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
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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 Good morning all, The results of our vaping survey are in! We had 93 responses in total. Almost exactly 2/3 (61/93) respondents said that they do not vape. Almost exactly 1/3 (32/93) respondents reported that they did vape at least one per week. Those respondents who did not vape rated its danger as 8.1 out of 10. Those who do vape rated its pleasurability as 6/10, and its danger as 7.3/10. (interesting that users ranked the pleasurability lower than the danger, isn't it?) Those who vape do so an average of 12x per week (range:1-100 times per week). 17/31 (42%) of those who vape do check the source/ingredients, while the majority (17/31, 55%) do not. The vaping materials used (and the number of people who reported using them) are don't know 1 Juul 2 mint 3 nicotine 3 blueberry 1 tobacco 12 other 12 These findings reflect much of what is reported in the recent news: - vaping is very popular among college-age students - additives or alternatives to tobacco are prominently used - users pay relatively little attention to the ingredients or sourcing of vaping products. These are dangerous trends! That one can directly and intentionally infuse nicotine is especially worrisome, as is the fact that users do not know with great confidence the source or identify of the other compounds that are inhaling. Our lungs are designed for exposure to atmospheric gases only - introducing any other compounds is potentially quite risky. We will continue to discuss this topic, and I will continue to pass along more information. Education and effort are the keys to behavioral change - with any luck, we can increase awareness of the dangers of vaping and reduce its prevalence. The numbers of vaping-associated cases of severe respiratory distress and mortality continue to climb - please be aware of the dangers, and use that knowledge to make good choices about your health. https://www.cdc.gov/tobacco/basic_information/e-cigarettes/severe-lung-disease.html Sincerely, Dr. Nealen Hi folks, Our next chapter (for Thursday) covers learning and cognition in animals, and I wanted to offer a couple of supplemental readings to accompany the material in our text. Our textbook describes a bit about the extent to which our closest relatives (the other members of the "great ape" lineage) may possess mental faculties approaching our own, and these two readings expand upon that idea, with the caveat that we may not also know how to best test, or interpret, animal behaviors. The first reading describes some of the work done by researchers at Kyoto University, which houses a rich group of researchers in primate cognition. This report describes an attempt to interpret the mental states of chimpanzees, based upon their reaction to stimuli. If animals possess the capacity for thoughts and behaviors related to traits like empathy, jealousy, or disbelief, we can predict that they may respond in specific ways to certain kinds of stimuli. It's a challenging argument, to be sure, but many in the primate community believe that our closest primate relatives share more of our "higher" cognitive abilities than many would care to admit. https://www.scientificamerican.com/article/chimps-may-be-capable-of-comprehending-the-minds-of-others/ The second reading is from a prominent primate behaviorist (Frans de Waal), who has long argued that we approach animal behavior too simplistically, and often erroneously. Taken to an extreme, he suggests that, at least at times, we are testing the wrong things and making interpretations that are illogical. I do not believe that his interpretations are widely held by members of the behavioral community, but they do serve as a useful reminder that we often make too many assumptions in our design and interpretation of behavioral experiments. https://www.wsj.com/articles/SB10001424127887323869604578370574285382756 When we delve into Chapter 07 on Thursday, it will be useful to keep these viewpoints in mind. See you this afternoon for collection of exam corrections. We'll have time to review and discuss any material we wish to cover today. Sincerely, Dr. Nealen Good morning all, We recently described human blood in lecture, noting that it is red in color (of course!), and that its color comes from the hemoglobin pigment inside of our red blood cells. How about a person whose whole blood is blue? In the news this week is a report about a woman who used excessive amounts of a common over-the-counter analgesic (benzocaine) which rendered her hemoglobin blue in color: https://www.cnn.com/2019/09/19/health/blue-blood-trnd/index.html Persons of low blood oxygen levels are considered to be 'cyanotic', and often have a pale or bluish cast to their skin. If their hemoglobin has been poisoned, it can impair oxygen transport/delivery, at worst, to a fatal degree. In this case, the blue color was not physiologically problematic. This woman's blood was still relatively high in oxygen content, but contained more cyanomethemoglobin (which causes the blue color) than is normal (few percent). Luckily for this woman, her problem was cosmetic only, and the antidote (ironically, doses of methylene blue) was both simple and effective. Interestingly, blue blood is perfectly normal in crustaceans (such as crabs and lobsters), because they employ hemocyanin (rather than hemoglobin) for oxygen transport. Their blood is of such great medical utility for testing of toxins and contamination that a large (and controversial) industry is devoted to its collection: https://www.theatlantic.com/science/archive/2018/05/blood-in-the-water/559229/ And, there is a known genetic disorder than causes cyanosis to run in (a small number of) families, including the famous 'blue Fugates of Kentucky': https://www.iflscience.com/health-and-medicine/the-science-behind-the-mysterious-blue-people-of-kentucky/all/ So, the next time you hear the term "blue bloods", you might wonder if it is genetic, pharmaceutical, or crustacean in its basis... Have a great weekend - Dr. Nealen Good morning all, We recently considered bat echolocation as a model for sensory coevolution. During our discussions, we noted that many animals have sensory capabilities outside of the range of humans. How about humans who can perform echolocation? https://phys.org/news/2018-04-humans-echolocation.html There are a small number (few dozen) people in the world who have developed some level of proficiency at echolocation for navigation. Daniel Kish is the most famous person with these abilities (but there are others): https://www.youtube.com/watch?v=A8lztr1tu4o In all of these cases, the ability came about after a loss of vision. Our human visual cortices make up a huge part of our brains, and once they are freed from visual responsibilities, it seems that they can be co-opted (at least in part) for other uses. This neural flexibility is well-known, as it is the basis for the recovery that is possible from brain trauma, including stroke. Blind persons who read Braille are known to have some expanded touch sensitivity in visual areas of the brain, and sensory re-mapping is known to occur in persons with high-levels of musical training, or in new mothers nursing infants. Still, the development of echolocation as a sensory capability is quite different, in that it adds to the human sensory repertoire, not simply expands upon an existing sense. There are lots of interesting articles about human echolocation, including: https://www.sciencealert.com/humans-can-echolocate-like-bats-and-whales-and-we-ve-finally-figured-out-how-it-works https://www.livescience.com/39231-humans-can-learn-to-echolocate.html https://www.newscientist.com/article/2145962-this-is-how-some-blind-people-are-able-to-echolocate-like-bats/ Next time you find yourself in a dark room, you might be tempted to give it a try! I think that I will stay close to the light switch... Have a great weekend - Dr. Nealen |
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