Musings: January 2020 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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   Introduction (separate page).
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Current posts -- 2020 (January - ??)
   New items Posted since most recent e-mail; they will be announced in next e-mail, but feel free... !
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   February 12 (Current e-mail)
   February 5    January 29    January 22    January 15    January 8

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New items

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


A handheld printer that can print cells onto a severe burn

February 16, 2020

Deep burns can be life-threatening. There are a variety of possible complications when the major barrier around the body is lost. That includes the risk of infection; after all, the skin is the first line of defense against invaders.

Skin grafts are a common approach to dealing with the loss of skin, but this procedure has its own limitations. For large burns, there may not be adequate skin available for grafting.

A new article offers a new way to provide replacement skin... Print some cells onto the burn area. The cells grow out over a few days to provide good coverage.

The current work is actually not the first to try this approach, but it seems to have come closer to practical success than any prior work.

Here is the device...

Briefly, it contains a reservoir of ink --- a cell suspension, in this case. And a printhead.

Run the printhead over the area lacking skin. That seeds the area with a small but significant number of cells.

Importantly, the device delivers cells quite uniformly over a wide range of surface topologies.

(If you prefer, you can also think of the device as something like a paint roller. But it is a little complex for that.)

The device is about 20 x 11 x 15 cm, and weighs 1.4 kg.

   This is Figure 1b from the article.


The next figure gives an example of how this plays out, under idealized lab conditions...

The four frames are for the same site over time, from 0 to 7 days.

The cells are quite sparse at time 0 (just after seeding). After a week, the cells have replicated enough to provide good coverage of the site.

The scale bar is 0.1 millimeter.

   This is Figure 3f from the article.


That's the idea. But this example is not a treatment of a burn; it is a test depositing the cells on a clean surface. It shows that the device delivers healthy cells.

The scientists go on and start large-animal testing. They treat deep burns on the backs of pigs using their device. The results are encouraging.


News stories:
* Handheld Bioprinter Treats Severe Burns by 'Printing' New Skins Cells Directly Onto Wound. (SciTech Daily (IOP Publishing), February 3, 2020.)
* Canadian researchers develop hand-held skin printer to treat burn patients -- An exciting, and compact, alternative to skin grafts. (A Micu, ZME Science, February 5, 2020.)

The article: Handheld instrument for wound-conformal delivery of skin precursor sheets improves healing in full-thickness burns. (R Y Cheng et al, Biofabrication 12:025002, April 2020.) The article starts with a nice overview of alternative approaches, including those under development, for treating burns.

A similar post... Print yourself new body parts (April 16, 2010). This post from a decade ago offers the same idea; the oringinal post provided little information. Technology, both for devices and stem cells, have advanced since then. (I have added some more information to that post, since it came up here.)

My page Biotechnology in the News (BITN) for Cloning and stem cells includes an extensive list of related Musings posts. One part of the list focuses on regeneration.



February 12, 2020 (Current e-mail)


Briefly noted...

February 12, 2020


1. Computer scientists determine that Earth revolves around Sun. It's an interesting story about how AI works.
* News story: Viewpoint: Physics Insights from Neural Networks. (M Krenn, Physics 13:2, January 8, 2020.) Links to the article.


2. Official names for the new coronavirus and its disease. The temporary name of the virus has been nCoV (for novel coronavirus). Now, officially... The virus is SARS-CoV-2. The disease is COVID-19; I suspect that COVID stands for COrona VIrus Disease.
* News story: Deaths from newly named coronavirus disease top 1,000. (L Schnirring, CIDRAP, February 11, 2020.) The daily CoV news from CIDRAP, with this story and more. The naming part notes the recent rules for naming such things, avoiding geographical or group references. The story includes a very nice picture of a coronavirus, clearly showing the crowns that give this group its name.
* I have added the new names to my BITN page section for SARS, MERS (coronaviruses).
* In an earlier "briefly noted" item (January 22), I gave a date for the first case. That information was probably wrong. (And at this point, I don't even have a source for it.) Determining the first cases for a disease can be tricky -- and contentious -- but it seems likely it goes back to November 2019. I'll delete the bad information.



Humans may be more like salamanders than we had thought (limb regeneration)

February 11, 2020

One thing salamanders can do that humans cannot is to regenerate limbs.

A recent article provides evidence that, in fact, we do regenerate cartilage to some extent, especially in the ankles. Further, the scientists suggest that regulation of regeneration occurs by similar pathways in humans and salamanders.

The two figures here give some of the evidence on each point.

First, humans do regenerate cartilage... The method used here may need some introduction. What the scientists do is to measure the age of the cartilage in some human joints. How do you measure the age of a protein? Two of the amino acids contain a group that is not very stable. The amide group of asparagine (Asn) and glutamine (Gln) is lost over time (forming aspartic acid and glutamic acid, respectively). Therefore, measuring the ratio of the deamidated and amidated forms of these amino acids gives a measure of the age of the protein. (For technical reasons, the work mainly uses deamidation of Asn.)

In this test, they measured the deamidation ratio for several proteins in the cartilage of human joints. The proteins are listed across the top. For each protein, the deamidation ratio was measured in three joints: hip, knee, ankle -- from left to right on the graph, and from top to bottom in the body (a point we will return to later).

The deamidation ratio is shown on the y-axis, compared to a reference. You can just take the y-axis scale as relative: a high value means more deamidation, which means older protein.

Look at the second set, as a good example. That's protein ACAN-G1. There is a clear trend... The highest value is for the hip; the lowest value is for the ankle. That means the protein is oldest in the hip (most deamidation), youngest in the ankle (least deamidation).

If we assume that the proteins were originally made at the same time, that means that the protein in the ankle must have been regenerated more recently.

The results for the full set of eight proteins vary, but for five of them, the authors show a statistically significant effect as noted here.

Not overwhelmed by the data? The point is that ankle seems to be one factor that affects degradation. There is no claim that it is the only factor. In fact, the article discusses more factors.

The cartilage samples were surgical waste, from standard medical care.

   This is Figure 1A from the article.


The general suggestion from data such as shown above is that cartilage proteins are younger in the ankle, implying that there has been more regeneration there.

The following figure shows a possible reason. In this test, they measure the levels of three micro RNAs (miR). These are small RNAs different from the types of RNA most commonly mentioned. Micro RNAs regulate genes.

The bar heights show the levels of each miR found in the three types of cartilage.

To start, focus on the left-hand data set, for miR-21. It is much more abundant in ankle cartilage than in the others. (Beware the split y-axis scale!)

Similar, but smaller, effects are seen for the other miRs tested here.

   This is Figure 3A from the article.


That is, the levels of these miRs correlate with the level of cartilage regeneration seen earlier.

And that's interesting. In salamanders -- and some other animals with good regeneration -- these particular miRs are known to stimulate limb regeneration.

Overall, the article provides evidence that there is some cartilage regeneration in humans, and that it might be due to a regulatory RNA known to play such a role in other animals. That leads to the question... Would RNAs such as these be useful drugs in treating diseases of cartilage damage, such as osteoarthritis?

What about the trend vs body position that we noted with the first figure? This actually agrees with what is found in animals such as salamanders: limb regeneration is best the further out on the limb you go.


News stories:
* Our 'inner salamander' could help treat arthritis, study finds -- Research links human ability to regrow cartilage to molecules that help amphibians sprout new limbs. (N Davis, Guardian, October 9, 2019.)
* Humans Have Salamander-Like Ability to Regrow Cartilage in Joints -- The process could be harnessed as a treatment for osteoarthritis. (S Avery, Duke University, October 8, 2019.) From the lead institution.

The article, which is freely available: Analysis of "old" proteins unmasks dynamic gradient of cartilage turnover in human limbs. (M-F Hsueh et al, Science Advances 5:eaax3203, October 9, 2019.)

Posts about cartilage, including damage, include...
* The role of zinc in arthritis (July 18, 2014).
* Using your nose to fix knee damage (January 28, 2017).

More about regeneration, salamanders vs humans: Regenerating a leg (September 1, 2009).

Most recent post about salamanders: Look who's dining on baby salamander (November 3, 2019).

More about ankles: Personal optimization of an exoskeleton (September 22, 2017).

My page Biotechnology in the News (BITN) for Cloning and stem cells includes an extensive list of related Musings posts. One part of the list focuses on regeneration.



How long does it take to invent a new language?

February 9, 2020

About 30 minutes, according to a new scientific article, which tested the matter. It seems to come quite naturally to children.

A few years ago there was a report that a group of deaf children had invented a sign language on their own, without any instruction. The new language was remarkably "language-like". There was an implication that language -- and the nature of language -- was innate. However, there was no record of how the language was developed.

A new article attempts to study language development under controlled conditions. It's an intriguing article. The goal is clear, but the work here is just a small step.

Here is the stage -- almost literally.

Two children were in separate rooms. Their only communication was by video. You can see that the girl in green could see the girl in red on her screen.

The easel showed a set of pictures; both children saw the same set. One picture was chosen, and one child was asked to describe it to the other, who had to figure out which picture it was. It is a communication game -- which is what the children were told.

   This is Figure 1 from the article.


The two children in a test were the same age, 4 or 6 years old in most tests, with normal verbal language skills. (Most were mono-lingual.) That is, they were used to communicating, using ordinary language. In the test they needed to communicate, but their normal means of communication was blocked. So they had to invent a new way to communicate.

They did. There is a lot of detail, but the big message is that the children did develop communication. Their communication built over time (multiple trials), and showed features of language. A tool (sign) used in one trial would be used, by either party, in subsequent trials. That is, a common vocabulary developed and grew. Over time, the children invented signs with more complex and abstract meanings. And they began to develop gesture sequences -- grammar -- to communicate more complex meaning. (Interestingly, their grammar did not simply follow their spoken language (German).)

Most of the 6-year-olds spontaneously initiated gesturing. The 4-year-olds needed some prompting to try gestures, but then built on the prompt on their own.

Is this really language? Did the children really invent a language? That's an overstatement, of course. The authors argue that the children developed a communication system -- to meet their immediate needs. It had features of language. And they did that over a very short time scale, in part in the first half-hour session.

The type of system used here should allow much further experimental testing of communication, including language development.


News stories:
* Children's ability to create language-like communication. (EurekAlert! (PNAS), December 2, 2019.) A short but useful overview of the project.
* Language forms spontaneously, and fast. (A Micu, ZME Science, December 5, 2019.) Includes good discussion of some of the experimental work.
* Children Create Foundation for New Language in Minutes. (S Nilsen, Science Connected, January 6, 2020.)

The article: Young children spontaneously recreate core properties of language in a new modality. (M Bohn et al, PNAS 116:26072, December 17, 2019.)

Among many posts about language: Mountains and human language? (June 28, 2013). It links to several other posts on language.



Will a wolf puppy play ball with you?

February 7, 2020

Throw a ball in front of a young dog, and it is likely to chase it and return it to you -- especially if you ask it to.

Dogs are domesticated wolves. So we might wonder... would a wolf puppy, too, play "fetch" with you?

We now have a scientific article on the matter.

You can imagine what was done (and you can check some videos in a moment). 13 wolf puppies were tested three times each. Each trial was given a score... 1 means no cooperation; the wolf puppy ignored the ball. 5 means full cooperation; the puppy got the ball and returned it to the person who threw it, upon command. Intermediate scores were assigned for intermediate levels of response.

The following table shows the full scoring scheme, for reference. It's fine to skip it for now, and check it later as needed.

This is Table 1 from the article, with its legend.


Here are the results...

You can see that most of the wolf puppies (8 of 13) showed no response -- flat "1" for three trials.

More interestingly, some wolves did respond. In fact, three of them -- about 1/4 -- got a "5" for full cooperation on at least two of the three trials.

The ball-throwers were people unfamiliar to the wolves (i.e., strangers, not their regular handlers).

The three wolves with the strong responses were all from the same litter. The significance of this is unknown at this point.

   This is Figure 1 from the article.


That's it for data.

What does this mean? It would suggest that "fetching" (as defined by such a test) is a trait found in some wolves, even if at a low level. The appearance of this trait in dogs, then, may well be selection for a higher frequency of an existing favorable trait. (The formal alternative is that it was selection for a new trait, requiring a mutation.)

The article is a step toward understanding what happened during domestication.


News stories:
* Scientists unexpectedly witness wolf puppies play fetch. (Phys.org (Cell Press), January 16, 2020.) Includes two of the videos that accompany the article. The wolves are identified; check them on the figure above.
* Fetching wolves, canine behavior documented. (K Wolk, Canine Hacking, January 23, 2020.)

The article, which is freely available: Intrinsic Ball Retrieving in Wolf Puppies Suggests Standing Ancestral Variation for Human-Directed Play Behavior. (C Hansen Wheat & H Temrin, iScience, in press.) A short and very readable article, with good discussion of domestication issues.

There are three videos posted with the article. However, they seem available there only as a zip file. Download the file of supplemental information; it comes as a zip file, which includes the three videos. Each video shows one trial. In order, they show full, intermediate, and no cooperation. The first two are available with the Phys.org news story, listed above.

More about wolves:
* How many species of wolf are there, and why does it matter? (October 16, 2016).
* It's a dog-eat-starch world (April 23, 2013). The article discussed in this earlier post is discussed in the new article (though listed with the wrong date, which is 2013, not 2014).

A recent post about domestication: Domestication of the almond (August 26, 2019). Links to more.

More about playing ball: Bumblebees play ball (March 20, 2017).



February 5, 2020


An Asgard in culture

February 4, 2020

Last August, we "briefly noted" an intriguing article prior to it being accepted for publication. The claim in the article was such a major development that I wanted it to at least pass peer review before committing to it. It has now appeared, so we look at it more closely.

The topic: Asgard. An Asgard has now been cultured in the lab.

We have discussed Asgard before [links at the end], but the word still may not be familiar. Asgards are prokaryotic organisms of the archaea type. Their special claim to fame is that they have more features of eukaryotic cells than any other prokaryote known. Therefore, we wonder how close they are to organisms that gave rise to the eukaryotic lineage -- and eventually to us. The Asgard story has been inferred from complex indirect -- and controversial -- work, based on metagenomics (sampling DNA found in the environment). No actual Asgard cell -- dead or alive -- had ever been seen. Until now.

The topic Asgard is subject to hype. As the previous paragraph hints, big ideas are being suggested based on little hard evidence. But now we have a scientific article about actual Asgards; the goal here is to present that article -- with little hype.


A new microbe has been isolated. One early test is to measure its growth. It's Figure 1a of the new article...

Five growth curves, in fact. In part, there are different growth media. CA and PM are sources of amino acids (casamino acids (hydrolyzed casein) and powdered milk, respectively). "20 AAs" means a mixture of the twenty standard amino acids. Two of the curves start by diluting a previous culture.

The y-axis shows the amount of ribosomal RNA (rRNA) gene found; it is a measure of the amount of cells. That is plotted vs time (x-axis). Time is shown in days (rather than minutes, so often used for bacteria).

We can take the amount of rRNA gene found as an estimate of the number of cells. They would be equal if the number of rRNA gene copies per cell was one.

Growth is slow. The doubling time is about "14-25 days" (p 520, just under the figure legend). And the final cell density achieved is quite low.

   This is part of Figure 1 from the article.


What do cells of this Asgard look like? Here are a couple of them...

Each frame shows one cell.

These are SEM (scanning electron microscope) images.

There is also debris around, probably membrane fragments. Most of the debris pieces are marked with arrows. But the big thing in the middle, taking up most of the space, is one cell in each case.

What's striking is that each cell has projections, or "protrusions" as the authors call them. (People even refer to them as tentacles.) Multiple projections, sometimes straight, sometimes long, sometimes branched, sometimes tangled. The projections are shown to be outgrowths of the cell membrane.

The scale bars. in each frame, are 1 micrometer. That is, the diameter of the main cell body is about a half µm.

Neither the images above nor extensive examination by a variety of techniques show evidence for any eukaryotic-type structures inside the cells.

   This is part of Figure 3 from the article.


Those protrusions are intriguing. And they might solve a problem.

In the standard model, the eukaryotic cell arose when an archaeon took up a bacterium. But prokaryotes don't take up other cells; they don't have "phagocytosis" (literally, cell eating). That is, the standard model for making the first eukaryotic cell requires a trait that the parents don't have -- so far as we know.

The projections perhaps offer an alternative. Maybe the archaeon did not take up the bacterium by engulfing it. Maybe, instead, the archaeon surrounded the bacterium with its membrane protrusions.

Another feature of this new microbe is that it grows in close association with other microbes, and almost certainly exchanges nutrients with them during its normal growth. One can imagine this as an early stage of a symbiotic relationship.

The following figure offers a cartoon of what this might have looked like.

The blue thing with gray protrusions is the Asgard. The red thing is a bacterium, perhaps on its way to becoming an organelle (a mitochondrion).

The figure shows some of the possible metabolic interactions.


This is Figure 5b from the article. The full figure shows several steps of the possible association. (There is a third cell in this association, at the lower left.)


This article has gotten a lot of attention. We noted it here when it was first posted on BioRxiv, even before it was accepted for publication. You might wonder then, what's the big deal? What have we learned from this "breakthrough" article? And the answer is, we don't know -- yet. The Asgard microbes have gotten attention in recent years because there are at least hints that they may have been involved in a major step in the development of life. Most of the evidence was indirect. Now, at last -- and after 12 years of effort by this lab to isolate this culture -- we have one Asgard in the lab, growing. What have we learned from it so far that helps us understand the origin of eukaryotic cells? Nothing, at this point. But we have an Asgard growing in the lab. That in itself is a big step.

That picture of the Asgard cell, above, is tantalizing. But remember, the middle figure above is a photo; the bottom figure is a drawing, using our imagination.

The authors have proposed the name Prometheoarchaeum syntrophicum for the newly discovered microbe.


News stories:
* Elusive Asgard Archaea Finally Cultured in Lab -- The 12-year-long endeavor reveals Prometheoarchaeum as a tentacled cell, living in a symbiotic relationship with methane-producing microbes. (N Lanese, The Scientist, August 12, 2019.) This news story was listed in the earlier "briefly noted" post about the current article, then available only as a preprint.
* Incubated Prometheoarchaeum syntrophicum samples may provide clues about origin of eukaryotic cells. (B Yirka, Phys.org, January 16, 2020.)
* This Strange Microbe May Mark One of Life's Great Leaps -- An organism living in ocean muck offers clues to the origins of the complex cells of all animals and plants. (C Zimmer, New York Times, January 15, 2020.)

* News story accompanying the article; it may be freely available: Microbiology: Meet the relatives of our cellular ancestor. (C Schleper & F L Sousa, Nature 577:478, January 23, 2020.)
* The article, which is freely available: Isolation of an archaeon at the prokaryote-eukaryote interface. (H Imachi et al, Nature 577:519, January 23, 2020.)

You might check the journal cover photo.

* * * * *

Background posts about the Asgard include...
* #2 in Briefly noted... (August 21, 2019). A brief mention of this work when it was posted as a preprint, prior to being considered for publication.
* The Asgard superphylum: More progress toward understanding the origin of the eukaryotic cell (February 6, 2017).
* Our Loki ancestor? A possible missing link between prokaryotic and eukaryotic cells? (July 6, 2015). This post discusses the first article published about an Asgard -- just five years ago.

More about the origin of eukaryotes:
* What if a yeast cell contained a bacterial cell? A step toward understanding the evolution of mitochondria? (January 29, 2019). An artificial system.
* Origin of eukaryotic cells: a new hypothesis (February 24, 2015). The article of this older post is reference 39 of the current article. The model discussed above supports the proposal made in this earlier article for how the archaeon took up the bacterium.
* Are there really three domains of life? (January 12, 2013).



Hückel at 40 -- that's n = 40: the largest known aromatic ring

February 1, 2020

Benzene, C6H6, is the classical example of a molecule that we call aromatic. It has nothing to do with its odor, but with how its electrons are distributed. Six of the electrons (one from each C) are in a loop, and can circulate around the molecule. Because they are circulating, or "delocalized", they are less reactive than one might have expected.

Are other things aromatic, in this sense? Well, fuse two benzene rings together, and you get naphthalene. It indeed behaves as aromatic, with ten of those circulating electrons.

There are other chemicals that behave as aromatic; some are along the lines of benzene and naphthalene and some are different. In 1931, the German scientist Erich Hückel developed a "rule": a molecule could behave as aromatic if the number of electrons available to circulate is 4n + 2, for any integer n, starting with zero. (Benzene and naphthalene have n = 1 and 2, respectively.)

The circulating electrons are all π electrons, in the language of quantum mechanics. Not all π electrons can circulate, but when discussing aromaticity, we will focus on the π electrons that do circulate.

Hückel's rule has worked well. A chemical with two π electrons circulating is aromatic; that is n = 0. Other chemicals with n as high as 5 fit the pattern.

I have a page on the general nature of aromaticity, as discussed above. That page is: What does "aromatic" really mean? It includes pictures of some of the other aromatic species beyond benzene. One of those shows how one can have a loop of two electrons.

What about larger molecules? In 2017, a team of chemists from Oxford University made a molecule with 78 π electrons, and showed that it behaved as aromatic, as expected from Hückel's rule (n = 19).

And now, more from the same team. Look at this molecule...

How many π electrons are there in its main loop?

Hard core chemists may be tempted to actually count them. If you do try... The "spokes" don't matter; just count the π electrons in the "wheel" (including those on one side of the porphyrin rings). But before you do, see the next point.

There is a little catch. The molecule shown here is neutral. It is actually an ion form of it that is aromatic. The molecule shown has a loop of 168 π electrons. Remove six of those π electrons, to form the 6+ cation, and you get 162. That is 4n + 2 for n = 40.

More about the structure of the chemical... One can think of it as a big wheel (the aromatic part), with spokes. We didn't mention it earlier, but the aromatic loop must be planar; here, the spokes hold the wheel in a plane. There are 12 spokes. Each is attached to a corner of a benzene ring at the center. But there are only six corners to a benzene ring. There are actually two benzene rings there, one behind the other, but rotated a bit. That gives 12 corners, on two benzenes. In the figure, the spokes alternate light and dark. The dark spokes attach to the upper benzene; the light spokes attach to the lower benzene -- which is not visible here.

   This is reduced from the figure in the news story at Nature Research Chemistry Community. If you want more detail, see the full-size figure there. The figure is equivalent to Figure 4a of the article.


That's the chemical. Is it aromatic? Measuring reactivity is not practical in such a case, because of the complexity. But another feature of aromaticity can be measured. We noted that the π electrons in an aromatic chemical circulate; that creates a current -- and it can be measured. The scientists measure it by its effect on the magnetic field. The ring current from aromaticity affects the NMR spectrum; that is what they measure. Here is an example...

The top of the figure shows a small cartoon of the chemical; it is the same one shown above.

The important part is at the bottom... a few data points. The scale shows the chemical shift for particular atoms in the NMR spectrum, as a function of the number of π electrons in the loop (x-axis). More specifically, it shows the difference between two similar atoms in different places.

The open circle is for the neutral molecule, with 168 π electrons. It is the reference point, shown as zero.

Other points are for various oxidized forms of the molecule, with fewer π electrons. Of particular interest is the point at 162 π electrons. There is now a small negative difference between what were equivalent atoms. It is what is expected if the molecule (or ion, 6+, in this case) has a ring current as predicted for an aromatic species.

   This is part of Figure 5 from the article. I have added some labeling at the right. The full figure shows similar results for various molecules they made in this work. The one shown here is the largest.


As noted, the team examined several large molecules in this work. The big observation is that aromaticity was detected, by ring current, in several cases -- all of which agree with Hückel's rule.

From this work, we now know that Hückel's rule holds out to n = 40, for a system with a loop of 162 π electrons. That's several times the size of readily available aromatic molecules, and about double the previous record -- set by the same group just three years ago.


News stories:
* Largest molecular wheel ever made pushes limits of aromaticity rules. (M Gross, Chemistry World, January 22, 2020.)
* Global aromaticity at the nanoscale -- The extraordinarily rich electrochemistry of porphyrin nanorings, in combination with the scope for using templates as scaffolding to control the conformations of these macrocycles, make them ideal systems for studying aromaticity at the nanoscale. (A Zakharova, SciGlow, January 20, 2020.
* Behind the paper -- Global Aromaticity at the Nanoscale. (H L Anderson, Nature Research Chemistry Community, January 21, 2020.) From an author of the article; a little of the story of the work.

The article: Global aromaticity at the nanoscale. (M Rickhaus et al, Nature Chemistry, in press.) Reference 8 is their 2017 article with the previous record.

As noted above, I have a page on the general nature of aromaticity: What does "aromatic" really mean?

The molecule shown above is related to one in an earlier Musings post: A new approach to making large molecules, using a Vernier process (February 12, 2011). The work is from the same group.

A post about a molecule that, perhaps surprisingly, isn't aromatic: Making triangulene -- one molecule at a time (March 29, 2017).

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.



January 29, 2020


Briefly noted...

January 29, 2020


The coronavirus problem: a big-picture view. Last week, The Scientist published an interview with one expert in the field. I offer it here not as "the answer", but as one useful view. Some things to think about.
* Interview: Where Coronaviruses Come From -- EcoHealth Alliance President Peter Daszak speaks with The Scientist about how pathogens like 2019-nCoV jump species, and how to head off the next pandemic. (S Williams, The Scientist, January 24, 2020.)



Is it possible to have a normal sense of smell without olfactory bulbs?

January 28, 2020

Maybe so, according to a new article. A small percentage of women seem to have this trait. Especially left-handed women.

What's an olfactory bulb? It's a distinct brain structure. Primary responses from the olfactory receptors (in the nose) travel to olfactory bulbs in the brain, where they are processed. People lacking olfactory bulbs (one on each side) lack the sense of smell. The olfactory bulbs are an integral part of the olfactory system. Or so we thought.

The following figures show some of the evidence from the new article. The first figure shows measurements of the size of the olfactory bulbs in a collection of people.

The figure shows the volume of the olfactory bulbs (OB; y-axis), with separate data for the left and right OBs. (The volumes were measured by MRI.)

The main data set is for an ordinary population (controls). The blue dots show the means, and the vertical bars show the standard deviations.

Then there are three points at the bottom on each side; these show the results for three specific people. OB volume essentially zero, both left and right. These people lack olfactory bulbs. They are identified here with NAB names.

   This is Figure 1E from the article.


The following figure shows measures of functional olfactory systems -- the sense of smell -- for these three people...

Part A shows one such test, and part B shows three parts of another test. We'll describe them briefly later; for now, the main point is that they are various measures of the olfactory sense.

The general plan for the results is the same as in the top figure. The blue dot summarizes the results for controls; the other three dots are for the three people lacking OBs.

Start with part A. Two of the three NAB points look quite normal; the third is very low.

The three scores in part B show the same pattern.

The controls are not the same people in the various tests; in fact, some of the controls shown are values from the literature. The NAB data is for specific individuals studied here by the current authors.

The test in part A is a person's own evaluation of the importance of odor to them. The x-axis label refers to a test called Subjective Importance of the Sense of Smell Questionnaire; it is referred to as both SISSQ and SSISQ in the article.

The test in part B is the Sniffin Sticks test. It is a standard test for measuring the sense of smell objectively. The three scores are for different aspects of that test.

   This is part of Figure 3 from the article.


Taken together, the data above show that individuals NAB1 and NAB2 lack olfactory bulbs but have a normal sense of smell.

The third NAB individual, NAB-CA, was known to have congenital anosmia (CA), lacking a sense of smell.

The finding is a surprise, and the scientists have no explanation at this point. It will the basis of follow-up work -- which inevitably should lead to a better understanding of the olfactory system.


At the top of this post, I suggested some statistics. After uncovering the two people who lacked olfactory bulbs but had normal smell -- both women, the scientists went on to screen a substantial number of people (from a public database). They found more such people (normal olfaction, but lacking olfactory bulbs), all of them women. Overall, they found that about 0.6% of women have this trait; for left-handed women, it is about 4%. No men with the trait have been found. What does this mean? They don't know. There may be some interesting biological connection, or it might be just a statistical fluke; the numbers are not very big.

The authors note that there have been occasional reports of mammalian olfaction without olfactory bulbs in the past, mainly in rodents. These reports have not been well accepted. The current article provides the best evidence yet on the matter, with live human subjects available for testing.


News stories:
* Typical olfactory bulbs might not be necessary for smell, case study suggests. (EurekAlert! (Cell Press), November 6, 2019.)
* An exception to the rule: An intact sense of smell without a crucial olfactory brain structure. (Science Daily (Weizmann Institute), November 11, 2019.)

The article, which is freely available: Human Olfaction without Apparent Olfactory Bulbs. (T Weiss et al, Neuron 105:35, January 8, 2020.)

Posts on olfaction include:
* Could smelling a piece of wood improve the growth of your hair? (November 5, 2018).
* Olfaction and obesity? (July 18, 2017).
* The chemistry of a tasty tomato (June 18, 2012).
* What does blue light smell like? (July 18, 2010).

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



A robust capsule for providing micronutrients

January 26, 2020

Many people don't get all the vitamins and minerals they need. What if one could just get them from a simple pill?

That suggestion may evoke various reactions. But in some parts of the world, delivery of such basic nutrients is a serious large-scale problem. Maybe we should at least consider the pill option, without judgment at this point.

A new article offers progress toward a basic nutrient pill or "capsule". It's an interesting story.

The following figure shows the idea and some results...

The particular testing shown here involves a capsule with four micronutrients, listed in the key at the right (in part G).

Part D (left) is a cartoon of the capsule. It looks a bit complicated. In fact, it is what the authors call a two-step capsule. By using a two-step process, they get good encapsulation of both water-soluble and fat-soluble nutrients.

The other three parts of the figure show the release of the four nutrients over time, under different conditions. In each part, there are four curves, one for each of the four nutrients. The curves for all four nutrients are similar; here we will just refer to them together.

What is more interesting are the three conditions. You can see that the nutrients are substantially released in about a half hour in part E, and only slightly released even over two hours in parts F and G.

Part E is for SGF at 37 °C. SGF? Simulated gastric fluid. That is, this condition represents your stomach -- where we want the nutrients to be released.

The other two parts are for water at RT (room temperature) and at boiling. The first represents simple storage; the second represents cooking. There is little loss of nutrients in either condition -- a good sign.

   This is part of Figure 2 from the article.

The following comment is not needed for what is written above, but may be helpful if you check the full figure in the article... The figure legend there suggests a color code for part D. However, it does not agree with the figure; that's fine if you take the figure as a diagram or cartoon. The color coding suggested -- incorrectly -- for part D does in fact hold for the other parts, as shown in the key.


That's encouraging. A single capsule with four nutrients (two water-soluble and two fat-soluble) behaves well in this test. It releases the nutrients under stomach conditions, but not during storage or cooking.

Overall in the article, the scientists test eleven nutrients (vitamins and minerals), using various simple and more complex capsules, such as the two-step capsule shown above. All the simple tests are encouraging. The test above is with a four-nutrient capsule, the most complex they have tested so far.

The article includes testing in rodents, and some testing in humans. In one case, a problem identified during such testing (on the bioavailability of iron), led to further development of capsule composition.

Capsule production itself is simple and inexpensive, even for the two-step process. (The article includes some general discussion of the economic issues.) Importantly, the practical considerations were invoked at the start; the goal was to develop practical capsules for large scale delivery of essential micronutrients. The capsules, which are tiny (about 0.2 mm diameter), might be used in a pill, or they might be used to fortify current foods.


News stories:
* New strategy for encapsulating nutrients makes it easier to fortify foods with iron and vitamin A. (Medical Xpress (MIT), November 13, 2019.)
* Fighting malnutrition: Could new nutrient delivery strategy help billions of people? (N Gray, Nutraingredients, November 14, 2019.)

The article: A heat-stable microparticle platform for oral micronutrient delivery. (A C Anselmo et al, Science Translational Medicine 11:eaaw3680, November 13, 2019.)

The work is, in part, from the lab of Bob Langer at MIT. Langer is a chemical engineer well known for clever and useful ideas.

* * * * *

My page Internet resources: Biology - Miscellaneous contains a section on Nutrition; Food safety. It includes a list of related Musings posts.



A Zika vaccine test: protection of the developing fetus?

January 24, 2020

A particular concern with Zika virus is that it can lead to fetal problems, collectively known as congenital Zika syndrome (CZS), if the mother is infected during pregnancy. (The best known of the problems is microcephaly, though it occurs at low frequency.)

A recent article reports a test, in macaque monkeys, of a vaccine against Zika. The big message is that vaccination of the mother helps protect the developing fetus.

The figures below show some data about the effectiveness of the vaccine. In the first figure, effectiveness is measured by virus replication or antibody level.

Part C (left). This graph shows the amount of viral RNA found in each monkey, for control and vaccinated animals. Each point shows the peak viral RNA (log scale) for one animal. The horizontal line in each data set shows the mean.

Part D is similar, but shows viral RNA by a different measure: the AUC (area under curve -- of virus level vs time), a measure of the total virus production.

By either measure, the levels of viral RNA are, in general, lower in the vaccinated animals. There is one vaccinated animal with high viral levels.

Part E shows the level of neutralizing antibodies (log scale) in the vaccinated animals. They are divided into two groups: those that did or did not develop measurable levels of virus ("viremia"). The results show that animals with the highest levels of antibody did not develop viremia.

   This is part of Figure 3 from the article.


The general picture is that the vaccine is effective. In general, vaccinated animals have lower viral levels. And low viral levels correlate with high levels of antibodies.

The next figure looks at the vaccine effectiveness as judged by fetal pathology.

The top graph is for fetuses from control (unvaccinated) mothers; the bottom graph is for fetuses from vaccinated mothers.

In each case, there are two sets of points, based on the overall "pathology score" for the fetus. Fetuses with low pathology scores (<3) are in the left set; those with higher scores are at the right. (We'll describe the score more later.)

Each point shows the number of days that the mother had viremia.

Observations...
- A smaller percentage of the animals in the vaccinated group had high pathology scores.
- For unvaccinated animals, longer periods of maternal viremia correlate with higher pathology scores.
- Duration of maternal viremia is greatly reduced in the vaccine group.


   This is part of Figure 7 from the article.


The first of those points is the key one. The vaccine, given to the mother prior to conception, reduced pathology in the fetus.

What are those pathology scores? The scientists looked for pathology in four regions of the fetus, and rated it from 0 to 4 (none to severe). The sum of those four region-scores is the pathology score for the fetus; it could range from 0 to 16. The cutoff of 3, used in the analysis above, means that any one case of "moderate" pathology or two cases of "mild" pathology put the fetus into the "bad" group.


Overall, the vaccine induced protective antibodies, and led to less virus production, as well as to reduced pathology in the fetus. That's all good. However, the study is quite small, with about ten animals in each group. And there are many details, such as the timing of vaccination and virus exposure, that might have complex effects. So this work is an encouraging step toward a useful vaccine that can reduce fetal pathology from Zika, but there is more to learn.

The vaccine is now being tested in humans. Interestingly, the incidence of Zika is now low enough that it will be hard to measure the vaccine's effect on fetal pathology. That's why these monkey tests, limited though they may be, are important.


News stories:
* NIH-developed Zika vaccine improves fetal outcomes in animal model. (National Institutes of Health, December 19, 2019.) NIH was a participating lab, as well as funding source.
* Zika vaccine protects fetus in pregnant monkeys . (Science Daily (University of California - Davis), December 18, 2019.)

The article, which may be freely available: DNA vaccination before conception protects Zika virus-exposed pregnant macaques against prolonged viremia and improves fetal outcomes. (K K A Van Rompay et al, Science Translational Medicine 11:eaay2736, December 18, 2019.)

Previous post about Zika: Asian Zika in Africa (October 12, 2019).

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



January 22, 2020


Briefly noted...

January 22, 2020


1. The new coronavirus. The big medical story of the new year. (The first case was reported on December 31, 2019,) It's too early for scientific articles, but there is a daily barrage of news, some straightforward, some confusing or even contradictory. The new virus, a coronavirus, is related to SARS and MERS. The disease is similar, and some of the news is eerily similar to the SARS story of two decades ago. The new disease probably got to humans via markets dealing in live animals, and it is being transmitted worldwide via airplanes.
* The US CDC (Centers for Disease Control and Prevention) has established a page for the new virus: 2019 Novel Coronavirus (2019-nCoV). An excellent official source of information, much of it intended for healthcare workers.
* For the latest, I recommend CIDRAP. They have an update almost every day. Their pages are well-written, and include links to their sources. Search on 'CIDRAP novel coronavirus' or such, check the CIDRAP web site, or even sign up for their daily e-mail. The CIDRAP home page is http://www.cidrap.umn.edu.
* My page Biotechnology in the News (BITN) -- Other topics has a section SARS, MERS (coronaviruses). I will start adding some basic information for the new virus.


2. An unusual bird song. The news from the fire scene in Australia is horrible. But in the middle of all that, something of some scientific interest happened -- and is noted in the video listed here.
* video. (1 minute; YouTube.)



An improved bandage, based on superhydrophobic carbon fibers

January 21, 2020

A team of scientists recently reported a better bandage. The following figure shows the story.

Caution... The layout of the figure is inconsistent, and some is not well-labeled.

The figure is about a test of the new bandage vs a traditional gauze bandage on a wound on the back of a rat.

Part a (left)... Immediately upon applying the bandage. Top photo is for the new bandage ("CNF gauze"); bottom photo is for the traditional bandage ("control"). Blood leakage through the control bandage is evident; there is no blood through the CNF bandage.

Part b... After 3 minutes, the bandages are peeled back. Top and bottom are for new and control bandages, as before. The wound under the new bandage is closed; the wound under the control bandage is not. The new bandage has promoted clotting.

Part c -- which does not follow the previous format... Part c is two images wide. The top two images are for the two types of bandages, peeled back after 2 hours. And the bottom two show what happens when the exposed wound is slightly stretched "by hand" (by the blue-gloved fingers); each bottom image goes with the bandage shown immediately above it. The performance of the new bandage is better in all respects.

Parts d and e show some data over several tests. Part d shows the blood recovered on the bandage; it is much lower for the new bandages. Part e shows the force required to remove the bandages; it, too, is much lower for the new bandages.

   This is part of Figure 5 from the article.


The results show that the new bandages have several advantages over the traditional gauze bandages.

What is this new bandage? CNF stands for carbon nanofiber. The bandage is basically ordinary gauze coated with CNFs.

The CNFs make the bandage surface hydrophobic -- even superhydrophobic. Some of the advantages are clearly related to the hydrophobic nature of the new bandage. It doesn't absorb liquids; it repels them. But the new bandage promotes clotting. That came as a surprise to the scientists, too. It is what led to considering the use of the material for bandages -- rather than for blood flow machines.

The new bandages also seem to be anti-bacterial. In part, that is due to their hydrophobic nature; the bandages themselves do not serve as a substrate for bacteria. Further, that the new bandages do not disrupt the wound when removed helps keep the wound clean.

The authors emphasize that they have an approach, not a final product at this point.


News stories:
* This new bandage stops bleeding without sticking to wound -- Scientists have devised a new king of bandage that simultaniously [sic] repels blood and promotes clotting. (T Puiu, ZME Science, January 10, 2020.)
* Bandage material helps stop bleeding without adhering to the wound. (Phys.org (F Bergamin, ETH Zurich), January 9, 2020.)

The article, which is freely available: Superhydrophobic hemostatic nanofiber composites for fast clotting and minimal adhesion. (Z Li et al, Nature Communications 10:5562, December 5, 2019.)

There are several movie files posted with the article at the journal web site. No sound; most are 10-15 seconds. The last two show the removal of the two types of bandages from the rat wound, discussed in the figure above.

* * * * *

More things superhydrophobic... Disease transmission by sneezing -- in wheat (July 29, 2019). Links to more.

More about wound healing... Targeting growth factors to where they are needed (April 21, 2014). Links to more.



Designing reconfigurable organisms

January 19, 2020

An example.

It is about a millimeter across.

   (For figure credit, see next paragraph.)

I suggest you watch a little "movie" (animated gif) of "it": [link opens in new window]. (The movie is about 3 MB; no sound. It loops; you can tell when it loops, because the thing suddenly jumps back to the original position.) (The movie is from the news story in The Scientist, listed below. It comes from the authors of the article. The top figure in this post is trimmed from the first frame of this movie file.)

What is it? A little machine. Perhaps you would call it a robot.

It was designed by a computer scientist-roboticist at the University of Vermont, then "built" by folks at Tufts University.

Genetically, it is Xenopus laevis, the African clawed frog, a common organism for lab work.

The thing is made from skin stem cells and heart stem cells of the frog. What makes it special is that the cells are laid down in a particular pattern -- one that the computer modeling suggested would lead to a meaningful device.

The meaning of this particular meaningful device is quite simple. It is a coherent device, capable of moving in one direction. It does seem to be a machine, even if a simple one. And the design was chosen based on computer modeling. It is a machine designed by humans (and computer) -- and it has an ordinary biological genome.

Another device that the team predicted and built can carry cargo.

The current work used only two kinds of cells. That computer modeling showed some success in predicting how the cells will function in various configurations is just a start.

The authors call this thing a xenobot. The "xeno" there refers to the genus name of the frog -- so they say.


News stories:
* Algorithm Designs Robots Using Frog Cells. (E Yasinski, The Scientist, January 13, 2020.)
* Living robots built using frog cells -- Tiny 'xenobots' assembled from cells promise advances from drug delivery to toxic waste clean-up. (Science Daily (University of Vermont), January 13, 2020.)
* Scientists use stem cells from frogs to build first living robots -- Researchers foresee myriad benefits for humanity, but also acknowledge ethical issues. (I Sample, Guardian, January 13, 2020.)

The article, which is freely available: A scalable pipeline for designing reconfigurable organisms. (S Kriegman et al, PNAS 117:1853, January 28, 2020.)

There are two movie files posted with the article. (About 3 minutes each; no sound.) The first describes the design process; you may find it helpful. The second shows some of the actual assembly. The videos are also available at YouTube: #1 and #2.

The article was posted online just a few days ago, and quickly attracted considerable attention. The news stories listed above all came out the day of posting of the article. More analytical stories will presumably appear over time. As always... If you want more about an article, I suggest putting the article title into a search engine.

There is a Wikipedia page for xenobots.

* * * * *

Previous posts using the term "reconfigurable organism": none.

A post about Xenopus: What if you had eyes on your tail? (July 27, 2013).

My page Biotechnology in the News (BITN) for Cloning and stem cells includes an extensive list of related Musings posts.



Alzheimer's disease: a role for inflammation?

January 18, 2020

A leading model for Alzheimer's disease (AD) is based on the accumulation of a peptide commonly called amyloid-beta (Aβ or AB, often with a number, e.g., AB-42, indicating the number of amino acids). However, attempts at treatment based on that simple model have failed. There must be more to AD.

It is likely that a protein called tau is involved in AD -- and in other neurodegenerative diseases. And there may be a role for inflammation.

A recent article provides evidence for a positive feedback loop between tau and inflammation. It's a very complex article, much of it with a mouse model of tau-related neurodegeneration. All we can do here is to show a couple of pieces of the story.

The first figure shows that inflammation promotes tau pathology.

The figure shows staining of brain (hippocampus) slices from 11-month-old mice. The stain shows hyperphosphorylated tau, which is considered important in the pathology. The different images are from different mouse strains.

Start with the two images at the left. The top one is for normal (wild type; WT) mice. The bottom one is for mice that over-express a particular tau protein (Tau22), one that is commonly used in mouse models. You can see that there is considerable staining for hyperphosphorylated tau in the mouse with high levels of tau.

The middle and right sets of images are for mice with additional mutations that interfere with formation of inflammasomes. They are labeled Asc-/- (middle) and Nlrp3-/- (right). The -/- means that both copies of the indicated gene have been disrupted.

The images in the bottom row show that the additional mutations, blocking inflammasome production, reduce the staining for hyperphosphorylated tau. (Those mutations have no effect in the top row, where there is no staining evident in the control.)

   This is Figure 2a from the article.

The adjacent figure in the article, 2b, shows quantification of these results over multiple mice. The overall data support the observations noted above, which are sample images of each type.

The scale bar (lower right) is 0.5 mm.


That test suggests that inflammasomes enhance the production of hyperphosphorylated tau, hence its pathology.

The following figure suggests that tau enhances inflammasomes.

This figure is actually for humans. It shows the levels of two proteins in the brains of people with frontotemporal dementia (FTD) and controls. FTD is another tau-dependent neurodegenerative disease. ASC (top row) is a protein of the inflammasome, as noted earlier.

You can see that the level of ASC is higher in each of the FTD people than in the controls.

   This is Extended Data Figure 1a from the article. (Extended Data Figures are not in the print version of the article.) The adjacent Figure 1b shows the quantitative data over all the people tested.


Knowledge of that result leads the scientists here to test their system. They find that high levels of tau indeed lead to higher levels of inflammasomes in their mouse model.

The results discussed above suggest there is a positive feedback loop between tau and inflammasomes. But there is no clear answer as to what is important. Indeed, there is still no clear understanding of how AD develops. The work here just provides more clues.

A possible implication of such work is that drugs targeted to the inflammasome might interfere with tau-dependent pathology, including AD.

What happened to amyloid-β, which we used to say was key to the development of AD? As the story develops, Aβ is still important, but is an early stage. For example, it may well be that Aβ triggers tau pathology, perhaps acting via the inflammasome.

Stay tuned.


News stories:
* Direct link shown between inflammasome activation and Alzheimer's -- A new study has demonstrated that NLRP3 inflammasome directly drives tau pathology in neurodegenerative diseases and Alzheimer's disease. (R Harper, Drug Target Review, December 2, 2019.)
* In Alzheimer's, Inflammasome Drives Both Amyloid and Tau Pathology. (GEN (US National Institute on Aging), November 22, 2019.)
* Microglia Inflammasome Stokes Tau Phosphorylation, Tangles. (ALZFORUM, November 22, 2019.) A high-level discussion of the article and its implications.

The article: NLRP3 inflammasome activation drives tau pathology. (C Ising et al, Nature 575:669, November 28, 2019.)

Previous post about AD: Alzheimer's disease: The role of vascular damage? (August 13, 2019).

Previous post about tau: Traumatic brain injury: long term effects? (October 8, 2019).

A post about tau and AD: Alzheimer's disease: What is the role of ApoE? (November 6, 2017).

A post exploring a possible role for inflammation in another disease: Chronic fatigue syndrome: a clue about the role of inflammation? (October 27, 2017).

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



January 15, 2020


Briefly noted...

January 15, 2020


Two -- very different -- items about CRISPR.


1. Early results from clinical trials of CRISPR for humans. Two recent news stories, one from last week, provide an overview. No big answers. Trials are in progress; some early observations are coming in. No big problems have emerged; evidence for benefit at this point is limited, but perhaps encouraging in some cases.
* News stories:
- Early Results Are Positive for Experimental CRISPR Therapies. Two clinical trial participants - one with β-thalassemia and one with sickle cell disease - appeared to benefit from the gene-editing treatments with minimal side effects, according to the companies. (J Akst, The Scientist, November 19, 2019.) Links to the press release from the companies, which has more details -- and disclaimers.
- Quest to use CRISPR against disease gains ground -- As the first clinical-trial results trickle in, researchers look ahead to more sophisticated medical applications for genome editing. (H Ledford, Nature, January 6, 2020. In print, with a slightly different title: Nature 577:156, January 9, 2020.)


2. Using CRISPR for controlled degradation of a gel. CRISPR is, most fundamentally, a way to make specific cuts in DNA. If you have a structure, such as a gel, that includes DNA, CRISPR could be useful for modifying the structure.
* News story: CRISPR-Based Tool Expands DNA-Hydrogel Versatility -- DNA-responsive polymer gels used for releasing drugs, encapsulating cells, and much more now have greater adaptability thanks to the Cas12a nuclease. (R Williams, The Scientist, December 1, 2019.) Links to the article.



Is it ok to eat while standing up?

January 14, 2020

Does eating standing up affect your perception of how the food tastes?

Let's look at a test, from a recent article...

The first two bars, to the left, are for a simple test -- the control, in this case. Groups of people were asked to rate the taste of a snack, on a scale of 0-7. Higher score means "more pleasant". One group did the test while sitting, one group while standing (dark and light bars, respectively; see key at the very bottom).

Bar heights show the average taste rating for each group, with error bars showing one standard deviation.

You can see that the taste rating was higher for the people who were sitting.

The other pairs of bars are for variations of that test. In the middle test, each participant had a physical stress imposed. (They had to hold a heavy bag.) The results for sitting and standing are now about the same. That is mainly because the sitting score is considerably lower than it was in the control test (without the stress).

In the right-hand test. a psychological stress was imposed. We'll skip that here.

   This is Figure 1 from the article.


Further testing helped to distinguish two possible explanations for the effect of standing on perceived taste. One possibility is that standing leads to a lower rating of taste. Another is that standing makes us less sensitive to taste effects. It was found that unpleasant-tasting foods were rated less unpleasant when standing; this supports the second suggestion: standing reduces our perception of taste, whether good or bad.

What are we to make of all this? I don't know. Some of the effects are plausible; some are fairly small.

Our response to food is complex. We know that what we commonly call taste is influenced by smell. And visual appearance of food matters. The current work explores a different type of sensory perception.

What may be as interesting as anything is the purpose of the work. It is marketing research. Is it ok to eat standing up? That's up to you. Does it affect how you perceive the food? Maybe, a little. It may not matter much to you, but it might matter a lot to a company testing consumers for their preferences.


News stories:
* Posture impacts how you perceive your food. (Science Daily (University of South Florida), June 7, 2019.)
* Distracted Eating: Less Tasty, But More Filling? (C Dinerstein, American Council on Science and Health, June 12, 2019.)

The article: Extending the Boundaries of Sensory Marketing and Examining the Sixth Sensory System: Effects of Vestibular Sensations for Sitting versus Standing Postures on Food Taste Perception. (D Biswas et al, Journal of Consumer Research 46:708, December 2019.)

From the Abstract...

... This research extends the boundaries of sensory marketing by examining the effects of the vestibular system, often referred to as the "sixth sensory system," which is responsible for balance and posture. The results of six experiments show that vestibular sensations related to posture (i.e., sitting vs. standing) influence food taste perceptions. ... These findings have conceptual implications for broadening the frontiers of sensory marketing and for the effects of sensory systems on food taste perceptions. Given the increasing trend toward eating while standing, the findings also have practical implications for restaurant, retail, and other food-service environment designs.

* * * * *

More about testing consumer preferences...
* The chemistry of a tasty tomato (June 18, 2012).
* Should the music industry use MRI scans to predict the success of new songs? (June 28, 2011).

More about gravity and blood flow: Which direction does blood flow in an astronaut? (January 7, 2020).



Cross-linking unreactive polymers, using carbenes

January 12, 2020

Cross-linking polymers can make them stronger -- as discovered by Charles Goodyear over a century ago. But some polymers are hard to cross-link, because they don't have any reactive sites. Polyethylene is a good example: the polymer contains only C-C and C-H bonds.

A new article offers a way to cross-link such polymers. It involves an unusually reactive cross-linking agent. It's a two-headed cross-linking agent; that is the basis of it linking together two chains. But an unusually reactive agent raises a new problem: how do you control it?

The first figure describes the idea. The second offers an example.

The key is carbene.

Part A shows the chemistry. It starts (at the left) with a diazirine, a chemical with a three-membered ring containing -N=N-.

Diazirines are not very stable. Three-membered rings are highly strained, and that N=N is so close to the stable common form of nitrogen, N2, that it "wants" to pop out. In fact, many such chemicals are explosive, but here the scientists designed one that is stable enough to handle.

Importantly, the decay of that compound can be triggered, by heat or light (shown as Δ and hν, respectively). Decay leads to N2 being released. What is left? A carbene (middle of part A). A chemical with a C atom with only two bonds, and a lone pair of electrons.

The carbene is highly reactive, and can react with an ordinary C-H bond. That leads to the product shown at the right.

Part B is similar, but this time shows the two-headed cross-linking agent. It has two of those things we just talked about; it is a bis-diazirine. Activate it, and two molecules of N2 are released, and a molecule with two carbenes in it is left. That double-carbene can now react with two C-H bonds, so long as they are not too far apart (as restricted by the linker between the carbene groups). If those two C-H bonds are in different chains of the plastic, the result is cross-linking of the chains. Part B shows those two carbene reaction steps, one after the other, leading to cross-linking two chains at the right.

This is slightly modified from Figure 1 of the article. I edited out one reaction pathway, as noted near the top of the figure, for simplicity of presentation here.


The following figure shows an example of the effect of cross-linking on the properties of the plastic.

In this test, two samples of polyethylene fabric were treated with the cross-linking agent. The samples were subjected to a tearing test. The test is standard, and is not described in detail in this article. But it measures the energy required to tear the fabric.

Start with the left set of bars (labeled as 75 g/m2, a measure of the thread thickness (linear density)).

The first two bars (to the left) are controls: fabric that was not treated, or was mock-treated (solvent but none of the cross-linking agent). The next two bars are for low and high levels of the cross-linking agent. You can see that both cross-linking treatments led to more energy being required to tear the fabric. That is, cross-linking strengthened the fabric.

The next set of bars (to the right; labeled as 90 g/m2) shows results of similar tests for a fabric with a slightly thicker thread.

Start by skipping the middle (orange) bar... The tests are the same as before, and the results are similar.

That orange bar? It's another negative control. The label says "1 wt% 7"; all the other treatment bars say 3 at the end. Those are numbers for the chemicals. 3 is the active cross-linking agent. 7 is a similar chemical that cannot cross-link; it didn't.

   This is Figure 3G from the article.


Bottom line... The scientists have made progress toward strengthening unreactive polymers such as polyethylene. They do this by making a very reactive cross-linking agent, and learning to control it.

They also show that their cross-linking method can work to bond two surfaces of otherwise-unreactive plastics. That's a task Super Glue cannot do.


News story: New 'hyper glue' formula -- Cross-linking technology tightly binds where commercial glues cannot. (Science Daily (University of British Columbia Okanagan), December 4, 2019.)

* News story accompanying the article: Polymer chemistry: Cross-linking polyethylene through carbenes -- A carbene-forming molecule can glue various polymers, even ones lacking functional groups. (F J de Zwart et al, Science 366:800, November 15, 2019.)
* The article: A broadly applicable cross-linker for aliphatic polymers containing C-H bonds. (M L Lepage et al, Science 366:875, November 15, 2019.)

Among posts about polyethylene: Degradable polyethylene isn't (October 17, 2011). Links to some other posts about plastics.



Strawberries, bees, and their bacteria: a complex alliance

January 11, 2020

Nature is complicated. Organisms interact with each other. Analyzing a complex biological system and trying to understand the interactions is difficult, but perhaps interesting.

A recent article explores a relatively simple system: strawberries growing in a greenhouse, with bees as pollinators. The scientists provide evidence that a particular bacterial strain, normally found in the soil, protects both the plants and the bees. We will note a couple pieces of the story.

The first figure shows evidence suggesting that the bacteria protect the strawberry plants from a fungal disease (gray mold disease).

The first two curves listed in the key show (a measure of) the number of a particular kind of Streptomyces bacteria found on the pollen or flowers (filled circles or open squares, respectively; left-hand y-axis scale) vs time (x-axis).

The last curve listed shows the disease incidence (open circles; right-hand y-axis scale).

The main observation is that there are plenty of bacteria around for about the first 12 weeks -- and minimal disease. Later, there is disease, but few bacteria. That pattern is what one might expect if the bacteria were preventing the disease. (Of course, this data set alone is hardly proof; it is simply one piece of evidence.)

   This is Figure 1g from the article.


The next figure provides evidence that the bacteria also protect the bees.

Look at the top graph, the red one. The graph shows bee mortality (y-axis) for four conditions.

The right-hand bar is for bees infected with a particular pathogen. Over 75% mortality. The bar next to that is for similar bees, but now also with the protective bacteria (called SP6C4). You can see that the presence of the bacteria substantially reduced the mortality.

The first two bars, to the left, are controls: bees alone or with only the treatment bacteria.

The bottom (blue) graph is the same idea, but with a different pathogen. Again, the treatment bacteria provided significant protection to the bees.

The bacterial pathogens are Serratia marcescens (top) and Paenibacillus larvae (bottom). Those names are shown on the figure, vertically, at the far right; hard to read.

The bees in this experiment are bumblebees (Bombus). (Some experiments reported in the article used honeybees (Apis).)

   This is Figure 5c from the article.


The results discussed above provide some evidence that the bacteria protect both plant and bees. The bacteria are Streptomyces, a type of bacteria known to make various anti-microbial agents. In fact, some of the strains isolated during this work were shown to do so. An interesting point is that these are normally soil bacteria, but are found here in the flower area of the plant. How did they get there? The article provides evidence that the bacteria distribute easily through the plant tissue. Further, the bees transfer the bacteria from one flower to another.

How convincing is all this? That varies. It may be best to think of this article as an exploration. It offers some insight into some of the interactions within this relatively simple system.


News story: Strawberry Fields Forever. (M Zambrano & R Kolter, Small Things Considered, October 28, 2019.)

The article, which is freely available: A mutualistic interaction between Streptomyces bacteria, strawberry plants and pollinating bees. (D-R Kim et al, Nature Communications 10:4802, October 22, 2019.)

Previous posts about strawberries: none.

A recent post about bees and plants: What should a plant do if it hears bees coming? (December 10, 2019).

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.



January 8, 2020


Briefly noted...

January 8, 2020


Beethoven's dream. On November 7, 2019, the scientific journal Nature published their 150th anniversary issue. Among the large and diverse collection in that special issue was an essay on Beethoven.
* Essay, chosen by competition. It is freely available: Beethoven's dream. (Y Ali, Nature, November 4, 2019. In print: Nature 575:53, November 7, 2019)
* I have also noted the essay on my page Internet resources: Miscellaneous in the section Art & Music.



Which direction does blood flow in an astronaut?

January 7, 2020

Humans on Earth spend about 2/3 of their time with a difference in gravitational potential between head and heart. Humans in the weightlessness of space lack this gravitational difference -- for extended periods. Does it matter?

A new article from NASA (and collaborating institutions) explores the question. The article reports measurements of the blood flow through the jugular veins, which return blood to the heart from the head. The measurements were made on eleven astronauts on the International Space Station (ISS), before, during and after extended periods in space.

The following figure shows some of the results...

Results are shown for some pre-flight measurements (first three columns, to the left), and at about day 50 of flight (right-hand column).

Results are shown as a "grade", based on Doppler ultrasound measurement of blood flow. Briefly, grade 1 is normal and 2 is probably ok. Grades 3 and 4 are not so good. We'll return to what the grades mean later.

The pre-flight grades are all 1 or 2. More specifically, they are all 1 when the person is seated (head above the heart). And they are mostly 2 when the person is supine (lying down; head and heart at same elevation), or HDT (head-down tilt).

The data at day 50 of flight show grade 3 or 4 for about half of the astronauts. Not so good. That's the main idea.

Two of the "crew number" entries have an "a" on them. The "a" means that these two crew members showed evidence of a thrombus -- a blood clot -- in the vein. Not so good. Both of these people scored a 3 at day 50. (The thrombi reported here were not associated with any symptoms during flight.)

   This is part of Figure 3A from the article.

The full Figure 3A in the article has more. There are more columns of grades during flight, at days 50 and 150. The general pattern continues: lots of 3 & 4 grades. There are also some post-flight grades. These are mostly back to 1 and 2, but not quite as good as the pre-flight grades.


Let's look at what those blood flow grades mean.
- Grade 1 means that the flow is always downward, from head to heart. The top frame of the attached figure shows an example: Figure 1 from the article [link opens in new window]. The light horizontal line near the top is at flow = zero. The entire data set in the top frame is below that line. The sign convention is that flow downward is negative. (That is, in this case, negative flow is normal.)
- Grade 2 means that the blood flow was mostly normal (downward), though occasional brief periods of backward (upward) flow were seen.
- Grade 3 means that there was very little blood flow at all, with intermittent periods of both upward and downward flow. This is referred to as "stagnant" blood.
- Grade 4 means that the blood flow is mainly backward (upward).
   * The y-axis scales are not the same for all frames. But they are close, and visual comparisons will not be far off.


It's a small study, but it raises concerns -- especially for long term space travel. About half the astronauts examined had unusual blood flow in the jugular vein, and about half of those showed signs of a blood clot.


News stories:
* Dangerous Health Risk to Human Spaceflight to Mars Revealed in New NASA Study. (Sputnik, November 18, 2019.)
* Long spaceflights found to lead to blood flowing in the wrong direction in some cases. (B Yirka, Phys.org, November 19, 2019.)

The article, which is freely available: Assessment of Jugular Venous Blood Flow Stasis and Thrombosis During Spaceflight. (K Marshall-Goebel et al, JAMA Network Open 2:e1915011, November 13, 2019.)

Added January 8, 2020. As I was finishing up this item, there was a story on the news about a medical problem that had come up on the Space Station. It was about a jugular vein blood clot, which required treatment. It is likely that this is one of the cases noted above. The short article has some details on the treatment.

News story: Ultimate Telemedicine: Expert helps treat astronaut's blood clot during NASA mission. (Science Daily (University of North Carolina), January 2, 2020.)

The article: Venous Thrombosis during Spaceflight. (S M Auñón-Chancellor et al, New England Journal of Medicine 382:89, January 2, 2020.) The authorship of this article overlaps with that of the one discussed above.

* * * * *

A post about genetic factors and blood clotting: Type O blood and survival after severe trauma? (July 7, 2018). (The current article does not mention genetics.)

More about astronauts:
* Photography from the space shuttle (June 4, 2012).
* One way trip to Mars (September 22, 2009).

More from the ISS: European journal open to authors around the world -- and beyond (January 2, 2012).

For more about the effects of space travel on people, see item #1 at: Briefly noted... 1. The effect of space travel on humans: a study of identical twins. (November 13, 2019).

Added January 14, 2020. More about gravity and blood flow: Is it ok to eat while standing up? (January 14, 2020).



Lesson from a worm: An endogenous anti-opioid system?

January 5, 2020

The biology of opioids is complicated. They are natural, and they are used as drugs. They have good effects -- and bad ones.

A recent article uncovers a new piece of the opioid story -- by testing a worm. What the scientists did is interesting. It may have implications for dealing with opioid use in people. Whether it turns out to be useful remains to be seen.

The work starts with some exploration. Add a gene for a mammalian opioid receptor to the worm, and see what the effect is. Then look for mutants (worm mutants) with altered behavior in response to the drug. Characterize mutants that arise, and see what we learn from the mutant worms.

The worm here is Caenorhabditis elegans, a workhorse model organism of biological research.

The first graph below shows the effect of fentanyl, an opioid, on the worms.

Each frame is a travel-log. That is, each line shows what the worm did. Most of them are about the same: the worms moved around a lot. There is one exception, at the lower right. That worm moved very little.

What is that condition, which stopped the worm from moving? That worm had the opioid receptor (called tgMOR). And fentanyl was added. At the 90-minute time point, that worm moved very little.

That is, the worm behavior is altered by the drug -- if they have a receptor for it.

The details...
- Two kinds of worms: wild type (wt) and the worm with the opioid receptor tgMOR (which stands for transgenic mu opioid receptor).
- Two additions: fentanyl, or a buffer as a control.
- And two time points, 0 and 90 minutes after adding the drug (or buffer control). More about time in a moment.

   This is Figure 1C from the article.


With that background, the scientists looked for mutant worms that behaved differently, using that lower right frame above as the reference point. It was brute force. They made mutants, and watched.

The following graph shows what one of the mutants did. The graph is based on the same type of test done above, but with a different way of showing the results. Above, they showed a picture of the movement. Here, they use a movement score (y-axis), and plot it as a function of time (x-axis). The score is the number of "thrashings" per minute. High score = lots of movement, as seen in most frames above.

Start with the black curve. It is for the tgMOR worm, with the opioid receptor. The thrashing score starts high, reaches a minimum at 90 minutes (the time shown in the top figure), and then rises as the worms adapt to the drug.

Now, the red curve, labeled tgMOR bgg9. Same worm as before, but now with an additional mutation that came up during the screen. The "bgg9" mutation disrupts a gene. And these worms show the effect of fentanyl more rapidly.

The scientists infer that bgg9 is in an anti-opioid gene, eventually identified as frpr-13. Inactivate it, and the worms respond more quickly to the drug.

Finally, the gray curve, labeled tgMOR bgg9 + hGPR139. Same worm as for the red curve, but with a new gene added. Compared to the red curve, this worm has a delayed response to the drug. That is, the added gene seems to compensate for the bgg9 mutation. If we take bgg9 as disrupting an anti-opioid gene, then it would seem that this added gene is also an anti-opioid gene.

What is this added gene, and why did they choose it? It is a human gene; note the leading h. Why did the scientists choose it? Well, they know the sequence of the protein for the bgg9-disrupted gene (frpr-13); they looked for human proteins that were similar. GPR139 was a leading candidate, and the test here suggests that it, like frpr-13, has anti-opioid activity.

   This is Figure 2F from the article.


Overall, the work shows that the worms respond to fentanyl if they are genetically modified to have a receptor. That finding allowed the scientists to uncover a native worm gene that seems to have anti-opioid activity: mutations in the gene enhance sensitivity to the opioid, implying that the gene normally reduces sensitivity to it. So what? At this point, the scientists examined the human genome and found that humans contain a gene that looks similar to the worm anti-opioid gene. The second test above provides evidence that the human look-alike gene indeed has anti-opioid activity -- in the worms.

The scientists went on to explore the role of the GPR139 gene in mice. The results suggest that the gene is indeed worth exploring further, and might be a possible drug target to modulate opioid activity. But that should all be taken as preliminary. The main point here is that a clever test in worms has uncovered an interesting candidate, one whose role was previously poorly understood. We await further work.


News stories:
* Anti-Opioid Pathway Discovered via Forward Genetics Approach with C. elegans. (GEN, August 20, 2019.)
* Genetic anti-opioid system: A protein that could make opioid use safer in the future. (B Yirka, Medical Xpress, August 16, 2019.)

* News story accompanying the article: Neuroscience: Countering opioid side effects -- A genetic screen in worms reveals a receptor target to battle opioid addiction. (N M Lindsay & G Scherrer, Science 365:1246, September 20, 2019.)
* The article: Genetic behavioral screen identifies an orphan anti-opioid system. (D Wang et al, Science 365:1267, September 20, 2019.)

Among posts about opioids:
* I feel your pain -- how does that work? (March 4, 2017).
* Do you make morphine? (May 18, 2010).

Among posts involving the use of C elegans as a model organism: Extending lifespan by dietary restriction: can we fake it? (August 10, 2016). Links to more.



Is copernicium noble?

January 3, 2020

Chemical element #112, Cn.

Well, it certainly does not fit in the noble gas column of the periodic table (group 18). But neither does gold, and we often call it a noble metal. Actually, Cn is in group 12, a group that has already revealed a surprise. Mercury (Hg), the previous member of group 12, is a liquid. Chemically, it fits reasonably within its group, but that physical property is not what one expects for a heavy metal. That unusual property of Hg is attributed to relativistic effects: the inner electrons of Hg have such a high speed that relativity has a significant effect on the atomic (electronic) properties.

Spurred on by the unusual behavior of Hg, scientists have been trying to predict the properties of element 112 long before it was ever made. But now it does exist, and one isotope has a long enough lifetime to allow experimental work. So far, theory and experiment have led to a confusing picture about the nature of copernicium.

A new article presents a new analysis of Cn, mainly theoretical. The general conclusion is that Cn is expected to be a liquid (under ordinary conditions), but a very unreactive one -- less reactive than oganesson, the "noble gas" of its period.

Here are some parts of the new analysis.

The first figure shows theoretical predictions of the melting and boiling points for Cn...

It's a complex figure. Let's go through parts of it slowly.

Start with the steep orange line, on the right. That line, labeled "gas", shows the Gibbs free energy (G; y-axis) of Cn gas vs temperature (T; x-axis).

At 331 K, near the lower right, that orange line crosses a light blue line; the point of intersection is shown as an open circle. The light blue line is G vs T for Cn liquid. That is, at 331 K, the Gibbs free energy of liquid and gas Cn are equal. That's the boiling point (BP).

The orange line also crosses a dark blue line at another open circle, at 316 K. That dark blue line is another possible curve for G vs T for Cn liquid, and the 316 K intersection is another prediction of the BP.

Why are there two G vs T curves for the liquid? Two different models. The scientists don't know which is right, so they show the results for both cases.

In fact, they use more than two models. The labeling at the upper right has the BP predictions for the two curves shown. It also has a "final" BP prediction of 340 +/- 10 K; that summarizes their predictions over all their models, including those not shown here.

Similarly, they use the various models to predict the melting point (MP), where G is equal for the solid and liquid phases. G for those phases is shown by green and blue lines, respectively, as labeled on the lower set of curves. The intersection points are shown as filled diamonds. As before, two such points are shown, but the "final" value listed is based on all their work. The predicted MP is 283 +/- 11 K (about 10 °C).

For perspective... The figure includes a broad vertical yellow band. That shows an approximate range for "ambient" T. You can see that the predicted melting point for copernicium is a little below ambient, and the predicted boiling point is a little above ambient. That is, the scientists predict that under ambient conditions, Cn will be a liquid -- a volatile liquid (low BP and a high vapor pressure). The atoms are only loosely bound in the liquid.

   This is Figure 2 from the article.


The next figure shows a prediction of how metallic Cn will be. The specific property shown is the band-gap, a measure of how tightly bound the highest-energy electrons in the atom are.

The graph shows the band gap energy (y-axis), calculated and/or measured, for elements of groups 12 (blue) and 18 (orange). The x-axis is labeled with the symbols for both elements.

We'll start by ignoring the elements at the extreme right side. That is, we will look at the basic pattern of the more common elements from these groups.

For group 12, the first three elements (Zn, Cd, Hg) have very low band gaps -- essentially zero on this scale, a sign they are metallic.

For group 18, the noble gases from Ne to Rn have high band gaps, above the dashed line that divides insulators from metals and semi-conductors.

And then those final two elements at the right, the superheavy elements Cn and Og. The curves cross! The group 12 "metal" Cn is predicted to be an insulator, whereas the group 18 "noble gas" Og is predicted to be near metallic.

   This is Figure 3c from the article.


The common message from both properties discussed above is that Cn is predicted to hold its electrons tightly. Cn atoms will not interact much. That leads to a weakly bound liquid state (with only 60 kelvins between melting and boiling points), and to poor metallicity. We now await experimental tests; the relatively long lifetime of one Cn isotope offers hope that such tests will become practical.

For Hg and Cd, the difference between MP and BP is about 400 kelvins. For Rn, the difference is 9 kelvins; that's a little more than for the lighter noble gases.

Why is Cn so unusual? As with Hg, the unusual behavior is due to relativistic effects. If the scientists carry out similar calculations without including the relativistic effects, they find that non-relativistic Cn would be a metallic solid with a high MP.


News stories:
* Copernicium behaves like a volatile noble liquid, simulations suggest. (T Wogan, Chemistry World, October 23, 2019.)
* Copernicium Is A Strange Element Indeed. (D Lowe, In the Pipeline (blog at Science Translational Medicine), October 11, 2019.) A delightful essay.

The article, which is freely available: Copernicium: A Relativistic Noble Liquid. (J-M Mewes et al, Angewandte Chemie International Edition 58:17964, December 9, 2019.)

Previous post on copernicium: Element #112: Copernicium (July 15, 2009).

My page of Introductory Chemistry Internet resources includes a section on New chemical elements (112 and beyond). It includes a list of related Musings posts.



Older items are on the archive pages, starting with 2019 (September-December).


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