Culture

Proteins make life and are made by ribosomes. In mitochondria, the repertoire of the mitoribosomal architectures turns out to be much more diverse than previously thought.

A paper published in eLife by Alexey Amunts lab reports extraction of the mitoribosome from a ciliated protozoan and its reconstruction using cryo-EM. The ciliate mitoribosome substantially differs with regard to its structure that reveals a 4.0-MDa complex of 94 proteins. The high resolution of the reconstruction allowed to identify nine novel proteins encoded in the mitochondrial genome.

Not only that the compositional complexity of the ciliate mitoribosome rivals that of human, it also provides a possible evolutionary intermediate that explains how translation in mitochondria has evolved. A particularly surprising feature is that a single functional protein uS3m is encoded by three complementary genes from the nucleus and mitochondrion, establishing a link between genetic drift and mitochondrial translation.

Among the functional characteristics, the analysis revealed a mitochondria-specific protein mL105 in the exit tunnel that features an intrinsic protein targeting system in mitochondria through a possible recruitment of a synthesized polypeptide.

The exploration of the ciliate mitoribosome structure gauges the full extent of mitochondrial structural and functional complexity and identifies potential evolutionary trends. The results emphasize the power of the cryo-EM based analysis of mitochondria in revealing novel proteins in different eukaryotic lineages.

Infection has been reduced up to 70% as of May 1st. Thanks to developed model, scenarios can be drawn regarding future containment measures.

While the pandemic caused by SARS-CoV-2 is still ravaging most countries of the world and containment measures are implemented worldwide, a debate is emerging on whether these measures might be partially alleviated, and in case how and when. This discussion requires appropriate models that guide decision-makers through alternative actions via scenarios of the related trajectories of the epidemic. This is the subject of a research whose results are published today in the journal Nature Communications by a team of Italian scientists from Università Ca' Foscari (Venice), Politecnico di Milano (Milan), Università di Padova (Padua), and École Polytechnique Fédérale de Lausanne (Lausanne, Switzerland).

The analysis is based on a spatially explicit model of the COVID-19 spread in Italy (first published in the journal Proceedings of the National Academy of Sciences USA by the team in April), inclusive of mobility among communities, progressive mobility restrictions and social distancing. The benchmark model has been updated through the estimation of parameters using the number of daily hospitalized cases in all 107 Italian provinces from February 24 to May 1st.

The researchers have generated scenarios of the Italian infection dynamics resulting from the bulk effect of lockdown lifting, which initiated on May 4. They wondered how the modes of relaxation of previous confinement measures might affect residual epidemic trajectories. The answer to this question is not trivial, because different activities have been allowed to resume at different times. In addition, acquired awareness may have different lasting effects on social behaviour regardless of imposed measures, and compliance to proper use of Personal Protective Equipment (such as masks) may fade away in time.

Using the epidemiological data up to June 17 the researchers have provided an ex-post assessment of the explored scenarios comparing them with the actual space-time progression of the outbreak. The actual change in overall transmission has been tracked via the departure of the epidemic curve from the one projected by using the transmission rate achieved during the lockdown (termed the baseline scenario). The great majority of Italian regions have been close to the baseline scenario for the considered one-month-and-a-half period.

Scientists have then addressed the mitigation of the likely increased exposure, in particular by estimating the sufficient number of case isolation interventions that would prevent rebounding of the epidemics. A control effort capable of isolating daily about 5.5% of the exposed and highly infectious individuals is necessary to maintain the epidemic curve onto the decreasing baseline trajectory.

An international team of researchers has discovered a new group of Chlamydiae - Anoxychlamydiales - living under the ocean floor without oxygen. These Chlamydiae have genes that allow them to survive without oxygen while making hydrogen gas. The researchers found that our single-cell ancestors 'caught' these hydrogen-producing genes from ancient Chlamydiae up to two-billion years ago - an event that was critical for the evolution of all complex life alive today. The results are published in Science Advances.

Life on Earth can be classified into two main categories: eukaryotes (e.g., plants, animals, fungi, amoeba) and prokaryotes (e.g., bacteria and archaea). In comparison to relatively simple prokaryotic cells, eukaryotic cells have complex cellular organisation. How such cellular complexity evolved has puzzled scientists for decades. The prevailing hypothesis for the evolution of eukaryotes involves the merger, or symbiosis, of two prokaryotes - an archaeon and a bacterium - nearly two-billion years ago, in environments with little oxygen. Scientists assume that these microbes co-operated with each other to survive without oxygen by exchanging nutrients. While we do not know what these nutrient were, many scientists think that hydrogen might be the answer.

To find an answer to this two-billion year old mystery, scientists look at genomes of modern prokaryotes and eukaryotes to find genes for living without oxygen and nutrient metabolism with hydrogen. Much like fossils, genomes hold clues to the evolutionary history of their ancestors. In our cells, we have a specialized factory called the mitochondrion - or powerhouse of the cell - that helps us make energy using the oxygen we breathe and the sugar we eat. However, some mitochondria are able to make energy without oxygen by producing hydrogen gas. Since hydrogen has been proposed to have been an important nutrient for the origin of eukaryotes, scientists think that hydrogen production was present in one of the two-billion year old partners: the archaeon or the bacterium. However, there is no evidence for this with present data.

In an article published in Science Advances, a team of international researchers has discovered an unexpected source of these genes at the bottom of the ocean from the Anoxychlamydiales, a newly discovered group of Chlamydiae. Anoxychlamydiales live without oxygen, and have genes for producing hydrogen - a trait that has never before been identified in Chlamydiae. The researchers were surprised to find that the chlamydial genes for hydrogen production closely resembled those found in eukaryotes. This strongly suggests that ancient chlamydiae contributed these genes during the evolution of eukaryotes.

"In our study we identified the first evidence for how eukaryotes got the genes to make hydrogen and it was from a completely unexpected source!" says co-lead author Courtney Stairs, postdoctoral researcher at Uppsala University in Sweden. Fellow co-lead author Jennah Dharamshi, PhD student from Uppsala University, adds: "We found new evidence that the eukaryotic genome has a mosaic evolutionary history, and has come not only from Archaea and the mitochondrion, but also from Chlamydiae".

"Understanding where hydrogen metabolism came from in eukaryotes is important for gaining insight into how our two-billion-year old ancestors evolved," says senior author Thijs Ettema, Professor at Wageningen University and Research in The Netherlands, and coordinator of the international team of researchers. "For years, I thought that if we ever found out where eukaryotic hydrogen metabolism came from, we would have a clearer picture of how eukaryotes evolved - however, finding out that these genes might have come from Chlamydiae has raised even more questions", Courtney Stairs adds.

How did the eukaryotes get a hold of these genes?

"We know that microorganisms routinely share genes with each other in a process called 'gene transfer'. We can find these transfer events by building family trees of each gene and looking for patterns in their evolution" explains Courtney Stairs. Today, the closest relatives of the archaeon that participated in the initial symbiosis are Asgard archaea. These archaea are also found at the bottom of the ocean where Anoxychlamydiales reside. "Asgard archaea and Anoxychlamydiales are both found living under the ocean floor where there is no oxygen" Thijs Ettema explains, "their cohabitation could have allowed for genes to be transferred between the ancestors of these microbes".

Finding chlamydiae that can live without oxygen has important implications in itself. These bacteria are typically known as pathogens of humans and other animals, even though they can also infect single-cell eukaryotes such as amoeba. All chlamydiae known to date live inside eukaryotic cells.

"Finding chlamydiae that might be able to live without oxygen, produce hydrogen, and live outside a eukaryote challenges our previously held conceptions" says Jennah Dharamshi, "our findings suggest that chlamydiae may be important members of the ecosystem on the ocean floor and that perhaps all chlamydiae are not that bad after all."

Cathode materials based on sodium and d-metals fluorophosphates are in great demand in the production of metal-ion batteries, because they have a rich chemical composition that allows to regulate their electrochemical properties. The research team of the scientists of Samara Center for Theoretical Materials Science of Samara Polytech, Institute of Solid State Chemistry and Mechanochemistry of the Siberian Branch of the Russian Academy of Sciences, Federal Research Center Boreskov Institute of Catalysis and P.N. Lebedev Physical Institute of the Russian Academy of Sciences found an original way to obtain monoclinic NaVPO4F by quenching. Research results are published in the journal of Physical Chemistry Chemical Physics.

A detailed study of NaVPO4F structure is conducted by means of X-ray diffraction analysis, infrared spectroscopy and nuclear magnetic resonance. A comparative analysis of NaVPO4F (with a monoclinic structure) and LiVPO4F (with a triclinic structure) is carried out. By means of theoretical methods it is proved that NaVPO4F composition has a low sodium atoms mobility, and thus its use as the cathode active material is impractical. It is also shown that the triclinic modification is energetically more favorable for the LiVPO4F compound than the monoclinic one, which, together with the sodium ions low mobility in NaVPO4F, makes the synthesis of monoclinic LiVPO4F by electrochemical exchange hardly possible.
The work of Samara Polytech employees in this area was supported by the Russian Science Foundation grant 19-73-10026.
By the way, the research team article "Crystal structure and migration paths of alkaline ions in NaVPO4F" was included in the list of the most relevant articles of 2020 according to the editors of the journal Physical Chemistry Chemical Physics.

"The field of electrochemical energy storage systems (lithium-ion batteries are the best known example) is extremely popular in modern science. The reason is the ongoing transition of modern society from fossil fuels to renewable energy sources and the wide spreading of mobile/autonomous devices", Artem Kabanov, the senior researcher of Samara Center for Theoretical Materials Science of Samara Polytech explains. "The search for new materials for such systems is very important. Our joint work with colleagues from Novosibirsk is devoted exactly to the study of new compounds - NaVPO4F, that can potentially serve as a positive electrode. We have synthesized NaVPO4F compound using quenching and shown that it possesses low sodium ion mobility and is useless as an active material for battery cathodes. Polyanionic compounds are very popular now in the field, and I believe this is the cause of why our article was included in the "hot list" of the PCCP journal (Q1, IF=3.5). Our collaboration with Dr. Nina Kosova's group from Novosibirsk is very fruitful and we have just published the second joint article in the Electrochimica Acta journal".

BEER-SHEVA, Israel...August 26, 2020 - People who consume frozen microbiome capsules derived from their own feces when dieting may limit their weight regain, according to a new study published in Gastroenterology, conducted by a team of researchers led by researchers at Ben-Gurion University of the Negev (BGU).

In an unprecedented, 14-month clinical trial in Israel, BGU Prof. Iris Shai, BGU Ph.D. student Dr. Ehud Rinott and Dr. Ilan Youngster from Tel-Aviv University, collaborated with a group of international experts from U.S. and European research institutes.

"It is well known that most weight-loss dieters reach their lowest body weight after 4-6 months, and are then challenged by the plateau or regain phase, despite continued dieting," says Prof. Shai. a member of the School of Public Health. In this groundbreaking study, the international group of researchers explored whether preserving the optimized personal microbiome from fecal transplants after six months of weight loss helps maintain weight loss by transplanting back the optimized microbiome during the subsequent expected regain phase.

In the weight loss trial, abdominally obese or dyslipidemic (high cholesterol) participants in Israel were randomly assigned to one of three groups (1) healthy dietary guidelines, (2) Mediterranean diet, and (3) green-Mediterranean diet, After six months during the weight-loss phase, 90 eligible participants provided a fecal sample that was processed into aFMT by frozen, opaque and odorless capsules. The participants were then randomly assigned to the groups that received 100 capsules containing their own fecal microbiota or placebo which they ingested until month 14.

In the green-Mediterranean diet group, participants were provided with Mankai, a specific duckweed aquatic strain in a green shake, green tea and 28g of walnuts. This was the group diet strategy that induced the largest significant change in the gut microbiome composition during the weight loss phase.

The 90 participants lost 8.3 kg (18.2 lbs.) on average after six months, However, only in the green-Mediterranean diet group did aFMT limit weight regain from only 17.1%, vs 50% for the placebo.

"The green-Mediterranean diet also resulted in preservation of weight loss-associated specific bacteria and microbial metabolic pathways, mainly glucose transport, following the microbiome intervention, compared to the control," says Dr. Rinott.

In a complementary Mankai-specific mouse model experiment conducted by Prof. Omry Koren at Bar-Ilan University, the researchers were able to reproduce the effects of weight-nadir-based transplantation on weight regain and insulin sensitivity, and to isolate the specific contribution of Mankai consumption to induce these effects.

"This study is the first of its kind to prove in humans that preservation of an "ideal" gut microbial composition can be used at a later time point to achieve metabolic benefits," says Dr. Youngster, director of the Pediatric Infectious Diseases Unit and the Center for Microbiome Research at Shamir Medical Center. "Using the patient's own stool after optimization is a novel concept that overcomes many of these barriers. It is my belief that the use of autologous fecal microbiota transplantation will be applicable in the future for other indications as well."

Furthermore, green plant-based diet such as Mankai, better optimizes the microbiome for the microbiota transplantation procedure. This potentially optimizes the conditions for the aFMT, collected during the maximal weight loss phase. The Mankai duckweed aquatic plant is being grown in Israel and other countries in a closed environment and is highly environmentally sustainable - requiring a fraction of the amount of water to produce each gram of protein compared to soy, kale or spinach.

According to Professor Omry Koren, at Bar-Ilan University who led the animal experiments: "The nutrition-microbiome axis has been proven in this study as high polyphenols diet, and specifically, Mankai, a protein-based plant and dietary fibers could ideally optimize the microbiome in the weight loss phase, to induce potent microbiome to recall the flora of germs related to regain attenuation and improved glycemic state after transplantation."

"These findings might be a good application of personal medicine," says Dr. Shai who is also an adjunct professor at Harvard. "Freezing a personal microbiome bank could be an effective way to maintain healthy weight while dieting as the rapid weight loss phase is accompanied by optimal cardiometabolic state. By optimizing the composition and function of the gut microbiome within the host, we have a novel approach for metabolic-memory preservation: taking a sample of the gut microbiome in its ideal phase, and administrating it when dieters start regaining their lost weight.

COLUMBIA, SC - Acute Respiratory Distress Syndrome (ARDS), when caused by a bacterial toxin known as Staphylococcal enterotoxin, can be completely prevented by treatment with Δ9-tetrahydrocannabinol (THC), a cannabinoid found in the cannabis plant. This exciting finding, recently published in the highly cited British Journal of Pharmacology, also suggests a possible treatment for ARDS caused by COVID-19.

This new paper is based on research studies from the laboratories of Dr. Mitzi Nagarkatti and Dr. Prakash Nagarkatti at the University of South Carolina (UofSC) School of Medicine, Department of Pathology, Microbiology and Immunology. The Nagarkattis published "Protective Effects of Δ9-Tetrahydrocannabinol Against Enterotoxin-induced Acute Respiratory Distress Syndrome is Mediated by Modulation of Microbiota," with co-authors Amira Mohammed, Hasan Alghetaa and Juhua Zhou, who also work in their UofSC School of Medicine laboratories, and Saurabh Chatterjee from the UofSC Arnold School of Public Health. Drs. Mitzi and Prakash Nagarkatti have for years studied how plant-derived compounds can be used to prevent and reduce inflammation throughout the body.

The incidence of ARDS in the United States is 78.9 per 100,000 persons/year and the mortality rate is 38.5 percent. When inhaled, Staphylococcal enterotoxin can cause ARDS by activating immune cells to produce massive amounts of cytokines leading to "cytokine storm," which can cause the lungs and other organs to fail, often resulting in death. This immune process is similar to that seen in patients with severe COVID-19 who are admitted to the hospital and develop ARDS accompanied by cytokine storm, which leads to respiratory and multi-organ failure. These studies therefore raise the exciting possibility of using cannabinoids to treat ARDS seen in COVID-19 patients.

These studies also showed that Staphylococcal enterotoxin alters the microbiome in the lungs leading to the emergence of pathogenic microbiota. But THC helps this symptom too, by promoting beneficial bacteria that suppress inflammation thereby preventing the damage to the lungs.

"Acute respiratory distress syndrome is triggered by a variety of etiologic agents. Currently, there are no FDA-approved drugs to treat ARDS because of which the mortality rate is close to 40 percent. Our studies suggest that THC is highly effective to treat ARDS and thus, clinical trials are critical to investigate if this works," said Mitzi Nagarkatti.

"Cytokine storm is a huge clinical issue which leads to multiorgan failure and often death. It is also seen in COVID-19 patients, and there are no effective treatment modalities against this syndrome. We have been working on cannabinoids for over 20 years and found that cannabinoids such as THC are highly anti-inflammatory. Thus, our studies raise the exciting suggestion to test THC against ARDS seen in COVID-19 patients," said Prakash Nagarkatti.

The Nagarkatti laboratory has performed decades of pioneering studies on cannabinoids. In fact, their studies on the use of another cannabinoid derived from the cannabis plant, cannabidiol (CBD), to treat autoimmune hepatitis have been well-recognized in the field and have led to FDA approval of CBD as an orphan drug to treat this disorder.

The Nagarkatti Laboratory has published extensively to demonstrate that cannabinoids are potent anti-inflammatory agents that can be used safely to treat a variety of inflammatory and autoimmune diseases such as multiple sclerosis, colitis, hepatitis and the like.

A new method of brain imaging analysis offers the potential to greatly improve the effectiveness of noninvasive brain stimulation treatment for Alzheimer's, obsessive compulsive disorder, depression, and other conditions. Duke researchers developed the new method, which for the first time analyzed the whole brain network rather than a single region of the brain. This new method identified brain areas that exert the most control on network function.

The study, published in the Journal of Neuroscience, has direct implications for improving the benefits of transcranial magnetic stimulation, which is currently used for major depression and obsessive compulsive disorder, and may soon lead to therapeutic treatment for memory disorders such as Alzheimer's and dementia.

Researchers at the Duke Brain Stimulation Research Center (BSRC) developed a method of analysis that relies on the concept of controllability, a network principle that helps to predict how one area of the brain influences a whole network involved in regulating behavior.

The authors measured controllability using functional magnetic resonance imaging (fMRI) to determine how much change TMS would induce as participants did a working memory task. In this task, individuals had to keep bits of information briefly in their memory and manipulate this information in their mind before answering questions about it. This task was used because of the importance of working memory in everyday life (like ordering your shopping list in your mind before walking through the grocery store) and because it is highly impacted by aging, particularly in conditions like Alzheimer's and dementia.

"Essentially, we look at the brain not as a set of discrete islands, but as a dense web of connections that have lots of mutual influence," said lead researcher Dr. Simon Davis, PhD, Assistant Professor of Neurology at Duke. "Controllability allows us a framework for identifying which nodes in this web are most likely to be influenced by brain stimulation, and for that reason likely to show plasticity and improvement after TMS treatments."

The controllability measure, which is based on a static, structural image of the brain, was used to predict dynamic activity. "Brain activity is like the spatial pattern of traffic in a city. Although the traffic pattern is ever-changing, it is always confined by the topology of the road network," said Lifu Deng, a Duke graduate student in the Department of Psychology and Neuroscience, and co-lead on the paper. "Controllability links the stimulation at one location to the global pattern of brain activity. In our study, for instance, this is the activation patterns signifying better working memory."

Previously, there has not been a systematic way to identify which brain areas are the most likely to produce global chances, because most studies have focused on just one region. This study, however, advanced the field by considering the whole brain network.

While healthy adults participated in the study, the research likely has implications for memory disorders. "Memory dysfunction as a network phenomenon that relies on multiple brain regions operating under coordinated dynamics. The typical focus on the TMS response at a single site represents a fundamental limitation in the approach of neurostimulation therapies because it neglects global impairments in whole network that underlies memory dysfunction," said Lysianne Beynel, PhD, a postdoctoral associate in the BSRC and first author on the study.

Ultimately, this non-invasive brain stimulation method will be used to promote healthy brain activity patterns and eventually enhance memory function, which has potential to enhance the efficacy of brain stimulation treatments for a range of cognitive disorders.

A revolutionary group of scientists has been rethinking for two decades how we understand bird song, with women leading the way. Several of these scientists are from UMBC, and their latest research has revealed findings not just about birds, but about bird researchers.

Elaborate bird song had been considered mostly a male trait for centuries, famously discussed by Charles Darwin. But Karan Odom, Ph.D. ’16, biological sciences, published a landmark paper on female bird song in 2014 that helped change that viewpoint. Odom’s study found that as many as 70 percent of female birds sing. Her extensive research also established firmly that both sexes almost certainly sang in the common ancestor of all bird species—a radical idea in ornithology.

Odom conducted research at UMBC with Kevin Omland, professor of biological sciences, whose lab has led much of the research in this area. Now, a new paper led by Casey Haines ’19, biological sciences, has documented what the Omland group and others have suspected all along: Women are more likely than men to be authors, and even more likely to be first authors (research leads), on papers about female bird song. Therefore, it is largely women who have reshaped this classical field of study. 

The findings, published this week in Animal Behaviour, suggest that a diverse group of researchers is critical for scientific innovation. Diversity could also help build a more accurate and complete understanding of bird biology and other fields.

A fresh perspective

Haines and Omland completed the research with co-authors Odom and Evangeline Rose, a Ph.D. candidate in Omland’s lab. They examined 59 bird song papers published between 1997 and 2016. 

The researchers found that women made up 56 percent of all authors on female bird song papers, compared with only 40 percent of authors of general bird song papers. Women held 68 percent of first-author positions on female bird song papers, but only 44 percent of first-author positions on general bird song papers. This means men were 24 percentage points less likely than women to lead a study on female bird song, and 16 percent less likely to contribute to a female song study in any way, compared with their contributions to general bird song papers.

“I believe this paper is a great example of how diversity expands the type of research scientists are doing,” Haines says. “Female bird song research has been underrepresented in the literature until only recently. A diverse pool of researchers may result in new questions being asked and new approaches to answering those questions. I would love to see this type of research applied in other areas of STEM.”

Other research cited in the new paper has found that women are more likely to study female animals (including humans), which have been historically understudied, as well as species that have gotten less attention in research. Female authors also publish more often with women co-authors, opening doors to greater funding and opportunities for more women in science. 

More generally, research has shown that diversity among scientists leads to greater creativity in questions, ideas, and methods.

A starting point

Omland acknowledges that this kind of study is outside his lab’s avian evolution wheelhouse, but he hopes it will spark further conversations. “We’re able to add an important data point to these discussions,” he says. And while the new paper has been in the works for some time, “In this moment, this research seems to have gained an increased weight.”

Haines and colleagues acknowledge that their study is imperfect. For example, “Our data represent gender in a binary framework, which is not reflective of society, potentially resulting in mis-gendering authors who are non-binary or gender minorities,” the paper states. “Gender minority authors make important contributions to science and are a vital part of increasing diversity. We recommend that more-detailed future studies provide opportunities for authors to self-identify their gender to avoid the possibility of mis-gendering.”

Even with its limitations, the paper provides an important glimpse into gender dynamics in ornithology. For an emerging researcher like Haines, it was an eye-opening experience. 

“Personally, it was amazing to find that the percentage of women who hold first-author positions on female bird song has increased so much within the last 20 years,” Haines says. “I think it speaks volumes on how far both female bird song and women in science have come.”

Creating space for new leaders

Haines herself is on a path to pursue graduate study in animal behavior based on her experience in the Omland lab. “Working with Dr. Omland, Evangeline, and the rest of the Omland lab was definitely the most memorable and enjoyable part of my time at UMBC,” she says.

Omland has a history of nurturing undergraduate researchers. In fact, Haines’s paper is the tenth peer-reviewed journal article published with an undergraduate first author from his lab. “Undergraduate researchers have really influenced the trajectory of our lab’s research by making consistent, significant contributions,” Omland says.

“It’s essential that we continue to build environments where researchers from all backgrounds are encouraged to explore new ideas and ask new questions,” Omland says. “Not only will this enable them to reach their potential as scientists, but it is also essential to expanding our knowledge of the world around us.”

Journal

Animal Behaviour

DOI

10.1016/j.anbehav.2020.07.021

Scientists at Johns Hopkins Medicine using MRI scans and computer modeling say they have further pinpointed areas of the human brain that regulate efforts to deal with fatigue.

The findings, they say, could advance the development of behavioral and other strategies that increase physical performance in healthy people, and also illuminate the neural mechanisms that contribute to fatigue in people with depression, multiple sclerosis and stroke.

Results of the research were published online Aug. 12 in Nature Communications.

"We know the physiologic processes involved in fatigue, such as lactic acid build-up in muscles, but we know far less about how feelings of fatigue are processed in the brain and how our brain decides how much and what kind of effort to make to overcome fatigue," says Vikram Chib, Ph.D., assistant professor of biomedical engineering at the Johns Hopkins University School of Medicine and research scientist at the Kennedy Krieger Institute.

Knowing the brain regions that control choices about fatigue-moderating efforts can help scientists find therapies that precisely alter those choices, says Chib. "It might not be ideal for your brain to simply power through fatigue," says Chib. "It might be more beneficial for the brain to be more efficient about the signals it's sending."

For the study, Chib first developed a novel way to objectively quantify how people "feel" fatigue, a difficult task because rating systems can vary from person to person. Physicians often ask their patients to rate their fatigue on a scale of 1 to 7, but like pain scales, such ratings are subjective and varied.

To standardize the metric for fatigue, Chib asked 20 study participants to make risk-based decisions about exerting a specific physical effort. The average age of participants was 24 and ranged from 18 to 34. Nine of the 20 were female.

The 20 participants were asked to grasp and squeeze a sensor after training them to recognize a scale of effort. For example, zero was equal to no effort and 50 units of effort were equal to half the participant's maximum force. The participants learned to associate units of effort with how much to squeeze, which helped to standardize the effort level among individuals.

The participants repeated the grip exercises for 17 blocks for 10 trials each, until they were fatigued, then were offered one of two choices for making each effort. One was a random ("risky") choice based on a coin flip, offering the chance to exert no effort or a predetermined effort level. The other choice was a predetermined set effort level. By introducing uncertainty, the researchers were tapping in to how each subject valued their effort -- a way, in effect, of shedding light on how their brains and minds decided how much effort to make.

Based on whether the participant chose a risky option versus the predetermined one, the researchers used computerized programs to measure how participants felt about the prospect of exerting particular amounts of effort while they were fatigued.

"Unsurprisingly, we found that people tend to be more risk averse -- to avoid -- effort," says Chib. Most of the participants (19 of 20) opted for the risk-free choice of a predetermined effort level. This means that, when fatigued, participants were less willing to take the chance of having to exert large amounts of effort.

"The predetermined amount had to get pretty high in relative effort for participants to choose the coin toss option," says Chib.

Among a separate group of 10 people trained on the gripping system but not given numerous, fatiguing trials, there was no significant tendency toward picking either the risky coin toss or defined effort.

Chib's research team also evaluated participants' brain activity during the gripping exercises using functional magnetic resonance imaging (fMRI) scans, which track blood flow through the brain and show which neurons are firing most often.

Chib's team confirmed previous findings that brain activity when participants chose between the two options seemed to increase in all participants in an area of the brain's known as the insula.

Also using fMRI scans, they took a closer look at the motor cortex of the brain when the participants were fatigued. This region of the brain is responsible for exerting the effort itself.

The researchers found that the motor cortex was deactivated at the time participants "decided" between the two effort choices. That finding is consistent, Chib says, with previous studies showing that when people perform repeated fatiguing exertions, motor cortex activity is decreased, associated with fewer signals being sent down to the muscles.

Participants whose motor cortex activity changed the least, in response to fatiguing exertion, were the ones who were most risk averse in their effort choices and were most fatigued. This suggests that fatigue might arise from a miscalibration between what an individual thinks they are able to achieve and the actual activity in motor cortex.

Essentially, the body attunes to the motor cortex when fatigued, because if the brain kept sending more signals to muscles to act, physiological constraints would begin to take over, for example, increased lactic acid, contributing to even more fatigue.

These findings, says Chib, may advance the search for therapies -- physical or chemical -- that target this pathway in healthy people to advance performance and in people with conditions that are associated with fatigue.

The Gerontological Society of America's highly cited, peer-reviewed journals are continuing to publish scientific articles on COVID-19, and all are free to access. The following were published between July 24 and August 25; all are free to access:

Modern Senicide in the Face of a Pandemic: An Examination of Public Discourse and Sentiment about Older Adults and COVID-19 Using Machine Learning: Research report in The Journals of Gerontology, Series B: Psychological Sciences and Social Sciences by Xiaoling Xiang, PhD, MSW, Xuan Lu, PhD, Alex Halavanau, PhD, Jia Xue, PhD, Yihang Sun, MSW, Patrick Ho Lam Lai, MSW, and Zhenke Wu, PhD

Calculated Ageism: Generational Sacrifice as a Response to the COVID-19 Pandemic: Research report in The Journals of Gerontology, Series B: Psychological Sciences and Social Sciences by Anne E. Barrett, PhD, Cherish Michael, MS, and Irene Padavic, PhD

Prisons and COVID-19: A Desperate Call for Gerontological Expertise in Correctional Healthcare: Brief report in The Gerontologist by Stephanie Grace Prost, PhD, Meghan A. Novisky, PhD, Leah Rorvig, MD, Nick Zaller, PhD, and Brie Williams, MD

Scientists have discovered that testing the levels of certain proteins in blood samples can predict whether a person at risk of psychosis is likely to develop a psychotic disorder years later.

The study is published in the current edition of JAMA Psychiatry and was led by researchers from RCSI University of Medicine and Health Sciences.

Based on certain criteria, such as mild or brief psychotic symptoms, some people are considered to be clinically at high risk of developing a psychotic disorder, such as schizophrenia. However, only 20% to 30% of these people will actually go on to develop a psychotic disorder.

The researchers analysed blood samples taken from people at clinical high risk of psychosis. These individuals were followed up for several years to see who did and did not develop a psychotic disorder.

After assessing the proteins in blood samples and using machine learning to analyse this data, the scientists were able to find patterns of proteins in the early blood samples that could predict who did and did not develop a psychotic disorder at follow-up.

Many of these proteins are involved in inflammation, suggesting that there are early changes in the immune system in people who go on to develop a psychotic disorder. The findings also suggest that it is possible to predict their outcomes using blood samples taken several years in advance.

The most accurate test was based on the 10 most predictive proteins. It correctly identified those who would go on to develop a psychotic disorder in 93% of high-risk cases, and it correctly identified those who would not in 80% of cases.

"Ideally, we would like to prevent psychotic disorders, but that requires being able to accurately identify who is most at risk," said Professor David Cotter, the study's senior and corresponding author and professor of molecular psychiatry at RCSI.

"Our research has shown that, with help from machine learning, analysis of protein levels in blood samples can predict who is at truly at risk and could possibly benefit from preventive treatments. We now need to study these markers in other people at high risk of psychosis to confirm these findings."

A patent application has been filed, and the research team is working to commercialise this research through licensing or partnering with industry.

Healthcare systems around the world need to develop ways of supporting people in the community who are recovering from COVID-19, say researchers.

If they don't, there is a risk that people experiencing long-term symptoms will get worse and put additional strain on already-stretched health resources.

Although COVID-19 starts as an acute infection of the lungs, it can develop into a "multi-system illness" leaving people with symptoms that can last for months and years - including breathlessness, fatigue, weakness, pain, cardiac problems, cognitive and psychological problems.

More than one-third of the people who have been severely ill with the disease could have long-term symptoms, some of them debilitating.

The study - Development of an integrated rehabilitation pathway for individuals recovering from COVID-19 in the community - by experts from the University of Leeds, Leeds Teaching Hospitals NHS Trust, Leeds Community Healthcare NHS Trust and NHS Leeds Clinical Commissioning Group has been published in the Journal of Rehabilitation Medicine.

Dr Manoj Sivan, Associate Clinical Professor at the University of Leeds and a Consultant in Rehabilitation Medicine in the NHS Trusts, led the research project. He said: "It has been estimated that to date, 23 million people worldwide have been infected by the disease. Most will have experienced a mild illness but a sizeable minority, up to one million, will have after-effects that will last for many months and possibly years.

"We know from previous outbreaks of Spanish flu, SARS and Ebola that up to a third of survivors can suffer from long term problems, particularly chronic fatigue that has implications on family life, work and health economy.

"With COVID-19, there is an opportunity to intervene early, provide timely specialist rehabilitation, and ensure people have the best functional recovery and return to their vocation as early as possible."

Lisa Hollingworth, Senior Commissioning Manager at NHS Leeds, said: "Collaboration between commissioners and providers in the city has resulted in the development of clinical guidance and new pathways for the provision of rehabilitation services post COVID-19, including a specialist Multi- Disciplinary Team.

"The resource investment to date is £500,000 supported by NHS Leeds Clinical Commissioning Group."

How patients in Leeds are screened

The researchers describe a telephone screening and referral service that has been pioneered by the Leeds COVID-19 rehabilitation teams at Leeds Teaching Hospitals and Leeds Community Healthcare NHS Trusts.

People who have been severely ill with COVID-19 are contacted either by their GP or a specialist member of the hospital's rehabilitation team six and 12 weeks after recovering from the acute phase of the illness. They are asked a series of questions about - and scored on - any persistent symptoms and how well they are functioning.

The questionnaire called C19-YRS (Yorkshire Rehabilitation Screen) takes about 15 minutes to complete.

The screening identifies symptoms that need to be urgently assessed by relevant specialist healthcare professionals in secondary or primary care services. Services include respiratory medicine, pulmonary rehabilitation, physiotherapy, occupational therapy, psychology or combined multidisciplinary clinics.

Self-help resources have been developed, and the NHS England is planning a website 'Your COVID Recovery' which is expected to go live soon.

Dr Ian Clifton, Honorary Senior Lecturer at the University of Leeds and Consultant in Respiratory Medicine, added: "One of the challenges we face is that COVID-19 is a new disease and we do not yet know the course that people will follow as they recover. It is essential that recovery services have input from a range of specialties, so expert help is on hand when and where it is needed."

Research by Dr Sivan and colleagues earlier in the summer identified the common longer-term symptoms experienced by COVID-19 survivors who were severely ill with the disease. The top three were fatigue, breathlessness and psychological distress.

Current sequencing techniques lack the sensitivity to detect rare gene mutations in a pool of cells, which is particularly important, for example, in early cancer detection. Now, scientists at KAUST have developed an approach, called targeted individual DNA molecule sequencing (IDMseq), that can accurately detect a single mutation in a pool of 10,000 cells.

Importantly, the team successfully used IDMseq to determine the number and frequency of mutations caused by the gene editing tool, CRISPR/Cas9, in human embryonic stem cells. Clinical trials are underway to test CRISPR's safety to treat some genetic diseases. "Our study revealed potential risks associated with CRISPR/Cas9 editing and provides tools to better study genome editing outcomes," says KAUST bioscientist Mo Li, who led the study.

IDMseq is a sequencing technique that involves attaching a unique barcode to every DNA molecule in a sample of cells and then making a large number of copies of each molecule using a polymerase chain reaction (PCR). Copied molecules carry the same barcode as the original ones.

A bioinformatics tool kit, called variant analysis with unique molecular identifier for long-read technology (VAULT), then decodes the barcodes and places similar molecules into their own "bins", with every bin representing one of the original DNA molecules. VAULT uses a combination of algorithms to detect mutations in the bins. The process works especially well with third-generation long-read sequencing technologies and helps scientists detect and determine the frequency of all types of mutations, from changes in single DNA letters to large deletions and insertions in the original DNA molecules.

The approach successfully detected a deliberately caused gene mutation that was mixed with a group of wild-type cells at ratios of 1:100, 1:1,000 and 1:10,000. It also correctly reported its frequency.

The researchers also used IDMseq to look for mutations caused by CRISPR/Cas9 genome editing. "Several recent studies have reported that Cas9 introduces unexpected, large DNA deletions around the edited genes, leading to safety concerns. These deletions are difficult to detect and quantitate using current DNA sequencing strategies. But our approach, in combination with various sequencing platforms, can analyze these large DNA mutations with high accuracy and sensitivity," says Ph.D. student Chongwei Bi.

The tests found that large deletions accounted for 2.8-5.4 percent of Cas9 editing outcomes. They also discovered a three-fold rise in single-base DNA variants in the edited region. "This shows that there is a lot that we need to learn about CRISPR/Cas9 before it can be safely used in the clinic," says Yanyi Huang of Peking University, who is an international collaborator co-funded by KAUST.

IDMseq can currently sequence only one DNA strand, but work to enable double-strand sequencing could further improve performance, say the researchers.

In a study published in the Journal of Morphology, a team of researchers from New Jersey Institute of Technology (NJIT), Florida Museum of Natural History, Louisiana State University and Thailand's Maejo University have successfully pieced together the ancestral relationships that make up the family tree of hillstream loaches (Balitoridae), detailing for the first time a range of unusual pelvic adaptations across the family that have given some of its members an ability to crawl, or even walk as salamanders do, to navigate terrestrial surfaces.

The team's DNA-based comparative analysis of the fish family, known to currently encompass more than 100 species native to South and Southeast Asia, is the first of its kind to include Cryptotora thamicola -- the only living species of fish known to walk on land in a step pattern similar to tetrapods, or four-limbed vertebrates such as reptiles and amphibians.

The results have revealed that three dominant variations of pelvic anatomy in the family, notably including key variations of a robust pelvic girdle and elongated sacral rib among many loaches, which researchers expect are central in explaining the different degrees of land-walking behavior exhibited by the fishes. The team says that the family's modified pelvic features enabling terrestrial locomotion, which were found most pronounced in Cryptotora thamicola, may have been adapted to enhance their odds of survival in rivers and other fast-moving water environments that many Balitoridae inhabit today.

"The modified morphology of these Balitoridae, particularly the enlarged sacral rib connecting the pelvic plate to the vertebral column, is a big part of why studying this family is so exciting," said Callie Crawford, the study's corresponding author and Ph.D. candidate at NJIT's Department of Biological Sciences. "These loaches have converged on a structural requirement to support terrestrial walking not seen in other fishes. What we've discovered is three anatomical groupings that have major implications for the biomechanics of terrestrial locomotion of these loaches, and the relationships among these fishes suggest that the ability to adapt to fast-flowing rivers may be what was passed on genetically, more than the specific morphology itself."

"Now that we have revealed a spectrum of pelvic morphologies among these fishes, we can compare the extent of skeletal support with the walking performance in a species," said Brooke Flammang, the study's lead principal investigator and assistant professor of biology at NJIT. "This will allow us to measure the mechanical contribution of robust hips to terrestrial locomotion."

Unlike most living fishes that feature pelvic fins located more anteriorly and attached to the pectoral girdle, balitorids typically boast a skeletal connection between the pelvic plate (basipterygium) and the vertebral column via a modified sacral rib and its distal ligament. These modifications are understood to help generate force against the ground useful for navigating land. The most extreme example emerged in 2016 with the discovery of Cryptotora thamicola in the fast-flowing aquatic conditions of the Tham Maelana and Tham Susa karst cave systems in northern Thailand. NJIT researchers then first identified that the rare species used a robust pelvic girdle attached to its vertebral column to walk and climb waterfalls with a salamander-like gait.

"This trait is likely key to helping these fishes avoid being washed away in the fast-flowing environment that they live in," said Zach Randall, co-author of the paper and biological scientist at Florida Museum of Natural History. "What's really cool about this paper is that it shows with high detail that robust pelvic girdles are more common than we thought in the hillstream loach family."

"The sacral ribs allow forces from the fins pressing against the ground to be transferred to the body so that every time the fin pushes down during a step, the body is pushed up and forward," explained Flammang. "The increased surface area of the more modified sacral ribs also offers more room for muscle attachment, so fishes such as Cryptotora thamicola can rotate their hips during walking, producing a salamander-like gait."

River Loach Family Factions

To better understand the evolution of the river loach family, the team conducted a broad sampling of μCT-scan data taken from 29 representative specimens, analyzing and comparing skeletal structures, muscle morphology as well as sacral rib shape across 14 of the 16 balitorid genera. The team also sampled genomic datasets of 72 loaches across seven families to reconstruct the evolutionary relationships in the Ballitoridae tree of life. "We were able to use a large survey of museum specimens and CT scanning to incorporate data even from specimens that didn't have tissue or genetic data intact," noted Randall.

The results showed that the loaches fall into three distinct morphotypes, which are expected to correlate to how well they are able to maneuver on land: species with a long, narrow rib that meets the pelvic plate; species with a thicker, slightly curved rib meeting the pelvic plate; and species with a robust crested rib interlocking with the pelvic plate. Of the species sampled, eleven fell into the third category with advanced land-walking abilities, such as Cryptotora thamicola, displaying the most robust sacral rib connection between the basipterygium and vertebral column.

"Our analysis showed that the morphotypes are not grouped by closely related taxa, but instead appear spread out across the phylogeny. That indicates to us that the extent of the modification of these features is less reflecting shared ancestry and more likely a product of adaptation to the flow regimes of their environments," explained Crawford. "To better understand how and why these distinct morphotypes developed, we need more knowledge of the habitat of each species, including water flow rates, substrate types and how the rivers and streams change between rainy and dry seasons."

Crawford and colleagues now aim to further investigate the stability physics and muscular forces at play that allow certain species to push their bodies off their ground as they walk. The team, including a recent Rutgers University graduate, Amani Webber-Schultz, recently completed fieldwork in Thailand earlier this year to collect more balitorid specimens, which they are studying using high-speed videos of the fishes walking.

"This will allow us to study details of their walking kinematics and gain even more insight into how walking performance might change between species with different pelvic morphologies," said Crawford.

Scientists at the U.S. Department of Energy's Ames Laboratory have discovered a metal-free carbon-based catalyst that has the potential to be much less expensive and more efficient for many industrial concerns, including manufacturing of bio- and fossil fuels, electrocatalysis, and fuel cells.

At their most fundamental, these industry processes involve splitting strong chemical bonds, like hydrogen-hydrogen, carbon-oxygen, and carbon-hydrogen bonds. Traditionally this has been accomplished with catalysts that use transition or precious metals, many of them expensive and low in natural abundance -- like platinum and palladium.

The scientists performed experiments with a type of heterogeneous catalyst, Nitrogen-Assembly Carbons (NACs), in which the design and placement of nitrogen on the carbon surface greatly influenced the catalytic activity of the material. These N atoms on carbon surfaces were previously believed to be distant from one another, as the close placement of N atoms is thermodynamically unstable. The team in Ames Lab correlated the N precursors and pyrolysis temperature for the NACs synthesis with the N distribution and discovered that meta-stable N assemblies can be made by design and deliver unexpected catalytic reactions. Such reactions include hydrogenolysis of aryl ethers, dehydrogenation of ethylbenzene and tetrahydroquinoline, and hydrogenation of common unsaturated functionalities (such as ketone, alkene, alkyne, and nitro groups). Moreover, the NACs catalysts are robust with consistent selectivity and activity for both liquid and gas phase reactions under high temperature and/or pressure.

"We discovered that how the nitrogen was distributed on the surface of these NACs really mattered, and in the process realized that this was an entirely new kind of chemical activity," said Ames Laboratory Associate Scientist Long Qi.

"The discovery should enable scientists to design nitrogen assemblies that are able to accomplish more sophisticated and challenging chemical transformations without the need for transition metals" said Ames Laboratory scientist Wenyu Huang. "It broadly applies to many different types of chemical conversions and industries."