from the world's big
Hypoxia researchers win 2019 Nobel Prize in Medicine
Three scientist friends, working separately, share the prestigious prize.
- Nobel recognizes breakthrough insights into cell's perception and response to changes in oxygen levels.
- Too title oxygen is a problem. Also too much.
- Their research unveiled a genuine "textbook discovery."
The 2019 Nobel Prize in Medicine has just been awarded to three scientists from the U.S. and U.K. working independently on the same problem: How cells sense and adapt to oxygen availability. They've unveiled the series of molecular events that allow cells to assess and respond to changing levels of available oxygen, with implications in the treatment of cancer, heart attacks, strokes, anemia, and other diseases.
According to the Nobel Assembly, these seminal discoveries "revealed one of life's most essential adaptive processes." The Assembly's Randall Johnson says, "Scientists often toss around this phrase 'textbook discovery.' But I'd say this is really essentially a textbook discovery." He envisions the discovery as "something basic biology students will be learning about when they study — at aged 12 or 13 or younger — biology, and learn the fundamental ways cells work."
Three scientists with three questions
Image source: Paramonov Alexander/Shutterstock
The three scientists who received the 5 a.m. call from Stockholm are Gregg Semenza (Johns Hopkins University), Sir Peter Ratcliffe (Oxford University), and William Kaelin, Jr. (Dana-Farber Cancer Institute/Harvard University). The three shared their work informally over the years in an ongoing conversation that moved the whole field of study forward. Each had his own reason for pursuing his research area, and their interests reflect the far-ranging impact of their findings.
Semenza wondered exactly what it was that cancer cells were seeking when they spread to new areas in the body. He suspected it was oxygen.
As a kidney specialist, Ratcliffe was intrigued by the manner in which the kidney regulated the production of a particular hormone, erythropoietin (EPO), which affects the production of red, oxygen-carrying blood cells in response to changes in levels of available oxygen. Others considered this to be a not-very-interesting question, but Ratcliffe was intrigued.
For Kaelin, it was a pursuit of answers behind a rare genetic form of cancer, Von Hippel-Lindau syndrome (VHL disease), known to involve exaggerated production levels of EPO, and an excess of blood vessels. He had a hunch it was something in cells' then-mysterious oxygen-sensing mechanism malfunctioning.
Why this is important
Image source: Daniel Prudek /Shutterstock
Cells need oxygen to live, and Earth's air-breathing organisms have developed ways to ensure their cells get the amount of oxygen they need. At high altitudes, for example, we produce more red blood cells to accommodate the relative scarcity of air and combat the onset of hypoxia. While a lack of oxygen can be deadly, so too can too much — it may be that an excess of oxygen can be exploited by some cancers, among other issues.
Human bodies have developed a couple of ways to monitor and respond to changes in oxygen levels. The carotid body associated with the large vessels on both sides of the neck have unique cells that sense oxygen levels, and, as noted above, the body produces more oxygen-carrying cells to maximize delivery of what O2 there is when there's not enough. Production of these oxygen-carrying cells is triggered by the production of erythropoietin (EPO) — it's this system that the Nobel winners explored.
A technical glimpse into a three-part puzzle
Image source: DragonTiger8/Shutterstock
The research that led to the Nobel-awarded discovery began back in the 1990s when, Semenza started studying the EPO gene to learn how its production was being controlled. He identified a DNA segment near the EPO gene that appeared to be regulating its production in response to hypoxia. Most interestingly, this DNA, also spotted around the same time by Ratcliffe, wasn't only in kidney cells known to produce EPO, but in all cells.
Eventually Semenza discovered a protein complex that binds to the DNA depending on the amount of oxygen available, and named it hypoxia-inducible factor, or HIF. HIF turned out to be a pair of different DNA-binding proteins, HIF-1α and ARNT.
The amount of HIF-1α increases when oxygen levels are low, apparently due to an oxygen-related reduction in the effect of ubiquitin, a peptide that normally would bind with and quickly decay HIF-1α.
As a result of his immersion in Von Hippel-Lindau research, Ratcliffe discovered why a lack of oxygen could dampen ubiquitin's bite: HIF-1α is tagged for destruction by ubiquitin via the VHL gene. (An absence of the VHL gene causes the disease by allowing the presence of too much HIF-1α.)
This implied an unknown interaction between the VHL gene and HIF-1α and Kaelin and Ratcliffe worked it out. They realized that at normal oxygen levels, two hydroxyl groups were added to two locations in HIF-1α. Aided by oxygen-sensitive enzymes, VHL thus binds to HIF-1α and moderates the production of EPO and the number red blood cells. With either too little or too much oxygen, this balance is upset.
In all, this daisy-chained sets of research has given us a new insight about our bodies — specifically, of the series of molecular events that constantly help our cells assess and respond to changing levels of oxygen. "Textbook discovery," indeed.
Educators and administrators must build new supports for faculty and student success in a world where the classroom might become virtual in the blink of an eye.
- If you or someone you know is attending school remotely, you are more than likely learning through emergency remote instruction, which is not the same as online learning, write Rich DeMillo and Steve Harmon.
- Education institutions must properly define and understand the difference between a course that is designed from inception to be taught in an online format and a course that has been rapidly converted to be offered to remote students.
- In a future involving more online instruction than any of us ever imagined, it will be crucial to meticulously design factors like learner navigation, interactive recordings, feedback loops, exams and office hours in order to maximize learning potential within the virtual environment.
A leading British space scientist thinks there is life under the ice sheets of Europa.
- A British scientist named Professor Monica Grady recently came out in support of extraterrestrial life on Europa.
- Europa, the sixth largest moon in the solar system, may have favorable conditions for life under its miles of ice.
- The moon is one of Jupiter's 79.
Neil deGrasse Tyson wants to go ice fishing on Europa<div class="rm-shortcode" data-media_id="GLGsRX7e" data-player_id="FvQKszTI" data-rm-shortcode-id="f4790eb8f0515e036b24c4195299df28"> <div id="botr_GLGsRX7e_FvQKszTI_div" class="jwplayer-media" data-jwplayer-video-src="https://content.jwplatform.com/players/GLGsRX7e-FvQKszTI.js"> <img src="https://cdn.jwplayer.com/thumbs/GLGsRX7e-1920.jpg" class="jwplayer-media-preview" /> </div> <script src="https://content.jwplatform.com/players/GLGsRX7e-FvQKszTI.js"></script> </div>
Water Vapor Above Europa’s Surface Deteced for First Time<span style="display:block;position:relative;padding-top:56.25%;" class="rm-shortcode" data-rm-shortcode-id="9c4abc8473e1b89170cc8941beeb1f2d"><iframe type="lazy-iframe" data-runner-src="https://www.youtube.com/embed/WQ-E1lnSOzc?rel=0" width="100%" height="auto" frameborder="0" scrolling="no" style="position:absolute;top:0;left:0;width:100%;height:100%;"></iframe></span>
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Can thinking about the past really help us create a better present and future?
- There are two types of counterfactual thinking: upward and downward.
- Both upward and downward counterfactual thinking can be positive impacts on your current outlook - however, upward counterfactual thinking has been linked with depression.
- While counterfactual thinking is a very normal and natural process, experts suggest the best course is to focus on the present and future and allow counterfactual thinking to act as a motivator when possible.
“Upward” versus “downward” counterfactual thinking<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMzQ1NDYxOS9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTY0NDM2MDY2OX0.njWs1qrV1vDBxU1V75tUduUW4TjJvEHglDWsK8ZF2l4/img.jpg?width=1245&coordinates=0%2C556%2C0%2C209&height=700" id="a15fa" class="rm-shortcode" data-rm-shortcode-id="98314d4d2b256ed08f42d369fe4ae080" data-rm-shortcode-name="rebelmouse-image" alt="concept of man thinking about the past one line drawing counterfactual thinking" />
What are upward and downward counterfactual thinking?
Image by one line man on Shutterstock<p><strong>What is upward counterfactual thinking?</strong></p><p>Upward counterfactual thinking happens when we look at a scenario and ask ourselves "what if" in terms of how our life could have turned out better. </p><p>Examples of upward counterfactual thinking are: </p><ul><li><em>"I wish I had taken that other job instead of this one 10 years ago - my life would be so much better if I had." </em></li><li><em>"I wish I would have gotten the part in that high school play, maybe I could have gotten into a theatre school and became an actor…"</em> </li></ul><p>Both of these examples have the ideology that if you had made different choices, your life right now would be improved. </p><p><strong>What is downward counterfactual thinking?</strong></p><p>Downward counterfactual thinking is, naturally, the opposite of upward counterfactual thinking in that we think about how things could have been worse if other decisions had been made. </p><p>Examples of downward counterfactual thinking are: </p><ul><li><em>"I'm so thankful I studied secondary education in university instead of psychology like I had originally planned - I love teaching high school kids and I never would have gotten to do that…" </em></li><li><em>"I'm so happy I left David when I got the chance, I can't imagine still being in an unhappy marriage with someone who doesn't support me…"</em> </li></ul><p>In these examples, we see the idea that if you had made different choices your life would not be as good as it is right now. </p>
How counterfactual thinking can impact your life<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMzQ1NDYxNy9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYyNjI2MDQxOX0.DIVQ-Yk0d6yE3tc743MH1Fz2pOg1TGHLmhp8dPp9UdY/img.jpg?width=1245&coordinates=0%2C0%2C0%2C0&height=700" id="522d7" class="rm-shortcode" data-rm-shortcode-id="da7df6ad916b043e3610223900d0f8df" data-rm-shortcode-name="rebelmouse-image" alt="man thinking what if written on chalkboard" />
How do upward and downward counterfactual thinking impact your life?
Photo by Brasil Creativo on Shutterstock<p>While many people don't see the point in "what if" scenarios, various studies have found that downward counterfactual thinking can be more associated with psychological health compared with upward counterfactual thinking. Not only that, but research has also shown upward counterfactual thinking can be linked with current and future depression.</p> <p><strong>Downward counterfactual thinking tends to be more associated with psychological health </strong></p><p>According to a <a href="http://journal.sjdm.org/jdm06136.pdf" target="_blank">2000 study</a>, downward counterfactual thinking can be linked with better psychological health compared to upward counterfactual thinking. More importantly, in cases where downward counterfactual thinking did lead to negative feelings, those feelings acted as something of a motivator for people to take productive actions to better their current situation. </p> <p><strong>Upward counterfactual thinking tends to be more associated with depression </strong></p><p><a href="https://www.sciencedirect.com/science/article/abs/pii/S0272735816301714#:~:text=An%20upward%20counterfactual%20(as%20opposed,Markman%20and%20McMullen%2C%202003)." target="_blank">According to a 2017 study</a> that pooled a sample of over 13,000 respondents, thoughts about "better outcomes" and regret (upward counterfactual thinking) were associated with current and future depression. </p> <p><strong>Downward counterfactual thinking can actually improve your relationships and is more often engaged in by women than men.</strong></p><p>In a <a href="https://dspace.sunyconnect.suny.edu/bitstream/handle/1951/67589/Studer_Thesis.pdf?sequence=1&isAllowed=y" target="_blank">2016 research paper submitted</a> to the Department of Psychology at the State University of New York at New Paltz, downward counterfactual thinking in regards to romantic relationships was associated with relatively positive relationship outcomes. Interestingly, women were more likely than men to engage in downward counterfactual thinking about their romantic life. </p> <p><strong>Upward counterfactual thinking can have some benefits in certain scenarios. </strong></p><p>When we look back after a failed test and think "I wish I would have studied more" - this motivates us to study harder the next time a test comes up. In this way, upward counterfactual thinking (or the negative version of "what if") can actually benefit us. </p> <p><strong>This can be difficult, though, because much of the time upward counterfactual thinking is more associated with a pessimistic outlook that can be unmotivating. </strong></p> <p>Thinking in the past tense can be motivational (and even healthy) at times, but the best thing to do is look forward. </p><p>While counterfactual thinking as a whole can be used to motivate us to make better choices or appreciate where we are in life, <a href="https://www.psychologytoday.com/us/blog/darwins-subterranean-world/201809/the-psychology-what-if" target="_blank">this Psychology Today</a> article suggests that we should come up with ways to move on and focus on the present and the future instead of the past. Using counterfactual thinking as a motivational tool can be very helpful if we don't get stuck in the "what if" mindset that tends to pull us out of the present and back into the past, where things will always remain the same. </p>
Despite fact check campaigns, anti-vaccination influence is growing.
- Despite announcing plans to combat disinformation, anti-vax groups continue to gain influence on Facebook.
- An analysis of over 1,300 Facebook pages with 100 million followers shows that anti-vaccination agendas are having a profound impact.
- Only 50 percent of Americans are certain they'll receive an approved COVID-19 vaccine.
Facebook announces plan to 'tackle vaccine misinformation'<span style="display:block;position:relative;padding-top:56.25%;" class="rm-shortcode" data-rm-shortcode-id="997c512b8b8afcd4db98fdb7ece75680"><iframe type="lazy-iframe" data-runner-src="https://www.youtube.com/embed/ZTZ3Lq67yiY?rel=0" width="100%" height="auto" frameborder="0" scrolling="no" style="position:absolute;top:0;left:0;width:100%;height:100%;"></iframe></span><p>This trend is having real-world consequences. Only <a href="https://www.sciencemag.org/news/2020/06/just-50-americans-plan-get-covid-19-vaccine-here-s-how-win-over-rest" target="_blank">half of Americans</a> are willing to get a coronavirus vaccine, with a quarter wavering and a quarter against. While we should be confident of efficacy—gossip about a <a href="https://www.webmd.com/lung/news/20200511/covid-19_vaccine_by_fall_possible_but_at_what_cost" target="_blank">vaccine arriving in the Fall</a> is ambitious and potentially unsafe—the idea that a quarter of the country will refuse any vaccine is a potential public health disaster (as if we're not experiencing one now).</p><p>Making matters worse, we can't fight disinformation with data. No matter how many articles <a href="https://bigthink.com/coronavirus/the-plandemic" target="_self">debunk Plandemic</a>, Mikki Willis gains momentum. Do <a href="https://www.facebook.com/mikki.willis/posts/2875973472513592" target="_blank">27,000 doctors</a> really support his efforts to "reform our corrupt global healthcare systems?" There's no way to tell, but that's the thing about Facebook: it doesn't have to be true. Willis's claim, which he made in conjunction with a fundraising effort for the film, has been shared 4.4k times. Convincing his fanbase that perhaps tens of thousands of doctors aren't on board will be a Herculean task. </p><p>Media Matters notes the official-sounding National Vaccine Information Center (NVIC), which, though sounding governmental, opposes every effort to vaccinate children. Beginning in February, the organization's website started publishing a "<a href="https://www.nvic.org/vaccines-and-diseases/Reports/covid-19.aspx" target="_blank">special report</a>" on COVID-19, laying the groundwork for vaccination disinformation. </p><p style="margin-left: 20px;">"The first three installments of the 'special report' adopt right-wing themes unrelated to vaccines, such as the claim that public health orders that promote social distancing result in a 'loss of civil liberties' and subject Americans to 'quarantine shaming.' The fourth installment, published on March 29, includes the first attacks on vaccine development in the series … The fifth installment of the 'special report,' published on April 1, frames the vaccine development efforts of pharmaceutical companies and other entities as a cash grab."</p>
A truck with writing "JESUS IS MY VACCINE" drives by demonstrators rallying outside the Pennsylvania Capitol Building to protest the continued closure of businesses due to the coronavirus pandemic on May 15, 2020 in Harrisburg, Pennsylvania.
Photo by Mark Makela/Getty Images<p>The irony is that NVIC's Facebook page is listed as an "Educational Research Center." Just today the organization posted about the <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2831678/" target="_blank">long-disproven link between the measles vaccine and autism</a> (via Robert F. Kennedy's anti-vax organization, Children's Health Defense), <a href="https://www.vice.com/en_ca/article/wxevj5/the-coronavirus-truthers-dont-believe-in-public-health" target="_blank">opportunist Joseph Mercola</a>'s questioning whether the COVID-19 surge in Texas has anything to do with the novel coronavirus, and conspiracy theory-rich GreenMedInfo, whose founder traffics in ridiculous ideas, such as <a href="https://www.facebook.com/watch/?v=1720256541450732" target="_blank">germ theory being false</a>. </p><p>And so here we are: instead of reporting on pressing global issues, Reuters has to <a href="https://www.reuters.com/article/uk-factcheck-metal-strip-medical-masks-5/fact-check-metal-strip-in-medical-masks-is-not-a-5g-antenna-idUSKBN24A2O1?fbclid=IwAR2nqo5OaXP3unV7v3jOhtdGY5JjivJgyBSqrKcW0pcEJfhdGWieDb1K5C8" target="_blank">fact check</a> whether the metal strip in face masks is really a 5G antenna or if Wayfair is <a href="https://www.reuters.com/article/uk-factcheck-wayfair-human-trafficking/fact-check-no-evidence-linking-wayfair-to-human-trafficking-operation-idUSKCN24E2M2" target="_blank">involved in human trafficking</a>. (The woman that posted the "medical doctor" video above is convinced Amazon is involved as well.) No matter how ridiculous these sound—and they should, to any functioning adult—common sense is losing ground: an <a href="https://www.sciencemag.org/news/2020/05/vaccine-opponents-are-gaining-facebook-battle-hearts-and-minds-new-map-shows" target="_blank">analysis</a> of over 1,300 Facebook pages with 100 million followers shows that anti-vax agendas are becoming more influential.</p><p>When the printing press was first invented, <a href="https://apple.news/Agz3WmeyWTEKLg-9yHo2BMA" target="_blank">anyone could hire a printer</a>. The idea of objective news took some time to work out, and it is questionable that it ever did get worked out. But we're in a truly disturbing place when one of the most effective therapeutics ever discovered—the <a href="https://www.tmrjournals.com/tmr/EN/abstract/abstract321.shtml" target="_blank">millennia-old idea</a> of allowing the body to build up immunity by introducing a small dose of an offending agent—is being used as, what? A political tool? An ideological battering ram? An apocalyptic battle song sung by the woke as they laugh at all the silly sheeple? </p><p>It's impossible to tell what the end game is. Being contrarian is now its own currency. Whether or not your agenda accomplishes anything is secondary to just being on the team—a participation trophy for simply showing up. Putting in the intellectual and emotional effort demanded by the complex and nuanced realm of science is proving too much for America to tolerate. When a nation descends into such intolerance, anything becomes possible. </p><p>--</p><p><em>Stay in touch with Derek on <a href="http://www.twitter.com/derekberes" target="_blank">Twitter</a>, <a href="https://www.facebook.com/DerekBeresdotcom" target="_blank">Facebook</a> and <a href="https://derekberes.substack.com/" target="_blank">Substack</a>. His next book is</em> "<em>Hero's Dose: The Case For Psychedelics in Ritual and Therapy."</em></p>
Gender and sexual minority populations are experiencing rising anxiety and depression rates during the pandemic.