Hi folks, As I mentioned in lecture on Tuesday, we are caught-up with our lecture material and will not meet for lecture on Thursday. Instead, I am offering a reading (attached) that I had described earlier, along with some explanation of one of the more important points described in this study. Last weekend, I sent to our class description (below) of a recent publication examining behavioral-genetic associations in domestic dogs. I hadn't yet seen the original research when I wrote to you last weekend, but forwarded a news report about it that came from the home institution of the senior author on the study. I described in my message to you that some of the behavioral-genetic associations the authors reported were as high as 0.7, near to the limit of those ever reported for narrow-sense heritabilities of behavior. Over the weekend, I requested a copy of the actual research paper from its senior author, and, upon seeing it, wanted to offer some interpretation. Early in the term, in chapter 03, we discussed trait variation within species, and we noted (using the canine example) that artificial selection has created an abnormally high amount of trait variation within the single species of domestic dog Canis lupus familiaris. In our next lecture (Chapter 04), we discussed behavioral genetics and narrow-sense estimates of heritability, describing the upper limit of such associations as around 0.7. We saw in that same chapter (as well as in later chapters, including Chapter 10) some estimates of narrow-sense behavioral-genetic heritability estimates that all were < 0.3, which is typical. In this new report, the authors report behavioral-genetic associations that are much higher than those typically reported. How can this be? It stems from the artificial (and unusually large) degree of trait variation within this domestic species. Typically, when one examines associations between traits within a natural (e.g., not artificially-selected) species, we expect some small, defined range of trait values, with correlation (association) between traits of some relatively low magnitude. Here in my Figure 1, I show the trait values and the within-species bivariate trait association for two (hypothetical) different species, such as a fox and a wolf. Within either species, there is some defined range of values for trait X (such as body length) and some defined range of values for trait Y (such as body mass). In my hypothetical example, these traits are correlated somewhat weakly within species A, and uncorrelated within species B. Notice that the two species do not overlap in trait values - a small wolf is always larger than than a large fox. If domestic dogs were a natural species, chances are good that their trait values would fall somewhere in between these two species, perhaps closer to the 'wolf' end of the spectrum. Nonetheless, they would be expected to occupy only a small potion of the overall trait ranges. Now, consider what the authors have done in their analysis. They have considered all domestic dog breeds to be of the same species, a fact that is technically true but which ignores the other fact that their range of trait values is anything but normal. They have analyzed behavioral-genetic associations across breeds within this single species, but here the individual breeds represent much more trait variation than natural species might, as size variation across domestic dog breeds is much greater than size variation across canine species in the wild. When associations are evaluated across multiple species (such as in my hypothetical Figure 2), the associations are often of higher magnitude. In the current study, analysis across the very artificially-distributed dog breeds behaves in the same way, resulting in behavioral-genetic associations much higher that those reported within single, natural species. 13/14 of their within-breed estimates (their Figure 1) are <0.3, just as one would expect. This study is quite interesting, and represent the application of some very modern techniques (canine SNP chip, anyone?) to this interesting question of the heritability of behaviors. It also serves as a very useful reminder of - the power of artificial selection - modern dog breeds are estimated to have been developed only over the last 300-500 years. For a natural species to evolve as much trait variation in this short time is unheard of. - the danger of reliance upon secondary news sources - the original news story that I sent to you accurately describes the gist of this research study, and highlights the very strong associations found. But, it also leaves out enough detail that it is not possible to immediately assess why the associations are of such magnitude. - the importance of proper modeling of evolutionary constraint - as shown in my hypothetical example Figure 2, trait associations across species can be artificially inflated if simple, linear techniques are used instead of methods that account for shared evolutionary history, such as independent contrasts analysis or nested ANOVA. The authors do have a phylogenetic model for their dog breeds; I am not schooled well-enough in the jargon of their analytical models to know if they have fully controlled for relatedness. Whether they have, or have not, these types of broad comparisons should always be examined with an eye for that type of concern. - the imperfection of any one study - this is a research report describing one body of work on this topic, and I'm certain we could find other, similar/related studies. Is this study perfect? Certainly not. Is it still interesting, and useful? Absolutely. Any one research study can only advance our understanding incrementally. It's too easy, and too common, to dismiss work outright for containing flaws - it's more important to ask, given such flaws, is there anything that we can learn? The latter approach is more fruitful, and provides a much better return on one's investment of time and effort. Here, the traits with the highest across-breed heritabilities are trainability, aggression, and attachment - exactly those traits we might expect to have been key in the artificial selection/shaping of the human-dog relationship. It's a nice confirmation that these are strongly heritable, in ways that have translated into very powerful differences among breeds. I've spent perhaps too much time dissecting some of these points, but I do so because they put some of our lecture material into sharp relief. Textbook examples are often too carefully culled to represent cutting-edge investigation; it's both fun as well as useful to see where current researchers in these areas actually are working. Have a great rest of the week - see you on Tuesday for Chapter 11. Sincerely, Dr. Nealen
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Good evening all, As I noted in lecture on Wednesday, we remain on-schedule with out lecture chapters, and do not have a chapter scheduled for tomorrow (Friday 25 Oct). So, I would like once again to propose that we do not meet in person for lecture tomorrow, and ask instead that you consider the reading that I am forwarding here. In our last lecture on the endocrine system, we noted the central role of the pancreas and its hormones in the regulation of blood glucose ("blood sugar") levels. When levels of blood glucose rise (such as when we are absorbing digested sugars into our bloodstream after a meal), the hormone insulin is released by the pancreas. Insulin causes our cells (especially liver and muscle cells) to uptake glucose - that is, to take glucose out of the bloodstream and move it into cells by means of membrane transporters. This allows cells to have glucose available for fuel, and also allows cells to store the excess glucose for later use. On the flip side, when our blood glucose levels decline (such as when we are several hours past a meal and done absorbing nutrients), other cells in the pancreas release the hormone glucagon, which causes our cells (especially liver and muscle cells) to release some of their stored glucose. Together, the use of the two hormones allows us to maintain a relatively even profile of blood glucose levels. As we discussed yesterday, when blood sugar levels are not well-controlled, diabetes may result. The primary symptom of diabetes is high (and poorly controlled) blood glucose levels. This causes a number of immediate effects, such as excess urination, thirst, and excessive fat metabolism. Over the long term, high levels of blood glucose are very damaging to our tissues, particularly through scarring of the inner lining of our blood vessels. This can lead to the failure of organs with extensive capillary beds (such as the retina of the eye, and the kidney), and has negative effects on circulation in general, especially in the lower periphery. Persons with uncontrolled blood sugar often suffer poor wound healing (especially of the feet), which can lead to infections and, in some cases, require amputation. In lecture, we distinguished the two general types of diabetes as well. "Type I" diabetes occurs when our own immune system causes the destruction of the insulin-producing cells of the pancreas. This is classified as an auto-immune disorder, as the disease stems from a problem with the immune system. Type I diabetes is often called "juvenile diabetes", because it is typically first diagnosed in one's youth. It can be treated (usually successfully) with injections of insulin - daily, often multiple times. Insulin pumps can also be used - these are small, battery powered pumps that infuse gradual, small amounts of insulin into a catheter. They are expensive and require maintenance, but are effective solutions for many. "Type II", or "adult onset diabetes" is more challenging. It tends to appear in people with a combination of risk factors: obesity, poor diet, little exercise. Over time, the cells of their body gradually become resistant to insulin, and stop responding to it. Their pancreas produces normal amounts of insulin, but it is ineffective - blood glucose remains elevated, cells become starved for sugar fuels, and metabolize other fuels (mostly fats). Tissue damage accumulates because of the persistently elevated blood glucose levels. Additional insulin (injections) can help somewhat, but the most effective treatment is improvements in diet and exercise. Some people can almost completely reverse their condition through these lifestyle changes, and nearly everyone can benefit at least somewhat from them. There is a lot of biology associated with diabetes: its causes, effects, and treatments. There also is a lot of sociology to it as well. Diabetes strikes populations very unevenly, and impacts populations of relatively poorer socioeconomic levels most severely. This is believed to be due to a number of factors, including reduced access to high-quality food, more-restrictive employment and familial responsibilities that limit time to exercise, and less access to good information about health. It has also been suggested that food corporations specifically target these populations with advertising and vendors for "fast food", including soft drinks ("soda", or "pop", depending upon where you were raised). As a food, soda is of very low quality. It is mostly water, but the other primary ingredients are sugar, and often caffeine. It is also quite acidic, and has quite damaging effects on our teeth. So, why do we buy/drink it? We do so at least in part of because of very successful, and very prominent, advertising, which has allowed some soda companies to develop enough clout that they can contractually deliver soda to schools, hospitals, corporations, and even cities. Think back to your middle- and high-school education: did soda vending machines exist in your school? Were fountain drinks available over the counter in the cafeteria? For most of us, the answer to these questions is "yes". Do you buy bulk quantities of soda? Do you see others around you who do? Again, for most of us, the answers here are "yes" as well. In recent years, public health experts have recognized the dangers of over-consumption of soda, and more importantly, the danger of exposure to it in our youth. Too often, adolescents develop a "soda habit", and maintain it into adulthood. This, in combination with other lifestyle choices, has led to skyrocketing rates of juvenile obesity. Even more alarming, "adult onset" diabetes is now diagnosed in adolescents at alarming rates. So what can be done? Well, the debate rages, because to eliminate soda from communities and diets is not really an option. Soda companies are large, and powerful, and they have an avid user base that wants their products. This is a situation similar to that faced years ago with the tobacco industry: large and powerful corporations, well-paid lobbies, a desirous user base, and mounting evidence of the dangerous health effects of the product. Here, too, numerous solutions were discussed and tried. One of the remedies that seemed to be most effective was to implement larger and larger taxes on tobacco, to the point at which fewer people were willing, or able, to financially support their tobacco habit. Because of the success of this strategy to reduce tobacco usage, we now live in an era of the "soda tax". The idea here is the same: if a popular consumer product is legal, but unhealthy, tax it in order to reduce the number of people using it, and/or the amounts that they use. This remains a controversial idea. Why should companies producing a legal, desirable product be punished? Is this ethical? Does this not also punish the people that work for them, and their suppliers, accountants, and all of the other people who work in associated jobs? Does this also punish consumers of relatively lower income unfairly, because they would be the ones least likely to be able to afford a price increase? With soda, too, the application of a tax is more complicated. Tobacco and alcohol are relatively uniform in how they are packaged and purchased, but sugary drinks exist across the spectrum (from soda, to sweetened milk, to orange juice and yogurt). Wait -- aren't milk, orange juice, and yogurt good for us? Well, yes, but less so if they have a lot of added sugar. Should they be taxed less than soda, because they are relatively more healthy? What about sugary cereals and granola bars? What about foods with artificial sweeteners? The lines are less clear in this current health debate. The news report I am forwarding describes a recent assessment of the effectiveness of "sugar taxes". Dozens of other countries, and multiple large cities in this country, have imposed this tax. They have existed for a relatively short time, so there is much yet to be learned about them. They do appear to cause a drop in soda consumption, but whether that translates into improved health of the population is still to be determined. Not surprisingly, the soda companies have responded aggressively, with a variety of tactics. This battle is far from settled. http://blogs.discovermagazine.com/crux/2019/10/22/do-soda-taxes-actually-work-heres-what-the-science-is-telling-us/ The next time you are at the grocery store, ask yourself if you are planning to put soda into your cart. And, look around: how many people do? It's common to see people pushing shopping carts with 6-packs of bottled soda (often multiple of them) draped over the edges of the cart. This behavior didn't exist 10 years ago! Have the bottles changed to make this more convenient? Or are we buying more? Our fast food restaurants and convenience stores offer *enormous* fountain drinks - 30, 40, even 50 ounces at a time! Does anyone rally need that much soda at once? On this, and all of our topics, stay informed. Healthy habits require good information, and wise choices. There is plenty of information available on the health aspects of soda and its social implications. Be wise shoppers and consumers! And, have a great weekend. See you on Monday for Chapter 17. Sincerely, Dr. Nealen Good morning all, At several points this term, we have discussed the genetics of behavior, including both the ability of single genes to influence behavior, as well as the heritability of individual behaviors and how traits can potentially be mapped onto phylogenetic histories. In the recent behavioral news is a report of a study that used large databases on dog behavior and genetics to look for behavioral traits that were associated with consistent genetic features. The researchers found >100 potential sites in the genome that were strongly associated with dog breed characteristics, including train-ability, aggression, excitability, and others. One of the strengths of the method used here was that the researchers restricted themselves to a subset of the data pertaining to purebred dogs. This has the advantage of eliminating cross-breed variation which could dilute the strength of the genetic signals they were trying to detect. Dogs also are an advantageous species for a study like this, because they are popular, have long been bred in relatively pure lines, and have been artificially selected for a range of behavioral characteristics. Some of the associations reported are quite strong, with heritability estimates as high as 60-70%. Those are very high values, near the limit reported for animal behavior-genetic comparisons. It's also surprising, in that, while this study has several strengths in its design, it also has one specific weakness: the researchers did not have genetic and behavioral information from the same individual animals, but instead were relying on databases (and breed averages) assessed across different individuals. That suggests that some of the associations, if tested within individual subjects, could be even stronger. https://penntoday.upenn.edu/news/genes-play-role-dog-breed-differences-behavior The human-dog relationship is a long one, and our artificial selection of dogs has been enormously powerful - when you think about all of the different dog breeds in the world, from Danes to dachshunds, Newfoundlands to chihuahuas, they all are the same species. That is testament to an enormous phenotypic plasticity (reaction norm) within their development. I'm going to request a copy of the original research article that this news report references, if anyone would like to see it - I'll bet it is interesting reading. Perhaps it will shed some light on my dog's (a rescue Rottweiler) behavior... Have a great rest of the weekend - see you on Tuesday. Dr. Nealen Good morning all, During our recent EMG lab, we considered muscle structure/function, and how muscle strength can be improved through enlargement of muscle fibers. We also noted that testosterone can support the development of larger muscles in both men and women. In the news this week is a report confirming that testosterone improves muscle and athletic performance in women, along with news of a strict limit on testosterone in female athletes being imposed by a track-and-field regulatory body. Testosterone is a potent steroid hormone, produced in abundance by the male gonads (the testes). Testosterone is also found in women. The female gonads (ovaries) do not produce testosterone directly, but do produce several estrogens, which can be converted to testosterone by enzymes (especially in the brain). Both sexes also produce other androgens (male-typical hormones) in the adrenal glands, which also can be converted into testosterone. So, we tend to think of testosterone as a 'male hormone', but the reality is not so simple. Both women and men have circulating testosterone, although men typically have levels that are 10-30x higher that those found in women. But, here too, our simplistic and convenient categorizations are not always reflected in reality. While men typically have much more testosterone in circulation than do women, the range of variation in each gender is large. What of women who produce unusually large amounts of testosterone? Will that give them a muscular and a competitive advantage in sporting events? The anecdotal and the experimental evidence say that it will. It is convenient to think of all persons as being purely binary in terms of their sex, such that all aspects of their sexual make-up (genetic sex, physical sex, physiological sex, gender identity) align to be either purely female or purely male, but the reality is, as always, more complicated. Persons of differential sexual development may not be perfectly aligned in all of their sexual characteristics, causing them to have characteristics which are not purely 100% typical of one gender or another. Apart from the social and physical challenges this poses, how such individuals can be evaluated in regulated sporting events recently has come into question. The most notable case has been that of the South African athlete Caster Semenya, a multi-medal winning foot race champion who has repeatedly been sanctioned because her testosterone levels are higher than the thresholds set for female athletes. And what of athletes that are making a gender transition? Their testosterone levels are highly variable, and may fall within the male-typical or the female-typical range. Should they be barred from, or limited in, participation in sporting events? These are important issues, beyond sporting regulation. Most aspects of society long have been male-biased, and it is becoming increasingly apparent that we suffer because of this. In science, it has become very clear that work done largely on male physiology serve females poorly. For decades, the standard experimental models for human physiology have been male mice and rats. Only one gender was used in order to reduce experimental variability. We long have known of differences in the female and male reproductive systems, but we never really appreciated how their influences translate into other systems (including the muscular system). But, now we are learning how surprisingly different male and female physiology outside of reproductive systems can be. And, the fact that this recent study of testosterone supplements in women was one of the first of its kind suggests that we have a lot of catching-up to do: https://www.theguardian.com/science/2019/oct/15/testosterone-boosts-womens-athletic-performance-study-shows There is much to be learned about differences in female and male physiology and their implications for our health and well-being, and our scientific community is finally waking up to this fact. How the sporting community deals with the complexities of our physiology is of relatively little importance, perhaps. But the issue of equality in general, in science, health, and society, is one that recent generations have failed to properly address. May your generation be more open, more mindful, and more egalitarian. Have a great weekend - Dr. Nealen Good afternoon all, Now that our second exam is completed, we will spend a bit of time discussing the nervous and endocrine systems as we start into the 3rd unit of our course. These are the two primary regulatory systems in the body, which makes their place in our homeostatic control very important. Accordingly then, when these systems are dysregulated or hijacked, the problems that arise can be very severe. We do not have a chapter assigned for tomorrow (Friday 18 Oct), so I would like to give you some supplemental reading, instead. You can review this material on your own, so we will not have to meet in person on Friday (tomorrow). In lecture yesterday, we outlined the cellular basis of the nervous system, and the method by which neurons communicate with each other and their targets at synapses. Synapses are points of communication between cells, but are not actual points of physical contact between cells. The communication is achieved not by direct cell-to-cell transfer of materials, but rather through neurotransmitters, chemical signals that are released from the 'signaling' cell, drift across the synapse space, and bind to receptors on the 'receiving' cell. If you think back to early in the term about our discussions of how cells can communicate with each other, you will picture that these neurotransmitters can have effects on their target cells by binding to receptors on the cells, and causing some change: perhaps ion channels open or close, ions move in or out of the cell (or stop flowing), or some enzyme is activated that changes the metabolism of the target cell. These changes might have the effect of stimulating the target cell (causing it to perform more of its cellular function), or inhibiting it. As I pointed out in lecture yesterday, synapses also are the place where most of our drugs (both legal and illegal) influence nervous system function. Our drugs may change the amount of neurotransmitter that is released, or cause it to stay in the synapse for a longer or shorter time. Some drugs block neurotransmitters from binding to their receptors, or artificially activate the receptors even when no neurotransmitter is present. These all are potentially very powerful effects on synaptic function, and thus brain function. If the effects of medications are targeted to specific neural systems (sensory, motor, motivation, reward, or other), they can drastically alter our behavior and our capabilities. When we quickly reviewed some some common drugs and their effects at the end of lecture yesterday, I noted that heroin is among our most dangerous drugs, for its ability to cause very high levels of dependence (users can't bear to be without the drug) and tolerance (users need successively larger doses to feel the same effect). Heroin is one of the opioid drugs, a class of drugs long known for their ability to relieve pain and provide pleasure/euphoria. This class of drugs includes morphine, long used clinically for pain relief. Historically, heroin was derived from natural (plant) sources, and humans have been cultivating and using opioids for thousands of years. Poppy plants have long been grown for their opium sap, which can be consumed as-is, or refined into more-potent forms. With the advent of global travel, poppies grown in Afghanistan can produce opium sap, which can be refined into heroin and trafficked for thousands of miles. This wave of heroin across the planet initiated the opioid crisis, decades ago. More recently, pharmaceutical advances have led to the development of many other opioids: hydrocodone, oxycodone, fentanyl, and others. They are so effective at providing pain relief that they have been heavily marketed, and heavily prescribed. Black-market sourcing and illegal use of synthetic opioids now far outstrips that of heroin, as the pharmaceuticals are typically cheaper, easier to obtain, and preferred by users because they are, in many cases, more potent. Fentanyl, for example, is estimated to be 20x as potent as heroin. Other synthetic opioids may be as much as 500x as potent. Prescription and illegal use of opioids now has reached a crisis point in our country. One cannot listen to the news without hearing of opioid uses and deaths (even here at IUP). Opioids do target the pleasure and pain centers of the brain, but they also serve as a general depressant of respiratory function. As users become dependent upon and more tolerant of these drugs, they acquire and use them in higher amounts. This puts them more and more at risk of respiratory failure: their brains simply stop signaling enough breathing. This is especially problematic when users consume illegal drugs, for their contents may not be well-regulated. Far too often, users overdose on drugs which are more concentrated, or in higher doses, than expected. And so, for your reading on this topic, I'm offering here below a link not to a recent news story, but rather to a more comprehensive news report that was issued last Fall. It describes some of the biology and the neuroscience of opioid addiction, but also presents a variety of personal perspectives from addicted individuals. In many ways, addiction can be considered to be a disease, and the viewpoints and anecdotes describing addiction are both powerful and scary. https://www.nytimes.com/interactive/2018/us/addiction-heroin-opioids.html This article also includes links to a few other resources on the topic of opioid addiction. But let us add to this discussion some good news: Because the action of opioids is relatively well-understood, pharmaceutical advances have made available a very effective antidote to opioid overdose. Commonly referred to by its product name (Narcan), naloxone is a substance that binds to opioid receptors, in place of the opioids themselves. But, naloxone does not activate the receptor in the same way as do the opioids; rather, it blocks the receptor from being activated by the opioids. Naloxone is remarkably effective, and many first responders and emergency personnel now carry it. They find themselves using more frequently than they would like, but there is no doubt that it has saved thousands of lives. Naloxone is so important in the fight against opioid abuse that the Pennsylvania Department of Health has issued a standing order that allows public citizens to obtain it, if they believe that having Narcan might help them prevent an opioid overdose. If you think that having it would benefit you or those around you, I'd encourage you to consider obtaining it. You can start at the PA Department of Health web site, especially the text pertaining to ACT 139, which described how private citizens might obtain naloxone, through a standing prescription order: https://www.health.pa.gov/topics/disease/Opioids/Pages/Naloxone.aspx There also are opioid resources available here at IUP, through IUP's Center for Health and Well-Being: https://www.iup.edu/chwb/ I can help you navigate these resources, if you like. I hope that these materials help to put our discussions of brain structure/function and synapses into some context. I'd be happy to provide more material on these topics, if anyone is interested. Have a great weekend - see you on Monday. Sincerely, Dr. Nealen These Butterflies Evolved to Eat Poison. How Could That Have Happened? - The New York Times10/12/2019 Good morning, We've considered recently the concept of aposematism, the display of warning coloration to indicate to potential predators that one is unpalatable or otherwise unsuitable as a prey item. As we have seen, there are many implications to this type of signaling, including the costs involved, the degree to which it is effective, and its potential to be mimicked (and thus rendered potentially less effective) by palatable species. The issue of aposematic costs is one that has been considered for some time, particularly the metabolic costs of producing warning coloration as well as the predation cost of being conspicuous. In addition to these are the metabolic costs of actually being unpalatable, and in no system has this been better explored than in monarch butterflies, conspicuous in both larval and adult forms, as well as highly unpalatable in each for the glycosidic compounds they acquire and sequester from milkweed plants (their near-exclusive forage). These compounds are highly toxic disruptors of Na+ channels, and being able to ingest and store them has required some evolutionary tinkering. In the recent science news is consideration of this phenomenon, with some genetic work that explains the evolution of caterpillar resistance to these glycosides. The plant defenses have evolved to deter caterpillar feeding, but the caterpillars were able to evolve resistance with as few as three genetic mutations. These researchers were able to induce these same mutations in fruit flies, rendering them resistant to the glycosides as well - a very powerful experimental demonstration. The researchers also demonstrate some of the costs associated with the evolution of resistance to glycosides, including reduced ability to withstand physical shock. No evolutionary benefit is free, and beneficial changes to genes often are paired with deleterious side-effects. Here, the benefit (unpalatability) appears to outweigh the costs (reduced ability to withstand physical rotation). Many of the plants and animals around us are conspicuous, while many others are cryptic. Those that are colorful and eye-catching may be silently playing potentially-deadly games of chemical warfare. Nature has been described as 'red in tooth and claw' (William Congreve); we might expand that to '... tooth, and claw, and toxin', for many toxins (including these glycosides) are quite deadly. What is remarkable to me is the role of simple sugars in glycosides, forming one side of the glycosidic bond. This is why some dangerous chemicals (such as automotive antifreeze, ethylene glycol) taste sweet and thus are dangerously attractive to the uninitiated. It makes me wonder whether glycosides have ever been used in nature as deadly bait, to lure, and then poison, potential prey. I'm willing to bet that it has... https://www.nytimes.com/2019/10/02/science/monarch-butterflies-milkweed.html Have a great weekend- Dr. Nealen Good morning all, In recent weeks we have considered the role of the circulatory and respiratory systems in collecting and delivering oxygen to our tissues, and just last week I sent you a long article about altitude-induced hypoxia and the physiological challenges that it stimulates. We've also discussed the kidney hormone EPO, and its role in stimulating the production of RBCs. Fresh on the heels of those discussions and reading, this week's science news included the awarding of this year's Nobel Prize in Medicine, to a group of three researchers who study this very phenomenon, the physiological responses to oxygen. Their work is crucial to an understanding of how cells adapt to changing oxygen levels. https://www.cnn.com/2019/10/07/health/nobel-prize-for-medicine-2019-intl/index.html Nobel Prizes in science fields are awarded to researchers who have long, established careers and who have made discoveries that defined their fields. This year's winners are no exception - these scientists are well-established and highly respected. And, not surprisingly, they are still active. They also are likely to follow another tradition in that they most likely will use the award not to enrich themselves personally, but to support the work of their research groups. It's a great example of the selflessness that drives much of science: exploration and discovery for the greater good. There are plenty of other news stories on these awards, including https://www.sciencemag.org/news/2019/10/medicine-nobel-honors-work-cellular-system-sense-oxygen-levels?utm_campaign=news_weekly_2019-10-11&et_rid=17390186&et_cid=3026386 https://www.the-scientist.com/news-opinion/cells-oxygen-sensing-discovery-earns-nobel-prize-66538 Breakthroughs in science normally come after long, hard work, built from many small steps of progress - and informed by many failed experiments, a lot of trial-and-error, and requiring much patience. One prize winner (of years past) said that 'if I have seen further than others, it is only because I have stood on the shoulders of those who came before me'. They say that 'no man is an island', and in science that is certainly true - modern science is a highly collaborative venture, and today's advances are built upon the progress of earlier investigators. When you contribute to a project, no matter how small or insignificant your part may seem, it's important to remember that it adds to our collective knowledge and capability. Who knows? Future Nobel Prizes may depend on you! Have a great weekend - Dr. Nealen Good morning all, In recent weeks, our lab exercises have considered EEGs, sensory function, as well as muscle control. In the news this week is a report that links all of these, in a way that may prove to be revolutionary for those with spinal injuries. Recall that from an EEG, one can evaluate the activity in underlying neural tissue. You also will remember our diverse tests of sensory systems, which were good reminders of how broad and how important our sensory capabilities are. Most recently, we discussed how action potentials in motor neurons can be used to activate skeletal muscle. Researchers have managed to marry all of these elements in new technology that is a real-life version of something from science fiction: a robotic suit. They have used sensory receivers and brain implants to allow a paralyzed man to control this suit, enabling him to walk for the first time in years. The subject received bran implants into his motor cortex, which recorded his motor signals. Because of his spinal injury, these signals could not be relayed to his muscles through the spine. Here, the signals were routed to electronic equipment, and then to prosthetic limbs. It look a lot of practice learning how to associate his own thoughts into the motions of his prosthetics, and there is much about the device yet to be improved, but the result remains extraordinary. https://www.bbc.com/news/health-49907356 We live in a world in which advances in neuroscience and advances in technology occur at a rapid pace, and their intersections are often astonishing, and fruitful. Have a great weekend - Dr. Nealen Good morning everyone, In the recent science news are articles related to several of the topics we have considered recently - this is a nice confirmation that our course topics are 'up-to-date'! Early in the term we considered the behavior of parasitic wasps, that stun prey and then oviposit eggs within them so that their larvae have a ready food supply during early growth. In the news this week is description of a different kind of parasitic wasp, one which parasitizes other wasps. Here, the form of parasitism is less direct, in that the parasite deposits its eggs into the same plant gall that its host occupies. The parasite larvae then can attack the host, and in doing so, they accomplish a form of behavioral and physiological 'hypermanipulation'. Not only do they use the host tissues for their own nourishment, but they actually trigger a malformed version of the hosts normal escape behavior, which ensures that the host itself doesn't escape the gall but which provides the parasite an escape route. https://www.sciencemag.org/news/2019/09/crypt-keeper-wasp-brainwashes-far-more-victims-thought https://www.nytimes.com/2019/09/27/science/crypt-keeper-wasps-parasitic.html https://www.bbc.com/news/science-environment-49692974 The degree to which parasites manipulate their hosts can be extraordinary. We are used to thinking that parasites can make use of host tissues, but examples like this reveal more complicated interactions, with some parasites hijacking host behavior as well. There are plenty of examples, such as these: https://www.nationalgeographic.com/news/2018/10/141031-zombies-parasites-animals-science-halloween/ All are good reminders that host behavior, as well as host tissues, can be exploited by parasites. Even more recently, I sent you some information about humans who have developed some ability to perform echolocation. Just this week came a report on this topic, suggesting real, functional remapping of the brain's visual cortex to support this new capability: https://www.sciencemag.org/news/2019/10/echolocation-blind-people-reveals-brain-s-adaptive-powers At some level, neural plasticity is responsible for all that we can learn, but to have whole-scale re-functioning of a part of the brain from one sense to another is very impressive. Have a good weekend - Dr. Nealen Good evening all, As we remain caught-up on our lecture schedule, we do not need to meet in person on Friday (04 Oct) for lecture. Instead, I'd like to you to consider a recent science news article that bears on our lecture material. In recent weeks, we have considered the properties of our blood, its red blood cells and hemoglobin, as well as the ways in which the circulatory and respiratory systems interact to deliver oxygen to our tissues. We've also described how erythropoietin (EPO, a hormone released from the kidneys in response to low blood oxygen levels) can stimulate the production of more RBCs. The article I am sending you considers these same phenomena in a human population that lives (but not thrives) in perhaps the highest-elevation city in the world, La Rinconada, Peru. La Rinconada sits at an elevation of 5,100 m (more than 16,500 ft) above sea level, and has a regular population of >50,000 at this very high altitude, there to work in gold mines. The air at this elevation contains only half as much oxygen as the air at sea level. Persons not accustomed to living at high altitude can become very ill (sometimes fatally) at elevations above 9,000 ft. To give you an idea of how high in the Andes this city is, consider that 'mountain climbing' here is the US is typically considered to be very technical above 12,000 ft in elevation, and not for amateurs. At La Rinconada, people may spend their entire lives above 16,000 ft in elevation. The physiological challenges of life at this altitude are many and severe. The low oxygen levels stimulate extremely high levels of RBCs and hemoglobin, as much as 3x those considered to be normal. This, in turn, causes blood viscosity to rise dramatically, which causes abnormally high blood pressures. These elevated blood pressures place extra strain on the heart, causing it to enlarge, often dramatically. Despite these adjustments, many suffer from chronic hypoxia, termed 'chronic mountain sickness', or CMS. Blue-ish skin, fatigue, and low endurance all are common symptoms of CMS, and all stem from low levels of blood oxygen. Curiously, populations long adapted to life at high altitudes (including some populations in these South American Andes mountains, and others in the Himalayas of Southern Asia) seem to have evolved at least some protections against chronic hypoxia and the challenges it poses. This suggests that there may be genetic tools that can be put to use in helping others who suffer from hypoxia not because of altitude, but because of diseases related to cardiac or respiratory function. This article describes one team of physiologists and their efforts to assess human physiology and health at this altitude. Their initial focus was on CMS and body responses to it, but they quickly became caught-up in the socio-economic plight of the people there - life is brutal for the residents of this city, and the researchers felt, in many ways, helpless to help them. They certainly could not improve the economic status of the town's residents, nor could they offer a cure for CMS. There, as in many parts of the world (including our own country), the working class are too easily exploited, too easily marginalized. Lack of access to basic health care is often one of the first signs of a population that is short of options and resources. When that combines with dangerous forms of employment for the un- or under-educated, health issues rise and life expectancy falls. https://vis.sciencemag.org/hypoxia-city/ There is a companion podcast for this article as well: http://traffic.libsyn.com/sciencemag/SciencePodcast_190913.mp3 As you review these materials, I'd like you to think about the basic physiological mechanisms at play: how low blood oxygen levels can stimulate RBC responses, and, in turn, how these can contribute to blood pressure, which itself can trigger responses (remember ANF, when blood pressure rises?). Keeping ourselves in homeostatic conditions is complex even under typical environmental conditions; life under extreme conditions only amplifies the challenge. I hope that you enjoy this article, and I hope that you enjoy the Homecoming weekend. Please be safe, and I will see you on Monday. Sincerely, Dr. Nealen |
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