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Musings: May-August 2020 (archive)

Musings is an informal newsletter mainly highlighting recent science. It is intended as both fun and instructive. Items are posted a few times each week. See the Introduction, listed below, for more information.

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   Introduction (separate page).
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2020 (May-August)
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Archive items may be edited, to condense them a bit or to update links. Some links may require a subscription for full access, but I try to provide at least one useful open source for most items.

Please let me know of any broken links you find -- on my Musings pages or any of my web pages. Personal reports are often the first way I find out about such a problem.

August 26, 2020

Can human lungs that are too damaged to be transplanted be fixed?

August 22, 2020

Apparently so, according to a recent article. Pigs can fix them.

Here's the set-up...

The scientists take various measurements. Here are some of them, summarized over six lungs...

The graph shows that 24 hr connected to a pig improves the functioning of the lungs. There is much more data in the article, at various levels including histological, immunological and biochemical. The general conclusion holds.

Perspective... It's actually known that damaged lungs can be improved by perfusion. The time between death of the donor and use of the lung is a time for decay. It's normal to attach a lung removed from a donor to a special device, pumping a blood-free solution through the lung. The procedure is known as ex vivo lung perfusion (EVLP). The development of EVLP devices, only a few years ago, provided a major improvement, allowing a few hours between donor death and lung use. But the devices have major limitations. Six hours of such machine-based perfusion is about all a lung can take. Even a donor lung in good condition from a fresh cadaver can't last much longer. The work here replaces a mechanical device using a lab-fluid with a biological one using real blood -- even if from a different species. A longer perfusion is practical, and the results are better. In fact, one of the lungs tested here had failed to improve on EVLP, but did improve to near-transplant quality after 24 hours attached to the pig.

No actual transplants have yet been done using organs repaired by the new procedure.

If a pig can do this, why not a human? In fact, at the end of the article, the authors suggest just that. If the person is already opened up, attaching an in-process lung would be possible. This avoids one extra step of immunological issues, but also raises its own concerns, in that it may be difficult to test the system.

The work here could lead to an increased supply of lungs for transplantation. Further, study of the system could lead to a better understanding of how the damaged lungs are repaired, and therefore to improvements in the mechanical perfusion devices.

News stories:
* Experiment Shows That Damaged Human Lungs Can Be Repaired By Attaching Them To Pigs. (A Shahab, MEDizzy Journal, July 23, 2020.)
* Severely Damaged Human Lungs Can Now Be Successfully Recovered -- Columbia Engineering and Vanderbilt researchers demonstrate that human lungs rejected for transplant can be recovered using cross-circulation, to provide much larger number of donor lungs to critically ill patients. (H Evarts, Columbia Engineering, July 13, 2020.) From one of the lead institutions.

* News story accompanying the article: Regenerative medicine: Ex vivo repair of human donor lungs for transplantation -- Injured human donor lungs deemed unsuitable for immediate transplantation may be successfully recovered by connection into the circulation of a porcine host with perfusion and ventilation ex vivo for 24 hours. (A J Fisher & J H Dark, Nature Medicine 26:1015, July 2020.)
* The article: Xenogeneic cross-circulation for extracorporeal recovery of injured human lungs. (A E Hozain et al, Nature Medicine 26:1102, July 2020.)

More about pigs and lungs:
* Making lungs in the lab -- and transplanting them into an animal (August 17, 2018).
* Pigs as organ donors for humans (February 16, 2010).

More about dealing with lung problems... If lungs fail, can you breathe with your intestines? (July 16, 2021).

A post about a similar issue: Using lab-grown organoids in medical treatment (May 3, 2021).

There is more about transplantation on my page Biotechnology in the News (BITN) for Cloning and stem cells. It includes an extensive list of related Musings posts.

More pigs... Oldest known picture of a pig (February 21, 2021).

August 19, 2020

A mosquito-like robot

August 18, 2020

I suggest you start by watching it -- a short video. Direct link: Quadcopter ground detection. (YouTube. Half minute. No important sound -- but it does sound like a mosquito, no?) (This video is in both news stories listed below.)

The point? The underlying robot is a common type of drone, a quadcopter. But this one has an unusual way of avoiding hitting surfaces -- a way it "learned" from mosquitoes.

Mosquitoes fly quite well in the dark -- and they don't hit things. Why not? The best understanding is that they sense the change in air pressure as they approach a surface. That is, they sense their self-induced air flows.

Self-induced air flows? Look...

It is not surprising that the mosquito affects the air pressure, and that a nearby surface matters. What is important is that the mosquito can detect the changes -- and act on them. In fact, there is neurophysiological work that documents the animal's sensitivity to such small changes.

What is even more important is that the engineers here have transplanted the idea into the design of their robot.

The drone has been engineered to detect changes in air pressure with exquisite sensitivity; it uses the air pressure as information about surfaces. The video noted at the start of the post shows the result.

The drone used here fits in a hand; it weighs less than 30 g. Implementation of the mosquito-inspired ground sensor was simple and effective.

The article represents an advance in our understanding of mosquitoes, as well as a practical improvement in drone technology.

News stories:
* Mosquitoes Inspires [sic] A Surface Detector. (UAV Expert News, May 22, 2020. Now archived.)
* Mosquito night navigation inspires new drone obstacle avoidance system. (D Szondy, New Atlas, May 8, 2020.)

* News story accompanying the article: Engineering: Drones become even more insect-like -- Mosquitoes' exceptional sensitivity to sound and airflow inspires new collision avoidance technology. (J Young & M Garratt, Science 368:586, May 8, 2020.)
* The article: Aerodynamic imaging by mosquitoes inspires a surface detector for autonomous flying vehicles. (T Nakata et al, Science 368:634, May 8, 2020.)

Also see:
* The smallest manmade flying devices (December 12, 2021).
* Crashworthy drones, wasp-inspired (October 16, 2017).
* How bumblebees detect the electric field (October 22, 2016).
* Science: Love songs (March 26, 2009).

For more about bio-inspiration, see my Biotechnology in the News (BITN) topic Bio-inspiration (biomimetics). It includes a listing of Musings posts in the area.

What's the connection: histones and copper ions?

August 15, 2020

The biology of copper is tricky. There are a few proteins that require Cu, but it is also quite toxic. Organisms manage their Cu carefully.

A recent article reports a new enzyme for reducing Cu(II) to Cu(I). Here are some data to demonstrate the enzyme...

The graph shows the amount of Cu+ made (y-axis) vs time (x-axis). The Cu+ is measured by absorbance. Actually, the scientists measured a complex of the Cu+ ion, a more sensitive measurement. The top curve, "Xl WT", shows the production of Cu+ in the presence of the wild type enzyme. The bottom curve, "buffers", is for a control without the enzyme. There is a low background production of Cu+.

The middle curve, very near the bottom, is for a modified enzyme. The enzyme has been changed so that a particular amino acid thought to be important for the catalytic activity has been replaced by an "inert" amino acid. As expected, the modified enzyme does not work. The label on the middle curve includes "C110A". That means that the amino acid C at position 110 has been changed to A. C = cysteine, A = alanine. We'll explain the rest of the name later.    This is Figure 2E from the article.

That graph provides good evidence that they have a copper(II) reductase enzyme. Both the buffer control and the intentionally-inactivated enzyme support the claim.

The reduction reaction requires a source of electrons --a reducing agent. In the work shown above, they add a separate reducing agent. That is, the enzyme catalyzes electron transfer from the added reducing agent to the Cu²⁺. The plateau in the top curve, above, seems to be due to depleting the reducing agent.

Where did they find this new enzyme? On your DNA. Or rather, on the DNA of a frog. Xl stands for Xenopus laevis, the African clawed toad, a common lab animal. The enzyme is one of the histones that are the major proteins binding to DNA. People had noticed that a site in the histone structure looked like it could bind copper. The work here builds on that observation. Not only does the histone bind Cu²⁺, it catalyzes its reduction.

The catalytic site is not simply in one protein, but is at the interface when the various histone proteins come together to make larger structures. More specifically, the site is formed at the interface between two H3 submits in the common histone tetramer (H3H4)₂.

Cu(II) is the more common form of copper in the environment. Cu(I) is less toxic. Thus one can imagine that the reduction is a detox mechanism.

Work with yeast, where they can do genetic manipulations, allowed further testing, in vitro and in vivo. Interestingly, the enzymatic site is weak in the wild type yeast. That allowed them to make both better and worse versions of the enzyme. (One of the changes is essentially the opposite of the modification shown in the figure above.) In vivo, the changes affected copper metabolism, and enzyme activity correlated with ability to grow in the presence of Cu²⁺. Thus the yeast work shows that the Cu reductase activity of the histone is biologically relevant.

Humans? The gene sequence for the human histone H3 suggests that the active site for copper(II) reduction is intact. Beyond that, there is no information.

Intriguingly, the catalytic site appears intact in the histones of the most primitive organisms, the archaea. Is this a hint about the evolutionary importance of the enzyme activity? The authors speculate on this point.

Overall, the article shows that a well-known DNA-binding protein also has an enzymatic activity. The finding raises many interesting questions.

News stories:
* The secret double life of histone H3 as a copper reductase enzyme. (EurekAlert! (AAAS), July 2, 2020.)
* Histone H3-H4 tetramer found to be a copper reductase enzyme. (B Yirka, Phys.org, July 3, 2020.)

* News story accompanying the article: Molecular biology: The secret life of histones -- Histone H3 leads a double life as a copper reductase. (J Rudolph & K Luger, Science 369:33, July 3, 2020.)
* The article: The histone H3-H4 tetramer is a copper reductase enzyme. (N Attar et al, Science 369:59, July 3, 2020.)

More copper biology...
* Bacteria that make atomic copper (May 8, 2021).
* Copper ions in your nose: a key to smelling sulfur compounds (October 10, 2016).

A post that mentions histones... Using CRISPR to change cell fate (September 10, 2016).

More Xenopus: Designing reconfigurable organisms (January 19, 2020).

August 12, 2020

Briefly noted...

August 12, 2020

Retraction notice. The article that was the basis of a recent Musings post has been retracted. The article claimed the smallest known dinosaur. The post noted that there was some challenge to that claim. The authors, now with further evidence, acknowledge that the challenge is probably correct, and therefore retract the original article. (The fossil itself is still of interest; the scientists will presumably submit a new article about it at some point. It is the interpretation of the fossil that is of concern. The wonderful picture of it, shown in the post, remains.)
* News story: World's smallest dinosaur is probably a lizard -- Paper that reported the animal's discovery was retracted following new evidence from a similar fossil. (G Viglione, Nature, July 23, 2020. In print: Nature 583:665, July 30, 2020.)
* Direct link to the retraction notice at the journal web site: Retraction Note: Hummingbird-sized dinosaur from the Cretaceous period of Myanmar. (L Xing et al, Nature, July 22, 2020.)
* I have added this update to the original post, at the top, as a retraction box. That post is: A Cretaceous dinosaur the size of a tiny bird? (June 2, 2020).

A better catalytic sponge: degrading plastics, and more

August 11, 2020

Solid-state catalysts are of considerable interest in industrial chemistry, but they also have limitations.

As solids, they are less of an environmental hazard than liquid-based materials. On the other hand, getting pieces of a system to work together can be harder.

Some crystalline zeolite materials have strongly acidic groups, often important for catalysis. But they have limited surface area. Some amorphous aluminosilicates are highly porous, with high surface area, but they lack the more acidic groups and have weak catalytic properties.

The terminology here can be confusing. Zeolites are in fact aluminosilicates -- typically crystalline. The real distinction of interest is between crystalline and amorphous materials. The latter have the potential to be more porous -- more spongy.

Here are some results for a novel catalytic material, as described in a new article...

The graph shows T50 for various tests. T50 is the temperature (T) needed to get 50% degradation in a standard test procedure. The lower the better. Three plastics were tested, each without and with the new catalyst. Start with the two bars at the left. Plastic bottles. The first bar shows the result without catalyst. T50 (bar height, also shown on the bar) is 439 °C. The next bar shows the result for the same material, but now with the new catalyst, labeled here as AAS. T50 is reduced, to 403 °C. That is, the AAS catalyst improved the process.

The next two bars show a similar comparison for a different plastic (lab test tubes). The two bars at the right show a comparison for a third plastic (common single-use plastic grocery bags). In each case, the catalyst lowered T50. In the final two cases, the improvement was over 100 degrees.    This is part of Figure 8 from the article. The line connecting the bars is meaningless.

The new catalyst works. But how does it compare to other catalysts? The following figure shows a comparison...

The reaction here is the degradation of LDPE (low density polyethylene) -- the plastic bag stuff. Various catalysts were tested. The graph is similar to the one above. Each bar is for one catalyst. The lower the bar height, the better (lower T50). The first bar (at the left) is for the newly developed material, called AC*-1.9; it is the best.    This is Figure 9b from the article.

The general picture is that the new material works -- rather well.

The authors carry out several reactions, in each case showing that the new material has merit in catalyzing difficult transformations. Some are specific chemical syntheses. The one shown above is an example of a more general use, aiding in the recycling of plastics. They also test the material for the reduction of CO₂ into a useful fuel.

What is the product from the reactions shown above, for degrading plastics? Hydrocarbons. There isn't much detail about the specifics, but presumably they are useful, as feedstock chemicals and/or fuels.

What is this stuff? AAS stands for acidic aluminosilicate. It is a material designed to have the catalytic advantages of a crystalline zeolite and the physical features of an amorphous aluminosilicate. The scientists made a variety of such materials; the one featured above was generally the best.

Here is what it looks like, with some numbers....

The two images are both electron micrographs of AC*-1.9. SA = (accessible) surface area. PV = pore volume.    This is part of Figure 1 from the article.

To put the numbers in perspective... Consider a cube with one gram of a material with the density of water (1 g/cm³). It's surface area consists of the six sides of the cube, for a total of 6 cm². That is 0.0036 m², using the units shown on the figure. The pore volume (empty space inside) is zero for an ordinary solid.

The bottom line is that the authors have produced a new type of catalytic material, with a combination of desirable properties. Their AAS AC*-1.9 has the strongly acidic catalytic sites typical of crystalline zeolites and the greater porosity and accessibility characteristic of amorphous materials.

Why is the material acidic? The acidity of aluminosilicates is due to silanol groups, ...Si-OH. The acidity of such groups depends on the details of the environment. It is easier to manipulate the local environment in a crystalline material than in an amorphous material. Both the procedures for making the more acidic material and the characterization seem fairly rough at this point.

News story: Nano-sponges of solid acid transform carbon dioxide to fuel and plastic waste to chemicals. (Phys.org (Tata Institute of Fundamental Research), July 31, 2020.)

The article, which is freely available: Catalytic nanosponges of acidic aluminosilicates for plastic degradation and CO₂ to fuel conversion. (A Maity et al, Nature Communications 11:3828, July 31, 2020.)

Here are other posts about zeolites. Note that zeolite is a term for a broad group of chemicals, with diverse properties.
* Upgrading ethanol? (April 11, 2016).
* Upsalite: a novel porous material (September 6, 2013).

Another sponge... A sponge that will soak up phosphate pollution from water (August 14, 2021).

Among other posts on degradation of plastics... Good enzymatic degradation of polyesters, by manufacturing the plastic with the enzymes in it (May 4, 2021).

More about catalysis:
* Briefly noted... A Swiss army knife for catalysis (February 15, 2022).
* Low temperature treatment for auto exhaust? (February 18, 2018). Links to more.

A background post about plastics: History of plastic -- by the numbers (October 23, 2017). Links to more.

How exercise benefits the brain

August 9, 2020

Musings has noted that blood from a young mouse can improve brain function in an old mouse [link at the end]. A recent article from the same lab provides evidence for a specific enzyme that mediates the effect.

The effect of young blood on the brain is related to the beneficial effect of exercise on brain function. The effect of blood is mediated by the plasma -- the liquid part. In the current work, the scientists started by exploring how exercise affected the composition of blood. One factor they found of interest was the enzyme glycosylphosphatidylinositol (GPI)-specific phospholipase D1, Gpld1 for short. (We'll come back to the nature of the enzyme later.) The level of this enzyme increased with exercise, and correlated with the benefits of exercise to the brain. Of course, correlation does not mean there is a causal connection, but it does lead to a hypothesis.

To test the idea that Gpld1 is a player in the exercise-brain story, the scientists did a direct test. They added the enzyme, and looked at the brain response. In this case, they added the enzyme genetically, adding a gene that targeted to the liver, where the enzyme is normally made.

Here are some of the results, comparing what happened upon adding the gene for the enzyme vs adding a control gene...

The first three graphs show the counts for one or another kind of cell. The top one (labeled F1) is for neural stem cells. The next two (F2 and F3) are for new neurons, measured by two methods. Direct measurement of the enzyme level showed that adding the gene increased the level of the Gpld1 enzyme. That is, increasing the enzyme level stimulated the formation of new neurons (with no effect on the number of stem cells). The bottom graph (K) shows the performance of the mice on a behavioral test. The mice with the higher level of Gpld1 did better. This is part of Figure 3 from the article. I have added labels for the individual graphs of part F (upper right of each graph). The full part F also contains photos showing stained cells; those photos are examples of the information underlying the graphs. Parts D and E of Figure 3 in the article show data for the amount of enzyme. Results are shown for mRNA level in the liver and for protein in the plasma, measured by Western blot. Those two results show 6-and 2-fold increase, respectively, due to the added gene.

Those results are qualitatively similar to those obtained with exercise alone, or with use of blood plasma from exercised mice.

The conclusion, then, is that increasing the level of the enzyme Gpld1 leads to stimulation of growth of new neurons and to improved brain performance. In this case, the enzyme level was manipulated by the scientists, allowing a specific test of that enzyme. Exercise increases the level of this enzyme, too; plausibly, the effect of exercise on brain function is mediated, at least in part, by the effect of exercise on the level of this enzyme.

What does this enzyme do? The short answer is that we don't know. It appears that the enzyme itself does not make it to the brain. It is a lipase. It can remove lipid-linked proteins from cell surfaces -- and that can have a variety of metabolic effects. That's about all we know at this point. (One simple suggestion is that the enzyme leads to reduced general inflammation, and that is good for the brain.)

The study here is in mice. What is the relevance to humans? It is known that exercise does benefit the brain in older people. And the current article shows that exercise leads to elevated levels of the enzyme Gpld1. Beyond that, further work is needed.

We can easily understand that exercise increases muscles, but it is not so obvious why it would benefit the brain. The work on blood transfer, now extended in the current work to implicating a specific enzyme, is telling us something about how it happens.

News stories:
* Blood Transplants from Active Mice Give Brain Boost to Others -- The researchers behind the results propose that an exercise-induced protein in circulation is responsible for the benefits. (L Winter, The Scientist, July 12, 2020.) Now archived.
* Brain benefits of exercise can be gained with a single protein -- Findings open door to drugs that could help protect the aging brain. (Science Daily (University of California - San Francisco), July 9, 2020.)
* Liver Enzyme Levitates with Exercise, Spurs Learning in Old Mice. (M B Rogers, ALZFORUM, July 10, 2020.)

* News story accompanying the article: Physiology: Exercising your mind -- A circulating factor induced by exercise contributes to keeping the brain young in mice. (V A Ansere & W M Freeman, Science 369:144, July 10, 2020.)
* The article: Blood factors transfer beneficial effects of exercise on neurogenesis and cognition to the aged brain. (A M Horowitz et al, Science 369:167, July 10, 2020.)

Background post, from the same lab: Would young blood be good for your brain? (October 21, 2011).

More about exercise:
* Artificial exercise, using a robotic device glued to the muscle (May 2, 2023).
* Effect of exercise on developing ALS (July 27, 2021).
* High-performing athletes: might they have performance-enhancing microbes in their gut? (June 28, 2019).

A post exploring the role of a lipase in disease: Cataloging gene knockouts in humans (July 10, 2017).

My page for Biotechnology in the News (BITN) -- Other topics includes a section on Brain. It includes a list of brain-related posts.

August 5, 2020

A sniff test to see if a person is conscious

August 4, 2020

Patient in the hospital. Unresponsive. Brain injury. What is the prognosis? Are they conscious but uncommunicative, or quite unconscious?

Those are important questions, but hard to get at. A new article proposes a simple test to tell if a person is conscious: give them something to smell.

Here is the idea...

Clinical evaluation showed that the patient on the left was in a vegetative state, whereas the person on the right was minimally conscious. Tests with 43 patients showed that the sniff test was good at distinguishing the two states, as good as more complex tests. That is, the sniff test is a good simple way to distinguish whether or not the person is conscious.

Follow-up study shows that the people with positive responses in the sniff test had better outcomes: more likely to recover good function and more likely to survive for an extended period.

There are complexities beyond what is discussed above. Of particular interest, sometimes a person judged to be vegetative showed a positive sniff response. In each case, the person later was judged to be conscious. That is, gaining the sniff response was an early indicator of improvement.

We also note... There are two kinds of responses being measured. One is whether the person responds to being offered an odor. Another is whether they distinguish different odors. The two individuals whose results are shown in the figure differ on both points.

The sniff test is quick and easy. It does not require active participation by the patient. It shows promise as a useful diagnostic tool for a difficult situation.

News story: Unconscious: 'Sniff test' predicts recovery of consciousness. (Science Daily (Weizmann Institute), May 21, 2020.)

The article: Olfactory sniffing signals consciousness in unresponsive patients with brain injuries. (A Arzi et al, Nature 581:428, May 28, 2020.)

A recent post on brain injury: Traumatic brain injury: long term effects? (October 8, 2019).

A recent post on olfaction: Is it possible to have a normal sense of smell without olfactory bulbs? (January 28, 2020). Links to more.

My page for Biotechnology in the News (BITN) -- Other topics includes a section on Brain. It includes a list of brain-related posts.

Pancreatic cancer: another trick for immune evasion

August 1, 2020

Pancreatic cancer is a big problem. For one thing, it is often discovered rather late. Beyond that, we don't know much about its secrets.

A recent article may have uncovered one of those secrets.

Let's start with the bottom-line test...

	32 tumor samples were transplanted into mice. Four different treatment conditions, eight tumors per condition. The final tumors are shown in the figure, one row per treatment condition. It's clear... The tumors are smaller in the bottom row. (In fact, three tumors disappeared completely, denoted by x.)
This is Figure 4f from the article. (Part g of the full figure shows quantitative data for the experiment, with the weight of each tumor.)

What did the scientists do in the bottom-row-treatment? And how did they figure out to try it?

The labeling shows that there are two treatment variables, IgG vs ICB, and PBS vs CQ.

ICB stands for immune checkpoint blockade therapy, often called cancer immunotherapy. This is based on the recent finding that cancers turn off the immune response. Scientists then developed antibodies that turn it back on. ICB therapy has become a hot topic in cancer biology. It leads to a significant number of spectacular responses, even with advanced cancers. (The 2018 Nobel Prize in Physiology or Medicine was awarded for the work leading to this therapy.) IgG is a control antibody treatment, with no target.

However, ICB therapy often does nothing, as seen in the second row. There is more to the story of how cancers evade the immune system. Experience so far suggests that cancers have a variety of other tricks for evading the immune response.

In the bottom-row-treatment, they used not only ICB, but also CQ. That is chloroquine. (Yes, that CQ. But the recent news about CQ and its close relative HCQ has nothing to do with the current work.) PBS is a buffer control for the CQ.

CQ + ICB works, rather well in this model system. What's the CQ doing? It is inhibiting autophagy -- and autophagy is how the cancer is evading the immune response.

The heart of the new article is working out that story, and it is complicated. A short version is that the scientists did much work that revealed that autophagy seemed to be eliminating the immune response. That led to the hypothesis: inhibit autophagy, and that may restore the immune response. The experiment shown above tests that hypothesis, and supports it.

What is autophagy? It is a normal process for cleaning up unwanted cell materials. The word literally means self-eating. But the tumors here have hijacked the autophagy system for their own benefit. They have directed the autophagy system to remove the components that cells use to present tumor antigens to the immune system. The tumors are now invisible to the immune system; simply unblocking it (with ICB therapy) doesn't help. It is necessary to also unblock the presentation of tumor antigens, and that means blocking autophagy; that is what the CQ does.

The work here is with a model system: pieces of tumor implanted into mice. The work seems to have provided a clue about how these tumors work, and what might be done about them. But real tumors are different, and human cancer is often different than mouse cancer. There is no claim that the work offers a cure, but it does offer a clue that can be followed up.

There have already been hints that CQ is of some benefit in the treatment of pancreatic cancer. The current work provides a basis for testing that further, in the context of ICB.

News story: Pancreatic cancer cells hijack basic cell mechanism to evade immunotherapy. (Medical Xpress (NYU), April 23, 2020.)

* News story accompanying the article: Pancreatic cancer: Hidden in plain sight -- Pancreatic cancer does not respond to certain anticancer treatments that boost immune responses. A mechanism active in tumour cells that contributes to this evasion of immune targeting has been uncovered. (A Maitra, Nature 581:34, May 7, 2020.)
* The article: Autophagy promotes immune evasion of pancreatic cancer by degrading MHC-I. (K Yamamoto et al, Nature 581:100, May 7, 2020.)

Previous post on pancreatic cancer: Role of neoantigens in surviving pancreatic cancer? (February 4, 2018).

More on cancer immunotherapy:
* Can fecal transplantation be useful in treating cancer? (April 27, 2021).
* Predicting who will respond to cancer immunotherapy: role of high mutation rate? (October 6, 2017).

A post about autophagy: An "antidote" for Huntington's disease? (February 29, 2020). In this case, scientists made use of the autophagy system to remove a disease-causing protein.

More about the pancreas: Making a functional mouse pancreas in a rat (February 17, 2017).

My page for Biotechnology in the News (BITN) -- Other topics includes a section on Cancer. It includes an extensive list of relevant Musings posts.

July 29, 2020

Rise of the Roman Empire: role of an Alaskan volcano?

July 28, 2020

This post is based on a recent scientific article about a volcano in the Aleutian Islands of Alaska. It starts by noting the assassination of Julius Caesar, in the year 44 BCE.

The first figure sets the stage...

The date bar across the top is for all parts of the figure. Part A shows some historical events, including the Ides of March in 44 BCE, the date of the assassination of Julius Caesar. It also notes one volcanic eruption and some food shortages and such shortly thereafter. Nothing important for us in Part A for now. Parts B and C show summer temperature profiles for two regions of the world. The locations are quite far apart, but both show a distinct decline in about 43 BCE.    This is part of Figure 2 from the article.

That there is a distinct temperature dip at the same time in two regions that far apart suggests that there was a world-class catastrophe -- such as a major volcanic eruption. Any such catastrophe could have led to some of the other consequences shown.

The Etna eruption shown in Part A might have had local significance, but it was not a major eruption.

If we are looking for an eruption with worldwide consequences, we can look anywhere. Arctic sites are good, because of the availability of ice cores, which can be reliably dated and analyzed.

In the current work, the scientists examined six sites in the Arctic, mostly in Greenland. They looked for volcanic debris ("tephra"), and compared its composition to that from known volcanoes around the world. The following figure shows the findings from one such analysis...

The graph shows various materials, plotted by two measures of their composition: percent silica, SiO2, on the x-axis; total alkali (sodium and potassium oxides) on the y-axis. The focus is on samples from a Greenland ice core, dated to 43 BCE. Red dots. Most of the red dots cluster very close to green and purple dots, which are for authentic samples from the Okmok volcano in Alaska. The figure also shows the composition range expected for other volcanoes around the world, including Etna. The red dots from Greenland do not match any of them. GISP? Greenland Ice Sheet Project. The inset at the upper left shows a piece of the debris.    This is Figure 3 from the article.

That figure is the heart of the new work. (Most of what is in the top figure was previously known.) Modern analysis shows that there was a major volcanic eruption in the year 43 BCE, and identifies an Alaskan volcano as the source. It was one of the largest eruptions in the last 2500 years. Large enough to cause major and long-lasting climate change. Large enough to have social impact. And it occurred at what was already a time of upheaval in Rome.

That's the story. But let's add one more figure. A map, to help you visualize the situation...

News story: Alaska's volcano linked to period of extreme cold in ancient Rome -- The Okmok volcano erupted in 43 BCE. (Archaeology Wiki, June 24, 2020.)

* Commentary "accompanying" the article. (It was posted online the day after the article appeared in print, but appeared in the print journal three weeks later). The sun of Rome is set! Volcanic dust veils and their political fallout. (C Oppenheimer, PNAS 117:17470, July 28, 2020.)
* The article: Extreme climate after massive eruption of Alaska's Okmok volcano in 43 BCE and effects on the late Roman Republic and Ptolemaic Kingdom. (J R McConnell et al, PNAS 117:15443, July 7, 2020.)

Previous posts about Okmok or Julius Caesar: none (except for posts about C-section births).

Among posts about volcanoes:
* Predicting the "side-effects" of geoengineering? (September 23, 2018). Discusses effects of volcanoes on crops.
* How frequent are volcanic eruptions that are truly catastrophic? (April 10, 2018).
* VPOW (July 14, 2010).

More from Alaska: What if a seismometer was "pointed" to the skies? (January 4, 2021).

More about Arctic ice: The thorium anomaly: was the Arctic Ocean formerly a body of fresh water? (March 8, 2021).

More about the effect of dust clouds: The Great Dimming of Betelgeuse (July 24, 2021).

Solar hydrogen -- with near 100% efficiency?

July 26, 2020

Using solar energy to make hydrogen from water could be a good way to get renewable energy. In principle. Actually doing it in a practical way remains a challenge.

In a recent article, a team of scientists reports progress: making H₂ from light-driven breakdown of water with near 100% efficiency. It's a model system, instructive but not practical.

The following figure shows some of the results...

Part a (top) shows the production of H2 and O2 for three of their systems. The systems vary in the nature of the catalysts. The graph at the right is for their base case. The left-hand and middle graphs are for improved catalysts. Both give improved rates of gas production. The rate of H2 production is twice the rate of O2 production in each case, as expected. Part b (bottom) shows further data from the best of those systems. The solid black line shows the absorption spectrum of the material, based on measuring reflectance. Note that it is over a narrow range of wavelengths, near the UV-visible boundary. At the shorter wavelengths the absorbance is about 100% (right-hand y-axis). The material is effectively black at those wavelengths. The red points show the efficiency of making H2 -- specifically the EQE (left-hand y-axis). You can see that the EQE follows the spectrum, and is near 100% at the shorter wavelengths. What about those dashed lines with arrowheads? Those are just to direct you to the appropriate axis. (But it seems that the two y-axes are scaled the same.)    This is Figure 1 from the article.

What is EQE? External quantum efficiency. It is the ratio of useful electrons produced to photons reaching the cell. EQE combines two steps. One is the absorption of the photons; one is the efficiency of use of those photons that are absorbed.

That second part of the EQE is called the IQE -- the internal quantum efficiency.

An EQE near 100% requires that both of those steps be near 100% efficient. The absorption of the photons was measured; the graph shows that it is near 100%. It follows that the use of the absorbed photons, the IQE, is also near 100%.

Getting IQE anywhere near 100% is quite an achievement -- even if it is over a narrow range of the spectrum. What did the scientists do to get this improvement?

The system consists of an absorbing material plus catalysts. The three systems shown in part a vary both in how the catalysts were applied and in which catalysts were used.

The underlying photocatalyst is an aluminum-doped strontium titanate, SrTiO₃:Al. For the right-hand system, co-catalysts rhodium and chromium(III) oxide (Rh/Cr₂O₃) were included in the material. For the left-hand system, the same catalysts were applied, but this time they were deposited sequentially on the SrTiO₃:Al base. For the middle system, the best one, cobalt oxyhydroxide (CoOOH) was also deposited. The results in the top graph show that both the nature of the catalysts and how they were applied matter.

The titanate crystals used here lead to the electrons and holes migrating to different surfaces. The catalysts for the two individual reactions are at different sites. This separation of the two catalysts substantially prevents loss of electrons/holes anywhere else. The result: high efficiency use of the electrons/holes for the desired reactions.

The work here demonstrates that it is possible to efficiently use photons to make hydrogen gas from water. That establishes the principle; the reason(s) for the improvement are at least partially understood. However, this work uses only a narrow bit of the spectrum. Work must continue to extend this to the main part of the solar spectrum.

News stories:
* Solar hydrogen production: Splitting water with UV is now at almost 100% quantum efficiency. (Science Daily (Shinshu University), June 3, 2020.)
* A better way to split water molecules to produce hydrogen using sunlight. (B Yirka, Phys.org, May 28, 2020.)

* News story accompanying the article: Materials science: A model of perfection for light-activated catalysts -- Efforts to make hydrogen from water directly using sunlight have been hampered by the inefficiency of the catalysts that promote the process. A model system demonstrates that almost perfectly efficient catalysts can be made. (S Pokrant, Nature 581:386, May 28, 2020.) Recommended!
* The article: Photocatalytic water splitting with a quantum efficiency of almost unity. (T Takata et al, Nature 581:411, May 28, 2020.)

A recent post on increasing efficiency of using solar energy... Solar cells: a new record for efficiency (May 26, 2020).

More about using hydrogen as a fuel: Storing hydrogen in salts (such as potassium formate) (November 7, 2022).

There is more about energy issues on my page Internet Resources for Organic and Biochemistry under Energy resources. It includes a list of some related Musings posts.

July 22, 2020

Briefly noted...

July 22, 2020

Police issues. The July 19 post (just a bit below) on "Police training" discusses a test of a specific intervention to change police behavior. I note there that the overall issue is complex. Nature has recently provided a news feature with a useful overview of the police issues. Recommended, for perspective.
* News feature, which is freely available: What the data say about police brutality and racial bias - and which reforms might work -- Some interventions could help to reduce racism and rein in the use of unnecessary force in police work, but the evidence base is still evolving. (L Peeples, June 19, 2020. In print: Nature 583:22, July 2, 2020.) The article discussed in the post below is reference 15 of this news story.
* Direct link to that earlier post: Police training (July 19, 2020).

Police training

July 19, 2020

Recent events in the United States have focused attention on how police work. That leads to questions such as...
- What could we do to improve the police system?
- How will we know if changes are beneficial?

Of course, the problems are not new, and there has been work addressing them. A recent article provides some data on the effectiveness of a particular training program for police.

The general idea of the work is that groups of police in a major (US) urban police department were given a training course in "procedural justice". Then, data were collected on indicators of police function.

The following figure summarizes some of the findings...

The big picture from the results above, and from the article as a whole, is that the new training system led to beneficial effects. The authors note that the training program used here is practical to implement at a large scale; it involves a one-day session.

That's all good, but also leads to many questions.

What is this new training? It is called procedural justice. The idea is to emphasize the police working as part of the community. This contrasts with the common "command and control" approach. (The syllabus for the training is included in the Appendix available with the article.)

The effect seen here is small. What does that mean? Is that the best this approach can do? Or is this just the start of an implementation that can be developed further? Certainly it is reasonable that multiple changes are needed.

Are there downsides to the new training? None were reported and there is no discussion of this possibility in the article. Most things are not that simple.

And then there are the usual questions associated with any such work, questions that can only be answered by further work. For example... Is the effect seen here long-lasting? reproducible? How is at affected by local differences?

As always, one article does not lead to an answer. This article is noteworthy for its approach, and the results are encouraging. Such work should continue.

News stories. The first is from a conventional source, based on the university press release. Two are substantive analyses. And then there is even a view from across the pond.
* Police training reduced complaints and use of force against civilians. (Phys.org (Northwestern University), April 20, 2020.)
* Can Procedural Justice Training Reduce Officer Misconduct? (A Cipriano, Crime Report (Center on Media Crime and Justice, John Jay College), May 27, 2020.)
* The 3 Largest Police Forces: What Training and Oversight Look Like Today -- Status Quo Under Fire. (J Gantz, Center for Illinois Politics, June 28, 2020.)
* Procedural justice training reduces police-public conflict in Chicago. (Gazette (Law Society of Ireland), June 12, 2020.)

The article, which is freely available: Procedural justice training reduces police use of force and complaints against officers. (G Wood et al, PNAS 117:9815, May 5, 2020.)

Other posts about justice...
* Racial disparities in policing: a detailed analysis from one city (March 16, 2021).
* False memories in the courtroom (September 10, 2013).
* Justice should be blind -- and well fed (April 29, 2011).
* Truth and reconciliation (February 12, 2010).

July 15, 2020

A light-activated coating that can kill bacteria on surfaces

July 14, 2020

Much effort is spent cleaning surfaces to reduce the microbial load. What if the surfaces could clean themselves?

An approach to doing just that is to coat the surface with something that generates chemicals to kill bacteria. Light stimulates the production of the antibacterial agent. However, coatings developed so far require intense light to be effective.

A recent article reports an improvement. The coating developed here combines a dye and small clusters of gold combined with -SH groups; these active ingredients are incorporated into standard silicone material. This more complex coating kills bacteria even when exposed to ordinary room lighting.

The first figure shows the basic phenomenon...

The following figure explores how the treated surface works...

That experiment shows that the coating works by making hydrogen peroxide, a known disinfectant. What is the peroxide made from? From moisture in the air.

It was known that the dye itself, crystal violet, could be photoactivated to kill bacteria, but it required very high light intensity. The gold compound, thiolated with -SH groups, apparently serves to stabilize the dye electrons excited by the light.

Overall, the scientists have developed a coating that helps reduce bacterial loads on surfaces. It seems more practical than previous suggested coatings, under ordinary conditions. (Cost of this gold device? Not an issue. The amount of gold is actually quite small.) One can imagine this coating being of value on surfaces in a doctor's waiting room. And maybe on things such as phones and keyboards, too.

News story: New bacteria-killing light-activated coating. (L Thomas, News-Medical.Net, March 5, 2020.)

The article, which is freely available: Photobactericidal activity activated by thiolated gold nanoclusters at low flux levels of white light. (G B Hwang et al, Nature Communications 11:1207, March 5, 2020.)

Previous post about an anti-microbial coating... An antiviral coating for medical textiles (July 12, 2020). The previous post, immediately below.

Among posts involving H₂O₂:
* A hydrogel tablet for rapid water purification (October 23, 2021).
* Transparent wood (March 6, 2021).

More gold chemistry: Air pollution: progress towards a process for ammonia oxidation (April 5, 2019).

An antiviral coating for medical textiles

July 12, 2020

A recent article reports a new way to modify textiles so that they adsorb less blood and viruses. The work is done with a type of polypropylene (PP) that is used for many garments worn by medical staff.

We'll start with some results showing what was accomplished by making the modification, and then note how the scientists did it.

This figure shows two samples of the material. Untreated on the left, treated on the right. Drops of various liquids were placed on the two materials. Some drops had an added coloring, for visibility. On the right side, with the modified PP, the drops stayed where they were put. And they are labeled there. On the left, with the original PP, all the liquids soaked in.    This is Figure 2a from the article.

The general point is that the modified PP is much less wettable than the original material.

Among the liquids tested was fetal bovine serum (FBS). It was chosen to represent blood.

The next figure shows some quantitative results about how the modified material binds protein from FBS (representing blood) or two viruses.

There are six graphs. Each shows the result for the control material (left) and the treated material (right). In each case, the bar is considerably lower for the treated PP. That is, all the tests "worked": the modification reduced binding of things. The top row of graphs (orange) is for FBS. What is measured here is binding of protein from this "blood". The next two rows (green) are for two viruses. (The viruses are two strains of adenovirus. These are viruses with simple protein coats, with no lipids.) What makes this experiment of particular interest is that the materials had experienced considerable "abuse" before the tests. The results in the left-hand column are for material that had been mechanically abraded. The results in the right-hand column are for material that had been washed. In both cases, the abuse was extensive.    This is Figure 5 from the article.

The results above show that the treated PP binds less blood protein or viruses, even after considerable abuse. That is, the material is not only effective but also robust. The authors emphasize this point, as a novel aspect of their work.

What is the modification that leads to these improved properties? Teflon-coating -- as with the pans in your kitchen, but this is Teflon coating of a plastic. They start with nanoparticles of polytetrafluoroethylene (commonly called Teflon), and bind them to the polypropylene by heat treatment.

The general appearance of the material is not changed, as you can tell from the top figure. But at high resolution...

Scanning electron microscopy (SEM) images: i (left) = untreated material, ii (right) = treated material. Of course, you can't tell anything about the binding properties from the images, but you can see that the surface has been extensively roughened.    This is Figure 1b from the article.

The main claim of the article is that they have developed a way to make polypropylene fabrics, commonly used in the medical field, exceptionally repellent to water, blood and some viruses. In particular, the modified PP is robust, able to survive washing, even scrubbing. The modified material should play less role in transmitting infectious agents. And since it is robust, it would seem to have potential as a material for making reusable PPE. (PPE? That's personal protective equipment. Surely, everyone knows that by now.)

Is this really a good idea? The science seems good, as the results above illustrate. But a couple of cautions are in order. The wettability of polypropylene is a complex issue; it is common to make it more wettable. Balancing the various needs is an issue. Further, we note that the viruses studied here both have simple protein coats. Reducing the binding of such viruses is good, but we can not anticipate how other types of viruses will behave with this material.

News story: Durable, washable textile coating can repel viruses -- New research could lead to safely reusable PPE. (Science Daily (University of Pittsburgh), May 13, 2020.)

The article: Superhemophobic and Antivirofouling Coating for Mechanically Durable and Wash-Stable Medical Textiles. (A J Galante et al, ACS Applied Materials & Interfaces 12:22120, May 13, 2020.)

More about special surfaces in the medical context...
* A light-activated coating that can kill bacteria on surfaces (July 14, 2020). The next post, immediately above.
* An improved bandage, based on superhydrophobic carbon fibers (January 21, 2020).
* Using a plasma to kill norovirus (June 5, 2015).
* Shark skin inspires design of a new material to reduce bacterial growth (March 13, 2015).

Posts about anti-viral agents include... Inhibiting the TMPRSS in your nose to protect against respiratory viruses (COVID, flu) (July 11, 2022).

More polypropylene:
* Using old clothes as building materials? (February 5, 2019).
* Nanotechnology leads to the development of a superoleophobic polypropylene -- and a better shampoo bottle (November 6, 2016).

More Teflon: Purifying water using fluorinated nanopores (August 16, 2022).

July 8, 2020

Briefly noted...

July 8, 2020

What kind of music do cats prefer? They prefer music written for cats. That's according to a recent scientific article. Why would someone study cat-specific music, you wonder? Actually, for a very good reason. The work was done in the context of a veterinary clinic, to see what kind of music would lead to the cats behaving better during medical examinations or treatments.
* News story: The 'purrfect' music for calming cats. (Phys.org (from Sage, the journal publisher), February 24, 2020.) Links to the article, in the Journal of Feline Medicine and Surgery; it is freely available. It also links to the music (YouTube; 18 minutes). Suggest.. Listen to it with a cat, to increase the chance that someone likes it. Remember, it wasn't written for you.
* This item is noted on my page Internet resources: Miscellaneous in the section Art & Music (sub-section Science). It includes a list of related Musings posts.

Another possibility for the origin of ribo- and deoxyribo- nucleosides

July 5, 2020

The common view is that RNA is the primordial nucleic acid, with DNA coming later. Correspondingly, ribose-based nucleosides came first, deoxyribose-based ones came later. In fact, making deoxyribose-based nucleosides in work intended to explore prebiotic chemistry has been difficult.

A recent article reports the development of lab chemistry, under reasonable prebiotic conditions, that leads to deoxyribose-based nucleosides. Interestingly, it leads to a mixture of the two kinds of nucleosides. And that leads to the idea that the first nucleic acids might have contained both ribose and deoxyribose.

It's complicated. After all, prebiotic chemistry occurred "out there" somewhere in Nature. But the following figure shows the key steps in getting to deoxynucleosides in this new lab chemistry work...

The reaction scheme above makes deoxynucleosides equivalent to two of the modern deoxynucleosides -- the two purines, A and G.

The authors emphasize that the details are all correct: groups are at the right place and pointing in the right direction.

The big picture...
- This can be done under plausible prebiotic conditions.
- It leads to all four bases in nucleoside form, two with ribose and two with deoxyribose. dA and dI are shown above; C and U (both ribo) are already known to be made under these conditions.

That supports the idea that the first nucleic acids might have contained both ribose and deoxyribose.

What do we make of this? Well, it is all lab chemistry. We don't know how life got started. Lab work is done to explore conditions that seem plausible, given our understanding of the early Earth. The work here adds new reactions to the list of things that might plausibly have happened. Scientists can now debate whether there is any evidence to support one route over another.

News stories:
* Did Life Emerge in the "Primordial Soup" via DNA or RNA? Surprising Answer From New Research. (SciTechDaily (UK Research and Innovation), June 7, 2020.)
* Primitive genetic alphabet based on RNA and DNA -- New research suggests that early informational polymers might have been formed from DNA and RNA building blocks at the dawn of life. (Cambridge University, June 3, 2020.)

* News story accompanying the article: Origins of life: A plausible route to the first genetic alphabet -- Understanding the prebiotic origins of the nucleic acids is a long-standing challenge. The latest experiments support the idea that the first nucleic acid encoded information using a mixed 'alphabet' of RNA and DNA subunits. (K Le Vay & H Mutschler, Nature 582:33, June 4, 2020.)
* The article: Selective prebiotic formation of RNA pyrimidine and DNA purine nucleosides. (J Xu et al, Nature 582:60, June 4, 2020.)

A background post, about earlier work from the same lab: On the road to life? (May 18, 2009). The article discussed here is reference 6 of the current article.

More about getting to the first nucleic acids: A novel type of polymer -- and its possible relevance to the origin of life (March 15, 2013).

July 1, 2020

Could we treat COVID by driving it to an error catastrophe?

June 30, 2020

A recent article presents results for a new antiviral agent. The agent may be widely applicable against RNA viruses, because it has an unusual mode of action. The agent causes a high mutation rate, thus leading to what is called an error catastrophe; effectively, the virus mutates itself to death.

The article focuses on the coronaviruses, with data for the three major ones. We'll start with some results on the effectiveness of the agent, in lab culture and in mice, then show some results on the mutation rate.

The first graph shows some basic lab results for the effectiveness of the agent, called NHC, against coronaviruses in lab culture.

A good start.

The next graph tests the agent in a mouse infection.

The graph shows the weight of the mice after infection with the MERS virus at day 0. The drug is given starting at various times, as shown in the key. They range from 2 hours prior to infection ("-2") to 48 hours after infection. The treatment called "vehicle" is a negative control. The mice got something, but there was no drug in it. The graph may seem cluttered, but there are two general results. There is an "upper" set of points, at about 100% over time: no weight change. The other results show a steady decline, starting about 2 days after infection. Sort out the color coding, and you will see that the mice given the drug 2 hours before infection (red) or 12 hours after infection (dark blue) did fine. Mice given the drug starting at later times showed about the same weight loss as the "vehicle" control.

The full figure shows a lot of measurements on these mice, including lung damage and virus production; the graph shown here is representative. Another figure shows a similar experiment with the SARS virus (SARS-1 in this case); again, the results are similar.    This is Figure 7A from the article.

Such experiments suggest that the drug is beneficial in coronavirus infections of mice. Benefit may occur if the drug is given prophylactically (before exposure) or early in the infection.

As we noted at the top, what makes this drug of particular interest is that it works by increasing the mutation rate. The next graph shows some results on that point.

Most mutations are harmful; many are immediately lethal. It is a real problem. DNA replication always has one or more error-correction mechanisms associated with it. Organisms with RNA genomes (some viruses) generally lack proofreading, and are limited to quite small genomes. The coronaviruses do have some proofreading, and indeed they have the largest genomes known for RNA viruses. The general picture is that organisms live close to the edge of how many mutations they can handle.

The drug NHC is a nucleoside used to make RNA. A sloppy nucleoside. It base pairs, but poorly, and that leads to a high mutation rate. Growing with this nucleoside, it doesn't take long before every virus genome contains a lethal mutation. That's what is meant by the genetic term "error catastrophe".

Comments...

There are two forms of the drug, both noted in the article. NHC (also called EIDD-1931) is the nucleoside itself. For use in animals (as in the second figure above), EIDD-2801 is used. That is a derivative of NHC, suitable for oral administration. Within the body, it is hydrolyzed to NHC.

NHC is β-D-N⁴-hydroxycytidine. EIDD-2801 is its 5'-isopropyl ester.

The second experiment above suggests that treatment must start very early. The details may be exaggerated by the way virus infections progress in mice. The authors suspect that treatment within the first week of a human infection would be useful. Note that NHC is a drug easily administered (oral pill); the hope is that it will be suitable for treatment of those who have been exposed to the virus, before symptoms. Of course, that remains to be tested.

Previous lab work with this drug has suggested it is widely effective against RNA viruses.

The drug will be entering into clinical trials in humans.

News stories:
* Experimental Drug Has Broad Spectrum Antiviral Activity against Multiple Coronaviruses. (Sci.News, April 9, 2020.)
* An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 in human airway epithelial cell cultures and multiple coronaviruses in mice. (AIRInforma, May 2, 2020.) This site is also available in Italian.

The article, which may be freely available: An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 in human airway epithelial cell cultures and multiple coronaviruses in mice. (T P Sheahan et al, Science Translational Medicine 12:eabb5883, April 29, 2020.)

More about this drug: Briefly noted... The Merck drug for COVID (October 27, 2021).

Another way to disrupt the viral genome: Targeted degradation of the viral genome as a treatment for COVID? (March 13, 2022).

Other posts about anti-viral agents include...
* Inhibiting the TMPRSS in your nose to protect against respiratory viruses (COVID, flu) (July 11, 2022).
* Baloxavir marboxil: a new type of anti-influenza drug (September 14, 2018).

Previous post about catastrophes: How frequent are volcanic eruptions that are truly catastrophic? (April 10, 2018).

The page for BITN -- Other topics includes a section on SARS, MERS (coronaviruses). That section now includes COVID-19. It lists Musings posts on coronaviruses.

How tau gets around

June 28, 2020

Tau is a protein in the brain -- a protein involved in various neurodegenerative diseases, including Alzheimer's disease. There are various forms of tau. Normal tau is a normal part of the brain. Altered forms of tau -- in particular, aggregated forms -- are toxic, and may induce further aggregation. (In some ways, tau behaves like a prion.)

A recent article uncovers how altered forms of tau move between cells.

The first figure shows that a protein called LRP1 is important for uptake of tau by cells.

In each part, three types of cells were tested for their ability to take up one or another altered tau. One of the three cell types had been altered using CRISPR to eliminate functional LRP1. The others were WT (wild-type), and a control cell type, which had been given a mock treatment with CRISPR (NT = not targeted). Each graph shows uptake (y-axis) of the tau for the three cell types (labeled at the bottom). Start with the graph to the left, labeled "oligomer". The result for WT is set to 100%. The result for "LRP1 sgRNA", where LRP1 has been disrupted, is very low. (And the result for "NT sgRNA", the control that should be like WT, is like WT.)

The graph to the right is for a similar experiment, with a different form of aggregated tau, called "sonicated fibril". The results are qualitatively similar, though the effect of disrupting LRP1 is less dramatic. sgRNA is the RNA used to guide CRISPR. LRP1 sgRNA is targeted to that gene. NT sgRNA gives a mock CRISPR treatment.    This is Figure 1c from the article.

The results above implicate LRP1 in the transport of these altered forms of tau into cells.

The next figure is logically similar, but in vivo, in mice.

Quick observation... The photo at the right is different. That is the one with LRP1 turned off. The photos show tau; turning off LRP1 reduces tau, to about zero. So, what did the scientists do here? The measurement is of tau, by staining brain slices -- cortex, in this case. The three photos are for mice with various treatments, analogous to those of the top figure. The key treatment is for the right-hand case; the mice were injected with an RNA designed to target and turn off the LRP1 gene. For the left-hand case, the mice were injected with the buffer (PBS = phosphate-buffered saline). For the middle case, they were injected with a non-targeted RNA; "scrambled" means it has the same bases as the LRP1-targeted RNA, but in a random order. The scale bars are 20 micrometers. That is the essence of the experiment, but technically it was more complicated. For example... The intent was to measure tau that got into a cell by spreading from another cell, not tau that might be produced within the cell. The measurement of tau per se can't tell the difference. But... They designed the original tau gene so that it produced both tau and GFP (green fluorescent protein). Cells that contained tau that it made would also show GFP. Cells that got tau by spreading would be GFP-negative.    This is Figure 4i from the article.

Overall, the work shows that LRP1 has a role in the cellular uptake of altered (aggregated) forms of tau. This can be shown both in lab-grown cells and in mouse brains.

That represents progress in our understanding of tau, and perhaps therefore of tauopathies (diseases involving tau).

How did LRP1 come to the scientists' attention? They suspected that tau transport might be due to a member of the family of low-density-lipoprotein receptors; they tested them one-by-one.

The current work does not directly examine disease, and does not show that reduction of LRP1 is safe.

News stories:
* Understanding how protein tau moves between neurons yields insight into treatments for neurodegenerative diseases. (Medical Xpress (S Fernandez, University of California - Santa Barbara), April 2, 2020.)
* Tau Receptor Identified on Cell Surface. (T Fagan, Alzforum, March 7, 2020.) This is based on a presentation of the work at a conference in February, but it notes the article.

* News story accompanying the article: Neurodegeneration: Neuronal gatekeeper for dementia protein. (K Deinhardt, Nature 580:326, April 16, 2020.)
* The article: LRP1 is a master regulator of tau uptake and spread. (J N Rauch et al, Nature 580:381, April 16, 2020.)

Posts about tau include:
* Brain imaging to detect and distinguish tauopathies, including Alzheimer's disease (January 18, 2021).
* A mutation in ApoE that protects against Alzheimer's disease? (February 22, 2020). Is there any connection between the current work and this recent report of a mutation that seems to affect tau function? At this point, it is an open -- but intriguing -- question.
* Alzheimer's disease: a role for inflammation? (January 18, 2020).
* Traumatic brain injury: long term effects? (October 8, 2019). Yes, that is a tauopathy, too.
* Alzheimer's disease: What is the role of ApoE? (November 6, 2017). A post that includes the term tauopathy.
* Should τ replace π? (July 1, 2011). A different tau.

My page for Biotechnology in the News (BITN) -- Other topics includes a section on Alzheimer's disease. It includes a list of related Musings posts.

For some background on GFP: Nobel prizes (October 8, 2008). Links to more.

June 24, 2020

Briefly noted...

June 24, 2020

1. Contact tracing: ethical guidelines. Contact tracing can be a valuable tool for dealing with communicable diseases, and it is considered important for dealing with COVID-19. It's an old tool, but now with high-tech versions -- which offer improved coverage and raise more ethical questions. A recent "comment" article in Nature discusses this, and suggests some criteria.
* "Comment" story: Ethical guidelines for COVID-19 tracing apps -- Protect privacy, equality and fairness in digital contact tracing with these key questions. (J Morley et al, Nature, May 28, 2020. In print: Nature 582:29, June 4, 2020.)

2. COVID-19 in pets? A question of practical interest to many people. We have heard anecdotes, but there is little systematic data. Now we have a scientific article studying the replication and transmission of the SARS-2 virus in cats and dogs (and a few other animals). The short answer is that cats support the virus rather well (though they typically don't get sick from it). Transmission? Airborne transmission between cats was shown. Beyond that, there is little information; for now, it seems more likely that cats will get it from people than transmit it to people, but I'd take that as very preliminary. Dogs seem to support the virus poorly. (Beyond those... ferrets (common lab animal) support it well; chickens, ducks and pigs, not at all.) The news stories give a good sense of what was done and the limitations.
* News stories:
- How susceptible are domestic animals to SARS-CoV-2? (T Meštrović, News-Medical.Net, May 31 2020.)
- Review of "Susceptibility of ferrets, cats, dogs, and other domesticated animals to SARS-coronavirus 2" (pdf file). (Public Health Ontario, April 12, 2020. Now archive.) Links only to a preprint.
* Direct link to the article: Susceptibility of ferrets, cats, dogs, and other domesticated animals to SARS-coronavirus 2. (J Shi et al, Science 368:1016, May 29, 2020.)

Electronic monitoring of plant health; it might even allow an injured plant to call a doctor

June 21, 2020

People wear various devices to monitor their health. Whether it is blood sugar level or simply pulse, it's an area of increasing activity.

Use of such monitoring for plants is much less developed. A recent article reports progress.

The idea is that injured plants produce hydrogen peroxide, H₂O₂. Simple assays for H₂O₂ are common; the new work developed an H₂O₂-sensor suitable for wearing by a plant.

The sensor is based on a type of carbon nanotube, which has been modified so that the presence of H₂O₂ affects its spectrum, in this case its fluorescence spectrum.

The first figure shows the sensor response...

Two spectra are shown: with (red) and without (blue) H2O2. You can see that the peroxide reduced (quenched) the fluorescence. The difference between the two curves is a measure of the amount of H2O2. Another part of the full figure (Figure 1c) shows a dose response curve; it is quite good. SWNT = single-walled carbon nanotube. The prefix G is for guanine. Yes, the DNA base -- a key part of the sensor.    This is part of Figure 1b from the article.

The next figure shows an example of the use of the assay...

In this work, the sensor is attached to a plant. The sensor is observed using a laser; the signal is recorded with a camera. H2O2 is measured (y-axis) over time (x-axis). In part b (top), you can see that the curve is flat over most of the time, but dips for one region. Why? Because the plant had been wounded, at the time marked with a black arrow. The wounding caused an increase in H2O2 -- and therefore a lower signal. What is the y-axis scale here? It is based on the response shown in the top figure. It is the normalized response, where the baseline level of peroxide is set to 1. The presence of the peroxide leads to a lower signal; it's just shown differently in the two figures. The top figure shows the raw data; the bottom figure shows it in a way that makes it easier to see the peroxide level over time. Further, the top figure shows the spectral information; the bottom figure shows the overall camera response.

Part d (bottom)? Same idea, but the plant carried a mutation in the peroxide signaling system. No signal. The plant tested is Arabidopsis thaliana. The top frame is labeled WT, for wild type. The bottom frame is labeled with the designation of the particular mutation used.    This is part of Figure 3 from the article.

So, the scientists can observe a response to wounding, using a "simple" device. And they have at least a general understanding of how it works, at the level of plant physiology.

Development of the sensor system, suitable for use with a plant, was a major achievement.

Several species of plants tested all gave responses. The details varied, reflecting different signaling parameters, but the general notion of remote detection of hydrogen peroxide seems widely applicable. Since the test does not require any special plant strains, it can be easily tried for any plant of interest.

Also note that what is measured is not the wounding itself, but a consequence of the wounding. Therefore, it works for other stresses that produce H₂O₂. In the article, the scientists report some testing with excessive heat and light; those stresses, too, generate responses that can be measured with their sensor.

The authors suggest that the sensor system they have developed could be useful in research. But they also note that, in principle, it could be used to monitor health of plants in the field. If it was automated properly, using a smartphone to record the signal, it could effectively allow a plant to call a doctor if it were sick.

Are the nanotube sensors safe for the plants? The authors have not found any problems, but note that effects of carbon nanotubes on plants have been found in other work.

News stories:
* SMART and MIT develop nanosensors for real-time plant health monitoring -- New nanobionic approach allows scientists to study the communication within plants, providing valuable insights to improve crop yields. (EurekAlert! (SMART), April 16, 2020.)
* Nanosensor can alert a smartphone when plants are stressed -- Carbon nanotubes embedded in leaves detect chemical signals that are produced when a plant is damaged. (Science Daily (MIT), April 15, 2020.)

The article: Real-time detection of wound-induced H₂O₂ signalling waves in plants with optical nanosensors. (T T S Lew et al, Nature Plants 6:404, April 2020.)

More about signaling in plants: Underground messaging between bean plants (July 29, 2013).

and maybe... The sounds that plants make (April 10, 2023).

Another measurement based on hydrogen peroxide... A simpler assay for detecting low levels of HIV, using gold nanoparticles (January 3, 2013).

Another monitoring device: A smart insulin patch that rapidly responds to glucose level (October 26, 2015).

Next post about plant wounds: If a bee visits a plant and there are no flowers, can the bee place an order? (June 23, 2020). The next post, immediately above.

More about fluorescence and quenching: How to get common fluorescent dyes to work in the solid state (September 4, 2020).

Among other posts about using Arabidopsis... Cauliflower math (July 26, 2021).

Posts about carbon nanotubes are listed on my page Introduction to Organic and Biochemistry -- Internet resources in the section on Aromatic compounds.

June 17, 2020

Does post-exposure administration of hydroxychloroquine prevent Covid-19? A clinical trial

June 16, 2020

It has become so politicized! Sometimes it is not even clear what the question is.

Is hydroxychloroquine (HCQ) useful against COVID-19? First, there are at least two questions one might ask here. One is whether it is useful for treating those in a hospital with severe COVID-19. Another is whether it is useful in preventing the disease in those who may have been exposed.

A new article addresses the second question. It reports what is apparently the first placebo-controlled clinical trial of HCQ for COVID prophylaxis. As so often, it quickly got headline coverage -- with a one line summary. But this is a real test; it has real data and real limitations. Let's look at some of it.

As I write this [original version], the article is "in press". That means it has undergone peer review, but not final editorial polishing. Peer review is a standard key step in publishing scientific articles, but by no means assures that the article is correct. (The final published article is indicated below. The article seems unchanged, at least for key points.)

Here is the main data summary from the article...

A few more numbers...

Another way to express the results is by the absolute change: the difference between the COVID incidence in the two groups. It is -2.4 percentage points. The minus sign shows that treatment group has lower incidence. The 95% confidence interval for that number is -7.0 to 2.2. That interval includes zero. This is just another way of saying that the result is not significant statistically.

Adverse events. 40% for the drug group; 17% for the placebo group. (Table 3 of the article lists them.) None were serious in either group, but some sound uncomfortable. If the drug were effective, the adverse events would probably not be a big concern.

What do we make of this?

The hypothesis underlying the trial was that the drug might prevent the development of disease in those with a significant exposure.

Do the trial results, some of which are shown above, support the use of HCQ for COVID prophylaxis? No.

Do the results disprove that there is a beneficial effect? No. The conclusions are statistical; they make benefit unlikely, but such a test cannot disprove benefit. (The test was planned to be large enough that it could show a 50% benefit. That is, they were not looking for smaller effects.)

Is it possible that the sample population tested here is heterogeneous, and that there was benefit for some sub-group? (Sub-groups of possible interest might be by sex, race, or a specific genetic feature.) To the extent examined, no such effect was seen. (And note that the sample size was even smaller for any sub-group.)

Is it possible that the drug would have provided benefit if used with a different dosage or treatment schedule? That wasn't tested.

Might it be reasonable for an individual, in consultation with their doctor and with appropriate medical supervision, take the drug for prophylaxis? That is a private matter for the individual and doctor.

The discussion here gives an idea of how one looks at the outcome of a clinical trial. There may appear to be a yes/no answer, but the reality is more complex. The current study has many limitations, as the authors note. It is a useful study, but cannot claim to be a final answer.

News stories:
* Hydroxychloroquine is Ineffective for Post-Exposure Prophylaxis. (A Swaminathan, REBEL EM, June 8, 2020.)
* Randomized trial finds hydroxychloroquine did not prevent COVID-19. (C Dall, CIDRAP, June 4, 2020.)
* Hydroxychloroquine as Postexposure Prophylaxis for COVID-19: Clinical Takeaways. (A Ward, ContagionLive, June 4, 2020.) Interview with one of the authors.

Both of the following are temporarily freely available at the journal web site.
* Editoiral accompanying the article: Hydroxychloroquine for the Prevention of Covid-19 - Searching for Evidence. (M S Cohen, New England Journal of Medicine 383:585, August 6, 2020.)
* The article: A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19. (D R Boulware et al, New England Journal of Medicine 383:517, August 6, 2020.)

Previous COVID-related post: Speech droplets: Can you transmit an infection to someone by yelling "Stay healthy" at them? (June 14, 2020). This is the post immediately below.

For more about the drug:
* Briefly noted... Might the doctor's politics affect how they treat COVID? (June 7, 2023).
* Briefly noted... The infection process for the SARS-2 (COVID-19) virus (September 8, 2021).

The page for BITN -- Other topics includes a section on SARS, MERS (coronaviruses). That section includes COVID-19.

Speech droplets: Can you transmit an infection to someone by yelling "Stay healthy" at them?

June 14, 2020

When you cough or sneeze, you eject a range of droplets into the air. The bigger ones quickly fall to a surface below. The smaller ones, called aerosols, may remain in the air for extended periods, and may be carried considerable distance by air currents. And of course, these droplets may contain infectious agents.

Ordinary breathing and talking produce droplets, too. And may, therefore, transmit disease.

A pair of recent articles explores droplet production from speech.

There are no infectious agents in this work. It is about characterizing droplets. We assume that these droplets are capable of carrying infectious agents, but that is not directly addressed here.

The main experimental tool in this work was measuring light scattering. Particles, including liquid droplets, in the air scatter light; this can be measured. A person speaks, and the air in front of them is observed. There are some high-tech details, but the basic plan is simple.

The following figure shows the idea, and some results.

Start with part B, at the bottom. It is a photograph for one measurement. Each speck results from one droplet. (Some of them have moved during the exposure time, thus forming a streak in the image.) Part A (top) shows some data. Measurements were made in front of a person. The graph shows the number of flashes (droplets; y-axis) seen vs time (frame number; note x-axis labeling at both top and bottom). At three times, the person spoke, saying the words "stay healthy". The curve is shown in green during speech. The speaking led to an increase in droplets. The biggest increase came at the "th" of "healthy". (Say it; you'll see why.) The three trials were with decreasing loudness. Below the main curve is a second curve. The level is zero; the curve is offset a bit for clarity. Again, the person spoke at the times shown in green. But this time, they wore a mask -- a wet mask. No droplets. The photograph in part B is for the time point marked with a red arrow in part A.    This is Figure 1 from article 1.

The next figure addresses the lifetime of the droplets in the air...

In this experiment, the person spoke for several seconds, leading to a build-up of droplets in the air. The person stopped speaking, and the droplet count was measured over time. The red curve is for the brightest 25% of droplets. The green curve is for the rest (75%). (Brighter droplets are presumably larger, but there are some technical issues that make this more complicated.) Both curves show loss of droplets over time; the big droplets are lost faster. Note the time scale: the green curve takes nearly an hour to decay to background. The solid lines show best-fit lines for exponential decay. They start at the black arrow.    This is Figure 1A from article 2.

Overall, the work here shows that a person speaking releases droplets into the air. The details depend on what was said and how loudly. The droplets remain in the air for an extended period, on the order of minutes. Time and distance will depend on details. The droplets are, one presumes, capable of carrying infectious agents.

Comment/opinion... Seems to me this work strengthens the case for wearing a face covering (mask) -- to protect those around you. Your speech droplets linger for many minutes. It is likely that the common guidance of maintaining six feet (two meters) distancing is not sufficient.

It would also help to avoid words with 'th" in them.

News stories:
* Virus 'eminently capable' of spreading through speech: study. (Medical Xpress, May 14, 2020.)
* Droplets from Speech Can Float in Air for Eight Minutes: Study -- The experiments did not involve SARS-CoV-2, but researchers say the results support precautions to avoid possibly spreading COVID-19 by talking. (K Grens, The Scientist, May 15, 2020.) Now archived.

Two articles, from the same team of scientists...
1) Visualizing Speech-Generated Oral Fluid Droplets with Laser Light Scattering. (P Anfinrud et al, New England Journal of Medicine 382:2061, May 21, 2020.) (May be temporarily freely available.)
2) Freely available: The airborne lifetime of small speech droplets and their potential importance in SARS-CoV-2 transmission. (V Stadnytskyi et al, PNAS 117:11875, June 2, 2020.)

Videos. There is a video posted with article 1. For article 2... there are three videos available. They show the experimental set-up and some of the work. Click on reference 17 of the article. There, you probably want to check the videos in the reverse order. (The first video listed contains 85 minutes of observations!)

As a little bonus... Attached to the end of article #1 is a letter from Matthew Meselson. Yeah, the guy who showed that DNA replication is semi-conservative, back in 1958. He is still on the Harvard faculty -- has been since 1960. Last month he turned 90. Musings has discussed more recent work from Meselson's lab in the post Lesbian necrophiliacs (March 8, 2010).

* * * * *

Also see:
* Production of aerosols by the winds of the Philadelphia Orchestra (October 24, 2022).
* How water droplets damage hard surfaces (June 18, 2022).
* Spontaneous formation of hydrogen peroxide from water (October 26, 2019).
* Disease transmission by sneezing -- in wheat (July 29, 2019).
* What determines the size of liquid droplets from a sprayer? (September 21, 2018).

Previous COVID-related post: Spike D614G: An emerging mutant strain of the virus that causes COVID-19 (May 12, 2020).

Next: Does post-exposure administration of hydroxychloroquine prevent Covid-19? A clinical trial (June 16, 2020). The next post, immediately above.

The page for BITN -- Other topics includes a section on SARS, MERS (coronaviruses). That section now includes COVID-19.

June 10, 2020

Briefly noted...

June 10, 2020

How good were older climate models? A recent article looks back to a collection of climate models published since the 1970s. The big picture is that most of them had the physics about right, correctly predicting how greenhouse gases would affect the Earth temperature. They were less good at predicting the actual level of greenhouse gases; that involves human culture, not just physics. If nothing else, this is an interesting bit of history. But it is more. It tells us that the physics behind climate change predictions has been rather good dating back to 1970. And evaluation of the weaknesses of older models is informative.
* News story: Early climate modelers got global warming right, new report finds. (R Sanders, University of California, Berkeley, December 4, 2019.) The press release from the lead institution. Links to the article. If you want a range of stories about the article, try a search using the article title ("Evaluating the Performance of Past Climate Model Projections"). (The article itself may be freely available, though it is not clear why. As always, if you want a copy, a good approach is to put the title into Google Scholar, and see what comes up.)

Effect of lockdowns on air pollution: it's not simple

June 7, 2020

It seems simple... Human activity causes air pollution. Reduce that activity, and we will have less air pollution. The COVID pandemic led to a reduction in human activity around the world. Indeed, people have noted reductions in air pollution.

A new article provides an interesting example -- one that shows it may not all be that simple. It is based on detailed analysis of a set of air pollutants over a region of northern China for the first two months of this year. The first month is just before the COVID-induced lockdown; the second month is just after the lockdown began.

Here are some of the data...

The big picture is that the levels of some pollutants decreased after the lockdown, but the level of one increased.

There is an explanation... Pollutants such as PM and NO₂ are indeed enhanced by human activity; reduced human activity leads to lower levels. However, ozone is different. The major source of ozone is atmospheric chemistry, largely unrelated to human activity. But the destruction of ozone is enhanced by NO₂. Therefore, reduced levels of NO₂ lead to higher levels of ozone.

This effect of NO₂ on ozone has been seen before. Success in reducing NO₂ pollution has led to increased ozone levels.

Pollution can be complicated -- at various levels. Not all air pollution is caused by human activity. And pollutants interact.

Caution... Graphs such as those above show correlations. It is up to us to understand what the correlations mean. There is no certainty that the only cause of the observed effects is the lockdown. The authors discuss some of the possible confounding factors.

We also note that the connection between nitrogen oxides (collectively, NO_x) and ozone is complex. Nitrogen oxides play roles in both the formation and destruction of O₃, depending on the conditions. During colder weather, when this study was conducted, destruction is the major effect.

News story: COVID-19 lockdowns significantly impacting global air quality. (American Geophysical Union, May 11, 2020.) This news story is about two articles, including the one discussed in this post.

The article, which is freely available: The Response in Air Quality to the Reduction of Chinese Economic Activities during the COVID-19 Outbreak. (X Shi & G P Brasseur, Geophysical Research Letters 47:e2020GL088070, June 16, 2020.)

Among many posts on air pollution...
* The importance of HPMTF in the atmosphere (June 9, 2020). The next post, immediately above.
* Indoor air pollution: is ventilation effective? (March 24, 2020).
* Geoengineering: the advantage of putting limestone in the atmosphere (January 20, 2017).
* A major algal bloom associated with the dinosaur extinction event? (May 13, 2016).

June 3, 2020

A Cretaceous dinosaur the size of a tiny bird?

June 2, 2020

Here is the sample of interest, from a recent article...

The scientists consider it a dinosaur, which they have named Oculudentavis khaungraae. It is the smallest known dinosaur. Aspects of the specimen, such as the presence of many teeth, indicate it is not like a modern bird.

The following figure helps put the size in context...

The graph plots the size of the eye ("orbit"; y-axis) vs the skull length (x-axis) for a collection of birds. Note the log-log scale, and remember that 1 on this scale means 101 = 10 millimeters (= 1 cm). The red square at the lower left of the graph is for this newly discovered specimen. It fits the trend line for birds quite well. There are also skull drawings for Mellisuga minima (vervain hummingbird) and Gallus gallus (chicken). The colors of the data points (squares for these) correspond to the colors of the labels on the skull. The scale bar at the lower left is for the three skull drawings; it is 10 mm.    This is Figure 2 from the article.

The sample, as you may guess from the top picture, is in amber. That has allowed for an unusual degree of preservation of detail.

Study of ancient remains found in amber is now common. The protective environment within the amber allows preservation of detail that would be lost in ordinary fossil formation. The amber pieces are typically small. Finding insects is perhaps most common. Finding a significant piece of a dinosaur is unusual.

It is now widely accepted that birds evolved from dinosaurs, but the story is quite incomplete. Finding a dinosaur of this size and age adds another piece of the puzzle.

Following publication, some experts have suggested that the specimen is not actually a dinosaur. It may, instead, be a lizard. This is noted in the Everything Dinosaur news story, listed below.

The specimen is of interest in any case. But whether it represents a miniaturized dinosaur is open for further work.

News stories:
* New Hummingbird-Sized Dinosaur Identified from Skull Trapped in Amber. (C Q Choi, Inside Science (from the American Institute of Physics), March 11, 2020.)
* Hummingbird-sized Dinosaur from Burmese Amber -- Oculudentavis khaungraae - Tiny Fossil Skull Could Represent the Smallest Dinosaur. (Everything Dinosaur, March 11, 2020.) Includes extensive discussion of the possibility that the specimen is a lizard, not a dinosaur.

* News story accompanying the article: Palaeontology: Tiny fossil sheds light on miniaturization of birds -- A tiny skull trapped in 99-million-year-old amber suggests that some of the earliest birds evolved to become miniature. The fossil illustrates how ancient amber can act as a window into the distant past. (R B J Benson, Nature 579:199, March 12, 2020.)
* The article: Hummingbird-sized dinosaur from the Cretaceous period of Myanmar. (L Xing et al, Nature 579:245, March 12, 2020.)

A post on the bird-dinosaur connection: How the birds survived the extinction of the other dinosaurs, why birds don't have teeth, and how those two points are related (July 30, 2016). Links to more.

Another specimen from amber: Bacteria found in rectum of old flea (October 16, 2015).

Previous post analyzing a dinosaur fossil: A claim of finding dinosaur DNA (May 31, 2020). The preceding post, immediately below.

May 27, 2020

Briefly noted... X-chromosome inactivation -- more complex than it seems.

May 27, 2020

In humans (and in mammals generally), females have two X chromosomes, but males have only one. That raises the issue of whether females make twice as much products from X as males do. The basic answer has long been known: females inactivate one X chromosome in each cell. The inactive X can be easily distinguished in chromosome preparations, and the general mechanism of X-inactivation has become clear over recent decades. But the real world is more complicated than our simple idealized story. Turns out that X-inactivation is incomplete -- and varies, between individuals and over time. A recent news feature in The Scientist discusses the story of X-inactivation, with emphasis on the complexities. (Careful that you don't get bogged down with too many details. For most people, the big story is that X-inactivation is complex, and that may have implications, which are poorly understood at this point.)
* News story: Genes that Escape Silencing on the Second X Chromosome May Drive Disease -- When X-linked genes evade silencing on the "inactive" chromosome in XX cells, some protect women from diseases such as cancer, but others seem to promote conditions such as autoimmunity. (A Dance, The Scientist, March 1, 2020. In print: March issue, p 24.) Now archived.
* Also see: X-chromosome inactivation in males -- in cancer (February 6, 2023).

Solar cells: a new record for efficiency

May 26, 2020

The theoretical limit for the efficiency of a basic solar cell is about 30%. A recent article reports a solar cell with an efficiency of about 47%. They didn't violate any fundamental theory; they made it rather complex -- and interesting.

Efficiency here refers to the conversion of solar energy to electrical energy.

Here is a diagram of the cell -- simplified...

A key feature is that it has multiple layers. Now, it is not news that multi-layer solar cells have improved performance. The multi-layer structure provides multiple active sites, and allows capture of a greater portion of the solar spectrum. This cell has six active junctions. What's new here is the refinement of the details. The heart of the article is developing materials with optimal absorption energies (bandgaps) as well as optimal physical size (lattice constant) to promote the layers efficiently integrating into a single functional unit. Overall, there are 140 layers.    This is Figure 1b from the article.

Here are some results...

The graph shows efficiency vs light intensity for a range of experiments. The light source was artificial lights. Light intensity is shown here as "suns"; note the log scale. For most of the graph, efficiency increased as light intensity increased. It then decreased at higher light intensity. The highest efficiency was 47.1%, at 143 suns. At "1 sun" of light, they obtained an efficiency of almost 40%. (39.2%.) There are two lines on the graph. As noted in the key, they correspond to different degrees of resistance in the cell. The solid curve fits the data rather well. The dashed line is for 10-fold less resistance -- and predicts improved performance, with peak efficiency over 50%.    This is the bottom part of Figure 5b from the article.

Both efficiency numbers noted above, for one sun and overall (i.e., for any light intensity), are records -- by fairly small amounts. What is important is that the scientists sought and developed rational improvements. There is no claim here of a practical device. It would be expensive, with so many different materials and a complex assembly process.

(Perhaps it could be used in space applications, where small amounts could be useful and cost is not a controlling factor. Even small improvements in efficiency can lead to a lighter device, a key consideration in space.)

The work represents progress in our understanding of solar cells, and shows, in principle, how they can be developed further. The authors think that the lowering of resistance needed to get to 50% efficiency is achievable.

News stories:
* Six-junction solar cell sets two world records for efficiency. (Science Daily (DOE/NREL), April 14, 2020.)
* Six-junction III-V solar cell with 47.1% efficiency. (E Bellini, pv magazine, April 14, 2020.)

The article, which may be freely available (at least in the US): Six-junction III-V solar cells with 47.1% conversion efficiency under 143 Suns concentration. (J F Geisz et al, Nature Energy 5:326, April 2020.)

Among posts about solar cells...
* Solar hydrogen -- with near 100% efficiency? (July 26, 2020).
* Caffeine: is it good for solar cells? (May 13, 2019).
* Is solar energy a good idea, given the energy cost of making solar cells? (March 24, 2017).
* Could vibration (or loud music) improve the performance of a solar cell? (December 11, 2013).

There is more about energy issues on my page Internet Resources for Organic and Biochemistry under Energy resources. It includes a list of some related Musings posts. (You can browse or search that list for 'solar'.)

Communicating scientific uncertainty to the public

May 22, 2020

Uncertainty is fundamental. For example, if we measure something with a ruler, we might say that the length is 1.00 cm, meaning that it is closer to 1.00 than to 1.01 cm. But we don't know whether it is 1.001 cm or 1.002 cm. For scientists, recognizing -- and expressing -- the uncertainty is as important as stating the measured value. But that uncertainty can also be annoying or distracting.

When news media report measurements, they often omit the uncertainty. Is that acceptable? What if they did give the uncertainty? Would we trust the reporter (the news media) less if they told us about the uncertainty in the measurements? Would we trust the original source of the measurements less if uncertainty was (properly) reported?

A recent scientific article addresses the implications of reporting uncertainties.

The general plan is that groups of volunteers were asked to read one or another statement, then give their ratings on three criteria.

The following figure shows the ratings for one set of tests. In this case, the statements gave the number of unemployed people for the current reporting period. In some cases, the statement included a numeric range or a verbal statement that the value was approximate.

For each criterion, each person was asked to score it on a scale from 1-7 or such. The individual values are shown (a "jitter plot"). (In some cases, the score shown on the graph is the average response for two questions.) It should be sufficient for now to look at the bar heights and associated error bars (95% confidence intervals).

Part A shows how the respondents rated the uncertainty. About 4, on average, for the control statement, and about 5 or 6 for the statements that included an explicit statement about uncertainty. That is, the respondents noticed the explicit uncertainty. Part B shows the rating for "trust in number". This value went down a little when uncertainty was stated explicitly. That would seem consistent with Part A. Part C shows the rating for "trust in source". "Source" here would mean the source of the data -- in this case, the government agency producing the report. It also includes the journalists themselves. The results here show that there is little effect of stating uncertainty on our trust in the source. It does test as statistically significant for the verbal statement of uncertainty; even then, the effect is small. As I write this, we are experiencing exceptional unemployment numbers, due to the COVID pandemic. That is not relevant to the results reported above; the study was done during a time of ordinary unemployment reports.    This is Figure 1 from the article.

That's the idea. The article includes more tests, with various types of data. The general message is that we don't blame the source for stated uncertainties. It is good to report uncertainty, as part of the full story.

It's an interesting article -- starting simply with the choice of topic. It's important. And the general message, that it is ok for the media to be upfront with uncertainties, is encouraging.

There are limitations to the study, and the authors discuss some of them. There are various kinds and levels of uncertainty, and they are not all equivalent. In the case discussed above, the control group rated the uncertainty as "4", which is medium. I would guess that most people recognized the control statement as approximate, and did not think it mattered much. If so, then adding explicit statements of uncertainty perhaps doesn't matter much. My point is that this article is a useful step, but should not be taken as a final general answer.

News stories:
* Uncertainty can be reported without damaging trust - and we need that more than ever. (M Andrei, ZME Science, March 25, 2020.)
* Uncertainty about facts can be reported without damaging public trust in news: study. (Phys.org (University of Cambridge), March 23, 2020.)

The article, which is freely available: The effects of communicating uncertainty on public trust in facts and numbers. (A M van der Bles et al, PNAS 117:7672, April 7, 2020.)

More about uncertainty... What does a p value mean? Statisticians make a statement (August 6, 2016).

May 13, 2020

Spike D614G: An emerging mutant strain of the virus that causes COVID-19

May 12, 2020

Original post...This post is based on a paper posted a few days ago at a preprint server. It has not been peer-reviewed. However, the major finding seems robust -- and it may well be important. So, here it is -- and I'll watch for the article to appear in published form.

Update August 23, 2020... The article has been published, in Cell. The general thrust of the article is not changed, but there is more data and more support. I have listed the Cell link below, in the usual place. Both figures shown below have been replaced with more extensive data. I have not made any substantive changes to the body of the post.

The main point of the article is that a mutant strain of the SARS-2 virus (which causes COVID-19) has appeared, and has become the predominant strain most everywhere over a few weeks. The new strain may be more easily transmitted, though that has not been shown directly. It may have other implications, too.

The mutation the scientists focus on is in the spike protein of the virus particle; that protein plays a key role in attaching the virus to the host cell. The mutation is D614G. That means that the amino acid D normally present at site 614 has been replaced by G. D = aspartic acid; G = glycine. That is, the mutation involves a significant change in both the charge and size of the amino acid side chain.

The following table is a simple, global summary. It is based on viral genome sequences that were reported at various times from labs around the world. The table shows the frequency of each amino acid at site 614 for four different dates. The final column (right-hand; blue) shows the fraction of G.

The table shows that the fraction ("fxn") of virus sequences reported with the mutant amino acid G increased over time. It is very low in the first report, and over half, globally, six weeks later. There is an error in the first row of the table. The D and G values do not give the fraction of G that is shown. I am fairly sure that the fraction is correct. It may be simply that the two values were switched. (Another table shows, for pre-March: D = 640, G = 71; fxn G = 0.099. That is in Figure 2A.)    This is part of Figure 1 from the [preprint] article.

The following figure shows the results for two continents and selected areas within them.

Overall, the data show that a new virus strain has emerged, and become the major strain.

What does the mutation do? There is no actual data on what it does. However, the mutation is a significant amino acid change in a protein important for the infection process. Computer analysis of the protein structure suggests that the mutation could have a significant effect, but there is no direct evidence for now.

How strong is the conclusion that the mutation enhances virus transmission? At this point, it is a correlation. The mutation clearly has increased in frequency, and has done so as the disease intensity has increased. Further, the nature of the mutation makes an effect on transmission plausible. But there is no direct experimental evidence to show that it is the specific mutation studied that causes the effect seen. The article analyzes available genome data, and offers a hypothesis -- one that needs to be tested. The analysis tools used here are important in being able to reveal the mutation as a candidate, and the consequences in this case are potentially important. The analysis system will continue to monitor the virus.

Does the mutation affect severity of the disease (as well as its frequency)? The article contains limited data on this point. It includes an analysis from one large hospital system. The data show that the frequency of the mutation was about the same in patients who required hospitalization and those who did not. The frequency of the mutation was a little higher in those admitted to the ICU, but that effect did not test as significant. The authors suggest that the mutation increases the transmission of the virus and therefore the number of cases, but does not affect disease severity. This should be taken as very tentative.

When and where did the mutation arise? That cannot be resolved with the available data. It is likely that the specific mutation arose more than once, but that one specific occurrence is the one that is the basis of the new strain. There is some evidence that the mutation may have occurred in China, but it is also likely that the new strain arose in Europe, probably during February. That is, it may be that the mutation occurred in a virus strain in China, but that strain did not lead to the current mutant strain. There are various possibilities consistent with the data at hand.

Other implications? Since the spike protein is central to the infection process, it is a prime target for vaccines. Any change in the spike protein could have implications for a vaccine. There is no specific prediction beyond that; it just needs to be tested. Importantly, this point holds regardless of whether the mutation is making the virus more transmissible.

Similarly, the change in the virus could allow re-infection. A person immune to the original strain may not have immunity to the new strain. Again, the article does not show that this is a problem. Rather, it alerts us to a change that might be a problem.

The article documents a change in the virus that may well be important. That part of the work seems solid, even while we work out what the actual effects are. The article has been criticized for over-emphasizing claims about effects, but simply documenting the mutation is important. (In fact, within the main body of the article, the distinction between what is suggested as a possibility and what is shown is generally quite clear.)

News stories:
* Covid-19: Does Mutation Increase SARS-CoV-2 Transmissibility? (M Smith, Physician's Weekly, May 7, 2020.)
* We don't know yet whether a mutation has made SARS-CoV-2 more infectious -- A mutation in the virus seems to be getting more common, but we don't know why. (J Timmer, Ars Technica, May 6, 2020.) A good news story, emphasizing the uncertainties. Science stories are always incomplete; discussing an article prior to peer review adds to that. Scientists -- and publishers -- are rushing to get information out about this important medical event. The article here provides evidence for a new form of the virus, one with a plausible connection to how the virus has behaved. The article opens the story, which needs to be followed up. But it is easy, in our enthusiasm or haste, to make hypotheses sound like conclusions.

The article, which is freely available -- as a preprint: Spike mutation pipeline reveals the emergence of a more transmissible form of SARS-CoV-2. (B Korber et al, BioRxiv, May 5, 2020 for version 2.) Check that you get the most recent version; watch for a note at the top that a more recent version is available. Some links, such as the one here, do not specify version number, and will take you to the most recent version available. But some sources do link to a specific version. (An error was corrected in version 2, though it did not impact the main conclusions.)

Update August 23, 2020... The article is now published. It is freely available: Tracking Changes in SARS-CoV-2 Spike: Evidence that D614G Increases Infectivity of the COVID-19 Virus. (B Korber et al, Cell 182:812, August 20, 2020.)

There is more about genomes on my page Biotechnology in the News (BITN) - DNA and the genome. It includes an extensive list of related Musings posts. (Coronaviruses have RNA genomes, but the idea is the same.)

The page for BITN -- Other topics includes a section on SARS, MERS (coronaviruses). That section now includes COVID-19. The current post is the first regular Musings post on COVID-19; most items that have been "briefly noted" here have also been noted there.

Next COVID-related post: Speech droplets: Can you transmit an infection to someone by yelling "Stay healthy" at them? (June 14, 2020). This post contains no work with viruses, but is done within the context of COVID transmission.

Also see: Briefly noted... How reliable are preprints? (October 26, 2022).

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