Synthetic stem cells?

April 30, 2017

Synthetic stem cells? That's in the title of both news stories below. What could that possibly mean? After all, the purpose of stem cells is to provide cells that can grow, and we don't really know how to make synthetic cells that can grow.

The work here addresses a special case. There has been a lot of work using cardiac stem cells, so-called adult stem cells, to treat heart damage. The results have been mixed, but over time scientists have come to understand that these stem cells may be of real benefit, but not by working the way we expected. These cardiac stem cells may act primarily by promoting growth of the host tissue, not by providing cells per se. They promote growth by providing growth factors -- and by stimulating the host cells by direct membrane interactions.

If the cardiac stem cells act primarily by providing those functions, perhaps we can make a substitute that will serve. And that's the idea in this new article.

The following figure shows some bottom line results...

What are these cell-mimicking microparticles? They are based on synthetic particles, but they contain growth factors from cardiac stem cells, and they are coated with membranes from cardiac stem cells.

If this result holds up, it supports the idea that cardiac stem cells may be useful, but not by providing cells per se. That is, work with the synthetic stem cells enhances out understanding of the system. Further, the CMMP may actually have advantages for treatment. They are robust and easily stored, and they avoid immunological concerns.

Whether the CMMP work in humans is open; the work is entirely with mice. And there is no implication here about stem cells in general -- except to remind us that stem cells may do different things in different cases.

News stories:
* Synthetic stem cells offer benefits of natural stem cells without the risks. (Kurzweil, January 13, 2017.)
* Synthetic stem cells repair damaged hearts. (P Waldron, BioNews, January 9, 2017.)

The article, which is freely available: Therapeutic microparticles functionalized with biomimetic cardiac stem cell membranes and secretome. (J Tang et al, Nature Communications 8:13724, January 3, 2017.)

A post about the use of cardiac stem cells: Cardiac stem cells as a treatment for heart damage: preliminary results are "very encouraging" (November 29, 2011).

A recent post about heart damage: The role of mutation in heart disease? (April 25, 2017).

Another post using a similar experimental system of artificial heart attacks in mice: Zebrafish reveal another clue about how to regenerate heart muscle (December 11, 2016).

and more...
* Heart regeneration? Role of MNDCMs (November 10, 2017).
* If an injured heart is short of oxygen, should you try photosynthesis? (June 25, 2017).

More about heart regeneration: Human heart organoids show ability to regenerate (May 2, 2017). That is the next post.

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, including those on the broader topic of replacement body parts.

The quality of science news

April 26, 2017

The quality of news is itself a news item. Recent months have brought considerable attention to the topic, including much discussion of "fake news". Of course, we can raise the same issues about science news.

Two organizations that do science news have boldly put forth an analysis and summary. They are the American Council on Science and Health (ACSH) and RealClearScience. Both groups posted the summary, each with their own commentary. These are listed below as the news stories, which are the heart of this post.

I broadly agree with their ranking of news sources, for those I know about. I do think that their analysis made things too complicated at times. Criticizing Physics World, published by the Institute of Physics, because they only cover physics is a cheap shot -- and detracts from the main point that it is high quality coverage. But overall, that is a minor criticism. (I suggest that they use one ranking criterion: quality. Their other comments can be shown as characteristics, but they are not quality per se.)

The ACSH page also links to a story in which they attempt to characterize fake news. I think this is less successful; it is over-reliant on generalities. Nevertheless, it makes some good points. Read it if you want, but I suggest you not take it too literally.

Analyzing news quality is not simple, in science or in general. The organizations here deserve credit for tackling the issue, and for making good, if imperfect, contributions.

News stories:
* Infographic: The Best and Worst Science News Sites. (A Berezow, American Council on Science and Health, March 5, 2017.)
* Ranked: The Best & Worst Science News Sites. (R Pomeroy & T Hartsfield, RealClearScience, March 6, 2017.)

I learned of the analysis from an editorial in Nature: Science journalism can be evidence-based, compelling - and wrong. A ranking of the best science-news outlets misjudges the relationship between research and reporting. (Editorial; Nature 543:150 March 9, 2017) It is critical of the rankings. It makes some interesting comments, but overall seems unduly harsh.

A previous post about science news reporting: Media hype about scientific articles: Who is responsible? (March 9, 2015). The post includes some comments about how I choose news items for Musings.

More about news: Comparing how true and false news stories spread (June 5, 2018).

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

Musings has referred to a few news stories from ACSH, most recently: Update: Ebola vaccine trial (January 24, 2017).

Immunization of devils: a treatment for a transmissible cancer?

April 24, 2017

We have another interesting development in the story of the Tasmanian devils and their common cancer, devil facial tumor disease (DFTD). This cancer is unusual in that it is directly transmissible from one animal to another. In fact, the devils transmit it efficiently; biting each other is a common behavior. The devils have become an endangered species.

Investigation of the cancer has suggested that one reason for its virulence is that it fails to induce an immune response, because it fails to display antigens properly. [Links to previous posts on the DFTD are at the end. The 2013 post is about this particular finding on the lack of immune response.]

A new article, from the same lab, builds on that finding. If there is a defective immune response, perhaps we can fix it. To try to do that, the scientists make DFTD cells that do display tumor antigens, and use those cells as a vaccine. It works, though it is more complicated than that statement might suggest.

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

That is, the figure above shows a successful treatment of the cancer. Let's look further at what is going on.

A key point in following the procedures is to realize that there are two forms of tumor cells here. The usual form does not display tumor antigens. However, in the lab, the scientists can make a form that does display them. The latter are called MHC-I⁺ DFTD cells. You can see that name on the key in the graphs, by the vertical red dashed line. The term MHC-1 refers to the part of the immune system that had failed, but which they have "fixed".

Here is the basic procedure for part d...
- The animals were immunized by injecting them with dead MHC-I⁺ DFTD cells. That is, the immunization is against material that displays the tumor antigens in a form appropriate for an immune response. (The control animal, in part e, was not immunized. It received only the adjuvant, the carrier for the immunization, which helps stimulate the response.)
- The animals were injected with live tumor cells. This is at time zero on the graphs. You can see that this resulted in tumor growth in all the animals shown above over the following months. (There are two tumor injections, one on each side of the animal. LHS = left hand side. Qualitatively, the results are similar for both, so we won't worry about this point further.)
- After tumor growth was apparent, the animals were injected with live MHC-I⁺ DFTD cells -- that is, with live, antigen-displaying tumor cells. This was done at the time marked by the vertical red dashed line. In the immunized animals (part d), the tumors regressed soon after the injection of antigen-displaying cells.

There is one more tumor to consider; it is at the site of the injection of the live treatment cells, and is labeled IS. In the immunized animals, this happened in one of the two animals; the IS tumor remained small. In the non-immunized animal, the IS tumor continued to grow.

In summary... This is a two-step procedure. First, animals are immunized against the tumor antigens. Second, animals with tumors are treated with antigen-displaying cells. That lets the immunized animals mount a significant immune response against the tumors, which then regress. Although the tumor cells do not display antigens in the form that stimulates the immune system, they are susceptible to the immune response once it is turned on.

This is difficult work. It is with an endangered species, and the supply of animals for lab work is very limited. Each graph is for one animal; each line is for one tumor. The entire work in the article used nine animals -- over five years. Most of the experiments were isolated, without direct controls. Nevertheless, it's encouraging. If this holds up, immunization of animals prior to contracting the disease followed by immune stimulation after they have tumors may be effective in treating the devil facial tumor. Perhaps simpler treatments can be developed.

It could save the species. What is the right way to proceed?

News stories:
* Immunotherapy trial cures Tasmanian devils of DFTD. (Phys.org, March 9, 2017.)
* Breakthrough boosts hope for treating contagious cancer in Tasmanian devils. (S Dasgupta, Mongabay, March 14, 2017.)

The article, which is freely available: Regression of devil facial tumour disease following immunotherapy in immunised Tasmanian devils. (C Tovar et al, Scientific Reports 7:43827, March 9, 2017.)

Key background post on the DFTD immunity problem: Why the facial tumor of the Tasmanian devil is transmissible: a new clue (April 5, 2013). The article of this post is reference 10 of the current article.

Other posts on the DFTD:
* Tasmanian devils: Are they developing resistance to the contagious cancer? (September 6, 2016).
* The devil has cancer -- and it is contagious (June 6, 2011). Includes pictures; one is of an animal with a tumor.

Another transmissible cancer: Is clam cancer contagious? (April 21, 2015).

Also see:
* Predicting who will respond to cancer immunotherapy: role of high mutation rate? (October 6, 2017).
* Cancer and pain -- and immunotherapy (July 7, 2017).

My page for Biotechnology in the News (BITN) -- Other topics includes a section on Cancer.

When rivers (or streams) join, what is the preferred angle between them?

April 18, 2017

It averages about 45° in very dry regions, and about 72° in humid regions.

How do we know? Because someone measured a million such angles, and published the analysis in a new article. The measurements were done with satellite photos that covered most of the "contiguous" United States (the original 48 states). Here is a summary...

In fact, the scientists compare the map of river angles with a map of aridity. Maps, for comparison [link opens in new window]. (That is Figure 2 parts a and b from the article.) The upper map there is the same as the one above. The lower map shows aridity across the country. The two maps are amazingly similar.

Their measure of aridity is a little more complex than one might expect at first. Their aridity index (AI) is the ratio of precipitation to transpiration. Qualitatively, that's fine, but the numbers won't be familiar.

Geologists have long thought about what affects river junctions, but had little systematic data. The results here suggest that, in dry regions, rivers tend simply to flow downhill. That is, they tend to be parallel, and joins are at low angles. In contrast, in wet regions, there is considerable spreading, accounting for joining at larger angles.

The correlation between river angle and climate is based on detailed analysis of the data summarized in the maps. This is, literally, real-world data. One might wonder whether other features of the landscape affect the river junction angles -- in addition to the aridity. Indeed, the authors examine several variables that have been offered as factors that might affect river junction angles. Their statistical analysis of all the data says that the aridity index is the most significant contributor.

The authors suggest that understanding how rivers join on Earth could help in interpreting observations from other bodies, such as Mars or Titan.

Most likely, you had not thought about this issue before.

News story: Stream Network Geometry Correlates with Climate. (T Cook, EOS, April 6, 2017.) From the American Geophysical Union.

The article, which may be freely available: Climate's watermark in the geometry of stream networks. (H Seybold et al, Geophysical Research Letters 44:2272, March 16, 2017.) Caution... It is a 21 MB pdf file for this 9-page article. Lots of high resolution maps.

River posts include...
* Earth: RSSA (September 18, 2018).
* Atmospheric rivers and wind (May 9, 2017).
* Groundwater depletion in the Colorado River Basin (October 3, 2014).

A post about a non-Earth river system... TALISE: A better boat for Titan? (October 16, 2012).

Hm, "AI" has multiple meanings... Is AI ready to predict imminent kidney failure? (August 24, 2019).

Can antibodies to dengue enhance Zika infection -- in vivo?

April 15, 2017

Infection with one strain of dengue virus can make a subsequent infection with a different strain worse. Somehow, the antibodies against one strain enhance the infection with a different strain. The phenomenon is not well understood, but it does have a name: antibody-dependent enhancement (ADE).

Zika virus is rather closely related to dengue virus. Is it possible that prior infection with dengue affects Zika infection -- in any way? In particular, is it possible that dengue makes Zika worse, because of ADE between these two related viruses?

Musings addressed this issue about a year ago, with an article dealing entirely with cell culture. The work showed that dengue antibodies could enhance Zika infection [link at the end].

A new article addresses the question in a mouse model of Zika infection. Here is a key experiment...

That is, these results fully support a role for ADE in this system. Antibodies to the distinct but closely related dengue virus enhance Zika infection -- in a real animal. West Nile is also related to Zika, but less closely; it has a similar -- but smaller -- effect.

The scientists found that high levels of the anti-dengue antibodies protected against Zika infection. That is, the dose response curve is complex! There is also some evidence that Zika strains vary in their response.

Interestingly, some scientists do not accept that dengue enhancement of Zika is likely. Mice are poor predictors of human immune responses -- and the experimental system here is more complex than we have explained. Nevertheless, there is considerable evidence showing at least the plausibility of the effect: it happens in at least some in vitro and in vivo systems. It would seem prudent to take seriously the possibility that it happens in humans.

The possible role of ADE has implications for understanding the natural history of these virus infections; multiple members of this group of viruses, the flaviviruses, are often found in the same area. Of course, it also has implications for vaccines.

News story: Anti-Flavivirus Antibodies Enhance Zika Infection in Mice -- Researchers report evidence of antibody-dependent enhancement in a Zika-infected, immunocompromised mouse model. (A Azvolinsky, The Scientist, March 30, 2017.)

* News story in an earlier issue of the journal: Dengue may bring out the worst in Zika -- Mouse study offers evidence of antibody "enhancement," which could explain severity of human cases. (J Cohen, Science 355:1362, March 30, 2017.)
* The article: Enhancement of Zika virus pathogenesis by preexisting antiflavivirus immunity. (S V Bardina et al, Science 356:175, April 14, 2017.)

Background post: A Zika-dengue connection: Might prior infection with dengue make a Zika infection worse? (May 7, 2016). The article discussed here is reference 14 of the current article.

More... The effect of prior dengue infection on Zika infection (April 20, 2019).

A post about how subsequent infections with dengue can be more serious than the first: Dengue fever -- Two strikes and you're out (August 10, 2010).

and... Dengue vaccine: a step backwards? (December 6, 2017).

* Previous post about Zika: Why some viruses may be less virulent in women (March 1, 2017).
* Next: Why does Zika virus affect brain development? (August 11, 2017).

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.

The nasal spray flu vaccine: it works in the UK

April 12, 2017

A recent article, from the UK, reports that the nasal spray flu vaccine works well. Why is this noteworthy? About a year ago, the (US) Centers for Disease Control (CDC) concluded that it did not work.

Why the discrepancy? No one knows. The purpose here is to note it -- a challenge to figure out.

Let's backtrack and get an overview of the flu vaccine. There are two broad types of flu vaccine. The traditional flu vaccine is based on inactivated virus, and is given by injection. The newer vaccine is based on modified flu virus; it can infect, but does not cause disease. This vaccine, known as live attenuated influenza vaccine (LAIV), is given as a nasal spray. In principle, the LAIV has two advantages. First, the live virus can promote antibody formation on a continuing basis. Second, it avoids the use of needles. With both vaccines, there is a problem of choosing which flu strains to target; the flu virus is notoriously variable, on a year-to-year basis. Both vaccines include a mixture of different virus strains.

The basic facts here are simple...
- Last summer, the US government, through the CDC, voted against the nasal spray vaccine, citing data that it was only 3% effective in children (ages 2-17). In contrast, the traditional flu shots were 63% effective. (All data for vaccine effectiveness have considerable uncertainties, but the simple numbers convey the message.)
- The current article shows that the nasal spray vaccine was 54% effective for children (ages 2-6) in the UK. The authors recommend its continued use.

There are a number of possible differences between the studies. The current article discusses them. The general conclusion is that there is no explanation at this time for the discrepancy.

It's a reminder that the flu vaccine situation is complex and confusing.

News story: Flu Scan for Jan 27, 2017. (CIDRAP, January 27, 2017.) Scroll down to second story: Study in UK kids shows modest LAIV protection against severe flu.

The article, which is freely available: Live attenuated influenza vaccine effectiveness against hospitalisation due to laboratory-confirmed influenza in children two to six years of age in England in the 2015/16 season. (R Pebody et al, Eurosurveillance, in Volume 22, Issue 4, January 26, 2017.) Since our main purpose here is to note the contradictory results, the most interesting part of the article may be the discussion. The authors analyze what they did, and compare their results to other work, including the US findings. As already noted, there is no resolution at this point.

A page from the CDC announcing the ineffectiveness of the nasal spray vaccine: ACIP votes down use of LAIV for 2016-2017 flu season. (CDC, June 22, 2016. Now archived at the CDC site.) ACIP = Advisory Committee on Immunization Practices. in the CDC.

The following item is for general information.
* A page about flu vaccines from the CDC, in Q-and-A format: Vaccine Effectiveness - How Well Does the Flu Vaccine Work? (CDC, February 15, 2017.) It does not specifically mention the nasal spray vaccine, or the current article.

The nasal spray flu vaccine was discussed in the post Predicting vaccine responses (August 22, 2011). In that case, it fared more poorly than the injectable vaccine.

More on flu vaccine problems: What's wrong with the flu vaccine? (February 16, 2018).

More on needleless delivery of vaccines: Aerospace engineers develop explosive device for supersonic delivery of vaccines (August 2, 2011).

and... Clinical trial of self-administered patch for flu immunization (July 31, 2017).

Posts on the flu virus are listed on the page Musings: Influenza (Swine flu).

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

Staph fighting Staph: a small clinical trial

April 8, 2017

An interesting feature of infection with the pathogen Staphylococcus aureus is that most people who have it don't get sick. Two Musings posts have noted that part of the reason is that other bacteria, including other Staphylococcus strains, keep the pathogenic strains in check [links at the end].

A recent article takes the story a little further. The scientists study a skin disease called atopic dermatitis (AD). They show that it correlates with a higher level of S aureus, and a lower level of other "Staph" strains. Some of those other Staph make antibiotics, which inhibit the pathogenic Staph.

Would adding more "good" bacteria help restore the balance? The scientists show, with a mouse model, that treatment with "good" Staph strains reduces the colonization by the "bad" Staph.

Here is an example of the results...

The results above show that, for this experimental Staph infection of mouse skin, treatment with "good" bacteria reduces the load of "bad" bacteria.

The scientists then do a small test with human subjects with AD. The general nature of the test is similar to the one shown above, except that this is with people who have the skin infection. It is, in effect, a small Phase I trial.

The bottom line is that the work provides evidence that use of good, antibiotic-producing Staph strains may be useful in treating Staph aureus infections in humans. Further testing is in order. Does the treatment actually reduce disease symptoms, or does it merely reduce the bacterial count? What strains should be used? (The type of personalized treatment used in this work seems impractical for general use. Surely it is not necessary?) What is the appropriate course of treatment? And what are the merits of treating with bacteria vs treating with one or more specific products (antibiotics) from the bacteria?

News stories:
* Next Generation: Personalized Probiotic Skin Care -- Scientists treat Staphylococcus aureus skin infections using lotions made with bacteria from atopic dermatitis patients' own microbiomes. (J A Krisch, The Scientist, February 27, 2017.)
* Transplanting Good Bacteria to Kill Staph. (Y Galindo, UC San Diego, February 22, 2017.) From the lead institution. This story notes that a phase II trial is in progress.

The article: Antimicrobials from human skin commensal bacteria protect against Staphylococcus aureus and are deficient in atopic dermatitis. (T Nakatsuji et al, Science Translational Medicine 9:eaah4680, February 22, 2017.)

Background posts:
* Staph in your nose -- making antibiotics (October 9, 2016).
* Can the Staph solve the Staph problem? (July 12, 2010).

Another story of skin bacteria: Propionibacterium acnes bacteria: good strains, bad strains? (April 1, 2013).

Previous post on the development of a probiotic product: A clinical trial of ice cream (June 2, 2015).

Next: Would a probiotic reduce sepsis in newborn babies? (October 20, 2017).

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.

The smallest radio receiver

April 4, 2017

It's advertised as a radio built from two atoms. There is a reason for that claim, but it is also an exaggeration, so beware. Nevertheless, it is an interesting radio. It's a radio housed in a diamond.

Listen... video: A diamond radio receiver. (YouTube, 2 minutes. Lots of sound; that's the point.) The music there is from this new radio. And the accompanying background text and pictures give a good idea of what it is about. Feel free to listen just once; you can study how it works later. (The video is also included in the Nanowerk news story.)

The radio makes use of a phenomenon we have encountered before [link at the end]. Diamonds with nitrogen vacancy (NV) defects are fluorescent. Shine green light on them, and they fluoresce red. What's new here is that the intensity of the fluorescence is modulated by radio waves. That is, the output of the radio -- the diamond-based receiver -- is red light whose intensity carries the radio signal. That light signal can be processed by the usual means, and connected to a loudspeaker.

What is an NV defect? A diamond has an orderly array of carbon atoms. Replace one C atom with an N atom, and then remove another C atom right next to it, creating a vacancy (V). That is, two adjacent C atoms of the diamond have been replaced by an N (atom) and a V; that gives an NV defect.

Is this really a two-atom radio? Well, the basic receiver unit is indeed a single NV vacancy, based on replacing two atoms in a diamond. The actual receiver is macroscopic, and contains billions of those units. Further, the part discussed here is just the receiver, not the entire radio. It's a stretch to talk about a two-atom radio, but there really is a key two-atom part.

An interesting point about this radio is its robustness. It is, after all, made of diamond. The authors test the radio at 350° C. It works, though with reduced signal strength above about 200° C. They suggest that their diamond-based radio receiver may be suitable for use in harsh environments, including corrosive environments and space.

The radio operates in the 2.8 gigahertz band. The authors note that other analogous materials, based on atomic defects, should operate at other frequencies.

News stories:
* World's smallest radio receiver has building blocks the size of 2 atoms (w/video). (Nanowerk, December 19, 2016.)
* Hacked Diamond Makes Two-Atom Radio. (D Maloney, Hackaday, December 20, 2016.) An interesting page. Browse the comments, too.

The article: Diamond Radio Receiver: Nitrogen-Vacancy Centers as Fluorescent Transducers of Microwave Signals. (L Shao et al, Physical Review Applied 6:064008, December 15, 2016.)

Background post, with another use of the fluorescence of nitrogen vacancies of diamonds: Where is the hottest part of a living cell? (September 23, 2013).

More about nitrogen: How many atoms can one nitrogen atom bond to? (January 17, 2017).

More about atomic vacancies: Progress toward an ultra-high density hard drive (November 9, 2016).

More about diamonds: Ice in your diamond? (April 23, 2018).

Making triangulene -- one molecule at a time

March 29, 2017

Here it is: a molecule of triangulene...

What is triangulene? Start with a benzene ring. You may know that you can connect two benzene rings together, sharing a side; that gives naphthalene. Connect three together, side by side, and you get anthracene. Continue... Connect six together side by side, and you get a bigger molecule, which is still aromatic, like benzene. (It is called hexacene.) In particular, you can draw a structural formula with alternating single and double bonds.

Now, instead of connecting those six benzenes side by side, imagine piling them up: three in a base, two above that, and one on top. You get a triangular structure -- like what is seen above. (A structural formula in a moment.)

But there is a catch. You can indeed stack six hexagons that way, and get a big triangle. However, the resulting chemical is not aromatic: you cannot draw it with alternating single and double bonds.

For those who take that as a challenge, and want to try drawing it... I suggest you use a drawing program, such as ChemSketch. You can lay out the big triangle; that is no problem. But look at the bonding. And to make it clearer, I suggest that you turn on the display of all hydrogens. You will see at least one C that has 2 H on it, in addition to 2 C. That is a "saturated", sp³-hybridized C -- and a sure sign this is not one big aromatic ring system.

The anomaly of triangulene was recognized decades ago. Attempts to make it failed, presumably because it was unstable.

A new article reports a synthesis of triangulene. It's of interest for fulfilling the promise -- and for the unusual route of synthesis.

The following figure shows how the scientists made it; it also shows the strange feature of triangulene.

Radicals, with their unpaired electrons, tend to be unstable. That is presumably why previous syntheses of triangulene failed. In this work, the triangulene molecules were stable over a few days of observation; that was under the extreme conditions of ultra-high vacuum and low temperature.

That's the synthesis of triangulene. A molecule that is more complicated than it might appear, now made one molecule at a time.

Some think that triangulene could be useful in electronics, including in quantum computers. Interestingly, some think that making it one molecule at a time might provide a useful supply.

News stories:
* Researchers use new approach to create triangulene molecule. (B Yirka, Phys.org, February 14, 2017.)
* Elusive triangulene created by moving atoms one at a time. (P Ball, Nature News, February 13, 2017.)

* News story accompanying the article: Graphene fragments: When 1 + 1 is odd -- Triangulene, an elusive open-shell magnetic molecule, is synthesized and characterized by electron microscopy. (M Melle-Franco, Nature Nanotechnology 12:292, April 2017.)
* The article: Synthesis and characterization of triangulene. (N Pavlicek et al, Nature Nanotechnology 12:308, April 2017.)

More about radicals: Science myths (February 23, 2016).

Also see:
* Hückel at 40 -- that's n = 40: the largest known aromatic ring (February 1, 2020).
* The longest acene (September 6, 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.

A classic example of using the AFM to move atoms: The 35 most famous xenon atoms (June 29, 2010).

A recent example... A new form of carbon: C₁₈ (September 24, 2019).

For more on AFM and related techniques, see a section of my page of Internet Resources for Introductory Chemistry: Atomic force microscopy and electron microscopy (AFM, EM).

A possible genetic cause for the large human brain

March 25, 2017

It's the gene ARHGAP11B.

The gene ARHGAP11B is unique to humans. It's very similar to a gene called ARHGAP11A, which is widespread in other organisms. A team of scientists has now explored the nature of these two genes, and has suggested a special role of ARHGAP11B in the development of the human brain.

For simplicity, let's refer to the genes as B and A.

The evidence suggests that the B gene arose a few million years ago by a duplication of the original A gene in an early member of the human lineage. Gene duplications are an important part of how organisms develop novel traits. With two copies of a gene, one can continue to play the original role, while the other is free to acquire some new function as mutations accumulate.

In this case, the B gene eventually acquired a mutation -- a single base change -- that led to a substantial change in its properties. The base change was in a critical site for mRNA splicing, and led to a substantial change in the resulting protein. The current article works out the role of this splice site mutation in determining the nature of the B gene protein.

The following figure shows some of what the scientists learned about the function of the B gene protein. It is based on a model system in mice. Normal mice do not have the B gene.

On the basis of such results, the scientists suggest that the B gene promotes cell division in this region of the brain, thus leading to a larger brain.

The brain region studied here is the neocortex, which plays an important part in the enhanced cognitive capabilities of the human brain. It is thought to be one of the more recently expanded parts of the human brain.

Emphasize that there are multiple parts to this story:
* One is the actual analysis of the genes as we find them in humans and other extant organisms.
* On the basis of that, the scientists infer how the genes are related to each other. This is fairly straightforward, given the data, but could be modified if further data become available.
* From what they observe about how the B gene functions, they infer that it has a role in the development of the large size of the modern human brain. This is a logical suggestion, but the evidence is limited. In particular, we do not know how complex the full story is, i.e., how many genes played some role in the story.

Clearly, the B gene -- the ARHGAP11B gene -- is interesting. It may well be important in the development of the human brain, but we have only hints of that for now.

The mutation leading to the modern B gene is an example of how a single base change can cause a major change in the protein function. It causes a major change in protein sequence, because it is in a splice site.

What will scientists do next to test the role of the B gene? What more can we learn about expanding the human brain from a mouse model?

News stories:
* Researchers find DNA mutation that led to change in function of gene in humans that sparked larger neocortex. (B Yirka, Medical Xpress, December 8, 2016.)
* A Tiny Change With Considerable Consequences. (Neuroscience News, December 9, 2016.)

The article, which is freely available: A single splice site mutation in human-specific ARHGAP11B causes basal progenitor amplification. (M Florio et al, Science Advances 2:e1601941, December 7, 2016.)

Also see:
* Can a "silent" mutation be harmful? (April 17, 2021).
* Developing a monkey with a gene for a human brain protein (July 6, 2019).
* Bird brains -- better than mammalian brains? (June 24, 2016).
* Sliced meat: implications for size of human mouth and brain? (March 23, 2016).
* As we add human cells to the mouse brain, at what point ... (August 3, 2015).
* Fish with bigger brains may be smarter, but ... (January 25, 2013).
* Swarming locusts have bigger brains (August 29, 2010).

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

What can we learn from a five thousand year old corn cob?

March 21, 2017

The idea that corn (maize) was domesticated from teosinte, a crop native to Mexico, is now widely accepted. Genome analysis of modern corn varieties as well as modern wild teosinte leads to a list of differences. One can begin to understand the changes, but we have little idea of the course of domestication.

A recent article reports a genome analysis of a cob about 5,300 years old, from Mexico. That is during the early history of what we would now call corn.

The big picture is that this corn has many of the genes associated with modern corn, but not all. Since it is only part way to being modern corn, the authors suggest that the process of domestication may have been gradual.

We need to be cautious interpreting the results. It is exciting to have this early corn, but it is only one sample. We don't know how many types of corn were around at this time. We can never be sure that any particular sample is on the main pathway. In fact, the genome analysis suggests that this cob may be a distinct strain that split off from the ancestor of modern corn varieties.

The article is a step toward filling in the history of corn. We await additional genome sequences from other ancient corn cobs.

News story: DNA evidence from 5,310-year-old corn cob fills gaps in history. (Science Daily, November 17, 2016.)

The article: Genome Sequence of a 5,310-Year-Old Maize Cob Provides Insights into the Early Stages of Maize Domestication. (J Ramos-Madrigal et al, Current Biology 26:3195, December 5, 2016.)

More about teosinte and the origin of corn:
* How long have Americans been eating corn? (July 21, 2020).
* Atmospheric CO₂ and the origin of domesticated corn (February 14, 2014).

Among other posts about corn...
* Why growing maize (corn) is bad for us (June 25, 2019).
* Development of insects resistant to Bt toxin from "genetically modified" corn (April 19, 2014).
* Pink corn or blue? How do the monkeys decide? (June 9, 2013).

More domestication: Domestication of the almond (August 26, 2019).

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

What to do if your telomeres get too long

March 19, 2017

You could zap them, using the protein TZAP.

Telomeres? The special structures at each end of each chromosome in eukaryotes.

A new article explores what TZAP does.

Here is one experiment to show the effect of TZAP...

The results show that TZAP reduces the length of telomeres.

The more interesting question, perhaps, is... why would one want to do that? The main thing we hear about telomeres is that we must not run out. Losing TEL is related to aging. With that mindset, it's not obvious why one would worry about TEL being too long. The longer the better, it might seem.

However, the role of telomeres is more complicated than that. Perhaps their original role was simply to protect chromosome ends from becoming too short. But in the modern world, TEL are important structures in their own right.

There are various proteins that bind to telomeres. Even if we don't understand all their roles, we can recognize that they are important. For example, proteins bound to TEL distinguish normal chromosome ends from the artificial ends of broken chromosomes. Extra-long telomeres can soak up proteins that are needed at regular sites. That might not be good. In fact, the scientists show that TZAP binds to telomere sequences that are otherwise free of regular proteins. That they are free is a signal that there is too much TEL; it's time to trim some off. That's what TZAP does.

There is nothing here about how TZAP works. It is likely that it is more of a regulator than a trimming enzyme itself. It may recruit the relevant enzymes to the long TEL. The point here is to recognize the process of trimming long telomeres, and to identify that TZAP is a key player in the process.

The abbreviation TZAP actually stands for telomeric zinc finger-associated protein.

News story: Scientists discover master regulator of cellular aging. (Medical Xpress, January 12, 2017.)

* News story accompanying the article: Chromosomes: TZAP or not to zap telomeres -- A protein triggers the trimming of overly long chromosomes. (G Lossaint & J Lingner, Science 355:578, February 10, 2017.)
* The article: TZAP: A telomere-associated protein involved in telomere length control. (J S Z Li et al, Science 355:638, February 10, 2017.)

More about telomeres:
* If a cell needs more telomeres, can it get some from another cell? (November 15, 2022).
* A 115-year-old person: What do we learn from her blood? (November 18, 2014).
* G (July 8, 2008).

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

A better way to get to Alpha Centauri?

March 15, 2017

Musings recently noted a proposal to visit the nearby star Alpha Centauri, along with the possibly-habitable planet Proxima b that is in the same star system [link at the end].

The proposal rated well on speed: the time scale was well within a human lifespan. However, it had a significant weakness: there was no way to slow down the craft. Observation of star and planet would be made on the fly -- a challenge in itself -- and would be limited to a few hours before the craft had passed out of range.

A new article offers a solution to slowing a craft down, and even putting it in orbit around one of the Centauri system stars. How? Photons -- light pressure, from the stars. And gravity. I suspect the authors are not alone in suggesting the tools. What they did here was to run the numbers, and see what conditions would be needed.

The original proposal also used light pressure -- to accelerate the craft. The lights needed to do that would be lasers, more powerful than anything yet developed.

The slowdown procedure uses a large sail as a target for the photons. The effectiveness of the procedure depends on many things, including the nature of the sail. The bigger the sail, the more photons act on it. The lighter it is, the easier it is to slow it down with light pressure.

The following figure summarizes some of their findings about how it would work.

Let's look at an example... There is a sloping line near the left, labeled 100 years. That line shows combinations of distance and sail density that would give a 100 year trip. For example, look at a sail mass corresponding to graphene. Read up to the 100-year line. It's about 5 stellar radii. That is, if we used a graphene sail, we could plan a 100-year trip that would lead to closest approach of 5 solar radii. (There are other parameters specified in the article; more in a moment. The main point for now is the idea of the graph, and the comparisons.)

The slope of that 100-year line tells us about a tradeoff. If the sail were a little denser, it would get too close to the star. Too much gravity, too little effect of photon pressure.

To the right is another sloping line, for 1000 years. You can see that, if we are willing to make a 1000-year trip, we can use a sail in the range of the aluminum lattice. But that is a long trip.

The travel times shown reflect the initial velocity, which is maintained for most of the trip.

How big is the proposed sail? It is about 10⁵ square meters in area. That would be a square about 300 m on a side. That is, it is the size of several football fields. It would weigh about 10 grams.

Using a low sail density is important. Something like a graphene sail, only atoms thick at most, is what makes the proposal practical. Practical? Well, no one has done it. The authors do suggest that the technical challenges of their proposal would be easier to meet than the technical challenges of the previous proposal.

So this article offers an approach for slowing down a craft at the Alpha Centauri star system, allowing observations for an extended time. The downside is already clear: it is a much longer trip. 100 years. The slowdown procedure is limited to fairly slow craft speeds, about 4% of the speed of light, c. (The previous proposal had the craft traveling at about 20% of c.) This would be a trip planned and executed over generations of scientists -- and observers.

As we have noted, the technology does not yet exist for either proposal. These are advanced proposals, which stimulate research to see if their challenges can be met. And they meet our needs for fantasizing about future space explorations.

News stories. Both of the following give good overviews of the article and its context; both are quite lengthy.
* Space travel visionaries solve the problem of interstellar slowdown at our stellar neighbor. (Science Daily, February 1, 2017.)
* A decelerating gravity slingshot and solar pressure could be used to slow an interstellar solar sail travelling up to 4.6% of lightspeed. (B Wang, Next Big Future, February 1, 2017.)

The article: Deceleration of High-velocity Interstellar Photon Sails into Bound Orbits at αCentauri. (R Heller & M Hippke, Astrophysical Journal Letters 835:L32, February 1, 2017.) Check Google Scholar for a preprint freely available at ArXiv.

Background post: Planning a visit to the nearest star -- and to its "habitable" planet (February 22, 2017).

A post that might be about Alpha Cenaturi: Quiz: what is it? (April 5, 2017).

* Previous post on graphene: How do you get silkworms to make stronger silk, reinforced with graphene? (October 24, 2016).
* Next: Water desalination using graphene oxide membranes? (April 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 Musings posts on graphene and carbon nanotubes.

A novel enzymatic pathway for carbon dioxide fixation

March 12, 2017

In the common type of photosynthesis in plants, carbon dioxide is incorporated into a five-carbon sugar derivative, ribulose bisphosphate. This step is catalyzed by the enzyme commonly called Rubisco, which stands for ribulose bisphosphate carboxylase. The pathway is called the Calvin-Benson-Bassham cycle, or more simply, the Calvin cycle.

There are other ways to capture CO₂. In fact, there are five other pathways for CO₂ fixation in various autotrophic bacteria (those that can use CO₂ as their sole or major C-source). And there are various other carboxylase enzymes around in nature.

A team of scientists has looked at all the enzymes they know, and developed a novel pathway that could be used for CO₂ fixation in photosynthesis. It involves 17 steps, using enzymes taken from nine different organisms representing all three domains of life. The scientists claim that their novel pathway is more efficient than any current pathway.

Here is one key step, for the actual incorporation of CO₂...

That "first" enzyme is better than the common Rubisco. It works much faster, and oxygen does not interfere. (Why the quotation marks around first? The pathway is a cycle, but there is some logic to calling the point where CO₂ enters as the first step.)

Not all the enzymes the team wanted to use worked very well. The following figure shows how they improved one of them...

The figures above show two small pieces of the story. Overall, the scientists have assembled a new biochemical pathway, with 17 steps. One key enzyme is much better than the more commonly used Rubisco. In another case, we see that they have been able to dramatically improve the enzyme in the lab. Further, they argue that the pathway is more efficient, energetically, than the common pathway for the process.

Is this useful? I don't know. The project shows how we can use our knowledge of diverse organisms to develop novel biochemistry. Whether anyone ends up using the particular pathway developed here, it's an interesting -- and very impressive -- exercise. It will be of particular interest to see whether they try to implement the pathway in a real organism, perhaps an alga.

News story: A synthetic biological metabolic pathway fixes CO₂ more efficiently than plants. (Phys.org, November 22, 2016.)

A news video from the lead institution: Tobias Erb on Designing a More Efficient System for Harnessing Carbon Dioxide. (Max Planck Institute, 4 minutes.) A useful overview of the work, by the senior author. Amusingly -- but tastefully -- done.

* News story accompanying the article: Biotechnology: Fixing carbon, unnaturally -- A synthetic enzymatic pathway is more energy efficient than natural aerobic carbon fixation pathways. (F Gong & Y Li, Science 354:830, November 18, 2016.) Good perspective on the limitations of the work at this point.
* The article: A synthetic pathway for the fixation of carbon dioxide in vitro. (T Schwander et al, Science 354:900, November 18, 2016.)

A recent post on improving photosynthetic efficiency, in vivo: Improving photosynthesis by better adaptation to changing light levels (February 27, 2017).

A post about the history of the Calvin-Benson-Bassham cycle... Discovering how CO₂ is captured during photosynthesis: The Andy Benson story (June 15, 2013). If you haven't seen the video, check it out.

More about artificial photosynthesis: An artificial forest with artificial trees (June 7, 2013).

More about CO₂ fixation: Turning E. coli into an autotroph (using CO₂ as sole carbon source) (December 9, 2019).

A recent post with another example of lab development improving an enzyme... Carbon-silicon bonds: the first from biology (January 27, 2017). The context here, too, is the development of a new biochemical pathway, though they actually have only one step for now.

A visit from a star?

March 8, 2017

In a recent post, we discussed planning for a mission to visit the star Alpha Centauri and its possibly-habitable planet Proxima b [link at the end].

What if a star visited us? We've discussed concerns about asteroids visiting Earth, and there is an active program to discover asteroids that seem to be headed for Earth. But a star?

A recent article discusses a star that is heading our way. It's not that it will hit Earth. It will just come near the outer Solar System. That's enough to be of concern. It's not entirely a new issue. We've known that this star, Gliese 710, is heading in our general direction for decades. However, new data refines the estimate, and suggests a much closer approach than previously suspected.

The work here is based on some of the first data from the Gaia mission (European Space Agency). That data is still limited. What the authors do is to take the information that is available, and run simulations to see what the orbit may look like.

The following figure shows the key findings of the new article...

Key observations from the figure above...
- The new estimates (green region) of where the star will cross into the Solar System are much more tightly clustered than the old ones (black region).
- The new estimate is within the region predicted by the old study. But barely.
- The new estimate is much closer to the Sun than the old one, as judged by the center of each distribution (the central dots). Much closer.

There is still considerable uncertainty about where Gliese 710 will come. But it is almost certain that it will pass through the Oort Cloud. That's the birthplace of comets; the disruption due to the star may make it a good time for comets. The authors estimate that there may be ten new observable comets per year, for a few million years.

The estimated distance of close approach is about 13,000 AU (about 77 light-days), with an uncertainty of about 6,000 AU.

To help with the units... An astronomical unit (AU) is the distance between Earth and Sun. It is about 93 million miles. Pluto is about 40 AU from the Sun. A parsec is about 3 light-years. A light-year is about 63,000 AU.

The authors also note that the star will probably not significantly perturb any of the major bodies in the Solar System.

When will this happen? In 1.35 +/- 0.05 million years.

The article is a testament to the improving quality of our space observations. It is also a reminder that "things can happen" out there.

News stories:
* Incoming Star Could Spawn Swarms of Comets When It Passes Our Sun. (G Dvorsky, Gizmodo, December 22, 2016.)
* A star is hurtling towards our solar system and could knock millions of asteroids straight towards Earth. (L Dodgson, Business Insider, January 8, 2017.)

The article, which is freely available: Gliese 710 will pass the Sun even closer -- Close approach parameters recalculated based on the first Gaia data release. (F Berski & P A Dybczyński, Astronomy & Astrophysics 595:L10, November 2016.)

Background post... Planning a visit to the nearest star -- and to its "habitable" planet (February 22, 2017).

Also see: Of disasters, asteroids and meteors (February 19, 2013).

I feel your pain -- how does that work?

March 4, 2017

If you get hurt, you may have pain. We understand that. But do you feel pain when someone else gets hurt? Sometimes we may say so, but it would seem a psychological point, reflecting empathy. After all, it is the other person who got hurt; we can't literally feel someone else's pain.

Or can we?

Let's look at the results of a simple experiment. It is with mice.

That is, the mice without morphine performed as poorly as the mice suffering morphine withdrawal -- when they were housed together. In other tests, the pain-inducing stimulus was irritation to the foot pad or alcohol withdrawal; the results were similar. As judged by tests such as this, it appears that untreated mice can feel the pain of their comrades -- if they are together. The criterion is that the affected mice behave physiologically as if they are in pain.

What's going on? The experimental design above allows for variation to see what the key variables might be. In one test, the transfer of bedding from mice with pain to naive mice caused the latter to show the mechanical hypersensitivity that reflects their own pain. This result suggests that pain is being transmitted by volatile chemicals, or, loosely, by odor.

The authors note an additional implication of the findings, beyond the simple point of pain being transmitted by olfactory cues... In experimental work with mice, it is possible for physiological states to be transmitted from one animal to another.

News stories:
* Sensitivity attributable to pain found transferable to other mice. (B Yirka, Medical Xpress, October 24, 2016.)
* With a Whiff, Mice Can Transmit Pain to Each Other. (N Scharping, Discover, October 20, 2016.) One part is a little garbled, but overall this is a useful overview of the work.

The article, which is freely available: Social transfer of pain in mice. (M L Smith et al, Science Advances 2:e1600855, October 19, 2016.)

More about pain...
* Chronic pain in flies? (October 6, 2019).
* Cancer and pain -- and immunotherapy (July 7, 2017).
* Can we predict whether a person will respond to a placebo by looking at the brain? (February 21, 2017).

More about opioids...
* Lesson from a worm: An endogenous anti-opioid system? (January 5, 2020).
* Do you make morphine? (May 18, 2010).

Also see... Why male scientists may have trouble doing good science: the mice don't like how they smell (August 22, 2014).

Why some viruses may be less virulent in women

March 1, 2017

Some viruses are less virulent in women than in men. Why? It is sometimes suggested that it's due to differences in the immune system of men and women.

A recent article offers a different suggestion. The authors suggest that it is to the benefit of the virus to be gentler with women. After all, women better serve the virus by transmitting it further, via childbirth and breastfeeding.

Here is an interesting situation that the authors consider... A particular virus, called HTLV-1, eventually kills people by leukemia. In the Caribbean, it kills men and women in about a 1:1 ratio. In Japan, it kills about 2.5 times more men than women. Why the different sex ratio in two places? The authors correlate it with breastfeeding, which is much more extensive in Japan than in the Caribbean.

The article develops mathematical models for how sex-specific virulence could benefit a pathogen. However, there is no evidence to test the suggestion, comparing it to alternatives. The article offers a hypothesis, one that is testable and should be the subject of future work. For example, is the HTLV-1 virus different in Japan and the Caribbean, in a way that can explain why it behaves differently in those areas? For now, it is just a hypothesis -- an intriguing hypothesis.

The Smithsonian news story notes that Zika virus could be a good counter-example: a virus that women transmit, but which seems to affect women more than men. Again we emphasize that the current article offers a hypothesis, which may be one factor affecting sex specificity in some viruses. The contribution of the article is to offer the hypothesis, for further consideration. The challenge is to sort out the various factors, and see when they apply.

News stories:
* For Viruses, the Best Way to Infect Baby Is Through Mama. (B Panko, Smithsonian, December 14, 2016.)
* Viruses target men and women differently, research suggests. (Dentistry.co.uk, December 15, 2016.)

The article, which is freely available: The evolution of sex-specific virulence in infectious diseases. (F Úbeda & V A A Jansen, Nature Communications 7:13849, December 13, 2016.) This is a fairly readable and interesting article, even if you don't want to get into the math. Just skip over the math, and you can follow most of the development.

Posts on leukemia include...
* Effect of low dose radiation on humans: some real data, at long last (July 24, 2015).
* Is clam cancer contagious? (April 21, 2015).

More Zika... Can antibodies to dengue enhance Zika infection -- in vivo? (April 15, 2017).

Another case of sex differences in disease susceptibility... SNO and the higher prevalence of Alzheimer's disease in women (January 14, 2023).

My page for Biotechnology in the News (BITN) -- Other topics includes sections on Cancer and on Zika. Each includes a list of related posts.

Did the Neandertals make jewelry? Evidence from ancient proteins

February 26, 2017

Briefly noted...

How do we know if an archeological find of an ancient human culture is from modern humans or from Neandertals? Sometimes, it is clear from bone morphology, which was the original basis for making the distinction. But sometimes it is hard to tell.

We now have genome sequences for both types of humans, but getting genome sequences from archeological samples is still often limited. However, genomes code for proteins, and an interesting development is that it is becoming possible to analyze proteins from ancient samples.

In a recent article, scientists reported using information about the proteins to tell what kind of human remains were at a particular site. Neither morphology nor DNA information was very helpful, but the protein information helped them recognize the site as Neandertal. In one case, the form of collagen that was present helped the scientists identify a specimen as being from an infant.

The samples are from the Grotte du Renne, in France. They are from a culture known as Châtelperronian, in France and Spain. They are 40-50 thousand years old, from the time of the transition from Neandertal to modern human in Europe.

Jewelry? An interesting point about the site is that it seemed that the natives used jewelry. Associating the site with Neandertals, we now conclude that Neandertals used jewelry. At least, these Neandertals used jewelry. It's not just jewelry that is of interest from the site, but also the types of tools found there. Overall, the work is part of understanding the lifestyle and culture of Neandertals -- assuming that the data are correct, and the interpretations hold up. This is a field where it is a lot of work to get even small pieces of information, and big conclusions require accumulated data.

It's an interesting development. The article itself is considerably more complex than I have suggested here. But the news stories give useful overviews, with an emphasis on the context.

News stories:
* Researchers Identify Archaic Hominins Associated with Chatelperronian Tool Technology. (Sci.News, September 23, 2016.)
* Palaeoproteomics helps differentiate between modern humans and Neandertals -- Researchers decode ancient proteins of Châtelperronian Neandertals. (Max Planck Institute, September 16, 2016.) From the lead institution.

The article, which is freely available: Palaeoproteomic evidence identifies archaic hominins associated with the Châtelperronian at the Grotte du Renne. (F Welkera et al, PNAS 113:11162, October 4, 2016.)

Background post on ancient proteins: Dinosaur proteins (July 6, 2009); it links to more. The proteins of the current work are less than 1% of the age of the dinosaur proteins from this earlier work. It is interesting to see the use of information from old proteins here, but the age per se is not remarkable.

More... Denisovan man: beyond Denisova Cave (May 7, 2019).

Previous post about Neandertals... The lost Neandertal Y chromosome (August 13, 2016).

A post about people who shouldn't wear jewelry: Should you ask your doctor to go BBE? (May 12, 2014).

Planning a visit to the nearest star -- and to its "habitable" planet

February 22, 2017

The nearest star outside our Solar System is Alpha Centauri, about 4.2 light-years away. An article last year suggested that a planet there, Proxima b, may be in the habitable zone.

Let's visit.

In fact, a program to develop a mission to visit Alpha Centauri and its planet Proxima b is in progress. It's Breakthrough Starshot, with start-up funding of a hundred million dollars (US) from Russian investor Yuri Milner. That's enough to bring together key people and develop a serious plan, with milestones. An important part of the project at this point is to define what needs to be done to make it possible. For example, the idea of using lasers to accelerate the craft to its intended speed, about 20% of the speed of light, is fine -- except that suitable lasers do not yet exist.

Nature recently ran a news feature on the project. It almost reads like a science-fiction fantasy. But it's not. It's a serious effort to try to visit a star within about 50 years. Hopefully, some of those involved in the early development of the project will live to see data from the encounter.

If this works, the tiny spacecraft -- the size of a small coin -- will send back pictures during the 2060s. Of course, it will be a while until we see them. The pictures will take 4.2 years to return, traveling at the speed of light. However, the project should yield interesting technical developments in the coming decades. For now, that's the point.

It's a delightful little article.

News feature: First trip to the stars -- A wild plan is taking shape to visit the nearest planet outside our Solar System. Here's how we could get to Proxima b. (G Popkin, Nature 542:20, February 2, 2017.) (Online version has a different title.) Outlines the plan, with a suggested timeline. Includes extensive discussion of the hurdles.

An alternative... A better way to get to Alpha Centauri? (March 15, 2017).

A post about our most distant explorations so far: At the edge of the solar system (September 28, 2012).

A post about planning space missions: Quiz: NASA's boat (June 29, 2011).

A recent post about habitable planets... Habitable planets very close to a star (June 19, 2016).

Also see...
* Titanium oxide in the atmosphere? (December 9, 2017).
* A visit from a star? (March 8, 2017).

Do apes have a "theory of mind"?

February 19, 2017

Imagine two people together; call them A and B. They have a ball, and a couple of pots, one red and one blue. They put the ball in the red pot. Person A leaves the room. While A is away, the ball is moved to the blue pot. A returns, and looks for the ball. Where will A look: in the red pot or the blue one? More importantly for our purpose here, where does person B think A will look?

You probably expect that A will look for the ball in the red pot, where it was when he left the room. You know what A knows -- and so does B. B knows that the ball is in the blue pot, but also knows that A thinks it is in the red pot. A has a false belief, but B understands that A has that false belief -- and that he will act on it.

A young child wouldn't make that prediction. If B was a young child, the child would predict that A would look in the blue pot. After all, the child knows the ball is in the blue pot; why wouldn't A know? The child does not understand that A has a false belief.

The ability to make that distinction requires what is called a theory of mind. An adult B understands what A thinks, even though it is wrong. Children acquire the ability to make the distinction around age 4 (though it varies with the details of the test).

That's a long introduction to set the stage for a recent article -- which reports such a test with three species of apes.

The challenge is to figure out how to do the test. The general logic of the test is similar to what was described above. The problem is, how do you tell what ape B predicts for where A will look?

The scientists addressed that problem with a method used for children too young to tell the investigator their choice. It relies on eye-tracking. The investigators watched the eyes of the ape (just as they would when testing an infant). The eyes reveal what the ape (or infant) expects.

The following figure shows the results for the various apes tested over two tests.

Overall, the eye tracking indicated that the apes made the correct prediction about 2/3 of the time -- significantly greater than chance. That is, the apes knew what A was thinking, even though they knew it was wrong. The apes appear to have a theory of mind, as judged by such a test.

The results here, suggesting that the apes have a theory of mind, disagree with previous work. The authors argue that they have a better test, one that finally shows what the apes really think. Is that correct, or is the current test, for some reason, giving a wrong answer? We can only await further testing, presumably with a range of tests.

News story: Apes understand that some things are all in your head. (Max Planck Institute, October 6, 2016.) From one of the institutions involved.

Videos. There are two videos posted with the article as Supplementary Materials. (2 minutes each, no sound.) They should be freely available. The videos show sequences from the testing. If you want to get into how the testing was done, the videos may be a good place to start; it's a little confusing from the article itself.

The article: Great apes anticipate that other individuals will act according to false beliefs. (C Krupenye et al, Science 354:110, October 7, 2016.)

A mind post: The animal mind (July 23, 2009).

A recent post about apes: Age-related development of far-sightedness in bonobos (January 10, 2017).

More... Is Bcbva anthrax a threat to wild populations of chimpanzees? (September 8, 2017).

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

Why does a durian smell so bad?

February 14, 2017

A new article reports the major chemicals responsible for the odor of an interesting fruit. In order, starting with the most important, the odors are described as: fruity; rotten onion; roasted onion; rotten, cabbage; sulfury, durian; fruity; fruity; fruity; rotten, durian; fresh, fruity; roasted onion; roasted onion; skunky. The list goes on, but that's enough for now. Rotten egg is a few places further down the list.

What do we mean by order of importance? It's based on the odor activity value (OAV). That is the ratio of the concentration (in the fruit) to the odor threshold (the amount we can detect). For example, the odor ingredient at the end of the list above, described as skunky, is present at about 0.9 µg per kg of fruit. We can detect that chemical at 0.00076 µg/kg (in water). Therefore, its OAV, the ratio of those two numbers, is about 1200.

The information above is from Tables 2 and 3 of the article. Table 2 presents their results for the concentrations; the results are then summarized and presented in order by OAV in Table 3. The names of the chemicals are given in both tables. That skunky odor, for example, is due to 3-methylbut-2-ene-1-thiol.

Now that you know what this fruit smells like, would you like to try some? It's apparently a quite tasty fruit -- if you can get by its odor. It's the durian, more specifically the Monthong durian (Durio zibethinus L. 'Monthong').

One type of follow-up test is to make artificial mixtures of selected compounds, and see how people respond. In this case, the scientists found that a mixture of two of the major odor chemicals was identified by a panel of human testers as durian about as often as the real thing. The two chemicals used here were the first and third from the list above: one that is very fruity and one that smells of roasted onion.

News stories:
* Compounds responsible for world's stinkiest fruit revealed. (E Stoye, Chemistry World, January 25, 2017.)
* Chemists Identify Key Compounds Responsible for Durian's Pungent Odor. (N Anderson, Sci.News, January 19, 2017.)

The article: Insights into the Key Compounds of Durian (Durio zibethinus L. 'Monthong') Pulp Odor by Odorant Quantitation and Aroma Simulation Experiments. (J-X Li et al, Journal of Agricultural and Food Chemistry 65:639, January 25, 2017.)

A recent post about sulfur odors... Copper ions in your nose: a key to smelling sulfur compounds (October 10, 2016). Links to more about odors.

A post about the chemical responsible for the rotten egg part of the durian odor: What's the connection: rotten eggs and high-temperature superconductivity? (June 8, 2015).

More about fruit ingredients...
* Is the lychee (litchi) a toxic food? (May 11, 2015).
* Grapefruit and medicine (March 26, 2012).

Antibiotic resistance genes in "ancient" bacteria

February 11, 2017

What if we had some bacteria that had not seen "modern civilization" for four million years? Perhaps they have not even seen animals during that time. Is it possible that they might be resistant to some modern antibiotics?

Of course, the answer is yes. After all, many of our antibiotics are natural chemicals, made by other microbes. These antibiotics undoubtedly play a role in competition between microbes in nature. It is natural that bacteria would develop resistance to them.

A team of scientists has been studying the bacteria in Lechuguilla Cave in New Mexico. (The cave is part of Carlsbad Caverns National Park.) From the nature of the situation, it is likely that these bacteria have been isolated from the surface world for four million years. Interestingly, one of the bacterial strains is resistant to most of our modern antibiotics.

The bacteria studied here are living modern bacteria. What's unusual is that, so far as we know, they have been isolated from the "outside world" for millions of years. They have not undergone genetic exchange with surface organisms, and have not been exposed to modern sources of pathogens or antibiotics. In that sense, they are "ancient".

In a new article, they explore the antibiotic resistance of this organism, called Paenibacillus sp. LC231. The study is based on analyzing the genome, and then doing follow-up biochemistry of genes of interest. For example, they studied the resistance genes they found in the cave Paenibacillus after transferring them to common Escherichia coli.

The basic finding is that numerous resistance genes were found. Some of them are similar to known modern genes, some appear to be novel. All of the resistance genes they found were on the main chromosome of the bacterium; none were on plasmids.

The scientists also found that most of these resistance genes from the cave bacteria were in some strains of the same type of bacteria from the surface. This raises a question about their origin.

It's an interesting view of an unusual situation. Finding resistance genes in ancient organisms is not a surprise. Importantly, it does not reduce our responsibility to monitor and limit modern antibiotic resistance. Antibiotics may have been around in ancient times, but human activity has increased their prevalence, and thus increased the pressure to develop resistance.

Nowadays, spread of antibiotic resistance is often via plasmids; it's easier to acquire a ready-made resistance from a neighbor than to make your own from scratch. The lack of plasmid-borne resistance genes in these cave bacteria is interesting.

News story: Multi-Drug Resistant Bacteria Found Deep in New Mexico's Lechuguilla Cave. (Sci.News, December 13, 2016.)

The article, which is freely available: A diverse intrinsic antibiotic resistome from a cave bacterium. (A C Pawlowski et al, Nature Communications 7:13803, December 8, 2016.)

Previous post about antibiotics: Staph in your nose -- making antibiotics (October 9, 2016).

Antibiotic resistance... On completing the course of the antibiotic treatment (September 19, 2017).

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.

More from caves and such...
* Life -- and old carbon -- in a blue hole (March 21, 2020).
* Our newest spiders: the cave robbers (September 5, 2012).
* Images from 30,000-year-old motion pictures (July 22, 2012).

Pangenomes and reference genomes: insight into the nature of species

February 7, 2017

The cost of genome sequencing has plummeted in recent years. That has allowed massive levels of sequencing, beyond what we might have dreamed of just a few years ago.

Sometimes, such massive sequencing may tell us more than we wanted to know.

In the early days of genome sequencing, getting one complete genome sequence for an organism was a significant achievement. We understood that genomes varied, but having one gave us a "reference genome" for the species.

However, cheap sequencing has allowed us to accumulate many genomes for a species, and sometimes there is a surprise. It's illustrated by the following cartoon.

What's shown there is what is actually found, especially for genomes of microbes. The details (such as how fast the upper curve levels off -- if at all) vary.

The lower curve is now considered to be the core genome for the species. The upper curve reflects a new idea, the pangenome: the collection of all genes associated with the species.

In one case, the bacterial genus Prochlorococcus, analysis of 45 strains has revealed about 80,000 genes -- the pangenome. The core genome is about a thousand genes.

The Scientist recently ran a news feature on the emerging idea of the pangenome. It's an interesting -- and incomplete -- story. It challenges our notions of what a species is. In particular, we see that getting one genome may tell us very little about the species.

Feature story, which is freely available: The Pangenome: Are Single Reference Genomes Dead? -- Researchers are abandoning the concept of a list of genes sequenced from a single individual, instead aiming for a way to describe all the genetic variation within a species. (C Offord, The Scientist, December 2016, p 31.)

Most recent post on the wonders from genome sequencing: The Asgard superphylum: More progress toward understanding the origin of the eukaryotic cell (February 6, 2017). That's the post immediately below.

A post on the cost of genome sequencing... The $1000 genome: we are there (maybe) (January 27, 2014).

A post about the possibility of getting too much genome information, though for a different reason: Are there genetic issues that we don't want to know about? (October 22, 2013).

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

One reason members of a species may have different genes is horizontal gene transfer (HGT), the direct transfer of genes between organisms. It's considered common in prokaryotes, but increasingly recognized to have some role in higher organisms. Here is an example: An extremist alga -- and how it got that way (May 3, 2013).

How much energy are we saving with energy-saving houses?

February 5, 2017

Not much, according to a new article.

The article deals with energy usage for houses in the State of California (CA), where a series of building regulations intended to reduce energy consumption was introduced starting in the late 1970s.

The following graph summarizes the basic data...

What does the graph show? Well, if you wanted to argue that energy usage declined for houses built after the red line (the start of regulations), you might note that gas usage declines after that time, and electricity usage levels off. (It may be questionable whether these trends really correlate with the regulations, but let's not worry that.)

Overall, there seems to be a decline in energy usage for newer houses. Perhaps 15% for houses built since the regulations were introduced.

Here is how I estimated that number of a 15% decline. It is a rough estimate, but what follows does not critically depend on the exact value.

I estimated the values for gas and electricity from the graph, and added them together to get the total energy usage. For the oldest houses (extreme left data), I estimate 67 MBTU. For the houses just before the red line, I get 72 MBTU. For the newest houses (extreme right data), I get 62 MBTU.

Using those numbers, it appears that the newest houses use about 15% less energy than the houses built just before the regulations were introduced.

So, it would seem that the regulations for making houses more energy-efficient led to a 15% decline in energy usage.

When the regulations were introduced, it was predicted that they would lead to an 80% reduction in energy usage. And therein lies the problem. The energy reduction that resulted from the regulations is -- according to the new analysis -- far less than promised or expected.

Why the discrepancy? Is there something wrong with the analysis above, or have the savings really been far less than expected?

The author examines some possible problems with the analysis. For example... Maybe there is some other difference between new houses and old ones that affects their energy usage. Maybe new houses are in areas of the state that need more energy. Maybe people who live in newer houses are more affluent, and tend to use more energy. The author looks at these and some other possibilities, and does not find any major flaw in the analysis.

One might wonder whether there is a political motivation here. Perhaps the author is anti-regulation, and trying to show that regulations don't work. I have not examined the author's background. But importantly, in the end, it is data that matters. If the analysis is flawed, someone needs to show why.

The author has done his analysis, and published it. If others have objections, or alternative analyses, they should do the same. I did not find much comment on the article at this point, but it is early.

What's the point of this post? The article caught my attention as being about an interesting issue -- and it is about my home state. It's interesting, and fairly readable -- and it challenges us. In science, we do not take a single article as "the answer"; let's see what comes from this article. Perhaps this article along with its follow-up will lead to a better understanding of what works well and what does not.

News stories:
* Have green building codes succeeded in saving energy? Energy savings from efficiency requirements prove hard to find. (T Hyde, American Economic Association, October 19, 2016.) Good discussion.
* I'm Not Really Down with Most Top Down Evaluations. (M Auffhammer, blog at Energy Institute, Haas School of Business, University of California Berkeley, September 19, 2016.) A discussion of the problem of evaluating energy efficiency in the real world. It is not specifically about the current article, though the article is noted in the comments that follow.

The article, which may be freely available: How Much Energy Do Building Energy Codes Save? Evidence from California Houses. (A Levinson, American Economic Review 106:2867, October 2016.)

A post about reducing energy usage of a house: What if your house could sweat when it got hot? (November 30, 2012).

More about energy efficiency... Is solar energy a good idea, given the energy cost of making solar cells? (March 24, 2017).

There is a section of my page Internet Resources for Organic and Biochemistry on Energy resources. It includes a list of some related Musings posts.

The Trump moth

January 31, 2017

We note two sentences from the article, in the section where the author explains the name (page 89, bottom). The sentences are in the opposite order in the article.
* "The specific epithet is selected because of the resemblance of the scales on the frons (head) of the moth to Mr. Trump's hairstyle." You may want to check a close-up of the (moth's) head, in Figure 2cd of the article (or the news story).
* "The reason for this choice of name is to bring wider public attention to the need to continue protecting fragile habitats in the US that still contain many undescribed species."

The specimen is from a collection at the University of California, Davis. It was originally collected in Imperial County, at the southern end of California. The range of the moth is the southeast of California and the north of Baja California (Mexico), based on the few specimens found so far.

News story: New species of moth named in honor of Donald Trump ahead of his swearing-in as president. (Phys.org, January 17, 2017.)

The article, which is freely available: Review of Neopalpa Povolný, 1998 with description of a new species from California and Baja California, Mexico (Lepidoptera, Gelechiidae). (V Nazari, ZooKeys 646:79, January 17, 2017.)

A previous moth post: The story of the peppered moth (July 9, 2012).

Another Lepidoptera discovery: Which came first: butterflies or flowers? (March 9, 2018).

Also see:
* Briefly noted... The Biden octopus (March 22, 2022).
* The Obama lizard (March 20, 2013).

Using your nose to fix knee damage

January 28, 2017

Cartilage damage in the knee is a significant health problem. There are various approaches to treating knee cartilage damage, but none are particularly satisfactory.

A recent article offers a new approach: use your nose. The structural material in the nasal septum is actually the same type of material as knee cartilage. Interestingly, the nasal chondrocytes (cartilage-forming cells) seem to have better regeneration capability than those from the joints. And it's much easier to get a sample from the nose than from the knee.

You might wonder about the size of the sample from the donor site. What the scientists do is to excise a small piece of the nasal septum, and then expand it in lab culture. The lab-grown material, derived from the nasal septum, is what is implanted into the knee.

The present study, a Phase I trial, is the first trial of the method in humans. It involved ten patients, with two years of follow-up. Analysis included MRI of the knee, as well as the patients' subjective evaluation of their status. Most of the results are encouraging. The article here is a preliminary report; the current trial will continue. A Phase 2 trial, comparing cell sources and procedures, is in progress. Nose-to-knee cartilage transfer seems a promising approach.

Pictures? There are many in the article, some with plenty of blood. Help yourself.

News stories:
* Engineered Autologous Nasal Chondrocytes Repair Articular Cartilage. (Rheumatology Advisor, October 24, 2016.)
* Nose cells could help repair damaged knee cartilage. (C Paddock, Medical News Today, October 21, 2016.)

* "Comment" accompanying the article: Cartilage repair across germ layer origins. (N Rotter & R E Brenner, Lancet 388:1957, October 22, 2016.)
* The article: Nasal chondrocyte-based engineered autologous cartilage tissue for repair of articular cartilage defects: an observational first-in-human trial. (M Mumme et al, Lancet 388:1985, October 22, 2016.)

More cartilage...
* Making new cartilage, using stem cells (January 5, 2022).
* Humans may be more like salamanders than we had thought (limb regeneration) (February 11, 2020).
* The oldest known syrinx (December 4, 2016).
* The role of zinc in arthritis (July 18, 2014).

More knees:
* The human body: Do you have fabellae? (August 17, 2019).
* Can we predict whether a person will respond to a placebo by looking at the brain? (February 21, 2017).
* Jumping -- flea-style (February 21, 2011).
* Should you run barefoot? (February 22, 2010).

A recent nose post... Copper ions in your nose: a key to smelling sulfur compounds (October 10, 2016). Links to more.

Update: Ebola vaccine trial

January 24, 2017

Original post: An Ebola vaccine: 100% effective? (August 7, 2015).

As the recent Ebola outbreak in West Africa waned, there was an important trial of an Ebola vaccine. It was a clever trial, focusing on those who were likely to be contacts of known cases, thus most likely to have been exposed. That strategy is called ring vaccination. Musings noted the preliminary report of the trial's results: the vaccine was 100% effective, though with small numbers.

The final report from the trial is now in. The short message is that the initial findings hold. In fact, the numbers are not much larger than in the preliminary report.

The original Musings post, which discussed the trial in some detail, still holds, too. I encourage you to read that for the general nature of the trial and its results. More, on the update, is below, but there is no big news in the update.

Perhaps the key limitation is that we do not know how well the current vaccine will do against other strains of Ebola, including those that develop during an outbreak. With that inevitable reservation, it appears that we now have an effective Ebola vaccine and a strategy for using it during an outbreak. Perhaps it will help to stop a new outbreak before it becomes serious.

Whether an Ebola vaccine should be used as a general preventive is another question. Ebola is still an uncommon disease. On the other hand, most Ebola has occurred within a fairly small area, and we now know that it can affect thousands of people in an outbreak. Public health authorities will need to consider whether general vaccination against Ebola is warranted in the affected areas.

News stories:
* Bye Bye Ebola? (J Bloom, American Council on Science and Health, December 23, 2016.) The question mark in the title is to emphasize an important point: the vaccine was tested in a particular situation, with a particular virus. We do not know how the virus will evolve, or what it will take to keep the vaccine effective.
* Ebola Vaccines Update. (Center for Vaccine Ethics & Policy, January 2, 2017.) A compilation of various things about the vaccine, including the announcement from WHO.

Both of the following are freely available.
* "Comment" accompanying the article: First Ebola virus vaccine to protect human beings? (T W Geisbert, Lancet 389:479, February 4, 2017.)
* The article: Efficacy and effectiveness of an rVSV-vectored vaccine in preventing Ebola virus disease: final results from the Guinea ring vaccination, open-label, cluster-randomised trial (Ebola Ça Suffit!). (A M Henao-Restrepo et al, Lancet 389:505, February 4, 2017.)

The background post for this topic is listed at the top of the post.

Most recent Ebola post: Ebola survivors: are they a risk to others? (June 5, 2016).

Next: The new Ebola outbreak (June 6, 2017).

and: Ebola vaccines: two brief updates (December 15, 2017).

Also see... An antibody treatment for Marburg virus disease? (May 14, 2017).

There is more about Ebola on my page Biotechnology in the News (BITN) -- Other topics in the section Ebola and Marburg (and Lassa). That section links to related Musings posts, and to good sources of information and news.

A post about science news, from one of the news sources listed above... The quality of science news (April 26, 2017).

Hydride-in-a-cage: the H₂₅^- ion

January 22, 2017

Although the structure shown above is theoretical, there is evidence for the H₂₅^- ion.

The scientists made hydride ions from H₂ dissolved in liquid helium, very near zero Kelvins. They measured the masses of what formed, using mass spectrometry. Here is what they found...

That is, the measurement of the mass distribution suggests that H₂₅^- ion is a particularly stable species. That leads them to propose the structure shown above, which provides a highly symmetrical cage for the hydride ion.

There's more in the figure above. There seem to be smaller points of stability at n = 65 and 89. There aren't exactly peaks at those n values, but there is a noticeable drop off to the next value. The authors suggest that those n values define second and third levels of shells of H₂ around the central ion.

There are no obvious points of stability beyond that, but there are certainly lots of bigger ions. The authors suggest this means there are no longer rigid structures, but that the ion is more fluid-like.

The graph provides evidence for ions as big as H₁₂₉^-. That would represent a species with a hydride ion plus 64 H₂ molecules.

How stable are these cluster ions? As the authors note, all they know is that they are stable enough to measure in the mass spec. That takes a few microseconds.

The point of all this? It's basic chemistry. H⁺ ions have been studied a lot, but H^- ions are harder to deal with. There has been no agreement on the structure of even fairly simply H^- ions. The current work is the first to provide evidence for much larger ions. There is also speculation that such structures might occur in outer space.

News story: New form of hydrogen created. (E Conover, Science News, January 9, 2017.)

* News story from the publisher's news magazine. Freely available: Synopsis: Hydrogen Clusters Go Negative. (M Schirber, Physics, December 27, 2016.)
* The article: Anionic Hydrogen Cluster Ions as a New Form of Condensed Hydrogen. (M Renzler et al, Physical Review Letters 117:273001, December 30, 2016.)

More about (molecular) cages:
* Liquids with holes (January 30, 2016).
* The smallest water bottle (January 5, 2011).
* Vodka chemistry (July 23, 2010).
* Ice on fire (August 28, 2009).

Among many posts involving mass spectrometry:
* Is there food on Enceladus? (May 21, 2017).
* Blood vessels from dinosaurs? (April 22, 2016). The mass spec results are not in the post, but the idea of doing mass spec on dinosaurs is intriguing.
* Close-up view of an unwashed human (July 29, 2015).
* Iridium(IX): the highest oxidation state (December 14, 2014).

Malaria history

January 18, 2017

A recent article explores a bit of the history of malaria. It is perhaps most interesting for how it was done.

By comparing genome sequences of related organisms, we can reconstruct their history. Sometimes we are even able to get genome sequences for extinct organisms. The development of genome sequences for Neandertal and Denisovan humans over recent years is an example; it has made a major contribution to our understanding of the history of our species.

We now have some genome sequences for extinct lines of the malaria parasite. The source of the samples is shown in the following figure...

Those slides date from 1942-4, and are from the collection of a leading Spanish physician, Dr. Ildefonso Canicio. The samples are of special interest, because there has not been any malaria native to Europe in several decades. Attempts, for example, to explain how malaria might have spread to the Americas from Europe have been hampered by lack of knowledge of what the European malaria actually was.

The scientists were able to recover parasite DNA from the slides. They found both of the common malaria species, Plasmodium vivax and P falciparum, and were able to relate them to other known strains.

We'll leave most of the detail; there are some complicated genealogy charts in the article. But we note that one of the P vivax strains the scientists found here is almost identical to one now found in the Americas. That supports the model that malaria was taken from Europe to the Americas, presumably sometime post-Columbus. (To be cautious... That is not a proof, only the simplest interpretation of the data at hand. Further, it is possible, even likely, that there many have been multiple introductions of malaria into the Americas.)

News stories:
* Missing Link in Malaria Evolution Discovered in Historical Specimens -- A family's collection of antique microscope slides became a trove of genetic information about the eradicated European malaria pathogen. (B A Henry, The Scientist, December 1, 2016.)
* Light shed on what European malaria was like, 50 years after its eradication. (Universitat Pompeu Fabra, September 27, 2016. Now archived.) From the lead institution.

The article, which is freely available: Mitochondrial DNA from the eradicated European Plasmodium vivax and P. falciparum from 70-year-old slides from the Ebro Delta in Spain. (P Gelabert et al, PNAS 113:11495, October 11, 2016.) The first paragraph of the Materials and Methods section tells the history of the samples. The news stories tell more of that history. At the end of the Discussion, the authors issue a plea for more slides of European malaria. We also note that the Introduction is a nice overview of what is known of the history of malaria.

A recent post about malaria: Can chickens prevent malaria? (August 12, 2016).

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

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

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

How many atoms can one carbon atom bond to?

January 14, 2017

You've answered the title question, and wonder why we would bring it up? Look at the following structure, which was reported in a recent article.

The C at the top of the pyramid is bonded to six other C: five in the base of the pyramid, and the methyl C at the top.

So what is this thing? Is this a real chemical?

The second part first... It's real. The structure shown above comes from an X-ray analysis of a chemical the authors made.

What is it? That's where this gets complicated. A short answer is that it is the hexamethylbenzene di-cation. We'll walk through that in a moment, but first note that this is not a neutral molecule. It is an ion. It's an unusual ion, a double cation (2+ charge) of a hydrocarbon, a type of molecule that's usually not very good at making ions. And it is shown here free of its counter-ion, the anion it is paired with. That's fine; it simplifies the picture, but remember that this unusual structure exists within the context of a more complex structure.

Hexamethylbenzene. A common benzene ring, with a methyl group at each position on the ring. Nothing unusual about that. Now imagine removing two electrons from that starting chemical. That gives the di-cation we noted above. It's not easy to do, but it is easy enough to imagine. The resulting di-cation is stable -- stable enough to determine its structure, which is shown above.

You can see that one of the C of the original benzene ring has "popped out", to form the apex of a pentagonal pyramid. Up there, it is now bonded to six other C.

Let's count electrons. Focus on how the C atoms in the ring bond to each other; we will assume that the other bonding is normal. In an ordinary benzene ring, there are 6 single bonds and 3 double bonds between the C atoms. That's 9 bonds, or 18 electrons. The di-cation has lost 2 of those; it has only 16 electrons bonding the ring carbons. There are 5 single bonds in the new ring, using 10 electrons. That leaves 6 electrons -- for those 5 bonds between the apex C and the base.

Those 5 bonds (apex to base) are not ordinary C-C bonds. In fact, each is, in a sense, only 3/5 of a bond -- where a "bond" has 2 electrons. The apex C actually has the equivalent of 4 bonds... It has 5 of those 3/5 bonds to the base; that totals 3 bonds. Add in the regular bond to the methyl group above, and you get 4 bonds total. Each of the C on the base has three ordinary bonds, plus a 3/5 bond to the apex. Each of the ring C, then, has a charge of +2/5. Five C each with +2/5 charge... that's 2+ total charge. That is, the 2+ charge of this di-cation is spread around the base of the ring.

Would one have predicted this structure? That's an interesting question. The scientists ran some theoretical calculations on the structure of the cation under the relevant conditions. They used two different, well-respected models for calculating the structure. And they got different answers from the two models. One predicts the unusual structure they found, but one does not. If nothing else, that's a reminder of the limitations of computational chemistry. I'm sure people will be looking at this in detail, to see what they can learn about how the models are predicting the structure.

Scientists have caught C doing unusual things before. However, this does appear to be the first reported case of it forming bonds to six other C atoms. We also note that the "3/5" bonds may remind some of the bonds found in compounds of boron with hydrogen.

Making the di-cation was a piece of rather exotic chemistry in itself. The scientists didn't actually start with hexamethylbenzene, but rather an isomer of it. If you're intrigued by Dewar benzene and magic acid, look at how the di-cation was made. But the result doesn't depend on that.

News stories:
* Carbon can exceed four-bond limit -- Chemists confirm links to six other atoms in unusual molecule. (L Hamers, Science News, January 4, 2017.)
* Carbon seen bonding with six other atoms for the first time. (R Boyle, New Scientist, January 11, 2017.)

The article: Crystal Structure Determination of the Pentagonal-Pyramidal Hexamethylbenzene Dication C₆(CH₃)₆²⁺. (M Malischewski & K Seppelt, Angewandte Chemie International Edition 56:368, January 2, 2017.)

The post immediately above raises a similar issue for nitrogen. Caution, it is entirely a theoretical article -- for now. How many atoms can one nitrogen atom bond to? (January 17, 2017).

Other posts about unusual chemical bonding:
* A chemical bond to an atom that isn't there (October 31, 2018).
* Can calcium act like a transition metal? (October 7, 2018).
* An unusual hydrogen bond, involving boron (March 26, 2016). Also involves benzene.

There are many posts about carbon. Among them...
* The longest C-C bond (April 17, 2018).
* The mass of an electron (March 23, 2014). The C⁵⁺ ion -- a C atom that has lost 5 electrons.
* Image of a carbon atom that isn't there (August 17, 2008). A C atom that has lost everything.

This post is listed on my page Introduction to Organic and Biochemistry -- Internet resources in the section on Aromatic compounds.

Age-related development of far-sightedness in bonobos

January 10, 2017

As people age, they lose the ability to focus at short distances. For example, they will tend to hold a newspaper further from their eyes as they age. It's rather reproducible; one can estimate a person's age from how they hold the newspaper (assuming that their vision is otherwise normal).

Bonobos don't read newspapers, but they do close-up work: grooming others. Scientists have now measured the distance a bonobo maintains from its grooming target -- as a function of age.

Here are some results...

It's rather clear: the results for bonobos are essentially the same as would be expected for humans.

The simple interpretation is that both human and bonobo inherited this vision-aging characteristic from a common ancestor.

For one of the bonobos, the authors happen to have a video from six years earlier. Analysis of that video, as best they can, suggests that this individual bonobo has developed farsightedness consistent with the curve shown above.

The authors note anecdotal evidence for similar farsightedness in older chimpanzees. They also note evidence for farsightedness in older rhesus monkeys, though these animals have a quite different scale for lifespan.

News stories:
* Just like humans, old bonobos suffer from long-sightedness. (M Andrei, ZME Science, November 9, 2016.)
* Aging bonobos in the wild could use reading glasses too. (Phys.org, November 7, 2016.)

Video. (0.4 minutes; no meaningful sound.) Two examples of bonobo grooming events. The bonobo at the far right is 45 years old. The one in the middle is 27. You can see the difference in the distances they maintain for grooming. A still from this video is in the article as Figure 1A; I found it hard to sort out what was in that figure. The video is clear.

The article: Long-sightedness in old wild bonobos during grooming. (H Ryu et al, Current Biology 26:R1131, November 7, 2016.)

Another post comparing bonobos and humans: The metabolic rate of humans vs the great apes: some data (August 1, 2016).

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

More apes...
* Do apes say "hello"? (September 14, 2021). Bonobos and chimpanzees.
* Is Bcbva anthrax a threat to wild populations of chimpanzees? (September 8, 2017).
* Do apes have a "theory of mind"? (February 19, 2017).

Improving soybean oil by gene editing

January 8, 2017

Fatty acids differ in their chain length and the number of double bonds. (They may also differ in the position of the double bonds, but that is not an issue here.) These features affect various properties -- physical, chemical, and biological.

Plant "oils" are typically high in fats with double bonds -- called unsaturated fatty acids. In fact, some have a high content of fatty acids with more than one double bond -- the polyunsaturated fatty acids.

The polyunsaturated fatty acids are more easily oxidized, becoming rancid. Related to that, they are not suitable for baking. In the old days, scientists developed ways to reduce the content of polyunsaturated fatty acids, by partial hydrogenation: converting some of the double bonds to single bonds by reaction with hydrogen. It worked, but, as a side effect, also produced a novel type of fatty acid, called trans fatty acids (or trans fats). These have a double bond, but it is oriented the wrong way. It turns out that trans fatty acids are bad for people, and they have been substantially eliminated from foods,

That leaves a question: How can we use highly polyunsaturated plant oils, such as soybean oil, for applications where that feature is undesirable? Two recent articles address this, with very different approaches. We'll present one of them in this post, and one in the following post.

The first approach is a variation of an old standby: genetics. Develop a soybean plant that makes a lower level of the polyunsaturated fats. What makes the new work novel is that the scientists do it with the relatively new tool of gene editing. They use TALENs, not the newer CRISPR, but the basic idea is the same. Gene editing allows targeted knock-out of a specific gene. In this work, the scientists knock out three genes, sequentially, to achieve the desired strain.

The following figure shows the relevant fatty acids, and gives an idea of the results...

That's the idea. That shows how gene editing can reduce the content of polyunsaturated fatty acids in a common plant oil.

Interestingly, all that was done prior to the current work. The same team of scientists now goes further... Using an additional round of gene editing, they remove the enzyme FAD3, shown as the enzyme between linoleic and linolenic acids (18:2 and 18:3). This reduces the level of polyunsaturated fatty acids even further, to about half the level shown above for the fad2-1 strain. (I chose to use the figure above because it is so clear, and it fully illustrates the idea, though not the final result.)

The work shows that it is practical to edit multiple genes to develop the intended characteristics. In this case, the early work edited two genes, and the current work edits a third gene.

We'll discuss another approach to reducing the content of polyunsaturated fatty acids in the next post, and then comment on the two articles together.

News story: Gene editing used to produce soybean oil with less trans fats. (Genetic Literacy Project, October 20, 2016.) This seems to consist entirely of selected excerpts from the article. That's ok, but it is misleadingly labeled, claiming more than that. The Genetic Literacy Project should do better than this. (To be clear, the content is ok, but the integrity is not.)

The article, which is freely available: Direct stacking of sequence-specific nuclease-induced mutations to produce high oleic and low linolenic soybean oil. (Z L Demorest et al, BMC Plant Biology 16:225, October 13, 2016.)

Related post, immediately above: Improving soybean oil by using high voltage plasma (January 9, 2017).

A previous post about work using TALENs: Polled cattle -- by gene editing (July 8, 2016).

A previous post about editing multiple genes. This used CRISPR, which is commonly regarded as easier to use. But it also targeted closely related genes, so a single guide could target many genes. In fact, editing the entire set of genes required only two guides. How to do 62 things at once -- and take a step towards making a pig that is better suited as an organ donor for humans (January 17, 2016).

A post that includes a complete list of posts on gene editing (including using TALENs): CRISPR: an overview (February 15, 2015).

More about linoleic acid: Cats, fats, and Toxoplasma. And mice. (October 21, 2019).

For more about lipids, see the section of my page Organic/Biochemistry Internet resources on Lipids. It includes a list of related Musings posts. It also includes some links to items about trans fats.

Previous post about soybeans: Effect of food crops on the environment (November 20, 2015).

More...
* How soybeans set up shop for fixing nitrogen -- and how we might do better (December 2, 2019).
* A sticky pesticide (June 21, 2019).

More gene knockouts: Cataloging gene knockouts in humans (July 10, 2017).

Doggy bags and the food waste problem

January 4, 2017

It is generally recognized that there is a food shortage, which will only get worse as the population continues to increase. Interestingly, a lot of food gets wasted -- at various stages, from losses on the farm to the home -- or restaurant. One solution to the food shortage is to waste less food.

A new article addresses one part of the food waste problem, with some intriguing observations.

We like it when a restaurant serves generous portions. But those generous portions may encourage both over-eating and waste. What do you do with the food left after a generous meal? One option is to take it home; after all, you have paid for it. Most restaurants will provide a container; it's often called a doggy bag. (It sounds better to say that we'll take it home for the dog. But it doesn't matter who eats it; we all share substantially the same food supply.)

The article explores attitudes toward the use of doggy bags in two European countries. 20 consumers in each country were asked a series of questions. The article is quite informal. Everything is presented as narrative, with no tables summarizing the results. But the major findings were interesting.

So what did the scientists find? On the one hand, most people were opposed to wasting food, and they liked the concept of the doggy bag. On the other hand, those same people thought it was not socially acceptable to ask for their left-over food to be packaged for them -- especially in higher class restaurants. Interestingly, many thought that doggy bags were not appropriate for the food of their country, though it might be for others.

The authors summarize the findings as indicating that people's personal values favor the use of doggy bags, but that they perceive it as against social norms. A paradox, as the authors note. And that is what makes the article interesting. It's interesting sociology.

Neither country involved in the study has a tradition of using doggy bags. One is starting a program to reduce food waste. The results here suggest that there will be barriers to reducing the wastage of food that has been served.

Perhaps it should be restaurant policy to offer customers doggy bags. (The authors suggest this.) Now, should that be mandated by law?

The study here is small. It is reasonable to think of it as raising some issues, rather than providing final answers.

Editorial, which is freely available: Researchers serve up suggestions to reduce food waste. A change in cultural and social factors -- such as overcoming a distaste for doggy bags -- will be required to shift people's behaviour. (Nature, 540:8, December 1, 2016.) It was posted at the Nature News site the previous day.

The article: Understanding the antecedents of consumers' attitudes towards doggy bags in restaurants: Concern about food waste, culture, norms and emotions. (L Sirieix et al, Journal of Retailing and Consumer Services 34:153, January 2017.)

More about the food supply:
* Implementing improved agriculture (January 6, 2017). Immediately above.
* What is the proper use of crop land? (August 23, 2013).

More about sharing with the dog:
* Sharing microbes within the family: kids and dogs (May 14, 2013).
* It's a dog-eat-starch world (April 23, 2013).

More about bags: How to fold a bag (May 13, 2011).