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EAST LANSING, Mich. - An acute loss of smell is one of the most common symptoms of COVID-19, but for two decades it has been linked to other maladies among them Parkinson's disease and dementia. Now, a poor sense of smell may signify a higher risk of pneumonia in older adults, says a team of Michigan State University researchers.

"About a quarter of adults 65 years or older have a poor sense of smell," said Honglei Chen, a professor in the Department of Epidemiology and Biostatistics within MSU's College of Human Medicine. "Unlike vision or hearing impairment, this sensory deficit has been largely neglected; more than two-thirds of people with a poor sense of smell do not know they have it."

In a first-of-its-kind study, Chen and his team found a possible link between poor sense of smell and a higher risk of pneumonia hospitalization. They analyzed 13 years of health data from 2,494 older adults, ages 71-82, from metropolitan areas of Pittsburgh, Pennsylvania, and Memphis, Tennessee. This study aimed to examine whether a poor sense of smell in older adults is associated with a higher future risk of developing pneumonia.

Chen's research was recently published in the journal The Lancet Healthy Longevity. The participants were given a Brief Smell Identification Test, or B-SIT, using common smells such as lemons and gasoline to determine if their sense of smell was good, moderate or poor. Then, the participants were monitored for the next 13 years using clinical exams and follow-up phone calls to identify hospitalization due to pneumonia.

The researchers found that compared with participants who had a good sense of smell, participants with a poor sense of smell were about 50% more likely to be hospitalized with pneumonia at any time point during the 13-year follow-up. Among participants (with a poor sense of smell) who never had had pneumonia before, the risk of having the first-ever pneumonia was about 40% higher.

"To our knowledge, this study provides the first epidemiological evidence that poor olfaction (sense of smell) is associated with a long-term higher risk of pneumonia in older adults," said Yaqun Yuan, a postdoctoral fellow in Chen's research group.

This study provides novel evidence that a poor sense of smell may have broader health implications beyond its connections to Parkinson's disease and dementia.

"This is just an example how little we know about this common sensory deficit," Chen said. "Either as a risk factor or as a marker, poor sense of smell in older adults may herald multiple chronic diseases beyond what we have known about. We need to think out of the box."

CAMBRIDGE, MA -- In early 2020, a few months after the Covid-19 pandemic began, scientists were able to sequence the full genome of the virus that causes the infection, SARS-CoV-2. While many of its genes were already known at that point, the full complement of protein-coding genes was unresolved.

Now, after performing an extensive comparative genomics study, MIT researchers have generated what they describe as the most accurate and complete gene annotation of the SARS-CoV-2 genome. In their study, which appears today in Nature Communications, they confirmed several protein-coding genes and found that a few others that had been suggested as genes do not code for any proteins.

"We were able to use this powerful comparative genomics approach for evolutionary signatures to discover the true functional protein-coding content of this enormously important genome," says Manolis Kellis, who is the senior author of the study and a professor of computer science in MIT's Computer Science and Artificial Intelligence Laboratory (CSAIL) as well as a member of the Broad Institute of MIT and Harvard.

The research team also analyzed nearly 2,000 mutations that have arisen in different SARS-CoV-2 isolates since it began infecting humans, allowing them to rate how important those mutations may be in changing the virus' ability to evade the immune system or become more infectious.

Comparative genomics

The SARS-CoV-2 genome consists of nearly 30,000 RNA bases. Scientists have identified several regions known to encode protein-coding genes, based on their similarity to protein-coding genes found in related viruses. A few other regions were suspected to encode proteins, but they had not been definitively classified as protein-coding genes.

To nail down which parts of the SARS-CoV-2 genome actually contain genes, the researchers performed a type of study known as comparative genomics, in which they compare the genomes of similar viruses. The SARS-CoV-2 virus belongs to a subgenus of viruses called Sarbecovirus, most of which infect bats. The researchers performed their analysis on SARS-CoV-2, SARS-CoV (which caused the 2003 SARS outbreak), and 42 strains of bat sarbecoviruses.

Kellis has previously developed computational techniques for doing this type of analysis, which his team has also used to compare the human genome with genomes of other mammals. The techniques are based on analyzing whether certain DNA or RNA bases are conserved between species, and comparing their patterns of evolution over time.

Using these techniques, the researchers confirmed six protein-coding genes in the SARS-CoV-2 genome in addition to the five that are well established in all coronaviruses. They also determined that the region that encodes a gene called ORF3a also encodes an additional gene, which they name ORF3c. The gene has RNA bases that overlap with ORF3a but occur in a different reading frame. This gene-within-a-gene is rare in large genomes, but common in many viruses, whose genomes are under selective pressure to stay compact. The role for this new gene, as well as several other SARS-CoV-2 genes, is not known yet.

The researchers also showed that five other regions that had been proposed as possible genes do not encode functional proteins, and they also ruled out the possibility that there are any more conserved protein-coding genes yet to be discovered.

"We analyzed the entire genome and are very confident that there are no other conserved protein-coding genes," says Irwin Jungreis, lead author of the study and a CSAIL research scientist. "Experimental studies are needed to figure out the functions of the uncharacterized genes, and by determining which ones are real, we allow other researchers to focus their attention on those genes rather than spend their time on something that doesn't even get translated into protein."

The researchers also recognized that many previous papers used not only incorrect gene sets, but sometimes also conflicting gene names. To remedy the situation, they brought together the SARS-CoV-2 community and presented a set of recommendations for naming SARS-CoV-2 genes, in a separate paper published a few weeks ago in Virology.

Fast evolution

In the new study, the researchers also analyzed more than 1,800 mutations that have arisen in SARS-CoV-2 since it was first identified. For each gene, they compared how rapidly that particular gene has evolved in the past with how much it has evolved since the current pandemic began.

They found that in most cases, genes that evolved rapidly for long periods of time before the current pandemic have continued to do so, and those that tended to evolve slowly have maintained that trend. However, the researchers also identified exceptions to these patterns, which may shed light on how the virus has evolved as it has adapted to its new human host, Kellis says.

In one example, the researchers identified a region of the nucleocapsid protein, which surrounds the viral genetic material, that had many more mutations than expected from its historical evolution patterns. This protein region is also classified as a target of human B cells. Therefore, mutations in that region may help the virus evade the human immune system, Kellis says.

"The most accelerated region in the entire genome of SARS-CoV-2 is sitting smack in the middle of this nucleocapsid protein," he says. "We speculate that those variants that don't mutate that region get recognized by the human immune system and eliminated, whereas those variants that randomly accumulate mutations in that region are in fact better able to evade the human immune system and remain in circulation."

The researchers also analyzed mutations that have arisen in variants of concern, such as the B.1.1.7 strain from England, the P.1 strain from Brazil, and the B.1.351 strain from South Africa. Many of the mutations that make those variants more dangerous are found in the spike protein, and help the virus spread faster and avoid the immune system. However, each of those variants carries other mutations as well.

"Each of those variants has more than 20 other mutations, and it's important to know which of those are likely to be doing something and which aren't," Jungreis says. "So, we used our comparative genomics evidence to get a first-pass guess at which of these are likely to be important based on which ones were in conserved positions."

This data could help other scientists focus their attention on the mutations that appear most likely to have significant effects on the virus' infectivity, the researchers say. They have made the annotated gene set and their mutation classifications available in the University of California at Santa Cruz Genome Browser for other researchers who wish to use it.

"We can now go and actually study the evolutionary context of these variants and understand how the current pandemic fits in that larger history," Kellis says. "For strains that have many mutations, we can see which of these mutations are likely to be host-specific adaptations, and which mutations are perhaps nothing to write home about."

When horseradish flea beetles feed on their host plants, they take up not only nutrients but also mustard oil glucosides, the characteristic defense compounds of horseradish and other brassicaceous plants. Using these mustard oil glucosides, the beetles turn themselves into a "mustard oil bomb" and so deter predators. A team of researchers from the Max Planck Institute for Chemical Ecology in Jena, Germany, has now been able to demonstrate how the beetle regulates the accumulation of mustard oil glucosides in its body. The beetles have special transporters in the excretory system that prevent the excretion of mustard oil glucosides. This mechanism enables the horseradish flea beetle to accumulate high amounts of the plant toxins in its body, which it uses for its own defense (Nature Communications, May 2021, doi: 10.1038/s41467-021-22982-8).

Sequestration: Well armed with the weapons of others

Many animals use chemical defense compounds to deter predators. These defense compounds are either produced by the animal itself or by symbionts of the animal, or they are acquired from the diet. The ability to acquire defense compounds from the diet is particularly widespread in insects that feed on toxic plants. One example is the horseradish flea beetle (Phyllotreta armoraciae), which can sequester mustard oil glucosides, also known as glucosinolates, in its body.

"The horseradish flea beetle belongs to an economically important group of insects, because several Phyllotreta species are crop pests. This beetle, which can accumulate vast amounts of host plant glucosinolates, regulates the levels and composition of glucosinolates in the body at least partially by excretion. This suggested that Phyllotreta armoraciae possesses very efficient transport and storage mechanisms, which we wanted to uncover," says first author Zhi-Ling Yang, explaining the goal of the new study.

The team led by Franziska Beran, head of the Sequestration and Detoxification in Insects Research Group at the Max Planck Institute, has already been able to demonstrate how the horseradish flea beetle effectively uses glucosinolates from its host plant to defend itself against a predatory ladybug (see press release, "Whether horseradish flea beetles can deter predators depends on their food plant and their life stage," March 2, 2020).

Special transporters for plant toxins in the excretory system of the beetles

Although it has long been known that horseradish flea beetles and related species can accumulate glucosinolates, how the beetle absorb and store high amounts of these substances in the body was unknown. The research team's goal, therefore, was to identify glucosinolate transporters in this insect. "The search for these transporters was literally like looking for a needle in a haystack," recalls Beran, "We found 1401 putative membrane transporters in the gut and excretory system of this beetle. Narrowing down our search to transporters that are specific for the horseradish flea beetle helped us to identify a group of glucosinolate-specific transporters."

These glucosinolate transporters are located in the excretory system, the so-called Malpighian tubules. The function of the Malpighian tubules in insects is similar to the function of the kidneys in vertebrates. The scientists determined the function of the identified transporters by using RNA interference, an approach in which the expression of a gene of interest is reduced in order to determine its function in the organism: "We silenced the expression of several transporter genes that are localized in the Malpighian tubules and found that the beetles excreted more glucosinolates than a control group of beetles with normal gene expression. Because of the higher excretion rate, the levels of defense compounds in the beetle body went down. Our study is the first to identify transporters in the Malpighian tubules that enable an insect to accumulate plant defense compounds," Yang summarizes.

With their study, the researchers show that sequestration is a complex process and much more than just the uptake of plant metabolites into the animal's body. The sequestering insect must adapt its entire physiology to use plant defense compounds for its own defense. These adaptations are driven by challenges in its environment: predators, parasites, and pathogens. "Sequestration is probably one of the most complex adaptations that herbivorous insects have evolved. It most certainly also contributes to the evolutionary success of insects that specialize in certain host plants, such as the horseradish flea beetle," says Beran.

Beran's team now wants to identify other transporters involved in sequestration. The scientists also want to know which natural enemies of the horseradish flea beetle the glucosinolates are providing protection from. Increased knowledge of how the horseradish flea beetle sequesters toxins and the effects on its ecological interactions with other organisms in the environment, will improve understanding of this pest and may lead eventually to better strategies for its control.

Researchers at the University of California San Diego have laid the groundwork for a potential new type of gene therapy using novel CRISPR-based techniques.

Working in fruit flies and human cells, research led by UC San Diego Postdoctoral Scholar Zhiqian Li in Division of Biological Sciences Professor Ethan Bier's laboratory demonstrates that new DNA repair mechanisms could be designed to address the effects of debilitating diseases and damaged cell conditions.

The scientists developed a novel genetic sensor called a "CopyCatcher," which capitalizes on CRISPR-based gene drive technology, to detect instances in which a genetic element is copied precisely from one chromosome to another throughout cells in the body of a fruit fly.

Details are explained in the journal Nature Communications.

Gene-drive technology is being developed to copy and distribute desired traits in reproductive cells of the body (sperm and eggs), which allows these traits to be spread throughout populations--potentially preventing transmission of insect-vectored diseases such as malaria and fortifying agricultural crops. For human health applications, next-generation CopyCatcher systems will measure how often such perfect copying might take place in different cells of the human body. As this system detects a very high rate of copying in fruit flies, similar success in human cells would allow scientists to make desired precise genome edits throughout the body, and particularly in cells that rely on the function of that gene for normal health.

"These studies provide a clear proof of principle for a new type of gene therapy in which one copy of a mutated gene could be repaired from a partially intact second copy of the gene," said Bier, senior author of the Nature Communications study and science director for the Tata Institute for Genetics and Society-UC San Diego. "The need for such a design occurs in genetic situations with patients with inherited genetic disorders, if their parents were carriers for two different mutations in the same gene."

Bier says the strategy of fixing a mutated gene in its normal context within the genome differs greatly from current gene therapy strategies in which a surrogate copy of a gene is placed at a different site in the genome and acts as a crude "patch."

"This method restores enough gene activity to allow the patient to limp by," said Bier. "In these cases, genes are often activated in cells where they should normally be silent and may not be activated in others where they should be."

If the high efficiency of precise in vivo gene editing detected by CopyCatchers in fruit flies could be achieved in human cells, then a variety of genetic disorders might be treated including blood diseases, diseases affecting vision or hearing and diseases targeting specific organs such as muscular dystrophy, cystic fibrosis (lung and kidney) and congenital heart defects.

"This restorative form of gene therapy would represent a major improvement over existing methods in which a functional copy of the gene is typically activated in all cells of the body but in an abnormal pattern," said Li.

Although the researchers detected highly efficient copying of genetic information in three genes active in different tissues of the fly body (eyes, epidermis and embryonic cells), this ability to copy information from one chromosome to another was less efficient in human cells (4-8% of cells) than in flies (in 30-50% of cells), the researchers found. However, in human cells where specific cuts were made to one chromosome using CRISPR, the researchers rigorously established that the other chromosome could be used to repair the damage resulting in a genetic element being precisely copied into the cut site. Moreover, measures to improve copying in flies also translated to enhanced copying in human cells suggesting that further research may increase the efficiency of human in vivo genetic repair.

CopyCatchers are designed based on the fact that cells have two copies of each chromosome. In its starting location, a CopyCatcher is rendered inactive, preventing it from producing a red fluorescent detector protein. If the CopyCatcher copies itself precisely to the other chromosome, however, then it can free itself from the constraint imposed on the original element thereby leading to cells becoming fluorescent. The fraction of red fluorescing cells tabulated throughout a tissue is a quantitative indicator of the frequency of precise CRISPR editing. Since cells of the body have been thought to be relatively recalcitrant to precise CRISPR editing, it was surprising that CopyCatchers reveal an unexpected potential of cells throughout the body to do so, such as in the eyes and in the epidermis.

In the next series of planned experiments Li and colleagues in the Bier lab will use CopyCatchers and related systems to further optimize the efficiency of corrective editing and develop model systems for human diseases to enhance the efficacy this technology for gene therapy applications.

Scientists at the Centro Nacional de Investigaciones Cardiovasculares Centro de Biología Molecular Severo Ochoa (CBM-CSIC-UAM) have discovered that the nitric oxide (NO) pathway is overactivated in the aortas of mice and patients with Marfan Syndrome and that the activity of this pathway causes the aortic aneurysms that characterize this disease.

The results of the study, published today in Nature Communications, reveal the essential role played by NO in Marfan Syndrome aortic disease and identify new therapeutic targets and markers of NO pathway activation that could be used to monitor disease status and progression.

Aortic aneurysm (AA) is a progressive dilatation and weakening of the aortic wall. AA can be harmless, but in some patients can lead to dissection (rupture) of the aorta, resulting in death.

Marfan Syndrome is a hereditary disease that affects connective tissues, which are the fibrous structures that bind and anchor all the organs and tissues in the body. Marfan Syndrome principally affects the skeleton, the eyes, the heart, and the blood vessels. A particularly common disease manifestation is thoracic aortic aneurysm and dissection (TAAD). "Aortic dissection accounts for more than 90% of deaths associated with Marfan Syndrome," explained CNIC investigator Dr. Juan Miguel Redondo, study co-director together with CBM-CSIC-UAM investigator Dr. Miguel Campanero.

Current treatments for Marfan Syndrome are aimed at reducing blood pressure on the artery wall, but do not prevent its deterioration. The only effective intervention for the aortic disease in Marfan Syndrom is surgery.

The researchers therefore recognize "the urgent need to identify new targets for the development of pharmacological treatments for TAAD in Marfan Syndrome."

The study, whose first authors are Andrea de la Fuente-Alonso and Marta Toral, reveals the essential role played by NO in Marfan Syndrome aortic disease. "We previously detected high expression of a protein with a high capacity for NO production in the aortas of Marfan Syndrome patients and an animal model of the disease, and we therefore undertook an in depth investigation of the role of NO in the associated aortic disease," explained Dr. Campanero.

"We observed that treatment of healthy mice with supra-pharmacological doses of an NO donor induced TAAD similar to that seen in Marfan mice. The NO donor treatment also reproduced the degeneration of the aortic wall, an essential step in the development of TAAD," added Dr. Redondo. "Through these experiments, we showed that elevated production of NO is necessary and sufficient for the development of TAAD in Marfan Syndrome."

Given this important role of NO in the development of TAAD, the researchers decided to focus on the enzymes soluble guanylate cyclase (sGC) and type I cGMP-dependent protein kinase (PRKG1), two NO-regulated proteins. "Our analysis detected elevated activities of both sGC and PRKG1 in samples from mice and patients with Marfan Syndrome," said Dr. Redondo.

"We were able to completely reverse the aortic disease in Marfan mice by treating them with inhibitors of these two proteins or by genetically silencing the expression of Prkg1, demonstrating that the NO-sGC-PRKG1 pathway mediates the development of TAAD in Marfan Syndrome," added Dr. Campanero.

Given the need for new pharmacological treatments for Mafan Syndrome aortic disease, "the results of this study open the way to the use of sGC and PRKG1 inhibitors in preclinical and clinical trials for this syndrome and possibly other aortic diseases," said Dr. Redondo.

The research team also explored possible "footprints" left by high NO levels in the blood. "Working with the CNIC Proteomics Unit and clinical groups at Vall D´Hebron, Puerta de Hierro, Marqués de Valdecilla, and Ghent University hospitals, we found that the high NO levels in Marfan Syndrome lead to increases in protein nitration and cGMP in the blood of mice and patients with this disease," said Dr. Campanero.

"This discovery has important implications for patients with this syndrome, because these molecules could be used as biomarkers for disease monitoring, and we are now studying their potential as prognostic indicators," explained Dr. Redondo.

The researcher conclude that their results are therefore "good news."

A team of researchers, affiliated with UNIST has recently introduced a new class of magnetic materials for spin caloritronics. Published in the February 2021 issue of Nature Communications, the demonstrated STE applications of a new class of magnets will pave the way for versatile recycling of ubiquitous waste heat. This breakthrough has been led by Professor Jung-Woo Yoo and his research team in the Department of Materials Science and Engineering at UNIST.

Spin thermoelectrics is an emerging thermoelectric technology that offers energy harvesting from waste heat. This has attracted substantial research interest with the potential advantages of scalability and energy conversion efficiency, thanks to orthogonal paths for heat and charge flow. However, magnetic insulators previously used for spin thermoelectrics pose challenges for scale-up due to high-temperature processing and difficulty in large-area deposition, noted the research team.

In this study, the research team introduced a molecule-based magnet, Cr-PBA, as an alternative magnetic insulator for the magnon-mediated thermal-to-electrical energy conversion. According to the research team, the studied molecular magnetic film has several advantageous characteristics over inorganic magnetic insulators in terms of spin TE (STE) applications. Indeed, it entails versatile synthetic routes amenable for large area deposition at room temperature, in addition to weak spin-lattice interaction and low thermal conductivity.

"The growth of Cr-PBA was done at room temperature by employing the electrochemical deposition (ECD) method, which could offer scalable production of thin films," noted the research team. "This deposition technique can be easily adapted for the large area and mass production of thin-film, which can boast an important merit of STE, that is, large-area scalability."

According to the research team, various other methodologies, such as painting and printing, can be also utilized for developing the PBA film. They also noted that the generation and transfer of magnons are essential processes for STE energy harvesting, as well as magnon information technology. Experimental results also indicated that the excitations of low-energy magnons in this class of magnet were much stronger than those in the typical inorganic magnets. Besides, the ferromagnetic resonance studies exhibited an extremely low Gilbert damping constant, which indicates a low loss of heat-generated magnons. Furthermore, the determined low thermal conductivity in the studied molecule-based magnetic film is an accessory benefit for STE energy harvesting because it assists in maintaining a higher temperature gradient across the film, noted the research team.

"Our study shows excitations and transfers of magnons in this hybrid magnet are very efficient, suggesting molecule-based magnets, along with their synthetic versatility, could be outstanding alternatives for various applications of spin caloritronics as well as magnon spintronics," said the research team.

The findings of this research have been published in the February 2021 issue of Nature Communications. This study has been jointly participated by Professor Joonki Suh (Department of Materials Science and Engineering, UNIST), Professor Byoung-Chul Min (Korea Institute of Science and Technology, KIST), and two graduates from UNIST's Department of Materials Science and Engineering - Dr. Jungmin Park (KBSI) and Professor Mi-Jin Jin (Dankook University).

LUND, Sweden--May 11, 2021--PolarCool AB (publ), a Swedish medical device company focusing on treatment of sports-related traumatic brain injury (TBI) and whiplash, today announced that it has submitted a 510(k) pre-market notification to the U.S. Food and Drug Administration (FDA) for the PolarCap® System.

This submission follows publication of statistically significant clinical results in the scientific journal Concussion, showing clear benefit for use of the PolarCap® System in the treatment of concussions among players of 15 elite Swedish Ice-Hockey teams in the Swedish Hockey Leagues (SHL).

The incidence of sports-related concussions is a significant national health concern in Sweden, as it is here in the U.S., and there is growing evidence that repetitive traumatic brain injury can cause long-term changes in brain structure and function. This is of particular concern in the field of contact sports, such as ice hockey, where available treatment options are limited.

"With this important FDA submission, we are paving the way for the first-ever sports-related TBI treatment model," said Martin Waleij, PolarCool Chairman of the Board. "Supported by robust clinical evidence enabling players to safely return to play much earlier, our 510(k) submission is the first step in the FDA review process. We look forward to this review and are confident that speedy clearance for the PolarCap® System is on the horizon."

The study, led by investigators from Lund University at Skåne University Hospital in Lund, Sweden, Luleå University of Technology in Luleå, and BrainCool AB, represents the largest study population focused on sports-related concussion treatment in Sweden or the U.S., and shows statistical benefits of therapeutic cooling using the PolarCap® System head and neck cooling technology.

"Publication of these study results in the journal Concussion marks a significant milestone for sports medicine around the globe," said Erik Andersson, Chief Executive Officer of PolarCool, maker of the PolarCap® System that was used in the Lund study. "We are eager to proceed with larger studies and to partner with academic medical centers and professional sports organizations to further validate the benefits of this medical cooling technology--with the ultimate goal of improving both short- and long-term safety for players of all contact sports."

The Swedish Hockey League, the players organization SICO and PolarCool are actively collaborating to improve player safety. Two PolarCap® Systems are available at all games and the league is working to establish a standardized acute treatment method concussion injuries.

"It is very positive that we can constitute that the introduction of the Polar Cap has meant fewer long time absences among players that were treated by cooling directly after a concussion, with this treatment we have another tool to use (against head injuries)," said SHL Sports Director & Vice CEO Johan Hemlin in a recent SHL press release.

Fifteen teams from elite ice-hockey leagues for males in Sweden were given the option to participate in the intervention group (receiving selective head-neck cooling after a sports-related concussion) or the control group (standard sports-related concussion management). Selective head-neck cooling was initiated at a mean of 12.3 ± 9.2 min after the concussion in 29 players, and 52 SRC controls received standard management. Results showed significant benefits of cooling in treating concussions with a median time to return to play for the players who underwent cooling of 7 days, versus 12 days for those who did not. The study also shows promising reduction in the proportion of long-term absence, which can be as long as three weeks or more, among treated players.

In order for metal nanomaterials to deliver on their promise to energy and electronics, they need to shape up -- literally.

To deliver reliable mechanical and electric properties, nanomaterials must have consistent, predictable shapes and surfaces, as well as scalable production techniques. UC Riverside engineers are solving this problem by vaporizing metals within a magnetic field to direct the reassembly of metal atoms into predictable shapes. The research is published in The Journal of Physical Chemistry Letters.

Nanomaterials, which are made of particles measuring 1-100 nanometers, are typically created within a liquid matrix, which is expensive for bulk production applications, and in many cases cannot make pure metals, such as aluminum or magnesium. More economical production techniquess typically involve vapor phase approaches to create a cloud of particles condensing from the vapor. These suffer from a lack of control.

Reza Abbaschian, a distinguished professor of mechanical engineering; and Michael Zachariah, a distinguished professor of chemical and environmental engineering at UC Riverside's Marlan and Rosemary Bourns College of Engineering; joined forces to create nanomaterials from iron, copper, and nickel in a gas phase. They placed solid metal within a powerful electromagnetic levitation coil to heat the metal beyond its melting point, vaporizing it. The metal droplets levitated in the gas within the coil and moved in directions determined by their inherent reactions to magnetic forces. When the droplets bonded, they did so in an orderly fashion that the researchers learned they could predict based on the type of metal and how and where they applied the magnetic fields.

Iron and nickel nanoparticles formed string-like aggregates while copper nanoparticles formed globular clusters. When deposited on a carbon film, iron and nickel aggregates gave the film a porous surface, while carbon aggregates gave it a more compact, solid surface. The qualities of the materials on the carbon film mirrored at larger scale the properties of each type of nanoparticle.

Because the field can be thought of as an "add-on," this approach could be applied to any vapor-phase nanoparticle generation source where the structure is important, such as fillers used in polymer composites for magnetic shielding, or to improve electrical or mechanical properties.

"This 'field directed' approach enables one to manipulate the assembly process and change the architecture of the resulting particles from high fractal dimension objects to lower dimension string-like structures. The field strength can be used to manipulate the extent of this arrangement," Zachariah said.

The tightly defined ratios of metals in MOFs makes them ideal starting materials for novel catalyst creation.

Heating bimetallic metal organic frameworks (MOFs) until their porous structure collapses into nanoparticles can be a highly effective way to make catalysts. This novel approach to catalyst design has now been used by KAUST and Spanish researchers to make a robust catalyst that converts carbon dioxide (CO2) into carbon monoxide (CO) gas with unprecedented selectivity.

The benefit of this method pioneered at KAUST is that it can generate mixed metal catalytic nanoparticles that have proven challenging or impossible to make by conventional means.

Capturing CO2 emissions and catalytically converting the greenhouse gas into CO, a valuable chemical feedstock, is one option for reducing greenhouse gases associated with climate change. Precious metals can catalyze this reaction, but they are costly and supplies are limited, says Samy Ould-Chikh, a research engineer in KAUST.

"Iron oxide catalysts are an inexpensive alternative," Ould-Chikh says. "However, in the presence of CO, the iron is carburized forming iron carbide, which leads to by-product formation and catalyst deactivation."

Adding titanium to the catalyst particles could stabilize iron oxide against carburization. Chemical incompatibilities between iron and titanium precursors, however, had made it impossible to synthesize nanoparticles incorporating a homogenous mixture of the two metals in the necessary ratio. To overcome this limitation, the team turned to MOFs, porous materials made from metal ions connected together by carbon-based linkers.

"The use of MOFs allows us to perfectly control the iron-titanium ratio on the parent MOF," says research engineer Adrian Ramirez Galilea. Heating decomposes the organic part of the MOF, leaving the two metals behind, homogenously mixed in the desired ratio and in neat octahedral nanoparticles that mirror the structure of the parent MOF.

The nanoparticles converted CO2 to CO with 100 percent selectivity, with no sign of deactivation after several days of use. "Our initial calculations suggested that nanoparticles with such atomic ratios should be able to do the job; however, the results far exceeded our original expectations," Gascon says.

As well as continuing to explore the properties and reactivity of the iron-titanium nanocatalyst, the team is examining other metal catalyst systems made from MOFs in the same way. "The use of MOFs opens the way to synthesize new catalysts that were not possible to make using conventional approaches," Ramirez Galilea says.

"We are looking at different metal combinations for applications ranging from traditional thermal catalysis to photo and photothermal catalysis," adds Jorge Gascon, who led the research. "This paper is just the tip of the iceberg."

Published today in Nature Communications, the team from the Peter Doherty Institute for Infection and Immunity (Doherty Institute), Alfred Health and Monash University sought to understand which patients would recover quickly from influenza and which would become severely ill.

The four-year project took samples from patients hospitalised with influenza at up to five time points during their hospital stay, and 30 days after discharge. They analysed the breadth of the immune response, enabling them to describe the specific roles of several different types of immune cells, including killer and helper T cells, B cells and innate cells.

University of Melbourne Dr Oanh Nguyen, Research Fellow at the Doherty Institute, said two significant findings of the research include understanding the biomarkers that drive recovery and identifying four specific cytokines that cause serious inflammation during influenza virus infection.

"Cytokines are key molecules needed for a robust immune response. However, too much of these cytokines can result in inflammation and in the case of influenza, much more serious infection," Dr Nguyen said.

"We found four specific types of cytokines that would cause severe inflammation, and this provides clinicians the ability to predict whether a patient will become really sick with influenza."

The team also consistently saw large populations of immune cells called T-follicular helper cells, working in parallel with antibody-secreting cells, in patients at around three days prior to their recovery.

"These findings are the first to report the importance of T-follicular helper cells during acute influenza virus infection, following previous discoveries from our work and others on the key role of these immune cells after influenza vaccination. Signs of these cells could be used as a biomarker for recovery from influenza," Dr Nguyen said.

Professor Allen Cheng, Director of Infection Prevention and Healthcare Epidemiology at Alfred Health and Professor of Infectious Diseases Epidemiology at Monash University, said this had been a great collaboration between clinicians and world-renowned immunologists, and a good example of 'bedside to bench' science.

"The COVID-19 pandemic, and before this, the swine flu pandemic, has highlighted the importance of improving our understanding of respiratory viral infections to improve the identification of patients at risk of severe outcomes and potentially future treatments," Professor Cheng said.

University of Melbourne Professor Katherine Kedzierska, Laboratory Head at the Doherty Institute and world-leading influenza immunologist, said this research laid the groundwork for her team's understanding of how the immune system responds to COVID-19.

"Because of our years of experience, experimental set up, knowledge and collaborations with Alfred Health for this and other influenza studies, we had the speed and agility to apply our work to immune studies of COVID-19," Professor Kedzierska said.

"This influenza study was the blueprint for our COVID-19 research."

A group of researchers from Osaka University developed a quadruped robot platform that can reproduce the neuromuscular dynamics of animals (Figure 1), discovering that a steady gait and experimental behaviors of walking cats emerged from the reflex circuit in walking experiments on this robot. Their research results were published in Frontiers in Neurorobotics.

It was thought that a steady gait in animals is generated by complex nerve systems in the brain and spinal marrow; however, recent research shows that a steady gait is produced by the reflex circuit alone. Scientists discovered a candidate of reflex circuit to generate the steady walking motion of cats, investigating locomotion mechanisms of cats by reproducing their motor control using robots and computer simulations.

Since experiments using animals are strictly controlled and restricted in terms of animal protection, it is difficult to study animal locomotion. So, it is still unknown how nerve systems discovered in prior research are integrated (i.e., how reflex circuits responsible for animal locomotion are integrated) in the animal body.

Toyoaki Tanikawa and his supervisors assistant professor Yoichi Masuda and Prof Masato Ishikawa developed a four-legged robot that enables the reproduction of motor control of animals using computers. This quadruped robot, which comprises highly back-drivable legs to reproduce the flexibility of animals and torque-controllable motors, can reproduce muscle characteristics of animals. Thus, it is possible to conduct various experiments using this robot instead of the animals themselves.

By searching for the reflex circuit that contributes to the generation of a steady walking in cats through robotic experiments, the researchers found a simple reflex circuit that could produce leg trajectories and a steady gait pattern, which they named "reciprocal excitatory reflex between hip and knee extensors."

In this study, the researchers found that:

- The robot generated steady walking motions by simply reproducing the reciprocal circuit in each leg of the robot.

- The robot's gait became unstable when the reciprocal circuit was cut off.

- When the mutual excitatory circuit was stimulated, the circuit produced a phenomenon called 'prolongation of the stance phase.' This result suggests that this circuit is an important component responsible for walking in cats.

This group's research results will benefit both the biology and robotics fields. In addition to bringing new knowledge to biology, if robotic animals could serve as a replacement for real animals in the future, it will give more scientists the chance to study the mechanisms of animal locomotion under various experimental conditions. Approximating a robot's structure to that of an animal will lead to the development of fundamental technologies for making robots that move and maneuver as effectively as animals.

Co-author Yoichi Masuda says, "Gaining knowledge about animals without using experimental animals is also significant for the humans that live with them. Further combination of robotics and biology through the creation of robots that mimic the structures of animals and their locomotion could become the first step towards understanding the principles underlying the behaviors of animals and humans."

Dr. HAN Fangpu's group from the Institute of Genetics and Developmental Biology of the Chinese Academy of Sciences reports the identification and functional study of the maize Knl1 gene in an article published online in PNAS. The gene is a major component of the KMN network that links centromeric DNA and the plus-ends of spindle microtubules. It also plays an important role in kinetochore protein recruitment.

The kinetochore complex that assembles on the centromeres mediates the proper partitioning of chromosomes to daughter cells during the cell cycle. However, kinetochore proteins undergo frequent mutations and coevolve with their interaction partners, leading to great diversity in kinetochore composition in eukaryotes.

Functional studies of kinetochore composition in plant model organisms are necessary to shed light on the evolutionary role of this intriguing component, and thus improve our collective understanding of the fundamentals of genetics.

The Knl1 is the constitutive component of the central kinetochore protein in plants. The researchers showed it was subcellularly localized and colocalized with other kinetochore components during interphase, mitosis, and meiosis. The functional importance of Knl1 in plants was demonstrated via characterization of the knl1 mutant.

The researchers revealed that Knl1 plays an essential role in chromosomal congregation and segregation during mitosis in maize, and deficiencies in Knl1 are linked to defective kernel development.

In addition, the researchers shed light on how spindle assembly checkpoint (SAC) proteins interact with kinetochores in plants.

In the present study, the scientists discovered that maize Knl1 interacts with BMF1/2 via a 145-aa region that does not contain well-known MELT repeats described in yeast and mammalian cells. This region displayed high divergence between monocots and eudicots, implying a rapid evolution of kinetochore proteins.

In fact, despite being evolutionarily conserved in function, KNL1 displayed low overall sequence similarity between species. The intricate species-dependent presence/absence of conserved sequence regions led the authors to propose an interaction network model of plant Knl1 with spindle assembly checkpoint signaling.

Understanding the evolutionary and functional importance of these fundamental individual components of the kinetochore complex may in turn improve the efficacy of downstream manipulations, such as the generation of haploid inducer lines for medical applications.

Quantum mechanics can be used to create more stable and more easily produced organic solar cells. These are the findings of new research from the University of Gothenburg.

Organic solar cells have many advantages compared with traditional silicon-based solar cells. They can be manufactured cheaply at a large scale using printing presses, and they are light, malleable and flexible. The problem is that today's organic solar cells are not as stable and effective as silicon-based solar cells. In a new study, a research group has taken on this problem and found a way that can lead to more cost-effective solar cell technology.

"There are excellent opportunities for utilising quantum efficiencies to change different chemical and material characteristics. In this study, we present a method that makes it possible to increase diffusion of energy in organic materials. This allows us to create organic solar cells with simpler structure," says Karl Börjesson, professor of physical chemistry at the University of Gothenburg and the main author of the study.

Basically, this is about making sure the energy in the solar cells is effectively transferred to the right place. Organic solar cells contain two materials, and the absorbed energy from the sun needs to be diffused - to travel - to the interface between the materials. But diffusion is an ineffective process since the energy travels slowly and risks being lost as heat before it reaches this interface. The solution has been to blend the two materials in solar cells to reduce the distance and so the energy reaches the interface more quickly. Unfortunately, this also leads to the solar cells not being in thermodynamic equilibrium, making design less durable over time than it could be.

The researchers show that the new method allows the energy to be transferred over a longer distance, which means that the complicated blending of materials in solar cells can be avoided. The key behind the method is quantum effects, where light and material are combined into hybrid light-matter states.

"When we couple light and matter strongly, the energy is spread out over the entire system. If the system - as in this case - consists of multiple materials, the energy can be channelled to the interface. We show in the study that the energy travels faster to the interfaces when the materials are strongly coupled. This means that the materials in solar cells do not need to be physically blended since they are blended at the quantum level. This also leads to the system being in thermodynamic equilibrium," says Karl Börjesson.

According to Börjesson, the discovery can influence how organic solar cells are manufactured, since it becomes possible to increase their durability while the solar cells can be made with a simple layered structure. He also notes that the research is really an outgrowth of a concept already found in nature.

"Nature uses strong coupling between molecules to effectively transfer solar energy in photosynthesis. In principle, we have shown that the same basic concept can be applied to organic solar cells."

The Sturtian Snowball Earth glaciation (717~660 million years ago) represents the most severe icehouse climate in Earth's history. Geological evidence indicates that, during this glaciation, ice sheets extended to low latitudes, and model simulations suggest global frozen ocean as well as a prolonged shut-down of the hydrological cycles. The Snowball Earth hypothesis poses that the Sturtian global glaciation is directly triggered by intense continental weathering that scavenges atmospheric CO2, while the global frozen condition is terminated by extremely high atmospheric CO2 level (~350 times of present atmospheric level), which is accumulated by synglacial volcanic eruptions for tens of million years. The deglaciation is an abrupt process, lasting for hundreds to thousands of years, and the sharp transition to a hothouse condition is accompanied with extremely high weathering rate and followed by the perturbations of marine sulfur cycle.

Unusual perturbation of the marine sulfur cycle after the Sturtian glaciation is hinted at worldwide precipitation of isotopically superheavy sedimentary pyrite (FeS2) in the interglacial sediments. In the classic sulfur cycle framework, pyrite, the predominant sulfide mineral in sediments is always depleted in 34S as compared with seawater sulfate, because sulfate reducing microbes preferentially utilize 32S enriched sulfate to generate sulfide. However, a compilation of pyrite sulfur isotope data shows extremely high values (up to +70‰, obviously higher than coeval seawater sulfate values) in the aftermath of the Sturtian glaciation. Although superheavy pyrite is also reported in other geological periods, the Cryogenian interglacial interval after the Sturtian glaciation represents the only time with superheavy pyrite formation in a global scale for ~10 million years. The traditional theoretical sulfur cycle model does not satisfactorily address the long-term and global occurrence of superheavy pyrite in the Cryogenian interglacial interval.

Dr. Lang and his colleagues proposed a novel sulfur cycle model that incorporates volatile organosulfur compounds (VOSC) to interpret the global occurrence of superheavy pyrite after the Sturtian glaciation. They carried out detailed petrographic observations and paired pyrite content and sulfur isotope data of superheavy pyrite from the Cryogenian interglacial deposits of the Datangpo Formation in South China. Both the petrographic and geochemical data from South China indicate that the Cryogenian interglacial oceans were mainly sulfidic (anoxic and H2S enriched). In sulfidic conditions, volatile organosulfur compounds (VOSC) could be pervasively generated via sulfide methylation. Because the VOSC always has a lower sulfur isotope value relative to seawater sulfate, continuous VOSC emission would elevate sulfur isotope of residual sulfur pool of sulfidic seawater, resulting a vertical isotopic gradient of seawater and the precipitation of superheavy pyrite near/at seafloor.

Their findings demonstrate that superheavy pyrite formation requires both high microbial sulfate reduction and VOSC formation rates so as to maintain such unusual perturbation of marine sulfur cycle. As organic matter and sulfate are prerequisites for these reaction, ~10 million-year occurrences of superheavy pyrite may suggest continuous high primary productivity and intense continental chemical weathering after the Sturtian glaciation. These findings improve our understanding of the Snowball Earth event and ancient marine sulfur cycle.

A new study from the University of Surrey has revealed 'real world' factors that influence people's interest in adopting a dietary pattern called time-restricted feeding.

According to NHS England, 67 per cent of men and 60 per cent of women in the UK are overweight or obese - with more than 11,000 yearly hospital admissions directly attributable to obesity.

Time-restricted feeding, which is a type of intermittent fasting, is the practice of restricting the time between the first and last food intake each day - therefore prolonging the daily fasting period.

In a study published by the journal Appetite researchers from Surrey surveyed 608 people to determine the factors that would help or hinder them in adopting a time-restricted feeding routine.

The study found that the majority of respondents had a feeding window of between 10 to 14 hours on workdays and free days. More than 400 respondents believed they could reduce their feeding window by three hours if there were clear health benefits associated with the practice.

The study also revealed that the percentage of participants' likelihood of taking up intermittent fasting declined as the duration of the time restriction increased - with 85 per cent believing they could reduce their window by up to 0.5 hours, to 20 per cent believing they could sustain a reduction of four or more hours.

The respondents also pinpointed time availability (69 per cent), ease of following (62 per cent), and work commitments (54 per cent) as key factors that might influence their decision to adopt intermittent fasting.

Jonathan Johnston, senior author of the study and Professor of Chronobiology and Integrative Physiology at the University of Surrey, said:

"Time-restricted feeding has the potential to become an extremely effective tool in the fight against the obesity epidemic facing many countries. However, the study clearly shows that the ability of people to restrict their daily feeding window is dependent on their individual lifestyles."