behavioral and physiologic responses after forced exercise by electrical shock vs. manual prodding. Exp Physiol. 2021 Feb 1. doi: 10.1113/EP089117. Epub ahead of print. PMID: 33527606.

Sue Bodine, PhD:

  • Hughes DC, Turner DC, Baehr LM, Seaborne RA, Viggars M, Jarvis JC, Gorski PP, Stewart CE, Owens DJ, Bodine SC, Sharples AP. Knockdown of the E3 ubiquitin ligase UBR5 and its role in skeletal muscle anabolism. Am J Physiol Cell Physiol. 2021 Jan 1320(1):C45-C56. doi: 10.1152/ajpcell.00432.2020. Epub 2020 Oct 14. PMID: 33052072.
  • Davidyan A, Pathak S, Baar K, Bodine SC. Maintenance of muscle mass in adult male mice is independent of testosterone. PLoS One. 2021 Mar 2516(3):e0240278. doi: 10.1371/journal.pone.0240278. PMID: 33764986 PMCID: PMC7993603.

Lucas Carr, PhD:

Thompson HG, Whitaker KM, Young R, Carr LJ. University stakeholders largely unaware and unsupportive of university pouring rights contracts with companies supplying sugar-sweetened beverages. J Am Coll Health. 2021 Mar 24:1-8. doi: 10.1080/07448481.2021.1891920. Epub ahead of print. PMID: 33760721.

Darren Casey, PhD:

  • Casey DP, Bock JM. Inorganic nitrate supplementation attenuates conduit artery retrograde and oscillatory shear in older adults. Am J Physiol Heart Circ Physiol. 2021 Jan 15. doi: 10.1152/ajpheart.00843.2020. Epub ahead of print. PMID: 33449848.
  • Bock JM, Hughes WE, Ueda K, Feider AJ, Hanada S, Casey DP. Glycemic management is inversely related to skeletal muscle microvascular endothelial function in patients with type 2 diabetes. Physiol Rep. 2021 Mar9(5):e14764. doi: 10.14814/phy2.14764. PMID: 33660935.

Kris DeMali, PhD:

DeWane G, Salvi AM, DeMali KA. Fueling the cytoskeleton - links between cell metabolism and actin remodeling. J Cell Sci. 2021 Feb 8134(3):jcs248385. doi: 10.1242/jcs.248385. PMID: 33558441 PMCID: PMC7888749.

Joseph Dillon, MB, BCh, BAO:

  • Dillon JS, Bushnell D, Laux DE. High-specific-activity 131iodine-metaiodobenzylguanidine for therapy of unresectable pheochromocytoma and paraganglioma. Future Oncol. 2021 Jan 28. doi: 10.2217/fon-2020-0625. Epub ahead of print. PMID: 33506713.
  • Scott AT, Tessmann JB, Braun T, Brown B, Breheny PJ, Darbro BW, Bellizzi AM, Dillon JS, O'Dorisio TM, Alderson A, Bennett B, Bernat JA, Metz DC, Howe JR. Presacral neuroendocrine tumors associated with the Currarino syndrome. Am J Med Genet A. 2021 Mar 1. doi: 10.1002/ajmg.a.62145. Epub ahead of print. PMID: 33650152.
  • Jha A, Taieb D, Carrasquillo JA, Pryma DA, Patel M, Millo C, de Herder WW, Del Rivero J, Crona J, Shulkin BL, Virgolini I, Chen AP, Mittal BR, Basu S, Dillon JS, Hope TA, Mari Aparici C, Iagaru A, Hicks RJ, Avram AM, Strosberg JR, Civelek AC, Lin FI, Pandit-Taskar N, Pacak K. High-specific-activity 131I-MIBG vs 177Lu-DOTATATE targeted radionuclide therapy for metastatic pheochromocytoma and paraganglioma. Clin Cancer Res. 2021 Mar 8:clincanres.3703.2020. doi: 10.1158/1078-0432.CCR-20-3703. Epub ahead of print. PMID: 33685867.

John Engelhardt, PhD:

  • Gibson-Corley KN, Engelhardt JF. Animal Models and Their Role in Understanding the Pathophysiology of Cystic Fibrosis-Associated Gastrointestinal Lesions. Annu Rev Pathol. 2021 Jan 2416:51-67. doi: 10.1146/annurev-pathol-022420-105133. PMID: 33497264.
  • Choi SH, Engelhardt JF. Gene Therapy for Cystic Fibrosis: Lessons Learned and Paths Forward. Mol Ther. 2021 Jan 12:S1525-0016(21)00010-1. doi: 10.1016/j.ymthe.2021.01.010. Epub ahead of print. PMID: 33472034.

Frank Faraci, PhD:

Claassen JAHR, Thijssen DHJ, Panerai RB, Faraci FM. REGULATION OF CEREBRAL BLOOD FLOW IN HUMANS: PHYSIOLOGY AND CLINICAL IMPLICATIONS OF AUTOREGULATION. Physiol Rev. 2021 Mar 26. doi: 10.1152/physrev.00022.2020. Epub ahead of print. PMID: 33769101.

Edward Filardo, PhD:

Lu AS, Rouhimoghadam M, Arnatt CK, Filardo EJ, Salem AK. Proteolytic Targeting Chimeras with Specificity for Plasma Membrane and Intracellular Estrogen Receptors. Mol Pharm. 2021 Mar 118(3):1455-1469. doi: 10.1021/acs.molpharmaceut.1c00018. Epub 2021 Feb 18. PMID: 33600191.

James Folk, MD:

Li AS, Velez G, Darbro B, Toral MA, Yang J, Tsang SH, Ferguson PJ, Folk JC, Bassuk AG, Mahajan VB. Whole-Exome Sequencing of Patients With Posterior Segment Uveitis. Am J Ophthalmol. 2021 Jan221:246-259. doi: 10.1016/j.ajo.2020.07.021. Epub 2020 Jul 21. PMID: 32707200 PMCID: PMC7736069.

Bernd Fritzsch, PhD:

  • Jahan I, Kersigo J, Elliott KL, Fritzsch B. Smoothened overexpression causes trochlear motoneurons to reroute and innervate ipsilateral eyes. Cell Tissue Res. 2021 Jan 6. doi: 10.1007/s00441-020-03352-0. Epub ahead of print. PMID: 33409653.
  • Xu J, Li J, Zhang T, Jiang H, Ramakrishnan A, Fritzsch B, Shen L, Xu PX. Chromatin remodelers and lineage-specific factors interact to target enhancers to establish proneurosensory fate within otic ectoderm. Proc Natl Acad Sci U S A. 2021 Mar 23118(12):e2025196118. doi: 10.1073/pnas.2025196118. PMID: 33723076.

Mark Greiner, MD:

Skeie JM, Nishimura DY, Wang CL, Schmidt GA, Aldrich BT, Greiner MA. Mitophagy: An Emerging Target in Ocular Pathology. Invest Ophthalmol Vis Sci. 2021 Mar 162(3):22. doi: 10.1167/iovs.62.3.22. PMID: 33724294.

Chad Grueter, PhD:

Alghanem AF, Abello J, Maurer JM, Kumar A, Ta CM, Gunasekar SK, Fatima U, Kang C, Xie L, Adeola O, Riker M, Elliot-Hudson M, Minerath RA, Grueter CE, Mullins RF, Stratman AN, Sah R. The SWELL1-LRRC8 complex regulates endothelial AKT-eNOS signaling and vascular function. Elife. 2021 Feb 2510:e61313. doi: 10.7554/eLife.61313. Epub ahead of print. PMID: 33629656.

Yumi Imai, MD:

  • Mishra A, Liu S, Promes J, Harata M, Sivitz WI, Fink BD, Bhardwaj G, O'Neill BT, Kang C, Sah R, Strack S, Stephens SB, King TH, Jackson L, Greenberg AS, Anokye-Danso F, Ahima RS, Ankrum JA, Imai Y. Perilipin2 down-regulation in β cells impairs insulin secretion under nutritional stress and damages mitochondria. JCI Insight. 2021 Mar 30:144341. doi: 10.1172/jci.insight.144341. Epub ahead of print. PMID: 33784258.

Randy Kardon, MD, PhD:

Reggie SN, Avery RA, Bavinger JC, Jivraj I, Alfaro C, Pistilli M, Kohli AA, Liu GT, Shindler KS, Ross AG, Kardon RH, Sibony PA, Tamhankar M. The sensitivity and specificity of retinal and choroidal folds to distinguish between mild papilloedema and pseudopapilledema. Eye (Lond). 2021 Jan 19. doi: 10.1038/s41433-020-01368-y. Epub ahead of print. PMID: 33469131.

Robert Kerns, PhD:

Kulkarni CA, Fink BD, Gibbs BE, Chheda PR, Wu M, Sivitz WI, Kerns RJ. A Novel Triphenylphosphonium Carrier to Target Mitochondria without Uncoupling Oxidative Phosphorylation. J Med Chem. 2021 Jan 1464(1):662-676. doi: 10.1021/acs.jmedchem.0c01671. Epub 2021 Jan 4. PMID: 33395531.

Catherina Pinnaro, MD:

  • O'Malley G, Ebekozien O, Desimone M, Pinnaro CT, Roberts A, Polsky S, Noor N, Aleppo G, Basina M, Tansey M, Steenkamp D, Vendrame F, Lorincz I, Mathias P, Agarwal S, Golden L, Hirsch IB, Levy CJ. COVID-19 Hospitalization in Adults with Type 1 Diabetes: Results from the T1D Exchange Multicenter Surveillance Study. J Clin Endocrinol Metab. 2021 Jan 23106(2):e936-e942. doi: 10.1210/clinem/dgaa825. PMID: 33165563 PMCID: PMC7717244.

Matthew Potthoff, PhD:

Flippo KH, Potthoff MJ. Metabolic Messengers: FGF21. Nat Metab. 2021 Mar3(3):309-317. doi: 10.1038/s42255-021-00354-2. Epub 2021 Mar 18. PMID: 33758421.

Kamal Rahmouni, PhD:

Rouabhi M, Guo DF, Morgan DA, Zhu Z, López M, Zingman L, Grobe JL, Rahmouni K. BBSome Ablation in SF1 Neurons Causes Obesity without the Comorbidities. Mol Metab. 2021 Mar 12:101211. doi: 10.1016/j.molmet.2021.101211. Epub ahead of print. PMID: 33722691.

Jennifer Robinson, MD:

  • Robinson JG. The neuropsychology of statin intolerance. Nat Rev Cardiol. 2021 Jan 6. doi: 10.1038/s41569-020-00502-3. Epub ahead of print. PMID: 33408360.
  • Navar AM, Wang TY, Li S, Mi X, Li Z, Robinson JG, Virani SS, Peterson ED. Patient-Perceived Versus Actual Risk of Cardiovascular Disease and Associated Willingness to Consider and Use Prevention Therapy. Circ Cardiovasc Qual Outcomes. 2021 Jan14(1):e006548. doi: 10.1161/CIRCOUTCOMES.120.006548. Epub 2021 Jan 13. PMID: 33435730.
  • Qian F, Ardisson Korat AV, Imamura F, Marklund M, Tintle N, Virtanen JK, Zhou X, Bassett JK, Lai H, Hirakawa Y, Chien KL, Wood AC, Lankinen M, Murphy RA, Samieri C, Pertiwi K, de Mello VD, Guan W, Forouhi NG, Wareham N, Hu ICFB, Riserus U, Lind L, Harris WS, Shadyab AH, Robinson JG, Steffen LM, Hodge A, Giles GG, Ninomiya T, Uusitupa M, Tuomilehto J, Lindström J, Laakso M, Siscovick DS, Helmer C, Geleijnse JM, Wu JHY, Fretts A, Lemaitre RN, Micha R, Mozaffarian D, Sun Q Fatty Acids and Outcomes Research Consortium (FORCE). n-3 Fatty Acid Biomarkers and Incident Type 2 Diabetes: An Individual Participant-Level Pooling Project of 20 Prospective Cohort Studies. Diabetes Care. 2021 Mar 3:dc202426. doi: 10.2337/dc20-2426. Epub ahead of print. PMID: 33658295.
  • Harris WS, Tintle NL, Manson JE, Metherel AH, Robinson JG. Effects of menopausal hormone therapy on erythrocyte n-3 and n-6 PUFA concentrations in the Women's Health Initiative randomized trial. Am J Clin Nutr. 2021 Mar 12:nqaa443. doi: 10.1093/ajcn/nqaa443. Epub ahead of print. PMID: 33710263.

Robert Roghair, MD:

Vass RA, Kiss G, Bell EF, Roghair RD, Miseta A, Bódis J, Funke S, Ertl T. Breast Milk for Term and Preterm Infants-Own Mother's Milk or Donor Milk? Nutrients. 2021 Jan 2813(2):424. doi: 10.3390/nu13020424. PMID: 33525560.

William Sivitz, MD:

Fink BD, Yu L, Coppey L, Obrosov A, Shevalye H, Kerns RJ, Yorek MA, Sivitz WI. Effect of mitoquinone on liver metabolism and steatosis in obese and diabetic rats. Pharmacol Res Perspect. 2021 Feb9(1):e00701. doi: 10.1002/prp2.701. PMID: 33547885.

Linda Snetselaar, PhD:

  • Luo J, Chen X, Tindle H, Shadyab AH, Saquib N, Hale L, Garcia L, Springfield S, Liu B, Nassir R, Snetselaar L, Hendryx M. Do health behaviors mediate associations between personality traits and diabetes incidence? Ann Epidemiol. 2021 Jan53:7-13.e2. doi: 10.1016/j.annepidem.2020.08.007. Epub 2020 Aug 15. PMID: 32805399.
  • Weaver CM, Fukagawa NK, Liska D, Mattes RD, Matuszek G, Nieves JW, Shapses SA, Snetselaar LG. Perspective: US Documentation and Regulation of Human Nutrition Randomized Controlled Trials. Adv Nutr. 2021 Feb 112(1):21-45. doi: 10.1093/advances/nmaa118. PMID: 33200185 PMCID: PMC7850145.
  • Bailey RL, Ard JD, Davis TA, Naimi TS, Schneeman BO, Stang JS, Dewey KG, Donovan SM, Novotny R, Snetselaar LG, de Jesus J, Casavale KO, Pannucci T, Stoody EE. A Proposed Framework for Identifying Nutrients and Food Components of Public Health Relevance in the Dietary Guidelines for Americans. J Nutr. 2021 Mar 9:nxaa459. doi: 10.1093/jn/nxaa459. Epub ahead of print. PMID: 33693925.

Long-Sheng Song, MD:

Romer SH, Metzger S, Peraza K, Wright MC, Jobe DS, Song LS, Rich MM, Foy BD, Talmadge RJ, Voss AA. A mouse model of Huntington's disease shows altered ultrastructure of transverse tubules in skeletal muscle fibers. J Gen Physiol. 2021 Apr 5153(4):e202012637. doi: 10.1085/jgp.202012637. PMID: 33683318.

Elliott Sohn, MD:

Ricca AM, Han IC, Sohn EH. Stargardt disease masquerades. Curr Opin Ophthalmol. 2021 Feb 26. doi: 10.1097/ICU.0000000000000750. Epub ahead of print. PMID: 33653979.

Milan Sonka, PhD:

van der Plas E, Gutmann L, Thedens D, Shields RK, Langbehn K, Guo Z, Sonka M, Nopoulos P. Quantitative muscle MRI as a sensitive marker of early muscle pathology in myotonic dystrophy type 1. Muscle Nerve. 2021 Jan 18. doi: 10.1002/mus.27174. Epub ahead of print. PMID: 33462896.

David Stoltz, MD, PhD:

Fischer AJ, Singh SB, LaMarche MM, Maakestad LJ, Kienenberger ZE, Peña TA, Stoltz DA, Limoli DH. Sustained Coinfections with Staphylococcus aureus and Pseudomonas aeruginosa in Cystic Fibrosis. Am J Respir Crit Care Med. 2021 Feb 1203(3):328-338. doi: 10.1164/rccm.202004-1322OC. PMID: 32750253 PMCID: PMC7874317.

Michael Tansey, MD:

Mauras N, Buckingham B, White NH, Tsalikian E, Weinzimer SA, Jo B, Cato A, Fox LA, Aye T, Arbelaez AM, Hershey T, Tansey M, Tamborlane W, Foland-Ross LC, Shen H, Englert K, Mazaika P, Marzelli M, Reiss AL Diabetes Research in Children Network (DirecNet). Impact of Type 1 Diabetes in the Developing Brain in Children: A Longitudinal Study. Diabetes Care. 2021 Feb 10:dc202125. doi: 10.2337/dc20-2125. Epub ahead of print. PMID: 33568403.

Yuriy Usachev, PhD:

Rysted JE, Lin Z, Walters GC, Rauckhorst AJ, Noterman M, Liu G, Taylor EB, Strack S, Usachev YM. Distinct properties of Ca2+ efflux from brain, heart and liver mitochondria: The effects of Na+, Li+ and the mitochondrial Na+/Ca2+ exchange inhibitor CGP37157. Cell Calcium. 2021 Feb 2296:102382. doi: 10.1016/j.ceca.2021.102382. Epub ahead of print. PMID: 33684833.

Michael Welsh, MD:

Simmering JE, Welsh MJ, Liu L, Narayanan NS, Pottegård A. Association of Glycolysis-Enhancing α-1 Blockers With Risk of Developing Parkinson Disease. JAMA Neurol. 2021 Feb 1. doi: 10.1001/jamaneurol.2020.5157. Epub ahead of print. PMID: 33523098.

Ling Yang, PhD:

Krongbaramee T, Zhu M, Qian Q, Zhang Z, Eliason S, Shu Y, Qian F, Akkouch A, Su D, Amendt BA, Yang L, Hong L. Plasmid encoding microRNA-200c ameliorates periodontitis and systemic inflammation in obese mice. Mol Ther Nucleic Acids. 2021 Feb 423:1204-1216. doi: 10.1016/j.omtn.2021.01.030. PMID: 33664998 PMCID: PMC7899952.

E. Dale Abel, MD, PhD:

  • Li X, Wu J, Sun X, Wu Q, Li Y, Li K, Zhang Q, Li Y, Abel ED, Chen H. Autophagy Reprograms Alveolar Progenitor Cell Metabolism in Response to Lung Injury. Stem Cell Reports. 2020 Mar 1014(3):420-432. doi: 10.1016/j.stemcr.2020.01.008. Epub 2020 Feb 13. PMID: 32059792 PMCID: PMC7066233
  • Shanmugam G, Wang D, Gounder SS, Fernandes J, Litovsky SH, Whitehead K, Radhakrishnan RK, Franklin S, Hoidal J, Kensler TW, Dell'Italia L, Darley-Usmar V, Abel ED, Jones DP, Ping P, Namakkal Soorappan R. Reductive Stress Causes Pathological Cardiac Remodeling and Diastolic Dysfunction. Antioxid Redox Signal. 2020 Feb 16:10.1089/ars.2019.7808. doi: 10.1089/ars.2019.7808. Epub ahead of print. PMID: 3206489
  • Riehle C, Weatherford ET, Wende AR, Jaishy BP, Seei AW, McCarty NS, Rech M, Shi Q, Reddy GR, Kutschke WJ, Oliveira K, Pires KM, Anderson JC, Diakos NA, Weiss RM, White MF, Drakos SG, Xiang YK, Abel ED. Insulin receptor substrates differentially exacerbate insulin-mediated left ventricular remodeling. JCI Insight. 2020 Mar 265(6):e134920. doi: 10.1172/jci.insight.134920. PMID: 32213702 PMCID: PMC7213803.
  • Ponce JM, Coen G, Spitler KM, Dragisic N, Martins I, Hinton A Jr, Mungai M, Tadinada SM, Zhang H, Oudit GY, Song LS, Li N, Sicinski P, Strack S, Abel ED, Mitchell C, Hall DD, Grueter CE. Stress-Induced Cyclin C Translocation Regulates Cardiac Mitochondrial Dynamics. J Am Heart Assoc. 2020 Apr 79(7):e014366. doi: 10.1161/JAHA.119.014366. Epub 2020 Apr 4. PMID: 32248761.
  • Badolia R, Ramadurai DKA, Abel ED, Ferrin P, Taleb I, Shankar TS, Thodou Krokidi A, Navankasattusas S, McKellar SH, Yin M, Kfoury AG, Wever-Pinzon O, Fang JC, Selzman CH, Chaudhuri D, Rutter J, Drakos SG. The Role of Non-Glycolytic Glucose Metabolism in Myocardial Recovery upon Mechanical Unloading and Circulatory Support in Chronic Heart Failure. Circulation. 2020 Apr 30. doi: 10.1161/CIRCULATIONAHA.119.044452. Epub ahead of print. PMID: 32351122.
  • Wende AR, Schell JC, Ha CM, Pepin ME, Khalimonchuk O, Schwertz H, Pereira RO, Brahma MK, Tuinei J, Contreras-Ferrat A, Wang L, Andrizzi CA, Olsen CD, Bradley WE, Dell'Italia LJ, Dillmann WH, Litwin SE, Abel ED. Maintaining Myocardial Glucose Utilization in Diabetic Cardiomyopathy Accelerates Mitochondrial Dysfunction. Diabetes. 2020 May 4:db191057. doi: 10.2337/db19-1057. Epub ahead of print. PMID: 32366681.
  • Veys K, Fan Z, Ghobrial M, Bouché A, García-Caballero M, Vriens K, Conchinha NV, Seuwen A, Schlegel F, Gorski T, Crabbé M, Gilardoni P, Ardicoglu R, Schaffenrath J, Casteels C, De Smet G, Smolders I, Van Laere K, Abel ED, Fendt SM, Schroeter A, Kalucka J, Cantelmo AR, Wälchli T, Keller A, Carmeliet P, De Bock K. Role of the GLUT1 Glucose Transporter in Postnatal CNS Angiogenesis and Blood-Brain Barrier Integrity. Circ Res. 2020 May 14. doi: 10.1161/CIRCRESAHA.119.316463. Epub ahead of print. PMID: 32404031.
  • Ritchie RH, Abel ED. Basic Mechanisms of Diabetic Heart Disease. Circ Res. 2020 May 22126(11):1501-1525. doi: 10.1161/CIRCRESAHA.120.315913. Epub 2020 May 21. PMID: 32437308.
  • Contat C, Ancey PB, Zangger N, Sabatino S, Pascual J, Escrig S, Jensen L, Goepfert C, Lanz B, Lepore M, Gruetter R, Rossier A, Berezowska S, Neppl C, Zlobec I, Clerc-Rosset S, Knott GW, Rathmell JC, Abel ED, Meibom A, Meylan E. Combined deletion of Glut1 and Glut3 impairs lung adenocarcinoma growth. Elife. 2020 Jun 239. pii: e53618. doi: 10.7554/eLife.53618. PubMed PMID: 32571479 PubMed Central PMCID: PMC7311173.
  • Li B, Lee WC, Song C, Ye L, Abel ED, Long F. Both aerobic glycolysis and mitochondrial respiration are required for osteoclast differentiation. FASEB J. 2020 Jul 6. doi: 10.1096/fj.202000771R. [Epub ahead of print] PubMed PMID: 32627870.
  • Brahma MK, Ha CM, Pepin ME, Mia S, Sun Z, Chatham JC, Habegger KM, Abel ED, Paterson AJ, Young ME, Wende AR. Increased Glucose Availability Attenuates Myocardial Ketone Body Utilization. J Am Heart Assoc. 2020 Aug 49(15):e013039. doi: 10.1161/JAHA.119.013039. Epub 2020 Jul 30. PMID: 32750298.
  • Kumar A, Xie L, Ta CM, Hinton AO, Gunasekar SK, Minerath RA, Shen K, Maurer JM, Grueter CE, Abel ED, Meyer G, Sah R. SWELL1 regulates skeletal muscle cell size, intracellular signaling, adiposity and glucose metabolism. Elife. 2020 Sep 159:e58941. doi: 10.7554/eLife.58941. PMID: 32930093 PMCID: PMC7541086.
  • Zhang Y, Taufalele PV, Cochran JD, Robillard-Frayne I, Marx JM, Soto J, Rauckhorst AJ, Tayyari F, Pewa AD, Gray LR, Teesch LM, Puchalska P, Funari TR, McGlauflin R, Zimmerman K, Kutschke WJ, Cassier T, Hitchcock S, Lin K, Kato KM, Stueve JL, Haff L, Weiss RM, Cox JE, Rutter J, Taylor EB, Crawford PA, Lewandowski ED, Des Rosiers C, Abel ED. Mitochondrial pyruvate carriers are required for myocardial stress adaptation. Nat Metab. 2020 Nov2(11):1248-1264. doi: 10.1038/s42255-020-00288-1. Epub 2020 Oct 26. Erratum in: Nat Metab. 2020 Nov 18: PMID: 33106689.
  • Tang M, Park SH, Petri S, Yu H, Rueda CB, Abel ED, Kim CY, Hillman EMC, Li F, Lee Y, Ding L, Jagadish S, Frankel WN, De Vivo DC, Monani UR. An early endothelial cell-specific requirement for Glut1 is revealed in Glut1 deficiency syndrome model mice. JCI Insight. 2020 Dec 22:145789. doi: 10.1172/jci.insight.145789. Epub ahead of print. PMID: 33351789.

Michael Abramoff, MD, PhD:

  • Channa R, Wolf R, Abramoff MD. Autonomous Artificial Intelligence in Diabetic Retinopathy: From Algorithm to Clinical Application. J Diabetes Sci Technol. 2020Mar 4:1932296820909900. doi: 10.1177/1932296820909900. [Epub ahead of print] PubMed PMID: 32126819.
  • Abramoff MD, Leng T, Ting DSW, Rhee K, Horton MB, Brady CJ, Chiang MF. Automated and Computer-Assisted Detection, Classification, and Diagnosis of Diabetic Retinopathy. Telemed J E Health. 2020 Mar 16. doi: 10.1089/tmj.2020.0008. [Epub ahead of print] PubMed PMID: 32209008.
  • van de Kreeke JA, Darma S, Chan Pin Yin JMPL, Tan HS, Abramoff MD, Twisk JWR, Verbraak FD. The spatial relation of diabetic retinal neurodegeneration with diabetic retinopathy. PLoS One. 2020 Apr 1615(4):e0231552. doi: 10.1371/journal.pone.0231552. eCollection 2020. PubMed PMID: 32298369 PubMed Central PMCID: PMC7161968.
  • Folk JC, Abràmoff MD. Evaluation and Care of Patients with Diabetic Retinopathy. N Engl J Med. 2020 Jul 30383(5):e31. doi: 10.1056/NEJMc2018871. PMID: 32726543.
  • Wolf RM, Channa R, Abramoff MD, Lehmann HP. Cost-effectiveness of Autonomous Point-of-Care Diabetic Retinopathy Screening for Pediatric Patients With Diabetes. JAMA Ophthalmol. 2020 Sep 3138(10):1–7. doi: 10.1001/jamaophthalmol.2020.3190. Epub ahead of print. PMID: 32880616 PMCID: PMC7489415.
  • Singh RP, Hom GL, Abramoff MD, Campbell JP, Chiang MF AAO Task Force on Artificial Intelligence. Current Challenges and Barriers to Real-World Artificial Intelligence Adoption for the Healthcare System, Provider, and the Patient. Transl Vis Sci Technol. 2020 Aug 119(2):45. doi: 10.1167/tvst.9.2.45. PMID: 32879755 PMCID: PMC7443115.
  • Char DS, Abràmoff MD, Feudtner C. Identifying Ethical Considerations for Machine Learning Healthcare Applications. Am J Bioeth. 2020 Nov20(11):7-17. doi: 10.1080/15265161.2020.1819469. PMID: 33103967.
  • Sun JK, Aiello LP, Abràmoff MD, Antonetti DA, Dutta S, Pragnell M, Levine SR, Gardner TW. Updating the Staging System for Diabetic Retinal Disease. Ophthalmology. 2020 Nov 17:S0161-6420(20)31005-8. doi: 10.1016/j.ophtha.2020.10.008. Epub ahead of print. PMID: 33218709.

Christopher Adams, MD, PhD:

  • Ebert SM, Bullard SA, Basisty N, Marcotte GR, Skopec ZP, Dierdorff JM, Al-Zougbi A, Tomcheck KC, DeLau AD, Rathmacher JA, Bodine SC, Schilling B, Adams CM. Activating transcription factor 4 (ATF4) promotes skeletal muscle atrophy by forming a heterodimer with the transcriptional regulator C/EBPβ. J Biol Chem. 2020 Jan 17. pii: jbc.RA119.012095. doi: 10.1074/jbc.RA119.012095. [Epub ahead of print] PubMed PMID: 31953319.
  • Rasmussen BB, Adams CM. ATF4 Is a Fundamental Regulator of Nutrient Sensing and Protein Turnover. J Nutr. 2020 Mar 19. pii: nxaa067. doi: 10.1093/jn/nxaa067. [Epub ahead of print] PubMed PMID: 32190894.

Ferhaan Ahmad, MD, PhD

  • Simon MA, Ahmad F, Eitzman DT, Gupta AK, Jneid H, Peterson P, Remme CA, Rice K, Schelbert EB, Sullivan LM, Weinberg JM. Equity, Diversity, and Inclusiveness in Cardiovascular Medicine and Healthcare. J Am Heart Assoc. 2020 Sep 17:e018288. doi: 10.1161/JAHA.120.019137. Epub ahead of print. PMID: 32941102.
  • London B, Ahmad F, Eitzman DT, Gupta AK, Jneid H, Peterson P, Remme CA, Rice K, Schelbert EB, Simon MA, Sullivan LM, Weinberg JM. Diversity, Equity, and Inclusiveness in Medicine and Cardiology: Next Steps for JAHA. J Am Heart Assoc. 2020 Sep 17:e018288. doi: 10.1161/JAHA.120.019307. Epub ahead of print. PMID: 32941090.
  • Simon MA, Ahmad F, Eitzman DT, Gupta AK, Jneid H, Peterson P, Remme CA, Rice K, Schelbert EB, Sullivan LM, Weinberg JM. Equity, Diversity, and Inclusiveness in Cardiovascular Medicine and Health Care. J Am Heart Assoc. 2020 Oct 209(20):e019137. doi: 10.1161/JAHA.120.019137. Epub 2020 Sep 17. PMID: 32941102.
  • London B, Ahmad F, Eitzman DT, Gupta AK, Jneid H, Peterson P, Remme CA, Rice K, Schelbert EB, Simon MA, Sullivan LM, Weinberg JM. Diversity, Equity, and Inclusiveness in Medicine and Cardiology: Next Steps for JAHA. J Am Heart Assoc. 2020 Oct 209(20):e019307. doi: 10.1161/JAHA.120.019307. Epub 2020 Sep 17. PMID: 32941090.

Ethan Anderson, PhD:

  • Nelson MM, Efird J, Kew KA, Katunga LA, Monroe TB, Doorn JJ, Beatty CN, Shi Q, Akhter S, Alwair H, Robidoux J, Anderson EJ. Enhanced catecholamine flux and impaired carbonyl metabolism disrupt cardiac mitochondrial OxPHOS in diabetes patients. Antioxid Redox Signal. 2020 Oct 16. doi: 10.1089/ars.2020.8122. Epub ahead of print. PMID: 33066717.

James Ankrum, PhD:

  • Moll G, Hoogduijn MJ, Ankrum JA. Editorial: Safety, Efficacy and Mechanisms of Action of Mesenchymal Stem Cell Therapies. Front Immunol. 2020 Feb 1811:243. doi: 10.3389/fimmu.2020.00243. eCollection 2020. PubMed PMID: 32133010 PubMed Central PMCID: PMC7040069.
  • Burand AJ Jr, Di L, Boland LK, Boyt DT, Schrodt MV, Santillan DA, Ankrum JA. Aggregation of Human Mesenchymal Stromal Cells Eliminates Their Ability to Suppress Human T Cells. Front Immunol. 2020 Feb 2511:143. doi: 10.3389/fimmu.2020.00143. eCollection 2020. PubMed PMID: 32158443 PubMed Central PMCID: PMC7052295.
  • Boyt DT, Boland LK, Burand AJ Jr, Brown AJ, Ankrum JA. Dose and duration of interferon γ pre-licensing interact with donor characteristics to influence the expression and function of indoleamine-2,3-dioxygenase in mesenchymal stromal cells. J R Soc Interface. 2020 Jun17(167):20190815. doi: 10.1098/rsif.2019.0815. Epub 2020 Jun 17. PubMed PMID: 32546114.
  • El-Hattab MY, Nagumo Y, Gourronc FA, Klingelhutz AJ, Ankrum JA, Sander EA. Human Adipocyte Conditioned Medium Promotes In Vitro Fibroblast Conversion to Myofibroblasts. Sci Rep. 2020 Jun 2410(1):10286. doi: 10.1038/s41598-020-67175-3. PubMed PMID: 32581231 PubMed Central PMCID: PMC7314785.

Deniz Atasoy, PhD:

Aklan I, Sayar Atasoy N, Yavuz Y, Ates T, Coban I, Koksalar F, Filiz G, Topcu IC, Oncul M, Dilsiz P, Cebecioglu U, Alp MI, Yilmaz B, Davis DR, Hajdukiewicz K, Saito K, Konopka W, Cui H, Atasoy D. NTS Catecholamine Neurons Mediate Hypoglycemic Hunger via Medial Hypothalamic Feeding Pathways. Cell Metab. 2020 Feb 431(2):313-326.e5. doi: 10.1016/j.cmet.2019.11.016. Epub 2019 Dec 12. PMID: 31839488.

Wei Bao, MD, PhD:

  • Li M, Rahman ML, Wu J, Ding M, Chavarro JE, Lin Y, Ley SH, Bao W, Grunnet LG, Hinkle SN, Thuesen ACB, Yeung E, Gore-Langton RE, Sherman S, Hjort L, Kampmann FB, Bjerregaard AA, Damm P, Tekola-Ayele F, Liu A, Mills JL, Vaag A, Olsen SF, Hu FB, Zhang C. Genetic factors and risk of type 2 diabetes among women with a history of gestational diabetes: findings from two independent populations. BMJ Open Diabetes Res Care. 2020 Jan8(1):e000850. doi: 10.1136/bmjdrc-2019-000850. PMID: 31958311.
  • ​Rong S, Wang L, Peng Z, Liao Y, Li D, Yang X, Nuessler AK, Liu L, Bao W, Yang W. The mechanisms and treatments for sarcopenia: could exosomes be a perspective research strategy in the future? J Cachexia Sarcopenia Muscle. 2020 Jan 2710.1002/jcsm.12536. doi: 10.1002/jcsm.12536. [Epub ahead of print]. PMID: 31989804.
  • Ley SH, Chavarro JE, Li M, Bao W, Hinkle SN, Wander PL, Rich-Edwards J, Olsen S, Vaag A, Damm P, Grunnet LG, Mills JL, Hu FB, Zhang C. Lactation Duration and Long-term Risk for Incident Type 2 Diabetes in Women With a History of Gestational Diabetes Mellitus. Diabetes Care. 2020 Feb 10:dc192237. doi: 10.2337/dc19-2237. Epub ahead of print. PMID: 32041900.
  • Peng X, Xu Z, Mo X, Guo Q, Yin J, Xu M, Peng Z, Sun T, Zhou L, Peng X, Xu S, Yang W, Bao W, Shan Z, Li X, Liu L. Association of plasma β-amyloid 40 and 42 concentration with type 2 diabetes among Chinese adults. Diabetologia. 2020 Feb 7:10.1007/s00125-020-05102-x. doi: 10.1007/s00125-020-05102-x. Epub ahead of print. PMID: 32034441.
  • Snyder BM, Baer RJ, Oltman SP, Robinson JG, Breheny PJ, Saftlas AF, Bao W, Greiner AL, Carter KD, Rand L, Jelliffe-Pawlowski LL, Ryckman KK. Early pregnancy prediction of gestational diabetes mellitus risk using prenatal screening biomarkers in nulliparous women. Diabetes Res Clin Pract. 2020 Apr 6163:108139. doi: 10.1016/j.diabres.2020.108139. [Epub ahead of print] PubMed PMID: 32272192.
  • Sun Y, Liu B, Smith JK, Correia MLG, Jones DL, Zhu Z, Taiwo A, Morselli LL, Robinson K, Hart AA, Snetselaar LG, Bao W. Association of Preoperative Body Weight and Weight Loss With Risk of Death After Bariatric Surgery. JAMA Netw Open. 2020 May 13(5):e204803. doi: 10.1001/jamanetworkopen.2020.4803. PubMed PMID: 32407504 PubMed Central PMCID: PMC7225906.
  • Gao C, Liu Y, Gan Y, Bao W, Peng X, Xing Q, Gao H, Lai J, Liu L, Wang Z, Yang Y. Effects of fish oil supplementation on glucose control and lipid levels among patients with type 2 diabetes mellitus: a Meta-analysis of randomized controlled trials. Lipids Health Dis. 2020 May 819(1):87. doi: 10.1186/s12944-020-01214-w. PubMed PMID: 32384902 PubMed Central PMCID: PMC7206824.
  • Chen G, Li Y, Zeng F, Deng G, Liang J, Wang J, Su Y, Chen Y, Mao L, Liu Z, Bao W, Zhang Z. Biomarkers of fatty acids and risk of type 2 diabetes: a systematic review and meta-analysis of prospective cohort studies. Crit Rev Food Sci Nutr. 2020 Jun 29:1-14. doi: 10.1080/10408398.2020.1784839. Epub ahead of print. PMID: 32598176.
  • Xu J, Hussain S, Lu G, Zheng K, Wei S, Bao W, Zhang L. Associations of Stay-at-Home Order and Face-Masking Recommendation with Trends in Daily New Cases and Deaths of Laboratory-Confirmed COVID-19 in the United States. Explor Res Hypothesis Med. 2020 Jul 8:1-10. doi: 10.14218/ERHM.2020.00045. PMID: 32734759 PMCID: PMC7361445.
  • Bao W, Liu B, Rong S, Dai SY, Trasande L, Lehmler HJ. Association Between Bisphenol A Exposure and Risk of All-Cause and Cause-Specific Mortality in US Adults. JAMA Netw Open. 2020 Aug 33(8):e2011620. doi: 10.1001/jamanetworkopen.2020.11620. PMID: 32804211.
  • Hart A, Goffredo P, Carroll R, Lehmann R, Nau P, Smith J, Ahad S, Bao W, Hassan I. Optimizing Bariatric Surgery outcomes: the impact of preoperative elevated hemoglobin A1c levels on composite perioperative outcome measures. Surg Endosc. 2020 Aug 12. doi: 10.1007/s00464-020-07887-9. Epub ahead of print. PMID: 32789589.
  • Sun Y, Liu B, Rong S, Du Y, Xu G, Snetselaar LG, Wallace RB, Bao W. Food Insecurity Is Associated With Cardiovascular and All-Cause Mortality Among Adults in the United States. J Am Heart Assoc. 2020 Sep 25:e014629. doi: 10.1161/JAHA.119.014629. Epub ahead of print. PMID: 32975173.
  • Qin C, Hu J, Wan Y, Cai M, Wang Z, Peng Z, Liao Y, Li D, Yao P, Liu L, Rong S, Bao W, Xu G, Yang W. Narrative review on potential role of gut microbiota in certain substance addiction. Prog Neuropsychopharmacol Biol Psychiatry. 2020 Sep 6:110093. doi: 10.1016/j.pnpbp.2020.110093. Epub ahead of print. PMID: 32898589.
  • Wu Y, Liu B, Sun Y, Du Y, Santillan MK, Santillan DA, Snetselaar LG, Bao W. Association of Maternal Prepregnancy Diabetes and Gestational Diabetes Mellitus With Congenital Anomalies of the Newborn. Diabetes Care. 2020 Oct 21:dc200261. doi: 10.2337/dc20-0261. Epub ahead of print. PMID: 33087319.
  • Gao R, Liu B, Yang W, Wu Y, Snetselaar LG, Santillan MK, Bao W. Association between maternal pre-pregnancy body mass index and risk of preterm birth in more than 1 million Asian American mothers. J Diabetes. 2020 Oct 19. doi: 10.1111/1753-0407.13124. Epub ahead of print. PMID: 33073932.
  • Yang W, Liu B, Gao R, Snetselaar LG, Strathearn L, Bao W. Association of Anemia with Neurodevelopmental Disorders in A Nationally Representative Sample of US Children. J Pediatr. 2020 Oct 6:S0022-3476(20)31172-0. doi: 10.1016/j.jpeds.2020.09.039. Epub ahead of print. PMID: 33035572.
  • Wu Y, Liu B, Sun Y, Du Y, Santillan MK, Santillan DA, Snetselaar LG, Bao W. Association of Maternal Prepregnancy Diabetes and Gestational Diabetes Mellitus With Congenital Anomalies of the Newborn. Diabetes Care. 2020 Dec43(12):2983-2990. doi: 10.2337/dc20-0261. Epub 2020 Oct 21. PMID: 33087319.
  • Hu X, Rong S, Wang Q, Sun T, Bao W, Chen L, Liu L. Association between Plasma Uric Acid and Insulin Resistance in Type 2 Diabetes: A Mendelian Randomization Analysis. Diabetes Res Clin Pract. 2020 Nov 20:108542. doi: 10.1016/j.diabres.2020.108542. Epub ahead of print. PMID: 33227361.
  • Sun Y, Liu B, Wallace RB, Bao W. Association of Cannabis Use With All-Cause and Cause-Specific Mortality Among Younger- and Middle-Aged U.S. Adults. Am J Prev Med. 2020 Dec59(6):873-879. doi: 10.1016/j.amepre.2020.07.010. Epub 2020 Nov 18. PMID: 33220757.
  • Kesse-Guyot E, Rebouillat P, Payrastre L, Allès B, Fezeu LK, Druesne-Pecollo N, Srour B, Bao W, Touvier M, Galan P, Hercberg S, Lairon D, Baudry J. Prospective association between organic food consumption and the risk of type 2 diabetes: findings from the NutriNet-Santé cohort study. Int J Behav Nutr Phys Act. 2020 Nov 917(1):136. doi: 10.1186/s12966-020-01038-y. PMID: 33167995 PMCID: PMC7653706.
  • Lehmler HJ, Simonsen D, Liu B, Bao W. Environmental exposure to pyrethroid pesticides in a nationally representative sample of U.S. adults and children: The National Health and Nutrition Examination Survey 2007-2012. Environ Pollut. 2020 Dec267:115489. doi: 10.1016/j.envpol.2020.115489. Epub 2020 Aug 29. PMID: 33254662 PMCID: PMC7708675.

Melissa Bates, PhD:

  • Bates ML, Gundry RL, Lindsey ML. Using an Investigative Journalism Approach to Design Mechanistic Experiments in Physiology. Physiology (Bethesda). 2020 Jul 135(4):218-219. doi: 10.1152/physiol.00006.2020. PubMed PMID: 32490747.
  • Barnard CR, Peters M, Sindler AL, Farrell ET, Baker KR, Palta M, Stauss HM, Dagle JM, Segar J, Pierce GL, Eldridge MW, Bates ML. Increased aortic stiffness and elevated blood pressure in response to exercise in adult survivors of prematurity. Physiol Rep. 2020 Jun8(12):e14462. doi: 10.14814/phy2.14462. PMID: 32562387 PMCID: PMC7305240.
  • Bates ML, Haack KKV. Everyone must be able to breathe: A plan to support diversity and inclusion in respiratory physiology. Am J Physiol Lung Cell Mol Physiol. 2020 Jun 17. doi: 10.1152/ajplung.00269.2020. Epub ahead of print. PMID: 32551863.
  • Lewandowski AJ, Levy PT, Bates ML, McNamara PJ, Nuyt AM, Goss KN. Impact of the Vulnerable Preterm Heart and Circulation on Adult Cardiovascular Disease Risk. Hypertension. 2020 Oct76(4):1028-1037. doi: 10.1161/HYPERTENSIONAHA.120.15574. Epub 2020 Aug 17. PMID: 32816574 PMCID: PMC7480939.
  • Bates ML, Levy PT, Nuyt AM, Goss KN, Lewandowski AJ, McNamara PJ. Adult Cardiovascular Health Risk and Cardiovascular Phenotypes of Prematurity. J Pediatr. 2020 Sep 12:S0022-3476(20)31147-1. doi: 10.1016/j.jpeds.2020.09.019. Epub ahead of print. PMID: 32931771.

Christopher Benson, MD:

Khataei T, Harding AMS, Janahmadi M, El-Geneidy M, Agha-Alinejad H, Rajabi H, Snyder PM, Sluka KA, Benson CJ. ASICs are required for immediate exercise-induced muscle pain and are downregulated in sensory neurons by exercise training. J Appl Physiol (1985). 2020 May 28. doi: 10.1152/japplphysiol.00033.2020. [Epub ahead of print] PubMed PMID: 32463731.

Sue Bodine, PhD:

  • Bodine SC. Adolph Lecture: Skeletal Muscle Atrophy: Multiple Pathways Leading to a Common Outcome. J Appl Physiol (1985). 2020 Jul 9. doi: 10.1152/japplphysiol.00381.2020. Epub ahead of print. PMID: 32644910.
  • van der Zwaard S, de Leeuw AW, Meerhoff LRA, Bodine SC, Knobbe A. Articles with impact: insights into 10 years of research with machine learning. J Appl Physiol (1985). 2020 Aug 13. doi: 10.1152/japplphysiol.00489.2020. Epub ahead of print. PMID: 32790596.
  • Hughes DC, Baehr LM, Driscoll JR, Lynch SA, Waddell DS, Bodine SC. Identification and Characterization of Fbxl22, a novel skeletal muscle atrophy-promoting E3 ubiquitin ligase. Am J Physiol Cell Physiol. 2020 Aug 12. doi: 10.1152/ajpcell.00253.2020. Epub ahead of print. PMID: 32783651.
  • Hughes DC, Turner DC, Baehr LM, Seaborne RA, Viggars M, Jarvis JC, Gorski PP, Stewart CE, Owens DJ, Bodine SC, Sharples AP. Knockdown of the E3 Ubiquitin ligase UBR5 and its role in skeletal muscle anabolism. Am J Physiol Cell Physiol. 2020 Oct 14. doi: 10.1152/ajpcell.00432.2020. Epub ahead of print. PMID: 33052072.
  • de Sousa LGO, Marshall AG, Norman JE, Fuqua JD, Lira VA, Rutledge JC, Bodine SC. THE EFFECTS OF DIET COMPOSITION AND CHRONIC OBESITY ON MUSCLE GROWTH AND FUNCTION. J Appl Physiol (1985). 2020 Nov 19. doi: 10.1152/japplphysiol.00156.2020. Epub ahead of print. PMID: 33211595.

Charles Brenner, PhD:

  • Matasic DS, Yoon JY, McLendon JM, Mehdi H, Schmidt MS, Greiner AM, Quinones P, Morgan GM, Boudreau RL, Irani K, Brenner C, London B. Modulation of the cardiac sodium channel Na(V)1.5 peak and late currents by NAD(+) precursors. J Mol Cell Cardiol. 2020 Mar 21. pii: S0022-2828(20)30073-0. doi: 10.1016/j.yjmcc.2020.01.013. [Epub ahead of print] PubMed PMID: 32209328.
  • Levine DC, Hong H, Weidemann BJ, Ramsey KM, Affinati AH, Schmidt MS, Cedernaes J, Omura C, Braun R, Lee C, Brenner C, Peek CB, Bass J. NAD(+) Controls Circadian Reprogramming through PER2 Nuclear Translocation to Counter Aging. Mol Cell. 2020 Jun 478(5):835-849.e7. doi: 10.1016/j.molcel.2020.04.010. Epub 2020 May 4. PubMed PMID: 32369735 PubMed Central PMCID: PMC7275919.
  • Gerasimenko M, Cherepanov SM, Furuhara K, Lopatina O, Salmina AB, Shabalova AA, Tsuji C, Yokoyama S, Ishihara K, Brenner C, Higashida H. Nicotinamide riboside supplementation corrects deficits in oxytocin, sociability and anxiety of CD157 mutants in a mouse model of autism spectrum disorder. Sci Rep. 2020 Jun 2210(1):10035. doi: 10.1038/s41598-019-57236-7. PMID: 32572044 PMCID: PMC7308284.
  • Nam TS, Park DR, Rah SY, Woo TG, Chung HT, Brenner C, Kim UH. Interleukin-8 drives CD38 to form NAADP from NADP+ and NAAD in the endolysosomes to mobilize Ca2+ and effect cell migration. FASEB J. 2020 Jul 27. doi: 10.1096/fj.202001249R. Epub ahead of print. PMID: 32717131.

Trudy Burns, PhD:

  • Hu T, Gall SL, Widome R, Bazzano LA, Burns TL, Daniels SR, Dwyer T, Ikonen J, Juonala M, Kähönen M, Prineas RJ, Raitakari O, Sinaiko AR, Steinberger J, Urbina EM, Venn A, Viikari J, Woo JG, Jacobs DR Jr. Childhood/Adolescent Smoking and Adult Smoking and Cessation: The International Childhood Cardiovascular Cohort (i3C) Consortium. J Am Heart Assoc. 2020 Apr 79(7):e014381. doi: 10.1161/JAHA.119.014381. Epub 2020 Apr 8. PubMed PMID: 32264731.
  • Hu T, Jacobs DR Jr, Sinaiko AR, Bazzano LA, Burns TL, Daniels SR, Dwyer T, Hutri-Kähönen N, Juonala M, Murdy KA, Prineas RJ, Raitakari OT, Urbina EM, Venn A, Woo JG, Steinberger J. Childhood BMI and Fasting Glucose and Insulin Predict Adult Type 2 Diabetes: The International Childhood Cardiovascular Cohort (i3C) Consortium. Diabetes Care. 2020 Sep 1:dc200822. doi: 10.2337/dc20-0822. Epub ahead of print. PMID: 32873588.

Lucas Carr, PhD:

Karvinen KH, Brunet J, Carr LJ. Family history of cancer as a cue to action for physical activity behaviour and beliefs. Psychol Health. 2020 Aug35(8):933-945. doi: 10.1080/08870446.2019.1693570. Epub 2019 Nov 22. PMID: 31757176.

Darren Casey, PhD:

  • Limberg JK, Casey DP, Trinity J, Nicholson WT, Wray DW, Tschakovsky ME, Green DJ, Hellsten Y, Fadel PJ, Joyner MJ, Padilla J. Assessment of resistance vessel function in human skeletal muscle: Guidelines for experimental design, Doppler ultrasound, and pharmacology. Am J Physiol Heart Circ Physiol. 2019 Dec 30. doi: 10.1152/ajpheart.00649.2019. [Epub ahead of print] PubMed PMID: 31886718.
  • Hughes WE, Kruse NT, Ueda K, Feider AJ, Hanada S, Bock JM, Casey DP. Dietary nitrate does not acutely enhance skeletal muscle blood flow and vasodilation in the lower limbs of older adults during single-limb exercise. Eur J Appl Physiol. 2020 Jun120(6):1357-1369. doi: 10.1007/s00421-020-04368-8. Epub 2020 Apr 17. PubMed PMID: 32303829.
  • Bock JM, Iwamoto E, Horak JG, Feider AJ, Hanada S, Casey DP. Aerobic Exercise Offsets Endothelial Dysfunction Induced by Repetitive Consumption of Sugar-Sweetened Beverages in Young Healthy Men. Am J Physiol Regul Integr Comp Physiol. 2020 May 13. doi: 10.1152/ajpregu.00055.2020. [Epub ahead of print] PubMed PMID: 32401628.
  • Iwamoto E, Hanson BE, Bock JM, Casey DP. Intermittent hypoxia enhances shear-mediated dilation of the internal carotid artery in young adults. J Appl Physiol (1985). 2020 Jul 23. doi: 10.1152/japplphysiol.00274.2020. Epub ahead of print. PMID: 32702263.
  • Bock JM, Iwamoto E, Horak JG, Feider AJ, Hanada S, Casey DP. Aerobic exercise offsets endothelial dysfunction induced by repetitive consumption of sugar-sweetened beverages in young healthy men. Am J Physiol Regul Integr Comp Physiol. 2020 Jul 1319(1):R11-R18. doi: 10.1152/ajpregu.00055.2020. Epub 2020 May 13. PMID: 32401628.
  • Bock JM, Hughes WE, Ueda K, Feider AJ, Hanada S, Kruse NT, Iwamoto E, Casey DP. Greater α1-adrenergic-mediated vasoconstriction in contracting skeletal muscle of patients with type 2 diabetes. Am J Physiol Heart Circ Physiol. 2020 Oct 1319(4):H797-H807. doi: 10.1152/ajpheart.00532.2020. Epub 2020 Aug 21. PMID: 32822215.
  • Ueda K, Janiczek DM, Casey DP. Arterial Stiffness Predicts General Anesthesia-Induced Vasopressor-Resistant Hypotension in Patients Taking Angiotensin-Converting Enzyme Inhibitors. J Cardiothorac Vasc Anesth. 2020 Aug 22:S1053-0770(20)30834-X. doi: 10.1053/j.jvca.2020.08.040. Epub ahead of print. PMID: 32921603.
  • Hanson BE, Joyner MJ, Casey DP. Sex-Related Differences in Rapid-Onset Vasodilation: Impact of Aging. J Appl Physiol (1985). 2020 Oct 29. doi: 10.1152/japplphysiol.00663.2020. Epub ahead of print. PMID: 33119464.
  • Bock JM, Hanson BE, Asama TF, Feider AJ, Hanada S, Aldrich AW, Dyken ME, Casey DP. Acute inorganic nitrate supplementation and the hypoxic ventilatory response in patients with obstructive sleep apnea. J Appl Physiol (1985). 2020 Nov 19. doi: 10.1152/japplphysiol.00696.2020. Epub ahead of print. PMID: 33211592.
  • Bock JM, Hughes WE, Ueda K, Feider AJ, Hanada S, Kruse NT, Iwamoto E, Casey DP. Greater α1-adrenergic-mediated vasoconstriction in contracting skeletal muscle of patients with type 2 diabetes. Am J Physiol Heart Circ Physiol. 2020 Oct 1319(4):H797-H807. doi: 10.1152/ajpheart.00532.2020. Epub 2020 Aug 21. PMID: 32822215.
  • Iwamoto E, Sakamoto R, Tsuchida W, Yamazaki K, Kamoda T, Neki T, Katayose M, Casey DP. Effects of menstrual cycle and menopause on internal carotid artery shear-mediated dilation in women. Am J Physiol Heart Circ Physiol. 2020 Dec 11. doi: 10.1152/ajpheart.00810.2020. Epub ahead of print. PMID: 33306444.

Mark Chapleau, PhD:

  • Barboi A, Gibbons CH, Axelrod F, Benarroch EE, Biaggioni I, Chapleau MW, Chelimsky G, Chelimsky T, Cheshire WP, Claydon VE, Freeman R, Goldstein DS, Joyner MJ, Kaufmann H, Low PA, Norcliffe-Kaufmann L, Robertson D, Shibao CA, Singer W, Snapper H, Vernino S, Raj SR American Autonomic Society. Human papillomavirus (HPV) vaccine and autonomic disorders: a position statement from the American Autonomic Society. Auton Neurosci. 2020 Jan223:102550. doi: 10.1016/j.autneu.2019.05.002. PubMed PMID: 31928708.
  • Chaurasia B, Ying L, Talbot CL, Maschek JA, Cox J, Schuchman EH, Hirabayashi Y, Holland WL, Summers SA. Ceramides are necessary and sufficient for diet-induced impairment of thermogenic adipocytes. Mol Metab. 2020 Dec 19:101145. doi: 10.1016/j.molmet.2020.101145. Epub ahead of print. PMID: 33352310.

Bhagirath Chaurasia, PhD:

  • Chaurasia B, Talbot CL, Summers SA. Adipocyte Ceramides-The Nexus of Inflammation and Metabolic Disease. Front Immunol. 2020 Sep 2311:576347. doi: 10.3389/fimmu.2020.576347. PMID: 33072120 PMCID: PMC7538607.
  • Chaurasia B, Summers SA. Ceramides in Metabolism: Key Lipotoxic Players. Annu Rev Physiol. 2020 Nov 6. doi: 10.1146/annurev-physiol-031620-093815. Epub ahead of print. PMID: 33158378.

Huxing Cui, PhD:

  • Davis KC, Saito K, Rodeghiero SR, Toth BA, Lutter M, Cui H. Behavioral Alterations in Mice Carrying Homozygous HDAC4A778T Missense Mutation Associated With Eating Disorder. Front Neurosci. 2020 Feb 2114:139. doi: 10.3389/fnins.2020.00139. PMID: 32153359 PMCID: PMC7046559.
  • Deng G, Morselli LL, Wagner VA, Balapattabi K, Sapouckey SA, Knudtson KL, Rahmouni K, Cui H, Sigmund CD, Kwitek AE, Grobe JL. Single-Nucleus RNA Sequencing of the Hypothalamic Arcuate Nucleus of C57BL/6J Mice After Prolonged Diet-Induced Obesity. Hypertension. 2020 Jun 8:HYPERTENSIONAHA12015137. doi: 10.1161/HYPERTENSIONAHA.120.15137. [Epub ahead of print] PubMed PMID: 32507042.
  • Yamanashi T, Malicoat JR, Steffen KT, Zarei K, Li R, Purnell BS, Najafi A, Saito K, Singh U, Toth BA, Lee S, Dailey ME, Cui H, Kaneko K, Cho HR, Iwata M, Buchanan GF, Shinozaki G. Bispectral EEG (BSEEG) quantifying neuro-inflammation in mice induced by systemic inflammation: A potential mouse model of delirium. J Psychiatr Res. 2020 Dec 15133:205-211. doi: 10.1016/j.jpsychires.2020.12.036. Epub ahead of print. PMID: 33360427.

Brandon Davies, PhD:

  • Qiao L, Shetty SK, Spitler KM, Wattez JS, Davies BSJ, Shao J. Obesity Reduces Maternal Blood Triglyceride Concentrations by Reducing Angiopoietin-like Protein 4 Expression in Mice. Diabetes. 2020 Feb 12. pii: db191181. doi: 10.2337/db19-1181. [Epub ahead of print] PubMed PMID:
  • Spitler KM, Davies BSJ. Aging and plasma triglyceride metabolism. J Lipid Res. 2020 Aug61(8):1161-1167. doi: 10.1194/jlr.R120000922. Epub 2020 Jun 25. PMID: 32586846.

Sanjana Dayal, PhD:

  • Gu SX, Sonkar VK, Katare PB, Kumar R, Kruger WD, Arning E, Bottiglieri T, Lentz SR, Dayal S. Memantine Protects From Exacerbation of Ischemic Stroke and Blood Brain Barrier Disruption in Mild But Not Severe Hyperhomocysteinemia. J Am Heart Assoc. 2020 Feb 189(4):e013368. doi: 10.1161/JAHA.119.013368. Epub 2020 Feb 13. PMID: 32067580.
  • Chu Y, Lan RS, Huang R, Feng H, Kumar R, Dayal S, Chan KS, Dai DF. Glutathione peroxidase-1 overexpression reduces oxidative stress, and improves pathology and proteome remodeling in the kidneys of old mice. Aging Cell. 2020 May 13. doi: 10.1111/acel.13154. [Epub ahead of print] PubMed PMID: 32400101.

Ayotunde Dokun, MD, PhD:

  • Alleboina S, Wong T, Singh MV, Dokun AO. Inhibition of protein kinase C beta phosphorylation activates nuclear factor-kappa B and improves postischemic recovery in type 1 diabetes. Exp Biol Med (Maywood). 2020 Apr 23:1535370220920832. doi: 10.1177/1535370220920832. [Epub ahead of print] PubMed PMID: 32326759.
  • Jain N, Agarwal MA, Jalal D, Dokun AO. Individuals with Peripheral Artery Disease (PAD) and Type 1 Diabetes Are More Likely to Undergo Limb Amputation than Those with PAD and Type 2 Diabetes. J Clin Med. 2020 Aug 319(9):E2809. doi: 10.3390/jcm9092809. PMID: 32878057.

John Engelhardt, PhD:

  • Choi SH, Reeves RE, Romano Ibarra GS, Lynch TJ, Shahin WS, Feng Z, Gasser GN, Winter MC, Evans TIA, Liu X, Luo M, Zhang Y, Stoltz DA, Devor EJ, Yan Z, Engelhardt JF. Detargeting Lentiviral-Mediated CFTR Expression in Airway Basal Cells Using miR-106b. Genes (Basel). 2020 Oct 611(10):E1169. doi: 10.3390/genes11101169. PMID: 33036232.

Frank Faraci, PhD:

Faraci FM. Neurovascular coupling: Sending this signal here, hope you pick it up loud and clear. J Physiol. 2020 Sep 1. doi: 10.1113/JP280630. Epub ahead of print. PMID: 32869875.

Edward Filardo, PhD:

  • Rouhimoghadam M, Lu AS, Salem AK, Filardo EJ. Therapeutic Perspectives on the Modulation of G-Protein Coupled Estrogen Receptor, GPER, Function. Front Endocrinol (Lausanne). 2020 Nov 2311:591217. doi: 10.3389/fendo.2020.591217. PMID: 33329395 PMCID: PMC7719807.

James Folk, MD:

Li AS, Velez G, Darbro B, Toral MA, Yang J, Tsang SH, Ferguson PJ, Folk JC, Bassuk AG, Mahajan VB. Whole-Exome Sequencing of Patients with Posterior Segment Uveitis. Am J Ophthalmol. 2020 Jul 21:S0002-9394(20)30378-0. doi: 10.1016/j.ajo.2020.07.021. Epub ahead of print. PMID: 32707200.

Bernd Fritzsch, PhD:

  • Erives A, Fritzsch B. A Screen for Gene Paralogies Delineating Evolutionary Branching Order of Early Metazoa. G3 (Bethesda). 2019 Dec 26. pii: g3.400951.2019. doi: 10.1534/g3.119.400951. [Epub ahead of print] PubMed PMID: 31879283.
  • Nichols DH, Bouma JE, Kopecky BJ, Jahan I, Beisel KW, He DZZ, Liu H, Fritzsch B. Interaction with ectopic cochlear crista sensory epithelium disrupts basal cochlear sensory epithelium development in Lmx1a mutant mice. Cell Tissue Res. 2020 Jan 13. doi: 10.1007/s00441-019-03163-y. [Epub ahead of print] PubMed PMID: 31932950.
  • Herranen A, Ikäheimo K, Lankinen T, Pakarinen E, Fritzsch B, Saarma M, LindahlM, Pirvola U. Deficiency of the ER-stress-regulator MANF triggers progressive outer hair cell death and hearing loss. Cell Death Dis. 2020 Feb 611(2):100.doi: 10.1038/s41419-020-2286-6. PubMed PMID: 32029702 PubMed Central PMCID: PMC7005028.
  • Yamoah EN, Li M, Shah A, Elliott KL, Cheah K, Xu PX, Phillips S, Young SM Jr, Eberl DF, Fritzsch B. Using Sox2 to alleviate the hallmarks of age-related hearing loss. Ageing Res Rev. 2020 May59:101042. doi: 10.1016/j.arr.2020.101042. Epub 2020 Mar 12. Review. PubMed PMID: 32173536.
  • Kersigo J, Gu L, Xu L, Pan N, Vijayakuma S, Jones T, Shibata SB, Fritzsch B, Hansen MR. Effects of Neurod1 Expression on Mouse and Human Schwannoma Cells. Laryngoscope. 2020 May 21. doi: 10.1002/lary.28671. [Epub ahead of print] PubMed PMID: 32438526.
  • Filova I, Dvorakova M, Bohuslavova R, Pavlinek A, Elliott KL, Vochyanova S, Fritzsch B, Pavlinkova G. Combined Atoh1 and Neurod1 Deletion Reveals Autonomous Growth of Auditory Nerve Fibers. Mol Neurobiol. 2020 Dec57(12):5307-5323. doi: 10.1007/s12035-020-02092-0. Epub 2020 Sep 3. PMID: 32880858 PMCID: PMC7547283.
  • Chizhikov VV, Iskusnykh IY, Fattakhov N, Fritzsch B. Lmx1a and Lmx1b are Redundantly Required for the Development of Multiple Components of the Mammalian Auditory System. Neuroscience. 2021 Jan 1452:247-264. doi: 10.1016/j.neuroscience.2020.11.013. Epub 2020 Nov 24. PMID: 33246067.

Katherine Gibson-Corley, PhD:

  • Kluz PN, Kolb R, Xie Q, Borcherding N, Liu Q, Luo Y, Kim MC, Wang L, Zhang Y, Li W, Stipp C, Gibson-Corley KN, Zhao C, Qi HH, Bellizzi A, Tao AW, Sugg S, Weigel RJ, Zhou D, Shen X, Zhang W. Cancer cell-intrinsic function of CD177 in attenuating β-catenin signaling. Oncogene. 2020 Feb 10. doi: 10.1038/s41388-020-1203-x. [Epub ahead of print] PubMed PMID: 32042113.
  • Holland MT, Seaman SC, Woodroffe RW, Fredericks DC, Kovach CK, Gibson-Corley KN, Gillies GT, Howard MA 3rd. In Vivo Testing of a Prototype Intradural Spinal Cord Stimulator in a Porcine Model. World Neurosurg. 2020 Feb 26. pii: S1878-8750(20)30375-2. doi: 10.1016/j.wneu.2020.02.100. [Epub ahead of print] PubMed PMID: 32112934.
  • Sapouckey SA, Morselli LL, Deng G, Patil C, Balapattabi K, Oliveira V, Claflin KE, Gomez J, Pearson NA, Potthoff MJ, Gibson-Corley KN, Sigmund CD, Grobe JL. Exploration of cardiometabolic and developmental significance of angiotensinogen expression by cells expressing the leptin receptor or Agouti-related peptide. Am J Physiol Regul Integr Comp Physiol. 2020 Mar 18. doi: 10.1152/ajpregu.00297.2019. [Epub ahead of print] PubMed PMID: 32186897[EDA1].
  • Hamity MV, White SR, Blum C, Gibson-Corley KN, Hammond DL. Nicotinamide riboside relieves paclitaxel-induced peripheral neuropathy and enhances suppression of tumor growth in tumor-bearing rats. Pain. 2020 May 15. doi: 10.1097/j.pain.0000000000001924. [Epub ahead of print] PubMed PMID: 32433266.
  • Webster JD, Solon M, Gibson-Corley KN. Validating Immunohistochemistry Assay Specificity in Investigative Studies: Considerations for a Weight of Evidence Approach. Vet Pathol. 2020 Sep 25:300985820960132. doi: 10.1177/0300985820960132. Epub ahead of print. PMID: 32975488.

Mark Greiner, MD:

  • Goldstein AS, Janson BJ, Skeie JM, Ling JJ, Greiner MA. The Effects of Diabetes Mellitus on the Corneal Endothelium: A Review. Surv Ophthalmol. 2020 Jan 8. pii: S0039-6257(20)30005-9. doi: 10.1016/j.survophthal.2019.12.009. [Epub ahead of print] Review. PubMed PMID: 31926185.
  • Skeie JM, Aldrich BT, Nishimura DY, Schmidt GA, Zimmerman MB, Ling JJ, Naguib YW, Salem AK, Greiner MA. Ubiquinol Supplementation of Donor Tissue Enhances Corneal Endothelial Cell Mitochondrial Respiration. Cornea. 2020 Jun 15. doi: 10.1097/ICO.0000000000002408. [Epub ahead of print] PubMed PMID: 32558735.
  • Ling JJ, Kyrillos R, Burckart KA, Aldrich BT, Skeie JM, Schmidt GA, Conwell C, Ramirez T, Reed CR, Zimmerman MB, Greiner MA, Li JY. Optimizing Visualization of Descemet Membrane Endothelial Keratoplasty Tissue: Assessing the Impact of Trypan Blue Exposure on Stain Duration and Corneal Endothelial Cell Function. Cornea. 2020 Jul 27. doi: 10.1097/ICO.0000000000002440. Epub ahead of print. PMID: 32732698.
  • Schlötzer-Schrehardt U, Zenkel M, Strunz M, Gießl A, Schondorf H, da Silva H, Schmidt GA, Greiner MA, Okumura N, Koizumi N, Kinoshita S, Tourtas T, Kruse FE. Potential functional restoration of corneal endothelial cells in Fuchs endothelial corneal dystrophy by ROCK inhibitor (ripasudil). Am J Ophthalmol. 2020 Dec 11:S0002-9394(20)30664-4. doi: 10.1016/j.ajo.2020.12.006. Epub ahead of print. PMID: 33316261.

Chad Grueter, PhD:

Ponce JM, Coen G, Spitler KM, Dragisic N, Martins I, Hinton A Jr, Mungai M, Tadinada SM, Zhang H, Oudit GY, Song LS, Li N, Sicinski P, Strack S, Abel ED, Mitchell C, Hall DD, Grueter CE. Stress-Induced Cyclin C Translocation Regulates Cardiac Mitochondrial Dynamics. J Am Heart Assoc. 2020 Apr 79(7):e014366. doi: 10.1161/JAHA.119.014366. Epub 2020 Apr 4. PubMed PMID: 32248761.

Isabella Grumbach, MD, PhD:

  • Grumbach IM. Cardio-Oncology at the Beginning of a New Decade. J Am Heart Assoc. 2020 Jan 219(2):e015890. doi: 10.1161/JAHA.120.015890. Epub 2020 Jan 21. PubMed PMID: 31959029.
  • Gupta AK, Jneid H, Addison D, Ardehali H, Boehme AK, Borgaonkar S, Boulestreau R, Clerkin K, Delarche N, DeVon HA, Grumbach IM, Gutierrez J, Jones DA, Kapil V, Maniero C, Mentias A, Miller PS, May Ng S, Parekh JD, Sanchez RH, Teodor Sawicki K, S J M Te Riele A, Ann Remme C, London B. Current perspectives on Coronavirus 2019 (COVID-19) and cardiovascular disease: A white paper by the JAHA editors. J Am Heart Assoc. 2020 Apr 29:e017013. doi: 10.1161/JAHA.120.017013. [Epub ahead of print] PubMed PMID: 32347144.

Charles Harata, MD, PhD:

  • Kawano H, Mitchell SB, Koh JY, Goodman KM, Harata NC. Calcium-induced calcium release in noradrenergic neurons of the locus coeruleus. Brain Res. 2019 Dec 271729:146627. doi: 10.1016/j.brainres.2019.146627. [Epub ahead of print] PubMed PMID: 31883849.
  • Oyabu K, Takeda K, Kawano H, Kubota K, Watanabe T, Harata NC, Katsurabayashi S, Iwasaki K. Presynaptically silent synapses are modulated by the density of surrounding astrocytes. J Pharmacol Sci. 2020 Jul 24:S1347-8613(20)30074-8. doi: 10.1016/j.jphs.2020.07.009. Epub ahead of print. PMID: 32736867.
  • White S, Kawano H, Harata NC, Roller RJ. Herpes Simplex Virus Organizes Cytoplasmic Membranes to Form a Viral Assembly Center in Neuronal Cells. J Virol. 2020 Jul 22:JVI.00900-20. doi: 10.1128/JVI.00900-20. Epub ahead of print. PMID: 32699089.

Yumi Imai, MD:

  • Imai Y, Cousins RS, Liu S, Phelps BM, Promes JA. Connecting pancreatic islet lipid metabolism with insulin secretion and the development of type 2 diabetes. Ann N Y Acad Sci. 2020 Feb1461(1):53-72. doi: 10.1111/nyas.14037. Epub 2019 Apr 2. PMID: 30937918.
  • Liu S, Promes JA, Harata M, Mishra A, Stephens SB, Taylor EB, Burand AJ Jr, Sivitz WI, Fink BD, Ankrum JA, Imai Y. Adipose Triglyceride Lipase is a Key Lipase for the Mobilization of Lipid Droplets in Human Beta Cells and Critical for the Maintenance of Syntaxin1a Level in Beta Cells. Diabetes. 2020 Mar 31. pii: db190951. doi: 10.2337/db09-0951. [Epub ahead of print] PubMed PMID: 32234723.
  • Cho J, Hiramoto M, Masaike Y, Sakamoto S, Imai Y, Imai Y, Handa H, Imai T. UGGT1 retains proinsulin in the endoplasmic reticulum in an arginine dependent manner. Biochem Biophys Res Commun. 2020 May 15. pii: S0006-291X(20)30903-7. doi: 10.1016/j.bbrc.2020.04.158. [Epub ahead of print] PubMed PMID: 32423812.
  • Cho J, Horikawa Y, Enya M, Takeda J, Imai Y, Imai Y, Handa H, Imai T. L-Arginine prevents cereblon-mediated ubiquitination of glucokinase and stimulates glucose-6-phosphate production in pancreatic β-cells. Commun Biol. 2020 Sep 83(1):497. doi: 10.1038/s42003-020-01226-3. PMID: 32901087 PMCID: PMC7479149.

Kathleen Janz, PhD:

  • Metcalf KM, Letuchy EM, Levy SM, Janz KF. An 8-Year Longitudinal Analysis of Physical Activity and Bone Strength From Adolescence to Emerging Adulthood: The Iowa Bone Development Study. Pediatr Exerc Sci. 2020 Jan 2:1-7. doi: 10.1123/pes.2019-0090. [Epub ahead of print] PubMed PMID: 31896075
  • Rowlands AV, Edwardson CL, Dawkins NP, Maylor BD, Metcalf KM, Janz KF. Physical Activity for Bone Health: How Much and/or How Hard? Med Sci Sports Exerc. 2020 May 21. doi: 10.1249/MSS.0000000000002380. [Epub ahead of print] PubMed PMID: 32453172.
  • van Ekris E, Wijndaele K, Altenburg TM, Atkin AJ, Twisk J, Andersen LB, Janz KF, Froberg K, Northstone K, Page AS, Sardinha LB, van Sluijs EMF, Chinapaw M International Children’s Accelerometry Database (ICAD) Collaborators. Tracking of total sedentary time and sedentary patterns in youth: a pooled analysis using the International Children's Accelerometry Database (ICAD). Int J Behav Nutr Phys Act. 2020 May 1817(1):65. doi: 10.1186/s12966-020-00960-5. PubMed PMID: 32423404 PubMed Central PMCID: PMC7236462.
  • Pashkova A, Hartman JM, Letuchy EM, Janz KF. Interscholastic Athletics and Bone Strength: The Iowa Bone Development Study. J Strength Cond Res. 2020 May 25. doi: 10.1519/JSC.0000000000003646. [Epub ahead of print] PubMed PMID: 32459739.
  • Bernhardsen GP, Stensrud T, Hansen BH, Steene-Johannesen J, Kolle E, Nystad W, Anderssen SA, Hallal PC, Janz KF, Kriemler S, Andersen LB, Northstone K, Resaland GK, Sardinha LB, van Sluijs EMF, Ried-Larsen M, Ekelund U International Children’s Accelerometry Database (ICAD) Collaborators. Birth weight, cardiometabolic risk factors and effect modification of physical activity in children and adolescents: pooled data from 12 international studies. Int J Obes (Lond). 2020 Jun 3. doi: 10.1038/s41366-020-0612-9. [Epub ahead of print] PubMed PMID: 32494037.

Randy Kardon, MD, PhD:

  • Ledolter J, Kardon RH. Focus on Data: Statistical Design of Experiments and Sample Size Selection Using Power Analysis. Invest Ophthalmol Vis Sci. 2020 Jul 161(8):11. doi: 10.1167/iovs.61.8.11. PMID: 32645134.
  • Gramlich OW, Brown AJ, Godwin CR, Chimenti MS, Boland LK, Ankrum JA, Kardon RH. Systemic Mesenchymal Stem Cell Treatment Mitigates Structural and Functional Retinal Ganglion Cell Degeneration in a Mouse Model of Multiple Sclerosis. Transl Vis Sci Technol. 2020 Jul 109(8):16. doi: 10.1167/tvst.9.8.16. PMID: 32855863 PMCID: PMC7422913.
  • Sibony PA, Kupersmith MJ, Kardon RH. Optical Coherence Tomography Neuro-Toolbox for the Diagnosis and Management of Papilledema, Optic Disc Edema, and Pseudopapilledema. J Neuroophthalmol. 2020 Sep 4. doi: 10.1097/WNO.0000000000001078. Epub ahead of print. PMID: 32909979.
  • Harper MM, Boese EA, Kardon RH, Ledolter J, Kuehn MH. High Correlation between Glaucoma Treatment with Topical Prostaglandin Analogs and BDNF Immunoreactivity in Human Retina. Curr Eye Res. 2020 Sep 27:1-7. doi: 10.1080/02713683.2020.1822417. Epub ahead of print. PMID: 32985274.

Modar Kassan, PhD:

Ait-Aissa K, Nguyen QM, Gabani M, Kassan A, Kumar S, Choi SK, Gonzalez AA, Khataei T, Sahyoun AM, Chen C, Kassan M. MicroRNAs and obesity-induced endothelial dysfunction: key paradigms in molecular therapy. Cardiovasc Diabetol. 2020 Sep 919(1):136. doi: 10.1186/s12933-020-01107-3. PMID: 32907629 PMCID: PMC7488343.

Rivera P, Miranda C, Roldán N, Guerrero A, Olave J, Cárdenas P, Nguyen QM, Kassan M, Gonzalez AA. Augmented transcripts of kidney injury markers and renin angiotensin system in urine samples of overweight young adults. Sci Rep. 2020 Dec 310(1):21154. doi: 10.1038/s41598-020-78382-3. PMID: 33273645 PMCID: PMC7713175.

Robert Kerns, PhD:

Aguirre AL, Chheda PR, Lentz SRC, Held HA, Groves NP, Hiasa H, Kerns RJ. Identification of an ethyl 5,6-dihydropyrazolo[1,5-c]quinazoline-1-carboxylate as a catalytic inhibitor of DNA gyrase. Bioorg Med Chem. 2020 May 1528(10):115439. doi: 10.1016/j.bmc.2020.115439. Epub 2020 Mar 13. PubMed PMID: 32234278.

Aloysius Klingelhutz, PhD:

  • Gourronc FA, Markan KR, Kulhankova K, Zhu Z, Sheehy R, Quelle DE, Zingman LV, Kurago ZB, Ankrum JA, Klingelhutz AJ. Pdgfrα-Cre mediated knockout of the aryl hydrocarbon receptor protects mice from high-fat diet induced obesity and hepatic steatosis. PLoS One. 2020 Jul 3015(7):e0236741. doi: 10.1371/journal.pone.0236741. PMID: 32730300 PMCID: PMC7392206.
  • Schlievert PM, Gourronc FA, Leung DYM, Klingelhutz AJ. Human Keratinocyte Response to Superantigens. mSphere. 2020 Oct 75(5):e00803-20. doi: 10.1128/mSphere.00803-20. PMID: 33028686.

Anne Kwitek, PhD:

Berillo O, Ouerd S, Idris-Khodja N, Rehman A, Richer C, Sinnett D, Kwitek AE, Paradis P, Schiffrin EL. Chromosome 2 Fragment Substitutions in Dahl Salt-Sensitive Rats and RNA Sequencing Identified Enpep and Hs2st1 as Vascular Inflammatory Modulators. Hypertension. 2020 Nov 9:HYPERTENSIONAHA12015690. doi: 10.1161/HYPERTENSIONAHA.120.15690. Epub ahead of print. PMID: 33161775.

Ashutosh Mangalam, PhD:

  • Mangalam AK, Ochoa-Repáraz J. Editorial: The Role of the Gut Microbiota in Health and Inflammatory Diseases. Front Immunol. 2020 Sep 1711:565305. doi: 10.3389/fimmu.2020.565305. PMID: 33042145 PMCID: PMC7527406.
  • Marietta E, Mangalam AK, Taneja V, Murray JA. Intestinal Dysbiosis in, and Enteral Bacterial Therapies for, Systemic Autoimmune Diseases. Front Immunol. 2020 Oct 2811:573079. doi: 10.3389/fimmu.2020.573079. PMID: 33193357 PMCID: PMC7655733.
  • Jensen IJ, Jensen SN, Sjaastad FV, Gibson-Corley KN, Dileepan T, Griffith TS, Mangalam AK, Badovinac VP. Sepsis impedes EAE disease development and diminishes autoantigen-specific naïve CD4 T cells. Elife. 2020 Nov 169:e55800. doi: 10.7554/eLife.55800. Epub ahead of print. PMID: 33191915.

Mohamad Mokadem, MD:

Ye Y, Abu El Haija M, Morgan DA, Guo D, Song Y, Frank A, Tian L, Riedl RA, Burnett CML, Gao Z, Zhu Z, Shahi SK, Zarei K, Couvelard A, Poté N, Ribeiro-Parenti L, Bado A, Noureddine L, Bellizzi A, Kievit P, Mangalam AK, Zingman LV, Le Gall M, Grobe JL, Kaplan LM, Clegg D, Rahmouni K, Mokadem M. Endocannabinoid Receptor-1 and Sympathetic Nervous System Mediate the Beneficial Metabolic Effects of Gastric Bypass. Cell Rep. 2020 Oct 2733(4):108270. doi: 10.1016/j.celrep.2020.108270. PMID: 33113371 PMCID: PMC7660289.

Andrew Norris, MD, PhD:

Rickels MR, Norris AW, Hull RL. A tale of two pancreases: exocrine pathology and endocrine dysfunction. Diabetologia. 2020 Oct63(10):2030-2039. doi: 10.1007/s00125-020-05210-8. Epub 2020 Sep 7. PMID: 32894313.

Brian O'Neill, MD, PhD:

Skurski J, Penniman CM, Geesala R, Dixit G, Pulipati P, Bhardwaj G, Meyerholz DK, Issuree PD, O'Neill BT, Maretzky T. Loss of iRhom2 accelerates fat gain and insulin resistance in diet-induced obesity despite reduced adipose tissue inflammation. Metabolism. 2020 Mar 2:154194. doi: 10.1016/j.metabol.2020.154194. [Epub ahead of print] PubMed PMID: 32135161.

Gary Pierce, PhD:

  • Holwerda SW, Holland MT, Green AL, Pearson ACS, Pierce GL. Dissociation between reduced pain and arterial blood pressure following epidural spinal cord stimulation in patients with chronic pain: A retrospective study. Clin Auton Res. 2020 Apr 22. doi: 10.1007/s10286-020-00690-5. [Epub ahead of print] PubMed PMID: 32323062.
  • Hoth KF, Moreau KL, Weinberger HD, Holm KE, Meschede K, Crapo JD, Make BJ, Moser DJ, Kozora E, Bowler RP, Pierce GL, Ten Eyck P, Wamboldt FS. Carotid Artery Stiffness is Associated With Cognitive Performance in Former Smokers With and Without Chronic Obstructive Pulmonary Disease. J Am Heart Assoc. 2020 May 59(9):e014862. doi: 10.1161/JAHA.119.014862. Epub 2020 Apr 26. PubMed PMID: 32338117.
  • Holwerda SW, Kardon RH, Hashimoto R, Full JM, Nellis JK, DuBose LE, Fiedorowicz JG, Pierce GL. Aortic stiffness is associated with changes in retinal arteriole flow pulsatility mediated by local vasodilation in healthy young/middle-age adults. J Appl Physiol (1985). 2020 May 21. doi: 10.1152/japplphysiol.00252.2020. [Epub ahead of print] PubMed PMID: 32437246.
  • Nuckols VR, Holwerda SW, Luehrs RE, DuBose LE, Stroud AK, Brandt D, Betz AM, Fiedorowicz JG, Scroggins SM, Santillan DA, Grobe JL, Sigmund CD, Santillan MK, Pierce GL. Beat-to-Beat Blood Pressure Variability in the First Trimester Is Associated With the Development of Preeclampsia in a Prospective Cohort: Relation With Aortic Stiffness. Hypertension. 2020 Sep 21:HYPERTENSIONAHA12015019. doi: 10.1161/HYPERTENSIONAHA.120.15019. Epub ahead of print. PMID: 32951467.
  • Holwerda SW, Carter JR, Yang H, Wang J, Pierce GL, Fadel PJ. Standardizing methodology for assessing spontaneous baroreflex control of muscle sympathetic nerve activity in humans. Am J Physiol Heart Circ Physiol. 2020 Dec 4. doi: 10.1152/ajpheart.00704.2020. Epub ahead of print. PMID: 33275522.

Catherina Pinnaro, PhD:

O'Malley G, Ebekozien O, Desimone M, Pinnaro CT, Roberts A, Polsky S, Noor N, Aleppo G, Basina M, Tansey M, Steenkamp D, Vendrame F, Lorincz I, Mathias P, Agarwal S, Golden L, Hirsh IB, Levy CJ. COVID-19 Hospitalization in Adults with Type 1 Diabetes: Results from the T1D Exchange Multi-Center Surveillance Study. J Clin Endocrinol Metab. 2020 Nov 9:dgaa825. doi: 10.1210/clinem/dgaa825. Epub ahead of print. PMID: 33165563.

Robert Piper, PhD:

  • MacDonald C, Shields SB, Williams CA, Winistorfer S, Piper RC. A Cycle of Ubiquitination Regulates Adaptor Function of the Nedd4-Family Ubiquitin Ligase Rsp5. Curr Biol. 2020 Jan 3. pii: S0960-9822(19)31588-X. doi: 10.1016/j.cub.2019.11.086. [Epub ahead of print] PubMed PMID: 31956026.
  • Piper RC. ESCRTs cut some slack. Nat Cell Biol. 2020 Aug22(8):915-916. doi: 10.1038/s41556-020-0557-1. PMID: 32753668.

Philip Polgreen, MD:

  • Miller AC, Comellas AP, Hornick DB, Stoltz DA, Cavanaugh JE, Gerke AK, Welsh MJ, Zabner J, Polgreen PM. Cystic fibrosis carriers are at increased risk for a wide range of cystic fibrosis-related conditions. Proc Natl Acad Sci U S A. 2019 Dec 27. pii: 201914912. doi: 10.1073/pnas.1914912117. [Epub ahead of print] PubMed PMID: 31882447.
  • Stapleton EM, Simmering JE, Manges RB, Chipara O, Stone EA, Zabner J, Peters TM, Herman T, Polgreen PM, Comellas AP. Continuous in-home PM(2.5) concentrations of smokers with and without a history of respiratory exacerbations in Iowa, during and after an air purifier intervention. J Expo Sci Environ Epidemiol. 2020 May 28. doi: 10.1038/s41370-020-0235-1. [Epub ahead of print] PubMed PMID: 32461549.
  • Simmering JE, Polgreen LA, Polgreen PM, Teske RE, Comellas AP, Carter BL. The Cardiovascular Effects of Treatment with Hydroxychloroquine and Azithromycin. Pharmacotherapy. 2020 Jul 16:10.1002/phar.2445. doi: 10.1002/phar.2445. Epub ahead of print. PMID: 32677113 PMCID: PMC7404845.
  • Winthrop KL, Brunton AE, Beekmann S, Polgreen P, Baddley J, Saag KG, Calabrese C, Calabrese L, Robinson PC, Wallace ZS, Curtis JR COVID-19 Study Team. SARS CoV-2 infection among patients using immunomodulatory therapies. Ann Rheum Dis. 2020 Aug 5:annrheumdis-2020-218580. doi: 10.1136/annrheumdis-2020-218580. Epub ahead of print. PMID: 32759259.

Matthew Potthoff, PhD:

  • Jensen-Cody SO, Flippo KH, Claflin KE, Yavuz Y, Sapouckey SA, Walters GC, Usachev YM, Atasoy D, Gillum MP, Potthoff MJ. FGF21 Signals to Glutamatergic Neurons in the Ventromedial Hypothalamus to Suppress Carbohydrate Intake. Cell Metab. 2020 Jun 30:S1550-4131(20)30309-0. doi: 10.1016/j.cmet.2020.06.008. Epub ahead of print. PMID: 32640184.
  • Nayak MK, Ghatge M, Flora GD, Dhanesha N, Jain M, Markan KR, Potthoff MJ, Lentz SR, Chauhan AK. Metabolic enzyme pyruvate kinase M2 regulates platelet function and arterial thrombosis. Blood. 2020 Oct 7:blood.2020007140. doi: 10.1182/blood.2020007140. Epub ahead of print. PMID: 33027814.
  • Flippo KH, Jensen-Cody SO, Claflin KE, Potthoff MJ. FGF21 signaling in glutamatergic neurons is required for weight loss associated with dietary protein dilution. Sci Rep. 2020 Nov 1110(1):19521. doi: 10.1038/s41598-020-76593-2. PMID: 33177640 PMCID: PMC7658965.
  • Jensen-Cody SO, Potthoff MJ. Hepatokines and metabolism: Deciphering communication from the liver. Mol Metab. 2020 Dec 4:101138. doi: 10.1016/j.molmet.2020.101138. Epub ahead of print. PMID: 33285302.
  • Markan KR, Boland LK, King-McAlpin AQ, Claflin KE, Leaman MP, Kemerling MK, Stonewall MM, Amendt BA, Ankrum JA, Potthoff MJ. Corrigendum to "Adipose TBX1 regulates β-adrenergic sensitivity in subcutaneous adipose tissue and thermogenic capacity in vivo" [Molecular Metabolism 36 (2020) 100965]. Mol Metab. 2020 Dec 24:101148. doi: 10.1016/j.molmet.2020.101148. Epub ahead of print. Erratum for: Mol Metab. 2020 Jun36:100965. PMID: 33358927.

Kamal Rahmouni, PhD:

  • Guo DF, Reho JJ, Morgan DA, Rahmouni K. Cardiovascular Regulation by the Neuronal BBSome. Hypertension. 2020 Mar 9:HYPERTENSIONAHA11914373. doi: 10.1161/HYPERTENSIONAHA.119.14373. [Epub ahead of print] PubMed PMID: 32148123.
  • Wu J, Agbor LN, Fang S, Mukohda M, Nair AR, Nakagawa P, Sharma A, Morgan DA, Grobe JL, Rahmouni K, Weiss RM, McCormick JA, Sigmund CD. Failure to Vasodilate in Response to Salt Loading Blunts Renal Blood Flow and Causes Salt-Sensitive Hypertension. Cardiovasc Res. 2020 May 19. pii: cvaa147. doi: 10.1093/cvr/cvaa147. [Epub ahead of print] PubMed PMID: 32428209.
  • Nakagawa P, Nair AR, Agbor LN, Gomez J, Wu J, Zhang SY, Lu KT, Morgan DA, Rahmouni K, Grobe JL, Sigmund CD. Increased Susceptibility of Mice Lacking Renin-b to Angiotensin II-Induced Organ Damage. Hypertension. 2020 Jun 8:HYPERTENSIONAHA12014972. doi: 10.1161/HYPERTENSIONAHA.120.14972. [Epub ahead of print] PubMed PMID: 32507043.
  • Wang P, Loh KH, Wu M, Morgan DA, Schneeberger M, Yu X, Chi J, Kosse C, Kim D, Rahmouni K, Cohen P, Friedman J. A leptin-BDNF pathway regulating sympathetic innervation of adipose tissue. Nature. 2020 Jul583(7818):839-844. doi: 10.1038/s41586-020-2527-y. Epub 2020 Jul 22. PMID: 32699414.
  • Jiang J, Morgan DA, Cui H, Rahmouni K. Activation of Hypothalamic AgRP and POMC Neurons Evokes Disparate Sympathetic and Cardiovascular Responses. Am J Physiol Heart Circ Physiol. 2020 Sep 18. doi: 10.1152/ajpheart.00411.2020. Epub ahead of print. PMID: 32946297.
  • Seoane-Collazo P, Diéguez C, Nogueiras R, Rahmouni K, Fernández-Real JM, López M. Nicotine' actions on energy balance: Friend or foe? Pharmacol Ther. 2020 Sep 26:107693. doi: 10.1016/j.pharmthera.2020.107693. Epub ahead of print. PMID: 32987056.
  • de Souza Cordeiro LM, Elsheikh A, Devisetty N, Morgan DA, Ebert SN, Rahmouni K, Chhabra KH. Hypothalamic MC4R regulates glucose homeostasis through adrenaline-mediated control of glucose reabsorption via renal GLUT2 in mice. Diabetologia. 2020 Oct 14. doi: 10.1007/s00125-020-05289-z. Epub ahead of print. PMID: 33052459.
  • Jiang J, Morgan DA, Cui H, Rahmouni K. Activation of hypothalamic AgRP and POMC neurons evokes disparate sympathetic and cardiovascular responses. Am J Physiol Heart Circ Physiol. 2020 Nov 1319(5):H1069-H1077. doi: 10.1152/ajpheart.00411.2020. Epub 2020 Sep 18. PMID: 32946297

Jennifer Robinson, MD:

  • Nanna MG, Navar AM, Wang TY, Li S, Virani SS, Li Z, Robinson JG, Roger VL, Wilson PWF, Goldberg AC, Koren A, Louie MJ, Peterson ED. Practice-level variation in statin use and low-density lipoprotein cholesterol control in the United States: Results from the Patient and Provider Assessment of Lipid Management (PALM) registry. Am Heart J. 2019 Aug214:113-124. doi:10.1016/j.ahj.2019.05.009. Epub 2019 May 22. PubMed PMID: 31202098 PubMed Central PMCID: PMC6639125.
  • Robinson JG. Low LDL-C Levels: Likely No Short-Term Cognitive Harm. J Am Coll Cardiol. 2020 May 1275(18):2294-2296. doi: 10.1016/j.jacc.2020.03.040. PubMed PMID: 32381159.
  • Wang J, Chi CL, St Peter WL, Carlson A, Loth M, Pradhan PM, Liang Y, Chen WY, Lenskaia T, Robinson JG, Adam TJ. A Population-Based Study of Simvastatin Drug-Drug Interactions in Cardiovascular Disease Patients. AMIA Jt Summits Transl Sci Proc. 2020 May 302020:664-673. eCollection 2020. PubMed PMID: 32477689 PubMed Central PMCID: PMC7233072.
  • Imamura F, Fretts AM, Marklund M, Ardisson Korat AV, Yang WS, Lankinen M, Qureshi W, Helmer C, Chen TA, Virtanen JK, Wong K, Bassett JK, Murphy R, Tintle N, Yu CI, Brouwer IA, Chien KL, Chen YY, Wood AC, Del Gobbo LC, Djousse L, Geleijnse JM, Giles GG, de Goede J, Gudnason V, Harris WS, Hodge A, Hu F InterAct Consortium, Koulman A, Laakso M, Lind L, Lin HJ, McKnight B, Rajaobelina K, Riserus U, Robinson JG, Samieri C, Senn M, Siscovick DS, Soedamah-Muthu SS, Sotoodehnia N, Sun Q, Tsai MY, Tuomainen TP, Uusitupa M, Wagenknecht LE, Wareham NJ, Wu JHY, Micha R, Lemaitre RN, Mozaffarian D, Forouhi NG. Fatty acids in the de novo lipogenesis pathway and incidence of type 2 diabetes: A pooled analysis of prospective cohort studies. PLoS Med. 2020 Jun 1217(6):e1003102. doi: 10.1371/journal.pmed.1003102. eCollection 2020 Jun. PubMed PMID: 32530938 PubMed Central PMCID: PMC7292352.
  • Koren MJ, Jones PH, Robinson JG, Sullivan D, Cho L, Hucko T, Lopez JAG, Fleishman AN, Somaratne R, Stroes E. A Comparison of Ezetimibe and Evolocumab for Atherogenic Lipid Reduction in Four Patient Populations: A Pooled Efficacy and Safety Analysis of Three Phase 3 Studies. Cardiol Ther. 2020 Jun 20. doi: 10.1007/s40119-020-00181-8. [Epub ahead of print] PubMed PMID: 32564340.
  • Lowenstern A, Li S, Virani SS, Navar AM, Li Z, Robinson JG, Roger VL, Goldberg AC, Koren A, Louie MJ, Peterson ED, Wang TY. Beliefs, risk perceptions, and lipid management among patients with and without diabetes: Results from the PALM registry. Am Heart J. 2020 Jul225:88-96. doi: 10.1016/j.ahj.2020.04.018. Epub 2020 Apr 30. PMID: 32485329.
  • Gooding HC, Gidding SS, Moran AE, Redmond N, Allen NB, Bacha F, Burns TL, Catov JM, Grandner MA, Harris KM, Johnson HM, Kiernan M, Lewis TT, Matthews KA, Monaghan M, Robinson JG, Tate D, Bibbins-Domingo K, Spring B. Challenges and Opportunities for the Prevention and Treatment of Cardiovascular Disease Among Young Adults: Report From a National Heart, Lung, and Blood Institute Working Group. J Am Heart Assoc. 2020 Oct 209(19):e016115. doi: 10.1161/JAHA.120.016115. Epub 2020 Sep 30. PMID: 32993438.
  • Robinson JG, Jayanna MB, Bairey Merz CN, Stone NJ. Clinical implications of the log linear association between LDL-C lowering and cardiovascular risk reduction: Greatest benefits when LDL-C >100 mg/dl. PLoS One. 2020 Oct 2915(10):e0240166. doi: 10.1371/journal.pone.0240166. PMID: 33119602 PMCID: PMC7595281.
  • Robinson JG. Low LDL-C Levels: Likely No Short-Term Cognitive Harm. J Am Coll Cardiol. 2020 May 1275(18):2294-2296. doi: 10.1016/j.jacc.2020.03.040. PMID: 32381159.

Robert Roghair, MD:

  • Vass RA, Bell EF, Colaizy TT, Schmelzel ML, Johnson KJ, Walker JR, Ertl T, Roghair RD. Hormone levels in preterm and donor human milk before and after Holder pasteurization. Pediatr Res. 2020 Jan 30. doi: 10.1038/s41390-020-0789-6. [Epub ahead of print] PubMed PMID: 32000260.
  • Vass RA, Roghair RD, Bell EF, Colaizy TT, Johnson KJ, Schmelzel ML, Walker JR, Ertl T. Pituitary Glycoprotein Hormones in Human Milk before and after Pasteurization or Refrigeration. Nutrients. 2020 Mar 412(3). pii: E687. doi: 10.3390/nu12030687. PubMed PMID: 32143273.

Stephen Russell, MD:

  • Russell JF, Flynn HW Jr, Sridhar J, Townsend JH, Shi Y, Fan KC, Scott NL, Hinkle JW, Lyu C, Gregori G, Russell SR, Rosenfeld PJ. Distribution of Diabetic Neovascularization on Ultra-Widefield Fluorescein Angiography and on Simulated Widefield OCT Angiography. Am J Ophthalmol. 2019 Nov207:110-120. doi: 10.1016/j.ajo.2019.05.031. Epub 2019 Jun 10. PubMed PMID: 31194952.
  • Al-Khersan H, Russell JF, Lazzarini TA, Scott NL, Hinkle JW, Patel NA, Yannuzzi NA, Fowler BJ, Hussain RM, Barikian A, Sridhar J, Russell SR, Haddock LJ, Smiddy WE, Hariprasad SM, Shi Y, Wang L, Feuer W, Gregori G, Rosenfeld PJ. Comparison Between Graders in Detection of Diabetic Neovascularization with Swept Source OCT Angiography and Fluorescein Angiography. Am J Ophthalmol. 2020 Dec 10:S0002-9394(20)30654-1. doi: 10.1016/j.ajo.2020.11.020. Epub ahead of print. PMID: 33309812.

Tom Rutkowski, PhD:

Gansemer ER, McCommis KS, Martino M, King-McAlpin AQ, Potthoff MJ, Finck BN, Taylor EB, Rutkowski DT. NADPH and Glutathione Redox Link TCA Cycle Activity to Endoplasmic Reticulum Homeostasis. iScience. 2020 May 2223(5):101116. doi: 10.1016/j.isci.2020.101116. Epub 2020 Apr 29. PubMed PMID: 32417402 PubMed Central PMCID: PMC7254477.

Julien Sebag, PhD:

  • Rouault AAJ, Rosselli-Murai LK, Hernandez CC, Gimenez LE, Tall GG, Sebag JA. The GPCR accessory protein MRAP2 regulates both biased signaling and constitutive activity of the ghrelin receptor GHSR1a. Sci Signal. 2020 Jan 713(613). pii: eaax4569. doi: 10.1126/scisignal.aax4569. PubMed PMID: 31911434.
  • Yin TC, Bauchle CJ, Rouault AAJ, Stephens SB, Sebag JA. The Insulinostatic Effect of Ghrelin Requires MRAP2 Expression in δ Cells. iScience. 2020 Jun 123(6):101216. doi: 10.1016/j.isci.2020.101216. [Epub ahead of print] PubMed PMID: 32535024 PubMed Central PMCID: PMC7300157.

Val Sheffield, MD, PhD:

Carter CS, Huang SC, Searby CC, Cassaidy B, Miller MJ, Grzesik WJ, Piorczynski TB, Pak TK, Walsh SA, Acevedo M, Zhang Q, Mapuskar KA, Milne GL, Hinton AO Jr, Guo DF, Weiss R, Bradberry K, Taylor EB, Rauckhorst AJ, Dick DW, Akurathi V, Falls-Hubert KC, Wagner BA, Carter WA, Wang K, Norris AW, Rahmouni K, Buettner GR, Hansen JM, Spitz DR, Abel ED, Sheffield VC. Exposure to Static Magnetic and Electric Fields Treats Type 2 Diabetes. Cell Metab. 2020 Oct 632(4):561-574.e7. doi: 10.1016/j.cmet.2020.09.012. PMID: 33027675.

Linda Snetselaar, PhD:

  • Korth AL, Bhutani S, Neuhouser ML, Beresford SA, Snetselaar L, Tinker LF, Schoeller DA. Comparison of Methods Used to Correct Self-Reported Protein Intake for Systematic Variation in Reported Energy Intake Using Quantitative Biomarkers of Dietary Intake. J Nutr. 2020 Feb 6:nxaa007. doi: 10.1093/jn/nxaa007. Epub ahead of print. PMID: 32030414.
  • Chlebowski RT, Aragaki AK, Anderson GL, Pan K, Neuhouser ML, Manson JE, Thomson CA, Mossavar-Rahmani Y, Lane DS, Johnson KC, Wactawski-Wende J, Snetselaar L, Rohan TE, Luo J, Barac A, Prentice RL Women’s Health Initiative. Dietary Modification and Breast Cancer Mortality: Long-Term Follow-Up of the Women's Health Initiative Randomized Trial. J Clin Oncol. 2020 Feb 7:JCO1900435. doi: 10.1200/JCO.19.00435. Epub ahead of print. PMID: 32031879.
  • Gong JH, Lo K, Liu Q, Li J, Lai S, Shadyab AH, Arcan C, Snetselaar L, Liu S. Dietary Manganese, Plasma Markers of Inflammation, and the Development of Type 2 Diabetes in Postmenopausal Women: Findings From the Women's Health Initiative. Diabetes Care. 2020 Jun43(6):1344-1351. doi: 10.2337/dc20-0243. Epub 2020 Apr 15. PubMed PMID: 32295807.
  • Shadyab AH, Manson JE, Luo J, Haring B, Saquib N, Snetselaar LG, Chen JC, Groessl EJ, Wassertheil-Smoller S, Sun Y, Hale L, LeBoff MS, LaCroix AZ. Associations of Coffee and Tea Consumption With Survival to Age 90 Years Among Older Women. J Am Geriatr Soc. 2020 Apr 24. doi: 10.1111/jgs.16467. [Epub ahead of print] PubMed PMID: 32329900.
  • Yun HY, Tinker LF, Neuhouser ML, Schoeller DA, Mossavar-Rahmani Y, Snetselaar LG, Van Horn LV, Eaton CB, Prentice RL, Lampe JW, O'Brien DM. The Carbon Isotope Ratios of Serum Amino Acids in Combination with Participant Characteristics can be Used to Estimate Added Sugar Intake in a Controlled Feeding Study of US Postmenopausal Women. J Nutr. 2020 Jul 25:nxaa195. doi: 10.1093/jn/nxaa195. Epub ahead of print. PMID: 32712658.
  • Luo J, Chen X, Tindle H, Shadyab AH, Saquib N, Hale L, Garcia L, Springfield S, Liu B, Nassir R, Snetselaar L, Hendryx M. Do health behaviors mediate associations between personality traits and diabetes incidence? Ann Epidemiol. 2020 Aug 14:S1047-2797(20)30288-X. doi: 10.1016/j.annepidem.2020.08.007. Epub ahead of print. PMID: 32805399.
  • Chou EL, Pettinger M, Haring B, Mell MW, Hlatky MA, Wactawski-Wende J, Allison MA, Wild RA, Shadyab AH, Wallace RB, Snetselaar LG, Eagleton MJ, Conrad MF, Liu S. Lipoprotein(a) levels and risk of abdominal aortic aneurysm in the Women's Health Initiative. J Vasc Surg. 2020 Aug 31:S0741-5214(20)31908-X. doi: 10.1016/j.jvs.2020.07.106. Epub ahead of print. PMID: 32882349.
  • Chou EL, Pettinger M, Haring B, Allison MA, Mell MW, Hlatky MA, Wactawski-Wende J, Wild RA, Shadyab AH, Wallace RB, Snetselaar LG, Madsen TE, Eagleton MJ, Conrad MF, Liu S. Association of Premature Menopause With Risk of Abdominal Aortic Aneurysm in the Women's Health Initiative. Ann Surg. 2020 Nov 4. doi: 10.1097/SLA.0000000000004581. Epub ahead of print. PMID: 33156064.
  • Weaver CM, Fukagawa NK, Liska D, Mattes RD, Matuszek G, Nieves JW, Shapses SA, Snetselaar LG. Perspective: US Documentation and Regulation of Human Nutrition Randomized Controlled Trials. Adv Nutr. 2020 Nov 17:nmaa118. doi: 10.1093/advances/nmaa118. Epub ahead of print. PMID: 33200185.
  • Chen GC, Chen LH, Mossavar-Rahmani Y, Kamensky V, Shadyab AH, Haring B, Wild RA, Silver B, Kuller LH, Sun Y, Saquib N, Howard B, Snetselaar LG, Neuhouser ML, Allison MA, Van Horn L, Manson JE, Wassertheil-Smoller S, Qi Q. Dietary cholesterol and egg intake in relation to incident cardiovascular disease and all-cause and cause-specific mortality in postmenopausal women. Am J Clin Nutr. 2020 Dec 17:nqaa353. doi: 10.1093/ajcn/nqaa353. Epub ahead of print. PMID: 33330926.
  • George SM, Reedy J, Cespedes Feliciano EM, Aragaki A, Caan BJ, Kahle L, Manson JE, Rohan TE, Snetselaar LG, Tinker LF, Van Horn L, Neuhouser ML. Alignment of dietary patterns with the Dietary Guidelines for Americans 2015-2020 and risk of all-cause and cause-specific mortality in the Women's Health Initiative Observational Study. Am J Epidemiol. 2020 Dec 16:kwaa268. doi: 10.1093/aje/kwaa268. Epub ahead of print. PMID: 33325511.

Peter Snyder, MD:

Polgreen LA, Carter BL, Polgreen PM, Snyder PM, Sewell DK, Bayman EO, Francis SL, Simmering JE, Parker C, Finkelstein R. A pharmacist intervention for monitoring and treating hypertension using bidirectional texting: PharmText BP. Contemp Clin Trials. 2020 Oct 7:106169. doi: 10.1016/j.cct.2020.106169. Epub ahead of print. PMID: 33038500.

Elliot Sohn, MD:

  • Kang SC, Sohn EH, Lee SR. Hydrogen Sulfide as a Potential Alternative for the Treatment of Myocardial Fibrosis. Oxid Med Cell Longev. 2020 Jan 232020:4105382. doi: 10.1155/2020/4105382. eCollection 2020. Review. PubMed PMID: 32064023 PubMed Central PMCID: PMC6998763.
  • Han IC, Cheng JL, Burnight E, Ralston CL, Fick JL, Thomsen GJ, Tovar EF, Russell S, Sohn EH, Mullins RF, Stone E, Tucker BA, Wiley LA. Retinal Tropism and Transduction of Adeno-Associated Virus (AAV) Varies by Serotype and Route of Delivery (Intravitreal, Subretinal or Suprachoroidal) in Rats. Hum Gene Ther. 2020 Sep 18. doi: 10.1089/hum.2020.043. Epub ahead of print. PMID: 32948113.
  • Ricca A, Boone K, Boldt HC, Gehrs KM, Russell SR, Folk JC, Zimmerman MB, Wilkinson ME, Sohn EH. Attaining functional levels of visual acuity after vitrectomy for retinal detachment secondary to proliferative diabetic retinopathy. Sci Rep. 2020 Sep 2410(1):15637. doi: 10.1038/s41598-020-72618-y. PMID: 32973186 PMCID: PMC7519031.

Milan Sonka, PhD

  • Bedanova H, Pazdernik M, Sonka M, Zhi C, Krejci J, Novakova M, Dobsak P, Nemec P. Effects of implanting a long-term left ventricle assist device on post-transplant outcomes. Int J Artif Organs. 2020 Apr 24:391398820914626. doi: 10.1177/0391398820914626. [Epub ahead of print] PubMed PMID: 32329386.
  • Minaee S, Kafieh R, Sonka M, Yazdani S, Jamalipour Soufi G. Deep-COVID: Predicting COVID-19 from chest X-ray images using deep transfer learning. Med Image Anal. 2020 Oct65:101794. doi: 10.1016/j.media.2020.101794. Epub 2020 Jul 21. PMID: 32781377 PMCID: PMC7372265.
  • Pazdernik M, Bedanova H, Chen Z, Kautzner J, Melenovsky V, Malek I, Slavcev A, Bartonova M, Karmazin V, Eckhardt T, Tomasek A, Ozabalova E, Kovarnik T, Wohlfahrt P, Sonka M. Donor specific anti-HLA antibodies and cardiac allograft vasculopathy: A prospective study using highly automated 3-D optical coherence tomography analysis. Transpl Immunol. 2020 Oct 15:101340. doi: 10.1016/j.trim.2020.101340. Epub ahead of print. PMID: 33069814.
  • Guo Z, Zhang H, Chen Z, van der Plas E, Gutmann L, Thedens D, Nopoulos P, Sonka M. Fully automated 3D segmentation of MR-imaged calf muscle compartments: Neighborhood relationship enhanced fully convolutional network. Comput Med Imaging Graph. 2020 Dec 1087:101835. doi: 10.1016/j.compmedimag.2020.101835. Epub ahead of print. PMID: 33373972.

Long Sheng-Song, MD:

  • Wang Y, Li C, Shi L, Chen X, Cui C, Huang J, Chen B, Hall DD, Pan Z, Lu M, Hong J, Song LS, Zhao S. Integrin β1D Deficiency-Mediated RyR2 Dysfunction Contributes to Catecholamine-Sensitive Ventricular Tachycardia in ARVC. Circulation. 2020 Mar 3. doi: 10.1161/CIRCULATIONAHA.119.043504. [Epub ahead of print] PubMed PMID: 32122157.
  • Wang J, Hall DD, Song LS. Nexilin is a New Player for Shaping T-Tubules in Cardiomyocytes. Circ Heart Fail. 2020 Jul13(7):e007196. doi: 10.1161/CIRCHEARTFAILURE.120.007196. Epub 2020 Jul 8. PMID: 32635767 PMCID: PMC7375922.
  • Mesubi OO, Rokita AG, Abrol N, Wu Y, Chen B, Wang Q, Granger JM, Tucker-Bartley A, Luczak ED, Murphy KR, Umapathi P, Banerjee PS, Boronina T, Cole RN, Maier LS, Wehrens XH, Pomerantz JL, Song LS, Ahima R, Hart GW, Zachara NE, Anderson ME. Oxidized-CaMKII and O-GlcNAcylation cause increased atrial fibrillation in diabetic mice by distinct mechanisms. J Clin Invest. 2020 Nov 5:95747. doi: 10.1172/JCI95747. Epub ahead of print. PMID: 33151911.

Douglas Spitz, PhD:

  • Falls-Hubert KC, Butler AL, Gui K, Anderson M, Li M, Stolwijk JM, Rodman SN 3rd, Solst SR, Tomanek-Chalkley A, Searby CC, Sheffield VC, Sandfort V, Schmidt H, McCormick ML, Wels BR, Allen BG, Buettner GR, Schultz MK, Spitz DR. Disulfiram causes selective hypoxic cancer cell toxicity and radio-chemo-sensitization via redox cycling of copper. Free Radic Biol Med. 2020 Feb 4150:1-11. doi: 10.1016/j.freeradbiomed.2020.01.186. Epub ahead of print. PMID: 32032663.
  • Ubellacker JM, Tasdogan A, Ramesh V, Shen B, Mitchell EC, Martin-Sandoval MS, Gu Z, McCormick ML, Durham AB, Spitz DR, Zhao Z, Mathews TP, Morrison SJ. Lymph protects metastasizing melanoma cells from ferroptosis. Nature. 2020 Sep585(7823):113-118. doi: 10.1038/s41586-020-2623-z. Epub 2020 Aug 19. PMID: 32814895 PMCID: PMC7484468.

Samuel Stephens, PhD:

Huynh FK, Peterson BS, Anderson KA, Lin Z, Coakley AJ, Llaguno FMS, Nguyen TN, Campbell JE, Stephens SB, Newgard CB, Hirschey MD. Beta-cell specific ablation of sirtuin 4 does not affect nutrient-stimulated insulin secretion in mice. Am J Physiol Endocrinol Metab. 2020 Aug 31. doi: 10.1152/ajpendo.00170.2020. Epub ahead of print. PMID: 32865009.

David Stoltz, MD, PhD:

  • Fischer AJ, Singh SB, LaMarche MM, Maakestad LJ, Kienenberger ZE, Peña TA, Stoltz DA, Limoli DH. Sustained Coinfections with Staphylococcus aureus and Pseudomonas aeruginosa in Cystic Fibrosis. Am J Respir Crit Care Med. 2020 Aug 4. doi: 10.1164/rccm.202004-1322OC. Epub ahead of print. PMID: 32750253.
  • Zarei K, Stroik MR, Gansemer ND, Thurman AL, Ostedgaard LS, Ernst SE, Thornell IM, Powers LS, Pezzulo AA, Meyerholz DK, Stoltz DA. Early pathogenesis of cystic fibrosis gallbladder disease in a porcine model. Lab Invest. 2020 Jul 27. doi: 10.1038/s41374-020-0474-8. Epub ahead of print. PMID: 32719544.

Stefan Strack, PhD:

  • Liu Y, Merrill RA, Strack S. A-Kinase Anchoring Protein 1: Emerging Roles in Regulating Mitochondrial Form and Function in Health and Disease. Cells. 2020 Jan 269(2). pii: E298. doi: 10.3390/cells9020298. Review. PubMed PMID: 31991888.
  • Flippo KH, Lin Z, Dickey AS, Zhou X, Dhanesha NA, Walters GC, Liu Y, Merrill RA, Meller R, Simon RP, Chauhan AK, Usachev YM, Strack S. Deletion of a neuronal Drp1 activator protects against cerebral ischemia. J Neurosci. 2020 Mar 3. pii: JN-RM-1926-19. doi: 10.1523/JNEUROSCI.1926-19.2020. [Epub ahead of print] PubMed PMID: 32144179.
  • Jong CJ, Merrill RA, Wilkerson EM, Herring LE, Graves LM, Strack S. Reduction of protein phosphatase 2A (PP2A) complexity reveals cellular functions and dephosphorylation motifs of the PP2A/B'δ holoenzyme. J Biol Chem. 2020 Mar 10. pii: jbc.RA119.011270. doi: 10.1074/jbc.RA119.011270. [Epub ahead of print] PubMed PMID: 32156701.
  • Edwards G, Perkins GA, Kim KY, Kong Y, Lee Y, Choi SH, Liu Y, Skowronska-Krawczyk D, Weinreb RN, Zangwill L, Strack S, Ju WK. Loss of AKAP1 triggers Drp1 dephosphorylation-mediated mitochondrial fission and loss in retinal ganglion cells. Cell Death Dis. 2020 Apr 2011(4):254. doi: 10.1038/s41419-020-2456-6. PubMed PMID: 32312949 PubMed Central PMCID: PMC7170863.
  • Song J, Merrill RA, Usachev AY, Strack S. The X-linked intellectual disability gene product and E3 ubiquitin ligase KLHL15 degrades doublecortin proteins to constrain neuronal dendritogenesis. J Biol Chem. 2020 Nov 16:jbc.RA120.016210. doi: 10.1074/jbc.RA120.016210. Epub ahead of print. PMID: 33199366.

Erin Talbert, PhD:

Montalvo RN, Doerr V, Kwon OS, Talbert EE, Yoo JK, Hwang MH, Nguyen BL, Christou DD, Kavazis AN, Smuder AJ. Protection against Doxorubicin-Induced Cardiac Dysfunction Is Not Maintained Following Prolonged Autophagy Inhibition. Int J Mol Sci. 2020 Oct 3021(21):8105. doi: 10.3390/ijms21218105. PMID: 33143122 PMCID: PMC7662380.

Eric Taylor, PhD:

Buchanan JL, Taylor EB. Mitochondrial Pyruvate Carrier Function in Health and Disease across the Lifespan. Biomolecules. 2020 Aug 810(8):E1162. doi: 10.3390/biom10081162. PMID: 32784379.

Eva Tsalikian, MD:

  • Harrison K, Afifi T, Zamanzadeh N, Davis S, Ersig A, Tsalikian E, Acevedo Callejas M. Parents' relationship maintenance as a buffer for the stress of their adolescent's type 1 diabetes. J Fam Psychol. 2020 Mar 12. doi: 10.1037/fam0000634. [Epub ahead of print] PubMed PMID: 32162943.
  • Sinha S, Renavikar PS, Crawford MP, Steward-Tharp SM, Brate A, Tsalikian E, Tansey M, Shivapour ET, Cho T, Kamholz J, Karandikar NJ. Altered expression of SIRPγ on the T-cells of relapsing remitting multiple sclerosis and type 1 diabetes patients could potentiate effector responses from T-cells. PLoS One. 2020 Aug 2715(8):e0238070. doi: 10.1371/journal.pone.0238070. PMID: 32853219 PMCID: PMC7451561.
  • Lagarde WH, Courtney KL, Reiner B, Steinmann K, Tsalikian E, Willi SM. Human plasma-derived alpha1 -proteinase inhibitor in patients with new-onset type 1 diabetes mellitus: A randomized, placebo-controlled proof-of-concept study. Pediatr Diabetes. 2020 Nov 26. doi: 10.1111/pedi.13162. Epub ahead of print. PMID: 33244872.

Aliye Uc, MD:

  • Ellery KM, Uc A. Recurrent Pancreatitis in Children: Past, Present, and Future. J Pediatr Gastroenterol Nutr. 2019 Dec 30. doi: 10.1097/MPG.0000000000002619. [Epub ahead of print] PubMed PMID: 31899736.
  • ​Dike CR, Zimmerman B, Zheng Y, Wilschanski M, Werlin SL, Troendle D, Shah U, Schwarzenberg SJ, Pohl J, Perito ER, Ooi CY, Nathan JD, Morinville VD, McFerron B, Mascarenhas M, Maqbool A, Liu Q, Lin TK, Husain SZ, Heyman MB, Gonska T, Giefer MJ, Gariepy CE, Fishman DS, Bellin M, Barth B, Abu-El-Haija M, Lowe ME, Uc A. Clinical and Practice Variations in Pediatric Acute Recurrent or Chronic Pancreatitis: Report From The Insppire Study. J Pediatr Gastroenterol Nutr. 2020 Feb 19. doi: 10.1097/MPG.0000000000002661. [Epub ahead of print] PubMed PMID: 32079978.
  • Abu-El-Haija M, Lowe M, Barth B, Bellin MD, Freedman S, Gariepy C, Giefer MJ, Gonska T, Heyman MB, Himes R, Husain S, Lin TK, Liu Q, Mascarenhas MR, Maqbool A, McFerron B, Morinville V, Nathan J, Ooi CY, Perito E, Pohl JF, Schwarzenberg SJ, Shah U, Troendle D, Werlin S, Wilschanski M, Zimmerman B, Uc A. Pediatric chronic pancreatitis without prior acute or acute recurrent pancreatitis: A report from the INSPPIRE consortium. Pancreatology. 2020 Apr 9. pii: S1424-3903(20)30130-7. doi: 10.1016/j.pan.2020.04.001. [Epub ahead of print] PubMed PMID: 32332002
  • Dike CR, Vanegas Calderon OG, Bishop W, Uc A. Drug-Induced Pancreatitis in a Pediatric Patient Following Acetaminophen Overdose. Pancreas. 2020 May/Jun49(5):e45-e46. doi: 10.1097/MPA.0000000000001555. PubMed PMID: 32433416.
  • Dike CR, Kao SC, Uc A. Progression from acute to chronic pancreatitis associated with CFTR and SPINK1 mutations. Pancreatology. 2020 Jun 6. pii: S1424-3903(20)30163-0. doi: 10.1016/j.pan.2020.05.012. [Epub ahead of print] PubMed PMID: 32553420.

Yuriy Usachev, PhD:

Flippo KH, Lin Z, Dickey AS, Zhou X, Dhanesha NA, Walters GC, Liu Y, MerrillRA, Meller R, Simon RP, Chauhan AK, Usachev YM, Strack S. Deletion of a neuronal Drp1 activator protects against cerebral ischemia. J Neurosci. 2020 Mar 3. pii: JN-RM-1926-19. doi: 10.1523/JNEUROSCI.1926-19.2020. [Epub ahead of print] PubMed PMID: 32144179.

Ajit Vikram, PhD:

  • Gaddam RR, Jacobsen VP, Kim YR, Gabani M, Jacobs JS, Dhuri K, Kumar S, Kassan M, Li Q, Bahal R, Roghair R, Irani K, Vikram A. Microbiota-governed microRNA-204 impairs endothelial function and blood pressure decline during inactivity in db/db mice. Sci Rep. 2020 Jun 2210(1):10065. doi: 10.1038/s41598-020-66786-0. PubMed PMID: 32572127 PubMed Central PMCID: PMC7308358.
  • Dhuri K, Bechtold C, Quijano E, Pham H, Gupta A, Vikram A, Bahal R. Antisense Oligonucleotides: An Emerging Area in Drug Discovery and Development. J Clin Med. 2020 Jun 269(6). pii: E2004. doi: 10.3390/jcm9062004. Review. PubMed PMID: 32604776.
  • Gaddam RR, Kim YR, Li Q, Jacobs JS, Gabani M, Mishra A, Promes JA, Imai Y, Irani K, Vikram A. Genetic deletion of miR-204 improves glycemic control despite obesity in db/db mice. Biochem Biophys Res Commun. 2020 Nov 5532(2):167-172. doi: 10.1016/j.bbrc.2020.08.077. Epub 2020 Sep 17. PMID: 32950230.

Michael Welsh, MD:

  • Rehman T, Thornell IM, Pezzulo AA, Thurman AL, Romano Ibarra GS, Karp PH, Tan P, Duffey ME, Welsh MJ. TNFα and IL-17 Alkalinize Airway Surface Liquid through CFTR and Pendrin. Am J Physiol Cell Physiol. 2020 May 20. doi: 10.1152/ajpcell.00112.2020. [Epub ahead of print] PubMed PMID: 32432926.
  • Thornell IM, Rehman T, Pezzulo AA, Welsh MJ. Paracellular bicarbonate flux across human cystic fibrosis airway epithelia tempers changes in airway surface liquid pH. J Physiol. 2020 Jul 5. doi: 10.1113/JP280120. [Epub ahead of print] PubMed PMID: 32627187.
  • Xie Y, Lu L, Tang XX, Moninger TO, Huang TJ, Stoltz DA, Welsh MJ. Acidic Submucosal Gland pH and Elevated Protein Concentration Produce Abnormal Cystic Fibrosis Mucus. Dev Cell. 2020 Jul 23:S1534-5807(20)30550-5. doi: 10.1016/j.devcel.2020.07.002. Epub ahead of print. PMID: 32730755.
  • Ostedgaard LS, Price MP, Whitworth KM, Abou Alaiwa MH, Fischer AJ, Warrier A, Samuel M, Spate LD, Allen PD, Hilkin BM, Romano Ibarra GS, Ortiz Bezara ME, Goodell BJ, Mather SE, Powers LS, Stroik MR, Gansemer ND, Hippee CE, Zarei K, Goeken JA, Businga TR, Hoffman EA, Meyerholz DK, Prather RS, Stoltz DA, Welsh MJ. Lack of airway submucosal glands impairs respiratory host defenses. Elife. 2020 Oct 79:e59653. doi: 10.7554/eLife.59653. PMID: 33026343 PMCID: PMC7541087.
  • Chorghade RS, Kim BR, Launspach JL, Karp PH, Welsh MJ, Burke MD. Amphotericin B induces epithelial voltage responses in people with cystic fibrosis. J Cyst Fibros. 2020 Dec 8:S1569-1993(20)30928-0. doi: 10.1016/j.jcf.2020.11.018. Epub ahead of print. PMID: 33309058.

Ling Yang, PhD:

Zhang Z, Qian Q, Li M, Shao F, Ding WX, Lira VA, Chen SX, Sebag SC, Hotamisligil GS, Cao H, Yang L. The Unfolded Protein Response Regulates Hepatic Autophagy by sXBP1-mediated Activation of TFEB. Autophagy. 2020 Jun 28. doi: 10.1080/15548627.2020.1788889. [Epub ahead of print] PubMed PMID: 32597296.


CA2871852A1 - Methods for using autologous fibroblasts to alter skin identity - Google Patents

Fibroblast Seeding. Following aeration of the skin pieces, 2 mL of fibroblast medium is carefully added to the well containing the dermis piece making sure to not disturb the dermis. This is accomplished by tilting the dish slightly so the medium is added slowly from the edge rather than directly onto the dermis. The culture plate is slowly returned to the horizontal position and transferred to a sterile 37 C, CO2 incubator. The plate is incubated undisturbed for 2-3 days. For example, if the dermis is processed on Friday, 2 mL of fresh fibroblast medium is added and the plate is left in the incubator until Monday afternoon.
Culture medium is changed three times per week, noting the color of medium at each change.
If the culture turns yellow the media should be changed more frequently, e.g.
every other day.
At every culture change the cells are visually inspected under an inverted microscope for presence of infection, i.e., presence of filaments, increased turbidity, or particulate matter or motile organisms. The culture is also observed for status of fibroblast expansion. Fibroblasts should begin to grow out of the dermis in about eight days. The culture supernatant is aspirated off using a sterile pipette and automatic pipettor.
Fibroblast Expansion. Fibroblast culture confluency is checked routinely and estimated based on the amount of free space on the well. In order to maintain confluency, 30-80% of the culture is split into new vessels as needed. If the confluency is greater than 80%, the culture is split and the fibroblast cells are sub-cultured as necessary to expand the cultures. For sub-culturing, cells are incubated in media supplemented with Trypsin LE-express (Invitrogen 12605-010) for minimal amount of minutes before cells lift off the plate (typically less than 5 minutes).
For the first passage, cells in each well are washed twice with 4mL each of sterile PBS. Two mL of trypsin are added to the dish and incubated for five minutes or until cells lift off the dish. One mL of sterile FBS is added to the well to neutralize the trypsin. Unwashed cells are plated after trypsinization. Ten iut of the trypsin inactivated solution are added to 5 iut of 0.4% trypan blue and loaded on a Countess cartridge. The total number of cells is determined using a Countess automated cell counter. Forty mL of sterile PBS
(supplemented with antibiotic/antimycotic solution) is added to cells in a 50 mL conical tube. Cells are centrifuged at 200 x g for 5 minutes, then resuspended in 12mL of fibroblast media. The number of cells is recorded in the production log as described above. Two million cells are added to labeled 75 cm2 (T-75) tissue culture flasks (Fisher Scientific).
For subsequent passages, cells are washed with two aliquots of 20mL each of sterile PBS followed by incubation of the culture in 5mL of trypsin for 5 minutes or until cells lift off the flask. One milliliter of sterile FBS is added to the flask to neutralize the trypsin. Cells are transferred to a 50 mL conical tissue culture tube followed by addition of 40 mL of sterile PBS (supplemented with antibiotic/antimycotic solution). Cells are counted in a Countess automated cell counter as described above. Cells are centrifuged for 5 minutes at 200 x g, and the pellet is resuspended in 12 mL of fibroblast media. Finally, the cells are added to a new labeled T-75 tissue culture flask. The seeding density will be 2 million cells per T-75.
For the final two passages, when the total cell number has reached 5 million cells, we subsequently maintain cells in the aforementioned media but the media will not contain any antibiotics or antimycotics. Therefore the media will be chemically Defined FGM-CD
fibroblast growth medium (Lonza CC-3132) supplemented with high quality defined Fetal Bovine Serum (Invitrogen 16000-044) to a 2% final concentration.
Cell Harvest. Cultured fibroblasts are harvested when the cellular density reaches 120% of the target cell number for injection. For example, for an injection of 37.5 x 106 cells, 45 x 106 cells are harvested. Before the final wash of cells, excess media will be saved for Mycoplasma testing. The cells are counted using the Countess automated cell counter.
Once 45 x 106 cells are isolated then an aliquot will be frozen. Three small aliquots containing approximately 1 x 106 cells each are packaged for sterility, endotoxin, potency, and stability testing.
The culture supernatant is first inspected visually both grossly and under a tissue culture microscope to ensure no evidence of contamination. Then, the culture supernatant is aspirated off using a sterile pipette and automatic pipettor. Cultured fibroblasts are removed from the growing surface with trypsin following the procedure described above for passaging the cultures except that cell are processed for cryopreservation as described below.
Cryopreservation of Cells. After trypsinization, the cell suspension is diluted with PBS and centrifuged at 200 x g for 5 minutes in a Beckman Coulter centrifuge (Model #392187). Cells are resuspened in PBS and pelleted again. The final wash is aspirated off and the pellet is resuspended in 95% cryopreservation media (cryoprotectant) consisting of 65 mL of Hespan (6% Hetastarch) (B. Braun Medical, Inc.), and 6.5mL of 25% Human Serum Albumin (HSA) (Gemini Bio-Products, catalog #800-126P).
Cells are resuspended at a density of 3-4 x 107 cells per 0.75 mL of crypoprotectant per 2-mL cryovial (Nalgene Cryovial, catalog #5012-0020). The vial(s) are subjected to slow freezing for at least 24 hour at -80 C in special room temperature isopropanol containers-Mr.
Frosty-Nalgene (Sigma, catalog #C1562). In this simple process, vials are simply placed inside the Mr. Frosty and allowed to slowly cool by placing the room temperature Mr. Frosty container in a -80 freezer. Once the slow freezing is completed the vials are transferred to a liquid nitrogen freezer and stored in the vapor phase (-150 C).
Autologous fibroblast preparations and administration. At the completion of culture expansion, the cells are harvested and washed, then formulated to contain an appropriate number of cells. Such pharmaceutical compositions comprising autologous fibroblasts include, but are not limited to about 0.1 to about 9.9 x 1019 cells/ml, about 0.5 to about 9 x 1019 cells/ml, about 1 to about 9 x 109 cells/ml, about 1 to about 8 x 108 cells/ml, about 1 to about 7 x 107 cells/ml, about 1 to about 6 x 106 cells/ml, about 1 to about 5 x 105 cells/ml. In more particular embodiments, the appropriate number of cells includes about 1 to about 9 x 107 cells/ml, about 1 to about 8 x 107 cells/ml, about 1 to about 7 x 107 cells/ml, about 1 to about 6 x 107 cells/ml, about 1 to about 5 x 107 cells/ml, about 1 to about 4 x 107 cells/ml, about 1 to about 3 x 107 cells/ml, and about 1 to about 2 x 107 cells/ml.
Alternatively, the target amount can be adjusted within the formulation range to accommodate different indication doses.
The autologous fibroblast composition may comprise at least about 80%, at least about 85%, at least about 88%, at least about 89%, and at least about 90%
fibroblasts. More specifically, the composition may comprise at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% fibroblasts.
The pharmaceutical compositions of the present invention may be administered by any effective route of administration. In specific embdoiments, the administration route is by injection. In certain embodiments, the composition is administered through a sub-epidermal injection (intradermis) very close to the epidermal/dermal junction.
Without further elaboration, it is believed that one skilled in the art, using the preceding description, can utilize the present invention to the fullest extent. The following examples are illustrative only, and not limiting of the remainder of the disclosure in any way whatsoever.
EXAMPLES
The following examples are put forth so as to provide those of ordinary skill in the art with a complete disclosure and description of how the compounds, compositions, articles, devices, and/or methods described and claimed herein are made and evaluated, and are intended to be purely illustrative and are not intended to limit the scope of what the inventors regard as their invention. Efforts have been made to ensure accuracy with respect to numbers (e.g., amounts, temperature, etc.) but some errors and deviations should be accounted for herein. Unless indicated otherwise, parts are parts by weight, temperature is in degrees Celsius or is at ambient temperature, and pressure is at or near atmospheric.
There are numerous variations and combinations of reaction conditions, e.g., component concentrations, desired solvents, solvent mixtures, temperatures, pressures and other reaction ranges and conditions that can be used to optimize the product purity and yield obtained from the described process. Only reasonable and routine experimentation will be required to optimize such process conditions.
Robust System for Testing KRT9 Induction. The present inventors are able to efficiently and rapidly test for the ability of fibroblasts to induce KRT9 expression in keratinocytes. In normal tissue, KRT9 is uniquely expressed in volar skin (FIG. 3).
Interestingly, we found that among volar sites, the sole has higher levels of KRT9, probably because of greater pressure at that site. To try to replicate these findings, we initiated a robust in vitro system.
We first obtained human biopsies from both volar and nonvolar sites of the hands and feet (Hopkins IRB approved NA 00033375) and expanded fibroblasts using conventional methods. Aliquoted fibroblasts (P2) were frozen for future use, then thawed and expanded.
We expanded keratinocytes from foreskin excisions. Then using optimized protocols for the ideal ratio (lkers:4fibros), and time (3 days), we cultured these cells together in a conventional 2-D plate and harvest for qRT-PCR.
We found that volar fibroblasts have the capacity to induce KRT9 (FIG. 4). We found that they did so through passage 16, and non-volar cells never spontaneously did so.
Normally KRT9 is expressed in KRT11+ suprabasal cells in vivo. Because the 2D
system consists of basilar type keratin expression (K4+, K15+, KRT11-), the KRT9 induction levels are lower than in vivo. Another reason for the lower levels of KRT9 with in vitro model systems is the absence of pressure which is hypothesized to augment KRT9 expression.
Within volar epidermis, KRT9 is most expressed at the center of papillary ridges that are thought to have the highest level of compressive stress. Nevertheless, our in vitro results also suggest a recapitulation of the normally higher amount of KRT9 induction by sole fibroblasts compared to palm fibroblasts (p=0.1).
Our laboratory also initiated the use of 3-D cultures to assess how volar fibroblasts affect not just KRT9 expression, but more broad features of volar epidermis.
The results show that the epidermis is thicker using volar fibroblasts (FIG. 5), similar to in vivo (FIG. 1).
Also, KRT9 is induced by RT-PCR (17 fold).

As additional validation for our system, we have confirmed the necessity of the distally active homeobox gene HoxA13 for the induction of KRT9. Expanded volar fibroblasts were treated with siRNA knockdown prior to co-culture with foreskin keratinocytes. While mock knockdown cells retain the ability to induce KRT9, deficient fibroblasts lose the ability (FIG. 6). While this experiment implies that HOXA13 is necessary for KRT9 induction, HOXA13 is unlikely to be involved specifically in the volar phenotype. Because HOXA13 is important for distal identity, it is likely only permissive for the volar phenotype. It has no described role in dorsal-ventral patterning and was not strongly associated with the volar skin gene signature (see below).
Microarray Characterization of Conserved Volar Gene Signature. Despite the few published reports on the histology of volar skin, to our knowledge none describe the unique gene expression patterns. We therefore have performed exhaustive microarrays on human whole tissue (24), epidermis (24)/dermis (24), and cultured fibroblasts (24) to search for a conserved volar gene signature. For statistical analyses, we capitalized on the presence of 2 volar tissues (palms, soles) to search for common genes.
We first confirmed that KRT9 was the highest expressed gene in volar epidermis (of 44726 transcripts, p=0.0001). As cultured volar fibroblasts have the ability to faithfully induce KRT9 ectopically (FIG. 4), we focused on gene expression of these cells.
Interestingly, homeobox gene mRNAs¨centrally important in embryonic patterning¨were still highly abundant in adult volar fibroblasts to presumably maintain their tissue identity (PAX9, SHOX, LMX lb, EMX2 Comparison to non-volar in Table 1). In comparison, signaling molecules published to promote KRT9 expression were comparatively lower expressed (Wnt5a, DKK1 Table 1). We therefore hypothesized that human adult skin tissue identity is actively maintained and that manipulations of these transcription factors might allow conversion of skin identity.
Table 1: Gene Chip Results for Normal Volar Fibroblast Gene Signature.
Genes up in volar fibroblasts rank (of name 46,878) fold p value PAX9 19 2 0.004 WNT5a 168 1.5 0.058 DKK1 8396 1.2 0.744 Genes down in volar fibroblasts rank (of name 46,878) fold p value SHOX 1 -4 0.005 LMX1b 162 -3.7 0.004 EMX2 9 -2.3, 0.017 ANOVA analysis done for triplicate samples of human volar/non-volar fibroblast (P2) of both hands and feet for RNA Affymetrix Exon chip transcript abundance values.
Based upon our microarray analysis, we focused on LMX1b. Heterozygous mutations result in Nail Patella syndrome, with defects on the dorsal nails and patellas (OMIM 161200). No homozygous mutations have been published in humans. However, homozygous knockout mice develop duplications of ventral structures.
Postembryonic functions for LMX1b are unknown. Our hypothesis was that LMX1b might be a master suppressor of the volar phenotype¨even active in adulthood. We confirmed LMX1b was almost completely suppressed in human volar whole dermis (data not shown). We then confirmed that LMX1b was suppressed in volar fibroblasts¨and noted that LMX1b inversely correlated with KRT9 levels not only with respect to volar/nonvolar but also upper/lower extremity (FIG. 7).
As a first step to determining LMX1b function, we next used siRNA treatment to knockdown LMX1b (80% reduction) to test whether it induced a signaling molecule known to promote the volar phenotype¨DKK-1. We discovered that LMX1b knockdown indeed increased DKK-1 (FIG. 8) levels, suggesting that LMX1b might act as a repressor for volar phenotype in fibroblasts.
LMX1b is a Master Suppressor of the Volar Phenotype. To probe LMX1b function, we then tested whether, under LMX1b knockdown, fibroblasts acquired the ability to induce KRT9. Indeed, as shown in FIG. 9 knockdown of LMX1b allowed non-volar fibroblasts from the dorsum of the foot to induce KRT9 in foreskin keratinocytes. We next tested if LMX1b knockdown could induce non-limb fibroblasts to stimulate KRT9 expression. We found that a diverse array of fibroblasts from foreskin, ear, cheek, lip and abdomen all acquired the ability to induce KRT9 with LMX1b knockdown (FIG. 10). These results clearly demonstrate that LMX1b suppresses a volar phenotype in a diverse collection of adult fibroblasts.
The ability of LMX1b knockdown in fibroblasts to induce KRT9 in non-volar keratinocytes gives a unique opportunity to dissect the necessary and sufficient pathways leading to the volar phenotype. To do so, we asked which genes follow three criteria: 1) genes highly enriched in palm fibroblasts relative to dorsum of the hands, 2) genes highly enriched in sole fibroblast relative to dorsum of the feet, and 3) genes which are highly enriched after LMX1b knockdown in diverse non-limb fibroblasts.
Candidate Downstream Genes from LMX1b. One of the primary candidate genes which fit these criteria is the homeobox gene PAX9. PAX9 is the transcription factor most enriched in volar tissues (Table 1). We confirmed the microarray by RT-PCR to verify that PAX9 is a volar homeobox gene (FIG. 11). Furthermore, knockdown of LMX1b in non-volar fibroblasts, results in significantly increased PAX9 gene expression (FIG. 12), consistent with results of LMX1b knockout mice. Finally, PAX9 null mice themselves show limb defects. These data suggest that PAX9 induction is downstream of LMX1b suppression.
While PAX9 is upregulated in volar tissues, it is possible that other genes are downregulated upon LMX1b knockdown that are responsible for volar phenotype induction.
The top genes which are suppressed in volar fibroblasts besides LMX1b are SHOX
and EMX2 (Table 1). We found a similar pattern on arrays of volar whole dermis and volar whole tissue methylation arrays. Also published arrays on LMX1b knockdown limb bud skin also demonstrate suppression of SHOX (FIG. 13 mouse homologue) and EMX2 (FIG.
14).
From our own microarray analysis of LMX1b knockdown fibroblasts at 24 hours, we also find early suppression of EMX2 (40%), and SHOX (30%) both ranking around the top 5% of most suppressed transcripts. Thus in a total of 3 distinct in vivo microarray studies, and 2 distinct knockdown array studies we find matching suppression of SHOX/EMX2 in conditions of volar tissue or knockdown LMX1b. These results again strongly suggest SHOX/EMX2 suppression might mediate LMX1b knockdown effects (FIG. 1).
Prophetic Investigation of the Transcription Factors and Cell Signaling Agents that Allow Fibroblasts to Induce Ectopic KRT9 in Non-Volar Keratinocytes. Multiple lines of evidence support a role for PAX9 to promote a volar phenotype. However, no gain-of-function or post-natal role in adult limb fibroblasts has been tested. PAX9 is both over-expressed and knocked-down to test its sufficiency and necessity for KRT9 induction in the context of both normal volar fibroblasts and LMX1b knockdown fibroblasts.
Whether PAX9 upregulation is necessary and/or sufficient to endow non-volar fibroblasts the ability to induce KRT9 in non-volar keratinocytes is determined. We first concentrate on PAX9 knockdown, using routine techniques established in the lab (FIGS. 6-10). As in FIG. 4, 6 and 9, volar and non-volar fibroblasts are expanded from extensive existing frozen stocks of 5 human donors. Knockdown using scrambled siRNA
(Dharmacon D-001910-10-05) or PAX9 siRNA (L-012242-00-0005) is performed with nucleofection (Lonza 4-D) on 1 million fibroblasts. After plating for 1 day in a 10cm2 dish, 250,000 foreskin keratinocytes are added. Following 3 days, cells are harvested and tested for KRT9 induction. This experiment is repeated, replacing volar fibroblasts with knockdown LMX1b non-volar fibroblasts (for PAX9/LMX1b double knockdown).
After testing the necessity of fibroblast PAX9 in KRT9 induction, its sufficiency is tested. As seen in FIG. 15, our lab has already performed transient transfections for the overexpression of GFP. We have already purchased PAX9 cDNA (Gene ID#5083)) and begun cloning into pcDNA3.1 vector. PAX9 or GFP is nucleofected into non-volar fibroblasts, and then incubated with foreskin keratinocytes and tested for KRT9.
In parallel, RT-PCR and western blotting are used to quantify the degree of over- or under-expression of manipulated gene. Successful results are verified with several distinct siRNA species and compared to scrambled controls. Finally, rescue studies are attempted where larger amounts of transfected transcripts should overcome the effects of limiting siRNA.
Based on our extensive microarrays demonstrating elevated PAX9 in volar fibroblasts, and increased PAX9 after LMX1b knockdown/KRT9 inductivity in non-volar fibroblasts, we anticipate that PAX9 overexpression in non-volar fibroblasts will endow them with the ability to induce KRT9. It is likely that PAX9 will also be necessary for induction and that knockdown of PAX9 will eliminate the capacity for volar fibroblasts or LMX1b knockdown non-volar fibroblasts to induce KRT9. If not the case, this raises the limitation that other homeobox transcription factors might compensate. For example, on several in vivo arrays we also see elevations of the homeobox LHX2 and LHX9 in volar fibroblasts¨though these were not elevated in LMX1b knockdown fibroblasts which have the ability to induce KRT9. This highlights that the mechanisms of volar fibroblasts and non-volar LMX1b knockdown fibroblasts to induce KRT9 are not likely identical. Although we are focusing on overlapping features as clues to function, redundant mechanisms might exist in native volar fibroblasts which are absent in LMX1b knockdown fibroblasts. LHX2/9 might be examples.
Thus, it is possible that PAX9 might be necessary for KRT9 induction in LMX1b knockdown non-volar fibroblasts, but perhaps not necessary in volar fibroblasts because of redundant pathways like LHX2/9. Therefore an alternative would be to then test double knockdowns of LHX2 or 9 and PAX9. Another alternative hypothesis might be that simultaneously transcripts which are upregulated by LMX1b (PAX9) and those downregulated (SHOX/EMX2) must be coordinately modified to stimulate KRT9. Another alternative effort would be knock-in of PAX9 and knock-down SHOX/EMX2 simultaneously.

Whether SHOX/EMX2 downregulation is sufficient and/or necessary to endow non-volar fibroblasts the ability to induce KRT9 in non-volar keratinocytes is determined. In these experiments, the transcription factors most downregulated in volar fibroblasts are investigated. Two transcription factors were together and highest as suppressed in volar fibroblasts: SHOX and EMX2. We found that SHOX/EMX2 is downregulated in the conserved mRNA signature of volar fibroblasts (Table 1). SHOX/EMX2 are downregulated by LMX1b knockdown in limb skin or in non-volar fibroblasts (30-40% at 24 hours data not shown) which acquire the ability to induce ectopic KRT9. Both are downregulated in LMX1b knockout mice (FIGS. 13 and 14). Also, both SHOX and EMX2 have dorsum-limited expression in the developing limb and brain respectively. This suggests they might specify dorsal versus ventral fates in multiple tissues. Also, SHOX is mutated in some conditions of altered limb development, Langer Mesomelic Dysplasia (OMIM
#249700).
EMX2 has no known limb defects, but as for both genes, their postnatal function¨in the skin or otherwise¨has not been examined. We hypothesize that as for LMX1b, their continued suppression in volar structures maintains their ongoing identity. Therefore we predict that SHOX/EMX2 downregulation may mediate KRT9 inductivity and is downstream of LMX1b suppression.
Whether SHOX (Dharmacon L-011107-00-0005) or EMX2 (Dharmacon L-017904-00-0005) knockdown can endow non-volar fibroblasts the ability to induce KRT9¨just as LMX1b knockdown does is tested first. Next, whether double knockdown of both and SHOX is additive (compared to each separately) or necessary for KRT9 induction is then tested. After testing the sufficiency of knockdown to endow KRT9 inductivity, EMX2 (GFP
tagged cDNA Origene RG228105), SHOX (GFP tagged cDNA Origene RG218605), and GFP plasmids (pCMV6-AC-GFP Origene PS100010) overexpressed in transient transfections to determine if downregulation is necessary for normal volar fibroblast induction of KRT9 expression. EMX2, SHOX or GFP plasmids with LMX1b siRNA are then overexpressed in non-volar fibroblasts to determine if these cells become resistant to the effects of LMX1b knockdown.
We anticipate that the specification of ventral fate will require the suppression of both EMX2 and SHOX simultaneously. While the LMX1b knockout mouse shows full duplication of ventral structures, this is not seen in EMX2 or SHOX knockout mice. Because both are downstream of LMX1b, and both suppressed in ventral tissue, we hypothesize that one might compensate for the other. We therefore also anticipate that overexpression of either will prevent LMX1b knockdown from endowing KRT9 inductivity in non-volar fibroblasts. Similarly, the overexpression of either will prevent volar fibroblasts from their normal ability to induce KRT9. These results will help define the genetic network which regulates volar skin identity, and add to evidence that this is an active process which maintains skin identity.
EMX2 and SHOX represent even still just a subset of downstream transcription factors from LMX1b. Although it is likely that EMX2 and SHOX are the dominant downstream factors given that they were the only ones to appear in both a conserved non-volar gene list (palm&sole) and an LMX1b knockdown gene list, others might exist. An alternative might then be to do CHIP arrays with LMX1b to determine a fourth array to define downstream genes. This would provide an even more robust bioinformatic platform to cross-reference biologically relevant genes. A minor limitation of this aim is the possibility that the GFP tag of EMX2 or SHOX might interfere with function. An alternative will be to use untagged EMX2 and SHOX cDNAs which are available. Alternatively, we will concentrate on direct signaling control by lmx lb on released factors such as DIck-1. Other alternative areas for consideration include entirely non-genomic mechanisms of volar induction such as volar connective tissue and could involve evaluating the capacity for devitalized volar dermis to promote KRT9 induction after seeding with non-volar fibroblasts.
The sufficiency and necessity of DKK-1 release for ectopic KRT9 induction in keratinocyte cocultures with volar fibroblasts, lmx lb knockdown non-volar fibroblasts, and mutants. As described above, the transcription factors which control the volar identity of fibroblasts and the capacity to induce KRT9 are defined. However, for full mechanistic insight into the process of keratinocyte phenotype control by fibroblasts, we must also define the down-stream signaling agents. These agents might even eventually be useful as adjunctive therapies in addition to volar fibroblasts to induce ectopic volar skin. These experiments focus on DKK-1 which has already been proposed to inhibit melanocytes function in volar epidermis. Addition of DKK-1 to skin cultures also causes epidermal thickening its necessity was not tested. Also, the sufficiency and necessity of DKK-1 to cause induce KRT9 has not been tested. Finally, the necessity of DKK-1 to mediate the capacity of LMX1b knockdown fibroblasts to induce KRT9 has also not been tested.
Supporting its likely role, we find that DKK-1 is indeed increased after LMX1b knockdown, coincident with the ability to induce KRT9 (FIG. 8). Therefore the sufficiency and necessity of DKK-1 in scenarios of KRT9 induction is tested¨first in normal volar fibroblasts, and if successful then in mutants.

First, sufficiency is tested by adding 0.03 ug/m1rDkk-1 (R&D 5439-DK) to foreskin keratinocyte cultures for 24 hours (based on co-culture conditions) and then measure for KRT9 induction. To test necessity, co-cultures are initiated as described above. Coincident with the addition of keratinocytes, 0.1m/m1 of neutralizing Dick-1 antibody (R&D AF1096) is added, which has been shown to decrease Dick-1 activity by 50%, with higher concentrations blocking >90%. After co-culturing, quantitative RT-PCR is performed as described above for KRT9. Volar fibroblasts are tested and, if successful, LMX1b knockdown fibroblasts. If PAX9 knock-ins or EMX2/SHOX knock-downs successfully induce KRT9, then these mutants are tested as well for the necessity of DKK-1.
We anticipate that DKK-1 will be sufficient for KRT9 induction, as has been shown for wnt5a. We also anticipate it will be partially required for KRT9 induction by volar fibroblasts, LMX1b knockdown fibroblasts, and possible PAX9/SHOX/EMX2 mutants.
If our above hypotheses are not supported by experimental evidence, then other signaling agents must be considered. It has already been published that wnt5a is sufficient for KRT9 induction, and wnt5a was elevated on our arrays of volar fibroblasts (Table 1). Although we find it only minimally elevated after lmx lb knockdown, this is an alternative to consider. To identify other candidates, we have performed bioinformatics on our gene lists to identify those signaling agents which are elevated normally in volar fibroblasts and are also elevated in LMX1b knockdown. These candidates may be pursued as alternative approaches and include: IL-24 (top 988th percentile), IL-12A (98.6t1) as well as less researched extracellular signalers such as SEMA3a (99.2th) and TFPI2(99.2th).
Although LMX1b knockdown and potentially modulation of PAX9/SHOX/EMX2 might stimulate KRT9¨and perhaps even requiring DKK1¨it remains possible that a full volar phenotype might not be induced by single gene/protein manipulation, and even that the means of volar induction of LMX1b knockdown fibroblasts might represent a subset of the in vivo mechanism of normal volar induction. Supporting the possibility that a single agent like LMX1b knockdown can indeed fully recapitulate normal volar induction are multiple lines of evidence. Firstly, we find that both normal volar fibroblasts and LMX1b knockdown fibroblasts induce KRT9 to the same degree-- by around 3-4 fold (FIGS. 4&10).
Secondly, KRT9 is a suprabasal keratin and thus a late-stage marker of volar identity.
Thirdly, it is likely that a limited set of extracellular signaling cues will define volar identity, and these will highly overlapping if not identical in both volar and LMX1b knockdown non-volar fibroblasts. Finally, the LMX1b knockout mouse shows full duplication of ventral structures which is the most convincing of all. However, since DKK-1/PAX9 upregulation and SHOX/EMX2 downregulation are downstream of LMX1b an equivalent argument cannot be made regarding fibroblasts with these agents manipulated. Therefore an alternative aim will be to define the transcriptional profile of "volarized" keratinocytes exposed to these cells and compare them to native volar keratinocytes. Similarly, a comparison of both in 3-D cultures (FIG. 5) could define any phenotypic differences. The results of this alternative aim would be defining whether partial "volarization" after manipulation of these volar factors occurs and support the further search for other signals.
If our results do not match those expected, then a second limitation is that in vivo signals might act differently from the proposed in vitro tests. Therefore, a second alternative would be to use mouse models such as crossing the available Col 1a2-cre-er mouse (JAX#
016237) to foxed LMX1b to see how much adult tissue identity could be fully converted.
We have acquired the foxed LMX1b mouse (Randy Johnson, MD Anderson see letter of support) to prepare for this possibility. If these mice have volarization of the back skin for example, then we will have an in vivo system to define the signaling agents which are responsible using exogenous proteins or inhibiting antibodies.
Prophetic Investigation of Tissue Homeostatic Mechanisms Which Maintain Non-Volar Skin Identity Using Both In Vitro and In Vivo Models. Whether volar fibroblast induction of KRT9 is inhibited in the presence of non-volar fibroblasts is determined. To overcome any inhibition, the ideal ratio of added volar-fibroblasts to established non-volar fibroblast/keratinocytes for KRT9 induction in both in vitro and in vivo assays is defined.
Tissue identity is remarkably static. Despite constant cellular turnover, even adjacent areas of skin such as at the transition of volar to non-volar maintain their identity. Therefore, it is likely the case that redundant mechanisms maintain tissue identity.
These have been investigated at the genetic level with epigenetic mechanisms for example.
However, to our knowledge, investigations on how multicellular tissue identity is maintained have not been performed. These questions will become increasingly important in regenerative medicine as cellular therapy is used. The present inventors address the hypothesis that in the case of volar tissue conversion, non-volar fibroblasts inhibit the ability of volar fibroblasts to induce ectopic KRT9 in keratinocytes. In the process, parameters for optimizing a human clinical trial are defined. Although 2-D cell culture system has the advantage of speed and reproducibility, in vivo mouse HAT assay (FIG. 16) experiments given their greater applicability to our eventual goal of human use are performed in parallel.
We have established that KRT9 is induced roughly 3-4 fold when 1 million volar fibroblasts are added to 250,000 non-volar keratinocytes. Here, co-cultures of increasing amounts of non-volar fibroblasts with 250,000 non-volar keratinocytes are first established.
One million volar fibroblasts are then added to determine the degree to which induction is inhibited (from 3-4 fold average). We then determine at which ratio of volar:non-volar fibroblasts KRT9 inhibition is minimized. Whether conditioned media from non-volar fibroblast mediates such an inhibitory effect is also tested, given that fibroblasts have little cell-to-cell contact. For in vivo studies, analogous studies in the HAT assay (FIG.
16) are performed. The present inventors have experience with reconstituting full hair follicles from cell slurries, both in subcutaneous injections and in the Lichti hat model (FIG.
16). Here, human non-volar fibroblasts (10 million) and keratinocytes(10 million) are combined to reconstitute non-volar skin in the lcm diameter silicon "hat"
chamber on a SCID
mouse. After graft take (4 weeks), sub-epidermal injections of 0.1, 1 and 10 million volar fibroblasts are performed, then epidermis thickness is measured using non-invasive confocal scanning laser microscopy as we do routinely on mice. We estimate thickening to occur at week 3-4 given typical reconstitution timelines (FIG. 5,). The graft is then excised and epidermal thickness is measured by histology and KRT9 levels by qRT-PCR to define which ratio optimally "volarizes" skin.
We anticipate that non-volar fibroblasts will inhibit KRT9 induction by volar fibroblasts. Evidence for success are the ligands which have been associated with inducing the volar phenotype and their functions. For example, wnt5a is published to induce KRT9.
Wnt5a activates I3-catenin independent pathways. Similarly, we have confirmed that wnt-inhibitory protein DKK-1 is elevated in volar tissues (FIG. 8) and it has been shown to decrease melanocytes function in volar skin. Given the role of canonical wnts in promoting hair follicles morphogenesis and cycling, the absence of hair follicles in volar skin, and the upregulation of wnt5a/Dkk-1, volar skin could be a product of a canonical wnt-poor environment. Therefore the presence of wnts in non-volar fibroblasts will likely inhibit KRT9 induction. Determining the exact degree of this inhibition is important for measuring an ideal elevated ratio of volar fibroblasts necessary to overcome this inhibition. This ratio can then be directly used to determine the quantity of volar fibroblasts to inject based on the known density of non-volar fibroblasts.
We anticipate that this negative effect of non-volar fibroblasts may be present in the conditioned media from non-volar fibroblasts. The evidence for this is that there is little physical contact of fibroblasts and keratinocytes in epithelial mesenchymal interactions in the skin given the extensive basement membrane. Therefore modulation of KRT9 expression likely occurs exclusively through paracrine signaling molecules.

Limitations are the possibility that no inhibition of KRT9 induction will occur from non-volar fibroblasts. If this is the case, then this bodes well for this therapy. Another limitation is the relative difficulty of in vivo animal experiments an alternative would be using 3-D systems (FIG. 5). A final limitation is that while we will not define the specific factors which inhibit KRT9 inductivity. An alternative would be to fractionate the media using protein size exclusion columns followed by mass spectrometry screening of responsible fractions, but this is beyond the scope of the grant.
Whether minority volar fibroblast have decreased survival, proliferation or gene expression in majority non-volar fibroblast cultures is then determined.
Whether fractionated dosing with serial injections of volar fibroblasts to non-volar fibroblasts/keratinocytes may overcome this indirect effect and enhance KRT9 induction in both in vitro and in vivo assays is defined.
As mentioned above, multiple mechanisms likely maintain tissue identity. For example, circulating fibroblasts or migrating fibroblasts during wounding likely die or adopt the phenotype of their surrounding cells at their destination. However, dermal fibroblasts default is to maintain their identity even after removal from the body.
Previous work demonstrated that dermal fibroblasts maintain their hox signature in culture.
Our results demonstrating a conserved volar phenotype corroborate that group's findings (Table 1). This is a paradox: if fibroblasts by default maintain their positional memory, how is this memory lost in the cases of ectopic fibroblasts such as would happen with migrating ectopic fibroblasts during wounding or hematogenously seeded ectopic fibroblasts?
Overcoming these mechanisms will be important for the ectopic injection of fibroblasts to induce KRT 9.
We hypothesize that cell signaling occurs in majority populations of fibroblasts to maintain their identity minority populations will show decreased proliferation, survival or native gene expression. The rationale is to test this hypothesis in vitro and in vivo.
Our first effort will be to quantitate survival, proliferation and gene expression in minority site-mismatched fibroblasts compared to the majority population in fibroblast co-culture experiments. Established commercially available techniques for cellular labeling are used prior to placement in co-cultures. Specifically, Cell Trace CFSE (green) and Cell Trace Violet cell labeling are employed which are stable up to 10 generations of cells, not transferred to adjacent cells, and can be distinguished by flow cytometry.
These approaches have been validated and published, mostly for T cell activation studies, but also for adherent cells. Proliferation and necrosis are quantitated by analytical flow cytometry of each distinct population. Cell sorting is also utilized for analyzing gene expression by RT-PCR.

We will first perform positive controls using both green and violet dyes in a homogenous population. Specifically, we will label a subset of volar cells with green, and a larger population of volar cells with violet. We will verify that these differently labeled groups in a homogenous population have identical rates of proliferation, cell death, and gene expression. We will do the same with non-volar cells. For both we will use serum starved and serum added fibroblasts as positive controls to demonstrate differences in proliferation.
After confirming these controls, we will label minority populations of volar and non-volar populations in majority non-volar and volar populations respectively. We will use analytical flow to determine up to 10 population doublings, and measure for differences in proliferation or necrosis (DAPI exclusion, LSRIIb with UV laser) in minority populations. We will sort minority and majority populations for RNA extraction and qRT-PCR to see for example if PAX9 expression decreases and LMX1b expression increases in minority volar populations¨so they match surrounding fibroblasts over time.
We will determine the length of time required for an effect of non-volar fibroblasts to inhibit the activities of volar fibroblasts. Then we will test if serial injections before this elapsed interval of volar fibroblasts into non-volar fibroblast/keratinocyte cocultures will increase KRT9 induction.
In parallel we will test with animal models. We will order inbred sex and strain (HLA
matched FVB) mice, one with a constitutive luciferase gene as a transgenic (JAX#008450).
Fibroblasts will be cultured from different areas of the transgenic mouse(hind-limb, back, paw & abdomen), expanded to 1 million fibroblasts and either injected with identical numbers homo-topically (same place) or hetero-topically (mismatched location) in the HLA-matched non-transgenic host. Graft survival will be measured by whole-mouse non-invasive IVIS luciferase imaging (available in our animal facility) over the course of 4 weeks. We will quantitate if heterotopic grafts have decreased survival compared to homotopic grafts.
Anticipated Results, Limitations and Alternatives: Given every tissue's fixed identity despite injury and constant cellular turnover, we predict tissue-level homeostatic mechanisms maintain tissue identity. (If this is not the case, see limitations below). We clearly demonstrate that volar and non-volar fibroblasts maintain very distinct mRNA
expression signatures in culture (Table 1). These lead to phenotypic differences which we have also noted, for example that sole fibroblasts proliferate more slowly at late passage (FIG. 17).
However, we have not tested the effect of mixed populations. We anticipate that in the same way that cultured cells release unidentified autocrine factors which require that they be plated at minimum densities, in vivo site specific fibroblasts will be homotrophic.

Beyond this theoretical evidence for the inhibition of ectopic fibroblasts, practical experience in the use of autologous fibroblasts for the treatment of wrinkles also supports these mechanisms. These trials all consisted of serial injections of mismatched fibroblasts, and serial injections are recommended also for clinical use. If ectopic fibroblasts survived equally, no repeat injections would be required¨but they are. We hypothesize that native fibroblasts will repress ectopic site-mismatched fibroblasts. The importance of this aim is creating an in vitro system to demonstrate this effect as a prelude to dissecting its mechanism.
We anticipate that in the presence of majority non-volar fibroblasts, minority volar fibroblasts ¨compared to their status in homogenous solo-cultures-- will demonstrate some combination of decreased proliferation, increased cell death, decreased PAX9, and increased LMX lb, SHOX or EMX2. Given the 3 day timeframe for KRT9 induction, we anticipate this effect to occur after 48 hours, and that divided serial injections every 48 hours will be superior to an equal total amount given once.
The main limitation of this aim is the possibility that there is no inhibition of minority volar fibroblast populations in majority non-volar fibroblast co-cultures.
While this seems unlikely, this negative result will itself be illuminating and bode well for Aim 3. Another limitation (also applicable to Aim 2c) is the relative difficulty of in vivo animal experiments
an alternative would be using 3-D systems (FIG. 5). A limitation of the in vitro effort is the possibility that other tissue components such as extracellular matrix, keratinocytes, or some other element not present in these fibroblast co-cultures might maintain non-volar tissue identity therefore we will also test an in vivo model in parallel.
2c: Determine if wounding augments KRT9 induction in cultures of non-volar keratinocytes with variable ratios of volar to non-volar fibroblasts using both in vitro and in vivo models. Test whether adult versus neonatal keratinocytes have similar potential for KRT9 induction.
Rationale: Methods of tissue conversion exist in mice. As illustrated in FIG.


Why Amish Are Immune to Allergies and Asthma

God&rsquos Word surely is the answer to all of life&rsquos problems. Psalm 119:104-105:

104 Through thy precepts I get understanding: therefore I hate every false way.

105 Thy word is a lamp unto my feet, and a light unto my path.

When once reviewing various archaeological discoveries, I came across an ancient foot lamp. The user would light this lamp and it would extend out from the body by about 5&rsquo&mdashjust above ground level. By the use of this contraption, one could safely walk on a starless night. The Word of God is a lamp unto our feet, but, as the foot lamp of old, it must lead in order to deliver the needed results. The Bible speaks of man&rsquos condition prior to salvation in Matthew 4:16:

The people which sat in darkness saw great light and to them which sat in the region and shadow of death light is sprung up.

Have you seen the Light? John 1:6-9:

6 There was a man sent from God, whose name was John.

7 The same came for a witness, to bear witness of the Light, that all men through him might believe.

8 He was not that Light, but was sent to bear witness of that Light.

9 That was the true Light, which lighteth every man that cometh into the world.

Have you been born again? Are you ready for the eternal Light that will eliminate all your darkness, the Light that will satisfy all your needs? Today is your day of salvation. Click onto &ldquoFurther With Jesus&rdquo for childlike instructions and immediate entry into the Kingdom of God. NOW FOR TODAY&rsquoS SUBJECT.

GOD SAID, Leviticus 25:2-4, 20-22:

2 Speak unto the children of Israel, and say unto them, When ye come into the land which I give you, then shall the land keep a sabbath unto the LORD.

3 Six years thou shalt sow thy field, and six years thou shalt prune thy vineyard, and gather in the fruit thereof

4 But in the seventh year shall be a sabbath of rest unto the land, a sabbath for the LORD: thou shalt neither sow thy field, nor prune thy vineyard.

20 And if ye shall say, What shall we eat the seventh year? behold, we shall not sow, nor gather in our increase:

21 Then I will command my blessing upon you in the sixth year, and it shall bring forth fruit for three years.

22 And ye shall sow the eighth year, and eat yet of old fruit until the ninth year until her fruits come in ye shall eat of the old store.

GOD SAID, Leviticus 25: 11-12:

11 A jubilee shall that fiftieth year be unto you: ye shall not sow, neither reap that which groweth of itself in it, nor gather the grapes in it of thy vine undressed.

12 For it is the jubilee it shall be holy unto you: ye shall eat the increase thereof out of the field.

GOD SAID, Galatians 6:7:

Be not deceived God is not mocked: for whatsoever a man soweth, that shall he also reap.

MAN SAID: Our science has mastered agriculture. We can chemically control the pests of the field and our genetically modified products will fill the earth with plenty.

Now THE RECORD. The Bible was authored by God and penned by His holy men. Its narrative is historically accurate, the miraculous accounts fully certified, and inherent within His commandments are a blessing or a curse. Because God&rsquos commandments are true and righteous altogether, obeying them yields the blessing of doing the right thing disobeying results in the curse of doing the wrong thing. It really is just that simple. The results of man continually rejecting the direction of the Creator are negative and even deadly. Those looking for proof need look no further.

The first five books of the Bible&mdashknown as the Torah or Pentateuch&mdashwere given by God to Moses. The examples and commandments pronounced by God in these books were given for the purpose of building a holy nation full of good fruits and contentment. The laws and directives were national in nature. Every Israelite was obliged to obey. For the purpose of this feature, GodSaidManSaid has placed the commandments in five categories:

  1. Myriad of laws that ensure the underwriting of the expense of government, that alleviate guilt and stress, regulate social conduct, and establish a national rhythm and identity.
  2. The strict commandment to bury in the ground all human waste&mdashnot to flush it into the waterways, treated and untreated, as is commonly done today.
  3. God&rsquos dietary laws concerning what not to eat or even touch, and what to eat, such as clean meats purged of blood and fat, and raw milk, raw honey, olive oil, and more.
  4. God&rsquos law of the quarantine for running issues of any nature, even the common cold. Contagious issues were separated from the general population for seven days outside the camp until the individual was pronounced clean by a priest.
  5. God&rsquos commandment to give the land its Sabbath, as well as the commandment of the Jubilee every 50 years, where two Sabbaths of the land were back-to-back.

These national laws were designed to build a powerful and happy people.

It should make good sense that obeying the instructions of the Manufacturer of life would be the right thing to do, but man has found a &ldquobetter&rdquo way. This feature will air several different pieces of information which seem slightly unrelated, but a closer look will reveal their commonality. First, several preparatory paragraphs from the GodSaidManSaid feature, &ldquoThe Dirt You Eat&rdquo follow:

  • Beans, snap green à 34%
  • Broccoli à 53%
  • Carrots à 27%
  • Peaches à 44%
  • Strawberries à 33%
  • Tomatoes à 62%

The following excerpts are from The Healthy Home Economist, November 13, 2014. The headline reads, &ldquoThe Real Reason Wheat is Toxic (it&rsquos not the gluten).&rdquo

  • Gastrointestinal disorders
  • Obesity
  • Diabetes
  • Heart Disease
  • Depression
  • Autism
  • Infertility
  • Cancer
  • Multiple Sclerosis
  • Alzheimer&rsquos disease and the list goes on and on.

RealFarmacy.com published the following under the heading, &ldquoScientists Reveal Why Amish Children are Immune to Allergies & Asthma:&rdquo

Studies in Sweden have determined that kids raised on dairy farms are considerably more resistant to allergies than those who live elsewhere, including nearby rural areas without non-dairy farms. This wasn&rsquot the only study displaying this phenomena.

Allergies and asthma have been on the rise in the West over the past few decades, especially among younger children. In addition to vaccinations and our immersion into chemicals that permeate a fetus from mothers&rsquo exposure to them, there has been conjecture that our obsession for cleanliness is a contributing factor.

The argument posits that exposure to dirt and its natural microbes helps an immune system develop in a young child, so playing in the dirt is a good thing. This theory is known as the &ldquohygiene hypothesis,&rdquo where too much hygiene or cleanliness for babies and toddlers disables development of a mature immune system.

Recently, researchers conducted an epidemiological study at the University of Gothenburg, located in Sweden&rsquos second largest city, Gothenburg. They monitored children&rsquos health from birth to age three in a large nearby rural district. Around half of them lived on dairy farms while the rest did not.

Those who lived on dairy farms tended to be allergy-free, while the others were 10 times more prone to developing allergies. (http://sahlgrenska.gu.se)

These farms were all smaller traditional farms. Besides breathing in or absorbing microbes from poop [animal dung] and earth in the immediate air, the kids drank or used raw milk. More importantly, so did their moms. The researchers mentioned the prevalent raw milk evidence briefly but tap-danced around it.

After Swiss Amish were studied with similar results as other traditional European farm studies, the researchers seemed stuck on what differentiated these types of farms from others.

But an American researcher followed up with Indiana (USA) Amish study to find similar results, higher immunity to disease, asthma, and allergies. The Amish tend to use raw milk from humanely-treated, grass-fed cows while avoiding or minimizing toxic chemicals on their crops.

You won&rsquot find higher immunity on factory farm dairies and large monoculture farms that indulge in excessive amounts of toxic pesticides, herbicides, and chemical fertilizers.

As a matter of fact, more and more children on or even near those farms are experiencing autistic spectrum disorders or autoimmune diseases beyond asthma or allergies. [End of quote]

Disregard for God&rsquos given ecological protocols generate debilitating results such as the rejection of a national law to give the land its Sabbath. Today&rsquos research has not even addressed the biological benefit of eating the preserved old fruit of the land during and following the Sabbath of the land. The Word of God is the foundation of all truth. Build your life here.

GOD SAID, Leviticus 25:2-4:

2 Speak unto the children of Israel, and say unto them, When ye come into the land which I give you, then shall the land keep a sabbath unto the LORD.

3 Six years thou shalt sow thy field, and six years thou shalt prune thy vineyard, and gather in the fruit thereof

4 But in the seventh year shall be a sabbath of rest unto the land, a sabbath for the LORD: thou shalt neither sow thy field, nor prune thy vineyard.

GOD SAID, Leviticus 25: 11-12:

11 A jubilee shall that fiftieth year be unto you: ye shall not sow, neither reap that which groweth of itself in it, nor gather the grapes in it of thy vine undressed.

12 For it is the jubilee it shall be holy unto you: ye shall eat the increase thereof out of the field.

GOD SAID, Galatians 6:7:

Be not deceived God is not mocked: for whatsoever a man soweth, that shall he also reap.

MAN SAID: Our science has mastered agriculture. We can chemically control the pests of the field and our genetically modified products will fill the earth with plenty.

Authorized King James Version

Louis, PF, &ldquoScientists Reveal Why Amish Children are Immune to Allergies & Asthma,&rdquo RealFarmacy.com

Sarah, &ldquoThe Real Reason Wheat is Toxic (it&rsquos not the gluten&rdquo, TheHealthyHomeEconomist.com


Gottumukkala S. Raju, M.D. FACG, FASGE

Dr. Gottumukkala Subba Raju is professor of the Department of Gastroenterology, Hepatology, and Nutrition. He holds the John Stroehlein Distinguished Professorship and leads the Charles Butt, H-E-B GI Cancer Prevention, Research, and Education Program. He also serves as the inaugural Editor-in-Chief of Video GIE, an official journal of the American Society for Gastrointestinal Endoscopy. Dr. Raju is the recipient of the American Society for Gastrointestinal Endoscopy President's Award in 2019. He is one of the finalists for the UT MD Anderson Cancer Center Julie & Ben Rogers Award for Excellence in Education (2020). Dr. Raju is developing a dedicated education program for Endoscopy Techs at the Coleman College for Health Sciences.

Dr. Raju graduated from the Andhra Medical College, Visakhapatnum (MBBS) with distinction. He secured first rank in the all India competition examination to enter PGIMER, Chandigarh and GB Pant Hospital, Delhi University where he completed his internal medicine residency (MD) and gastroenterology fellowship (DM) respectively. Dr. Raju also served as clinical and research registrar in Dr. K.D.Bardhan’s unit under the Royal College of Physicians of UK Overseas Doctor Training Program during this period he completed his membership exam of the Royal College of Physicians (MRCP). He is certified by the American Board of Internal Medicine in Gastroenterology in 1997,2007, and 2017 (top 10 decile).

Dr. Raju underwent training in this country at the Cleveland Clinic, Cleveland, where he graduated as the best outgoing resident. After completing his gastroenterology fellowship at the University of Iowa Hospitals and Clinics, Iowa City, Dr. Raju underwent therapeutic endoscopy training at Beth-Israel Deaconess Hospital, Harvard Medical School, Boston.

Dr. Raju assumed his first academic appointment at Kansas University Medical Center, Kansas City and subsequently moved to the UTMB, Galveston, and joined the University of Texas MD Anderson Cancer Center, Houston in 2009. He has continually risen through the academic ranks, achieving associate professor in 2001, promotion to professor in 2007 and endowed professor in 2015.

Dr. Raju is repeatedly listed in the Best Doctors, Top Doctors, and Super Doctors of America and is a Fellow of the American Society of Gastrointestinal Endoscopy, & American College of Gastroenterology. Other accolades include Distinguished Service Award from the American Society for Gastrointestinal Endoscopy, which is presented to someone who has made a long-term contribution to GI endoscopy in the areas of equipment research and development, and who has been a strong supporter of the educational and research mission of ASGE. Rated in the top 1% nationally on Consumer Assessment of Healthcare Providers & Systems measures related to patient care experience by the Agency for Healthcare Research and Quality / US Department of Health & Human Services.

Dr. Raju's YouTube colonoscopy education channel shares colonoscopy techniques to prevent COLON CANCER PREVENTION through better detection and resection with over 800 videos and 2,750,000 views.

Dr. Raju is passionate about service - "Hands that serve are holier than lips that pray", Saibaba.

Present Title & Affiliation

Primary Appointment

John Stroehlein Distinguished Professor of Gastroenterology, Department of Gastroenterology, Hepat,& Nutr, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX

Research Interests

An author of over 100 peer-reviewed publications, Dr. Raju is internationally recognized for his pioneering work on endoscopic closure of colon perforations and contributions to colonoscopy, adenoma detection, and endoscopic mucosal resection of large and complex colon polyps. His current clinical research efforts focus on improving the quality of colonoscopy screening and endoscopic resection and translational research efforts focus on collaboration with basic scientists to improve the understanding of genome and microbiome interaction in colorectal neoplasia.

Dr. Raju is a pioneer in video journalism and serves as the inaugural co-editor-in-chief of VideoGIE, an official journal for the American Society for Gastrointestinal Endoscopy.

Dr. Raju is a member of several professional organizations and has served on many national society committees.

Dr.Raju's team is interested in colon cancer prevention and endoscopic resection of colon polyps as an alternative to surgery.

Endoscopic closure of colon perforations: This investigative work in the animal laboratory at the University of Texas Medical Branch, Galveston, formed the basis for clinical care of patients with large polyps who are at high risk for perforation. Endoscopic mucosal resection of colon polyps as an alternative to surgery: Our team is able to avoid surgery in 75% of patients with large and flat lesions that could not removed in a community practice. Invited to give the BJ Vakil Oration at the 1st World Conference on GI Endoscopy on February 18, 2017 by the President of World Endoscopy Organization, Nagi Reddy. Quality improvement in colonoscopy: Developed the Natural Language Processing Program as an alternative to manual method to measure quality of colonoscopy (recipient of the University of Texas MD Anderson Cancer Center DOIM First Annual Quality Improvement Distinguished Paper Award) Past Research Profile: Publications for lookup. Future Research: Dr. Raju started two studies to understand the biology of subtle and flat precancerous lesions that are difficult to recognize and resect in collaboration with basic scientists and epidemiologists. A. Prospective Cohort Study of Endoscopic Resection of Large & Flat Lesions B. Serrated Lesions of the Colon

Clinical Interests

Dr. Raju’s clinical practice involves colon cancer screening and endoscopic resection of complex colon polyps as an alternative to surgery. As a clinician educator, he focuses on improving the quality of colonoscopy not only in his practice, but also aids in the education of his peers using a dedicate YouTube channel.

Endoscopic Mucosal Resection: Dr. Raju has resected over 400 large flat lesions between 2009 and 2014, with over 200 lesions referred from outside that would have required surgery. The bleeding rate is less than 5%, perforation rate less than 1% and none required surgery for management of bleeding or perforation. The residual adenoma at 6 months was less than 3% (you could check his EMR experience and look up his outcomes ).

Colon cancer screening: Dr.Raju offers colon cancer screening, with a high adenoma detection rate (>50% in men > 35% in women you could look up the adenoma detection rates.)

Dr. Raju's YouTube colonoscopy education channel shares colonoscopy techniques to prevent COLON CANCER PREVENTION through better detection and resection with over 700 videos and 1,000,000 views.

Dr. Raju's facebook education channel - Endoscopist -shares tips on endoscopy and colonoscopy.

Education & Training

Degree-Granting Education

1992Royal College of Physicians, London, GBR, MRCP, Medicine
1989Delhi University, New Delhi, IND, DM, Gastroenterology
1986PGIMER, Chandigarh, IND, MD, Internal Medicine
1982Andhra Medical College, Visakhapatnam, IND, MBBS, Medicine

Postgraduate Training

1997-1998Interventional Endoscopy, Beth Israel & Deaconess Center, Harvard Medical School, Boston, MA
1995-1997GI Fellowship, University of Iowa, Iowa, IA
1993-1995Internal Medicine Residency, Cleveland Clinic, Cleveland, OH

Board Certifications

Experience & Service

Academic Appointments

Professor, Department of Gastroenterology, Hepat,& Nutr, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, 2009 - Present

Professor, The University of Texas Medical Branch, Galveston, TX, 2006 - 2008

Associate Professor, The University of Texas Medical Branch, Galveston, Galveston, TX, 2001 - 2006

Assistant Professor, The University of Kansas Medical Center, Kansas City, KS, 1998 - 2001

Administrative Appointments/Responsibilities

GI Fellowship Site Director, Department of Gastroenterology, Hepat,& Nutr, The University of Texas MD Anderson Cancer Center, Houston, TX, 2011 - 2016

Director of Endoscopy, University of Texas Medical Branch, Galveston, Galveston, TX, 2001 - 2008

Director of Endoscopy, Kansas University Medical Center, Kansas City, KS, 1998 - 2001

Other Appointments/Responsibilities

Chairman, WEO Webinar, World Endoscopy Organization, Munich, 2020 - 2022

Editor-in-Chief, Video GIE, American Society for Gastrointestinal Endoscopy, Downers Grove, IL, 2018 - 2020

Institutional Committee Activities

Member, Endowed Positions and Awards Committee, 2019 - 2022

Steering Committee, Premalignant Genome Atlas Program, 2014 - 2018

Chair, GHN Tissue Bank, 2013 - 2020

Member, The University of Texas MD Anderson Cancer Center GME, 2011 - 2016

Honors & Awards

2021Robert McKenna Memorial Lecture at the Canadian Digestive Diseases Week, Canadian Digestive Diseases Week
2020The Julie & Ben Rogers Excellence in Education Finalist, The University of Texas MD Anderson Cancer Center
2020Top 1% Nationally Recognised for Patient & Family Communication, CGCAHPS
2020Chair, WEO Webinar Committee, World Endoscopy Organization
2020Chair, ASGE Virtual Congress 2021, American Society for Gastrointestinal Endoscopy
20202020 - Top 1% Nationally on CAHPs, with a perfect score, Rated in the top 1% nationally on CAHPS (Consumer Assessment of Healthcare Providers & Systems) measures related to patient care experience - Granting Institution: Agency for Healthcare Research and Quality / US Department of Health & Human Services
2019American Society for Gastrointestinal Endoscopy President's Award, American Society for Gastrointestinal Endoscopy
2019Helio Disruptive Innovators: Social Media Influencer Finalists, Helio Gastroenterology and Liver Diseases, Annual Meeting of the American College of Gastroenterology, 2019, San Antonio
2018Editor-in-Chief, Video GIE, an Official Journal of the American Society for Gastrointestinal Endoscopy, American Society for Gastrointestinal Endoscopy
20182018 MD Anderson Top Performer -Top 1% Nationally on CAHPs, Rated in the top 1% nationally on CAHPS (Consumer Assessment of Healthcare Providers & Systems) measures related to patient care experience - Granting Institution: Agency for Healthcare Research and Quality / US Department of Health & Human Services
2017BJ Vakil Oration - First World Congress of GI Endoscopy, Hyderabad, India - Endoscopic Resection of Colon Polyps as an Alternative to Surgery, Society for Gastrointestinal Endoscopy of India and World Endoscopy Organization
2016American College of Gastroenterology Edgar Achkar Visiting Professorship, American College of Gastroenterology
2016Founding Co-Editor-in-Chief of Video GIE, an official journal of the American Society for Gastrointestinal Endoscopy
2016American Society for Gastrointestinal Endoscopy President's Recognition at the World Cup of Endoscopy, San Diego for service to the society & launch of a video journal for endoscopists
2016H-E-B Gastrointestinal Cancer Prevention, Research, & Education Endowment, Donor: Mr. Charles Butt, H-E-B
2016DOIM First Annual Quality Improvement Distinguished Paper Award, The University of Texas MD Anderson Cancer Center - Department of Internal Medicine
2016Listed in Top Doctors of Houston, Compiled by industry specialist Castle Connolly, to identify America's Top Doctors located in the Houston area
2016Nominee for the Provost's Distinguished Mentoring Awards, The University of Texas MD Anderson Cancer Center
201692nd Japanese Gastroenterological Endoscopy Society President's Invited Lecture at the Japanese Digestive Diseases Week, Kobe, Japan - "Video Journalism for Endoscopists"
2016Chair, Advisory Board for Coleman College for Health Sciences - Endoscopy Tech Training Program, Houston Community College
2015John Stroehlein Distinguished Professorship, The University of Texas MD Anderson Cancer Center
2014American Society for Gastrointestinal Endoscopy Distinguished Service Award
2014President's Recognition for Faculty Excellence, The University of Texas MD Anderson Cancer Center
2013Editor, Video GIE, American Society of Gastrointestinal Endoscopy
2013Chair, ASGE Educational Products Committee, American Society of Gastrointestinal Endoscopy
201233rd Annual Telly Award for the Colorectal Cancer Screening: A Story of Choices. Patient Education Video, The Telly Awards
2012King of the American Society of Gastrointestinal Endoscopy - EndoFest, American Society of Gastrointestinal Endoscopy
2012Co-Director - ASGE Postgraduate Course at the Annual ACG Meeting, American Society of Gastrointestinal Endoscopy
2012Super Doctors, SuperDoctors.com
2012GOLD LEVEL AWARD in the Association TRENDS' 2012 All-Media Contest for the American Society of Gastrointestinal Endoscopy Self Assessment Program (GESAP VII), the TRENDS ALL Media Contest
2011Health and Science Communications Association Award -"Colonoscopy & Colon Cancer Prevention" Patient Education Video, National Health Information Awards Judges
2011Who's Who in Medicine and Healthcare, Marquis
2011National Health Information Award, National Health Information Award
2011MarCom Award - Gold Level Award for the Online Learning Center of the American Society of Gastrointestinal Endoscopy, Association of Marketing and Communications Professionals
2010ASGE Audio-Visual Award for the production of an educational video "Endoscopic Management of GI Leaks", American Society of Gastrointestinal Endoscopy
2010Editor, CME Section of GIE (an official journal of the American Society for Gastrointestinal Endoscopy), American Society of Gastrointestinal Endoscopy
2008Alfa Omega Alfa Society, AOA of the University of Texas Medical Branch, Galveston, TX
2007Fellow, American Society of Gastrointestinal Endoscopy
2007Top Docs of America, Top Doctors of America
2006Physician of the year honoree, Mardi Gras, Galveston, TX, Galveston, Texas
2005Editor, CME Section of GIE (an official journal of the American Society for Gastrointestinal Endoscopy), American Society of Gastrointestinal Endoscopy
2004Best Doctors of America, Best Doctors of America
2004Fellow, Royal College of Physicians, UK
2002Fellow, American College of Gastroenterology
1993Best Graduating Resident of the Year in Internal Medicine, Cleveland Clinic Foundation, Cleveland, Ohio
1981Vemuri Shivaji Rao Gold Medal in Medicine, Andhra Medical College, Visakhapatnum, India
1980Ranked second in Eye & ENT among 150 medical students, Andhra University, Visakhapatnum, India
1980Ranked first in Internal Medicine among 150 medical students, Andhra University, Visakhapatnum, India
1980Ranked second in Final MBBS among 150 medical students, Andhra University, Visakhapatnum, India
1980Sri Ramachandrula Hanumantha Rao & Rajya Lakshmi Merit Scholarship, Andhra Medical College, Visakhapatnum, India
1980Tatachari Gold Medal in Pathology, Andhra Medical College, Visakhapatnum, India
1979Ranked first in Second MBBS among 150 medical students, Andhra University, Visakhapatnum, India
1979Ranked first in Microbiology among 150 medical students, Andhra University, Visakhapatnum, India
1979Ranked first in Pathology among 150 medical students, Andhra University, Visakhapatnum, India
1976Andhra Pradesh State Merit Scholarship- Top 1% of the candidates, Andhra Pradesh High School Board, Hyderabad, AP, India
1976Ranked first in Organic Chemistry among 150 medical students, Nagarjuna University, Guntur, AP, India

Professional Memberships

American Society for Gastrointestinal Endoscopy

Editor-in-Chief, Video GIE, 2018 - 2020

American Society of Gastrointestinal Endoscopy, Downers Grove, IL

Member of the ASGE Strategic Planning Committee, 2015 - 2015

American Society of Gastrointestinal Endoscopy, Dover Grove, IL

Narrow Band Imaging Task Force, 2015 - 2015

American Society of Gastrointestinal Endoscopy, Downers Grove

Co-Chair, Planning Committee for the ASGE-DDW Video Plenary Session & World Cup of Endoscopy, 2014 - 2016

American Society of Gastrointestinal Endoscopy, Chicago

Editor, VideoGIE, Gastrointestinal Endoscopy Journal, 2013 - 2016

American Society of Gastrointestinal Endoscopy, Chicago, IL

Chair, ASGE Educational Products Committee, 2013 - 2016

American Society of Gastrointestinal Endoscopy, Downers Grove, IL

Chair, ASGE - Gastrointestinal Endoscopy Self Assessment Program VIII, 2013 - 2014

American Society of Gastrointestinal Endoscopy, Chicago, IL

Member of Strategic Planning Committee, 2011 - 2011

American Society of Gastrointestinal Endoscopy, Chicago

Chair, Web Education Committee, 2010 - 2012

American Society of Gastrointestinal Endoscopy, Downers Grove, IL

Co-Chair, ASGE - Gastrointestinal Endoscopy Self Assessment Program VII, 2010 - 2011

American Society of Gastrointestinal Endoscopy, Downers Grove, IL

Editor, CME Section - Gastrointestinal Endosocopy, 2010 - 2014

American Society of Gastrointestinal Endoscopy

American Society of Gastrointestinal Endoscopy

Vice-Chair, Web Education Committee, 2007 - 2010

American Society of Gastrointestinal Endoscopy, Oakbrook, IL

Co-Chair, ASGE - Gastrointestinal Endoscopy Self Assessment Program VI, 2007 - 2008

American Society of Gastrointestinal Endoscopy, Oakbrook, IL

Editor, CME Section - Gastrointestinal Endoscopy, 2005 - 2009

Royal College of Physicians, UK

American Society of Gastrointestinal Endoscopy, Oakbrook, IL

Co-Chair, ASGE - Gastrointestinal Endoscopy Self Assessment Program V, 2004 - 2005


Watch the video: Animal Nutrition Differences in Digestive Systems (January 2022).