Information

Is there a reason for the lack of full RTK structures?


Bocharov et al. (2013) write that

As there are no structures of full-length RTKs [receptor tyrosine kinases], we do not fully understand how different domains function together to mediate signal transduction inside the cell.

True to the above quote, I've so far only found isolated domains of some RTKs in the PDB, but no complete structures (neither X-ray nor NMR). I am a chemist by training, so am hardly an expert in this area, but it does seem counterintuitive given the general importance of RTKs in cell signalling. Is there a fundamental reason for the lack of RTK structures?

In contrast, there are examples of full-length GPCRs, e.g. rhodopsin (Palczewski et al. 2000). As tsttst brought up in the comments, this seems to be an issue with RTKs being single-pass membrane proteins, whereas GPCRs are multi-pass. How does this affect the ability to obtain a structure?


Bocharov EV, Lesovoy DM, Goncharuk SA, Goncharuk MV, Hristova K, Arseniev AS. 2013. Structure of FGFR3 transmembrane domain dimer: implications for signaling and human pathologies. Structure 21(11):2087-2093. doi: 10.1016/j.str.2013.08.026.

Palczewski K, Kumasaka T, Hori T, Behnke CA, Motoshima H, Fox BA, Le Trong I, Teller DC, Okada T, Stenkamp RE, et al. 2000. Crystal structure of rhodopsin: a G protein-coupled receptor. Science 289(5480):739-745. doi: 10.1126/science.289.5480.739.


Large proteins are challenging for NMR: the more amino acids, the more peaks one has to assign. Peak overlap is also more likely the more amino acids you have, making assignment difficult. Some NMR strategies work well for studying dynamics of large proteins, but as far as structure determination is concerned, there definitely is a critical size past which NMR is simply not the tool for the job.

Flexible proteins are challenging for crystallography: too much flexibility can simply prevent crystallization, you can spend years only trying to get crystals, and once you do manage to grow crystals they might diffract poorly or not at all. But crystallography is often very useful to solve high-resolution structures of individual, isolated domains; this is of great help down the road to interpret a lower-resolution cryoEM map of the full-length protein.

Membrane proteins are challenging for biochemistry: purifying them and getting them to remain stable in solution is difficult.

Receptor Tyrosine Kinases (RTKs) are all of that at the same time! Large, flexible membrane proteins.

Now, with tremendous technological progress of cryo-electron microscopy (cryoEM) recently, such challenging structures become more tractable. Conformational flexibility is still an issue, but unlike with crystallography it can be dealt with to some extent (i.e. it won't prevent you from collecting initial data and getting preliminary results that can guide your next attempt).


Why the shortage of women in physics? They are hindered not by lack of talent, but biases and outmoded structures, says Chicago astrophysicist

"Gender bias in science is not a women's issue -- it's a science issue," said University of Chicago astrophysicist Evalyn Gates, speaking in Kaufmann Auditorium April 23. "This is a problem that affects all of us, and it's not going to fix itself."

The academic community has long realized that there are too few women in science, Gates said in her talk, sponsored by Cornell's Graduate Women in Physics and the Cornell Women's Resource Center.

The low numbers of women in physics, she said, are especially shocking: Women in the United States hold less than 5 percent of full professor positions and make up only 22 percent of the undergraduate majors and 16 percent of the doctoral candidates. At Cornell, women comprise 17 percent of physics graduate students.

Gates urged scientists to think of the problem as a physics experiment, in which humans are the detectors, albeit biased detectors. As such, scientists must acknowledge that "men and women respond to and evaluate male and female students/candidates differently."

She said that the scientific community also needs to approach this problem like any other: "First identify the problem, review what's already known, analyze the data, account for biases and backgrounds and then experiment to improve the next generation."

That's a revolutionary approach, considering that many physicists think the discrepancy is simply generational, and that time itself will even out the gender imbalance, she said.

"They're in denial. Meritocracy is a deeply cherished belief -- it's in everyone's best interest to believe that the brightest and most motivated students will succeed," said Gates. The data show, however, that merit is not what is keeping women out of physics.

According to a 2006 National Academy of Sciences report, "it is not lack of talent, but unintentional biases and outmoded institutional structures that are hindering the access and advancement of women."

Gates showed that the percentage of women in physics plummets most dramatically during college for unknown reasons, yet nearly 50 percent of undergraduate math and chemistry majors today are women. There's something different about the field of physics, she said.

"Physics has a unique history in academia," Gates pointed out in an interview after her talk. The largest numbers of physics faculty hires, exclusively men, were made in the 1960s after Sputnik. When this generation began to retire in the 1990s, the percentages of female faculty members went up by only 4 percent. "I'd been hearing since the 1970s that there'd be these mass retirements and then things would change, but they haven't," Gates said.

The slides used in her talk will be posted online at http://pages.physics.cornell.edu/gwp/.

Graduate student Melissa Rice is a writer intern at the Cornell Chronicle.


Was There a Wuhan Lab Leak?

President Joe Biden tours the Viral Pathogenesis Laboratory at the National Institutes of Health Laboratory in Bethesda, Maryland, on Feb. 11. D r. Anthony Faucci, chief medical adviser to the president, on his left. (White House, Adam Schultz)

/>A year ago, the idea that Covid-19 leaked from a lab in Wuhan – a short distance from the wet market that is usually claimed to be the source of the virus – was dismissed as a crackpot theory, supported only by then President Donald Trump, QAnon and hawks on the right looking to escalate tensions dangerously with China.

Now, after what has been effectively a year-long blackout of the lab-leak theory by the corporate media and the scientific establishment, President Joe Biden has announced an investigation to assess its credibility. And as a consequence, what was treated until a few weeks ago as an unhinged, rightwing conspiracy is suddenly being widely aired and seriously considered by liberals.

Every media outlet is running prominent stories wondering whether a pandemic that has killed so many people and destroyed the lives of so many more can be blamed on human hubris and meddling rather than on a natural cause.

For many years, scientists at labs like Wuhan’s have conducted Frankenstein-type experiments on viruses. They have modified naturally occurring infective agents — often found in animals such as bats — to try to predict the worst-case scenarios for how viruses, especially coronaviruses, might evolve. The claimed purpose has been to ensure humankind gets a head start on any new pandemic, preparing strategies and vaccines in advance to cope.

Viruses are known to have escaped from labs like Wuhan’s many times before. And there are now reports, rejected by China, that several staff at Wuhan got sick in late 2019, shortly before Covid-19 exploded on to the world stage. Did a human-manipulated novel coronavirus escape from the lab and spread around the world?

No Interest in Truth

Here we get to the tricky bit. Because nobody in a position to answer that question appears to have any interest in finding out the truth — or at least, they have no interest in the rest of us learning the truth. Not China. Not U.S. policy-makers. Not the World Health Organization. And not the corporate media.

The only thing we can state with certainty is this: our understanding of the origins of Covid has been narratively managed over the past 15 months and is still being narratively managed. We are being told only what suits powerful political, scientific and commercial interests.

We now know that we were misdirected a year ago into believing that a lab leak was either fanciful nonsense or evidence of Sinophobia — when it was very obviously neither. And we should understand now, even though the story has switched 180 degrees, that we are still being misdirected. Nothing that the U.S. administration or the corporate media have told us, or are now telling us, about the origins of the virus can be trusted.

No one in power truly wants to get to the bottom of this story. In fact, quite the reverse. Were we to truly understand its implications, this story might have the potential not only to hugely discredit Western political, media and scientific elites but even to challenge the whole ideological basis on which their power rests.

Which is why what we are seeing is not an effort to grapple with the truth of the past year, but a desperate bid by those same elites to continue controlling our understanding of it. Western publics are being subjected to a continuous psy-op by their own officials.

Virus Experiments

Last year, the safest story for the Western political and scientific establishments to promote was the idea that a wild animal like a bat introduced Covid-19 to the human population. In other words, no one was to blame. The alternative was to hold China responsible for a lab leak, as Trump tried to do.

But there was a very good reason why most U.S. policy-makers did not want to go down that latter path. And it had little to do with a concern either to refrain from conspiracy theories or to avoid provoking unnecessary tension with a nuclear-armed China.

Nicholas Wade in 2005. (Jane Gitschier, CC BY 2.5, Wikimedia Commons)

Nicholas Wade, a former New York Times science writer, set out in May, in an in-depth investigation, why the case for a lab leak was scientifically strong, citing some of the world’s leading virologists.

But Wade also highlighted a much deeper problem for U.S. elites: just before the first outbreak of Covid, the Wuhan lab was, it seems, cooperating with the U.S. scientific establishment and WHO officials on its virus experiments — what is known, in scientific parlance, as “gain-of-function” research.

Gain-of-function experiments had been paused during the second Obama administration, precisely because of concerns about the danger of a human-engineered virus mutation escaping and creating a pandemic. But under Trump, U.S. officials restarted the program and were reportedly funding work at the Wuhan lab through a U.S.-based medical organization called the EcoHealth Alliance.

The U.S. official who pushed this agenda hardest is reported to have been Dr. Anthony Fauci – yes, the U.S. president’s chief medical adviser and the official widely credited with curbing Trump’s reckless approach to the pandemic. If the lab leak theory is right, the pandemic’s savior in the U.S. might actually have been one of its chief instigators.

And to top it off, senior officials at the WHO have been implicated too, for being closely involved with gain-of-function research through groups like EcoHealth.

Colluding in Deceit

This seems to be the real reason why the lab-leak theory was quashed so aggressively last year by Western political, medical and media establishments without any effort to seriously assess the claims or investigate them. Not out of any sense of obligation towards the truth or concern about racist incitement against the Chinese. It was done out of naked self-interest.

If anyone doubts that, consider this: the WHO appointed Peter Daszak, the president of the EcoHealth Alliance, the very group that reportedly funded gain-of-function research at Wuhan on behalf of the U.S., to investigate the lab-leak theory and effectively become the WHO’s spokesman on the matter. To say that Daszak had a conflict of interest is to massively understate the problem.

He, of course, has loudly discounted any possibility of a leak and, perhaps not surprisingly, continues to direct the media’s attention to Wuhan’s wet market.

The extent to which major media are not only negligently failing to cover the story with any seriousness but are also actively continuing to collude in deceiving their audiences — and sweeping these egregious conflicts of interest under the carpet — is illustrated by this article published by the BBC at the weekend.

“In visiting the market, it was clear this is a place where all forms of life collide. We learned that before the pandemic, 10,000 people a day would visit the 700 stalls of the crowded marketplace.” https://t.co/HQaKqXBcX0

&mdash Peter Daszak (@PeterDaszak) June 3, 2021

The BBC ostensibly weighs the two possible narratives about Covid’s origins. But it mentions none of Wade’s explosive findings, including the potential U.S. role in funding gain-of-function research at Wuhan. Both Fauci and Daszak are cited as trusted and dispassionate commentators rather than as figures who have the most to lose from a serious investigation into what happened at the Wuhan lab.

Given this context, the events of the past 15 months look much more like a pre-emptive cover-up: a desire to stop the truth from ever emerging because, if a lab leak did occur, it would threaten the credibility of the very structures of authority on which the power of western elites rests.

Media Blackout

So why, after the strenuously enforced blackout of the past year, are Biden, the corporate media and the scientific establishment suddenly going public with the possibility of a China lab leak?

The answer to that seems clear: because Nicholas Wade’s article, in particular, blew open the doors that had been kept tightly shut on the lab-leak hypothesis. Scientists who had formerly feared being associated with Trump or a “conspiracy theory” have belatedly spoken up. The cat is out of the bag.

Or as The Financial Times reported of the new official narrative, “the driving factor was a shift among scientists who had been wary of helping Trump before the election or angering influential scientists who had dismissed the theory.”

The journal Science recently upped the stakes by publishing a letter from 18 prominent scientists stating that the lab-leak and animal-origin theories were equally “viable” and that the WHO’s earlier investigation had not given “balanced consideration” to both — a polite way of suggesting that the WHO investigation was a fix.

WHO headquarters in Geneva. (I, Yann, CC BY-SA 3.0, Wikimedia Commons)

And so we are now being subjected by the Biden administration to Plan B: damage limitation. The U.S. president, the medical establishment and the corporate media are raising the possibility of a Wuhan lab leak, but are excluding all the evidence unearthed by Wade and others that would implicate Fauci and the U.S. policy elite in such a leak, if it occurred. (Meanwhile, Fauci and his supporters have been preemptively muddying the waters by trying to redefine what constitutes gain-of-function.)

The growing clamor on social media, much of it provoked by Wade’s research, is one of the main reasons Biden and the media are being forced to address the lab-leak theory, having previously discounted it. And yet Wade’s revelations of U.S. and WHO involvement in gain-of-function research, and of potential complicity in a lab leak and a subsequent cover-up are missing from almost all corporate media reporting.

Evasion Tactic

Biden’s so-called investigation is intended to be cynically evasive. It makes the administration look serious about getting to the truth when it is nothing of the sort. It eases pressure on the corporate media that might otherwise be expected to dig out the truth themselves. The narrow focus on the lab leak theory displaces the wider story of potential U.S. and WHO complicity in such a leak and overshadows efforts by outside critics to highlight that very point. And the inevitable delay while the investigation is carried out readily exploits Covid news fatigue as Western publics start to emerge from under the pandemic’s shadow.

The Biden administration will hope the public’s interest rapidly wanes on this story so that the corporate media can let it drop off their radar. In any case, the investigation’s findings will most likely be inconclusive, to avoid a war of dueling narratives with China.

But even if the investigation is forced to point the finger at the Chinese, the Biden administration knows that the Western corporate media will loyally report its accusations against China as fact — just as they loyally blacked out any consideration of a lab leak until they were forced to do so over the past few days.

Illusion of Truth

Wuhan Institute of Virology is a research institute by the Chinese Academy of Sciences in Jiangxia District, south of the Wuhan city, Hubei province, China. (Ureem2805/Wikimedia Commons)

The Wuhan story provides a chance to understand more deeply how elites wield their narrative power over us — to control what we think, or are even capable of thinking. They can twist any narrative to their advantage.

In the calculations of Western elites, the truth is largely irrelevant. What is of utmost importance is maintaining the illusion of truth. It is vital to keep us believing that our leaders rule in our best interests that the Western system — despite all its flaws — is the best possible one for arranging our political and economic lives and that we are on a steady, if sometimes rocky, path towards progress.

The job of sustaining the illusion of truth falls to the corporate media. It will be their role now to expose us to a potentially lengthy, certainly lively — but carefully ring-fenced and ultimately inconclusive — debate about whether Covid emerged naturally or leaked from the Wuhan lab.

The media’s task is to manage smoothly the transition from last year’s unquestionable certainty — that the pandemic had an animal origin — to a more hesitant, confusing picture that includes the possibility of a human, but very much Chinese, role in the virus’ emergence. It is to ensure we do not feel any cognitive dissonance as a theory we were assured was impossible by the experts only weeks ago suddenly becomes only too possible, even though nothing has materially changed in the meantime.

What is essential for the political, media and scientific establishments is that we do not ponder deeper questions:

  • How is it that the supposedly skeptical, disputatious, raucous media once again spoke mostly with a single and uncritical voice on such a vitally important matter — in this case, for more than a year on the origins of Covid?
  • Why was that media consensus broken not by a large, well-resourced media organization, but by a lone, former science writer working independently and publishing in a relatively obscure science magazine?
  • Why did the many leading scientists who are now ready to question the imposed narrative of Covid’s animal origin remain silent for so long about the apparently equally credible hypothesis of a lab leak?
  • And most importantly, why should we believe that the political, media and scientific establishments have on this occasion any interest in telling us the truth, or in ensuring our welfare, after they have been shown to have repeatedly lied or stayed silent on even graver matters and over much longer periods, such as about the various ecological catastrophes that have been looming since the 1950s?

Class Interests

Those questions, let alone the answers, will be avoided by anyone who needs to believe that our rulers are competent and moral and that they pursue the public good rather than their own individual, narrow, selfish interests — or those of their class or professional group.

Scientists defer slavishly to the scientific establishment because that same establishment oversees a system in which scientists are rewarded with research funding, employment opportunities and promotions. And because scientists have little incentive to question or expose their own professional community’s failings, or increase public skepticism towards science and scientists.

Similarly, journalists work for a handful of billionaire-owned media corporations that want to maintain the public’s faith in the “benevolence” of the power structures that reward billionaires for their supposed genius and ability to improve the lives of the rest of us. The corporate media has no interest in encouraging the public to question whether it can really operate as a neutral conduit that channels information to ordinary people rather than preserves a status quo that benefits a tiny wealth-elite.

And politicians have every reason to continue to persuade us that they represent our interests rather than the billionaire donors whose corporations and media outlets can so easily destroy their careers.

What we are dealing with here is a set of professional classes doing everything in their power to preserve their own interests and the interests of the system that rewards them. And that requires strenuous efforts on their part to make sure we do not understand that policy is driven chiefly by greed and a craving for status, not by the common good or by a concern for truth and transparency.

Which is why no meaningful lessons will be learnt about what really happened in Wuhan. Maintaining the illusion of truth will continue to take precedence over uncovering the truth. And for that reason we are doomed to keep making the same screw-ups. As the next pandemic will doubtless attest.

Jonathan Cook is a former Guardian journalist (1994-2001) and winner of the Martha Gellhorn Special Prize for Journalism. He is a freelance journalist based in Nazareth. If you appreciate his articles, please consider offering your financial support.

This article is from his blog Jonathan Cook.net.

The views expressed are solely those of the author and may or may not reflect those of Consortium News.


INTRODUCTION

In early Drosophila embryogenesis, signals mediated by different receptor tyrosine kinases (RTKs) establish cell fates in a wide range of developmental processes. All RTK pathways transduce signals via the canonical Ras/Raf/MEK/MAPK cascade, yet they clearly elicit diverse outcomes: the Torso RTK pathway defines the embryonic termini(Furriols and Casanova, 2003)two FGF receptors (FGFR) are required for the patterning of the mesoderm and trachea (Huang and Stern,2005) and the EGF receptor (EGFR) pathway controls various processes such as the formation of the ventral neuroectoderm, the specification of muscle precursors and the invagination of tracheal branches(Shilo, 2003). These differential transcriptional and morphological responses to RTK activation are context specific, and probably depend on the strength, range and duration of the signal. Additional specificity of the response is conferred by crosstalk between RTK and other signalling pathways(Culi et al., 2001), as well as by the combinatorial activity of nuclear pathway effectors together with distinct tissue-specific factors, at the level of specific DNA enhancers(Flores et al., 2000 Simon, 2000).

The EGFR pathway induces broad changes in target gene expression in responding cells by activating, as well as inactivating, specific DNA-binding transcription factors belonging to the Ets family(Shilo, 2005). We have recently found that this pathway also modulates the function of Groucho (Gro),a pivotal global corepressor that contains two putative, evolutionarily conserved MAPK consensus sites. Specifically, Gro is phosphorylated in response to EGFR-dependent signalling, and this modification leads to the downregulation of its repressor capacity(Hasson et al., 2005). In particular, we have shown that the activation of the EGFR pathway attenuates Gro-mediated repression in vivo, whereas mutations in either Egfr or Ras produce an opposite effect, i.e. Gro-mediated repression is strengthened. Significantly, the ubiquitously expressed Gro and its Transducin-like Enhancer-of-split (TLE) mammalian homologues interact with,and potentiate the repressor function of, a large number of transcription factors (Buscarlet and Stifani,2007 Chen and Courey,2000). By compromising the ability of Gro/TLE to function as a general negative transcriptional co-regulator, EGFR signalling can thus simultaneously override an entire group of repressors, affecting the spatial and temporal regulation of their target genes. In this way, relief of Gro/TLE-dependent gene silencing in response to EGFR signalling could potentially permit the coordinated derepression of a large number of genes,allowing for wide-range changes in gene expression profiles, and consequently in cell fates (Hasson and Paroush,2006).

Here, we have generated antibodies that specifically recognise the phosphorylated form of Gro, allowing us to detect it in its modified state during the different stages of embryonic development. We use these anti-sera to explore the dynamics of Gro phosphorylation in vivo, and find that it is modified downstream of several RTK pathways. Our data suggest that Gro is phosphorylated directly by MAPK or by the MAPK kinase MEK. Importantly, a large proportion of the pool of Gro molecules per nucleus is phosphorylated,indicating that the repressor capability of Gro is attenuated by an efficient mechanism. We focus on the regulation of terminal patterning by the Torso RTK pathway, and show that Gro phosphorylation and the resulting downregulation of its repressor function is essential for the transcriptional output of this pathway and for terminal cell specification. Finally, we demonstrate that phosphorylation of Gro does not alter its subcellular localisation, nor does it bring about its degradation. Rather, nuclear Gro persists in its phosphorylated state long after MAPK/ERK activation has terminated. We propose that inactivation of Gro via phosphorylation is an essential, shared response to RTK signal transduction, and discuss a model whereby phosphorylation of Gro provides a transcriptional `memory' mechanism that allows RTK cascades to confer long-lasting effects on target gene expression.


WHAT IS SPECIAL ABOUT TYROSINE PHOSPHORYLATION?

From a chemical perspective there is nothing particularly unusual about the chemical properties of the O 4 -phenolic phosphate ester bond of P.Tyr, which, like those of phosphoserine (P.Ser) and P.Thr, is a relatively high-energy bond (8–10 kcal). However, because the phosphate on Tyr is linked to the O 4 position of the phenolic ring, it lies much further away from the peptide backbone than the phosphate on the β-OH groups of Ser and Thr, and, in consequence, this in itself provides an element of binding specificity. In addition, the phenolic ring of P.Tyr is unique in providing significant additional binding energy for phosphospecific-binding domains that are mediated by hydrophobic or π bond-ring interactions, which P.Ser/Thr cannot make. These properties allowed the evolution of selective P.Tyr-binding domains, which have much deeper binding pockets than those for P.Ser and P.Thr-binding domains. In addition, the greater distance of the O 4 hydroxyl from the peptide backbone allowed evolution of Tyr-specific kinases, and also P.Tyr-specific phosphatases. Fortuitously, the distinct chemical properties of P.Tyr also allow the immune system to generate antibodies that selectively recognize P.Tyr over P.Ser and P.Thr, and such anti-P.Tyr antibodies have been extraordinarily useful in studying Tyr phosphorylation.


SPATIAL SIGNAL PROPAGATION

Imaging data and computational models suggest that the propagation of RTK signaling from the plasma membrane to targets in the nucleus is tightly controlled by a variety of regulatory mechanisms (Kholodenko et al. 2010 Vartak and Bastiaens 2010 Grecco et al. 2011 Alam-Nazki and Krishnan 2012). RTK signaling pathways are highly spatially organized within cells. Activator enzymes, such as kinases or guanine nucleotide exchange factors (GEFs), and inactivating enzymes (e.g., phosphatases and GTPase-activating proteins [GAPs]) often localize to different cellular locales (Kholodenko 2009). For a protein phosphorylated by a membrane-bound kinase and dephosphorylated by a cytosolic phosphatase, it was predicted that there can be a gradient of the phosphorylated form, which is high close to the membrane and low within the cell (Brown and Kholodenko 1999). Instructively, the shape of the gradient depends mainly on the phosphatase activity. If the phosphatase is not saturated, the concentration profile of the active, phosphorylated form of the target protein decays almost exponentially with the distance from the membrane. Such exponential decrease in the activity of G proteins can also be observed if GEF activity is associated with a cellular structure, such as chromatin, and when GAP activity is excluded from this structure (Kholodenko 2006). Spatial gradients of protein activities organize signaling around cellular structures, such as membranes, chromosomes and scaffolds, and provide positional cues for key processes, including cell division. Such intracellular gradients of protein activities have been detected in live cells using imaging technologies based on fluorescence resonance energy (Maeder et al. 2007).

Raf-1, the initial kinase in the MAPK/ERK cascade is activated near the plasma membrane where activated downstream of RTKs, the small GTPase Ras resides. How can the phosphorylation signal that was initiated at the plasma membrane propagate through the cytoplasm where it is terminated by phosphatases? Central mechanisms of spatial signal propagation have been suggested. First, a kinase cascade can be assembled on a scaffold protein that protects transmission of phosphorylation against phosphatase activity. Second, even for a soluble cascade of (de)phosphorylation cycles, the phosphorylation signal reaches further into the cell interior, when the cascade has more levels, and this might be one of the reasons that cascades exist (Munoz-Garcia et al. 2009). Third, kinesin motor-mediated movement of the endosomes and kinase complexes along microtubules can transfer phosphorylation signals, guarding against dephosphorylation (Kholodenko 2002 Perlson et al. 2005, 2006). Finally, and most intriguingly, it was suggested that RTK signals can propagate as nonlinear traveling waves that create global spatial switches or pulses of kinase and GTPase (in)activation (Munoz-Garcia and Kholodenko 2010). These mechanisms facilitate signal propagation from activated RTKs across single cells.


‘Survival of the laziest’: Finally, there’s a scientific reason to not get off the couch

No one is questioning whether leaving the couch to go for a walk or run or to lift heavy objects would personally do you some good — accelerating your heart rate, burning some calories, maybe even adding a few years to your life.

But consider this: All that exercise may be a selfish act, a shortsighted game of checkers in an evolutionary chess match that’s been going on for eons. And by not stepping, you may have already taken the first step toward saving the species.

Finally, there is a study that, if read in just the right way, can lend credence to wasting away a Sunday (or Monday or Tuesday) afternoon. Think of it as a not-entirely airtight rebuttal to the American Heart Association, the NFL, to Michelle Obama and your smartwatch’s gentle but judgmental reminder that you’ve taken only nine steps in the last hour.

There is proof in the form of a scientific paper, whose authors may be typing out an angry email to The Washington Post at this very moment. An article in the Journal of Proceedings of the Royal Society B: Biological Sciences this month has found evidence that species that exert less energy on average have a better shot at making another rotation around the circle of life.

CrossFit-averse people everywhere can send thank-you notes to Luke Strotz, a postdoctoral researcher at Kansas University’s Biodiversity Institute, who spent years studying the fossils of mollusks and bivalves. His most recent study shows that there’s a significant connection between a low basal metabolic rate (that’s the amount of energy an organism expends while at rest) and a species’s evolutionary endurance. The paper, he told The Washington Post, gives us more insight into what causes species to go extinct.

“It’s not a be-all and end-all of extinction that’s not the case,” Strotz told the Lawrence, Kan., Journal-World. “But what this study does for the first time is show that metabolism and physiology is a component of extinction, and no one has done that before. No one has shown that previously.”


The Surprising Brain Differences Between Democrats and Republicans

Chris Mooney

It is still considered highly uncool to ascribe a person’s political beliefs, even in part, to that person’s biology: hormones, physiological responses, even brain structures and genes. And no wonder: Doing so raises all kinds of thorny, non-PC issues involving free will, determinism, toleration, and much else.

There’s just one problem: Published scientific research keeps going there, with ever increasing audacity (not to mention growing stacks of data).

The past two weeks have seen not one but two studies published in scientific journals on the biological underpinnings of political ideology. And these studies go straight at the role of genes and the brain in shaping our views, and even our votes.

First, in the American Journal of Political Science, a team of researchers including Peter Hatemi of Penn State University and Rose McDermott of Brown University studied the relationship between our deep-seated tendencies to experience fear&mdashtendencies that vary from person to person, partly for reasons that seem rooted in our genes&mdashand our political beliefs. What they found is that people who have more fearful disposition also tend to be more politically conservative, and less tolerant of immigrants and people of races different from their own. As McDermott carefully emphasizes, that does not mean that every conservative has a high fear disposition. “It’s not that conservative people are more fearful, it’s that fearful people are more conservative,” as she puts it.

I interviewed the paper’s lead author, Peter Hatemi, about his research for my 2012 book The Republican Brain. Hatemi is both a political scientist and also a microbiologist, and as he stressed to me, “nothing is all genes, or all environment.” These forces combine to make us who we are, in incredibly intricate ways.

And if Hatemi’s and McDermott’s research blows your mind, get this: Darren Schreiber, a political neuroscientist at the University of Exeter in the United Kingdom, first performed brain scans on 82 people participating in a risky gambling task, one in which holding out for more money increases your possible rewards, but also your possible losses. Later, cross-referencing the findings with the participants’ publicly available political party registration information, Schreiber noticed something astonishing: Republicans, when they took the same gambling risk, were activating a different part of the brain than Democrats.

Republicans were using the right amygdala, the center of the brain’s threat response system. Democrats, in contrast, were using the insula, involved in internal monitoring of one’s feelings. Amazingly, Schreiber and his colleagues write that this test predicted 82.9 percent of the study subjects’ political party choices&mdashconsiderably better, they note, than a simple model that predicts your political party affiliation based on the affiliation of your parents.

I also interviewed Schreiber for The Republican Brain. He’s a scientist who was once quite cautious about the relevance of brain studies to people’s politics. As he put it to me: “If you had called me four years ago and said, ‘What is your view on whether Republicans and Democrats have different brains?’ I would have said no.” Now, his own published research suggests otherwise.

One again, though, there’s a critical nuance here. Schreiber thinks the current research suggests not only that having a particular brain influences your political views, but also that having a particular political view influences and changes your brain. The causal arrow seems likely to run in both directions&mdashwhich would make sense in light of what we know about the plasticity of the brain. Simply by living our lives, we change our brains. Our political affiliations, and the lifestyles that go along with them, probably condition many such changes.

The two new studies described here are likely connected: It is hard not to infer that fear of outsiders or those different from you&mdashalong with greater fear dispositions in general&mdashmay be related to the role of amygdala, a brain structure that has been dubbed the “heart and soul of the fear system.” The amygdala has been repeatedly implicated in politics. Indeed, Schreiber’s research builds on prior brain studies: In a group of University College of London students, for instance, conservatives showed more gray matter in the right amygdala.

So what’s the upshot? How about this: We need a much broader and more thoughtful discussion about what it means if political ideology turns out to be nothing like what we actually thought it was. Scientists working in this new field tend towards the conclusion that the new research should make us more tolerant, not less, of political difference&mdashnot to mention a whole lot more humble about our own deeply held beliefs.


Regulation of the Cell Cycle by External Events

Both the initiation and inhibition of cell division are triggered by events external to the cell when it is about to begin the replication process. An event may be as simple as the death of a nearby cell or as sweeping as the release of growth-promoting hormones, such as human growth hormone (HGH). A lack of HGH can inhibit cell division, resulting in dwarfism, whereas too much HGH can result in gigantism. Crowding of cells can also inhibit cell division. Another factor that can initiate cell division is the size of the cell as a cell grows, it becomes inefficient due to its decreasing surface-to-volume ratio. The solution to this problem is to divide.

Whatever the source of the message, the cell receives the signal, and a series of events within the cell allows it to proceed into interphase. Moving forward from this initiation point, every parameter required during each cell cycle phase must be met or the cycle cannot progress.


Antarctic Seals Vocalize in Ultrasonic&mdashbut Not for the Usual Reason

Above the frozen ocean, Antarctica can be eerily quiet. Gusts of wind are often all one hears. Below, though, the Southern Ocean is a living soundscape dominated by Weddell seals. These pinnipeds typically emit high-pitched pings that sound like laser guns in a science-fiction movie. But that is not their entire repertoire. Research now reveals that a significant portion of their calls are at ultrasonic frequencies, high pitches well beyond the 20-kilohertz limit of most human hearing.

University of Oregon marine biologist Paul Cziko installed a livestreaming audio and video system at Antarctica&rsquos McMurdo Station in 2017, allowing scientists to listen in on the massive mammals&rsquo underwater calls. Data from the setup yielded surprising results: The seals sometimes vocalized at extremely high, ultrasonic frequencies of more than 200 kilohertz, Cziko and his colleagues reported in the Journal of the Acoustical Society of America.

Ultrasonic calls cast a narrower, more precise sound beam than lower-frequency ones. Bats and toothed whales have specialized anatomy that lets them use such beams for echolocation, sensing their surroundings by deciphering the rebounding sound waves. Seals, however, lack the necessary anatomical structures. So why do they make these sounds?

With true echolocation ruled out, Cziko and his colleagues suspect Weddell seals use ultrasonic calls for less specific orientation purposes. In the early 1970s, William Schevill and William Watkins, both at the Woods Hole Oceanographic Institution, came to a similar conclusion after using the era&rsquos limited technology to record Weddell seals&rsquo ultrasonic vocalizations, likely for the first time. &ldquoWe have no evidence for echolocation [in Weddell seals], yet it seems that a directional sound beam would be especially useful in echolocation,&rdquo they wrote in Antarctic Pinnipedia.

Cziko notes the 1970s team only recorded one call type, a chirp that started at 30 kilohertz and then descended in frequency. With the new system&rsquos advanced hydrophone, Cziko&rsquos team was able to record Weddell seals making at least nine call types spanning the ultrasonic range, including chirps, trills and &ldquoU-shaped whistles.&rdquo In two years&rsquo worth of recording, 17 percent of all Weddell seals&rsquo calls were ultrasonic, with the animals using this range more often during the Southern Hemisphere winter.

Annual sunlight cycles may play a role in the seals&rsquo seasonal call behavior. Antarctica experiences four months of 24-hour sunlight during summer, and winters have long periods of complete darkness. &ldquoWe know that seals have really good low-light vision,&rdquo says Lisa Munger, a marine mammal bioacoustician at the University of Oregon and a co-author of the new research. &ldquoBut when there&rsquos no light, they&rsquove got to be using something else to find their way around.&rdquo Echoes from ultrasonic calls may provide enough basic environmental information to help seals return to breathing holes in the ice or to locate food&mdasheven if their sound-processing is not specialized enough to be called true echolocation.

High-frequency vocalizations travel shorter distances than lower-frequency ones, and this may also help Weddell seals communicate without alerting predators. &ldquoThese sounds might be really useful if you&rsquore trying to communicate with someone that&rsquos a few feet away,&rdquo Munger says. &ldquoBut you don&rsquot want the sound to get out into the open water, where there are killer whales.&rdquo

Peter Tyack, an animal behaviorist at the Woods Hole Oceanographic Institution and the University of St. Andrews in Scotland, who was not involved with the study, notes another possible communication hypothesis. &ldquoIf you have territorial males broadcasting threats to each other and you just hear the low-frequency [calls], you might interpret that as a background threat,&rdquo he says. &ldquoBut if all of the sudden you hear the high-frequency &hellip that could mean &lsquoI&rsquom threatening you, not the general world.&rsquo&rdquo

The new findings may have a simpler explanation, Tyack adds. Humans define &ldquosonic&rdquo and &ldquoultrasonic&rdquo ranges based on the limits of our own hearing, but for Weddell and other seals, a range of about 50 to 100 kilohertz may be optimal. As he puts it: &ldquoWhy would you not make sounds in the best range of your hearing?&rdquo