Culture

Hubble inspects a contorted spiral galaxy

image: This spectacular image from the NASA/ESA Hubble Space Telescope shows the trailing arms of NGC 2276, a spiral galaxy 120 million light-years away in the constellation of Cepheus. At first glance, the delicate tracery of bright spiral arms and dark dust lanes resembles countless other spiral galaxies. A closer look reveals a strangely lopsided galaxy shaped by gravitational interaction and intense star formation.

Image: 
ESA/Hubble & NASA, P. Sell Acknowledgement: L. Shatz

This striking image showcases the unusually contorted appearance of NGC 2276, an appearance caused by two different astrophysical interactions -- one with the superheated gas pervading galaxy clusters, and one with a nearby galactic neighbour.

The interaction of NGC 2276 with the intracluster medium -- the superheated gas lying between the galaxies in galaxy clusters -- has ignited a burst of star formation along one edge of the galaxy. This wave of star formation is visible as the bright, blue-tinged glow of newly formed massive stars towards the left side of this image, and gives the galaxy a strangely lopsided appearance. NGC 2276's recent burst of star formation is also related to the appearance of more exotic inhabitants -- black holes and neutron stars in binary systems.

On the other side of the galaxy from this burst of new stars, the gravitational attraction of a smaller companion is pulling the outer edges of NGC 2276 out of shape. This interaction with the small lens-shaped galaxy NGC 2300 has distorted the outermost spiral arms of NGC 2276, giving the false impression that the larger galaxy is orientated face-on to Earth [1]. NGC 2276 and its disruptive companion NGC 2300 can both be seen in the accompanying image, which shows a wider view of the interacting galaxies.

NGC 2276 is by no means the only galaxy with a strange appearance. The Atlas of Peculiar Galaxies -- a catalogue of unusual galaxies published in 1966 -- contains a menagerie of weird and wonderful galaxies, including spectacular galaxy mergers, ring-shaped galaxies, and other galactic oddities. As befits an unusually contorted galaxy, NGC 2276 has the distinction of being listed in the Atlas of Peculiar Galaxies twice -- once for its lopsided spiral arms and once for its interaction with its smaller neighbour NGC 2300.

Credit: 
ESA/Hubble Information Centre

Researchers develop technique to functionally identify and sequence soil bacteria one cell at a time

image: A technique to sort and sequence the genome of bacteria in soil one bacterial cell at a time

Image: 
LIU Yang

Researchers from the Single-Cell Center at the Qingdao Institute of Bioenergy and Bioprocess Technology (QIBEBT) of the Chinese Academy of Sciences have developed a technique to sort and sequence the genome of bacteria in soil one bacterial cell at a time, while also identifying what its function is in the soil environment.

Their study was published in the journal mSystems on May 27.

Soil is home to a vast and complex microbiome, which features arguably the highest genomic diversity and widest heterogeneity of metabolic activities of cells on Earth. In turn, these metabolic activities can in principle provide the foundation for industrial production of numerous compounds of value.

The ability to pinpoint "who is doing what" in the soil microbiome has until now been extremely difficult at the resolution of a single cell, as normally a great many cells, typically millions of them, have had to be analyzed at the same time.

In 2020, researchers from the QIBEBT Single-Cell Center developed a bacteria-profiling technique called Raman-Activated Gravity-driven single-cell Encapsulation and Sequencing, or RAGE sequencing. This sequencing technique uses laser "tweezers" and takes advantage of the properties of gravity to permit analysis of bacteria cells one by one. The form and structure of a bacterium are then investigated using 'Raman spectroscopy', a method of analysis that uses how light interacts with the chemical bonds in a molecule to enable identification.

They have now developed their RAGE sequencing technique into a new scientific instrument they are calling a Raman-activated Cell Sorter-Sequencer or RACS-Seq. It is the first instrument in the world that can pinpoint "who is doing what" at precisely one-cell resolution in complex ecosystem. And they applied it to the bacteria in soil.

The Raman spectra of a single cell offers an intrinsic biochemical fingerprint, and this in turn can be used as a proxy of its metabolic activity. When this single-cell Raman spectra (SCRS) is coupled with probing of the isotopes involved in this activity, the technique can reveal the amount of chemical from the cell's environment that it is taking up.

Isotopes are often used as a way to track or trace chemical processes. Deuterium, for example, is an isotope of hydrogen with one neutron (regular hydrogen has zero neutrons), and is found in heavy water (water molecules where the regular hydrogen is replaced by deuterium: D2O instead of H2O).

By feeding the bacteria with heavy water, the general metabolic activity of the cells can be tracked via Raman spectra. The technique can also detect not only uptake of D2O but also different isotopes of carbon or nitrogen. This can even reveal the particular cellular profile of synthesis of biological molecules.

This metabolic tracking can then be linked via the RAGE technique to individual cells whose genome can be sequenced.

"This should allow researchers to 'mine' soil to find bacteria of interest that are in the business of producing particular carotenoids, lipids, polysaccharides, protein and even antibiotics," said JING Xiaoyan, a microbiome scientist with the QIBEBT Single-Cell Center and the article's lead author.

The researchers now want to further improve the throughput of their technique, at a few cells per minute currently, to speed up and fully automate the process.

"Our goal ultimately is to keep optimizing the RACS-Seq instrument, so that it becomes a universal and highly versatile tool for precisely probing target cells or metabolic activities of interest," added XU Jian, the article's corresponding author and Director of the QIBEBT Single-Cell Center. "And not just from soil, but from any other complex natural ecosystem."

Credit: 
Chinese Academy of Sciences Headquarters

Quark-gluon plasma flows like water, according to new study

What does quark-gluon plasma - the hot soup of elementary particles formed a few microseconds after the Big Bang - have in common with tap water? Scientists say it's the way it flows.

A new study, published today in the journal SciPost Physics, has highlighted the surprising similarities between quark-gluon plasma, the first matter thought to have filled the early Universe, and water that comes from our tap.

The ratio between the viscosity of a fluid, the measure of how runny it is, and its density, decides how it flows. Whilst both the viscosity and density of quark-gluon plasma are about 16 orders of magnitude larger than in water, the researchers found that the ratio between the viscosity and density of the two types of fluids are the same. This suggests that one of the most exotic states of matter known to exist in our universe would flow out of your tap in much the same way as water.

The matter that makes up our Universe is made of atoms, which consist of nuclei with orbiting electrons. Nuclei consist of protons and neutrons known collectively as nucleons and these in turn consist of quarks interacting via gluons. At very high temperatures - about one million times hotter than the centre of the Sun- quarks and gluons break free from their parent nucleons and instead form a dense, hot soup known as quark-gluon plasma.

It is thought that shortly after the Big Bang the early universe was filled with incredibly hot quark gluon plasma. This then cooled microseconds later to form the building blocks of all the matter found within our universe. Since the early 2000s scientists have been able to recreate quark-gluon plasma experimentally using large particle colliders, which has provided new insights into this exotic state of matter.

The ordinary matter we encounter on a daily basis are thought to have very different properties to the quark-gluon plasma found in the early beginnings of the Universe. For example, fluids like water are governed by the behaviour of atoms and molecules that are much larger than the particles found in quark-gluon plasma, and are held together by weaker forces.

However, the recent study shows that despite these differences the ratio of viscosity and density, known as the kinematic viscosity, is close in both quark-gluon plasma and ordinary liquids. This ratio is important because the fluid flow does not depend on viscosity alone but is governed by the Navier-Stokes equation which contains density and viscosity. Therefore, if this ratio is the same for two different fluids these two fluids will flow in the same way even if they have very different viscosities and densities.

Importantly, it's not just any liquid viscosity that coincides with the viscosity of quark-gluon plasma. Indeed, liquid viscosity can vary by many orders of magnitude depending on temperature. However, there is one very particular point where liquid viscosity has a nearly-universal lower limit. Previous research found that in that limit, fluid viscosity is governed by fundamental physical constants such as the Planck constant and the nucleon mass. It is these constants of nature that ultimately decide whether a proton is a stable particle, and govern processes like nuclear synthesis in stars and the creation of essential biochemical elements needed for life. The recent study found that it is this universal lower limit of viscosity of ordinary fluids like water which turns out to be close to the viscosity of quark-gluon plasma.

Professor Kostya Trachenko, Professor of Physics at Queen Mary University of London and author of the recent paper, said: "We do not fully understand the origin of this striking similarity yet but we think it could be related to the fundamental physical constants which set both the universal lower limit of viscosity for both ordinary liquids and quark-gluon plasma."

"This study provides a fairly rare and delightful example of where we can draw quantitative comparisons between hugely disparate systems," continues Professor Matteo Baggioli from the Universidad Autónoma de Madrid. "Liquids are described by hydrodynamics, which leaves us with many open problems that are currently at the forefront of physics research. Our result shows the power of physics to translate general principles into specific predictions about complex properties such as liquid flow in exotic types of matter like quark-gluon plasma."

Understanding quark-gluon plasma and its flow is currently at the forefront of high-energy physics. Strong forces between quarks and gluons are described by quantum chromodynamics, one of the most comprehensive physical theories that exist. However whilst quantum chromodynamics provides a theory of strong nuclear force, it is very hard to solve and understand quark-gluon plasma properties using this alone.

"It is conceivable that the current result can provide us with a better understanding of the quark-gluon plasma," added Professor Vadim Brazhkin from the Russian Academy of Sciences. "The reason is that viscosity in liquids at their minimum corresponds to a very particular regime of liquid dynamics which we understood only recently. The similarity with the QGP suggests that particles in this exotic system move in the same way as in tap water."

Credit: 
Queen Mary University of London

Physical activity levels and well-being sink worldwide during coronavirus restrictions

Twenty scientists from 14 countries warn of a hidden "pandemic within the pandemic" in two current publications. On the one hand, physical activity levels have gone down significantly, on the other hand, psychological well-being has suffered. "Governments and those responsible for health systems should take our findings seriously," emphasizes the author team, headed by Dr Jan Wilke from the Institute for Sport Sciences at Goethe University Frankfurt.

About 15,000 people in participating countries answered standardised questionaires as part of an international survey. In April/May 2020, they reported physical activity levels (13,500 participants) as well as their mental and physical well-being (15,000 participants) before and during the pandemic-related restrictions.

Older individuals especially affected

"The results show drastic reductions in physical activity and well-being," says Wilke. More than two thirds of those questioned were unable to maintain their usual level of activity. Moderate exercise decreased by an average of 41 percent according to self-reported data - this includes anything that increases heart rate and breathing, such as brisk walking, running, cycling or even strenuous gardening.

The proportion of vigorous exercise during which people sweat and clearly run out of breath fell by a similar amount (42 percent). The effects were somewhat higher among professional athletes and particularly active people, as well as comparatively young and old people. The decline in activity was particularly noticeable among people over 70 years of age, who were 56 to 67 percent less active than before. "We know that physical inactivity, especially in older people, can lead to changes that are difficult to reverse after only two weeks - for example, in body fat percentage or insulin sensitivity," warn the study authors.

Exercise helps prevents disease and reduces mortality

The WHO recommends at least 150 minutes of moderate or 75 minutes of intensive physical activity per week - 81 percent of the study participants achieved this before the pandemic, but only 63 percent during the lockdowns. Yet sufficient exercise can reduce mortality by up to 39 per cent, as a 2015 study showed. Data suggests that too little exercise plays a role in about one in ten premature deaths, because physical activity reduces the likelihood of, for example, high blood pressure, metabolic disorders such as type 2 diabetes, and cancer.

Exercise is known to activate the immune system because it promotes blood circulation and activates lymphocytes and messenger substances (cytokines) that are important for immune defence. Studies show that physically active people are less susceptible to influenza, rhino and herpes viruses and respiratory infections in general. So it may be that exercise also offers protection against severe COVID-19 by reducing risk factors such as obesity. Physical health and exercise also reduce the risk of mental health problems such as depression and anxiety disorders.

Mental well-being drastically reduced

In another part of the study, the team of authors asked about mental well-being during the pandemic restrictions. 73 percent of the study participants stated that their well-being had deteriorated. The perceived quality of life as measured by the WHO well-being Index, which measures mood, relaxation, activity, rest and interest, dropped on average from 68 percent before the pandemic to 52 percent during the first lockdown phase.

Above all, people felt less "active and full of energy" and led a life less "filled with interesting things". The proportion of very low scores indicating a possible risk of depression tripled from 15 to 45 percent. "These effects were stronger among women and younger people, " the study says. "More attention should be paid to the needs of women in particular, as they are significantly more vulnerable."

Nonetheless, 14 to 20 percent of the respondents also stated that their health had improved - the authors see more family time, greater work autonomy, fewer business trips or a changed perception of health as possible reasons. "But a large part of the population may still be suffering from barely visible health effects of the pandemic," the team of authors warns.

This could also translate into rising health costs: According to US data, the annual expenditure for inactive or insufficiently active people increases by 1200 and 600 euros respectively - this would add up to two to four million euros after one year just for the 3104 people from the survey who did not exercise enough during the lockdown.

The results of these first multinational studies are likely to be relevant for an estimated four billion people worldwide who were affected by the restrictions of the first coronavirus wave in the spring of 2020. However, the data was predominantly collected through electronic media, so populations without internet were not included. Also, no differentiation was made according to factors such as living environment, education and social status. In addition, the data is based on self-assessments, not measurements, which may distort retrospective perceptions in particular. "Nevertheless, our results show that the issues of physical activity and well-being belong on the policy agenda," Wilke emphasises.

"Governmental and health-related decison-makers need to develop strategies to mitigate the loss of physical activity," write the authors. They suggest better public education, creating exercise opportunities with a low likelihood of infection, or offering effective home exercise programmes. Among numerous other health facets, this would have a particularly positive effect on mental well-being.

Negative effects similar to those observed in these studies should be avoided at all costs in future pandemics. "Unfortunately, physical activity and exercise do not have a strong lobby and are usually neglected in public discourse," says Wilke. "Yet they can greatly help us to better cope with the pandemic."

Credit: 
Goethe University Frankfurt

Parasites as fountains of youth: Study finds infected ants live much longer

image: Two ants of the species Temnothorax nylanderi: The lighter colored ant is infected with larvae of the tapeworm Anomotaenia brevis (bottom right) and thus has a different cuticle color as well as, more importantly, a considerably longer lifespan.

Image: 
photo/©: Susanne Foitzik

Ant workers that are infected with a tapeworm live much longer than their uninfected nest-mates. Parasitic infections are usually harmful to their hosts, but there are some exceptions. According to the results of a multi-year scientific study, ants of the species Temnothorax nylanderi show exceptionally high survival rates when infected with a tapeworm. "The lifespan of the infected ants is significantly prolonged. According to our observations, such workers have a survival rate similar to that of queens," said Professor Susanne Foitzik of Johannes Gutenberg University Mainz (JGU), leader of the study. Queens of this species can live for up to 20 years, while female workers rarely reach the age of two. Among possible explanations for this extended lifespan are the change in the physiology of infected ants caused by the parasites and the fact that infected workers are better supplied with food.

Social care in the nest linked to longer life

In the case of ants, there is a stark divergence in lifespan between female castes. Many ant queens can survive for several decades. They spend almost all their lives safely in the nest where they are cared for by the workers, their daughters. In contrast, ant workers live for only a few weeks or months or, in rare cases, a few years. The infertile workers carry out all tasks in the nest, starting in brood care and progressing to riskier activities outside the colony as they grow older, such as foraging for food. The high life expectancy of queens is due to their low mortality rate, which is attributable to the high levels of social care they receive, their safe environment, and the activation of physiological repair mechanisms.

These factors may also contribute to the extremely high survival rates of Temnothorax-nylanderi workers infected with a tapeworm. This species of ant is common in Central Europe and forms small colonies on the forest floor, inside acorns or wooden branches. The insects are relatively small, with a body length of just two to three millimeters. They serve as an intermediate host for the tapeworm Anomotaenia brevis, whereby a single ant can be infected by up to 70 parasitic larvae. The parasites survive in the hemolymph, the body fluid of insects. Their complex life cycle is completed once they have been ingested by a woodpecker that feeds on the ants.

The research team led by Professor Susanne Foitzik looked at the long-term consequences of the parasitic infection by collecting ant colonies from forests around Mainz and observing them in the laboratory. "We tracked the survival rate of the workers and queens in both infected and uninfected ant colonies over three years, until more than 95 percent of the uninfected workers had died," explained Foitzik. At that point, over half of the infected workers were still alive - exhibiting a survival rate practically identical to that of the long-lived queens. "It is quite extraordinary that a parasite can trigger such a positive change in its host. This lifespan extension is very unusual," emphasized the JGU-based evolutionary biologist.

Infected workers differ in appearance, behavior, and physiology

The infected ants are easily distinguished from their brown nest-mates due to their lighter, yellow color, an effect that results from their cuticle being less pigmented. They are also less active and receive enhanced care from other workers in the nest. "The infected insects get more attention and are fed, cleaned, and looked after better. They even benefit from slightly more care than the nest's queen," explained Professor Susanne Foitzik. The tests also revealed that infected ants have metabolic rates and lipid levels similar to those of younger ants. It would seem that these ants remain in a permanent juvenile stage as a result of the infection. This is likely down to both the tapeworm larvae altering the expression of ant genes that affect aging and to the parasites' release of proteins containing antioxidants into the ants' hemolymph.

Even though the mystery of their long life has not yet been fully resolved, the behavior of the infected ants themselves does not seem to be the decisive factor. The research team, which included scientists from the Max Planck Institute for Biology of Ageing and Tel Aviv University, found no evidence that the insects actively beg for better care. However, chemical signals on the cuticle of infected ants were found to elicit more attention of their nest-mates. "The infected insects live a life of luxury, but the fact that they receive more social care cannot alone account for their prolonged lifespan," concluded Foitzik. The scientists will undertake further research in order to identify the factors, particularly on the molecular and epigenetic level, behind the infected workers death-defying attributes.

Credit: 
Johannes Gutenberg Universitaet Mainz

Discovery may point to Parkinson's disease therapies

image: Dr. Scott Ryan

Image: 
University of Guelph

A new discovery by University of Guelph researchers may ultimately help in devising new therapies and improving quality of life for people with Parkinson's disease.

By showing how entangled proteins in brain cells enable the neurodegenerative disease to spread, the researchers hope their findings will lead to drugs that halt its progression, said PhD candidate Morgan Stykel, first author of a paper published this month in Cell Reports.

Parkinson's disease is the world's fastest-growing neurodegenerative disease and Canada has some of the world's highest rates, according to Parkinson Canada. Its exact cause is unknown.

Current therapies only treat symptoms rather than halting the disease, said Dr. Scott Ryan, a professor in the Department of Molecular and Cellular Biology who led the study.

Parkinson's disease can be triggered by the misfolding of a protein called alpha-synuclein that accumulates in a part of the brain called the substantia nigra. The disease causes loss of nerve cells in the brain that produce dopamine, a chemical messenger that helps control motor function.

Misfolded alpha-synuclein aggregates and eventually spreads to other parts of the brain, impairing areas responsible for other functions such as mood and cognition.

The U of G team used stem cells to model neurons with and without Parkinson's disease and look at the effects of synuclein mutations.

They discovered that in Parkinson's neurons, misfolded synuclein binds to another protein called LC3B. Normally, LC3B targets misfolded proteins to be degraded. In Parkinson's disease, the study showed, LC3 gets trapped in the protein aggregates and is inactivated.

Without degradation, the cells eject the aggregates, which then spread to nearby neurons, propagating the disease throughout the brain.

"Normally misfolded proteins are degraded. We found a pathway by which synuclein is being secreted and released from neurons instead of being degraded," said Ryan. "We hope to turn the degradation pathway back on and stop the spread of disease."

The team showed that activating LC3B restores degradation, enabling cells to clear the misfolded proteins and prevent disease spread.

"Regular protein turnover is part of a healthy cell," said Stykel. "With Parkinson's disease, that system is not working properly."

Ryan said their finding could help in devising therapies.

"We may not be able to do anything about brain regions that are already diseased, but maybe we can stop it from progressing. We might be able to turn the degradation pathway back on and stop the spread of the disease."

He cautioned that other biochemical pathways are also likely involved in the spread of the disease through the brain. Still, the finding provides a target for potential drug development.

"Most current therapies centre around increasing the release of dopamine, but that works for a brief period and has a lot of side effects," said Ryan.

This research may help improve quality of life for Parkinson's patients. Many patients are diagnosed in their 40s or 50s, meaning that they live with the progressive disease for decades.

"Reduced quality of life can be a huge burden on patients, their families and the health-care system," he said.

Credit: 
University of Guelph

Genetic risk factors revealed by largest genome study of depression to date

image: Health science specialist Yasamin Azadzoi removes Million Veteran Program samples from a cryotank at the Boston MVP facility.

Image: 
Frank Curran

In the largest genetic analysis of depression to date, Veterans Affairs researchers identified many new gene variants that increase the risk for depression. The groundbreaking study helps researchers better understand the biological basis of depression and could lead to better drug treatments.

The study involved genetic data on more than 300,000 participants of VA's Million Veteran Program (MVP), along with more than a million subjects from other biobanks, including 23andMe. With such a large participant pool, the researchers were able to spot trends in genetic risk of depression not previously known.

Co-primary investigator Dr. Joel Gelernter, a researcher with the VA Connecticut Healthcare System and Yale University School of Medicine, explained the significance of the findings. "This study uncovered more of the genetic architecture of depression than was previously known," he said. "This implicates new regions of the genome for more targeted investigation and allows us to use this information to identify drugs that are currently approved for other indications and might be repurposed for treatment of depression."

The findings appear in the May 27, 2021, issue of the journal Nature Neuroscience.

Major depressive disorder is the most common psychiatric disorder. About 20% of the U.S. population experiences depression. Over 300 million people worldwide, 4% of the global population, have depression. For U.S. Veterans, that rate is 11%.

Previous research has shown that genetics play a large role in depression risk. To gain more insight into exactly what genes are involved, VA researchers and colleagues assembled a large dataset to perform a genome-wide association study (GWAS). A GWAS compares the genomic codes of many people to see what gene variants people with a particular condition tend to have in common. This project was the first genomic study of depression to include more than a million participants.

The researchers first analyzed the genomes of over 250,000 MVP participants of European ancestry. They then combined the findings with previous analyses from several other genetic repositories--the UK Biobank, FinnGen, and 23andMe. The other biobanks added more subjects, for a total of more than 1.2 million participants, to the primary study.

The analysis revealed 178 loci--specific parts of the genome--that are involved in a person's risk for depression. The finding includes 77 loci not detected in previous research.

The analysis also identified 223 single -nucleotide polymorphisms (SNPs) at these 178 locations that appear to affect a person's depression risk. An SNP is a specific variation of a single DNA building block.

The researchers also examined the genomes of nearly 60,000 Veterans of African ancestry in the MVP database. They found that 125 of the SNPs identified in the European ancestry group (61%) directly affected the African ancestry participants' risk for depression.

The team validated the results by checking them against 1.3 million additional samples from 23andMe, a private genetic testing company. This check confirmed the findings of the initial analysis. By combining such large databases, the researchers were able to draw broader and more accurate conclusions. "One of the underappreciated elements of GWAS is how reproducible the findings are," explained co-lead author Dr. Daniel Levey of the VA Connecticut Healthcare System and Yale University School of Medicine. "Now that we've achieved adequate power, we are finding great consistency in findings from different groups study. We hope this consistency provides a stable foundation for new discoveries that can improve treatments."

Further analysis revealed genetic overlap between depression and several other psychiatric conditions, which has been suggested by other studies. Depression shares genetic risk factors with anxiety disorders and PTSD, as well as with risky behavior and cannabis use disorder, the study found.

The findings could be used to identify new drug therapies for treating depression, according to the researchers. By identifying what genes are involved in depression, researchers may be able to repurpose existing drugs that are known to act on these genes. For example, riluzole, a drug used to treat amyotrophic lateral sclerosis (ALS), could be of interest for depression. It works on one of the genes identified by the MVP study.

Gelernter explained how MVP makes groundbreaking studies such as this possible. "This study, like many before it, highlights the value of the MVP sample in identifying genes for common genetic traits, especially those that are important in the veteran population. Another unique value of the MVP is that it allows us to study populations other than Europeans. We didn't find nearly as much in African-ancestry subjects as in European-ancestry, but we made a good start, and our results will be of great value in future meta-analysis efforts," he said. "This is a critical advantage of the MVP."

Together, the results greatly add to the understanding of how depression operates and who is most at risk. As the researchers explain, "This study sheds light into the genetic architecture of depression and provides new insight into the interrelatedness of complex psychiatric traits."

Credit: 
Veterans Affairs Research Communications

Microbial gene discovery could mean greater gut health

image: University of Illinois researchers have identified the last of three key genes in the microbial conversion of bile acids to beneficial - or harmful - forms, paving the way for future medical interventions of GI diseases

Image: 
Lauren D. Quinn, University of Illinois

URBANA, Ill. - As the owner of a human body, you're carrying trillions of microbes with you everywhere you go. These microscopic organisms aren't just hitching a ride; many of them perform essential chemical reactions that regulate everything from our digestion to our immune system to our moods.

One important set of reactions relates to fat absorption via bile acids. Our livers make these acids to help digest fats and fat-soluble vitamins as they travel through the small intestine. Near the end of the small intestine, microbes convert the acids into new forms, which can either be beneficial or harmful.

New research from the University of Illinois identifies the last in a set of microbial genes involved in these conversions.

"Locating these bacterial genes will allow mechanistic studies to determine the effect of bile acid conversion on host health. If we find this is a beneficial reaction, therapeutic strategies can be developed to encourage production of these bile acids in the gastrointestinal tract," says Jason Ridlon, associate professor in the Department of Animal Sciences at U of I and corresponding author of a new article in Gut Microbes.

Microbes produce enzymes that flip the orientation of three hydroxyl groups on bile acid molecules. Flipping them into different configurations rearranges the acid molecules into forms that can be harmful or beneficial. Ridlon and other scientists had already identified the genes for two of these enzymes, but one was still unknown.

To find the missing gene, Ridlon and his collaborators looked back in time. Previous research links the flipping of a specific hydroxyl group - one attached to a location on the acid molecule known as carbon-12 - with a microbe called Clostridium paraputrificum.

"We knew from literature published a few decades ago what species this function was reported in. We confirmed it in a strain of Clostridium paraputrificum that we have in our culture collection. This function is known to be catalyzed by certain enzymes known as reductases," Ridlon says.

"Using the genome sequence of Clostridium paraputrificum, we identified all the candidate reductases, engineered the genes into E. coli and determined which reductase was able to flip the polar group on bile acids," he adds.

The research team then searched for similar sequences in the human microbiome.

"We were able to identify the gene in numerous bacterial species that were previously unknown to have this bile acid metabolizing function. This is helpful for human microbiome researchers because the field is moving towards trying to link function with disease. Now we know the precise DNA sequences that encode an enzyme that flip carbon-12 of bile acids," Ridlon says.

The researchers haven't yet figured out if flipping the hydroxyl group at carbon-12 is a good or a bad thing. In the "good" category, the flip may play a role in detoxifying harmful bile acids such as deoxycholic acid (DCA) and lithocholic acid (LCA), chemicals known to damage DNA and cause cancers of the colon, liver, and esophagus. But Ridlon notes that "good vs. bad" framing oversimplifies reality.

"While we tend to think of DCA and LCA as 'bad,' the context is very important. Infection by Clostridium difficile (C. diff) seems to correlate with low levels of DCA and LCA, for instance, so these bile acids seem to be protective in preventing unwanted colonizers. Chronic high levels of DCA and LCA due to Western lifestyle are 'bad,' however, so it is a balancing act," he says. "A major goal of this research is trying to establish and maintain a 'Goldilocks zone' of bile acids - not too much or too little."

While there is still more to learn, Ridlon says identifying and characterizing these new microbial genes responsible for bile acid conversion is a major step forward for gut health.

Credit: 
University of Illinois College of Agricultural, Consumer and Environmental Sciences

Climate skeptics not easily persuaded by available evidence, now or later

EUGENE, ORE. -- May 27, 2021 -- Climate skeptics who aren't persuaded by the existing evidence from climate change are unlikely to change their minds for many years, according to a newly published quantitative study by a University of Oregon environmental economist

The central question posed by the study published in the journal Climate Change was "How much evidence would it take to convince skeptics that they are wrong?" The answer depended on the degree of skepticism. The study modeled two types of hypothetical skeptics -- those who were less extreme and believed the change in temperature was slight, as well as more extreme skeptics who believed the change was nonexistent -- and exposed them to climate data recorded between 1866 and 2005, as well as future projections until the end of the century.

"If a climate sceptic is unpersuaded by the evidence that is already available to them today, my model implies that they will likely remain a skeptic for many years into future," said author Grant McDermott, an assistant professor in the University of Oregon Department of Economics interested in the interaction between human and natural systems. "Why? Because it suggests their prior beliefs are so strong that even decades of continued warming may not be enough to convince them."

Moderate skeptics on the other hand were highly likely to change their beliefs once given more evidence of recorded temperature change.

A secondary goal of the paper was to bridge competing theories of climate skepticism as a social phenomenon by looking closely at "source credibility" from the skeptic's perspective. In other words, McDermottt said, there is a need to acknowledge that many skeptics regard mainstream sources of climate science as untrustworthy. They may not trust scientists over their own sources, which in turn could help to explain why they don't update their beliefs as scientists provide more information.

"One implication of that is that if you're trying to think about who to target with messaging to persuade people that climate change is a real and observable phenomenon, you should just accept that some people you're just not going to convince, even with more years' worth of evidence."

Because McDermott employed a quantitative model, he calls the project "a grandiose thought experiment" that uses "hypothetical, stylized skeptics." While some climate scientists have employed complicated supercomputer models, McDermott's Bayesian mathematical model uses simpler, standard econometric techniques - bread and butter to environmental economists like him. At its essence, the model provides a framework for combining prior beliefs with new information and seeing how beliefs are updated.

McDermott suggests that further research could be directed to disentangle the root causes of strongly-held skeptic beliefs. Specifically, are skeptics extremely sure of their priors, or simply mistrustful of scientific sources about climate change? Or, perhaps it is some combination of the two?

"The actions of others may often seem irrational to us, and vice versa, but it's important to recognize that a person's actions are, more than likely, perfectly congruent with their internal belief system," McDermott said. "Acknowledging that is an important first step towards crafting effective public policy."

Credit: 
University of Oregon

Not fear, but goal importance and others' behavior makes you favour COVID-19 measures

While earlier research has mostly looked into factors such as fear, perceived risk, age and political views to determine what makes individuals and societies more or less willing to drastically change their lifestyle and support government-imposed strict restrictions, in order to mitigate the spread of the COVID-19 pandemic, psychologists at the University of Zurich Charlotte Kukowski, Katharina Bernecker and Veronika Brandstätter took a different perspective.

Instead, they chose to find out the impact of people's perception of others' behaviour when it comes to the public good, as well as people's own self-control in sticking to behaviour guidelines. By using data from the United Kingdom and Switzerland, they concluded that, indeed, valuing fair contribution to the public good and the ability to practice self-control make people more likely to undertake health-protective behaviour, though the effects for self-control are not entirely consistent across the countries the authors sampled. Further, people who are more concerned with the cooperation of their fellow citizens and expect them to do their own part are more supportive of government regulations, possibly as a means of ensuring that others comply. However, the authors stress that future studies need to test this possible link. The study is published in the peer-reviewed, open-access scientific journal Social Psychological Bulletin.

Successfully overcoming conflicting desires and needs, such as taking public transportation, meeting with friends, and participating in large gatherings, for the benefit of society means that people must practice self-control. People will only be willing to control their desires and needs, however, if they value the higher goal, that is, managing the pandemic, even though their own health-protective behavior might not affect them directly. In this sense, self-control in the service of a societal goal is quite different from self-control for a personal goal, such as sticking to a healthy diet or meeting career goals.: While exercising and career achievements are largely private concerns, we all depend on each other's cooperation when it comes to a societal goal like managing COVID-19 pandemic. Therefore, in the context of the COVID-19 pandemic, higher goal importance and perception of others' behavior are key factors in practicing health-protective behavior.

"(...) we would like to emphasise that the effects of self-control and cooperation emerged above and beyond the effects of variables such as personal cost of engaging in health-protective behaviors, perceived risk and anxiety, and political orientation. If future work replicates these findings, one might cautiously conclude that, in a time of crisis, people - including decision-makers - are indeed able to "rise above themselves" and lay aside political differences and personal costs for collective goal attainment," say the researchers.

The authors note that in collective actions, it is essential that one sees others put in the same effort.

In conclusion, the scientists note that, in order to improve public efforts in combating the COVID-19 pandemic, as well as other collective goals, including climate change mitigation, it is essential that we identify the factors contributing to successful self-control and cooperation in the service of higher, society-level goals.

Credit: 
The Polish Association of Social Psychology

Fight against antibiotic-resistant bacteria has a glowing new weapon

image: A new chemical probe glows in the presence of a bacterial enzyme that contributes to antibiotic resistance.

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The University of Texas at Austin

AUSTIN, Texas -- In the perpetual arms races between bacteria and human-made antibiotics, there is a new tool to give human medicine the edge, in part by revealing bacterial weaknesses and potentially by leading to more targeted or new treatments for bacterial infections.

A research team led by scientists at The University of Texas at Austin has developed chemical probes to help identify an enzyme, produced by some types of E. coli and pneumococcal bacteria, known to break down several common types of antibiotics, making these bacteria dangerously resistant to treatment.

"In response to antibiotic treatment, bacteria have evolved various mechanisms to resist that treatment, and one of those is to make enzymes that basically chew up the antibiotics before they can do their job," said Emily Que, assistant professor of chemistry and one of the leading researchers on the team. "The type of tool we developed gives us critical information that could keep us one step ahead of deadly bacteria."

In a paper published online yesterday in the Journal of the American Chemical Society, the researchers zeroed in on the threat posed by the bacterial enzyme called New Delhi metallo-beta-lactamase (NDM). They set out to create a molecule that glows when it comes into contact with the NDM enzyme. When these chemical probes are added to a test tube, they bind to the enzyme and glow. Such a tool could be used to alert doctors to what kind of bacterial threat is affecting their patients and tell them which antibiotics to use.

NDM breaks down antibiotics in the penicillin, cephalosporin and carbapenem classes, which are some of the safest and most effective treatments for bacterial infections. Other classes of antibiotics exist, but they may carry more side effects, have more drug interactions and may be less available in some parts of the world.

In addition to indicating the presence of the NDM enzyme, the florescent chemical probe developed by Que and Walt Fast, a professor of chemical biology and medicinal chemistry, may help find a different way to combat these resistant bacteria. One treatment option that doctors use with resistant bacteria is to combine common antibiotics and an inhibitor. Although there is no known clinically effective inhibitor for NDM-producing bacteria, Que's probe could help find one.

Once the probe has bound to the enzyme and begun to glow, if an effective inhibitor is introduced, it will knock the probe loose and the glow would stop. This allows scientists to test a high volume of potential drugs very quickly--research Que and Fast hope to continue in the future.

"This allows us to work towards developing therapies and eventually understanding evolutionary characteristics of such proteins," said Radhika Mehta, a recent UT Austin doctoral graduate and lead author on the paper. Mehta is currently a postdoctoral fellow in the Merchant Lab at the University of California, Berkeley.

The study also examined a process called nutritional immunity, which comes from the human body's production of proteins in response to an infection. The proteins snatch up all the available metals in the body, such as the zinc required to make NDM, rendering the bacteria more susceptible to attack.

"The evolution of this bacteria since its discovery in 2008 indicates that not only is it developing antibiotic resistance, it's attempting to combat this natural human immune process. That's particularly scary," Que said.

Que's probe can also be used to study nutritional immunity and NDM because it will glow only in the presence of the zinc needed to form the enzyme.

Credit: 
University of Texas at Austin

Exploring optimization of duplex velocity criteria for diagnosis of ICA stenosis

Study Exploring Optimization of Duplex Velocity Criteria for Diagnosis of Internal Carotid Artery (ICA) Stenosis Published Online

Online first in Vascular Medicine, researchers from the Intersocietal Accreditation Commission (IAC) Vascular Testing division report findings of their multi-centered study of duplex ultrasound for diagnosis of internal carotid artery (ICA) stenosis. 1

The study was developed in response to wide variability in the diagnostic criteria used to classify severity of ICA stenosis across vascular laboratories nationwide and following a survey of members of IAC-accredited facilities supporting efforts toward standardization.2 The primary objective of the study was to evaluate widely used SRU Consensus Criteria (SRUCC) and, if needed, to propose further optimization to these criteria.3

Researchers found that carotid duplex interpretation using SRUCC produced significant overestimation of stenosis for both moderate (50-69%) and severe (> 70%) ICA lesions as determined by catheter angiography. The authors conclude that laboratories currently using SRUCC should consider modification of existing criteria to incorporate more stringent and accurate parameters for ICA stenosis greater than 50% by increasing the peak systolic velocity (PSV) threshold to > 180 cm/sec or requiring the ICA/CCA PSV ratio > 2.0 in addition to PSV of > 125 cm/sec.

"This study reflects more than six years of work of a team of IAC staff and multi-specialty volunteers with case study materials collected from 11 centers nationwide. While the SRUCC are broadly used, they had never been formally compared to the gold-standard of catheter angiography. We have shown that use of SRUCC overestimated degree of ICA stenosis and identify potential opportunities for modifications that can ultimately enable greater accuracy and consistency in ICA interpretation across vascular laboratories," said lead investigator, Heather L. Gornik, MD, IAC Vascular Testing Immediate Past-President.

"Through its use of real world data from IAC-accredited vascular laboratories, this paper highlights the opportunity to improve the quality of care for patients with carotid disease," said Tatjana Rundek, MD, PhD, IAC Vascular Testing President. "By modifying existing criteria to incorporate more accurate parameters and implementing these criteria broadly, the accuracy of diagnostic ultrasound testing can be improved across our vascular community."

As a next step, IAC Vascular Testing will disseminate a white paper document summarizing the study results and providing guidance to vascular laboratories for implementation of criteria and further steps toward standardization across the vascular testing community. The complete study report can be accessed through open access of Vascular Medicine at https://journals.sagepub.com/doi/full/10.1177/1358863X211011253. The authors' affiliations and disclosures of conflicts of interest and a listing of participating study centers are available in the article.

Credit: 
Intersocietal Accreditation Commission

Aging: Clinical trial on potential reversal of epigenetic age using a diet and lifestyle

image: Intervention group age change. Participants scored an average of 1.96 years younger than baseline (p=0.066). Of 18 participants included in the final analysis, 8 scored age reduction, 9 were unchanged, and 1 increased in methylation age.

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Correspondence to: Kara N. Fitzgerald email: kf@drkarafitzgerald.com

Aging published "Potential reversal of epigenetic age using a diet and lifestyle intervention: a pilot randomized clinical trial" which reported on a randomized controlled clinical trial conducted among 43 healthy adult males between the ages of 50-72. The 8-week treatment program included diet, sleep, exercise and relaxation guidance, and supplemental probiotics and phytonutrients.

Genome-wide DNA methylation analysis was conducted on saliva samples using the Illumina Methylation Epic Array and DNAmAge was calculated using the online Horvath DNAmAge clock (also published in Aging).

The diet and lifestyle treatment was associated with a 3.23 years decrease in DNAmAge compared with controls.

DNAmAge of those in the treatment group decreased by an average 1.96 years by the end of the program compared to the same individuals at the beginning with a strong trend towards significance.

This randomized controlled study, published in Aging, suggests that specific diet and lifestyle interventions may reverse Horvath DNAmAge epigenetic aging in healthy adult males.

This randomized controlled study, published in Aging, suggests that specific diet and lifestyle interventions may reverse Horvath DNAmAge epigenetic aging in healthy adult males.

The study’s lead author, Kara Fitzgerald ND IFMCP, from The Institute for Functional Medicine said, "Advanced age is the largest risk factor for impaired mental and physical function and many non-communicable diseases including cancer, neurodegeneration, type 2 diabetes, and cardiovascular disease."

Methylation clocks are based on systematic methylation changes with age.

DNAmAge clock specifically demonstrates about 60% of CpG sites losing methylation with age and 40% gaining methylation.

Almost a quarter of the DNAmAge CpG sites are located in glucocorticoid response elements, pointing to a likely relationship between stress and accelerated aging. Cumulative lifetime stress has been shown to be associated with accelerated aging of the methylome.

Other findings include that PTSD contributes to accelerated methylation age; and that greater infant distress is associated with an underdeveloped, younger epigenetic age.

This is to say the authors have tentatively accepted the hypothesis that the methylation pattern from which the DNAmAge clock is computed is a driver of aging, thus they expect that attempting to directly influence the DNA methylome using diet and lifestyle to set back DNAmAge will lead to a healthier, more “youthful” metabolism.

The Fitzgerald Research Team concluded in their Aging Research Output, "it may be that emerging ‘omics’ approaches continue to evolve our understanding of biological age prediction and reversal beyond DNA methylation alone. Integration of our future understanding of multi-omics data should therefore be considered in the future trials of candidate age-delaying interventions."

Credit: 
Impact Journals LLC

Books on health, economic inequalities in Latin America, Caribbean shed light on content, impact of health policies

More than 500,000 people have died from COVID-19 in Latin America and the Caribbean, demonstrating the health and economic inequalities throughout the region. A new article analyzes seven books* that discuss these inequalities, including questions of who gets health care and what interdependent roles societies, social movements, and governments play. To end inequality in the region, the author calls for a universal approach to health care.

The article, by a professor at Carnegie Mellon University (CMU), appears in the June 2021 issue of Latin American Research Review, a journal published by the Latin American Studies Association.

"These books break new ground and contribute to our understanding of some of the most important health care systems in Latin America," says Silvia Borzutzky, teaching professor of political science and international relations at CMU's Heinz College, who wrote the article. "In so doing, they help us understand the content and impact of health policies, an issue that has taken on new urgency during the pandemic."

With the seven books as a backdrop, the author begins with a brief historical overview of health policies in the region, then examines the role of social movements, subnational governments, and policy implementation in ensuring access to health care. She also addresses the role of international organizations.

Borzutzky notes that most of the books' authors are concerned with equitable and universal health care policies, but that this goal has been hampered. Even in countries with a universal right to health care, citizens have unequal access due to regional inequalities, traditional patronage relations, and the exclusion of minorities or minoritized groups.

During the COVID-19 pandemic, individuals who lack power have borne the brunt of this lack of access. In addition, because illness results from poverty, in a post-pandemic Latin America and Caribbean, the task will be not only to provide universal, good-quality health care but also to reduce poverty across the continent, suggests the author.

"The authors of the books I reviewed are clear that health policies in this part of the world are far from universal," Borzutzky explains. "Instead, they are fragmented and respond to the power and actions of critical groups or individuals in critical roles at specific times and places."

Borzutzky suggests that to end inequality and expand health care to all in this region, Latin America and the Caribbean need a universal approach based on equity and inclusion, and the recognition that health care should not be parceled out in regional, economic, gender, or ethnic terms. She argues that only this approach will allow the people in the region to fulfill their capabilities and contribute to their societies' development and success.

Credit: 
Carnegie Mellon University

Bacterium causing rabbit fever remains virulent for months in cold water

image: Northern Arizona University professor David Wagner, director of the Pathogen and Microbiome Institute's (PMI) Biodefense and Disease Ecology Center, led a study to better understand the life cycle and behavior of F. tularensis, funded through a $2.25 million grant from the U.S. Defense Threat Reduction Agency (DTRA).

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Northern Arizona University

Although it is not spread through human contact, Francisella tularensis is one of the most infectious pathogenic bacteria known to science--so virulent, in fact, that it is considered a serious potential bioterrorist threat. It is thought that humans can contract respiratory tularemia, or rabbit fever--a rare and deadly disease--by inhaling as few as 10 airborne organisms.

Northern Arizona University professor David Wagner, director of the Pathogen and Microbiome Institute's (PMI) Biodefense and Disease Ecology Center, began a three-year project in 2018 to better understand the life cycle and behavior of F. tularensis, funded through a $2.25 million grant from the U.S. Defense Threat Reduction Agency (DTRA).

One of the most puzzling behaviors of the pathogen is its ability to remain dormant, possibly in what is called a "viable but nonculturable" state--which means the bacteria is alive, but cannot be grown in the laboratory. That makes it much more difficult to study, because scientists can typically only study bacteria that can be cultured. Wagner's goal was to study the bacterium so as to determine the environmental and genetic factors that contribute to the pathogen's ability to apparently remain dormant for months at a time--a phenomenon that has remained mostly a mystery despite more than 100 years of research.

Now, Wagner and his collaborators have published their findings, "Long-Term Survival of Virulent Tularemia Pathogens outside a Host in Conditions That Mimic Natural Aquatic Environments," in the journal Applied and Environmental Microbiology. In the paper, the team shows how they were able to prove, by replicating environmental conditions in the lab, including low temperatures and low-nutrient water, that the bacterium can persist for months in cold water without any nutrients and remain fully virulent. Their results provide a plausible explanation for how it can overwinter in the environment outside of a host.

"We are making some very interesting discoveries in this project," Wagner said. "The main finding is that Francisella tularensis can persist in a dormant state for more than six months in cold water without any nutrients. This means it has the ability to persist in the environment outside of a mammalian host or arthropod vector. This was unexpected because many other bacteria that persist like that long-term in the environment form spores when they are outside of a host, such as Bacillus anthracis, the bacterium that causes anthrax forms spores, but F. tularensis doesn't do that. Others, like Yersinia pestis - the bacterium that causes plague - are always either in a mammalian host or a flea vector. F. tularensis has the ability to persist long-term in the environment long-term outside of a host without forming spores while remaining fully virulent."

"These study results have completely changed our perspective on the ecology of this bacterium. We now understand that mammals are likely just a small (but still important) aspect of its survival strategy. We now think that it spends most of its time in the environment outside of a host and only periodically causes disease in mammals. But those disease events in mammals are still very important as they serve to amplify the amount of F. tularensis that is deposited back in the environment."

Working with co-principal investigator Jason Sahl, associate professor and assistant director of PMI, and with PMI senior research scientists Dawn Birdsell and Joe Busch, Wagner conducted the study along with colleagues at two of the team's long-term collaborating institutions in Sweden: The Swedish Defence Research Agency and Umeå University.

Along with their Swedish collaborators, Wagner and his team are known worldwide for their work developing the phylogeny, or global family tree, of F. tularensis and its phylogeography--mapping where different groups of the species are found throughout the world and understanding the species' genetic diversity.

"As we continue with the DTRA research grant, we are now investigating the genes and proteins that regulate the ability of F. tularensis to persist in the environment outside of mammals and hosts. This work involves a number of current and recently graduated undergraduate students at NAU: former student Kathleen Soria, current students Natalie Hart and Rebecca Ballard, and current student and Flinn Scholar Kailee Savage.

Although the bacteria are naturally occurring throughout the northern hemisphere, including Arizona, the number of reported cases in the U.S. is small, with only 230 cases in 2016, three of which occurred in Arizona. Humans can be infected through insect bites; by drinking contaminated water, which happens in developing countries such as Turkey; by handling infected animals; and by breathing aerosolized particles containing the bacteria. Humans cannot transmit the disease to other humans. There is no vaccine to prevent the disease, which is treated with antibiotics. Wagner's team recently completed a related project funded by the DTRA studying the pathogen's antibiotic resistance.

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Northern Arizona University