Musings -- January 2018 to ?? (current posts)

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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Current posts -- 2018 (January - ??)
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   February 21 (Current e-mail)
   February 14    February 7    January 31    January 24    January 17    January 10    January 3

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New items

Posted since most recent e-mail; they will be announced in next e-mail, but feel free...


February 21, 2018 (Current e-mail)


CRISPR: Making specific base changes -- at the RNA level

February 20, 2018

CRISPR is often described as a tool for editing genes. However, in its familiar form, CRISPR most commonly inactivates genes. A Cas enzyme is guided by a piece of RNA to a specific site in a gene, where it cuts the gene. Subsequent repair of the cut leads to inactivation of the gene. There have been numerous technical developments to work out practical applications of the original CRISPR approach as well as variations.

A recent article on CRISPR has two novel features that we have not discussed in previous Musings posts. First, it targets RNA rather than DNA. Second, it makes a specific base change in the RNA, rather than cutting it.

We'll illustrate the new system with a specific example from the article...

Part A (left) describes the system. Part B (right) shows some results.

The header for Part A gives some background information. The work here involves a mutant gene with a disease-causing mutation from G to A at site 878. That mutation changes codon 293, which should code for tryptophan, to a stop (termination) codon.

The goal is to edit that particular A back to a G. In fact, what is actually done is to edit it to an I (inosine); I and G are equivalent in this context. That is, a codon with I is translated just as if the I were a G.

Part of the messenger RNA sequence is shown. Several A bases are numbered. One of them is colored; that is A-46, the mutant A.

Below the mRNA are three guide RNAs. Look at the first of those. It has a hairpin at the left end. The rest of it is almost entirely paired with the mRNA; pairing is shown by a vertical line between guide and message. The one exception is for that A-46. The guide RNA has a C at that position, giving an A-C mispair. That mispair targets the editing event.

The other two guide RNAs are almost the same. The only difference is that the region of pairing with the mRNA is moved slightly to the right. But the basic plan -- including the specific mispair for targeting -- is the same.


The results are shown in two ways in Part B.

The graph shows that each of the three guides resulted in about 20-40% editing at the desired site. One of them appears to be significantly better. Positioning of the guide matters.

The bar labeled NT is for a negative-control guide RNA, which is non-targeting (NT). It leads to a low, but not zero, level of editing.

The heat map shows the same results, but also shows a little more. It also shows the editing that was observed at any of the other A sites -- off-target sites. It's hard to tell from the figure, but there is a low level of editing at A-40 using the first guide.

   This is from Figure 4 of the article.


Overall, the results above show that Cas-mediated RNA editing -- to make a specific base change -- works at a significant level. Getting 20-40% editing would restore useful protein levels in many cases. The results also show that details matter, and that we must be alert for off-target effects.


Comments...

How do we get Cas to act on RNA? This is a different Cas: Cas13 (rather than the more common Cas9). Cas13 acts naturally on RNA.

How do we edit a base? The editing here uses a variant of a natural enzyme, called adenosine deaminase. That enzyme removes the amino group from base A to make base I (which, as noted, behaves just like base G for many purposes).

The enzyme is abbreviated ADAR, which stands for adenosine deaminase acting on RNA.

That is, the editor here is built from known parts. The Cas13 protein targets RNA, but has been modified here so that it does not cut it. The adenosine deaminase has been modified to partner with the Cas13 protein and its guide RNA. (Development continues... The scientists have already improved the editing enzyme to reduce off-target changes.)

Why do we want a system to edit RNA rather than DNA? One answer is that we want both; we want more tools so we have more choices. But an advantage of editing RNA is that it may be more flexible. An edit to DNA is presumably permanent; any ill effects are permanent, too. Messenger RNAs and their resulting proteins are typically shorter-lived. Repeated treatment may well be necessary, but that also means that the treatment can be tuned over time. That is probably a good tradeoff, especially for new and profound tools such as gene editing.


The work here adds more tools to the gene-editing toolbox.


News stories:
* RNA Editing Possible with CRISPR-Cas13. (R Williams, The Scientist, October 25, 2017.)
* Researchers engineer CRISPR to edit single RNA letters in human cells. (Broad Institute, October 25, 2017.) From the lead institution.

* News story previewing the article (in an earlier issue of the journal): 'Base editors' open new way to fix mutations. (J Cohen, Science 358:432, October 27, 2017.) Also discusses a recent article that reports doing a similar specific base edit in DNA.
* News story accompanying the article: Molecular biology: Enhancing the RNA engineering toolkit. (L Yang & L-L Chen, Science 358:996, November 24, 2017.)
* The article: RNA editing with CRISPR-Cas13. (D B T Cox et al, Science 358:1019, November 24, 2017.)

Previous CRISPR post: Laika, the first de-PERVed pig (October 22, 2017).

A post with a complete list of Musings posts on various gene-editing tools, including CRISPR, TALENs and ZFNs... CRISPR: an overview (February 15, 2015).



Low temperature treatment for auto exhaust?

February 18, 2018

A recent trend in automotive engineering is that engines are releasing exhaust at lower temperatures (T) than they used to. More efficient use of the fuel means that less heat is wasted. And that is creating a new problem: the catalytic converters that remove pollutants from the exhaust require high T to function properly.

There is now an official goal of achieving emissions standards at exhaust T of 150° C. That is about 100 degrees lower than before.

A recent article reports progress in developing a catalyst that will oxidize carbon monoxide, CO, in the exhaust at 150° C.

Here are some results...

The graph shows how two catalysts deal with CO as a function of T.

For simplicity, let's say that the y-axis is a measure of the rate of oxidation of CO.

You can see that one curve, to the right (orange symbols), shows that the catalyst becomes effective between 200-300 °C.

The other set of results, to the left (black, blue symbols), shows that this catalyst becomes effective between 50-150 °C. There are multiple curves here. The catalyst was tested after various amounts of use. It didn't matter much; the catalyst gave about the same results each time it was tested.

The y-axis is not a simple measure of rate. The scientists are using a flow cell system; that, of course, mimics a real auto exhaust treatment system. T is ramped up during the test. It is not clear in the article exactly how they calculate the y-axis parameter that is shown. I do think it is intended to be effectively a rate measurement.

   This is Figure 1C from the article.


Taken at face value, the results above show that the new catalyst, at the left, is effective at about 150 degrees lower T than the old one. In particular, it is very effective at the new target T of 150 °C. Further, it is reasonably effective even during a cold start.

What are these catalysts? The labels say Pt/CeO2 (old catalyst; right) and Pt/CeO2_S (new catalyst; left). Pt/CeO2 means they are based on cerium oxide, with Pt atoms on the surface. And that "_S"? It means that the catalyst was steam-treated before use: 750 °C, several hours. This "hydrothermal aging", as they call it, changes the nature of the surface and allows it to operate at lower T.

As usual for catalyst development, what the scientists did here was largely empirical. They tried various ways of making catalysts to see what works. They have only limited information about how the improvement actually works, but it seems that the steam pre-treatment stabilizes the position of the Pt atoms on the cerium oxide surface. (Similar treatment of other potential catalysts leads to various results, sometimes making them worse.)

The catalyst works at a lower T, but it also retains its activity when exposed to high T. That's important, too; sometimes, with high loads, engines operate very hot.


News story: New catalyst meets challenge of cleaning exhaust from modern engines. (Phys.org, December 14, 2017.)

The article: Activation of surface lattice oxygen in single-atom Pt/CeO2 for low-temperature CO oxidation. (L Nie et al, Science 358:1419, December 15, 2017.)

Posts about catalysts and catalyst development include...
* Making hydrocarbons -- with an enzyme that uses light energy (November 17, 2017).
* Photocatalytic paints: do they, on balance, reduce air pollution? (September 17, 2017).
* 2 + 2 = 4: Chemists finally figure it out (October 9, 2015).

More cerium oxide: A Christmas present: Using concentrated sunlight to split water and CO2 (February 18, 2011).

A post about vehicle emissions: What's the connection: ships and lightning? (October 14, 2017).



What's wrong with the flu vaccine?

February 16, 2018

Warning...Confusion ahead. This is about the flu vaccine -- and why it doesn't work very well.

You've probably heard that the vaccine doesn't work very well. You've probably heard it during the current flu season. And last flu season. Maybe each flu season -- back to about 2005.

So, the flu vaccine effectiveness (VE) dropped starting in 2005? No, it's just that was the first year anyone actually measured it. It's not a trivial matter to measure it. It's not even trivial to decide what the term means. Somehow, it should reflect effectiveness out in the real world, not just a lab measurement.

A new article reports a systematic analysis of the flu vaccine in Canada during the 2015-6 season. The big message is that the VE wasn't very good.

The details don't matter much, and some of the findings may not be well accepted. However, here is an example of the findings, so you have a sense of what people are dealing with...

The vaccine contained two main components. The VE for them turned out to be about 43% and 54%. For one of them, there was a good match between the vaccine virus and the virus that actually circulated in Canada that year. For the other, there was not a good match. The one with the good match gave the 43% VE. Now, the two VE numbers may not be significantly different, but still... don't we expect the matched vaccine to do better? Anyway, neither VE is good.

The big conclusion is that there is more to flu VE than antigenic match. The article explores other factors -- with no clear conclusions. If you read further into this work, be prepared for lots of numbers, sometimes interesting numbers, and plenty of confusion.

What to do? There are two major areas of work to improve the flu vaccine. One is to develop a universal flu vaccine -- at least one that is effective against a wide range of strains. Currently we have the annual ritual of guessing what strain to use for the vaccine, and then hoping the match is good. Sometimes it is, sometimes not; as the current work indicates, even a match does not guarantee success.

Universal -- or broad-range -- flu vaccines are in the works. Will they really work? We'll see -- eventually. There is no guarantee that a universal vaccine will solve the problems. However, it would at least allow focus on a single vaccine.

The other major area of work is to move from making flu vaccines in eggs to cell culture. Again, this is undoubtedly a good idea, but it -- alone -- may or may not affect VE.

Developing effective control of influenza remains a challenge.


A reminder... Musings does not give medical advice. This post is not intended to influence a person's choice of what to do with the flu vaccine.

It is important that scientists are analyzing the vaccine, and trying to figure out what its weaknesses are. Understanding its weaknesses is, one might expect, a key to developing better flu vaccines. Thus we focus here on the negatives because that is central to developing better vaccines. But it is a different issue than whether a person should take the current vaccine -- or not.


News story: Study identifies factors that may lower flu vaccine protection. (L Schnirring, CIDRAP, October 6, 2017.) Good overview of the work, including its uncertainties.

* Commentary accompanying the article; it may be freely available: Beyond Antigenic Match: Moving Toward Greater Understanding of Influenza Vaccine Effectiveness. (E Belongia, Journal of Infectious Diseases 216:1477, December 19, 2017.)
* The article, which is freely available: Beyond antigenic match: possible agent-host and immuno-epidemiological influences on influenza vaccine effectiveness during the 2015-16 season in Canada. (D M Skowronski et al, Journal of Infectious Diseases 216:1487, December 19, 2017.)

The day before I posted this item, the US CDC published their current estimates of the VE in the US for this flu season. I have not had time to read the article carefully, but the bottom line is clear enough... It's not very good. The article, which is freely available: Interim Estimates of 2017-18 Seasonal Influenza Vaccine Effectiveness -- United States, February 2018. (B Flannery et al, MMWR 67:180, February 16, 2018.) Those with a serious interest in the flu vaccine issue may well find the article worth reading. (E Belongia, listed above as author of the commentary, is a co-author of this article. There are no Canadian institutions listed for author affiliations.)

* * * * *

A recent post about flu vaccine problems: The nasal spray flu vaccine: it works in the UK (April 12, 2017). (From the title, it may not seem to be a problem. However... )

Posts on flu and flu vaccines are listed on the supplementary page Musings: Influenza (Swine flu).



February 14, 2018


An eye that forms an image using a mirror

February 13, 2018

The human eye has a lens, which focuses the incoming light onto the retina, where the actual light receptors are.

There is another way to focus light -- with a mirror. Is it possible that Nature discovered this, too?

A recent article provides a rather detailed analysis of the eye of the scallop Pecten maximus. This unusual eye has intrigued biologists for centuries; one reference in the article is from 1795. But only in recent decades have biologists come to understand that a mirror is a key part of the scallop eye -- and that a few other animals, invertebrate and vertebrate, also have mirrors in their eyes.

Here are some pictures. They are at increasing magnification; see the scale bars.

A photograph showing five of the eyes. There be as many as 200 eyes on such an animal.

Having trouble finding them? One is directly above the "2 mm" label, lower right. A small dark circle. The others are in a line towards the left.

   This is Figure 1B from the article.




A cross-section of an eye, showing the major structures... (i) cornea, (ii) lens, (iii) distal retina, (iv) proximal retina, (v) concave mirror.

Yes, that seems to be a rather long parts list; we'll come back to this later.

The image is taken with fluorescence microscopy, with the nuclei labeled. The dots are cell nuclei. You can see that the lens area has few cells, and that the retinas are rich in cells.

This is Figure 1C from the article. The yellow arrow (upper right) is the direction of incoming light. The red rectangle marks the region studied further.


The mirror, as seen from the top by scanning electron microscopy.

The squares are crystals of guanine (the base known from nucleic acids).

The mirror is not just a plane of guanine crystals. The crystals are stacked, in a regular spacing. It is the ordered alternation of different materials, guanine crystals and cellular fluids, that makes the mirror.

Those squares really are squares. The authors state, in the figure legend: "The crystals are 1.23 × 1.23 ± 0.08 µm (N = 20) with internal corner angles of 90.16 ± 2.78 ° (N = 28) (means ± SD)."

It must be quite a feat of biosynthesis to make these mirrors!

Some of them don't look so good. I suspect that there was considerable damage during preparation for electron microscopy, and that the authors chose good crystals to measure.

   This is Figure 2B from the article.


What about the properties of these mirrors? Some results...

The graph shows three things, each plotted against the wavelength of light (x-axis).

Start with the worst-looking curve... the rather jagged black dashed curve. It shows the reflectivity of the mirror, as measured in the lab. The reflectivity is shown on the left-hand y-axis scale. The curve shows a peak near 500 nm.

The blue curve shows the spectrum of light that the animal would typically receive (at a depth of 20 meters). For this curve, use the right-hand y-axis scale. The important observation is that the reflectivity response of the eye-mirror is similar to the spectrum of available light.

Finally, the solid black curve near the top. That is a curve the scientists have calculated for the reflectivity of the mirror. It's similar to the actual, measured curve. This suggests that the scientists have a reasonable understanding of the mirror's properties.

   This is slightly modified from Figure 3B from the article. (I removed an inset from the figure.)


We started by noting that the scallop eye uses a mirror to form an image. Then, we found that it actually contains a lens, too. The authors note that the lens is not very good. That would seem to lead to many questions, but the general answer for now is that we have no idea why this animal developed this optical system.

The picture of the eye structure, above, also shows there are two retinas. The work in the article suggests that the mirror can focus light onto both of them. It may be that the two retinas are used for different parts of the field of view.

Overall, the article presents a fascinating analysis, at multiple levels, of an unusual eye. Those interested in biology, chemistry, physics, or astronomy may enjoy browsing the article or even pursuing this topic further.


News stories:
* Understanding How Scallops View the World. (Inside Science (American Institute of Physics), November 30, 2017.)
* Scallops Have Eyes, and Each One Builds a Beautiful Living Mirror. (E Yong, Atlantic, November 30, 2017.)
* The Scallop Sees With Space-Age Eyes - Hundreds of Them. (C Zimmer, New York Times, November 30, 2017.)

The article: The image-forming mirror in the eye of the scallop. (B A Palmer et al, Science 358:1172, December 1, 2017.)

Other posts on the diversity of animal eyes include...
* A see-shell story (February 21, 2016).
* Where are the eyes? (August 19, 2011).
* How many eyes does it have? (March 12, 2010).

And even one about a non-animal... Is the warnowiid ocelloid really an eye? (October 12, 2015).

For more mirrors... Could we block seismic waves from earthquakes? (June 23, 2014).

Squares are not common in biology, but another example is included on my page Unusual microbes: Square bacteria.



When did mammals take on daylight?

February 11, 2018

The dominant large animals are now the mammals. But until about 66 million years ago the dinosaurs played that role.

Mammals were around back then, they just weren't dominant. They were small, often underground -- and nocturnal. Being nocturnal presumably helped them avoid getting eaten by the big ones.

We need some terms, to describe when an animal is active. Unfortunately, a couple of the terms are not common, so ...
- Nocturnal: active mainly at night.
- Cathemeral: no particular daily rhythm; may be active day or night.
- Diurnal: Active mainly during daytime.

In the modern world, we are diurnal, as are many of our common mammals. What happened? There has long been a hypothesis that mammals emerged to dominance after the dinosaurs left -- making it safe. (More specifically, it was the non-avian dinosaurs that left.) It could well be that mammals also began to explore daytime on the same time scale.

Evidence? Not much. It's hard to tell whether a fossil animal was nocturnal or diurnal; skeletal features are not a reliable indicator of day-use preferences.

A recent article provides some evidence on the matter. Look at the following graph...

The graph shows the number of lineages of mammals with various life styles over time.

The life styles are the three we listed above.

The x-axis scale is shown at the top; the scale is in Ma -- millions of years ago. Of particular interest is the vertical red-dashed line, labeled K-Pg, at about 65 Ma. That is the Cretaceous-Palaeogene mass extinction event.

The pattern is clear: Before the K-Pg line, all mammals were nocturnal. Cathemeral mammals began to appear at about the time of the dinosaur extinction, with diurnal mammals to follow.

The blue and green regions of the time scale are for the Jurassic and Cretaceous periods, respectively.

   This is Figure 3b from the article.


What is the basis of the graph? We have already noted that fossils are not reliably informative on the issue. What the scientists did here was to collect information about the day-use preferences of 2,415 modern mammals. They then made a phylogenetic analysis, focusing on the character at hand. It leads to a best estimate of when new day-use traits developed in mammalian lineages.

The graph shows a correlation. It does not -- cannot -- show causality. In fact, a second analysis in the article, with somewhat different assumptions, shows the emergence of cathemeral mammals slightly before the dinosaur extinction. In that case, it is still plausible that the dinosaur extinction allowed for a major expansion of mammals using daylight. In any case, the article is an interesting exploration of mammal history, with a focus on how we use the day.


News story: Mammals switched to daytime activity after dinosaur extinction. (Phys.org, November 6, 2017.)

The article: Temporal niche expansion in mammals from a nocturnal ancestor after dinosaur extinction. (R Maor et al, Nature Ecology & Evolution 1:1889, December 2017.) Check Google Scholar for a freely available copy. What's available there includes a preprint at BioRxiv.

A post about a nocturnal monkey: Monogamy (January 30, 2013).

Most recent post on dinosaur extinction: 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.



Is Mars wetter than Earth -- underground?

February 9, 2018

The headline was Martian water stored underground. And the following graph was prominent...

The y-axis is the water content of the rocks, and the two curves are clearly labeled Earth and Mars.

The Mars curve is always higher. The Mars rocks always have more water.

The x-axis is depth below the planetary surface. This is underground water.


   This is Figure 1 from the news story in Nature (by Usui).


That's what got my attention. Mars' water is underground. Or at least, it would be if this were real data.

Following up -- checking out the article behind the headline and news story... It's not quite as exciting as we might have hoped, but it is interesting.

First, some background... Mars is generally thought to be low on water. However, why it is dry is quite unclear. It should have started with about the same percentage of water as Earth. It's certainly plausible that a lot of water has evaporated from the lightweight Mars or got swept away by solar winds, but the best estimates of such losses really suggest there should still be plenty around. If so, where is it?

Sub-surface ice is one possibility. The new article provides another. The authors did computer modeling of Earth and Mars crustal rocks. The conclusion is that the Martian rocks are, relatively speaking, sponges. They hold more water than Earth rocks. The difference increases with depth, which corresponds to higher pressure.

What's the difference between Earth and Mars rocks that leads to their different water-binding? That's complicated, but it is based on at least some evidence. The basalt rocks on Mars are more highly oxidized. And the temperature profile with depth leads to hydrated minerals sinking, thus helping to ensure that water is sequestered underground.

The amount of water the modeling predicts is substantial. The authors estimate that underground hydrated rocks could account for the entire estimated water content of Mars.

How robust are the conclusions? It's hard to tell. There are a lot of assumptions. What the article does is to show that, at least with certain reasonable assumptions, it is plausible that Mars could have a lot of underground water, in the form of hydrated rocks.

So, the graph above is for computer water -- theoretical water. Maybe we should send someone up there and dig a hole.


News stories:
* Study: Martian Surface Water Was Absorbed by Planet's Crust. (Sci-News.com, December 24, 2017.)
* Water on Mars absorbed like a sponge, new research suggests. (Phys.org, December 20, 2017.)

* News story accompanying the article: Planetary science: Martian water stored underground. (T Usui, Nature 552:339, December 21, 2017.)
* The article: The divergent fates of primitive hydrospheric water on Earth and Mars. (J Wade et al, Nature 552:391, December 21, 2017.)

Posts that may be -- but probably aren't -- about water on Mars:
* What causes gullies on Mars? (September 8, 2014).
* Water at the Martian surface? (August 27, 2011). A recent follow-up article, by the authors of the article discussed in this post, makes the water interpretation of the work less likely.

Among recent posts about or referring to Mars...
* Nanopore sequencing of DNA: How is it doing? (November 13, 2017).
* Perchlorate on Mars surface, irradiated by UV, is toxic (July 21, 2017).



February 7, 2018


The origin of SARS: getting closer

February 6, 2018

Briefly noted...

Considerable evidence has been accumulating to implicate bats as a major reservoir of coronaviruses. However, the specific origin of any specific virus, such as the SARS virus, is not clear.

A recent article provides more evidence, and perhaps brings us closer to the origin of SARS.

The article involves extensive surveillance, over several years, of a particular cave. Many coronaviruses were isolated and sequenced. The big finding is that the collection of coronaviruses in the cave includes all of the key gene sequences found in the SARS virus.

The scientists did not find the SARS virus itself in the cave. However, one can easily imagine it arising by recombination between the viruses that were found there.

The article does not show that this cave is the source of the SARS virus. There may be other sites that contain the necessary viral genes. Perhaps some other cave already contains the SARS virus itself. The scientists have not demonstrated that the suspect recombination actually occurs, or that the virus can get from this cave to the human populations. What the article does is to provide more support for simple plausible scenarios for what might have happened. We no longer need to hypothesize that all the SARS sequences were near to each other in a somewhat restricted environment. We now know of one specific example.

Could it happen again? Could another "SARS" arise in a bat cave and cause problems in humans? The authors suggest that continuing surveillance would be prudent.


News stories:
* Bat cave study sheds new light on origin of SARS virus -- Newly discovered SARS strains in bats hold genetic clues to the evolution of a human pandemic strain. (EurekAlert!, November 30, 2017.)
* Scientists Close in on Origin of SARS. (Chinese Academy of Sciences, December 8, 2017.)

The article, which is freely available: Discovery of a rich gene pool of bat SARS-related coronaviruses provides new insights into the origin of SARS coronavirus. (B Hu et al, PLoS Pathogens 13:e1006698, November 30, 2017.)

A recent post broadly about coronaviruses: Bats and the coronavirus reservoirs (July 25, 2017).

There is more about SARS and coronaviruses on my page Biotechnology in the News (BITN) -- Other topics in the section SARS, MERS (coronaviruses). It includes links to good sources of information and news, as well as to related Musings posts.



Stone age human violence: the Thames Beater

February 5, 2018

Can you break someone's head open by beating them over the head with a club?

When did humankind discover the answer to that question?


Would the club shown in the following picture do the trick?


   This is Figure 2 from a recent article. We'll explain it a little more below.


Well, there is one way to find out.

Some results...


It worked.

   This is Figure 8 from the article. The scale bar is for the left-hand item only.


Let's fill in some of the details...

In the first figure, the top item is an actual wooden club, known as the Thames Beater. It is considered Neolithic, about five thousand years old. The bottom item is a replica, used in the current work. It was made to match the original as closely as possible, including using the same kind of wood.

The actual test was done with a model for the human skull. The model is designed to recreate the response to injury. In the second figure above (Fig 8) the left-hand item shows the model after having been hit with the replica club. The right-hand item is an old skull from an archeological site. The nature of the damage is similar in both cases. The pattern of damage is consistent with high-impact trauma, rather than a fall or crushing.

There is much one can wonder about here, as to how closely the scientists have in fact made revenant replicas of the club and the skull. Presumably, the test system will be critiqued and developed.

Taken at face value, the work provides evidence that Neolithic man could break skulls. And that he wanted to.


News stories:
* Morbid Experiment Proves This Neolithic Weapon Was an Effective Skull Crusher. (G Dvorsky, Gizmodo, December 14, 2017.)
* Experiments show Neolithic Thames beater could be used to kill a person. (B Yirka, Phys.org, December 12, 2017.)

The article: Understanding blunt force trauma and violence in Neolithic Europe: the first experiments using a skin-skull-brain model and the Thames Beater. (M Dyer & L Fibiger, Antiquity 91:1515, December 2017.)

From the abstract: "The difficulty in identifying acts of intentional injury in the past has limited the extent to which archaeologists have been able to discuss the nature of interpersonal violence in prehistory. Experimental replication of cranial trauma has proved particularly problematic due to the lack of test analogues that are sufficiently comparable to the human skull."

* * * * *

A recent post on human violence: In the aftermath of gun violence... (January 8, 2018). Links to more.

A recent post with more about what ancient man could do: The oldest known dog leash? (January 23, 2018).



Role of neoantigens in surviving pancreatic cancer?

February 4, 2018

More survival curves. This time for pancreatic cancer, a cancer with notoriously poor prognosis. They are from a recent article, which offers a clue as to why some people survive pancreatic cancer longer than others.

For each graph in the following figure, a population of people with pancreatic cancer is divided into two parts of approximately equal size. The survival curves for those two sub-populations are then compared.



A quick inspection...

In one part, the survival curves for the two sub-populations are about the same.

In the other case, they are not. And that's the point.


   This is the right-hand side of Figure 2b from the article.


What's this about? It is about cancer immunology. And that means it is hard to explain.

The upper graph is labeled neoantigen quality. The lower graph is labeled neoantigen quantity. You can see, then, that it is quality that matters.

Neoantigens? This is about the tumor antigens: those found on the surface of the tumor. The term neoantigens means that they are new antigens -- ones not found normally.

Let's step back...

The role of the immune system in fighting cancer has become a hot field. Recent developments of immunotherapy are allowing people with advanced cancers to be cured. However, only a small percentage of the patients treated show much response. In a recent post, we noted that cancers with a high mutation rate are more susceptible to immunotherapy [link at the end].

It is known that the tumors of those who survive longer with pancreatic cancer are more infiltrated with T cells. This is evidence of a greater immune response. The question is, why do some people have more of an immune response?

That leads to the current work... The scientists looked at the antigens -- the neoantigens -- on the tumors. Cataloging tumor antigens is complicated, but that is what they did. Beyond that, they developed a model to rank the antigens by "quality": how well each antigen works in promoting an effective immune response. For now, let's accept that they did these things, and not worry about how.

What the figure above shows is that, whatever it is they did, it is of some value. Simply counting the antigens wasn't informative. Comparing survival of people with more neoantigens to survival of those with fewer showed no difference (lower graph). However, quality of antigens was informative. Comparing survival of people with "higher quality" antigens to survival of those with lower quality antigens showed a difference (upper graph).

And what do they mean by high quality antigens? There is no easy answer. The work involves looking at multiple characteristics, including similarity to known pathogen antigens and known binding affinities in the immune system. It also involves a lot of modeling and fitting. The work should not be taken as a definitive presentation of antigen quality, but rather as an indication that it is an important idea, and may be accessible

The conclusion? People will survive pancreatic cancer longer if their tumor makes more good new antigens. That enhances the ability of the immune system to fight the cancer.

What's the significance of the finding? Most importantly, it would seem to represent a step forward in our understanding of cancer. The ability to predict antigen quality probably will improve. But what do we do with the information? We'll see. As we have already noted, cancer immunology is becoming a hot field, but one still full of mysteries.


News story: New Study Findings Unlock the Secret of Why Some People with Pancreatic Cancer Live Longer than Others. (Memorial Sloan Kettering Cancer Center, November 8, 2017.) From the lead institution.

* News story accompanying the article: Cancer immunotherapy: How T cells spot tumour cells. (S Sarkizova & N Hacohen, Nature 551:444, November 23, 2017.) This item accompanies two articles. One is the article discussed here. The other is more broadly about cancer immunotherapy; it also deals with predicting antigen quality.
* The article: Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer. (V P Balachandran et al, Nature 551:512, November 23, 2017.)

Background post on cancer immunotherapy: Predicting who will respond to cancer immunotherapy: role of high mutation rate? (October 6, 2017).

Previous pancreas post: 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.



A mutation, found in a human population, that extends the human lifespan

February 2, 2018

Here are two survival curves, from a recent article....

You can see that the blue curve is shifted to a longer lifespan, compared to the red curve. (The mean is shifted by about 7 years; the median is shifted by 10 years.)

The red curve is labeled +/+; the blue curve is +/-. That is, the red curve is for wild types; the blue is for heterozygotes -- those who carry one copy of a mutation.

What organism? Humans.

Individuals who died prior to age 45 were not considered in this analysis, as you can see from the x-axis above.

   This is slightly modified from Figure 2 of the article. I added the genotype symbols for the curves.


What is this mutation? It is in a gene called SERPINE1, which codes for a protein called plasminogen activator inhibitor-1 (PAI-1). The particular mutation studied here is a null mutation, leading to total loss of active protein. SERPINE1 is known to affect senescence; work in lab mice has shown that those with a mutant copy of SERPINE1 have various metabolic improvements -- and live longer. The graph above extends this to humans. Other results reported in the article show other metabolic improvements, consistent with what was expected from the mouse work.

For example, the frequency of diabetes was 7% in the wild types (8 out of 127), and zero (0/43) in the heterozygotes.

How did we get a test of this gene in humans? The results are for a natural population, a small community that is reproductively isolated. Genealogical analysis identified a particular couple that introduced the mutation into the community six generations ago.

It is an intriguing finding. Taken at face value, we have a single mutation that affects human lifespan by several years. That lifespan change is accompanied by metabolic changes that are considered good. Further, the effects are supported by work in the mouse model system; that means that we have at least some understanding of how the mutation works.

The SERPINE1 gene protein, PAI-1, is important. People in the population with two copies of the mutant gene have significant bleeding and heart problems; they clearly have too little PAI-1. The current work may suggest that we normally have too much of it. But why? The heterozygotes have half the normal (homozygote) level of PAI-1. If that is better as judged by lifespan and some metabolic studies, why do we normally have twice as much? Why isn't the gene regulated to produce a lower level of PAI-1, if that would be better? Are we missing something more in the story -- something important?

Would it be beneficial to try to inhibit SERPINE1 with a drug? Would drug development based on the mouse model be useful? If anti-aging drugs are tested in humans, how long would it take to become convinced they are helpful? And safe? In fact, work with such a drug is in progress.


News stories:
* Rare Gene Mutation Linked to Longer Lifespan in Amish. (Sci-News.com, November 17, 2017.)
* Why these Amish live longer and healthier: An internal 'Fountain of Youth'. (Science Daily, November 15, 2017.) Includes a discussion of the early history of studying the mutation in the community, and also a discussion of the drug work.

The article, which is freely available: A null mutation in SERPINE1 protects against biological aging in humans. (S S Khan et al, Science Advances 3:eaao1617, November 15, 2017.)

A recent post on senescence: A treatment for senescence? (June 4, 2017).

Another example of looking at isolated populations for gene effects: Cataloging gene knockouts in humans (July 10, 2017).

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



January 31, 2018


Wind energy: effect of climate change?

January 30, 2018

Use of wind energy is increasing. Wind energy is a renewable energy source, not using fossil fuels. Increased use of wind energy is one good response to the threat of global warming.

But we might ask... Will climate change affect the availability of wind energy? After all, wind is an aspect of climate.

A new article addresses the question. The conclusions are not very clear, but the article is worthy of note just for addressing the question.

Here is the general plan... Take a particular proposed scenario for overall climate change. Calculate predictions for wind, using various climate models.

Of course, there are various possible climate scenarios; what happens will depend much on how we reduce C emissions. And there currently are multiple climate models that can be used to predict the winds. We also note that useful wind energy depends in a complex way on wind speed.

The following figure shows a sampling of the predictions...

The graphs show predicted change in available wind energy, as a percentage, vs time over this century.

Each graph is for one geographical region. These four are for parts of the Americas, north to south as you go across the figure.

The results shown here are all for one particular climate scenario.

The various curves on each graph are for different climate models -- ten of them.

The big picture...
* The predictions are very different for different regions.
* There is sometimes major disagreement between the models for a particular region.

Looking at some specifics... The models generally predict that, under this climate scenario, wind energy availability in the Mexico area will be fairly stable. In the eastern Brazil area, it may increase substantially over this century. In the two US areas, it may decrease substantially. All of those statements are generalities, with substantial uncertainty because of the different predictions from the different models.

This is part of Figure 4a from the article. The rest of Fig 4a contains 12 more such graphs, for other regions around the world. I chose the ones above just as a sampling -- conveniently the top row of the figure.


What do we get out of all of this?
- First, the results show that there may be changes -- large changes -- in the availability of wind energy as climate change proceeds. There even seems to be a general pattern... As climate change progresses, there will be, broadly, less wind in the northern hemisphere and more in the southern hemisphere.
- Second, our ability to predict those changes is limited at this point. A striking example is the one model for Central US that makes a very different prediction from all the other models. Scientists can ask why the model does this. What feature of this model, compared to the others, leads to the big difference? Then, can we resolve which model -- which feature -- is "correct"?

Overall, the article is a caution that wind energy may not be easily predictable over the long term.

Comment... Climate change is a highly politicized issue. Science gets caught in the political debate, and both sides use it poorly at times. There are things that science understands well about climate change -- and things it does not. When people on one side exaggerate how much science does or does not know, it encourages the other side to do likewise. That doesn't help!


News stories:
* As The Climate Warms, Wind Power Could Shift Southward. (P Patel, Anthropocene, December 14, 2017.)
* UK wind power potential could fall by 10% by 2100 because of climate change. (Carbon Brief, December 11, 2017.) Includes the complete Fig 4a (even the complete Figure 4) from the article, if you want to see the predictions for the other regions. It also includes a discussion of the reasons behind the north-south wind shift.
* Expert reaction to research on the impact of global warming on wind energy in the northern hemisphere. (Science Media Centre, December 11, 2017.) As usual, this source presents comments from several people in the field. Unusually, the several comments here are in general agreement... An interesting study, the conclusions of which are questionable. Again, that is not so much a criticism as a plea that more is needed in a difficult area. But we should specifically note... All of the commenters are from the UK, and they tend to emphasize the UK. In fact, the effects predicted for the UK are quite small compared to the predictions for most other regions.

The article: Southward shift of the global wind energy resource under high carbon dioxide emissions. (K B Karnauskas, Nature Geoscience 11:38, January 2018.)

Musings has had little to say about wind energy, but wind is the subject of several posts. Here are a couple; each links to more.
* Atmospheric rivers and wind (May 9, 2017).
* Improved high altitude weather monitoring (July 18, 2016).

I have listed this post on my page Internet Resources for Organic and Biochemistry under Energy resources. It includes a list of some related Musings posts.



Lightning and nuclear reactions?

January 28, 2018

One recent morning, as I worked on a draft of this post, the weather forecast offered a chance of thunderstorms for the afternoon. Had they occurred, there might have been an increase in the amount of the carbon isotope C-13 in the atmosphere. So says a recent article.

We all know that lightning involves energy. A lot of energy. But did you know... that energy can cause nuclear reactions in the atmosphere?

Here's the idea...

The figure starts with a lightning bolt. Among other things, it can lead to gamma (γ) rays.

If a γ-ray of appropriate energy strikes the nucleus of an ordinary nitrogen atom in the atmosphere, it can lead to the ejection of a neutron. The original N-14 nucleus is converted to the lighter isotope N-13. The ejected neutron is shown, as a light blue dot, just below the new N-13 nucleus. (Nuclear symbols can be written in the form 14N or N-14. The former is more formal; the latter is easier to type, and I will usually use it.)

N-13 is an unstable nucleus. Half life 10 minutes. It soon emits a positron. That leaves a C-13 nucleus, which is stable.

The positron (β+) is antimatter; it soon encounters its matter counterpart, the ordinary electron (β-). They annihilate, with the production of a pair of γ-rays. Those γ-rays are shown at the right, though not labeled there. What's particularly important is that the γ-rays from the annihilation have a distinctive energy -- the energy that corresponds to the mass of the particles.

   This is Figure 1 from the news story by Babich in Nature. The figure is also in the Science Alert news story.


What's above is theory. We might expect those things to happen.

What's new is that scientists have now detected the distinctive γ-rays from the positron-electron annihilation during a thunderstorm. Look...

The figure shows an energy spectrum of the γ-rays for a particular event during a thunderstorm.

The y-axis is a measure of the γ-rays; the x-axis shows their energy.

There is a clear peak at about 0.5 megaelectronvolt (MeV). The predicted value for the positron-electron annihilation is 0.511 MeV.

The analysis is considerably more complex than the graph might suggest. The graph here is for a time period already determined to be a time of increased γ-rays, and suspected of being due to annihilation.

   This is Figure 4a from the article.


Those results provide evidence for what is shown in the figure above: nuclear reactions, releasing antimatter positrons, during thunderstorms.


News stories:
* Breaking: Thunderstorms Observed Triggering Nuclear Reactions in The Sky -- They what now? (P Dockrill, Science Alert, November 22, 2017.)
* Storms Generate Thunder, Lightning and ... Antimatter? (C Choi, Discover (blog), November 22, 2017.)

* News story accompanying the article: Atmospheric science: Thunderous nuclear reactions. (L Babich, Nature 551:443, November 23, 2017.)
* The article: Photonuclear reactions triggered by lightning discharge. (T Enoto et al, Nature 551:481, November 23, 2017.)

Recent post about lightning: What's the connection: ships and lightning? (October 14, 2017).

Recent post about positrons, and also dealing with the distinctive γ-rays upon positron-electron annihilation: The major source of positrons (antimatter) in our galaxy? (August 13, 2017).

More about C-13: Life on Earth 4.1 billion years ago? (November 2, 2015). The amount of C-13 in a material is used to help identify its origins. The current work might make one wonder whether the production of C-13 during thunderstorms could upset our usual interpretations of what C-13 levels mean. The amount of C-13 made during storms, while interesting, is probably negligible, and not likely to affect our usual interpretations of C-13. However, this is just one of the possible reactions; there is a possibility that C-14 production during thunderstorms might be comparable to that from the usual sources.



Can prions, which cause brain disease, be transmitted by skin?

January 26, 2018

Prion diseases are degenerative brain diseases caused by a misfolded protein. That misfolded protein, called a prion, can cause other copies of the protein to misfold, thus promoting the agent. The most common human prion disease is Creutzfeldt-Jakob disease (CJD); a variant form is related to bovine spongiform encephalopathy (BSE; mad cow disease).

Prion diseases are dependent on the host having a copy of the gene for the protein; the prions are not autonomous. However, they can be transmitted, usually with low efficiency, in some cases. The transmission of BSE to humans by eating beef, resulting in vCJD, is well documented, but inefficient. Prions can also be transmitted by medical procedures; for example, brain material that happens to contain prions might be put into the brain of another person. Medical practice now recognizes this possibility, and there is little current transmission of prions by such procedures.

What about skin? Is it possible that prions could be transmitted via the skin? Could a brain disease be transmitted by skin tissue?

Look at the following figure...

There are three lanes of data, each with results for the prion protein in a patient with vCJD. The first lane (left) is for brain tissue, the second (center) is for skin tissue. You can see a strong response in the brain lane, and a very weak response in the skin lane. Weak but positive.

To reinforce the observation for the skin lane, the sample was incubated longer: 50 minutes instead of 5 min (see times at the bottom). That makes the skin result clearer. Weak but positive.

The test here is a Western blot. Protein samples are run on a gel, and then tested with an antibody that binds to the desired protein.

The antibodies are labeled with radioactivity; that is what is detected here. The times shown at the bottom are time of exposure of the film.

The messy result seen in the first lane is typical of prion preparations.

   This is Figure 1A from the article.


The result above shows that, for one particular vCJD patient, there is a low level of prion protein in the skin tissue.

Follow-up work showed that a low level of prion was found in all 23 CJD patients (sporadic or variant) tested. This work included using a more sensitive assay, one that detects in vitro function of the prion protein. As a control, 15 people without prion disease were tested; none had any detectable prion protein in the skin samples.

The question we asked at the start was whether the skin could be a source for transmission. The evidence above merely shows prion protein that can be detected by lab assays. Is it in a form that is transmissible? A good test would be to try to infect an animal with the material from the skin. Here are some results...

Survival curves. Mice were injected with skin samples from three people.

The green line across the top shows the results for mice that received skin samples from a healthy human donor. All the mice survived.

The other two curves are for mice that received skin samples from people with CJD. All these mice died.

   This is Figure 4A from the article.


Overall, the article shows that people with CJD have a low level of infectious prion in their skin.

What are the implications? There is no suggestion that people with CJD transmit the disease by ordinary contact, such as shaking hands. However, there is reason for some concern about handling any tissue from people -- or presumably other animals -- with prion diseases. Reasonable precautions are in order.

An intriguing question is... Might the finding allow for a simpler method of diagnosis of prion diseases?


News stories:
* Researchers find infectious prions in Creutzfeldt-Jakob disease patient skin. (Medical Xpress, November 22, 2017.)
* Infectious Prions Detected in Skin of Patients With Neurodegenerative Creutzfeldt-Jakob Disease. (MedicalResearch.com, November 23, 2017.) Interview with a senior author.

The article: Prion seeding activity and infectivity in skin samples from patients with sporadic Creutzfeldt-Jakob disease. (C D Orrú et al, Science Translational Medicine 9:eaam7785, November 22, 2017.)

A previous post about tissue specificity of prions: Prion diseases -- a new concern? (March 19, 2012).

For more about prions, see my page Biotechnology in the News (BITN) - Prions (BSE, CJD, etc). It includes a list of related Musings posts. Some of these deal with the possibility that Alzheimer's disease is something like a prion disease, and may be transmissible.



January 24, 2018


The oldest known dog leash?

January 23, 2018

Here is the data...


   This is part of Figure 4 from the article.

The figure shows a person and several dogs. The person has a bow and arrow; he is presumably a hunter.

Importantly, two of the dogs appear attached to the hunter. The connections would seem to be leashes.

The picture above is a cave painting, from Saudi Arabia. (It is a tracing of the original. The full figure in the article also includes a photograph of the actual art.) It is thought to be about 8000 years old.

There is considerable uncertainty about the date, as usual for cave paintings. Perhaps there is uncertainty about interpreting the picture.

Why is this of interest, beyond being a nice picture? Uncertainties aside, let's assume those really are dogs on leashes, part of a hunting scene a few thousand years ago. The cave painting then provides evidence for one stage of the story of dog and man. That is, it is a document with historical information -- about the history of dog domestication.

The figure above shows more than just leashes. There are numerous dogs, all peacefully around the hunter, and looking in the same direction.

That figure is one of 147 paintings, from two sites, that seem to show dogs as part of a hunting scene. Several include leashes.

Is it possible that the art is fictional? Sure, but it presumably builds on the real world. Would an artist have invented the scene shown above without some knowledge of dogs involved in hunting?


News stories:
* Wall carvings in Saudi Arabia appear to offer earliest depiction of dogs. (B Yirka, Phys.org, November 21, 2017.)
* 8,000 years old rock art in Saudi Arabia documents the earliest known use of dog leashes. (A Micu, ZME Science, November 21, 2017.)

The article: Pre-Neolithic evidence for dog-assisted hunting strategies in Arabia. (M Guagnin et al, Journal of Anthropological Archaeology, in press.)

Previous post that involved a leash: The opah: a big comical fish with a warm heart (July 13, 2015).

Among other ancient art...
* Images from 30,000-year-old motion pictures (July 22, 2012).
* Leopard horses (December 2, 2011).

There is more about art on my page Internet resources: Miscellaneous in the section Art & Music. It includes a list of related Musings posts.

More old things from Saudi Arabia: The oldest known plants (November 2, 2010).

More about dog domestication: It's a dog-eat-starch world (April 23, 2013).

Previous post on dogs: Predicting success in training guide dogs -- role of good mothering (November 27, 2017).

Added February 5, 2018. More about what ancient man could do: Stone age human violence: the Thames Beater (February 5, 2018).



Gene therapy and stem cells: A child gets new skin

January 22, 2018

A simple story... A child has a genetic disease that destroys his skin. He now has normal skin. The treatment? Take skin cells from the child, add to them a normal copy of the gene that is defective, grow new skin, and transplant it to the child. It worked.

Of course, there is much detail, and much uncertainty, but it does seem an important development.

Here is a diagram of what happened...

Start with the diagrams of the child at the sides. At the left (part 1 of the figure) is what he looked like before the treatment. You can take the red color in this drawing as meaningful; he (substantially) lacked normal skin. At the extreme right (part 7), 8 months into the treatment, he has normal skin.

The child has junctional epidermolysis bullosa (JEB). It is due to a mutation in a gene for laminin. The mutation prevents the skin layers from staying attached properly; the result is extreme blistering and, effectively, loss of skin. That's not just a cosmetic issue; the skin is a primary defense against pathogens. JEB is a serious disease, often fatal.

The scientists constructed a retroviral vector that contained a normal copy of the laminin gene (part 2a, at the top). They isolated skin (epidermal) cells from the child, and infected them with the new vector (part 2b).

The cell preparation at this point contained cells at various stages of development, or "stemness". These are shown in part 3 with various colors, to help you follow them (and with some names, which may not be so helpful).

The cell mix was grown in the lab into a skin layer (specifically the epidermis layer; part 4). It is a mixture of the various cell types, as you can see from the colors.

The lab-grown genetically-corrected skin was transplanted to the child. The resulting skin was analyzed at various times (parts 5, 6, 7). By 8 months, the child had normal skin over 98% of his body. The amounts from the various original cell types varied. The main trend was an increasing fraction of cells derived from the original "holoclone" cells; these are the cells that are most fundamentally stem cells -- capable of proliferating. That is, the new skin was ultimately derived from the stem cells in the transplant.

This is slightly modified from Figure 1 from the news story, by Aragona & Blanpain, in Nature. I added numbers for the individual parts, for ease of referring to them.

Figure 1 of the article itself includes photographs of the child "before" and "after".


At the time of the treatment, the child was considered in critical condition. The treatment was done as a last resort. Although all of the steps are logical, there had been only limited experience putting it all together to treat skin loss by transplantation of genetically modified skin. The current case is far more severe than any treated this way previously, with multiple operations to transplant skin to about 80% of the child's body.

It's now two years since the treatment began, and the child continues to do well. He is going to school, playing football (soccer), and generally living a normal life -- of course with plenty of monitoring.

What are the uncertainties? They fall into two classes. First, we do not know the long term outcome for this child. Second, we do not know the generality of the treatment. Nevertheless, this seems to be a very exciting development -- for this child, and who knows for how many more.


News stories:
* Extraordinary epidermis regeneration in child via combo stem cell-gene therapy. (The Niche (blog from a stem cell lab), November 8, 2017.)
* 'Extraordinary' tale: Stem cells heal a young boy's lethal skin disease. (M Blau, STAT, November 8, 2017.)
* Boy is given new skin thanks to gene therapy. (Science Daily, November 8, 2017.)

* News story accompanying the article: Gene therapy: Transgenic stem cells replace skin. (M Aragona & C Blanpain, Nature 551:306, November 16, 2017.)
* The article: Regeneration of the entire human epidermis using transgenic stem cells. (T Hirsch et al, Nature 551:327, November 16, 2017.)

An earlier post reporting a bold pioneering step in dealing with a very sick child: Genome sequencing to diagnose child with mystery syndrome (April 5, 2010).

Another post involving a genetic condition affecting skin: Why some people don't leave fingerprints (September 19, 2011).

See my Biotechnology in the News (BITN) pages for Cloning and stem cells and for Agricultural biotechnology (GM foods) and Gene therapy. Each contains an extensive list of related Musings posts. It is interesting how the two topics have come together.



How to "dye" carbon fiber -- with titanium dioxide

January 20, 2018

Carbon fiber is a useful material, with excellent mechanical properties and chemical inertness. And it is black.

The inability to dye carbon fiber almost follows from its chemical inertness. It's hard to get anything to stick.

A recent article reports making carbon fibers any color you want, by putting a white powder on the surface.

Here is an example...

Start with the pretty pictures. They are pieces of woven carbon-fiber fabric that have been colored, using the new treatment.

The first picture (upper left) shows the original, untreated fabric. The others show pieces of fabric after various amounts of treatment.

What is that treatment? Addition of a surface layer of titanium dioxide, TiO2, by atomic layer deposition (ALD).

The graph x-axis shows the number of cycles of ALD. The y-axis shows the thickness of the resulting TiO2 layer. The thickness depends linearly on the amount of treatment; it is about 0.1 nm per cycle. The pictures then show the resulting fabric colors.

   This is Figure 3a from the article.


The color here is "structural color", a term used to indicate color by a process distinct from the common absorption of light. It is due to reflection at the thin TiO2 layer. The thickness of that layer is on the order of the wavelength of the light, leading to complex reflection, including interference patterns. Exactly how the light reflects depends on the thickness of the film; that's the basis of the effect seen above.

You might wonder why the TiO2 sticks. The authors note the concern and offer some hypotheses, but really aren't sure. It may have to do with the small TiO2 interacting with occasional reactive groups on the fiber surface. However it gets started, as the process continues, TiO2 is binding to the previous layer of TiO2.

The colored fabrics can be washed repeatedly (ordinary home laundering), with only little loss of color. Further, the colored fabrics have only slightly reduced mechanical properties.

Although the process is not fully understood, it may be a step toward being able to make carbon fiber materials colored as you wish.


News story: Carbon fibre gets a colourful makeover. (E Stoye, Chemistry World, October 13, 2017.)

The article: Facile and Effective Coloration of Dye-Inert Carbon Fiber Fabrics with Tunable Colors and Excellent Laundering Durability. (F Chen et al, ACS Nano 11:10330, October 24, 2017.)

A recent post about structural color: Coloring with graphene: making a warning system for structural cracks? (June 2, 2017).

Also see: Why do many tarantulas have blue hair? (March 7, 2016).

A recent post about TiO2: A "greener" way to make acrylonitrile? (January 6, 2018). Carbon fiber was also noted in this post.



Monkey malaria in humans?

January 19, 2018

If we are going to keep track of diseases, and try to reduce them, it would help if we really knew what caused them.

A recent article illustrates the problem. It shows that an outbreak of malaria was not caused by the usual suspects, but by a distinct pathogen: a monkey malaria parasite, Plasmodium simium.

The common human malaria pathogens are P falciparum and P vivax. About twenty other malaria parasites are known for primates, eight of which are known to be able to infect humans. P knowlesi, whose primary host is macaque monkeys, causes considerable human malaria in Southeast Asia. Except for that, it is thought that most human malaria is transmitted (by mosquitoes) from other humans. Transmission of malaria from non-humans to humans -- so-called zoonotic transmission -- is considered uncommon.

What now? The short version of the story is that (human) malaria recently reappeared in a region of Brazil from which it had been eliminated. It appeared to be vivax malaria. However, the new work shows that it was actually simium malaria, which is known to be in the area. Why the confusion? The two parasites are hard to tell apart -- except by using modern molecular techniques. In the new work, the scientists used sequencing of the mitochondrial genome.

Does it matter? Well, it may not matter to those who got sick. But it does matter to those who want to understand disease transmission. In this case, the two diseases are transmitted differently. One is transmitted between humans, whereas the other is transmitted from monkeys to humans. (In both cases, transmission is by a mosquito vector.)

As you read this story... What really matters is the source of the infection. It matters whether the disease is being transmitted only from humans or from monkeys. It isn't the name of the bug that matters, but the transmission pattern.

If the new malaria is indeed monkey malaria from the reservoir in the forest, it means that the disease had never really been eliminated from the region. It was merely held in check. The re-emergence may well be due to changing patterns of forest use, including for tourism.

Disease is complicated.


News stories:
* Malaria parasite spreads from howler monkeys to humans. (S Boseley, Guardian, September 1, 2017.)
* Zoonotic Malaria: Back in Southern Brazil, or Did It Never Leave? -- Potential wildlife reservoirs could threaten public health. (M Walker, MedPage Today, September 1, 2017.)

* "Comment" article accompanying the article. Freely available: Plasmodium simium: a Brazilian focus of anthropozoonotic vivax malaria? (M J Grigg & G Snounou, Lancet Global Health 5:e961, October 2017.)
* The article, which is freely available: Outbreak of human malaria caused by Plasmodium simium in the Atlantic Forest in Rio de Janeiro: a molecular epidemiological investigation. (P Brasil et al, Lancet Global Health 5:e1038, October 2017.)

You will encounter the word autochthonous in this story, especially in the article itself. It means native. In context, an autochthonous case is one that has not been imported (say by someone who had been in a region with malaria). Therefore, there must be a local (native) source.

There is apparently some uncertainty whether the vivax and simium are really distinct species, or just different strains; it doesn't matter.

* * * * *

A recent post on malaria: Malaria and bone loss (September 10, 2017).

A recent post exploring other zoonoses -- diseases transmitted to humans from other animals: Bats and the coronavirus reservoirs (July 25, 2017). Also check the linked item there on "One health".

There is a section of my page Biotechnology in the News (BITN) -- Other topics on Malaria. It includes a list of Musings posts on malaria, and on mosquitoes in general.



January 17, 2018


A new species of orangutan?

January 16, 2018

There are three species of orangutans, not two, according to a new article.

It's not that the scientists found a new animal, but that they examined the knowns more carefully, and concluded that one population is sufficiently distinct that it deserves species status.



Pongo tapanuliensis, the Tapanuli orangutan.

Tapanuli refers to three districts in Sumatra (such as South Tapanuli).


   This is trimmed and reduced from a figure in the Mongabay news story.

Determining species is not easy. The common separation of orangutans into two species, Bornean and Sumatran, was established only in 2001. It required genome analysis to make the distinction clear.

In the new work, a team of scientists reports that one population of orangutans in Sumatra is morphologically and genetically distinct from the other orangutan species.

The work began with a single specimen of a dead animal. Features of the head, including the teeth, seemed quite distinct from what is considered normal for Sumatran orangutans. Genetic analyses, including animals from all three groups, confirmed the differences, and suggested that the new species split off from the others about 3.4 million years ago (mya). For comparison, the split between the other two orangutan species is dated at only 0.7 million years ago.

There is very limited data behind the proposal to designate a new species here. The article makes the case, but it needs confirmation, probably including more data, and discussion. The population of the proposed new species is only about 800 individuals, in a limited area -- as best they understand it now. Whether the species designation holds up or not, the work is a call for further investigation of the Sumatran orangs. The Tapanuli orangutans are at least an endangered population; they may be an endangered species.


If you are struck by the hair of the animal shown above... The authors note that the hair of this species is "frizzier" than for the others. (I doubt that any orangs use combs.)


News stories:
* Anthropologists describe third orangutan species. (Phys.org, November 2, 2017.)
* The Eighth Great Ape: New orangutan species discovered in Sumatra. (M Erickson-Davis, Mongabay, November 2, 2017.) Eight great ape species? That refers to living species. Three orangs, as discussed here; two gorilla species; chimps; bonobos; humans.

The article: Morphometric, Behavioral, and Genomic Evidence for a New Orangutan Species. (A Nater et al, Current Biology 27:3487, November 20, 2017.)

More orangs... Re-introducing captive animals into the wild: an orang-utan mix-up (June 27, 2016).

More from Sumatra... Does the moon affect earthquakes? (October 21, 2016).

More about dividing things up among species: An interesting skull, and a re-think of ancient human variation (November 12, 2013).



How long does a supernova event last?

January 14, 2018

A nova is a new object appearing in the sky. A supernova is an unusually bright nova. It is now understood that supernovae are due to stars exploding as they die. As one might expect in some general sense for an explosion, a supernova rapidly becomes much brighter; it then decays.

Here are some supernova data, from a recent article...

That's a complex figure, but we can summarize it and get the main message.

The figure shows data for the brightness of two supernova events over time. The data for one event are shown by the big colored points over the top part of the graph. The data for the other event are shown by the dashed lines at the lower left.

The big picture... The brightness for one event (iPTF14hls; top) remained high over at least the first 400 days shown here. It declined slowly after that. The brightness for the other event (SN1999em; lower left) declined dramatically over about 100-150 days.

SN1999em is a typical supernova of this type. In fact, it was thought that such supernova events could not last more than about 150 days. And that's the point: the event shown across the top lasted far longer. iPTF14hls is an unusual supernova event.

A new article presents this recent unusual supernova event. The data for SN1999em are shown for comparison.


Don't try to compare the brightness of one supernova with the other here. They are plotted on different scales -- though this is not very clear in the article. Since the spacing of magnitude units is the same on both scales, we can compare the rates of decline; that's what we want here.

And yes, the bigger the magnitude number, the less bright the object is.

The big gap at around 300 days? The object was behind the Sun during that time.

The various colors for the data are for different spectral bands. The various symbols are for different observing stations.

This is slightly modified from Figure 1 of the article. I added the label identifying the supernova for the top data set. Also, I removed some stuff at the top of the full figure that I did not want to get into.


Not only is the new event extended, but there seem to be increases in brightness along the way. For example, there is a substantial increase in brightness at about 100 days, and there is a small peak at about 200 days.

It's probably not hard to look at the new data and suggest that this is a more complex event, with multiple explosions along the way. It is as if the star is exploding one piece at a time. That's fine, but astronomers have not seen such a complex supernova event before. Further, the authors are unable to provide any simple explanation in terms of current understanding of how stars collapse and explode.

Interestingly, there is evidence that this star may have exploded a little about 60 years ago, though one cannot connect the earlier event to the current one with certainty. "Exploded a little"? That's an interesting idea in itself.

The new supernova may be an example of a pulsational pair-instability supernova. But what that really means -- what really happened here -- is not at all clear. It is something new, something that cannot be explained at this point. It is truly a scientific discovery.


News stories:
* Zombie star' cheats death again and again, dumbfounding scientists. (T Puiu, ZME Science, November 9, 2017.)
* Supernova Discovery Challenges Theories of How Certain Stars End Their Lives. (Sci-News.com, November 9, 2017.)

* News story accompanying the article: Astronomy: The star that would not die. (S Woosley, Nature 551:173, November 9, 2017.)
* The article: Energetic eruptions leading to a peculiar hydrogen-rich explosion of a massive star. (I Arcavi et al, Nature 551:210, November 9, 2017.)

More supernovae...
* The major source of positrons (antimatter) in our galaxy? (August 13, 2017).
* Could you find debris from a supernova in your backyard? (April 27, 2016).



Pumping tin

January 12, 2018

You know how to pump water? You could pump tin the same way, right? Well, you would have to melt it first. And that creates a new problem: the pump must be able to operate at high temperature.

The melting point of tin is actually fairly low, only 232 °C. However, being able to pump it at much higher temperature (T) could facilitate its use in heat transfer systems. That is actually the big motivation behind the current work, besides simply demonstrating a high-T pump. In a new article, scientists develop a pump that can operate at over 1200 °C. Maybe even at 1400 °C.

Here is the plan for the pump...

Most of the figure is a diagram of the pump. In general, it looks fairly normal at this level.

At the lower left is a photo of part of the pump in action. The color is due to the heat. That's the main point of showing the figure. (The color in the upper part, which is a diagram, is artistry.)

This is trimmed from Figure 1 of the article. (I have removed one part of the figure, at upper right. The two lines going up from the gears go to the part I cut out.)


The secret to operating a pump at such a high T? The materials, of course. Ceramics. Graphite. The chemical inertness of such materials at high T is known, but ceramics can be brittle. What is novel is making a functioning pump out of them.

How well did the pump survive? The following figure shows the gears after 72 hours of operation...

Look at the gear on the right. The black line shows the original shape. You can see that there is significant wear.


   This is Figure 5 from the article.


It works, but needs improvement.

The authors note plans for such improvement. For example, they note that the gear material used here was chosen partly for convenience for initial testing; better materials are available.

The article claims that this is the highest temperature at which pumping has been demonstrated. It shows that ceramics can be used to make a high-T pump; the scientists plan work to make it practical. They even envision going on to pump silicon. The melting point is 1420 °C, and they would hope to pump it at over 2000 °C. Pumping molten tin or silicon could be a good way to transfer energy.


Video: Pumping Liquid Metal (Tin) at 1200C (~2200F). (YouTube, 2 minutes.) Interesting, but not well labeled. Background music, but no useful narration. Some of it is too fast to follow at a single viewing.


News stories:
* Pumping liquid metal at 1,400 °C opens the door for better solar thermal systems -- A ceramic pump can handle the heat; careful engineering prevents it from cracking. (M Geuss, Ars Technica, October 13, 2017.)
* Ceramic pump moves molten metal at a record 1,400 degrees Celsius. (Phys.org, October 11, 2017.)

* News story accompanying the article: Engineering: Liquid metal pumped at a record temperature . (K Lambrinou, Nature 550:194, October 12, 2017.)
* The article: Pumping liquid metal at high temperatures up to 1,673 kelvin. (C Amy et al, Nature 550:199, October 12, 2017.)

Posts about pumping include...
* Lamb-in-a-bag (July 14, 2017).
* pH and the color of petunias (March 26, 2014).
* Caltech engineer turns rat into jellyfish (September 22, 2012).

Previous posts about tin: none.



January 10, 2018


A look at Chopin's heart

January 9, 2018

That's it.

It's in a jar of a brown fluid, which is probably cognac.


   This is the Figure from the article.


Frederic Chopin died in 1849. His heart was removed from his body, according to his wishes. It was put in a bottle, as shown above, and given to his sister. The heart is now at a church in Warsaw, and is examined from time to time.

Chopin was only 39 when he died, and the cause of his death has never been clear.

A new article reports briefly on the most recent examination of Chopin's heart, in 2014 -- 69 years after the previous examination.

Among the prominent findings are three lesions near arrow A in the figure. The authors note that these are most likely from tuberculosis.

Arrow B points to stitching to the left ventricle, following its opening during the autopsy.

There is more, but not much more. It's a two-page article, with observations and some interpretation -- and much uncertainty. Heart specialists may enjoy the detail. But the big story here is the big picture: the preservation and examination 165 years later of Chopin's heart.


News stories, both of which provide good overviews:
* Chopin's Preserved Heart May Offer Clues About His Death -- Scientists who recently examined the organ have suggested that Chopin died of complications from tuberculosis. (B Katz, Smithsonian, November 9, 2017.)
* Examination of Chopin's pickled heart solves riddle of his early death -- Scientists diagnose rare complication of tuberculosis following analysis of heart stored in jar of cognac for 170 years. (R McKie, Guardian, November 4, 2017.) Overstates the conclusions, but still, a useful story.

The article: A Closer Look at Frederic Chopin's Cause of Death. (M Witt et al, American Journal of Medicine 131:211, February 2018.)

Previous heart post: Heart regeneration? Role of MNDCMs (November 10, 2017).

Another examination of an old specimen for possible TB... A new approach for testing a Llullaillaco mummy for lung infection (August 17, 2012).

There is more about music on my page Internet resources: Miscellaneous in the section Art & Music. It includes a list of related Musings posts.



In the aftermath of gun violence...

January 8, 2018

Guns are a political issue in the United States.

In December 2012 a gunman went into the Sandy Hook Elementary School in the US state of Connecticut and killed 20 children (and six adults). Such a mass killing, especially of children, provokes debate about gun laws -- a least for a while.

A new scientific article reports some data about guns, in the context of the Sandy Hook incident.

The question the authors examined is... What is the effect of a major shooting, which becomes a major news event, on subsequent gun events?

The following figure summarizes some of the main findings...

The graph plots data for two gun-related phenomena over time. One is shown as blue bars; the other is shown as a black line.

A quick inspection of the graph shows that both phenomena reached a peak in early 2013 -- immediately after the Sandy Hook event.

What are these two phenomena? The graph labels them well. The black line shows sales of guns in the US (left-hand y-axis). The blue bars show accidental gun-related deaths of children (right-hand y-axis). (The death data is given as deaths per 100,000 population per month.)

In both cases, the data is shown in a way that emphasizes the variation from "average". Zero is the average value over the time period. There is nothing of particular interest except for the peak values already mentioned. The magnitudes of the values at that peak were the largest magnitudes found, whether positive or negative.

   This is Figure 2 from the article.


That is, the Sandy Hook event, with its news coverage, was quickly followed by a burst of gun sales and accidental gun-deaths of children.

The data above for accidental deaths of children is given as a rate, and compared to the average. We can add that the blue bar for that peak period represents 18 deaths above the average -- an increase in the absolute death rate of about 60%. (There were also 39 extra deaths of adults. The overall increase in the gun-death rate was about 20%.) Note that these numbers are all for accidental deaths from guns, not criminal activity.

The graph shows a correlation; it does not show there is a causal connection. However, if we assume, for the moment, a causal connection... It may be good to note that most people who responded to Sandy Hook had no direct connection with the original event itself. The results shown above are national data. Most who responded -- if indeed the data shown are a "response" -- knew of the story only through the news media, including the political discussion.

I will just leave it at that: an example of collecting evidence about the effect of guns. There is no claim that we understand what is behind the data shown here, or that this is the complete story. And it is not for me to get into the political issues.


News stories:
* Sandy Hook shooting aftermath: Increased gun sales, more accidental deaths by firearms. (EurekAlert!, December 7, 2017.) Includes some general discussion of gun issues, including the importance -- and difficulty -- of collecting data.
* After a Mass Shooting, a Surge in Accidental Deaths -- Research on the Sandy Hook massacre shows public focus on firearms after a massacre leads to more tragedy, particularly among children. (P Mosendz, Bloomberg, December 7, 2017.) An example of coverage by the general news media.
* Sandy Hook mass shooting triggers weapons purchase. (K Jaramillo, LatinAmerican Post, December 17, 2017. Now archived.) A view from outside the US.
* Wellesley Faculty Find that a Jump in Gun Sales and Accidental Gun Deaths Followed the 2012 Sandy Hook Shootings. (Wellesley College, December 8, 2017.) From the lead institution -- a two-hour drive from Sandy Hook. Links to several news stories in the mainstream general media.

* "Policy forum" accompanying the article: Gun-violence research: Saving lives by regulating guns: Evidence for policy. (P J Cook & J J Donohue, Science 358:1259, December 8, 2017.) This is a broader discussion of gun violence and gun laws. The emphasis is on right-to-carry laws. There is only minimal discussion of the current article,
* The article: Firearms and accidental deaths: Evidence from the aftermath of the Sandy Hook school shooting. (P B Levine & R McKnight, Science 358:1324, December 8, 2017.)

More about human violence...
* Added February 5, 2018. Stone age human violence: the Thames Beater (February 5, 2018).
* Violence within the species -- in various mammals; implications for the nature of humans (December 6, 2016).
* Human violence (November 28, 2011).

The previous mention of a gun was in the post What happens when a lithium ion battery overheats? (February 19, 2016). It was a heat gun in this case.



A "greener" way to make acrylonitrile?

January 6, 2018

Acrylonitrile, for use in making polymers and carbon fiber, is made from petroleum. A new article offers a possible new way to make it from a biological product.

The following figure outlines the process, and shows some data for an early version.

Start with Part B, on the right. This shows the new process, at two levels of detail. It's not important to follow all the detail, especially at the start, but we will use some of it as we go along.

The bottom section of Part B shows the overall process (equation 4). Compound 5 is converted to compound 7. Compound 7 is acrylonitrile, the desired product. Compound 5 is the ethyl ester of 3-hydroxypropanoic acid. Previous work had established a bacterial fermentation to make compound 5 from sugar; it is the starting material here.

The top two sections of Part B show the two steps -- one on each end of the starting compound. The first step is dehydration: removing the -OH group and an -H from the next C, leading to a double bond (equation 1). That gives compound 6, an intermediate here. The second step is to remove the ester group, and replace it with a nitrile group (equations 2-3). That gives compound 7, the desired product.


Part A shows an example of how this works. In this case, the overall process was run at various temperatures (T). The graph shows what happened as a function of T. For example, at the lowest T (150 °C), the process led to about 90% of the original compound 5, and 10% of the intermediate 6. There was essentially none of the desired product 7. That is, not much happened at this low T. With higher T, more and more 7 was obtained, reaching over 50% at the highest T shown here. The level of 6, the intermediate, first rises with T, then falls -- as more is converted to the final product.

The top line in the graph (labeled "8")? It's pretty much flat, at 100%. That's good; that's the sum of all the chemicals they analyzed. It's a test to see that the analyses make sense; all of the material is accounted for.

This is slightly modified from parts of Figure 1 in the article. I added more numbers for labeling. The authors numbered reactions 1-3 in part B. I added the numbers 4-8 for various equations, chemicals, and lines.


That's the idea, but the best yield is not very good. The authors went further, and did the two steps separately. The first step is done at a fairly low T, making the intermediate, compound 6. That product stream is passed on to a second reactor, at a higher T. Doing the two steps separately, at different T, leads to an overall yield of the desired product of about 98%. Excellent!

In addition to avoiding petroleum and having a high yield, the proposed process is actually simpler than the current process. And it avoids the release of hydrogen cyanide (HCN), so it may be safer, too. Nevertheless, we emphasize that the article is a presentation of something new, with only small-scale testing.

The article summarizes an economic projection for the process, suggesting that the product cost would be competitive with current prices, based on petroleum. These numbers are encouraging. However, the current price fluctuates, depending on market forces, and the projected prices have considerable uncertainty. Further, cost projections for new processes are usually optimistic. If nothing else, it takes a while to get a new process running efficiently.


News stories:
* A Sweet Approach to Renewable Acrylonitrile Production. (S Himmelstein, Engineering 360 (IEEE), December 8, 2017.) Includes a flow chart of the overall proposed process, as shown in Figure 3 of the article.
* NREL Develops Novel Method to Produce Renewable Acrylonitrile. (National Renewable Energy Laboratory (NREL), December 7, 2017.) From the lead institution.

The article: Renewable acrylonitrile production. (E M Karp et al, Science 358:1307, December 8, 2017.) Check Google Scholar for a freely available copy.

A post about acrylonitrile polymers: Fixing the heart with some glue and light (July 27, 2014). Acrylonitrile is called cyanoacrylate in this earlier post. As usual in organic chemistry, the prefix cyano and the suffix nitrile are interchangeable.

Another post proposing an improved way to make a chemical used in plastics: A simpler way to make styrene (July 10, 2015).

A post about use of titanium dioxide as a catalyst: Photocatalytic paints: do they, on balance, reduce air pollution? (September 17, 2017).

Added January 20, 2018. More TiO2: How to "dye" carbon fiber -- with titanium dioxide (January 20, 2018).

A broad view of plastics... History of plastic -- by the numbers (October 23, 2017).



Treating obesity: A microneedle patch to induce local fat browning

January 5, 2018

This post ties together several issues that have come up before. They include...
- brown fat, especially the more specific issue of beige fat;
- the implications of developing beige fat for obesity, and also for diabetes;
- the use of microneedle patches to deliver a drug through the skin.

There are some background links about those issues at the end, but the key biology issue is the beige fat. Our traditional view of fat is that it is an energy reserve. We store fat for later use, when food is scarce. Of course, if we don't use it later, we get obese. We now recognize a second type of fat cell, which actively burns fat molecules -- without collecting the energy in any useful form, except heat. This "thermogenic" fat is called brown fat. (Its brown color is due to a high level of mitochondria, with their brown cytochromes.) Beige fat is a type of brown fat; more specifically it is brown fat made from the ordinary storage (or "white") fat. Since brown fat burns food without collecting the energy, it seems logical that it might be useful in preventing weight gain. Since the brown fat affects energy metabolism, perhaps it would have an impact on diabetes.

The stories of brown -- and especially beige -- fat are fairly new. We are beginning to understand them, but still have little idea how we might make use of the information.

A new article explores a way to exploit beige fat. The scientists have a drug that stimulates the conversion of ordinary white fat calls to beige fat cells. They deliver the drug, locally, through the skin by use of a microneedle patch. They then observe what happens.

The study is done with mice, with diet-induced obesity.

Here is the idea...

Start with the layer of skin. Below it are some fat cells (adipocytes). Above it is a microneedle patch, labeled "browning agent patch", with three of the needles penetrating the skin.

The patch contains a drug called rosiglitazone (Rosi), which is packaged in nanoparticles (NP) in the patch. The drug is slowly released under the skin. It then converts some of the white fat cells to beige fat cells.

   This is the Figure from the abstract of the article.


Here is an example of the results...

This is a glucose tolerance test. A big dose of glucose is given; the blood sugar level is measured over time. You can see that it rises rapidly due to the glucose that was given. It then falls.

The two main curves here are "EV" (blue, top) and "Rosi" (red, bottom). Rosi is the drug; EV stands for empty vehicle -- a mock needle patch without any drug.

You can see that the mock EV treatment shows a high peak glucose level, but the Rosi treatment results in a lower peak.

There is a third curve, labeled "CL" (green). It is for a different drug. The results for the two drugs, Rosi and CL, are similar.

   This is Figure 5c from the article.


The results show that the drugs improved glucose tolerance in this mouse model. Other data show that the drugs reduced weight gain. Overall, the article shows that induced browning of fat can be of practical benefit, and that the microneedle patch is an effective delivery tool. The patch allows local slow-but-sustained delivery; it may be a "gentle" way to provide the drug. Thus it may minimize some of the problems that have been observed with systemic delivery of such drugs.

We noted at the outset that our understanding of brown and beige fat is new and limited. That holds, too, for steps toward treatment. The current article is an interesting step, but it is important to understand how early it is.


News stories:
* Microneedle skin patch that delivers fat-shrinking drug locally could be used to treat obesity and diabetes. (Phys.org, September 15, 2017.)
* Nanoparticle Drug Delivery Patch for Obesity Treatment. (B Cuffari, AZoNano, September 21, 2017.)

The article: Locally Induced Adipose Tissue Browning by Microneedle Patch for Obesity Treatment. (Y Zhang et al, ACS Nano 11:9223, September 26, 2017.)

Background posts include ...
* Beige fat, with a connection to obesity: An obesity gene: control of brown fat (October 2, 2015).
* A post on diabetes, including glucose tolerance tests: Making a functional mouse pancreas in a rat (February 17, 2017).
* Microneedle patches: Clinical trial of self-administered patch for flu immunization (July 31, 2017).

More on diabetes is on my page Biotechnology in the News (BITN) -- Other topics under Diabetes. That includes a list of related Musings posts.



January 3, 2018


Diagnosing diabetes in people of African ancestry: a race-dependent variable

January 3, 2018

Diabetes is a disorder that affects the level of glucose in the blood. Of course, blood sugar level varies. A single measurement of the level is just one snapshot.

One way to diagnose diabetes is to measure a stable change that accumulates over time depending on the blood sugar. A useful example is glycated hemoglobin, a product of the hemoglobin reacting with the sugar. A single measurement of glycated hemoglobin integrates the entire history of the person's blood glucose level over the lifetime of the red blood cells (RBC).

It is known that there are factors other than diabetes that can affect the level of glycated hemoglobin, but doctors still find the measurement useful. for both diagnosis and monitoring.

A recent article reports a special problem with the glycated hemoglobin measurement in people of African ancestry.

The following graph summarizes some of the key results. We'll work through it slowly; it takes a while to get to the important data.

The y-axis shows the amount of glycated hemoglobin found in the blood of various groups of people. All the people studied here were thought to be free of diabetes.

The x-axis is labeled by ancestry and GS. The GS is the genetic score, a measure of how many genetic variants the person has that seem to have some effect on the glycation level.

To get the idea of the graph, look at the first group of measurements, at the left. These are for people of European ancestry. The three points are for the lowest 5% of the distribution, the middle 90%, and the top 5%. The values for glycated hemoglobin range from about 5.2 to 5.6 for these points. This shows that genetic variation does affect the level of glycation.

The second group of three points is for a sub-population of those of European ancestry. The results are similar.

The next two groups of data are for people of Asian ancestry. For these people, the range of values is smaller.

And now, the "important" part... The next two data sets are for people of African ancestry. There is a now a very wide range of values. In particular, the scores for the lowest 5% of those of African ancestry are very low compared to the scores for the other groups.

   This is Figure 5 from the article.


That is, some people of African ancestry have an unusually low level of glycated hemoglobin. This is shown on the graph by the average value for the lowest 5%. It is about 5.0 for Africans, over 5.2 for the other groups.

What is it due to? A particular mutation in the gene for the enzyme glucose-6-phosphate dehydrogenase (G6PD). This is a gene on the X chromosome, so men have only one copy. Look at the last (right-most) set of data on the graph above. It is for African-ancestry men ("AA men"). Those who have the base T at this site have a glycated hemoglobin level of about 5.0. Those who have C at that site have about 5.8.

Next to that data set are the results for AA women. They have two copies of the gene, of course, so the situation is a little more complicated. But the general pattern is the same. T leads to low glycation.

What does this mutation do? It affects the lifetime of the RBC. The allele with T leads to short-lived RBC. If the RBC don't live as long, they don't accumulate as much modified hemoglobin. That is, we understand how the T allele leads to low glycation.

The point is that the T allele could interfere with the diagnosis of diabetes, by leading to a low level of glycation that is not reflecting the actual blood sugar level. The authors note that this T allele is almost unique to people of African ancestry. About 11% of African Americans have a T; "almost no one of any other ancestry" [author summary, p7] has it. It thus seems clear that this is a race-related variable that could bias the detection of diabetes.


The current article does not provide specific information on how the newly discovered mutation affects glycation level in diabetics. That remains for future work, as does then working out what an appropriate response should be. For example, it might be appropriate to check for the G6PD mutation as part of diabetes screening, at least for those of African ancestry.


News story: Type 2 diabetes is being misdiagnosed in African-Americans, genetic study suggests. (EurekAlert!, September 12, 2017.)

The article, which is freely available: Impact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations: A transethnic genome-wide meta-analysis. (E Wheeler et al, PLoS Medicine 14:e1002383, September 12, 2017.)

Other posts about race differences include...
* Alcohol consumption, an "ethnic" mutation, and a possible new drug (October 28, 2014).
* Why African-Americans have a high rate of kidney disease: another gene that is both good and bad (August 17, 2010).

Previous post on diabetes... Making a functional mouse pancreas in a rat (February 17, 2017).

There is a section of my page Biotechnology in the News (BITN) -- Other topics on Diabetes. It includes a list of related Musings posts.

Another effect of some mutations in the G6PD gene: Genes that protect against malaria (January 19, 2010).



The spider with the mostest ... (and such)

January 2, 2018


Most mass... Specimens of this spider as heavy as 170 grams have been found.

It is Theraphosa blondi, the Goliath bird-eater.

170 grams is more than 1/3 of a pound. More than an ordinary hamburger patty.

This spider is also one of the "Most delicious." Roasted.

   This is reduced from the first figure in the news story by Moscato. Figure 3A of the article shows a specimen of this spider, but the figure here is better for sense of scale.


And at the right...


Most web... As much as 2.8 square meters.

Made by a Caerostris darwini, Darwin's bark spider.

The creature at the bottom is presumably about 2 meters tall -- or at least was before the photographer truncated him. The spider? Don't know if it is visible in there. However, there is one featured in part e of the full figure in the article.


   This is Figure 3f from the article.


There are 96 more spider records in the article. Some are quantitative, some qualitative or subjective (such as "most delicious", mentioned above). Some are the biggest for some feature, some the smallest. Most are about the spiders themselves from nature. A few are about odd things from the lab (such as a ten-legged spider); a few are about those who study spiders.

Let's end this with a quiz... The spider Dipoena santaritadopassaquatrensis. What record does it hold? You may be able to guess from the information given here. You can check yourself in the article.


News stories:
* Only the very best make it into the 'spider world records'. (D Moscato, Earth Touch News, November 6 2017.)
* Ninety Nine World Records. (A Reis, Lab Times, November 16, 2017.)

The article, which is freely available: Record breaking achievements by spiders and the scientists who study them. (S Mammola et al, PeerJ 5:e3972, October 31, 2017.) It's fun to browse. The authors' purpose is to promote interest in spiders. There are many pictures, though perhaps not enough.

The article says that the spider records will be maintained -- and updated -- as a web page at the site for the International Society of Arachnology. I don't see it there, so maybe it is just a plan for now. If anyone finds it, let me know.

* * * * *

Among spider posts in Musings...
* How a spider can help you do better microscopy (September 9, 2016). Most recent spider post.
* What to do if your brain won't fit in your head (February 18, 2012). The spider discussed in this post is noted under "largest central nervous system."
* How to seat a spider in front of the computer (September 28, 2010). The purpose here is to give the spider an eye exam. That's not easy with a spider, especially one that has eight eyes. The article notes various things about spider vision -- and hearing. Also, jumping spiders (a large group) are often mentioned.
* Spiders (December 21, 2009). Peacock spiders. The winner for "most elaborate courtship." This post also notes (with pictures) the happy-face spider. It's relative, the Caribbean smiley-faced spider, is the winner for "genus with most species named after celebrities."
* The vegetarian spider (October 21, 2009). The winner for "strangest diet."

The last time Musings started a new year with a post on arthropods... A new year (January 1, 2010).



Older items are on the archive pages, starting with 2017 (September-December).


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