Musings: May 2022 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...


Selenium and neurodegenerative diseases?

June 25, 2022

Sodium selenate, Na2SeO4. A few years ago, scientists found that it activates an enzyme that removes the phosphate group from phosphorylated tau protein.

Tau is a brain protein that has bean implicated in various neurodegenerative diseases. The phosphorylated form of tau is thought to be particularly important.

Is it possible that selenate could slow the progression of a neurodegenerative disease by dephosphorylating tau?

That's the question behind a recent article testing the effect of selenate on people with behavioral variant frontotemporal dementia -- bvFTD, for short. It's a very small study, but the results are at least intriguing.

It's a phase I trial, where the main goal is to test the safety of the proposed treatment. That's simple: the drug was well tolerated (as it had been in some other tests). The test involved 12 people treated for a year, and there were no serious adverse events attributable to the drug. (There were various "minor" effects, some of which are listed in the article (Table 2). These are effects that would be noticed, but would not preclude a treatment if it had meaningful benefit.)

A phase 1 trial is not primarily about benefit, but does include some observations. The following figure offers a glimpse of the effect of the drug on the course of the disease.

The graph shows changes in two measures of the disease over the treatment time. The x-axis is for percent brain volume change (PBVC; measured with MRI). The y-axis is for a score on a test of mental function (NUCOG, a test of COGnition). For both measures, patients with bvFTD typically show negative changes; zero is good.

Each point is for one patient, showing how they progressed by these two measures.

Observations...
- The points seem to form two clusters.
- One cluster, to the lower left, shows negative values for both measures. This is about as expected for patients with normal disease progression.
- One cluster, to the upper right, shows higher values -- closer to zero, though mostly still negative -- for both measures. The disease progressed less than typical in these people.

The two colored points are for two patients with specific known mutations. Since there was only one of each type in the study, no generalizations are possible.

   This is Figure 2A from the article.


Are those two clusters responders and non-responders? Over half of those treated seemed to benefit from the sodium selenate (showing less loss of both brain volume and function).

The test is too limited to reach any big conclusions; there are only 12 patients, and no controls. But it is intriguing; more testing is clearly warranted -- and is in progress.


The article contains another intriguing result. Is it possible to predict which patients will respond to the treatment? Here is what one analysis showed...

The graph shows the likelihood of response (y-axis) plotted against a measure of tau on the x-axis. More specifically, what is plotted here is the ratio. at baseline (the beginning of the trial). of phosphorylated tau to total tau in the cerebrospinal fluid (CSF).

The curve suggests there is a trend: that people with a higher percentage of phosphorylated tau are more likely to respond to the treatment.

That's a lot of fancy graph for a very small amount of data. The pattern must be taken as only a hint, but it is interesting.


   This is Figure 3C from the article.


It's all very preliminary. Remember, the main point of a phase 1 trial is safety. The treatment seems to have passed the safety test rather well, and it also offers hints of some benefit. There is some logic to the story... Phosphorylated tau is a special problem, thought to be relevant in some cases of bvFTD. Increasing the removal of phosphate from tau might be good; sodium selenate does that. That's logical, but remember, there is a huge amount about such neurodegenerative diseases that we do not know.

A small trial of selenate in patients with Alzheimer's disease has yielded ambiguous and confusing results. This is discussed in the Introduction to the current article.


News story: Promising treatment for dementia -- Sodium selenate slows behavioural variant frontotemporal dementia -- second most common dementia in under 60s. (Science Daily (Monash University), May 5, 2022.)

The article, which is open access: A phase 1b open-label study of sodium selenate as a disease-modifying treatment for possible behavioral variant frontotemporal dementia. (Lucy Vivash et al, Alzheimer's & Dementia: Translational Research & Clinical Interventions 8:e12299, May 5, 2022.)

A post about the role of tau in a disease other than Alzheimer's: Tau and ALS (February 19, 2022).

More selenium biology... Did selenium deficiency play a role in mass extinctions? (February 5, 2016)

More selenium... A step toward a practical thermoelectric converter: get the oxide out (October 11, 2021).

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



June 22, 2022 (Current e-mail)


Briefly noted... COVID and pets?

June 22, 2022

It's something we have been wondering about, and we now have an update, based on collecting data in Toronto. Bottom line... Household cats and dogs do get infected with COVID-19. They develop antibodies, and sometimes get sick; occasionally, but not often, they may die from COVID. They probably get COVID from their human companions. There is no evidence that they transmit it to humans, but that cannot be excluded. The article also notes the issues of COVID in minks and deer; these are more serious.
* News story: Pets living in households with COVID-19 are high [sic] likely to seroconvert and become ill. (Neha Mathur, News-Medical.net, May 3, 2022.) Links to the article, which is open access.
* Direct link to the article, which is open access: Risk Factors for SARS-CoV-2 Infection and Illness in Cats and Dogs. (Dorothee Bienzle et al, Emerging Infectious Diseases 28:1154, June 2022.)
* There is a BITN section for SARS, MERS (coronaviruses). It includes a list of Musings posts in the field.



Silicates and gene expression -- a new way to induce making cartilage?

June 21, 2022

The following figure shows an effect of a silicate material on stem cells in lab culture...

The cells were stained for the enzyme alkaline phosphatase, after 14 days.

You can see that the cells grown with "nanosilicates" are different: they have more of the enzyme.

The other parts are for various ions from the material. They generally gave a response, too, especially the one with Si alone (as a soluble silicate).

   This is part of Figure 2B from the article. The full Fig 2B also includes quantitative results from an enzyme assay for the same enzyme.


Here is more. More proteins responding to the nanosilicates (and its ions)...

In each case, more protein was made in response to the nanosilicates. The left-hand graph is for a form of collagen associated with making cartilage; the effect is about 15-fold in this case.

The quantitative results shown here are based on measuring bands on Western blots, normalized to a "standard" protein (β-actin).

This is part of Figure 2C from the article. The full Fig 2C contains data for other proteins, and also images of the Western blots.


What is this nanosilicate stuff? Many natural minerals are silicates. The nanosilicates used here are similar. The special feature is that the particles are small enough that they are readily taken up by cells. Then, they dissolve in the cell, releasing ions. The silicate ion may be the most important, but there are metal counter-ions in it, and they may also be relevant. (In the article, the Si product is described as Si(OH)4; don't take that literally.) (The evidence on the metal ions is mixed.)

What is the silicate material doing? It is affecting gene function, with the result of driving the stem cells toward being chondrocytes (cartilage). The figures above are pieces of the evidence. The proteins noted are important for those cells.

Why is that interesting? At one level, this is an exploration of how inorganic substances can control gene expression and, therefore, cell fate. In addition, the authors think this might be useful -- that using inorganic triggers might have advantages over using the more conventional growth factors (proteins). That, of course, is for future work to test.


News story: Minerals can be key to healing damaged tissue. (Nanowerk News (Texas A&M Engineering), May 6, 2022.)

The article, which is open access: Dissociation of nanosilicates induces downstream endochondral differentiation gene expression program. (Anna M Brokesh et al, Science Advances 8:eabl9404, April 27, 2022.)

Posts about cartilage include:
* Making new cartilage, using stem cells (January 5, 2022).
* Humans may be more like salamanders than we had thought (limb regeneration) (February 11, 2020).

Biology-related posts about silicon include:
* Miller-Urey revisited: the role of the glass container (January 22, 2022).
* Carbon-silicon bonds: the first from biology (January 27, 2017). Links to more about silicon.

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



A connection between eating fish and skin cancer?

June 20, 2022

Computer databases are full of information about us. They can be queried to look for possible relationships between various factors. We now have an article asking whether there is a relationship between eating fish and getting melanoma (a form of skin cancer).

The following table shows part of the top-level analysis...

People were divided into five groups, based on how much fish they reported eating. The second column shows the average daily fish consumption for each quintile.

The next column shows the number of cases of malignant melanoma for each group. You can see that there is an upward trend: more fish correlates with more melanoma.

The final column shows the HR (hazard ratio), with 95% confidence limits, for each quintile, after some statistical adjustments. The first group (lowest fish consumption) is set to 1, as the reference value. The groups with higher fish consumption all showed about a 20% higher risk of malignant melanoma.

   This is the left side (first analysis) of Table 2 from the article.


That's a correlation. The result says nothing about why this might happen. It is simply a lead for further work.

The next figure shows further analyses, each with only certain kinds of fish consumption considered...

This figure has three small tables. Each is similar to the one above, but for a subset of the data -- a subset of the fish.

The first table is for tuna consumption. It shows the same correlation. (The trend actually seems more consistent.)

The next two tables are for fried and non-fried fish. The correlation for fried fish is negative; that is, eating fried fish correlates with reduced levels of melanoma. The correlation for non-fried fish is positive.


   This is the left side of Table 3 from the article.


What does this all mean? I don't know, and the authors really don't either. (One possibility is that the results are due to environmental contaminants in fish.) They asked a question, and got an interesting and complex answer.

The authors note that there have been previous attempts to address the overall question of fish and melanoma, with widely varying results. The current study is the biggest yet. The second table suggests that we need to ask more specific questions. The effect of fish may depend on the type of fish and how it is prepared. It may also depend on where it comes from.

That's progress. We learn to ask better questions.

Other kinds of cancer? The authors note that previous analyses of the full data set showed an effect of fish on cancer only for melanoma.


News stories:
* Large Study Found a Strange Link Between Eating Fish And Skin Cancer. (Tessa Koumoundouros, Science Alert, June 11, 2022.)
* A novel study hints at a surprising link between eating fish and skin cancer -- The study followed 491,367 Americans aged between 50-71 to detect a link between skin cancer and fish consumption. (Loukia Papadopoulos, Interesting Engineering, June 12, 2022.)
* Could eating more fish raise your melanoma risk? - Expert Reaction. (Science Media Centre (New Zealand), June 10, 2022.) Links to more at other SMC sites.

The article: Fish intake and risk of melanoma in the NIH.AARP diet and health study. (Yufei Li et al, Cancer Causes & Control 33:921, July 2022.)

Among posts about melanoma: Anti-oxidants and cancer? (October 18, 2015).

Among posts about eating fish:
* Can an insect catch fish for its dinner? (October 8, 2018).
* DNA evidence in restaurants: is the fish properly labeled? (June 5, 2017).
* Omega-3 fatty acids; fish oil (March 29, 2010).

My page Internet resources: Biology - Miscellaneous contains a section on Nutrition; food and drug safety.

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



How water droplets damage hard surfaces

June 18, 2022

The figure, from a recent article, shows how falling water droplets can damage a surface...

The structure in part a (left) consisted of tiny glass beads (about 90 micrometers diameter).

The structure in part b (right) consisted of a piece of plaster.

The structures were damaged by falling water drops. The nature of the drops was similar in the two cases.

The damage in a was done by a single water drop.

The damage in b was done by 2500 water drops.

The scale bars are 5 millimeters.

   This is Figure 1 from the article.


The result in a is expected. But what's going on in b?

Here is some high speed photography....

Each row is a sequence of images showing what happened after a single drop hit the plaster surface.

The plaster contained a fluorescent marker, which could be tracked photographically. That allowed the scientists to measure the deformation in the material. The camera took 40,000 frames per second.

The top row is for a hard drop (a steel ball). The bottom row is for a water drop. (The size and speed of the drops were similar.)

The bright region shows where the shear stress is. What's important is the different pattern in the two rows. With the soft drop, the region of maximum stress moves along the material over time. With the hard drop, the region of maximum stress stays at about the same position.

The scale bar is 1 mm.

   This is part of Figure 3 from the article.


The development of the high speed analysis was the heart of the current work. It's more than just optics. The measurements include shear stress and pressure in the object as a function of position and time. That lets them see what is effectively a shock wave that moves through the object when a soft drop impacts a hard surface. The results are fairly preliminary, but the scientists have developed a useful tool.

They call their method "high-speed stress microscopy".


News stories:
* Scientists find out why dripping water hollows out stone. (Stone-Ideas, April 7, 2022.) The site is about the architectural uses of stone, an area where erosion caused by water is an issue.
* New study solves mystery of how soft liquid droplets erode hard surfaces. (University of Minnesota, March 31, 2022.)

The article, which is open access: Stress distribution and surface shock wave of drop impact. (Ting-Pi Sun et al, Nature Communications 13:1703, March 31, 2022.)

Among posts about liquid drops...
* What would raindrops be like on other planets? (April 13, 2021).
* Speech droplets: Can you transmit an infection to someone by yelling "Stay healthy" at them? (June 14, 2020).
* Disease transmission by sneezing -- in wheat (July 29, 2019).
* The aroma of rain (June 13, 2015). Perhaps rather related to current article.



June 15, 2022


Briefly noted... How rotifers silence transposons

June 15, 2022

Transposons (mobile genetic elements, or, casually, jumping genes) increase the genetic variability in an organism -- for better or worse. For bdelloid rotifers they could be especially detrimental; these organisms lack sexual reproduction, which helps clean up the genome. In fact, rotifers have a relatively low content of transposons. A recent article shows that they have a novel way to keep transposons silent, based on an enzyme apparently acquired from bacteria by horizontal gene transfer.
* News story: New DNA modification system discovered in animals, captured from bacteria more than 60 MYA. (Science Daily (Marine Biological Laboratory), February 28, 2022.) Links to the article, which is open access.
* Direct link to the article, which is open access: Bacterial N4-methylcytosine as an epigenetic mark in eukaryotic DNA. (Fernando Rodriguez et al, Nature Communications 13:1072, February 28, 2022.)
* Why bring this up? Well, it is interesting science. But also, we note it to mark Transposon Day, which is tomorrow. Transposon Day, not surprisingly, is on the birthday of ...
- Transposon Day. This page is for 2021. I don't see a page for 2022. I wonder...
* Background post about rotifers: Lesbian necrophiliacs (March 8, 2010). Includes the discovery of HGT in rotifers; "paper 2" of that post is reference 16 of the current article. Includes music.



Male mice are stressed by the odor of bananas or pregnant females

June 14, 2022

It's a complicated story, but fun and perhaps even important. Let's just jump in and look at some of the results. We'll put the story together after a couple of figures.

The basic experimental tool here is a test of response to a pain stimulus. A defined pain stimulus (heat) is given to one paw; the time it takes for the mouse to withdraw the paw is measured. A slow response (compared to control conditions), may reflect stress. The test conditions all involve olfactory (odor) exposures.

The following figure establishes the basic phenomena...

The y-axis shows the response. It is labeled as the change (Δ) in latency: how fast (in seconds) the mouse responds to the pain stimulus under the specific conditions compared to control conditions. The measurements are for various conditions, listed along the x-axis. Part C (left) is for male mice; part D (right) is for female mice. The set of conditions is the same for both.

Messy data; each point is for one mouse, and they vary. To start, you can look at the marked central measures: the mean (big horizontal line) and its error bar. Even easier, you can just look across the top for asterisks, indicating that the result tests as statistically significant. The more *, the higher the statistical significance.

The most significant results are for two treatments with the male mice. These are shown with *** in red at the top. Male mice, exposed to female mice either in late pregnancy or lactating, with pups present. That is, males exposed to those females respond poorly to a pain stimulus. That condition is called pain analgesia.

There are three conditions with one *; we'll skip those, except to note that two are for small effects in the opposite direction.

   This is part of Figure 1 from the article.


Another test, with the male mice...

Part B (left) shows the results for several specific chemicals. These are volatile chemicals; the test was done simply by exposing the male mice to the odor.

Three of the chemicals tested gave a ** or *** result.

Part C (right) shows a test using banana oil, from the grocery store. It gave a strong response (right side). (The left side of Part C shows the results for the individual mice: latency before and after the treatment.)

Female mice showed no response to these chemicals.

   This is part of Figure 4 from the article.


The story? Male mice are a threat to females with pups. That is well-known. They may even kill the pups. Females act to protect the pups.

The first figure here shows this behavior, translated into a quantitative test that can be used in the lab. The male mice show a behavioral change, pain analgesia, in response to females near birth (late-pregnant or lactating).

Analysis of the urine from female mice at various stages showed that several chemicals were present at high levels during that same time. That is, the presence of these chemicals in the female's urine correlated with the resulting male behavior.

The second figure above shows a test of those chemicals, alone. Some of them are active in promoting the response. That is, not only do these chemicals correlate with male behavior, but they cause it.

One of those chemicals -- the most active one, perhaps -- is very similar to the major odor in bananas. n-Pentyl (amyl) acetate in the urine, isopentyl (isoamyl) acetate in bananas. That led the scientists to test banana oil; it worked -- very well. Is there any significance to the banana result? Not obvious, but it is fun to note it.

The big story here is working out how female mice protect their young from competing males. That involved developing a lab test, and identifying specific chemicals involved in repelling the males.

The work is relevant to the use of mice in lab work. In recent years people have become aware that the way lab animals are treated can affect the experimental results. An earlier post about this is noted below.


News stories:
* A coincidental finding shows that male mice are afraid of bananas. Here's why -- A compound called n-pentyl acetate has something to do with it. (Mert Erdemir, Interesting Engineering, May 30, 2022.)
* Why are male mice afraid of bananas? (Phys.org (McGill University), May 24, 2022.)

The article, which is open access: Olfactory exposure to late-pregnant and lactating mice causes stress-induced analgesia in male mice. (Sarah F Rosen et al, Science Advances 8:eabi9366, May 20, 2022.)

Posts about mice behavior include...
* Why male scientists may have trouble doing good science: the mice don't like how they smell (August 22, 2014).
* Would wild mice use an exercise wheel? (July 11, 2014).

Posts about bananas, including the odor, include...
* Food security: the potential of enhanced cultivation of enset (February 22, 2022).
* What does blue light smell like? (July 18, 2010).



Graphdiyne: helping make silver a better anti-bacterial agent

June 11, 2022

Graphdiyne? It's a variation of graphene, but with some triple bonds. A new article reports an interesting use of graphdiyne, to stabilize silver so that it is more effective as an anti-bacterial agent.

More about the nature of graphdiyne towards the end, but that is not needed to follow the main story of the current article.

Here are some results...

Three agents were tested against two types of bacteria.

The graphs show the MIC for each agent. MIC = minimum inhibitory concentration. The lower the MIC, the more potent is the agent.

The bacteria are Bacillus subtilis (left side) and Escherichia coli (right), taken as representative of gram-positive and gram-negative bacteria, respectively.

The three agents are, starting at the right: AgNPs (silver nanoparticles), GDY (graphdiyne), and GDY@Ag (graphdiyne with Ag in it).

In each case, the MIC was much lower for the new combined agent, GDY@Ag. (Note that the y-axis scale is split, just below the 60. So the difference is greater than it appears visually.)

In particular, the GDY@Ag complex was more effective than the silver alone. The GDY alone had no activity, as judged by these tests.

   This is part of Figure 3 from the article.


The following figure shows the effect of the combined agent as judged by growth curves.

The graphs show bacterial growth vs time. Bacterial growth was measured by OD600, the optical density at 600 nm.

In each case, the light gray curve (at the left) shows the growth of the control culture, with no drug added.

The red curve shows the growth when GDY@Ag was added at the MIC level (as shown in the first figure). In both cases, that level led to essentially no growth over the time period studied.

The middle curve (darker gray) shows the growth at a level of the agent that was half the MIC level. In both cases, that level delayed growth, compared to the control curve. The growth delay was more for the E coli bacteria (right-hand graph). However, once growth started, it was fairly normal, both for rate and final amount of bacteria.

Note that the x-axis scale is mixed linear and log, with no marking to show the change. Most important for us is the first part of the graphs, in the linear-scale region (0-18 h).

   This is part of Figure 4 from the article.


What is this combined agent GDY@Ag? Rather simple, actually. They just mix silver nitrate, as a source of silver ions, with the graphdiyne. The GDY reduces the Ag+ to elemental Ag, which is contained within the GDY structure.

Why is GDY@Ag better than Ag alone? There is much consideration of the use of Ag as an anti-bacterial agent. But it is hard to use. It may be that ordinary Ag preparations lose their effectiveness as the Ag aggregates into larger particles. The GDY@Ag may be good precisely because it holds the Ag at multiple sites throughout the GDY, thus limiting the ability of the Ag to aggregate further.

Overall, the work is an interesting development in the often-murky story of the use of Ag as an anti-bacterial agent, and is also an exploration of a new form of carbon.


News story: Graphdiyne functionalized by silver nanoparticles to combat the threat of antibacterial resistance. (Yashwant Mahajan, Nanowerk, May 11, 2022.)

The article, which is open access: Insight into the antibacterial resistance of graphdiyne functionalized by silver nanoparticles. (Simin Qin et al, Cell Proliferation 55:e13236, May 2022.)

* * * * *


A bit about graphdiyne...

The figure shows graphene (at the right), graphdiyne (the major structure shown, in yellow), and part of a carbon nanotube (left, in black; not labeled here). It's an artist's view, showing the basic geometry. It omits some chemical details. For example, the alternating double and single bonds in the rings are not shown, nor are the triple bonds of the linker.

The linker is based on butadiyne: H-C≡C-C≡C-H. That molecule is linear; the C atoms are all sp-hybridized. The linker itself is that without the H; that is, it is linear, and includes two triple bonds (di-yne). Graphene itself is planar; adding a linear linker such as this does not change that.

The structure of graphdiyne may give you some ideas. What if there were only one triple bond? That would be graphyne -- another material, but not the immediate subject.

In the graphdiyne structure shown above, note the large "empty" triangular regions. It is likely that the Ag atoms are deposited in those regions.

This is part of a figure accompanying some versions of the following article: Architecture of graphdiyne nanoscale films. (Guoxing Li et al, Chemical Communications 46:3256, 2010.) The figure is not in the original article, but is part of the pdf of the article from the authors. Check Google Scholar for a freely available copy. The following link is one: pdf, with the full version of this figure as the first page. The full figure has more structures!

* * * * *

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

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



June 8, 2022


Briefly noted... Can a fish drive a truck?

June 8, 2022

Humans can navigate under water. Can fish navigate on land? And will they seek rewards there? A recent article addresses those questions. It's a fun story, but also some good science about animal behavior.
* News stories. Both link to the article.
- Scientists taught a goldfish to drive a watery tank on wheels - and it's pretty good at it. (Fermin Koop, ZME Science, January 12, 2022.)
- Goldfish driving 'cars' offer new insight into navigation. (Maria Temming, illustrated by JoAnna Wendel, Science News for Students, February 16, 2022.) Presented in part as a comic strip.
* Direct link to the article: From fish out of water to new insights on navigation mechanisms in animals. (Shachar Givon et al, Behavioural Brain Research 419:113711, February 15, 2022.) Check Google Scholar for a freely available copy from the authors.



Encoding peptides from primordial RNA?

June 6, 2022

A common view of how life got started is expressed in the RNA World model. RNA can both carry genetic information and do catalysis; it seems likely that RNA was the key player in the early stages of life.

In the modern world, nucleic acid (RNA or DNA) codes for protein, which does (most of) the catalysis. How did that transition happen? A new article provides evidence for a simple form of RNA-encodes-protein.

Here's the idea...

Part a (left) shows how modern protein synthesis occurs. Briefly, an amino acid is transferred to the end of a growing peptide chain. Both the incoming amino acid and the growing chain are attached to RNA molecules, specifically transfer RNA (tRNA) molecules. Both tRNA molecules are paired to the messenger RNA (mRNA) molecule.

Part b (right) shows the scheme proposed in the current work. Briefly, an amino acid is transferred to the end of a growing peptide chain. Both the incoming amino acid and the growing chain are attached to RNA molecules. The two RNA molecules, carrying the incoming amino acid and the growing chain, are paired to each other.

   This is Figure 1 from the news story (by Bonfio) accompanying the article.


Those two processes are rather similar -- so long as there is a requirement that the incoming amino acid's RNA actually pairs properly with the RNA of the growing chain. That is the feature that can lead to encoding.

Here is an example of what they actually did...

Start at the upper left. There are two amino acids (G & V -- glycine and valine), each attached to a small RNA molecule (blue, red). Those two RNAs are paired, in the usual way.

The details are such that the two amino acids react with each other, forming a peptide (amide) bond. That step is labeled 'coupling'.

The top amino acid (G) is cleaved from its RNA (and the RNA is removed). This exposes the -NH2 group of the G. That step is labeled 'cleavage'. We now have a dipeptide, still attached to the lower RNA.

The cycle is now repeated in the right-hand column, adding another G to the growing chain.

This is part of Figure 3b from the article. The full Figure 3b shows more cycles. The first three parts can be considered a sequence (the two parts shown above, plus one more). The last two parts can be taken as examples.


What's behind this scheme? It is quite likely that amino acids and small peptides were around during the RNA World stage. They may have even been abundant. And they may have been attached to RNAs -- just as they are in the modern world. Suggesting that such hybrid molecules were around got the scientists thinking how that might lead to a coding system. The current system begins to show how that might work.

As always, distinguish what they have shown from any claim that this is what happened. The point of the current article is that it gets us thinking about the problem of how nucleic-acid-codes-for-protein might have developed, and it offers a specific example.

Notes...

The current work includes an experiment testing the length of the paired region that is needed. Interestingly, it is about three bases. Is that related to the length of the modern codon, or just a coincidence?

The direction of chain growth here is opposite to modern protein synthesis.


News stories:
* The origin of life: A paradigm shift. (Science Daily (Ludwig-Maximilians-Universität München), May 12, 2022.)
* A pair of experiments reveal new details regarding the origin of life on Earth. (Philip Guelpa, World Socialist Web Site, June 2, 2022.) Interesting source. But it is a useful presentation of the work. As the tittle suggests, it actually deals with two articles. One is the article of a recent (March 26) post listed below.

* News story accompanying the article: Origins of life: A possible path towards encoded protein synthesis -- How did the biological machinery for protein synthesis evolve from simple chemicals on ancient Earth? Experiments suggest an intriguing role for modified RNA nucleotides in directing stepwise peptide synthesis. (Claudia Bonfio, Nature 605:231, May 12, 2022.)
* The article, which is open access: A prebiotically plausible scenario of an RNA-peptide world. (Felix Müller et al, Nature 605:279, May 12, 2022.)

A recent post about early life... An RNA replicator network (March 26, 2022).

Another unusual way to make protein... Making peptides in space: a new pathway (April 15, 2022).

My page Internet Resources for Organic and Biochemistry has a section on Amino acids, proteins, genes. It includes a list of posts about making proteins.



Acholetin: a new polymer from bacteria

June 4, 2022

A recent article reports a new polymer. There are various reasons it might be interesting, but we first need to establish what it is.

The following figure gives some basics, on two issues. Both parts are fairly complex, but we'll focus here on some key points.

Let's start with Part B (bottom). The molecule at the left (blue) is based on glucose, with two modifications. First, it has a phosphate group, at position 1; this activates the sugar, so it can join with others. Second, it has an amino group, at position 2; actually, it is an N-acetyl amino group. This 2-N-acetylamino is found in chitin; more about that later.

The next structure (black) is a polymer, built from the first molecule. The n at the lower right of the big brackets indicates that the bracketed unit is repeated n times. What's important is the linkage, which is between the 1-position of the left-hand sugar and the 3-position of the right-hand sugar. 1,3. Actually, it is β-1,3, where the beta describes the orientation.

To the right of the arrow... Those first two molecules are now joined. Again, 1,3. The polymer is one sugar longer than before. And a phosphate was released.

The arrow is labeled AchP. That's the enzyme, which was discovered in this work. The arrow is bi-directional. That same enzyme catalyzes both the polymerization and depolymerization.

Overall, part B describes the basic claim: a polymer of 2-(N-acetylamino)glucose linked β-1,3. That is a new polymer. Further, they have the enzyme that can both make and degrade the polymer.


Part A (top) shows some of the properties of the enzyme, in lab tests. The basic plan was to test various donor and acceptor molecules to see if the joining occurred. The donor is the one with the phosphate; the acceptor is the growing chain. The properties are fairly complex; we'll just note some highlights.

Three donors were tested. They all have that 1-phosphate group. The first two rows are donors based on glucose (Glc); the bottom row is for a donor based on galactose (Gal). The color of the boxes shows how good the reaction was. The Gal donor did very little. The two Glc donors worked, but the one with the N-acetylamino (NAc) worked best.

Several acceptors were tested. Let's just look at the first three for now. Glucose, aminoglucose, and N-acetylaminoglucose. The last of those worked best, but the full picture is more complicated. Among the other acceptors tested, it is interesting to note that the Gal-based acceptors worked rather well, too.


The numbering of the positions on the sugar is standard, and is consistent. I have added some numbers on the molecule at the left. The phosphate is at the 1-position. The N (in this case with an acetyl group) is at 2. I added numbers for the -OH at 3, 4, and 6. The numbers should be on the C atoms, but I put them where there was some space. In the larger unit to the right, you can see that the linkage between sugars is 1,3. It is beta, due to the orientation.

   This is part of Figure 2 from the article.


That's a long discussion of (part of) a single figure! In brief...
- We have a novel polymer.
- It's from nature, from bacteria.
- We have the enzyme to make it. The enzyme properties are consistent with the polymer found, but also suggest there could be additional complexity.
- The enzyme can also degrade the polymer.

The discovery was rather accidental. The scientists were screening genome databases for enzymes that might degrade chitin. Of course, enzymes that work on things similar to chitin might pop up.

The bacterial source here is an unusual one, without a cell wall. It is Acholeplasma laidlawii. Of course, database screens require only that a genome has been deposited, and are not biased by the nature of the organism.

As to the polymer... There are three ways to connect two molecules of the starting sugar in the β orientation: 1,3; 1,4; and 1,6. See the right hand molecule in part B, above. The 1,4 version is the familiar polymer chitin. The 1,6 version is also known. Thus finding the 1,3 version completes the set.

The new polymer has been given the name acholetin, reflecting the name of the bacteria and the connection to chitin. The enzyme is called acholetin phosphorylase (AchP).

Is the polymer (or the enzyme) of practical use? That remains to be seen.

Are there other molecules out there in the natural world still waiting to be discovered? Probably.


News stories:
* Bacterial Enzyme Makes New Type of Biocompatible, Biodegradable Polymer. (SciTechDaily (American Chemical Society), March 16, 2022.)
* Bacterial enzyme produces biodegradable polymer. (Nanowerk News (Advanced Light Source, Lawrence Berkeley National Laboratory), May 21, 2022.)

The article, which is open access: A Synthetic Gene Library Yields a Previously Unknown Glycoside Phosphorylase That Degrades and Assembles Poly-β-1,3-GlcNAc, Completing the Suite of β-Linked GlcNAc Polysaccharides. (Spencer S Macdonald et al, ACS Central Science 8:430, April 27, 2022.)

More about chitin, and its derivative, chitosan: Some shrimp in your wine? (August 27, 2016).

My page Organic/Biochemistry Internet resources has a section on Carbohydrates. It includes a list of related Musings posts.



June 1, 2022


Briefly noted... Do cats know the names of their house-mates?

June 1, 2022

Cats recognize their names. Do they also recognize the names of other cats they live with? To test that, scientists tested how the cats responded to seeing a picture of one of their cat-friends on the computer screen, along with hearing a name that either did or did not match. Housecats, who would be familiar with hearing the names of their cat-friends, showed a small difference in how they responded to a match vs mismatch. Cats from an environment where they were not exposed to the names did not show such an effect. It's hard to know what to make of this. The idea is interesting, and the experiments clever. But the results are hard to interpret. There are some hints, but no big conclusions. One wonders what the follow-up will be. Apparently one of the subjects didn't think much of the work, and simply left after the first trial.
* News stories. Both link to the article, which is open access.
- Cats learn the names of their feline friends. (Big Think, May 25, 2022.)
- Cats can remember each other's names, study says. (Chris Melore, Study Finds, May 16, 2022.)
* Direct link to the article, which is open access: Cats learn the names of their friend cats in their daily lives. (Saho Takagi et al, Scientific Reports 12:6155, April 13, 2022.)



How many exoplanets are known? Three (four?) fewer than we thought

May 31, 2022

Recent years have seen the discovery of thousands of exoplanets -- planets beyond our Solar System. Musings has noted some of the investigations, including the methodology for recognizing a planet at a distance [links at the end].

A recent article re-examines some of the identifications, and argues that at least three objects previously reported by the Kepler mission as planets are, more likely, stars.

The following figure shows the key evidence. The issue is that the reported sizes of some planets are in doubt. That is because the sizes of their host stars are in doubt, and the reported planet size is directly related to the size of the host star.

The graph plots the apparent size of a collection of exoplanets -- based on two different catalogs (KIC & TIC) that give the sizes of the host stars. The green diagonal line shows what would be expected if the catalogs agreed.

Planet size is shown as RJup. That is radius, relative to Jupiter.

Most of the planets fall fairly close to the diagonal line.

However, four are particularly noteworthy; they are shown in red. These four are all above the line; they are larger when judged by the TIC than by the KIC. The KIC was used for the original classification. The TIC is based on newer and better data. (In particular, there is better data for the distance of each star from Earth, which is used to find the size -- of the star, and hence of the planet.) The graph, then, suggests that these planets might be considerably larger than expected during the original analysis. And they are big -- 2-3 times the size of Jupiter (by radius), if the larger number is correct.

KIC = Kepler Input Catalog; TIC = TESS Input Catalog.

   This is the lower left part of Figure 1 from the article.


The basic story is about that simple. (There is considerable additional detail, to check that other known features of the system fit.) Remember, a factor of 2 in radius gives a factor of 8 in volume. The biggest planet candidates are just too big to be planets, now that we have better data on their sizes.

The work actually began with a different purpose. The scientists wanted to examine the shape distortion that can occur when two massive objects are near each other. Of course, they started with planets that seemed rather large. But the results showed effects that were considerably larger than expected.

That led them to re-examine the reported sizes. Turns out that the measurements of star size have improved. Kepler may seem to be a very recent mission, but star measurements have improved since then. The TIC is based on the European Space Agency's Gaia mission, launched only in 2013. (Kepler was launched in 2009, and did most of its successful work by 2013.)

For the smallest of this set of four suspects, the size per se is marginal, but other factors suggest to the scientists that it may well not be a planet.


News story: Look! Up in the sky! Is it a planet? Nope, just a star. (Science Daily (Massachusetts Institute of Technology), March 15, 2022.)

The article, which is open access: Revisiting Kepler Transiting Systems: Unvetting Planets and Constraining Relationships among Harmonics in Phase Curves. (Prajwal Niraula et al, Astronomical Journal 163:172, April 2022.)

Background posts about exoplanets include...
* A new trick for the Kepler planet-hunters (June 25, 2012). The post includes a prediction "that over 90% of Kepler candidates will be validated as planets." Losing 3 or 4 is not a big deal. What is important about the new article is the improved characterization.
* The Kepler Orrery (June 3, 2011). Links to more.



Sleep genes and Alzheimer's disease?

May 28, 2022

It is known that Alzheimer's disease (AD) is associated with poor sleep.

It is also known that there are some people who thrive on a relatively small amount of sleep. In some cases, the trait runs in families, and is called FNSS = Familial Natural Short Sleep. FNSS has been associated with mutations in at least two genes. So far, it seems that people with FNSS do not have high levels of neurodegeneration, such as AD. That is, such people sleep less, but do not have the common correlates of reduced sleep.

A new article provides evidence, in a mouse model of AD, suggesting that those with FNSS mutations have reduced development of some AD features.

Here are the results from one test...

This test is about tau, a protein associated with AD (and with other neurodegenerative conditions). The measurement is for the amount of a particular form of tau (phosphorylated tau) that is associated with AD. It is measured with an antibody that is specific for that form of tau. Green indicates a response.

Part A shows representative images of what was found for three mouse strains; part B (right) shows the quantitative results, over the multiple mice examined.

PS19 (at the left) is the basic mouse strain used as the AD model. (It carries human genes that lead to AD.) DEC2 is one of the genes that can lead to FNSS. The middle image is for the WT (wild type) form of the gene. The right-hand image is for P384R, a mutant form of the DEC2 gene, leading to short sleep.

Visual inspection of Part A suggests that the mouse with the 'short sleep' mutation has less phosphorylated tau. Part B confirms that there is a significant effect of the mutation on reducing the amount of phosphorylated tau. We also note that the distributions in part B are not simple; there is a hint that the effect of the mutation is to reduce outliers at the high end.

   This is part of Figure 1 from the article.


That's tau. Another protein associated with AD is the amyloid beta peptide, Aβ42. The following figure shows some results for that AD-related protein...

The first two bars (left; gray and blue) are for the same two DEC alleles used in the first test, in mice at age three months. The results show the amount of Aβ42 in one brain region. They are very different. This is the key result from this figure.

The right side of the figure shows results for mice at six months. Look at the same color bars (gray and blue) there, and there is no significant difference. Again, the eye may suggest otherwise.

The other two bars (black and red) show results for wild type and mutant alleles of another 'short sleep' gene tested. Although there is no significant effect in this test, that mutation did have other effects on Aβ42.

In this test, 5XFAD is the mouse strain used as the AD model.

   This is Figure 3B from the article.


Overall, both FNSS mutations tested, in different genes, affected AD markers, but differently.

What does this all mean? As so often with AD, that is not clear. At a minimum, the work offers some clues about the connection between sleep and AD. Two genes first described as affecting sleep also affect AD proteins -- at least in a mouse model.

"This study employs an understudied approach for AD (both Aβ and tau) by investigating strong genetic factors that have potential in conferring resistance to onset and progression of AD-like pathology. This work was motivated by our idea that natural short sleepers are accomplishing restorative aspects of sleep more efficiently. The results indicate that there is great potential in identifying the means to use improved sleep as a target for protecting against neurodegeneration, thus decreasing the prevalence of AD, and potentially, other forms of neurodegeneration." (From the Discussion section of the article, near the end (p 10 of the pdf).)

The 'short sleep' genes allow people to thrive on a small amount of sleep. That would seem to be a beneficial trait. However, the trait is rare. Why? Are we missing something important about what these mutant alleles are doing? In any case, study of FNSS and its genetics should continue to be of interest. (The main research teams of this work are sleep researchers. They used AD as a tool in their study of sleep.)

There is more to be done.


News stories:
* Genes May Decide How Much Sleep We Need. (Dylan Roche, Sleep Foundation, April 8, 2022.)
* Genes for shorter sleep linked with reduction of Alzheimer's changes in mice brain. (Alzheimer's Research UK, March 16, 2022.)
* When it comes to sleep, it's quality over quantity. (Science Daily (University of California - San Francisco), March 15, 2022.)

The article, which is open access: Familial natural short sleep mutations reduce Alzheimer pathology in mice. (Qing Dong et al, iScience 25:103964, April 15, 2022.)

A recent post about sleep, including the role of a mutation: What happens to capillary blood flow in the brain during sleep -- and why? (November 8, 2021).

A recent post about AD: How many types of Alzheimer's disease are there? (June 15, 2021).

My page for Biotechnology in the News (BITN) -- Other topics includes sections on Alzheimer's disease and Brain. Each includes a list of related Musings posts. The 'brain' section includes many posts on sleep.



May 25, 2022


Briefly noted... How useful is it to emphasize a "natural" approach to removing CO2 from the air?

May 25, 2022

One way to reduce atmospheric carbon dioxide is to promote its use by plants. That can be thought of as a nature-based, or "natural", approach to CO2 reduction. A concern about that approach is that it could be temporary; CO2 in plants can have various fates; one of them is to be returned to the atmosphere. A recent article analyzes the approach, and how it interacts with other approaches. The take-home lesson is that incorporation of CO2 into plants is good. However, it must be done in conjunction with other approaches to reduce CO2 for a robust long-term effect. That balance is probably not a surprise, but the article provides good analysis.
* News stories. Both link to the article, which is open access.
- Nature-based carbon removal can help protect us from a warming planet. (Nanowerk News (Simon Fraser University), March 29, 2022.)
- Planting trees can help the climate, but only if we also stop burning fossil fuels. (The Conversation, March 30, 2022.) From three of the authors of the article.



Effect of the COVID pandemic on the incidence of dengue

May 24, 2022

During the COVID-19 pandemic there has been a major reduction of the incidence of influenza. Musings noted an early report of the effect [link at the end]; it has held up.

The incidence of dengue has also declined during the COVID pandemic. COVID and flu are both due to respiratory viruses; their modes of transmission are probably similar. But dengue is transmuted by mosquitoes; the connection between COVID and dengue may raise different issues. We now have an article exploring that connection.

Here is the basic phenomenon...

The figure shows the incidence of dengue in 23 countries (listed along the left side) during the months of 2020 (x-axis); these are all countries with a high incidence of dengue. As many will recall, COVID restrictions began around March 2020.

The monthly incidence is reported relative to the incidence in recent years for the same month. Red is for higher levels; blue is for lower levels.

The big picture is that most countries started the year with relatively high levels of dengue. After March, the rest of the year was largely marked by low levels of dengue.


The article notes that some countries with high levels of dengue were not included in the analysis here, because the necessary monthly data was not available.

   This is Figure 1C from the article.


It is clear that a substantial reduction of dengue occurred during the time of COVID restrictions. (For 2020 as a whole, this set of countries showed about a 44% decline in dengue.)

The authors went on to analyze the nature of COVID restrictions, to see if they could identify any features that seemed of particular relevance to the reduction of dengue.

The analysis involved statistical modeling, using a variety of data, from various sources. The authors discuss the limitations of the analysis.

The following figure summarizes one part of the analysis...

The figure shows the two features of COVID restriction that showed the biggest effects in the analysis. The results are shown here for two geographic groups of countries.

This is the bottom part of Figure 4 from the article. (The rest of the figure shows the results for the individual countries. The big picture is that they are similar.)


As you can see there, the analysis suggests that the time spent away from home (in school or 'other') is a major factor.

The authors are not interested in restoring restrictions as a tool against dengue. Instead, they hope that their analysis might offer clues about where to focus anti-dengue efforts. For example, the results shown above might suggest that mosquito control should be focused on places where people congregate (including schools), rather than on the home.


News stories:
* Pandemic restrictions could be linked to 750,000 fewer dengue cases -- The insight could help us better manage the disease. (Fermin Koop, ZME Science, March 4, 2022.)
* COVID-19 restrictions linked to nearly 750,000 fewer dengue cases in 2020 -- New study shows COVID-19 measures such as school closures and 'high-traffic and mixing' areas had the strongest association, providing clues for new intervention approaches. (Science Daily (London School of Hygiene & Tropical Medicine), March 3, 2022.)

* "Comment" accompanying the article: Movement dynamics: reduced dengue cases during the COVID-19 pandemic. (R Tedjo Sasmono & Marsha S Santoso, Lancet Infectious Diseases 22:570, May 2022.) Caution... The authors are from Indonesia. They spend much of their Comment discussing the situation there. Only after presenting that in some detail do they reveal that the article analysis does not include Indonesia (a country that did not have the monthly data needed here). It's still an interesting story, but the way it is organized leads to a letdown.
* The article, which is open access: Measuring the effects of COVID-19-related disruption on dengue transmission in southeast Asia and Latin America: a statistical modelling study. (Yuyang Chen et al, Lancet Infectious Diseases 22:657, May 2022.)

Background post about influenza during the COVID pandemic: How bad will the upcoming COVID-era winter flu season be? (September 25, 2020).

My page for Biotechnology in the News (BITN) -- Other topics includes sections on Dengue virus (and miscellaneous flaviviruses) and SARS, MERS (coronaviruses). They include lists of related Musings posts.



What to do with silicon waste from dead solar cells

May 23, 2022

It's a sign of progress, I suppose. We've been using solar (photovoltaic) panels long enough that we are facing a new waste problem: what to do with dead solar cells.

A new article reports work on converting solar cell waste into thermoelectric (TE) generators, which make electricity from temperature (T) gradients.

A key insight was to realize that, while both can be silicon-based, they use the silicon in different ways. Specifically, the TE device is not affected by the impurities that convert bulk Si into useful solar cells. So, one can just take the waste solar panels, grind them, extract things that seem valuable, and then re-purpose the Si to the new task. It is not necessary to purify out the dopants used to make solar cells.

The following figure gives an idea of how the resulting TE devices perform...

The graph shows zT vs T for various materials.

zT is a complex parameter, often taken as a single number reflecting the efficiency of the TE system; it is called the figure of merit.

TE devices are driven by a temperature difference. The T shown on the x-axis is the hot end. The cold end was constant, at 323 K.

The lowest curve is for the "pristine" silicon, as recovered from the solar cell waste. The other curves are for that material, with additions of germanium and phosphorus. The Ge is constant (at 1%), but P is varied. All are better than without additives, but there is an optimum at 4% P.

The germanium helps reduce the thermal conductivity. The phosphorus increases the electrical conductivity.

   This is Figure 5d from the article.


The waste Si from the solar panels is now working in functioning TE devices.

These are not particularly good TE devices. TE still has limited use, due to poor performance. The highest zT obtained here is high for Si-based TE devices, but well below state-of-the-art for TE. On the other hand, these Si-based TE devices are rather light, which may be a significant advantage for some uses (such as on airplanes). Further, they may be relatively inexpensive, given the Si source.

Of course, further work may result in better Si-based TE devices.

In any case, the work represents a step toward figuring out what to do with a new waste material.


News story: Upcycling strategy turns discarded solar cells into thermoelectrics. (Michael Berger, Nanowerk Spotlight, May 16, 2022.)

The article: Upcycling Silicon Photovoltaic Waste into Thermoelectrics. (Jing Cao et al, Advanced Materials 34:2110518, May 12, 2022.)


A recent post about both solar cells and TE devices: A solar cell that generates electricity at night (April 12, 2022). The news story listed above mentions the work behind this recent post.

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



How to make bricks on Mars

May 21, 2022

At some point, we are going to need building materials on Mars.

Here are some Martian bricks, from a recent article...

Actually, they are pseudo-Martian bricks. Made on Earth, but by a process that suggests how one might make bricks on Mars.

They were made using Martian Simulant Soil (MSS), which one can buy from a company in Florida.

The major dimensions are probably about 3 centimeters, judging from the description of the apparatus. The process should be scaleable to any size desired.

The scientists had previously made Lunar bricks, using Lunar Simulant Soil (LSS), which apparently they had to make for themselves. Work with LSS continued here.

   This is Figure 2 from the article.


How do you do that? The general idea is straightforward. There is soil on Mars. We know there are various kinds of soil, including some that is very hard; we even use the term brick-hard soil. The issue is, how do we take the soil we find, and convert it to something suitable for use as bricks.

The scientists try various things, including adding metal ions and polysaccharide gums. In particular, they use a bacterial process, with the bacterium Sporosarcina pasteurii.

How good are the bricks? The following figure shows some data. The graph shows the strength -- compression strength -- for samples of Martian brick made in different ways.

The bar labels all include MSS-SP: Martian Simulant Soil and the bacterium.

GG and N refer to guar gum and nickel ions, Ni2+, respectively.

You can see that the right-hand bar, for bricks made with all these additives, is the strongest.

Samples made with MSS-SP alone, with neither GG or N, were not strong enough to be tested.

   This is Figure 5a from the article.


The compression strengths found here are not very high, but may be high enough for making useful temporary structures. Remember, the starting material (MSS) used here is loose soil.

What are the bacteria doing? The scientists think the key role is to make ammonia, NH3, thus raising the pH of the soil; that promotes precipitation of minerals such as calcite (calcium carbonate). (The bacteria used here make the enzyme urease, which makes NH3 from urea. The growth conditions include urea. The bacteria infiltrate the soil, and thus make NH3 throughout. The urease enzyme requires Ni2+.)

The work opens the door to making bricks on site on Mars. As noted earlier, they also made Lunar bricks, by more or less the same procedure. More generally, they call their results space bricks.


News stories:
* ISRO-IISc team develops prototype of bacteria-infused bricks for Martian, lunar soil -- New method is proof of concept for sustainable way to make bricks for construction on Mars & Moon using soil found on surface. (Sandhya Ramesh, The Print, April 22, 2022.)
* Using bacteria to build settlements on Mars. (Nanowerk News (Indian Institute of Science Bangalore), April 20, 2022.)

The article, which is open access: Microbial induced calcite precipitation can consolidate martian and lunar regolith simulants. (Rashmi Dikshit et al, PLoS ONE 17:e0266415, April 14, 2022.)

More from Mars...
* Another underground lake on Mars -- near the equator? (April 5, 2022).
* Perchlorate on Mars surface, irradiated by UV, is toxic (July 21, 2017). This issue is not dealt with in the current article.



May 18, 2022


Briefly noted... The youngest known asteroids

May 18, 2022

Two asteroids were (independently) discovered "near" Earth in 2019. Study of them suggests that they are siblings -- and that they were born only about 300 years ago, That would make them the youngest known asteroids. It is likely that they originated from a comet. The data is limited at this point. Much of what is claimed is based on modeling, and much is unclear. More data should become available in 2033, when these baby asteroids will next be close enough for observation.
* News story: Astronomers Spot The Youngest Pair of Asteroids Ever Discovered in The Solar System. (Michelle Starr, Science Alert, February 7, 2022.) Links to the article.



A gold-based spray to treat heart damage

May 17, 2022

Heart tissue tends to die after a myocardial infarction (heart attack). A treatment that reduced that tissue death would be good.

A recent article reports development of a spray that might help. That raises a number of questions. Let's start with some evidence that it works -- in mice...

The mice were given an artificial (lab-induced) myocardial infarction. They were then given various treatments, and evaluated by several measures a month later.

The graph shows a measure of scarring.

The left-hand bar is a control, with a mock treatment (PBS = phosphate-buffered saline) The scarring is about 50%. The right-hand bar is for the preferred treatment. The scarring is reduced to about 10%, a major improvement.

That preferred treatment is labeled Multi-AuNP. The two components of that were tested individually, and gave some improvement. A couple of other things were tested; we'll skip them here.

   This is Figure 4c from the article.


The treatment worked. It substantially reduced scarring. Several measures of structure and function were consistent on this point.

What is this Multi-AuNP stuff? AuNP stands for gold nanoparticles. Multi is a peptide that the scientists studied. (Leg-4 is another peptide; it didn't work as well.)

How is the treatment done? How do you spray a treatment onto a damaged heart? They really did spray a solution containing the active agent directly onto the heart. And they note that the sprayer design anticipated "future minimally invasive surgical procedures." The authors compare their treatment mode to using patches; spraying gives a coating that conforms to the heart shape.

How does the treatment work? That's not at all clear. Survival of heart tissue following a heart attack is rather mysterious, and certainly generally not good (in mammals). It is plausible that the gold is important here, perhaps in providing a more conductive surface, and that a key role of the protein is to organize the gold nanoparticles. It is also possible that there are multiple effects, and that the overall effect seen above is due to synergy. The data might actually hint at this.

Whatever is going on, there is evidence it works, in the mouse model. The material itself is practical to make, and the delivery method is thought to be practical, if not ideal. Thus the work here deserves follow-up.

"In summary, we have demonstrated that by combining peptide design and an on-the-spot application, a therapeutic approach was developed that allows nanomolar concentrations of nanogold to restore cardiac function in a clinically relevant animal model of myocardial infarction. However, the mechanism of action by which the application of nanogold restores cardiac function postmyocardial infarction remains to be fully elucidated, including delivery of the therapy at different time points after heart injury. Our findings illustrate how peptide engineering can finely tune the properties of nanomaterials for use in therapeutic applications that, in our case, improved cardiac contractility and electrical signal propagation." That is the first paragraph of the Conclusions section of the article.


News stories:
* Spray of gold nanoparticles can potentially treat heart disease. (Nanowerk News (University of Ottawa), March 15, 2022.)
* The golden future of cardiac tissue repair. (The Beat, University of Ottawa Heart Institute, March 2022.) Interesting name for a newsletter from a heart institute.

The article, which is open access: Nanoengineered Sprayable Therapy for Treating Myocardial Infarction. (Marcelo Muñoz et al, ACS Nano 16:3522, March 22, 2022.)

A post about work involving the use of artificial heart attacks in lab rodents (rats, in this case); it is a standard lab system. Treating a heart attack using a microneedle patch (January 11, 2019).

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

Previous post about gold nanoparticles: Super-resolution microscopy -- without special labels (May 15, 2022). Just two days ago. Any connection? One is on analysis, one on use.



Briefly noted... How long can you track magpies fitted with a GPS device?

May 16, 2022

Until they remove them. That may take only a few minutes, because they help each other remove the devices. At one level, it is just a fun story, but there may be interesting implications for our understanding of these smart birds.
* News stories. Both link to the article, which is open access.
- Australian birds opt out of experiments. By removing tracking devices? -- "The birds outsmarted us". (Ameya Paleja, Interesting Engineering, February 23, 2022.) Also links to the following...
- Altruism in birds? Magpies have outwitted scientists by helping each other remove tracking devices. (Dominique Potvin, The Conversation, February 21, 2022.) By one of the authors of the article.
* More about the corvids: Ravens: planning for the future? (September 11, 2017). Links to more.



Super-resolution microscopy -- without special labels

May 15, 2022

A new article reports another advance in high-resolution microscopy. In this case, the key development is that the procedure does not require any special pre-treatment of the sample.

The following figure shows examples of what could be seen...

Each part shows two images of the same material, which consists of tiny gold nanoparticles -- sometimes, groups of them.

The top images are from light microscopy (LM), using the method developed here. They are labeled 'laser scan images'. The bottom images are from (scanning) electron microscopy ((S)EM).

The LM images are not as good as the EM images. But they are very good. The EM images clearly show the particles. The particles are not so clear in the LM images, but they can be resolved by mathematical analysis of the image. The red circles in each EM image show the particles as deduced from the LM image. Not bad.

The scale bars are 532 nm -- the wavelength of the light they used.

The authors note that the LM images were taken first, because the EM imaging damaged the samples.

   This is part of Figure 3 from the article.


The authors claim resolution of "several nanometers".

The resolution of ordinary image formation is limited to about half the wavelength of the light used. In this case, that would be about 266 nm.

There have been many developments in high-resolution microscopy over recent years. The big idea is to avoid that ordinary image formation, which loses information. Instead, the light is analyzed in more detail. Often, it is necessary to first modify the material, for example, to make it fluorescent.

In this case, the system starts with laser scanning -- high intensity monochromatic light, localized. Then there is complex analysis of the light, including polarization and scattering. The details are worked out to be useful; what matters, for the moment, is that the microscope is based on complex analysis of the light, not simply ordinary image formation. Importantly in this work, no pre-treatment of the sample is used.

The authors note limitations of what they have done here, and will try to extend the usefulness of the approach.


News stories:
* Researchers demonstrate label-free super-resolution microscopy. (Nanowerk News (from the journal), April 21, 2022.)
* Noninvasive Imaging Method Measures Below the Diffraction Limit. (Photonics Media, April 29, 2022.)

The article, which is open access: Sub-diffraction-limit Fourier-plane laser scanning microscopy. (Jörg S Eismann & Peter Banzer, Optica 9:455, May 2022.)

More about advances in microscopy:
* Visualizing atoms with electron ptychography -- approaching the theoretical resolution (June 5, 2021).
* Expansion microscopy: making an object bigger can make it easier to see (February 23, 2015). Includes a link to the recent Nobel Prize for super-res microscopy.

There is a section of my page Internet resources: Biology - Miscellaneous on Microscopy. It includes a list of related Musings posts.

Added May 17, 2022. Next post about gold nanoparticles: A gold-based spray to treat heart damage (May 17, 2022). Two days later; just above.



May 11, 2022


Briefly noted... Does the word 'rough' sound r-r-r-rough?

May 11, 2022

It's that trill. And it's not just an accident of English. A recent article analyzed more than 300 languages, from many language families around the world. Not all languages have the trilled-r sound, but for languages that do, it is far more likely to be in the word for rough than in random adjectives or specifically the word for smooth. It is a connection between sound and touch. For the Indo-European language family, the use of trilled-r in 'rough'-like words dates back at least 6,000 years.
* News story: 'Rough' Words Feature a Trill Sound in Languages Around the Globe. (Neuroscience News (University of Birmingham), January 21, 2022.) The main figure summarizes some of the findings: there are far more red points than blue. Links to the article, which is open access.
* Also see: Mountains and human language? (June 28, 2013). Links to more about language.



Briefly noted... Dinosaur extinction: What time of year was it?

May 10, 2022


It's spring (in the North). An appropriate time, according to a recent article, to discuss dinosaur extinction. A team of scientists examined fossil fish found at the geological boundary marking the extinction of the (non-avian) dinosaurs. The fish were likely killed within a hour or so of the event, and they are remarkably well preserved. Detailed examination of the fish indicates that they died during the spring; yes, some fish have annual growth rings, too. That's boreal (northern hemisphere) spring; it was autumn in the South. Simply getting that timing leads to ideas about why some organisms may have been more vulnerable. Although the logic of the work is straightforward, the details of the analysis are not easy to follow. The news stories should give you the ideas and some context.
* News stories. The last two both link to the article, which is open access.
- The Last Day of the Mesozoic - It was Boreal Spring. (Everything Dinosaur, February 24, 2022.) Notes a study from last year which came to a similar conclusion, from different evidence.
- The reign of the dinosaurs ended in spring. (Geology Page (Uppsala University), February 27, 2022.)
- The Reign of the Dinosaurs Ended in Spring: Revelations From Bones of Fish That Died When the Asteroid Hit. (SciTechDaily (European Synchrotron Radiation Facility), February 23, 2022.)
* Also see...
- Do animal bones have something like annual growth rings? (August 7, 2012).
- What caused the extinction of the dinosaurs: Another new twist? (January 26, 2016).



Environmental sensors that can be dispersed by the wind and land upright

May 9, 2022

Engineers are interested in developing ways to monitor the environment. Spreading tiny sensor devices around would be good.

As one approach, engineers turn to nature for inspiration. Various plant seeds are dispersed by the wind. Engineers learn how this works, and design artificial devices to use similar approaches. Musings recently noted an example of tiny flying devices inspired by maple seeds [link at the end].

A recent article reports another example, inspired by dandelion seeds. Dandelion seeds drift in the wind while falling, and land upright. That behavior served as the inspiration for designing a tiny environmental sensor, which can be distributed around by the wind. The ability to land upright means it can work with solar energy, rather than heavier batteries.

Look...

The figure shows a dandelion seed and an example of the devices developed in the current work.

Both have a canopy, which serves to keep the thing airborne, and a weight at the bottom, which helps keep it right-side-up.


   This is Figure 1a from the article.


Nature worked out the dandelion seed. The scientists here had to explore the details to make an effective wind-dispersed sensor device. They explored a range of canopy sizes and structures. Of course, their device must be able to carry useful equipment, some of which is on the canopy and some of which is at the bottom.

Note that the canopy of the sensor device has a ring around it. That is an example of how the scientists built on nature's seed to make the current device. The ring adds stability to the device, which is about 30 times heavier than the dandelion seed.

One important design goal was that the device land upright, so the solar cell would work efficiently. The following figure shows how well this worked out...

The figure shows the percent of the devices that landed upright (y-axis), vs the size of the canopy structure (x-axis), and the "fill %" (color coding; see key at the right).

The results suggest a good size range for devices that reliably land upright. (It's hard to tell much about the fill % from this graph alone.)


   This is Figure 2f from the article.


The device is good over about a 50-100 meter range. That is the range over which light-moderate wind will disperse it, and the range its wireless signals can reach.


News stories:
* Tiny battery-free devices float in the wind like dandelion seeds. (Sarah McQuate, University of Washington, March 16, 2022.)
* 'Floating Sensors' Spread Like Dandelion Seeds -- Dropped by a drone, the battery-free devices hover 100 meters in the air. (Tech Briefs, April 14, 2022.) Includes an interview with the first author, Vikram Iyer.

The article: Wind dispersal of battery-free wireless devices. (Vikram Iyer et al, Nature 603:427, March 17, 2022.)

Background post: The smallest manmade flying devices (December 12, 2021). The article of this earlier post is reference 23 of the current article.

Also see: Smart dust: A central nervous system for the earth (July 20, 2010).

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



Pupil dilation as an indicator of visual imagination

May 7, 2022

The pupil of the eye gets larger (dilated) when there is less light. That is familiar.

Here are some data from a recent article -- with a twist...

The y-axis shows the change in pupil diameter, under various conditions. Blue data is for dark conditions, red is for bright conditions.

In the first segment (1-6 seconds), called perception, one or another condition was provided. The results show that the pupils got larger under dark conditions, smaller under bright conditions. As expected.

In the next segment, called rest, the stimulus was removed. Over a few seconds, the pupils of those from both types of stimuli became similar.

In the third segment, called imagery, each person was asked to imagine what they had perceived in the first segment. Those who had perceived and now imagined a dark stimulus got larger pupils than those who had perceived and now imagined a bright stimulus.

   This is Figure 1B from the article.


That is, light intensity can cause changes in pupil size not only during direct observation but during mental imagery. In the latter case, the pupil change is a physical manifestation of an act of imagination, and one that can be objectively measured.

That is the first major finding of the work.


Here are the results of a similar experiment with another group of people...

The results are generally similar to the top set, with one important exception: there is no difference between the dark ad bright groups during the imagery segment.

The people in this test have aphantasia, as labeled in the title of the figure. That means they lack visual imagination.

   This is Figure 3A from the article.


People self-report having aphantasia; there has been no test for it. The current work would seem to provide such a test, and to validate the self-reported condition.

Overall, the work here shows that a simple physical measurement may yield information about how the imagination works.


News stories:
* Windows to the soul: Pupils reveal 'aphantasia' -- the absence of visual imagination. (Science Daily (University of New South Wales), April 20, 2022.)
* Pupil Size May Reflect the Strength of Your Imagination -- Pupil size indicates the vividness of imagination and mental imagery strength. (Christopher Bergland, Psychology Today, May 1, 2022.) Includes some discussion of another article in the field.

The article, which is open access: The pupillary light response as a physiological index of aphantasia, sensory and phenomenological imagery strength. (Lachlan Kay et al, eLife 11:e72484, March 31, 2022.)

Another post about pupil dilation: Bright lights and pupil contraction (March 2, 2012). It, too, suggests that dilation is more complex then we might have thought.



May 5, 2022


Briefly noted... Progress toward making a more people-friendly (hypoallergenic) cat

May 5, 2022

Many people are allergic to cats. The major allergen, called fel d, is known. The question is, can we do anything about it? A recent article reports some explorations, including the use of CRISPR to inactivate one of the genes for fel d. Examination of the gene sequences for a wide range of cats, including several of the "big cats", shows that the gene is highly variable, perhaps suggesting it is not essential. The variability of expression in domestic cats is in agreement. That might suggest that eliminating the protein would be of no consequence to the cat. The work here is with cell cultures, and is successful. It is not clear where this leads. The authors do not think it is worthwhile to breed allergen-free cats. Instead, they envision a treatment to reduce the allergen levels of adult cats. We'll see. In any case, it is a fun article, and the issues are worth thinking about.
* News story: Scientists Are Inching Closer to Creating Truly Hypoallergenic Cats -- The gene-editing technology CRISPR could knock out a protein that's the major source of cat allergies, a new study says. (Ed Cara, Gizmodo, March 28, 2022.) Links to the article, which is open access.
* Here is an earlier news story, from last Fall. It gives an overview of various approaches to reducing the amount of cat allergen. It includes the current approach, but this story predates the current article. The Next Weird Way We're Changing Cats -- What if you could make your cat hypoallergenic with biotechnology? (Sarah Zhang, The Atlantic, November 5, 2021.)
* The article, which is open access: Evolutionary Biology and Gene Editing of Cat Allergen, Fel d 1. (Nicole F Brackett et al, CRISPR Journal 5:213, April 2022.)
* Posts about CRISPR are listed at: CRISPR: an overview (February 15, 2015).
* Previous mention of cat allergies: Pet Diary (September 25, 2009).



Atomic clock measurements of the difference in gravity over one millimeter

May 4, 2022

Gravity -- the gravitational field of a massive object -- distorts space-time. As a result, clocks run more slowly at higher gravity; clocks run more slowly on the surface of Earth than up above.

Look...

Part a (left) shows an experiment done 50 years ago. Clocks on the ground and in a high-altitude spacecraft were compared. It was found that the clock on the ground ran more slowly; the Earth clock reports less time elapsed, as predicted.

Parts b and c show two experiments reported in a pair of recent articles. Both involved the use of clouds of strontium atoms as atomic clocks. In one case, two clouds a centimeter apart were compared. In the other case, the top and bottom of a single cloud, a millimeter high, were compared.

In both cases, the predicted effect was seen: the lower clock ran more slowly.

   This is Figure 1 from the news story accompanying the article (Khabarova).


What's remarkable here is the sensitivity of the experimental systems -- the quality of the clocks.

Such atomic clocks operate by measuring the frequency of a particular transition within the atom. The observed time measurement may be affected by the gravitational field.

Here is an example of the results, from article 1...

Part a (left) shows results from a single test. The y-axis shows the measured frequency -- as the difference from the mean value. Note that 1 on the y-axis scale means 1 part in 1019. Green is for the raw data; purple is for corrected data.

The x-axis is for the elevation of the measurement; it covers about a one millimeter range.

The graph includes a best-fit line through the data. You can see that the line has a slight negative slope. The frequency varies with elevation.

Part b summarizes the results from 14 tests. Each point summarizes one test, with a mean and error bar. The black line at y = -1 shows the mean of those 14 tests, along with error bars. The red line is the expected value, from theory.

The left-hand y-axis is much like that in part a, but is now the change in frequency per millimeter of elevation. The right-hand y-axis is for the same results, but now reported as a change in gravity.

   This is Figure 3 from article 1 (Bothwell et al).


Overall, the results show that there is a change in the observed frequency of the clock by about 1 part in 1019 per millimeter of elevation. The measured result is very close to what is predicted.

For perspective... The difference in gravity between the head and feet of a child (height 1 meter) is a thousand times larger than what is observed here.

Is this for real? The point of the work is to push the limits. That is what experimental physicists do. The clocks here are about 50 times better than the previous best.

As for the results... Well, they were as expected. But an interesting point is developing the ability to measure gravity over extremely short distances. Is this a step toward unifying the theory of gravity, best understood at the large scale, with quantum mechanics, best understood at the small scale?


News stories:
* New Atomic Clocks Measure Time Dilation of Einstein's General Relativity at Millimeter Scale. (SciTechDaily (National Institute of Standards and Technology (NIST)), February 16, 2022..) Article 1.
* Ultraprecise Atomic Clock Poised for New Physics Discoveries - Loses Just One Second Every 300 Billion Years. (SciTechDaily (University of Wisconsin-Madison), February 20, 2022.) Article 2. Briefly mentions article 1.

* News story accompanying the articles: Metrology: Atomic clouds stabilized to measure dilation of time -- Tests of relativity once required accurate clocks separated by thousands of kilometres. Optical techniques have now made such tests possible in an atomic cluster measuring no more than one millimetre in size. (Ksenia Khabarova, Nature 602:391, February 17, 2022.)
* Two articles:
1) Resolving the gravitational redshift across a millimetre-scale atomic sample. (Tobias Bothwell et al, Nature 602:420, February 17, 2022.)
2) Differential clock comparisons with a multiplexed optical lattice clock. (Xin Zheng et al, Nature 602:425, February 17, 2022.)

More about gravity and time Which is older, the center of the Earth or the surface? (September 7, 2016). Links to more, broadly about gravity.

More strontium...
* Atoms within atoms? (May 25, 2018).
* Revealing the alabaster sources of ancient artists (March 7, 2018).



Design criteria for mRNA: the start codon

May 2, 2022

The start codon -- the first codon of a messenger RNA that is translated -- is AUG. It codes for methionine.

Of course, the real world is more complex than that. Other codons also serve as start codons, at lower frequency. The start codons vary in the first base; that is, they are all of the form NUG, where N stands for any base. Whichever start codon is used, it codes for methionine. The details vary, especially for prokaryotes vs eukaryotes, which use rather different procedures for initiation of protein synthesis.

A new article explores the effect of modified bases in the mRNA on the use of various start codons. The findings offer some clues for the details of how initiation works, but also has implications for how mRNA made for therapeutic use might be made better.

The following figure summarizes some of the findings...

The general plan is that various artificial genes were made, and tested to see how well they worked -- in human cells in lab culture. Each construct led to production of green fluorescent protein (GFP); the amount of GFP made is easily measured, and was used to evaluate the level of initiation.

Eleven sequences were tested. They are listed along the left side, and numbered at the right, along with the sequence of the initiation codon and nearby region.

For each sequence, there were two variations. As a control, the RNA was made using the natural (standard) bases. And then the main experimental variable... the mRNA was also made using two modified bases: 5-methylcytosine (5mC) and pseudouridine (PsU or ψ). These changes do not change the general nature of the base pairing, but they may affect details of interactions.

Let's look at some of the results...

Set 1 is labeled Kozak AUG. That refers to the consensus sequence for a good start codon (as originally elucidated by Marilyn Kozak). The result for natural bases is set to 100%. The result with modified bases is the same.

Set 2 is labeled Kozak GUG. Same as #1, except that the AUG start codon has been changed to GUG. In the sequences shown at the right, the start codon is underlined, and the change is shown in red. With this start sequence, it now functions poorly (about 10%) with natural bases, but rather well (about 60%) with the modified bases.

Set 3 introduces the actual initiation region from a specific human gene, called NAT1. This gene has a GUG start codon. The results show that it responds similarly to the Kozak GUG case (#2).

In set 5, that GUG start codon has been changed to AUG. It now behaves like the Kozak AUG case (#1).

Skip down to set 10. That NAT1 start codon is now UUG. It functions much like the GUG cases, working well only with the modified bases.

NAT stands for N-acetyltransferase.

   This is Figure 1C from the article.


The general picture is that the modified bases in the mRNA make little difference when there is a standard AUG start codon. However, genes with other start codons, which are normally translated poorly, are translated much better with the modified bases.

mRNA is being explored as a type of drug. The COVID vaccines are an example. Pseudouridine (actually, 1-methylpseudouridine) is used in COVID mRNA vaccines, because it reduced the immune response to the RNA. The new work opens up further possibilities for how modified bases can be a tool in designing therapeutic mRNAs. For example, an mRNA designed with a UUG start codon and made with the modified bases of the current work will be translated rather efficiently. However, if it gets copied, it won't be translated much, because UUG is a very poor start codon on its own.

Notes...

Both modified bases used here are found naturally, including in mRNA.

The authors provide some information on how the modified bases affect initiation, by altering the interaction with one of the initiation factors. This is based on calculations using computer models of the initiation mechanism.


News stories:
* Chemical markers that may unlock future uses of messenger RNA. (Ria Kakkad, Drug Target Review, April 28, 2022.)
* Scientists identify chemical markers that may unlock future therapeutic uses of mRNA. (Nanowerk News (Hiroshima University), April 26, 2022.)

The article, which is open access: Translational recoding by chemical modification of non-AUG start codon ribonucleotide bases. (Yoshihiko Fujita et al, Science Advances 8:eabm8501, April 8, 2022.)

Another post exploring how protein synthesis can be tweaked... Ribosomes with subunits that are tethered together (October 5, 2015).

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



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