Information

Are SLC52A2 and GPR172A really the same?


The official HUGO gene nomenclature page says that GPR172A (Gamma-hydroxybutyrate receptor) and SLC52A2 (riboflavin transporter, member 2) are the same. The sequence reported by Andriamampandry seems to be the same, but I find no other evidence. Can anyone enlighten me?

(I'm wondering if I should add the SLC52A2 information to the GHB receptor Wikipedia page.)


This isn't a case of gene splicing causing different protein variants. In the studies that identified these two functions (GHB sensitivity and riboflavin transport), they were using DNA derived from mRNA (cDNA), which means what was being expressed in their experiments did not have introns, so there was no chance for alternative splicing.

This gene has a weird history, here is the summary:

Takeda et al. 2002: Identification of G protein-coupled receptor genes from the human genome sequence

Takeda and co. download a copy of the human genome and translate it looking for GPCRs. They look at all the ORF that DIDNT have introns: "We collected intronless open reading frames (ORFs), which were long enough to cover GPCRs from the human genome". They also only look at things with 6-8 transmembrane helices as determined by the prediction program SOSUI. One of the GPCRs they found was named hGCRP41 (hypothetical protein similar to GPCR) accession number: AB083623. They report it probably has 8 transmembrane helices, and 418aa. This protein probably doesn't exist because they read straight through two introns in their analysis. The protein also terminates in the middle of a frame-shifted exon.

Ericsson et al. 2003: Identification of receptors for pig endogenous retrovirus

Next, Ericsson et al come along looking for receptors for the pig endogenous retrovirus and find this gene. They used cDNA to make a bunch of transduced cell lines that had difference human cDNAs expressed. They found two related proteins that could serve as receptors to the pig endogenous retrovirus. They named the first one HuPAR-1, which is 445aa long and has 11 transmembrane helices. This is the length of one of the proper splice variants of this gene.

Andriamampandry et al. 2007: Cloning and functional characterization of a gammahydroxybutyrate receptor identified in the human brain

Andriamampandry is looking for gammahydroxtbutyrate (GHB) receptors by using cDNA and seeing which cDNA-transduced cells become sensitive to GHB. They find two nice proteins that are sensitive to GHB, GHBh1 and C12K32. GHBh1 is identical to HuPAR-1, it has 445aa and 11 transmembrane helices. C12K32 is a frameshifted version of GHBh1 that is slightly longer, but has the same number of helices. They had previously found a 512aa ortholog in rats, in 2013.

Yao et al. 2010: Identification and Comparative Functional Characterization of a New Human Riboflavin Transporter hRFT3 Expressed in the Brain.

Finally, we have Yao et al, who searched for homologs to their Riboflavin transporters. They found one in a cDNA library, and it was 445aa long. But they noticed upon BLASTing it that people had been calling it a GPCR. They point out that this is weird since it has 11 transmembrane helices, and go on to show that it is a Riboflavin transporter, concluding: "The molecular function of GPR172A has yet to be determined. We designated it hRFT3 (GenBank accession no. AB522904) based on its functional characterization as shown below." This paper is in pretty poor form, because somehow they don't address the Andriamampandry paper which presented data supporting its function as a GPCR.


So this protein, in this specific spliced formation, has been shown to be a virus receptor, a GHB G protein-coupled receptor, and a riboflavin transporter. It is very weird that it is a GPCR with 11 transmembrane domains… they very rarely have more or less than 7. I'd wait for more studies to confirm both of these findings before I'd accept that this protein is an XXL GPCR moonlighting as a riboflavin transporter.


Its fairly common for a gene to have multiple names. I cant say for certain, but Jax and GeneCards also lists them as being synonymous so I would say its safe to say they are the same

http://www.informatics.jax.org/marker/MGI:1289288

http://www.genecards.org/cgi-bin/carddisp.pl?gene=SLC52A2

Edit in reply to comment:

In higher level Eukaryotes the vast majority of genes have more than one isoform as a result of alternative splicing, and this can drastically change the protein sequence and function of that protein. So even if it comes from the gene, two different isoforms can have completely unrelated functions.

According to ensembl, this gene has 14 isoforms.

http://useast.ensembl.org/Homo_sapiens/Gene/Splice?g=ENSG00000185803;r=8:145577795-145584932

Of course there could also be some type of post translational modification that could also change the function, but Id say mostly likely if the same gene produces two different functioning proteins its because of alternative splicing.


Answer Desk

In many cases cell division depends on the stage of development an organism is in. The rate of cell division is obviously much faster in a developing organism and from what I understand fully differentiated cells such as neuron and those in skeletal muscles don't divide (correct me if I'm wrong here).

In early development totipotent cells (stem cells that can become anything) begin to differentiate dependent on environmental factors, turning into multipotent (partially differentiated) cells that can only lead to certain cell types. For example: mesodermal precursors can differentiate to myoblasts, which can go on to differentiate into myotubes, later forming muscles.

Epithelial and and blood cells are the two of the main types of cells that need to be constantly replaced in developed organisms. As far as I know cells lining the gut epithelium are fastest to divide. They are created from stem cells in 'crypts' (pockets) in the lining and are pushed outwards, where they are later broken down (by what I would assume would be abrasion and intestinal juices). My book gives them a lifespan of 3-5 days. External skin cells are much slower to divide (though I'n not sure by exactly how much).


Sunday, 29 June 2008

Pharmacology - How long does it take for the Opioids listed in the Description to induce Analgesia when Administered via IV?

These are 'peak' values when administered via IV, with the exception of oxycodone. There will be some variation person to person depending on their opioid tolerance and any concomitantly administered medications.

Oxycodone: Not administered intravenously

What happens to potassium after an action potential?

During the repolarization, relatively few ions need to cross the membrane for the membrane voltage to change and therefore the change in ions concentration outside and inside the cell is neglible. After repolarization, the concentrations are restored by the continuous action of Na⁺/K⁺-ATPase. The same happens for calcium, but I don't know exactly what kind of pump is used.

Coding theory - Binary codes with large distance

No. If we take $<-1/sqrt n,1/sqrt n>^n$ instead of $<0,1>^n$, the problem reduces to asking if we can have many unit vectors $v_j$ with pairwise scalar products $-gamma$ or less where $gamma>0$ is a fixed number. But if we have $N$ such vectors, then the square of the norm of their sum is at most $N-gamma N(N-1)$. Since this square must be non-negative, we get $N-1legamma^<-1>$ regardless of the dimension.


Are SLC52A2 and GPR172A really the same? - Biology

Tseng, W-S Huang, N-C Huang, W-S Lee, H-C

Neurological decompression sickness (DCS) is a rare condition that commonly leads to spinal cord injury. We report the case of a 30-year-old man who developed left-sided weakness and numbness after diving to a maximum depth of 15 m with a total dive time of 205min (10 repetitive dives). To the best of our knowledge, only six cases diagnosed as Brown -Séquard syndrome caused by DCS have been reported in the literature. Divers should be aware of the risk factors of DCS before diving and clinicians should make the diagnosis of spinal cord DCS based primarily on clinical symptoms, not on magnetic resonance imaging findings. © The Author 2015. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: [email protected]

Beer-Furlan, André Luiz Paiva, Wellingson Silva Tavares, Wagner Malagó de Andrade, Almir Ferreira Teixeira, Manoel Jacobsen

Introduction: Stab wounds resulting in spinal cord injuries are very rare. In direct central back stabbings, the layers of muscles and the spinal column tends to deflect blades, rarely causing injuries to the spinal cord. We report an unusual case of traumatic spinal cord injury by a screwdriver stab, presented as Brown -Séquard syndrome and discuss possible pitfalls on the surgical treatment. Case report: A 34 year-old man was brought to the emergency department after a group assault with a single screwdriver stab wound on the back. Neurological examination revealed an incomplete Brown -Sequard syndrome , with grade IV motor deficit on the left leg and contralateral hemihypoalgesia below T9 level. Radiological evaluation showed a retained 9 cm screwdriver that entered and trespassed the spinal canal at T6 level, reaching the posterior mediastinum with close relation to the thoracic aorta. Vascular injury could not be excluded. The joint decision between the neurosurgery and the vascular surgery teams was the surgical removal of the screwdriver under direct visualization. A left mini-thoracotomy was performed. Simultaneously, a careful dissection was done and screwdriver was firmly pulled back on the opposite path of entry under direct visualization of the aorta. The neurological deficit was maintained immediately after the surgical procedure. Follow-up visit after 1 year showed minor motor deficit and good healing. Conclusions: It is important to consider all aspects of secondary injury on the surgical planning of penetrating spinal cord injury. The secondary injury can be minimized with multidisciplinary planning of the surgical procedure. PMID:24482724

Desai, Mehul J Desai, Mehul Jacob, Lisa Leiphart, James

The objective of this study is to present a novel approach to the treatment of thoracic radiculitis following Brown -Sequard syndrome with peripheral nerve field stimulation (PNFS). Furthermore, we endeavor to discuss the role of PNFS in the management of refractory neuropathic pain conditions including post-traumatic and post-surgical neuropathy particularly with regards to the post-surgical spine. Presented is a 57-year-old man with history of thoracic microdiscectomy resulting in Brown -Sequard syndrome presented with chronic post-operative thoracic radicular pain radiating to the abdomen, refractory to conservative management. The patient underwent three intercostal nerve blocks from T7 to T9 with transient symptomatic relief. The patient's options were limited to chemomodulation, neuromodulation, or selective intercostal nerve surgical neurectomy. He subsequently underwent a PNFS trial and reported >75% pain reduction. Permanent percutaneous PNFS electrodes were implanted subcutaneously over the right T7 and T9 intercostal nerves and replicated the trial results. Neuromodulation produced pain relief with >90% improvement in pain compared with baseline both during the trial and following permanent implantation of the PNFS system. Chronic radicular pain may be difficult to manage in the post-surgical patient and often requires the use of multiple therapeutic modalities. In this case, we successfully utilized PNFS as it demonstrated greater technical feasibility when compared with dorsal column stimulation and repeat surgery therefore, it may be considered for the management of post-surgical neuropathy. Further controlled studies are needed to evaluate the efficacy of PNFS as a treatment option. © 2011 International Neuromodulation Society.

Leven, Dante Sadr, Ali Aibinder, William R

Brown -Séquard syndrome is characterized by a hemisection of the spinal cord most commonly after spinal trauma or neoplastic disease. The injury causes ipsilateral hemiplegia and proprioceptive sensory disturbances with contralateral loss of pain and temperature sensation. Patients with Brown -Séquard syndrome have the best prognosis of all spinal cord injury patterns. At this time, the ideal management for Brown -Séquard syndrome after penetrating trauma has yet to be defined. To report a case of a gun shot wound to the upper cervical spine that resulted in Brown -Séquard syndrome and was treated effectively with early cervical spine decompression and fusion. Observational case report. A 28-year-old woman presented after sustaining a low-velocity gun shot wound in to the upper cervical spine in a civilian assault. On initial presentation, she had 0/5 motor scores in the left upper and lower extremities and normal motor scores on the right. Sensory examination was limited as she was intubated and sedated on admission due to airway compromise. A computed tomography scan revealed a bullet lodged in the vertebral body of C3 with boney fragments and soft tissue encroaching on the spinal cord. Subsequently, she underwent C3 corpectomy, bulletectomy, and anterior cervical decompression with fusion. Intraoperatively, no dural disruption or cerebral spinal fluid leak was noted, and her posterior longitudinal ligament was intact. One month postoperatively, her left lower extremity motor score was 5/5 with movement of her left thumb and all fingers. Strength in her biceps, triceps, and wrist extensors and flexors was 3/5. Her functional capacity and strength gradually improved. Reinke et al. support surgical intervention for patients with incomplete paraplegia after the patient is medically stabilized, although their case report discussed lower thoracic injury, which carries a more favorable prognosis. All other prior case reports and prospective studies that reported

Zimova, Marketa Mills, L. Scott Lukacs, Paul M. Mitchell, Michael S.

As duration of snow cover decreases owing to climate change, species undergoing seasonal colour moults can become colour mismatched with their background. The immediate adaptive solution to this mismatch is phenotypic plasticity, either in phenology of seasonal colour moults or in behaviours that reduce mismatch or its consequences. We observed nearly 200 snowshoe hares across a wide range of snow conditions and two study sites in Montana, USA, and found minimal plasticity in response to mismatch between coat colour and background. We found that moult phenology varied between study sites, likely due to differences in photoperiod and climate, but was largely fixed within study sites with only minimal plasticity to snow conditions during the spring white-to- brown moult. We also found no evidence that hares modify their behaviour in response to colour mismatch. Hiding and fleeing behaviours and resting spot preference of hares were more affected by variables related to season, site and concealment by vegetation, than by colour mismatch. We conclude that plasticity in moult phenology and behaviours in snowshoe hares is insufficient for adaptation to camouflage mismatch, suggesting that any future adaptation to climate change will require natural selection on moult phenology or behaviour.

Rothenburger, Jamie L Bennett, Katarina R Bryan, Lorraine Bollinger, Trent K

The bacterium Listeria monocytogenes causes disease in a wide variety of mammals including rabbits and hares . We describe naturally acquired metritis and septicemic listeriosis in wild female hares from Saskatchewan, Canada. Between April 2012 and July 2013, two white-tailed jackrabbits (Lepus townsendii) and a snowshoe hare (Lepus americanus) were presented to the Veterinary Medical Centre at the Western College of Veterinary Medicine, Saskatoon, Saskatchewan, Canada with nonspecific neurologic signs. The hares were euthanized and autopsied. Necrotizing fibrinosuppurative metritis was present in all. Additional findings in individual hares included fetal maceration, multifocal necrotizing myocarditis, multifocal hepatic necrosis, and nonsuppurative encephalitis. Listeria monocytogenes was cultured from multiple tissues in each hare . Although listeriosis in pregnant domestic rabbits has been studied, this is the first detailed description in wild North American hares . The epidemiology of listeriosis, including prevalence and the role of environmental sources and coprophagy in transmission among hares , requires further investigation.

Thulasi, Venkatraman Veerapandiyan, Aravindhan Pletcher, Beth A. Tong, Chun M.

Brown -Vialetto-Van Laere syndrome is a rare disorder characterized by motor, sensory, and cranial neuronopathies, associated with mutations in SLC52A2 and SLC52A3 genes that code for human riboflavin transporters RFVT2 and RFVT3, respectively. The authors describe the clinical course of a 6-year-old girl with Brown -Vialetto-Van Laere syndrome and a novel homozygous mutation c.1156T>C in the SLC52A3 gene, who presented at the age of 2.5 years with progressive brain stem dysfunction including ptosis, facial weakness, hearing loss, dysphagia, anarthria with bilateral vocal cord paralysis, and ataxic gait. She subsequently developed respiratory failure requiring tracheostomy and worsening dysphagia necessitating a gastrostomy. Following riboflavin supplementation, resolution of facial diplegia and ataxia, improvements in ptosis, and bulbar function including vocalization and respiration were noted. However, her sensorineural hearing loss remained unchanged. Similar to other cases of Brown -Vialetto-Van Laere syndrome , our patient responded favorably to early riboflavin supplementation with significant but not complete neurologic recovery. PMID:28856173

Hu, Tao Yuan, Xiaoxue Ye, Rongcai Zhou, Huiqiao Lin, Jun Zhang, Chuanhai Zhang, Hanlin Wei, Gang Dong, Meng Huang, Yuanyuan Lim, Wonchung Liu, Qingsong Lee, Hyuek Jong Jin, Wanzhu

Polycystic ovary syndrome (PCOS) is a complex endocrinopathy that is characterized by anovulation, hyperandrogenism and polycystic ovary. However, there is a lack of effective treatment for PCOS at present because the pathologic cause of PCOS has not been elucidated. Although it has been known that brown adipose tissue transplantation ameliorates PCOS by activating endogenous BAT, BAT transplantation is not applicable in clinic. Therefore, BAT activation with natural compound could be an effective treatment strategy for PCOS patients. Here, we found that 3 weeks of rutin (a novel compound for BAT activation) treatment increased BAT activation, thereby it improved thermogenesis and systemic insulin sensitivity in dehydroepiandrosterone (DHEA)-induced PCOS rat. In addition, the expression levels of ovarian steroidogenic enzymes such as P450C17, aromatase, 3β-HSD, 17β-HSD and STAR were up-regulated in rutin-treated PCOS rat. Furthermore, acyclicity and the serum level of luteinizing hormone were normalized, and a large number of mature ovulated follicle with a reduction of cystic formation were observed in PCOS rat after rutin treatment. Finally, rutin treatment surprisingly improved fertility and birth defect in PCOS rat. Collectively, our results indicate that rutin treatment significantly improves systemic insulin resistance and ovarian malfunction in PCOS, and our findings in this study provide a novel therapeutic option for the treatment of PCOS by activating BAT with rutin. Copyright © 2017 Elsevier Inc. All rights reserved.

Jost, Patrick W Marawar, Satyajit O'Leary, Patrick F

A case report. To present a previously unreported cause of neurologic compromise after cervical spine surgery. Several different causes of postoperative neurologic deficit have been reported in the literature. The authors present a case of acute postoperative paralysis after posterior cervical decompression by a mechanism that has not yet been reported in the literature. A 54-year-old muscular, short-statured man underwent posterior cervical laminectomy from C3-C5 without instrumentation and left C5 foraminotomy. Within hours of leaving the operating room, he began to develop postoperative neurologic deficits in his extremities, which progressed to a classic Brown -Sequard syndrome . Magnetic resonance imaging revealed regional kyphosis and large swollen paraspinal muscles impinging on the spinal cord without epidural hematoma. Emergent operative re-exploration confirmed these findings large, swollen paraspinal muscles, a functioning drain, and no hematoma were found. The patient was treated with immediate corticosteroids at the time of initial diagnosis, and emergent re-exploration and debulking of the paraspinal muscles. The patient had complete recovery of neurologic function to his preoperative baseline after the second procedure but required a third procedure in which anterior discectomy and fusion at C4-C5 was performed, which led to improvement of his preoperative symptoms. When performing posterior cervical decompression, surgeons must be aware of the potential for loss of normal lordosis and anterior displacement of paraspinal muscles against the spinal cord, especially in muscular patients.

Bashford, James A Chowdhury, Fahmida A Shaw, Chris E

The clinical diagnosis of Brown -Vialetto-Van Laere syndrome in this woman with rapidly progressive pontobulbar palsy led to empirical high-dose oral riboflavin (1200 mg/day) therapy. This resulted in a dramatic improvement in her motor function from being anarthric, dysphagic, tetraparetic and in ventilatory failure to living independently with mild dysarthria and distal limb weakness. DNA sequencing of the SLC52A3 gene found compound heterozygous C-terminus mutations, V413A1/D461Y, consistent with recent reports of mutations within the riboflavin transporter genes (SLC52A2 and SLC52A3) in this condition. Early diagnosis and empirical riboflavin therapy can lead to major motor recovery in this condition, that can be sustained with long-term maintenance therapy. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Luter, Heidi M. Whalan, Steve Webster, Nicole S.

Background Marine diseases are being increasingly linked to anthropogenic factors including global and local stressors. On the Great Barrier Reef, up to 66% of the Ianthella basta population was recently found to be afflicted by a syndrome characterized by brown spot lesions and necrotic tissue. Methodology/Principal Findings Manipulative experiments were undertaken to ascertain the role of environmental stressors in this syndrome . Specifically, the effects of elevated temperature and sedimentation on sponge health and symbiont stability in I. basta were examined. Neither elevated temperature nor increased sedimentation were responsible for the brown spot lesions, but sponges exposed to 32°C developed substantial discoloration and deterioration of their tissues, resulting in death after eight days and a higher microbial diversity in those samples. No shifts in the microbial community of I. basta were observed across a latitudinal gradient or with increased sedimentation, with three previously described symbionts dominating the community of all sponges (Alphaproteobacteria, Gammaproteobacteria and Thaumarchaea). Conclusions/Significance Results from this study highlight the stable microbial community of I. basta and indicate that thermal and sedimentation stress are not responsible for the brown spot lesions currently affecting this abundant and ecologically important sponge species. PMID:22745827

Luter, Heidi M Whalan, Steve Webster, Nicole S

Marine diseases are being increasingly linked to anthropogenic factors including global and local stressors. On the Great Barrier Reef, up to 66% of the Ianthella basta population was recently found to be afflicted by a syndrome characterized by brown spot lesions and necrotic tissue. Manipulative experiments were undertaken to ascertain the role of environmental stressors in this syndrome . Specifically, the effects of elevated temperature and sedimentation on sponge health and symbiont stability in I. basta were examined. Neither elevated temperature nor increased sedimentation were responsible for the brown spot lesions, but sponges exposed to 32°C developed substantial discoloration and deterioration of their tissues, resulting in death after eight days and a higher microbial diversity in those samples. No shifts in the microbial community of I. basta were observed across a latitudinal gradient or with increased sedimentation, with three previously described symbionts dominating the community of all sponges (Alphaproteobacteria, Gammaproteobacteria and Thaumarchaea). Results from this study highlight the stable microbial community of I. basta and indicate that thermal and sedimentation stress are not responsible for the brown spot lesions currently affecting this abundant and ecologically important sponge species.

Rohner, Christoph Krebs, Charles J

We show evidence of differential predation on snowshoe hares (Lepus americanus) by great horned owls (Bubo virginianus) and ask whether predation mortality is related to antipredator behaviour in prey. We predicted higher predation on (1) young and inexperienced hares , (2) hares in open habitats lacking cover to protect from owl predation, and (3) hares in above average condition assuming that rich food patches are under highest risk of predation. Information on killed hares was obtained at nest sites of owls and by monitoring hares using radio-telemetry. The availability of age classes within the hare population was established from live-trapping and field data on reproduction and survival. Great horned owls preferred juvenile over adult hares . Juveniles were more vulnerable to owl predation before rather than after dispersal, suggesting that displacement or increased mobility were not causes for this increased mortality. Owls killed ratio-collared hares more often in open than in closed forest types, and they avoided or had less hunting success in habitats with dense shrub cover. Also, owls took hares in above average condition, although it is unclear whether samples from early spring are representative for other seasons. In conclusion, these results are consistent with the hypothesis that variation in antipredator behaviours of snowshoe hares leads to differential predation by great horned owls.

Evelyn L. Bull Thad W. Heater Abe A. Clark Jay F. Shepherd Arlene K. Blumton

Relative abundance, survival, home range, and habitat use of snowshoe hares (Lepus americanus) were evaluated in five precommercial thinning treatments in lodgepole pine (Pinus contorta Dougl. ex Loud.) stands in northeastern Oregon between June 2000 and July 2003. A combination of track surveys, trapping grids, and.

Grieneisen, Laura E Brownlee-Bouboulis, Sarah A Johnson, Joseph S Reeder, DeeAnn M

White-nose syndrome (WNS), an emerging infectious disease caused by the novel fungus Pseudogymnoascus destructans, has devastated North American bat populations since its discovery in 2006. The little brown myotis, Myotis lucifugus, has been especially affected. The goal of this 2-year captive study was to determine the impact of hibernacula temperature and sex on WNS survivorship in little brown myotis that displayed visible fungal infection when collected from affected hibernacula. In study 1, we found that WNS-affected male bats had increased survival over females and that bats housed at a colder temperature survived longer than those housed at warmer temperatures. In study 2, we found that WNS-affected bats housed at a colder temperature fared worse than unaffected bats. Our results demonstrate that WNS mortality varies among individuals, and that colder hibernacula are more favourable for survival. They also suggest that female bats may be more negatively affected by WNS than male bats, which has important implications for the long-term survival of the little brown myotis in eastern North America.

Uresk, D.W. Cline, J.F. Rickard, W.H.

A fecal pellet analyses showed that black-tailed hares (jackrabbits) were selective in plants chosen as food. The most abundant herbaceous plant, cheatgrass, was not found in the pellets. Sagebrush and bitterbrush, woody plants, were not an important part of the hares ' diet. Forbs, rabbitbrush, and certain grass species were preferred foods. (auth)

Bosch, Annet M Stroek, Kevin Abeling, Nico G Waterham, Hans R Ijlst, Lodewijk Wanders, Ronald J A

The Brown -Vialetto-Van Laere syndrome is a rare neurological disorder which may present at all ages with sensorineural deafness, bulbar palsy and respiratory compromise. Fazio-Londe syndrome is considered to be the same disease entity. Recently it was demonstrated that in some patients the disease is caused by mutations in the SLC52A3 gene which encodes the intestinal (hRFT2) riboflavin transporter. In these patients riboflavin deficiency is the cause of the BVVL/FL syndrome and supplementation of riboflavin proved a life saving treatment. Mutations in the SLC52A2 gene and the SLC52A1 (GPR172B) gene, coding for human riboflavin transporters hRFT3 and hRFT1 have been associated with the BVVL syndrome as well. We performed a review of the literature, with emphasis on the natural history and the effects of treatment in these patients. A total of 35 publications were traced reporting on the clinical presentation of 74 patients who presented before age 18. The most prevalent symptoms were bulbar palsy, hearing loss, facial weakness and respiratory compromise. Death was reported in 28 of the 61 untreated patients, with a very low survival in patients presenting before age 4. All 13 patients who were treated with riboflavin survived, with a strong clinical improvement after days to months of treatment in eight patients. Three patients demonstrated a stable clinical course and treatment was stopped early in two patients. Abnormalities in plasma flavin levels and/or plasma acylcarnitine profiles were observed in some but not in all patients, and also patients with normal plasma flavin levels and acylcarnitine profiles demonstrated a striking clinical improvement on riboflavin supplementation. It is now clear that proper diagnosis requires mutation analysis of all three transporter genes and treatment should be started immediately without first awaiting results of molecular analysis. Clinical improvement may be rapid or gradual over a period of more than 12 months.

The Brown -Vialetto-Van Laere syndrome is a rare neurological disorder which may present at all ages with sensorineural deafness, bulbar palsy and respiratory compromise. Fazio-Londe syndrome is considered to be the same disease entity. Recently it was demonstrated that in some patients the disease is caused by mutations in the SLC52A3 gene which encodes the intestinal (hRFT2) riboflavin transporter. In these patients riboflavin deficiency is the cause of the BVVL/FL syndrome and supplementation of riboflavin proved a life saving treatment. Mutations in the SLC52A2 gene and the SLC52A1 (GPR172B) gene, coding for human riboflavin transporters hRFT3 and hRFT1 have been associated with the BVVL syndrome as well. We performed a review of the literature, with emphasis on the natural history and the effects of treatment in these patients. A total of 35 publications were traced reporting on the clinical presentation of 74 patients who presented before age 18. The most prevalent symptoms were bulbar palsy, hearing loss, facial weakness and respiratory compromise. Death was reported in 28 of the 61 untreated patients, with a very low survival in patients presenting before age 4. All 13 patients who were treated with riboflavin survived, with a strong clinical improvement after days to months of treatment in eight patients. Three patients demonstrated a stable clinical course and treatment was stopped early in two patients. Abnormalities in plasma flavin levels and/or plasma acylcarnitine profiles were observed in some but not in all patients, and also patients with normal plasma flavin levels and acylcarnitine profiles demonstrated a striking clinical improvement on riboflavin supplementation. It is now clear that proper diagnosis requires mutation analysis of all three transporter genes and treatment should be started immediately without first awaiting results of molecular analysis. Clinical improvement may be rapid or gradual over a period of more than 12 months. PMID

DeAngelis, Donald L. Bryant, John P. Liu, Rongsong Gourley, Stephen A. Krebs, Charles J Reichardt, Paul B

A necessary condition for a snowshoe hare population to cycle is reduced reproduction after the population declines. But the cause of a cyclic snowshoe hare population's reduced reproduction during the low phase of the cycle, when predator density collapses, is not completely understood. We propose that moderate-severe browsing by snowshoe hares upon preferred winter-foods could increase the toxicity of some of the hare 's best winter-foods during the following hare low, with the result being a decline in hare nutrition that could reduce hare reproduction. We used a combination of modeling and experiments to explore this hypothesis. Using the shrub birch Betula glandulosa as the plant of interest, the model predicted that browsing by hares during a hare cycle peak, by increasing the toxicity B. glandulosa twigs during the following hare low, could cause a hare population to cycle. The model's assumptions were verified with assays of dammarane triterpenes in segments of B. glandulosa twigs and captive hare feeding experiments conducted in Alaska during February and March 1986. The model's predictions were tested with estimates of hare density and measurements of B. glandulosa twig growth made at Kluane, Yukon from 1988–2008. The empirical tests supported the model's predictions. Thus, we have concluded that a browsing-caused increase in twig toxicity that occurs during the hare cycle's low phase could reduce hare reproduction during the low phase of the hare cycle.

Michael K. Schwartz Kristine L. Pilgrim Kevin S. McKelvey Pilar T. Rivera Leonard F. Ruggiero

Snowshoe hare (Lepus americanus) abundance has been of interest to wildlife biologists, as hares are essential prey items for many rare and endangered predators. Snowshoe hare abundance has most commonly been estimated through indices such as pellet counts. While pellet counts may be useful in the areas they are developed and when hares are dense.


Watch the video: Parinaud Syndrome (January 2022).