A sense is a physiological capacity of organisms that provides data for perception. The nervous system has a specific sensory nervous system, and a sense organ, dedicated to each sense.
Humans have a multitude of senses. Sight (vision), hearing (audition), taste (gustation), smell (olfaction), and touch (somatosensation) are the five traditionally recognized senses. The ability to detect other stimuli beyond those governed by these most broadly recognized senses also exists, and these sensory modalities include temperature (thermoception), kinesthetic sense (proprioception), pain (nociception), balance (equilibrioception), vibration (mechanoreception), and various internal stimuli (e.g. the different chemoreceptors for detecting salt and carbon dioxide concentrations in the blood). However, what constitutes a sense is a matter of some debate, leading to difficulties in defining what exactly a distinct sense is, and where the borders between responses to related stimuli lay. This process is called sensory transduction.
There are two broad types of cellular systems that perform sensory transduction. In one, a neuron works with a sensory receptor, a cell, or cell process that is specialized to engage with and detect a specific stimulus. Stimulation of the sensory receptor activates the associated afferent neuron, which carries information about the stimulus to the central nervous system. In the second type of sensory transduction, a sensory nerve ending responds to a stimulus in the internal or external environment: this neuron constitutes the sensory receptor itself. Free nerve endings can be stimulated by several different stimuli, thus showing little receptor specificity. For example, pain receptors in your gums and teeth may be stimulated by temperature changes, chemical stimulation, or pressure.
How Can We Sense Infection? Helping to Treat Sepsis
00:00:13.04 Hello everyone.
00:00:14.06 I'm Jianjin Shi,
00:00:15.25 a PhD student from Dr. Feng Shao's lab
00:00:17.26 at National Institute of Biology Sciences.
00:00:20.15 What we study
00:00:22.01 is a deadly disease called sepsis.
00:00:24.02 Sepsis can kill many people
00:00:26.17 around the world,
00:00:28.01 but currently we do not have any drugs
00:00:29.24 to treat this disease.
00:00:31.10 And what we study,
00:00:32.26 and what we've discovered,
00:00:35.15 might provide new treatment for this deadly disease.
00:00:38.06 To begin with, I would like to introduce.
00:00:40.22 what is sepsis?
00:00:42.07 Sepsis, by definition, is
00:00:44.12 systemic inflammation caused by infection.
00:00:47.08 As shown here, this old man
00:00:49.06 had a tooth infection,
00:00:50.28 but didn't get proper treatment with antibiotics,
00:00:53.18 and later this infection
00:00:55.25 spread into the bloodstream
00:00:57.20 and his body mounted
00:00:59.14 a very strong immune response,
00:01:01.02 just like unleashing a very strong army.
00:01:04.17 Sometimes, this army
00:01:06.12 can cause collateral damage to his own body
00:01:08.28 and lead to sepsis.
00:01:11.12 So, what do you feel after you have sepsis?
00:01:13.21 You may feel fever, chills,
00:01:16.07 you can breathe rapidly,
00:01:18.09 and your heart beats rapidly,
00:01:20.04 and you can may experience confusion,
00:01:24.01 as well as nausea and vomiting.
00:01:26.22 So, why is susceptible to sepsis?
00:01:28.28 In general, people with weakened immune sytems
00:01:32.04 are more susceptible to sepsis,
00:01:34.08 including the elderly, pregnant women,
00:01:37.01 children and infants,
00:01:39.01 and people with chronic illness,
00:01:41.10 including AIDS, diabetes, and cancer.
00:01:43.29 This man lost his spleen
00:01:46.15 after an accident
00:01:48.27 and therefore lost the majority of his immune system,
00:01:52.08 and several years later
00:01:54.24 he had sepsis.
00:01:56.14 And this little girl also had sepsis
00:01:58.23 because her immune system is not strong enough yet.
00:02:02.07 Luckily, these two people survived sepsis.
00:02:05.21 But sepsis doesn't
00:02:09.11 only kill susceptible people,
00:02:12.19 it can kill anyone,
00:02:14.19 including you and me.
00:02:16.12 This young lady,
00:02:18.17 she was a model from Brazil,
00:02:22.23 and she was healthy.
00:02:26.13 In the beginning, she had a urinary tract infection,
00:02:30.01 which is a quite common infection,
00:02:32.21 and later the infection
00:02:34.25 developed into sepsis,
00:02:36.15 and within only a few days
00:02:38.19 she died in the hospital
00:02:40.25 at the age of 20.
00:02:43.05 And one scary thing for sepsis
00:02:45.19 is that sepsis can kill people,
00:02:48.04 and kill people rapidly.
00:02:50.08 So, why should we care about sepsis?
00:02:52.26 In the United States alone,
00:03:00.23 over 750,000 people develop sepsis.
00:03:04.27 Among them, over 200,000 people die.
00:03:08.17 That is more than the population of Salt Lake City.
00:03:13.28 And sepsis kills more people
00:03:16.21 than breast cancer, colon cancer,
00:03:18.20 and AIDS combined.
00:03:21.21 And sepsis also accounts
00:03:24.12 for at least one third of all hospital deaths.
00:03:29.16 Because sepsis generally need
00:03:32.28 special care in the ICU,
00:03:34.27 it is a very expensive disease,
00:03:37.11 and in the United States alone in 2011,
00:03:40.09 sepsis cost more than 20 billion US dollars.
00:03:43.27 But most people
00:03:45.24 don't even know about this disease.
00:03:49.15 And sepsis has three main stages:
00:03:52.10 in the beginning, it's called sepsis.
00:03:54.27 You have a local infection
00:03:56.27 that's in the lung or other places,
00:03:59.22 and this infection
00:04:02.11 breaks your immune defense
00:04:05.01 and gets through to the bloodstream,
00:04:07.11 and your body mounts
00:04:09.07 a systemic inflammatory response.
00:04:11.29 So, this is stage one.
00:04:14.09 And in stage 2,
00:04:16.16 you will experience several organ dysfunctions,
00:04:19.29 and this is called severe sepsis.
00:04:23.01 And in the last stage,
00:04:25.05 people will have multiple organ failure,
00:04:27.25 as well as a sudden drop of blood pressure,
00:04:30.15 and this is called septic shock.
00:04:32.22 And for septic shock,
00:04:35.00 there will be a 50% mortality rate.
00:04:39.21 One thing I want to mention is that
00:04:41.28 sepsis is caused by
00:04:44.08 our own reaction to the infection,
00:04:46.16 but not due to the pathogen.
00:04:50.19 Unlike other deadly diseases,
00:04:53.23 sepsis has no drugs.
00:04:55.27 Even after decades of clinical drugs,
00:04:59.19 none of them succeeded.
00:05:03.00 So, I think that most important thing
00:05:06.05 is that we don't know enough about sepsis.
00:05:10.08 So, what causes sepsis?
00:05:12.06 This is still an open question
00:05:14.11 to the scientific community,
00:05:17.26 and I think maybe.
00:05:20.27 I think scientists are making progress now
00:05:24.01 towards understanding what causes sepsis.
00:05:28.01 It begins with the late 19th century.
00:05:32.11 Then, Richard Pfeiffer,
00:05:34.15 a German military doctor
00:05:36.14 who worked with Robert Koch,
00:05:38.03 a very famous bacteriologist,
00:05:40.11 at that time what they found is that
00:05:43.27 injection of heat killed bacteria,
00:05:45.29 which caused cholera.
00:05:48.19 and injection of dead bacteria
00:05:51.04 can cause sepsis in guinea pigs.
00:05:53.23 He then hypothesized that
00:05:56.06 there are some toxic substances
00:05:58.26 inside the dead bacteria.
00:06:02.14 It took about fifty years
00:06:05.18 to find this toxic substance,
00:06:10.00 the lipopolysaccharide,
00:06:12.00 or LPS for short.
00:06:13.21 LPS is the major component
00:06:15.17 of the cell walls of nearly all Gram-negative bacteria.
00:06:19.03 As shown here.
00:06:20.21 this is a scanning electron microscopy picture of E. coli,
00:06:26.07 a Gram-negative bacteria,
00:06:28.05 and this is what the cell wall looks like.
00:06:29.29 The most abundant molecule
00:06:32.24 on the cell outer membrane is LPS.
00:06:36.10 If you zoom in,
00:06:37.29 this is what the LPS molecule looks like.
00:06:39.18 It contains two parts:
00:06:41.03 one is the sugar part,
00:06:42.16 the other is lipid A.
00:06:43.26 The lipid A, as shown in yellow,
00:06:46.21 is the active part of this LPS molecule.
00:06:50.02 If you inject LPS or lipid A into mice,
00:06:55.16 those mice will develop sepsis.
00:06:58.21 So, the question is,
00:07:01.20 how can LPS cause sepsis?
00:07:03.11 If you remember what I told you before,
00:07:06.05 sepsis is caused by
00:07:08.05 our own reaction to infection,
00:07:09.27 not by the pathogens.
00:07:12.19 So the similar question is,
00:07:14.09 how can we respond to LPS?
00:07:16.27 This is the pathway that people think
00:07:22.13 plays an important role in LPS sensing.
00:07:26.23 The membrane-bound receptor,
00:07:28.24 called TLR4/MD2,
00:07:32.03 can directly interact with LPS molecules,
00:07:36.05 just like the eyes of a cell.
00:07:39.04 When the eye sees an LPS molecule,
00:07:41.14 it can trigger the expression of
00:07:44.27 a series of proinflammatory genes,
00:07:47.00 including cytokines.
00:07:48.27 And people use to, for a long time,
00:07:51.14 thought about that.
00:07:53.25 that these cytokine armies
00:07:56.01 are actually the cause of human sepsis.
00:07:59.18 And more than ten clinical trials
00:08:01.17 have been performed with sepsis patients
00:08:06.14 with targeting these cytokine army molecules,
00:08:09.14 but none of them have succeeded,
00:08:11.20 and later on people thought about.
00:08:14.23 what about inhibiting this eye?
00:08:17.06 If you blind the eye of the cell to LPS,
00:08:21.04 then you will block all the cytokines
00:08:25.09 from being produced.
00:08:27.09 So, this is a molecule people developed
00:08:29.12 to inhibit TLR4, the eye of our cell,
00:08:33.20 and indeed this molecule
00:08:36.06 can inhibit the production of these cytokine armies,
00:08:40.07 but after years of trying
00:08:43.01 and after a billion dollars spent on this project,
00:08:46.13 and after recruiting of thousands of people
00:08:49.22 on these clinical trials,
00:08:51.10 this is what they got.
00:08:54.12 As shown here,
00:08:57.02 by looking at the survival rate of sepsis patients,
00:09:00.01 the Eritoran, the drug that can blind the eye to LPS,
00:09:05.28 saves no more people that than placebo.
00:09:09.07 So, it failed.
00:09:11.18 But why?
00:09:15.18 Did we miss something?
00:09:19.06 This is indeed the case, as shown here.
00:09:22.14 Recently, people have identified
00:09:26.02 another pathway that can recognize LPS,
00:09:28.24 inside the cell,
00:09:31.09 in mouse macrophages.
00:09:33.11 In this pathway, there is
00:09:36.24 an unknown LPS sensor,
00:09:38.13 which can recognize LPS
00:09:40.18 and lead to a signal
00:09:43.20 to a gene called capase-11
00:09:46.01 in mouse macrophages,
00:09:47.24 and caspase-11 is
00:09:50.07 a proinflammatory caspase.
00:09:52.07 It has two domains.
00:09:53.29 One is a CARD domain at the N-terminus,
00:09:55.28 and the other is the protease domain
00:09:57.23 at the C-terminus,
00:09:59.06 and the protease
00:10:01.27 looks like molecular scissors
00:10:03.23 that can cut through other protein substrates.
00:10:07.16 And activation of caspase-11
00:10:09.29 can lead to proinflammatory cell death,
00:10:12.23 and this cell death
00:10:15.18 may eventually lead to sepsis,
00:10:18.14 because this cell death
00:10:20.27 has a much stronger effect
00:10:23.18 than the production of the cytokine armies.
00:10:26.09 So, I will call this cell death
00:10:28.06 "unleashing the special forces".
00:10:31.05 This is what this cell death looks like.
00:10:33.14 As you can see here,
00:10:35.09 in the beginning cells look fine.
00:10:37.23 Then all of a sudden,
00:10:39.28 the cell just blows up
00:10:41.25 and it releases all of the cellular contents,
00:10:44.07 which is very proinflammatory.
00:10:50.22 You can see nearly all of these cells died
00:10:53.12 after triggering this proinflammatory cell death.
00:10:57.15 The importance of this pathway
00:10:59.09 was further highlighted
00:11:01.09 by the fact that caspase-11 knockout mice
00:11:04.08 are resistant to sepsis.
00:11:06.10 As shown here, wildtype mice.
00:11:08.21 nearly all wildtype mice
00:11:10.18 died within a day
00:11:13.03 after you induce sepsis with LPS,
00:11:16.24 and caspase-11 knockouts
00:11:19.13 are still very resistant to this disease.
00:11:23.12 And thinking about that.
00:11:25.07 caspase-11 has a functional TLR4,
00:11:27.17 which is the eye that can recognize LPS
00:11:30.23 outside the cell.
00:11:34.00 This suggests that
00:11:36.15 this pathway that senses LPS
00:11:38.26 inside the cell
00:11:40.16 plays a more important role in sepsis,
00:11:43.01 at least in mice.
00:11:45.10 So, let's summarize what we have known
00:11:48.03 before we get into this field.
00:11:50.11 There is a pathway that can recognize LPS
00:11:53.29 when LPS gets into the cell,
00:11:56.21 and this sensor is not known.
00:11:59.27 And this sensor can activate caspase-11
00:12:03.22 in mouse macrophages
00:12:06.08 and lead to proinflammatory cell death,
00:12:09.03 and therefore may trigger sepsis.
00:12:11.24 But we care more about humans,
00:12:14.18 and because humans do not have
00:12:16.23 caspase-11 genes,
00:12:19.05 so the first question we want to answer is,
00:12:21.10 does this pathway,
00:12:24.02 which senses LPS once it gets into the cell,
00:12:26.06 exist in humans?
00:12:28.28 To begin to study this question,
00:12:31.23 we need an efficient method
00:12:33.24 to deliver LPS to the inside of the cell.
00:12:36.12 This is what we use,
00:12:37.28 called electroporation.
00:12:39.09 If you put a cell into an electric field
00:12:42.10 and then give an electric shock,
00:12:44.23 you can punch holes in this cell membrane,
00:12:48.07 and then these molecules
00:12:50.10 that are outside the cell
00:12:53.18 can get into the cell through these holes.
00:12:55.16 And this is what will happen to the cell membrane.
00:12:58.19 In the beginning,
00:13:00.07 the cell membrane is okay,
00:13:01.24 and after electroporation
00:13:03.21 you can really see these holes
00:13:05.21 on this cell membrane.
00:13:08.00 And after electroporation,
00:13:09.24 and more importantly,
00:13:12.22 the cell can recover from this electroporation.
00:13:16.09 So, this is the method
00:13:18.28 that was used to deliver LPS,
00:13:21.19 and if you deliver LPS
00:13:23.15 to a human immune cell
00:13:24.29 called U937,
00:13:26.24 which is a human monocyte,
00:13:28.09 you can see here the cell just blows up.
00:13:31.10 It pretty much looks like the mouse macrophages.
00:13:36.14 So, this blow up
00:13:38.13 will release all the cellular contents,
00:13:40.26 unleashing the special forces,
00:13:43.01 which can trigger sepsis in humans.
00:13:46.09 And if you perform electroporation
00:13:48.05 with control ligand,
00:13:50.17 then the cells are just fine.
00:13:52.16 We can also measure the cell death.
00:13:54.11 You can see here,
00:13:56.12 if you deliver LPS into the cell,
00:13:58.06 it can cause about 80-100% of cell death,
00:14:03.06 but control ligands do not cause any cell death.
00:14:07.07 So, in human,
00:14:09.14 we do not have capase-11,
00:14:11.19 but we have two other closely related genes,
00:14:15.03 called caspase-4 and caspase-5.
00:14:17.09 We first detected the expression level
00:14:19.25 of these two genes
00:14:22.00 in human monocyte cell lines.
00:14:24.01 As shown here,
00:14:26.04 we can easily detect the protein,
00:14:28.09 as well as the mRNA,
00:14:29.27 of caspase-4,
00:14:31.15 but we cannot detect any caspase-5 expression,
00:14:35.06 even using more sensitive methods
00:14:38.09 that detect mRNA.
00:14:40.12 So, the next question we want to answer is,
00:14:43.13 does this pathway
00:14:45.19 depend on caspase-4?
00:14:47.14 We then used a method
00:14:50.13 that is a small molecule
00:14:52.24 that can inhibit, transiently inhibit,
00:14:55.09 caspase-4 expression in human cells.
00:14:58.04 By using this small molecule,
00:15:00.22 we can see here,
00:15:03.09 by transient knockdown of caspase-4,
00:15:06.14 this LPS-induced proinflammatory cell death
00:15:09.12 is totally blocked.
00:15:11.10 So this data suggests that
00:15:14.17 LPS can activate caspase-4
00:15:16.21 in human cells.
00:15:18.14 And quite unlike the mouse studies.
00:15:21.21 in mouse, caspase-11
00:15:23.14 is only expressed in macrophages,
00:15:25.06 that is, an immune cell.
00:15:26.24 And for human cells,
00:15:28.09 we have found that
00:15:30.18 several other non-immune cells
00:15:32.17 also have caspase-4 expression,
00:15:34.20 as well as they can also
00:15:37.24 respond to LPS inside the cell.
00:15:41.01 So, let's summarize the previous two slides.
00:15:43.15 We have found that, in human,
00:15:46.25 we also have this pathway
00:15:48.17 that can sense LPS
00:15:50.09 that gets into the cell,
00:15:51.27 and that this pathway can activate caspase-4,
00:15:54.17 rather than caspase-11
00:15:56.25 in mouse macrophages.
00:15:58.18 And this pathway
00:16:00.12 also can induce the proinflammatory cell death,
00:16:03.12 unleashing the special forces,
00:16:05.10 and may cause sepsis in humans.
00:16:10.19 This is a possible reason
00:16:13.09 for why the TLR4 blockers
00:16:15.19 failed in clinical trials,
00:16:17.21 because [those drugs]
00:16:20.03 only blocked the pathway
00:16:22.08 that can sense LPS outside the cell,
00:16:24.08 and data from mouse
00:16:26.16 suggests that the caspase-11 pathway,
00:16:28.15 which recognizes LPS inside the cell,
00:16:30.22 plays a major role in sepsis.
00:16:33.08 And it is possible that
00:16:36.29 targeting caspase-4 in humans
00:16:38.26 might be the right target.
00:16:41.13 The next question,
00:16:43.10 and most important question for this pathway, is,
00:16:45.27 what is the LPS sensor?
00:16:48.24 Because if you know what the sensor is,
00:16:52.11 you can design small molecules
00:16:54.05 to inhibit this sensor,
00:16:56.01 just like they did on TLR4.
00:16:58.29 So, after trying and trying.
00:17:01.28 we almost tried everything we could,
00:17:05.03 but we cannot find this direct receptor.
00:17:08.22 Then, one day,
00:17:10.20 after characterizing the biochemical function
00:17:12.26 of caspase-4 and caspase-11,
00:17:15.25 we got some hints suggesting that
00:17:18.17 caspase-4 and caspase-11
00:17:20.23 might directly bind to the LPS molecule.
00:17:24.27 This is the data
00:17:28.05 and this is an assay called a pulldown.
00:17:30.21 So, there is a molecule A and a molecule B.
00:17:34.05 If you pulldown molecule A
00:17:36.02 and you get both,
00:17:37.29 it suggests these two molecules have an interaction.
00:17:39.29 If you pulldown molecule A
00:17:41.24 and only get molecule A,
00:17:44.02 then it is possible that the two molecules
00:17:46.01 do not bind each other.
00:17:47.12 By using this method,
00:17:49.04 we can see that both lipid A,
00:17:51.25 the active part of LPS,
00:17:53.23 or LPS,
00:17:55.19 can bind to caspase-4 in human
00:17:57.26 and caspase-11 in mouse.
00:17:59.22 And control ligand,
00:18:01.17 which is lipopeptide,
00:18:04.05 or MPD, the muramyl dipeptide,
00:18:07.09 cannot bind to these two caspases.
00:18:11.10 By using similar assays,
00:18:12.28 we found that the N-terminal CARD domain,
00:18:16.18 which represents about 90 amino acids,
00:18:20.17 is the LPS binding domain.
00:18:22.14 As shown here,
00:18:24.20 the full length protein can bind to LPS
00:18:27.17 and the CARD domain can also bind to LPS,
00:18:34.25 but if you delete the CARD domain
00:18:34.28 the C-terminal protease domain
00:18:36.16 can no longer bind to LPS.
00:18:39.20 So, there are
00:18:41.25 no hypothetical LPS sensors
00:18:44.28 other than caspase-4 and caspase-11.
00:18:50.01 The direct sensors are caspase-4 and caspase-11.
00:18:55.28 This is quite surprising
00:18:58.11 and this is the big deal.
00:19:00.25 So, for caspase proteins,
00:19:03.03 no one has shown
00:19:05.17 that this protein can be a direct sensor
00:19:07.21 for a molecule.
00:19:09.12 This is the first case.
00:19:11.28 And the next question we want to answer is,
00:19:13.28 what happens after caspase-4
00:19:15.26 and caspase-11 recognize LPS?
00:19:20.00 So, this is the data we have.
00:19:21.27 In the normal condition,
00:19:23.22 without any treatment,
00:19:25.04 the caspase-4 protein
00:19:26.23 migrates as a monomer
00:19:28.18 in our polyacrylamide native gels,
00:19:31.05 and if you incubate LPS or lipid A
00:19:34.14 with caspase-4,
00:19:36.13 this protein sticks together
00:19:39.04 to form large oligomers,
00:19:41.10 as shown here.
00:19:43.03 Control ligand does not have this activity.
00:19:46.09 We also have similar results
00:19:48.12 with mouse caspase-11 proteins.
00:19:52.11 So, this is what we see:
00:19:54.15 after binding with LPS,
00:19:56.13 the caspase-4 in human
00:19:57.23 and caspase-11 in mouse
00:20:00.21 become oligomers.
00:20:03.13 If you're familiar with other caspases,
00:20:06.18 for example, caspase-1, caspase-8,
00:20:09.03 or caspase-9,
00:20:10.23 these proteases are all activated
00:20:12.15 through protein complexes,
00:20:14.06 but not self-assembled protein complexes.
00:20:17.10 So, the next question we want to answer is,
00:20:20.02 does caspase-4 in human
00:20:22.05 and caspase-11
00:20:24.09 get activated by this self-assembled protein oligomers?
00:20:28.24 This is the assay we used.
00:20:30.26 We first incubate LPS
00:20:33.22 with this caspase-4 or caspase-11,
00:20:36.27 and then monitor the protease activity.
00:20:39.27 Remember, the C-termini
00:20:42.02 of these two proteins
00:20:44.01 are proteases.
00:20:45.25 So, as shown here,
00:20:47.10 incubation of LPS
00:20:49.13 leads to the oligomerization,
00:20:51.02 and by monitoring the protease activity,
00:20:53.22 you can see that, for caspase-11,
00:20:56.29 we have about
00:20:59.21 20-fold protease activity increase,
00:21:05.21 and for caspase-4
00:21:07.16 we have about 60-fold
00:21:10.27 protease activity increase.
00:21:13.24 So, let's summarize what we have found.
00:21:17.08 There is a pathway.
00:21:19.24 when LPS gets into the cell,
00:21:22.03 it can be recognized directly
00:21:24.21 by caspase-4 in human
00:21:26.13 and caspase-11 in mouse,
00:21:28.22 with the N-terminal CARD domain.
00:21:30.23 This activation may well lead
00:21:32.20 to the oligomerization of caspase-4 and caspase-11,
00:21:37.27 and caspase-4 and caspase-11
00:21:40.01 actually get activated
00:21:41.27 through this oligomerization.
00:21:43.11 Because these caspases are proteases,
00:21:47.15 when they activate
00:21:49.16 they can cleave other substrates,
00:21:51.13 and maybe cleaved substrates
00:21:55.05 may cause something
00:21:57.00 to lead to this proinflammatory cell death.
00:22:00.20 And remember I said earlier
00:22:02.23 that proinflammatory cell death
00:22:04.24 releases the special forces,
00:22:09.05 which may trigger sepsis.
00:22:12.09 Since this pathway is very important
00:22:15.06 in a mouse sepsis model,
00:22:17.08 we have hypothesized that
00:22:19.09 this pathway might also play an important role
00:22:21.23 in human sepsis.
00:22:23.11 So what I'm working on
00:22:26.11 is performing a large-scale small molecule screen
00:22:31.12 which contains 300,000 small molecules.
00:22:34.20 We are aiming to find some molecules
00:22:36.26 that can inhibit this proinflammatory cell death,
00:22:39.17 as well as the whole pathway. We hope, in the near future,
00:22:44.14 our small molecule compound
00:22:46.29 might provide new treatment
00:22:48.20 for this deadly disease.
00:22:50.27 Okay, here's my acknowledgements.
00:22:54.17 I'd first like to thank by supervisor,
00:22:56.26 Dr. Feng Shao,
00:22:58.11 for his guidance and support
00:23:00.08 during these years.
00:23:02.17 And I would also like to thank my major collaborator,
00:23:05.05 Dr. Yue Zhao,
00:23:06.18 and all other members in our labs.
00:23:09.25 And this is Dr. Feng Shao,
00:23:11.28 and this is Dr. Yue Zhao.
00:23:13.29 And thank you for your attention!
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- Educators of H. School / Intro Undergrad
- Educators of Adv. Undergrad / Grad
Surroundings and Evolution Shape Human Sight, Smell and Taste
Understanding how the five senses evolved can help inform how human sight, smell and taste continue to shift based on the environment, according to three researchers at the 2017 AAAS Annual Meeting in Boston.
We are currently experiencing “a state of mismatch” between the ways our senses evolved and our current surroundings, according to Kara C. Hoover, associate professor of anthropology at the University of Alaska, Fairbanks.
Our ancestors’ visual acuity evolved outside in the natural world, said Amanda Melin, assistant professor of anthropology and archeology and medical genetics at the University of Calgary. Yet, humans now spend significant amounts of time inside and this is adjusting our vision, she said.
“There’s mounting evidence that our anthropogenic light environments are having a real cost on our acuity,” said Melin, with rates of myopia – or nearsightedness – skyrocketing in recent years. While myopia does have a genetic component, evidence suggests that dark rooms, artificial lighting and “near-work tasks,” like staring at a computer screen or into a microscope, contribute as well.
Humans can correct nearsightedness with glasses, contact lenses or surgery, but myopia can put individuals at risk for other diseases such as glaucoma and retinal detachment, she said. Studies have shown that 40 minutes outside each day decreases chances of getting myopia between 25% and 50%, Melin said.
Yet the environmental changes wrought by human activity impact non-human primates as well, she said. Primates in general, even those that are nocturnal, are highly visually dependent. Sight drives nearly every aspect of their lives, including catching prey and communicating with other animals. In areas without light pollution, skies are actually getting darker due to pollutants and greenhouse gases in the atmosphere scattering light. Scientists do not know how non-human primates will cope with global darkening, Melin said.
Additionally, natural light even with its beneficial ability to lessen chances of acquiring myopia can be tainted with pollutants and less-than-fresh air can play with our sense of smell, Hoover said. The ability of humans to smell has adapted over time to aid survival and reproduction, helping humans identify nutritious foods, select partners and avoid spoiled food and other dangers, she said.
Much research has been done on our “smell-being,” particularly on how our environment continues to transform – and disrupt – our sense of smell, Hoover said. People in polluted environments have been found to have a diminished sense of smell, which will only become more common as the global population continues to urbanize, she said.
Studies have shown the ability to detect smells can modify mental, social and physical health, but some people – those who live near factories or mining communities, for instance – are at greater risk of a diminished sense of smell and all of the attendant problems that can spark, she said. We are living in an age of “sensory inequities,” Hoover said.
“We’re not going to leave buildings, we’re not going to leave our computers, we’re not going to abandon that, so we need to actually create environments that engage us with the outdoors and also that, when we go outside, we’re not in a polluted space,” Hoover said.
Paul Breslin, professor of nutritional sciences at Rutgers University, has looked at our sense of taste to understand why we are drawn to certain flavors – and how taste preferences can harm or help our health.
Not every species loves sugar, but humans do – and so do apes, who are omnivores who love fruit and obtain about 80% of their calories from fruit, Breslin said. We’re also drawn to sour, acidic tastes, the other flavor present in fruit, he noted. Unlike other animals, humans and other primates have lost the gene that codes an enzyme to allow us to produce our own Vitamin C, likely because we were eating enough Vitamin C-rich fruit, he said.
To get these crucial nutrients and calories, other apes will go into a tree and gorge themselves on fruit until it’s gone. Humans do this, too, though metaphorically, Breslin said.
“We climb up into this tree that our society has created, and we gorge on the fruit, but the tree never runs out of fruit and we never come out of the tree,” Breslin said. “We have to keep in mind that we need to force ourselves down … periodically.”
Another type of food we are primed to prefer could help mitigate a persistent health problem and save lives, Breslin said. Humans are attracted to fermented food and drinks, including wine, beer, bread, fermented meats like pepperoni and fermented dairy like cheese and yogurt, he said. Properly fermented foods can promote a healthy gastrointestinal microbiome by delivering probiotics and prevent diarrheal diseases, the most common disease on the planet among humans and the second-largest killer of children, he said.
“I believe that if we eat more fermented foods we’ll be able to have a positive impact on helping prevent and treat this,” said Breslin.