Musings -- September 2017 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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New items

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

Triplet-repeats: Do they act through the RNA?

September 24, 2017

Huntington's disease (HD) is a classic example of a "triplet-repeat" disease. People with the disease carry an unusual type of mutation: a particular 3-base sequence (triplet) is repeated, many times. The severity of the disease, including the age of onset, correlates with increasing number of repeats.

What's going on? In the case of HD, the result of the mutation is that the encoded protein, called huntingtin, contains many consecutive copies of the amino acid glutamine, as predicted by the genetic code. Long stretches of polyglutamine have been shown to have various toxic effects. It becomes plausible that the toxicity of the poly-Q (to use the standard symbol Q for the amino acid glutamine) is what causes HD. (However, it is also worth noting that the details of what is important are not clear.)

That is, the repeats in the genome lead to repeats in the messenger RNA sequence; that, in turn, leads to repeats in the protein, and that is toxic. Such an explanation is considered likely for many cases where the mutation is a triplet repeat or similar.

But not all. There are cases where this explanation for why a triplet-repeat mutation leads to disease cannot hold. In some cases, the mutation is in a region that is not translated into protein at all.

A recent article suggests that RNA containing triplet repeats may itself form aggregates.

The following figure shows the idea, with simple tests in vitro...

Consider the top row. It uses RNA molecules carrying repeats of the triplet sequence CAG. Ten repeats per molecule in the left frame, increasing to as many as 66 repeats at the right. The molecules carry a fluorescent tag.

You can see that the RNA molecules aggregate into clusters in the right-hand frames (≥ 31 repeats). There are few such aggregates when the number of repeats is smaller, at the left.

The second row shows the same kind of experiment, but using the triplet repeat CUG. The results are similar.

Controls using RNA of similar overall base composition, but lacking repeats showed no such effect.

   This is Figure 1c from the article.

The results above show that RNA containing certain triplet repeats can aggregate in vitro. The effect occurs, rather distinctly, above some critical repeat length.

What is the nature of these RNA aggregates? The authors provide evidence that they may be either liquid droplets or near-solid gels.

That's in vitro. Does this happen in cells? Does the effect seen above have any actual biological relevance?

The next test shown here is in vivo, in cells. The repeat in this case is a hexamer, but the idea is the same. The particular hexamer repeat was chosen because it is associated with two diseases: GGGGCC, found in some people with amyotrophic lateral sclerosis (ALS) or frontotemporal dementia (FTD).

The left-hand frame shows a cell that made an RNA with 29 repeats of this disease-related hexamer. The white spots are RNA aggregates.

The right-hand frame shows a similar test, but using a control repeat. No white spots.

   This is Figure 5d from the article.

The experiment shows that an RNA carrying a particular repeating sequence in its RNA can aggregate in cells. The particular repeat studied here is relevant to a known disease. The effect is sequence-specific: it does not occur for a different repeat.

The RNA repeat that aggregated here is a special case: it contains four consecutive G. It's known that GGGG can form an unusual structure, known as a G-quadruplex. That's presumably what happened here, probably involving many RNA stands.

This article provides an interesting development. It shows that small repeats in RNA can cause the RNA to aggregate. This can be shown and studied in a clean, in vitro system. The article also provides evidence that RNA repeats can have effects in vivo. At least, physical effects.

The authors note that they do not see any signs of toxicity due to the RNA aggregates in the cells (over the rather short time scale of their experiments). At this point, there is no evidence that the phenomena found here, aggregation of RNA containing repeats, is relevant to the disease process.

There is much more to be done here, but the article may open up a new approach to studying so-called triplet-repeat diseases.

News story: Not Just for Proteins -- Expanded RNA Repeats Form Gels, Too. (M B Rogers, ALZFORUM, June 3,2017.)

* News story accompanying the article: Neurodegenerative disease: RNA repeats put a freeze on cells. (D W Sanders & C P Brangwynne, Nature 546:215, June 8, 2017.)
* The article: RNA phase transitions in repeat expansion disorders. (A Jain & R D Vale, Nature 546:243, June 8, 2017.)

More HD... Huntington's disease: Mutant human protein disrupts singing in birds (April 18, 2016).

More ALS... Is a "dead" virus in the human genome contributing to the neurological disease ALS? (January 11, 2016).

A post about quadruplex DNA structures -- with some implication for disease: G (July 8, 2008).

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

Personal optimization of an exoskeleton

September 22, 2017

An exoskeleton, in this context, is a device one wears to enhance walking. The device may provide both support and energy; in general terms, it enhances strength. For example, the military is interested in exoskeletons because they may allow people to carry heavier loads. A disabled person might use an exoskeleton to compensate for deficiencies.

Although the general principles are clear enough, it is a technological challenge to make a practical device. Musings has presented work on exoskeletons [links at the end], but the big picture is that the devices have seen limited use.

A recent article takes another step: rapid customization of the exoskeleton device to meet an individual's needs.

The following figure summarizes one set of findings. Before you look at it, you might want to get up, take a few steps, and watch your ankles. The angle between ankle and leg varies during a step, in a regular (cyclic) way. The exoskeleton studied here provides torque to assist with that ankle twist. The question is, how much assist should be provided at each stage of the step cycle?

The figure shows the optimum torque cycle developed for 11 able-bodied people using the device.

Each curve shows the optimum torque pattern found for one person. The y-axis shows the amount of torque. The x-axis is a time scale, mapping out a single step.

The curves are similar in nature; that is by design. What is important is that each person's optimum is somewhat different.

   This is Figure 3D from the article.

How do the scientists do this? It involves a series of rapid tests, which lead to optimizing the software that runs the exoskeleton.

They set four parameters: peak torque, timing of peak torque, rise time, and fall time.

The subject walks on a treadmill, wearing a mask that allows the scientists to monitor their respiratory gases, hence their metabolism. You can see the set-up, including the mask, in the news stories or video. It takes about two minutes to get a good measurement. The optimization software adjusts the operating parameters. After about an hour of testing, the person's optimal settings are established, leading to the most effective assist by the device for that person. Attempting to optimize further usually leads to little improvement.

The following figure summarizes some other tests, each with one person...

Frames A-E, all for one subject, compare the device for various types of walking. For each type, the person is tested with regular shoes, with the exoskeleton device, but not providing assist (labeled "zero torque"), and with the device providing optimized assist. The percentage shown in each frame is the metabolic savings due to turning the device on.

Frame A is for slow walking. The metabolic cost is similar -- and low -- under all conditions tested here. (Remember, this is with an able-bodied person.)

For the other walking modes (frames B-E)... There is a small penalty due to wearing the device. However, turning it on to assist more than makes up for that penalty.

Frame F shows similar tests for running. This test is with a different subject. The results are again similar.

Frame G shows results for an optimization done with measuring (calf) muscle activity rather than metabolic gases; the results, for a different subject, are similar. The details of how this was done are not in the article. The main point is that there are various ways to do the optimization.

Do you want to question whether the overall benefit, compared to ordinary shoes, is significant for frames E-F? There is no information to address that. Remember, the results in this figure are for one person. It's fine to take this figure as preliminary, and to question what is significant.

   This is Figure 4 from the article.

The benefits seen here are generally better than in previous work. That comes mainly from improved -- and rapid -- customization of the device for each user. (It also comes, in part, from having a lightweight device.) It is a step toward making exoskeletons more practical.

News stories:
* Smart algorithm automatically adjusts exoskeletons for best walking performance. (Kurzweil, June 25, 2017.)
* Customizable 'Smart' Exoskeleton Learns from Your Steps. (T Staedter, Live Science, June 23, 2017.)

Video. There is a short promotional video from the publisher. It may help you visualize the system, but doesn't do much more than that. The video is at YouTube. (1 minute; narrated.) Each news story contains that video or a similar one.

* News story accompanying the article: Robotics: Fast exoskeleton optimization -- An algorithm optimizes exoskeleton walking assistance in 1 hour. (P Malcolm et al, Science 356:1230, June 23, 2017.)
* The article: Human-in-the-loop optimization of exoskeleton assistance during walking. (J Zhang et al, Science 356:1280, June 23, 2017.)

Background posts about exoskeletons for assisting humans include...
* An exoskeleton that assists with walking but does not require an external energy source (September 8, 2015).
* Another FDA approval: exoskeleton (August 11, 2014).
* Berkeley Bionics: From HULC to eLEGS (October 22, 2010).

Another exoskeleton issue: How do you breathe while changing your skeleton? (October 31, 2014).

More about walking... What is it? (March 8, 2011).

Also see my Biotechnology in the News (BITN) page for Cloning and stem cells. It includes an extensive list of Musings posts in the fields of stem cells and regeneration -- and, more broadly, replacement body parts, including prosthetics.

September 20, 2017 (Current e-mail)

On completing the course of the antibiotic treatment

September 19, 2017

You've heard it... Complete the course of antibiotics. It doesn't matter how you feel, complete the antibiotics.

Why? Well, that's an interesting question. You usually don't ask. You just do as the prescription indicates; the doctor has followed standard procedures.

A recent article in the BMJ (British Medical Journal) questions the advice. In particular, it questions one of the reasons commonly given, that completing the course of antibiotics reduces the development of antibiotic resistance. That's actually not very logical: the continuing use of antibiotics might be expected to increase the pressure leading to resistance. Further, there is not much evidence for it. What little there might be is almost folklore, from an earlier era with little understanding of the microbiome and of antibiotic resistance. It is rarely from controlled tests.

Where does this lead? Unfortunately, it leads some to suggest that you can just stop the antibiotics when you want to, when you feel better. That's not really the point, though I must say that the article itself sends mixed messages. The best message is that we need to learn more about the proper use of antibiotics, to maximize effectiveness and minimize side effects, including development of resistance. Easier said than done.

A reminder... Musings is a place to explore scientific developments. Musings does not give medical advice. That's partly because I am not qualified to do so. But it is also important to realize that individual posts typically focus on one article, presenting one result or one view. We don't reach scientific or medical conclusions from hearing one presentation.

With that disclaimer, I can say that I find the article intriguing but incomplete. The authors argue that the justification for the current policy is weak; they make a good case. But to replace that, we need good data about what is the proper antibiotic course, and that data is usually lacking. The authors understand that. I think it is fair to say that their main case is to re-open the topic, with a plea for more data. It is not a suggestion that consumers should just stop their antibiotics when they feel better.

It's an interesting and provocative little article. It raises issues of concern. With luck, it will stimulate discussion -- and experiment -- in the medical research community. Just be careful about jumping to conclusions based on this article alone.

News story: That Age-Old Advice to Finish Your Antibiotics Might Do More Harm Than Good. (M McRae, Science Alert, July 27, 2017.) A quite complete presentation of the article.

The article is labeled as analysis; it is not a research article. It is: The antibiotic course has had its day. (M J Llewelyn et al, BMJ 358:j3418, July 26, 2017.) Check Google Scholar for a freely available copy. It's a short and readable article. If you are interested in the topic, either as a biologist or a consumer, give the article a try. The main part is 3 pages, but note the "Key messages" summary at the top of page 4.

A recent post on antibiotic resistance: Antibiotic resistance genes in "ancient" bacteria (February 11, 2017).

Another part of the problem of antibiotic overuse: Restricting excessive use of antibiotics on the farm (September 25, 2010).

More on antibiotics is on my page Biotechnology in the News (BITN) -- Other topics under Antibiotics. It includes an extensive list of related Musings posts.

What is the proper shape for an egg?

September 18, 2017

Egg-shaped, you suggest? That's really not helpful. Look...

The figure shows pictures of several bird eggs.

There is a pattern to how those pictures are arranged, and that pattern is the basis of the graph.

At the lower left is the egg of the brown hawk-owl. It's pretty much round, nearly a sphere.

At the upper left is the egg of the maleo. It's ellipsoidal: quite elongated compared to the sphere, but symmetric from one end to the other.

At the upper right is the egg of the common murre. It's not only ellipsoidal (elongated), but also asymmetric: one end is blunt and the other end is pointy.

Those examples illustrate the bigger study. The scientists measured the eggs of 1400 bird species. (49,175 eggs!) They calculated the ellipticity (y-axis) and asymmetry (x-axis) of each egg. The graph shows the eggs of 1400 species plotted by their ellipticity and asymmetry, with a sampling of them illustrated.

   This is Figure 1 from the article.

The x-axis (A) scale goes from 0 to 0.5; the y-axis (E) scale from 0.1 to a little over 0.7. The numbers are hard to read unless you blow up the pdf, and some of the numbers are covered by eggs. Anyway, you can get the idea from the numbers shown with the pictured eggs.

There is a 2 centimeter scale bar at the lower right.

One of the eggs illustrated is that of the red junglefowl, which is the ancestor of the modern domestic chicken. You can see that this egg is not particularly typical for bird eggs. Not only is the term egg-shaped ambiguous, but defining it in terms of the common chicken egg is misleading.

That's fun. But it leads to a question... Why? Is there some reason birds have different shaped eggs? Is there a reason why some birds have an egg with E over 0.6 and A over 0.4?

The authors tried to correlate the egg shape parameters with other things they know about the birds. On the grand scale, over all types of birds, egg shape was most correlated with flight ability. Birds with strong flight tend to have elongated or asymmetric eggs.

There is no explanation for the correlation at this point. This is a statistical work, not experimental. However, one can imagine how the adaptation to flight, which makes serious demands on both anatomy and physiology, might have affected egg shape. Very simply, elongated eggs may be consistent with the streamlined body shape associated with flight. The current work, finding a basic correlation, should lead to further work asking what is behind that correlation.

There are other ideas about why birds make eggs with various shapes. The current study does not disprove any of them. It just says that the biggest factor, over the entire range of birds, is flight ability.

News stories:
* Cracking the mystery of avian egg shape. (EurekAlert!, June 22, 2017.) Includes the picture from the journal cover.
* How eggs got their shapes -- Adaptations for flight may have driven egg-shape variety in birds. (Science Daily, June 22, 2017.)

* News story accompanying the article: Evolution: The most perfect thing, explained -- The requirements of flight best explain the evolution of different egg shapes. (C N Spottiswoode, Science 356:1234, June 23, 2017.)
* The article: Avian egg shape: Form, function, and evolution. (M C Stoddard et al, Science 356:1249, June 23, 2017.)

Where does one find eggs of 1400 bird species to measure? The Museum of Vertebrate Zoology, University of California, Berkeley. It's the largest egg collection in North America. The article itself is not from Berkeley, but from an international collaboration about as odd as the egg collection. The senior author alone is a Professor of Applied Mathematics, Organismic and Evolutionary Biology, and Physics.

* * * * *

Among many posts about flight...
* How to fly a beetle (April 27, 2015).
* Might it be good if airplanes emitted more CO2? (September 5, 2014).
* Why don't penguins fly? (August 24, 2013).
* Mosquitoes that can't fly (May 3, 2010).

Searching Musings files suggests that most posts about eggs are about human eggs, such as...
* Triparental embryos: the FDA and the regulatory dispute (September 12, 2017). An ongoing story, scientific and ethical.
* What are they? (September 14, 2011). It's interesting that we can connect an egg post to one about the Cassini spacecraft, which died last week.

But there is ... Bird lays egg (March 19, 2011).

Photocatalytic paints: do they, on balance, reduce air pollution?

September 17, 2017

Paint that removes air pollution? Sounds like a good idea, and it is based on good science. The question is whether currently available paints of that type are, on balance, beneficial. A new article provides evidence that they are not.

Such paints are based on titanium dioxide, TiO2. That chemical is activated by light, and then serves as a catalyst to oxidize various molecules it encounters. For example, if TiO2-containing paint is exposed to xylene, in the light, the xylene is degraded. That is good.

For this use, the TiO2 is in the form of nanoparticles. TiO2 is also used in paints as a white pigment, but that involves the use of larger particles.


In this work, TiO2-containing paints were exposed to light, and the emissions measured. VOC = volatile organic carbon.

We'll fill in some details in a moment, but first... Note that in each pair of bars, the left-hand (reddish) bar is higher -- often much higher. Reddish bars? Those are the bars for "pristine" (fresh) paint. The accompanying gray bars are for paint that has been aged.

That is, the TiO2 is promoting degradation of the paint itself.

There are two kinds of paint in the study, PM2 in the top row and PM1 in the bottom row. (PM2 is the more effective at removing air pollution. It's also more effective in creating its own pollution, as seen here.)

Paints were aged in the lab with light. It's an accelerated aging, typical of how products are tested in the lab.

The four sets of data bars are shown as peak sizes from mass spectrometry. The peaks, from left to right, are for formaldehyde, methanol, acetaldehyde and formic acid. They are being made from paint materials They are made upon light irradiation of the paint with the catalyst -- the same procedure used to destroy pollutants such as xylene from the air. They are made until they are gone, when the paint is aged.

Further, with aged paint, there may be release of the TiO2 particles. That's probably not good, either.

   This is Figure 7 from the article.

The authors suggest that the current state of characterizing such photocatalytic paints is inadequate. It is not enough to show some beneficial effects. As they show here, there may also be detrimental effects.

The authors are optimistic about the future of such paints. Identifying the problems is step one to solving them. They note that they are working on improvements, in collaboration with paint manufacturers.

News story: Smog eating paint does more harm than good. (H Fletcher, Chemistry World, September 4, 2017.)

The article: Characterization of photocatalytic paints: a relationship between the photocatalytic properties -- release of nanoparticles and volatile organic compounds. (D Truffier-Boutry et al, Environmental Science: Nano, in press.) This article is temporarily freely available -- until October 13.

A post on the use of TiO2 as a photocatalyst: How do you know if you have been in the sun too long? (August 5, 2016).

A recent post about titanium: The major source of positrons (antimatter) in our galaxy? (August 13, 2017).

More about paint degradation: Did the Pioneer spacecraft violate the law of gravity? (July 15, 2012).

Inter-plant communication via the Cuscuta parasite

September 15, 2017

Communication of hazards is useful. If someone in the room is bitten, others might want to take precautions. That's true for animals and plants.

A new article shows one way that a plant can tell its neighbor that it was bitten.

The following figure illustrates the experimental plan, and the result...

Frame A is a cartoon of the set-up: two plants with a parasitic Cuscuta (or "dodder") plant wound around the stems of both. In this case, the two plants are different: Arabidopsis on the left, tobacco on the right.

In the experiment, the left-hand plant was subject to an attack, and the response of the right-hand plant was measured. The response was compared to that found in a control, where there had been no attack.

Frame B shows the response as measured by the amount of TPI in the right-hand plant. TPI is trypsin protease inhibitors -- known to be part of the defense system. It is about 8-fold higher when the plant's connected neighbor had been attacked ("herbivory pretreatment"). (The graph shows a relative response. The control value was set to 1.)

Frame C show the effect on a subsequent attack on the tobacco plant. What's measured is the growth of the attacking insect, Spodoptera litura larvae (tropical armyworm, a major agricultural pest). You can see that the insect grew significantly less when the neighboring plant had been attacked previously.

   This is part of Figure 2 from the article.

Both of those measurements show that a signal had been transmitted from the left-hand plant, which was attacked originally, to the right-hand plant, which was tested to see how it responds.

The basic result was obtained whether the two plants were different types, as above, or the same type. The same result was also obtained when six plants were connected together in a chain, with a Cuscuta connecting each with its neighbors.

The implication is that the signal is being transmitted by the parasitic plant. The authors show that the transmission is not simply via the air.

It has long been known that the Cuscuta takes nutrients from its host. The current work suggests that it may provide a benefit, too.

There is no claim that the parasite is of net benefit to the host. The current work does not address what the net effect is; it only reveals that there is a positive contribution. The type of work here could be extended to measure the net effect on the host; the magnitude, of course, would depend on the insect load.

Biochemical work suggests that the nature of the signaling is via the usual plant defense system.

News stories:
* Dodder -- a parasite involved in the plant alarm system. (Max Planck Institute, July 24, 2017.) From one of the institutions involved. Includes a photo of a real pair of experimental plants, connected by the parasitic plant wound around their stems.
* Plant parasite dodder transmits signals among different hosts. (EurekAlert!, July 25, 2017.)

The article, which is freely available: Stem parasitic plant Cuscuta australis (dodder) transfers herbivory-induced signals among plants. (C Hettenhausen et al, PNAS 114:E6703, August 8, 2017.)

More Cuscuta ... How the tomato plant resists the Cuscuta (November 4, 2016). A useful introduction to the parasite.

Another example of inter-plant communication for defense: Underground messaging between bean plants (July 29, 2013).

Other posts on parasites include...
* Malaria and bone loss (September 10, 2017).
* Silent crickets (June 30, 2014).

September 13, 2017

Triparental embryos: the FDA and the regulatory dispute

September 12, 2017

A triparental embryo is formed using a third donor to provide the mitochondria. The original intent is to allow mothers with defective mitochondria to have children using their own genetic material. The technique is new, and only allowed -- with restrictions -- in one country so far. In a recent case, a doctor in the US tried to circumvent the US prohibition of the method by doing the final steps in another country. Musings has noted parts of this story [link at the end].

The (US) Food and Drug Administration (FDA) recently issued a formal letter of disapproval to the doctor. The FDA is the key regulatory agency in the US. The FDA acts, of course, according to the laws passed by Congress. These laws establish the general regulatory framework. Sometimes -- wisely or not -- Congress legislates specific regulatory points; that is true in this case.

The FDA letter, and a couple of news stories, are linked below.

One can read these items at various levels. It is easy to pick on the particular doctor here, who may seem to be deliberately flouting the rules. But whatever you may think about the doctor, there is a very real issue of how complex new treatments get regulated. The FDA -- and their counterparts around the world -- are charged with promoting good advances and protecting us from bad ones. Yet both of those points can be hard to establish. The use of triparental embryos is logical, and there is evidence to support its use. However, there are questions about its long term effects. It may take decades before we understand the treatment. Unless we try it, we won't learn what the long term effects are. What is the appropriate regulatory framework?

The job of the regulatory agencies, such as the FDA, is not an easy one.

The FDA letter (pdf file). (M A Malarkey, FDA, August 4, 2017.)

News stories:
* FDA Cracks Down on Pioneering Doctor Who Created a Three-Parent Baby. (E Mullin, MIT Technology Review, August 7, 2017.)
* The 'three-parent baby' fertility doctor needs to stop marketing the procedure, FDA says. (R Becker, Verge, August 5, 2017.)

Background post: Tri-parental embryos: the first human birth (October 1, 2016). Links to more, including the publication of the doctor's work with that child.

My page for Biotechnology in the News (BITN) -- Other topics includes a section on Ethical and social issues; the nature of science. It includes a list of related Musings posts.

Added September 18, 2017. More about eggs... What is the proper shape for an egg? (September 18, 2017).

Ravens: planning for the future?

September 11, 2017

Given a choice, would you choose some food or a key to the food cabinet? Some food, or a token that could be exchanged later for a larger amount of food?

Here are some results, from a recent article...

Each curve shows the results for a single subject. The x-axis shows the trial number.

Part A (left) shows the results for tests involving the "key" to the food cabinet. The authors call it a "tool".

Part B (right) shows the results for tests involving a token. This is a "bartering" test.

Each curve has T and F labels on its y-axis. The T stands for tool or token; the F, for food.

The results vary. Some subjects chose the delayed reward -- tool or token -- as many as 12 times out of 14. The worst case is the bartering test with the subject interestingly named "None"; she did 50% here. (And she was excluded from the tool test, because she figured out how to get into the food cabinet without a key, thus making the whole test pointless.)

   This is Figure 1 from the article.

The test subjects here were ravens. These birds are known to show some planning behavior; they stash food. The significance has been questioned. Is this simply some innate focused behavior, or does it reflect a portable planning skill. The results here suggest the latter. The test involves behaviors that are not natural; nevertheless, the ravens are able to weigh their options, and choose the one with the better ultimate benefit.

The general design of the tests... The raven was offered a tray containing several items. They included some food, a tool or token (per the specific test), and some distractors. The bird's choice was recorded. Later (15 minutes or 17 hours later, in one test or another), the birds were given a chance to use their tool or token. In general, they did so at a high frequency; that is, they remembered why they had chosen the delayed-reward item. (Data on how often they did so are included in the article.)

The authors compare what the ravens did here with what other animals have done on similar tests. The ravens compare favorably with apes and do about as well as four-year-old children.

It is tempting to analyze and question the significance of work such as this. But perhaps it is best just to follow the story, and wonder. More experiments and more comparisons will undoubtedly follow. In the long run, it's not about comparing animal A and animal B, but about understanding each. It's also about the broader topic of how brains work.

News stories:
* Ravens Can Plan for the Future -- They join an elite group of animals that includes great apes, but not monkeys or 3-year-old human children. (E Yong, The Atlantic, July 13, 2017.) Excellent discussion of what the work might mean.
* Ravens parallel great apes in their planning abilities. (Lund University, July 14, 2017.) From the lead institution.

* News story accompanying the article: Cognition: A raven's memories are for the future -- Ravens can plan for expected future events based on past experiences. (M Boeckle & N S Clayton, Science 357:126, July 14, 2017.)
* The article: Ravens parallel great apes in flexible planning for tool-use and bartering. (C Kabadayi & M Osvath, Science 357:202, July 14, 2017.)

Posts on ravens and other birds in the corvid group, with some emphasis on their "intelligence" include...
* Bird brains -- better than mammalian brains? (June 24, 2016).
* Complex tool use by birds (May 28, 2010).
* Why is a raven like a writing desk? (February 17, 2009).
* Self (October 8, 2008).

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

Malaria and bone loss

September 10, 2017

Malaria is a complicated disease. There are two distinct causative agents of human malaria, leading to related but distinct diseases. The disease course is complicated, and even those who become free of the parasite may suffer continuing effects.

The following figure shows the effect of a malaria infection on bone growth in young mice, as reported in a recent article.

Frame F (left) shows pictures of representative femurs (leg bones), from uninfected (naive) and infected (PyNL) mice.

You can see that the infected mice have shorter leg bones.

Frame G (right) shows the numbers. It shows the measured femur lengths for the complete sets of the two groups of mice.

   This is from Figure 1 of the article.

PyNL? That's Plasmodium yoelii nonlethal. That's a different species from those that infect humans. This is a mouse model of malaria. The scientists consider it a model close to P. vivax in humans.

The following figure explores how the malaria infection interferes with bone formation.

The figure shows a measure of bone volume for three groups of mice.

The left-hand data (white) is for uninfected (naive) mice.

The other sets of data are for two types of malaria infection. One, in the middle (red), is for malaria that we can consider as wild type or control. The other, on the right (green), is for a mutant malaria parasite, which cannot break down the host hemoglobin.

   This is Figure 5D from the article.

The PbA (control) infection led to reduced bone volume, in agreement with the result in the first figure. However, the mutant parasite unable to break down the host hemoglobin allowed near-normal bone formation. (Other data show that the two infections were generally similar. That is, the smaller effect on bone formation was not due to reduced degree of infection.) The implication is that the hemoglobin breakdown products inhibit bone formation, probably by inducing an inflammatory response.

It's a complex story. It's in mice, with mouse strains of the parasite; at best, it can only offer clues about human malaria. But it does offer clues, and they can be followed up in human malaria.

Bone formation is a complex process. There are two competing processes, with both bone formation and resorption going on in a regulated balance. Malaria infection interferes with both of them, but tips the scale toward less bone.

One clue that might be easily tested... The scientists showed that a vitamin D treatment enhanced bone formation in malaria-infected mice. That's plausible, of course, given the known role of vitamin D. Perhaps that can be tested as a simple and inexpensive treatment in human malaria, even before the details are understood.

News stories:
* Malaria Linked to Long-term Bone Loss. (C I Villamil, Medical News Bulletin, August 8, 2017.)
* Bone loss is another hidden pathology caused by malaria infection. (Science Daily, June 2, 2017.)

The article: Plasmodium products persist in the bone marrow and promote chronic bone loss. (M S J Lee et al, Science Immunology 2:eaam8093, June 2, 2017.)

Previous post on malaria: A highly effective malaria vaccine -- follow-up (May 3, 2017).

More on hemoglobin degradation as part of the malaria infection process: Pop goes the hemozoin: the bubble test for malaria (January 24, 2014).

Vitamin D... Vitamin D: How much is too much? (July 9, 2013).

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

Added September 15, 2017. More parasites: Inter-plant communication via the Cuscuta parasite (September 15, 2017).

Is Bcbva anthrax a threat to wild populations of chimpanzees?

September 8, 2017

Some data, from a new article...

The key point... The red dots represent animal carcasses that tested positive for anthrax; the black dots represent carcasses that tested negative. You can see that a substantial percentage of the dots are red. It's about 40%.

And the anthrax is widespread.

That should get your attention. Let's fill in the story.

The map shows a part of the Taï National Park in Côte d'Ivoire (Ivory Coast). The dotted line outlines the research area for the current work; the shaded area shows the chimpanzee habitat.

This is slightly edited from Figure 2a from the article. (I have removed an inset that seemed extraneous, and have included most of the key at the bottom.)

More about the results...

The carcasses referred to above were found during the scientists' surveillance of the research area over several years.

Finding anthrax on a carcass does not prove that the animal died of that disease. However, they tested a small sample of the carcasses, and found that all that tested positive for the anthrax showed pathology suggesting that the animal died of anthrax.

The study is about mammals. Many of the carcasses were of chimpanzees; the frequency of anthrax among the chimpanzee carcasses was about the same as noted above. (Actually, it was a little higher, but that may not be significant.)

Anthrax? The figure key above says Bcbva. That stands for Bacillus cereus biovar anthracis. That's a B. cereus with a plasmid carrying the anthrax genes. It's a variant anthrax. The disease is pretty much anthrax; the host is slightly different. ( B. cereus and B. anthracis are closely related bacteria.)


This is a study of anthrax in a rain forest. There are many studies of anthrax in arid lands, but much less is known about anthrax in rain forests, where the issues of disease transmission may be rather different.

The anthrax is novel. At least, it is being carried by a novel host, and that might reasonably affect the transmission. The importance of the novel host is unclear at this point.

The host range of the Bcbva anthrax seems to be wide -- wider than for traditional anthrax, and perhaps all mammals. Remember, the rain forest is species-rich.

All mammals? Does that include humans? There seems to be no information at this point, but the authors express their concern.

Carrion flies may be aiding in the transfer of anthrax. In particular, the flies may be transferring the bacteria, usually soil-borne, to animals in the trees. In any case, monitoring flies for anthrax DNA is a useful tool for the scientists.

Overall, Bcbva anthrax is a significant threat in the area.

A specific finding is that the chimpanzees are at risk. The novel anthrax is a major contributor to chimp deaths. Modeling of the next 150 years suggests that the anthrax may decimate the chimp population.

News stories:
* Mysterious Hybrid Strain of Anthrax Is Running Rampant in African Rainforests -- It's killing chimps and spreading to other species. (P Dockrill, Science Alert, August 7, 2017.)
* A Strange Type of Anthrax Is Killing Chimpanzees -- No one knows where it came from, how it spreads, or why it infects so many mammal species. (E Yong, The Atlantic, August 2, 2017.)
* Anthrax: a hidden threat to wildlife in the tropics. (Robert Koch Institute, August 3, 2017.) This is a "Joint press release by the Robert Koch Institute, the Max Planck Institute for Evolutionary Anthropology, the University of Glasgow and Laboratoire Central Vétérinaire de Bingerville, Ivory Coast".

* News story accompanying the article: Ecology: Chimps at risk from anthrax. (A Armstrong, Nature 548:38, August 3, 2017.)
* The article: Persistent anthrax as a major driver of wildlife mortality in a tropical rainforest. (C Hoffmann et al, Nature 548:82, August 3, 2017.)

Previous post on anthrax... Playing music can make you sick (July 31, 2010).

There is more about anthrax on my page for Biotechnology in the News (BITN), under Anthrax.

Recent posts about apes...
* Do apes have a "theory of mind"? (February 19, 2017).
* Age-related development of far-sightedness in bonobos (January 10, 2017).

September 6, 2017

The longest acene

September 6, 2017

That's it. Decacene. Ten benzene rings fused side-by-side.

Naphthalene, with two such rings, is probably the most familiar member of the family. The -acene ending is introduced with the next member, anthracene, with three rings. Those two are isolated from coal tar. Larger acenes are not found naturally, but some have been synthesized.

   This is part of Figure 1 from the article. The full figure also shows heptacene, octacene, and nonacene -- all of which have recently been synthesized.

In a new article, a team of chemists reports making decacene. Here's a picture...

A molecule of decacene.

You can see the ten ring structures quite clearly. Count them.

It's sitting on a gold surface -- where it was made.

   This is Figure 2a from the article.

They made the decacene by first making an oxygenated precursor with the desired carbon skeleton. Deposition on the gold surface led to reduction to the hydrocarbon. The details of the reduction are not entirely clear. The imaging, as shown above, was done by scanning tunneling microscopy.

Once again, this is a story of chemists stretching their tools to make new things. The amounts made in such work are small, but they are a start, and they do allow some study of the chemical. Acenes have interesting electronic properties, and may find use in electronic devices. But so far, the largest acene that has been isolated is heptacene. Perhaps the current work will lead to alternative syntheses of decacene -- and to larger amounts.

News stories:
* Researchers obtain decacene, the largest acene synthesised ever. (Nanowerk News, August 14, 2017.)
* Decacene takes title of longest acene. (K Krämer, Chemistry World, August 8, 2017.)

The article: Decacene: On-Surface Generation. (J Krüger et al, Angewandte Chemie International Edition 56:11945, September 18, 2017.)

Another difficult synthesis of a benzene-related molecule: Making triangulene -- one molecule at a time (March 29, 2017). The article of this recent post is reference 9b of the current article.

This post is listed on my page Introduction to Organic and Biochemistry -- Internet resources in the section on Aromatic compounds. That section includes a list of related Musings posts.

Human heart tissue grown in spinach

September 5, 2017

Need some new heart tissue? You might get a transplant from another human, or, at least in principle, a xenotransplant from a pig. Or perhaps a heart organoid grown in vitro. Or perhaps some heart tissue grown in spinach -- or on spinach.

That's a piece of spinach leaf, from which the cells -- the spinach cells -- have been removed.

The red things are human stem cells, growing on the surface. (The red is a dye. The label hMSC, upper right, stands for human mesenchymal stem cells.)

The black lines or streaks are veins. Leaf veins.

The main scale bar is 250 µm; 50 µm for the insert. (They are labeled, but hard to read.)

   This is Figure 5B from the article.

Why? The decellularized spinach leaf could play two roles. At the simplest, it is a physical support. It's a cellulosic support; cellulose is a good human-compatible material. One can imagine transplanting a structure based on what you see in that picture above into a human. Further, providing nutrition to cells in 3D culture is a problem. Leaves have a good vascular system, which could be used to provide nutrients to the human tissue.

In the article, the scientists first describe how they decellularize the leaves. The vascular system is still in good condition; small particles, about the size of normal blood cells, can flow through it quite well.

They then examine various human cells in or on the decellularized leaves. Some cells may grow within the leaf vasculature, some on the leaf surface. They imagine being able to make more complex 3D tissues by using layers of leaves.

In one case, they used cardiomyocytes (heart muscle cells) that had been differentiated in the lab from pluripotent stem cells and then put on the surface of a decellularized spinach leaf.. Three weeks later, they had small pieces of heart tissue, which showed heart behavior, such as contractility. The tissue pieces weren't quite as good as when grown on a lab plastic, but the leaf support is potentially transplantable into a human.

Is this silliness, or a breakthrough? The scientists have tried something unusual, and they have some intriguing results. Many questions remain, but it seems worth pursuing. It certainly attracts attention, but it does deserve consideration as a serious approach.

News stories:
* Beating Human Heart Tissue Grown on Spinach. ( Anti-Aging News, March 29, 2017.) From the American Academy of Anti-Aging Medicine.
* Beating human heart cells were grown on a spinach leaf. (E Motivans, ZME Science, March 24, 2017.)
* Scientists grow beating heart tissue on spinach leaves. (Kurzweil, March 31, 2017.) This is somewhat disorganized, but it does offer more detail than the other news stories. It includes a nice flow chart summarizing the work.

The article, which is freely available: Crossing kingdoms: Using decellularized plants as perfusable tissue engineering scaffolds. (J R Gershlak et al, Biomaterials 125:13e22, May 2017.) It is quite readable.

Also see:
* If an injured heart is short of oxygen, should you try photosynthesis? (June 25, 2017). This has nothing to do with the current post. Absolutely nothing. Except, of course, that it makes another connection -- a very different one -- between a heart and something photosynthetic.
* Human heart organoids show ability to regenerate (May 2, 2017).
* Long term survival of a pig heart in a baboon (April 30, 2016).

My Biotechnology in the News (BITN) page for Cloning and stem cells includes an extensive list of related Musings posts, including those on the broader topic of replacement body parts.

How much of the human genome is functional?

September 1, 2017

The human genome consists of about three billion base pairs (in the haploid set). How much of that is "functional", and how much is "junk"?

It's an interesting and surprisingly elusive question.

A recent article makes an argument that the percentage of functional DNA is at most about 25%, and is more likely half that or even less. It's an interesting argument. Let's look...

The argument is based on some basic ideas in genetics. In particular, it is based on the idea of genetic load. That is the number of deleterious mutations in the genome. Such harmful mutations are being continually produced by mutation. The higher the genetic load, the more children a couple must have in order to have two good healthy ones, who continue the species.

To estimate the genetic load, we need two key numbers. One is the mutation rate. More specifically, it is the rate of deleterious mutations.

The other key number is the genome size. The number of deleterious mutations depends on the mutation rate and the genome size. That's the effective genome size: the actual size times the percent that is functional.

In the new article, the author builds a mathematical model based on those basic points. Here are some examples of what he found...

rate of deleterious
mutations, µdel
functional fraction
of genome:
0.05 0.10 0.25 0.50 0.80 1.00
4.0x10-10   1.1 1.3 1.8 3.4 7.1 12
1.0x10-9   1.4 1.8 4.6 22 136 466
4.0x10-9   3.4 12 466 2.2x105 3.5x108 4.7x1010
1.0x10-8   22 466 4.7x106 2.2x1013 2.2x1021 4.8x1026

The numbers in the table are the fertility values needed to maintain the species (constant population), for a given mutation rate and genome size. The mutation rate is shown as the rate of deleterious mutations (left column); the genome size is shown as the fraction of functional DNA (top row).

µdel is in mutations per nucleotide site per generation.

The results, fertility values F, are number of children needed per person to maintain constant population size.

This small table is a subset of Table 1 from the article.

Here are some examples of how to read the table... Suppose that the rate of deleterious mutations, µdel, were 1.0x10-8, the highest value shown here (bottom row of the table). If the entire genome were functional (right-hand column), a person would need to have 4.8x1026 children in order to get one who would survive. Even if only 5% (0.05) of the genome were functional, a person would need to have 22 children. (44 children for a couple.)

Now look at the top row, for µdel = 4.0x10-10. That is 25-fold lower than the rate for the bottom row. If 100% of the genome were functional, a person would need to have 12 children; if 5% were functional, the person would need to have 1.1 children (2.2 for a couple).

There are two trends in the table. As either the rate of deleterious mutations or the fraction of functional-genome become lower, one can get by with fewer children to maintain the population. But as these numbers get bigger, the number of children needed to maintain the population becomes large -- astronomically large. It's all the idea of genetic load.

There are three kinds of numbers in the table: rate of deleterious mutations, fraction of functional-genome, and fertility needed. The table shows how they are interrelated.

If we knew any two of them, we could figure out the third, from the table -- assuming only that the model used here is correct. In particular, if we knew µdel and the fertility F, we could determine the fraction of functional-genome. That's the goal here.

The difficulty is that we have only estimates for the numbers we need; therefore, the conclusions are somewhat limited.

The author uses a fertility value of 1.8 as the limit. (3.6 for a couple.) That's a little arbitrary, but let's use it for now.

The total mutation rate is thought to be about 1x10-8, the highest number shown in my table above (bottom row). What's less clear is what fraction of the mutations are deleterious. The author discusses this at length, and argues that it is almost certainly at least 4%. 4% of 1x10-8 is 4x10-10, the lowest number in the table (top row). That is, he strongly believes that the rate of deleterious mutations is within the range shown in the table above.

Using those assumptions... F = 1.8 gives a functional-genome fraction of 0.25 or 0.10 for the two lowest µdel values in the table. That's the basis of the summary statement made at the top of the post; the author prefers the second mutation rate, and points to 0.10 as the most likely fraction of functional DNA.

It's all very interesting, and logical. It is worth trying to follow the ideas. However, getting to a number involves considerable uncertainty, so don't invest too much in that. The author discusses the various uncertainties, including more than we have noted here.

A little context...

A few years ago, a team known as the ENCODE consortium published work showing that as much as 80% of the genome was functional. Many people thought that 80% was unreasonably high, that only a few percent was likely to be functional. The current work is presented as something of an antidote to the ENCODE number.

The first point is that the two groups have taken very different approaches to defining what "functional" means. ENCODE called a region of DNA functional if an RNA was made from it -- even if they had no idea what the RNA did, or even any evidence that it did anything of interest. On the other hand, the current work focuses on function as doing something useful -- as judged by the possible interference by a deleterious mutation.

Over time, we'll learn more, and will be able to understand the two results. For now, it is more an interesting story in progress than choosing an answer.

News stories:
* 75 percent of human genome is junk DNA. (I Herlekar, BioNews, July 24, 2017.)
* New Research Suggests at Least 75% of The Human Genome Is Junk DNA After All. (P Dockrill, Science Alert, July 18, 2017.)
* Only 10-25% of Human Genome is Functional, New Estimate Says. (, July 19, 2017.)

The article, which is freely available: An upper limit on the functional fraction of the human genome. (D Graur, Genome Biology and Evolution 9:1880, July 2017.)

A post about the mutation rate in humans... Accumulation of mutations in the sperm of older fathers (November 19, 2012). The current article refers to the article discussed here, as giving one good measurement of the mutation rate.

More about junk DNA: Junk DNA: message from the bladderwort (June 4, 2013).

There is more about genomes and sequencing on my page Biotechnology in the News (BITN) - DNA and the genome. It includes an extensive list of Musings posts on the topics.

Older items are on the archive pages, starting with 2017 (May-August).

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Last update: September 25, 2017