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A University of Colorado Boulder astrophysicist is searching the light coming from a distant, and extremely powerful celestial object, for what may be the most elusive substance in the universe: dark matter.

In two recent studies, Jeremy Darling, a professor in the Department of Astrophysical and Planetary Sciences, has taken a deep look at PSR J1745-2900. This body is a magnetar, or a type of collapsed star that generates an incredibly strong magnetic field.

"It's the best natural dark matter detector we know about," said Darling, also of the Center for Astrophysics and Space Astronomy (CASA) at CU Boulder.

He explained that dark matter is a sort of cosmic glue--an as-of-yet unidentified particle that makes up roughly 27% of the mass of the universe and helps to bind together galaxies like our own Milky Way. To date, scientists have mostly led the hunt for this invisible matter using laboratory equipment.

Darling has taken a different approach in his latest research: Drawing on telescope data, he's peering at PSR J1745-2900 to see if he can detect the faint signals of one candidate for dark matter--a particle called the axion--transforming into light. So far, the scientist's search has come up empty. But his results could help physicists working in labs around the world to narrow down their own hunts for the axion.

The new studies are also a reminder that researchers can still look to the skies to solve some of the toughest questions in science, Darling said. He published his first round of results this month in the Astrophysical Journal Letters and Physical Review Letters.

"In astrophysics, we find all of these interesting problems like dark matter and dark energy, then we step back and let physicists solve them," he said. "It's a shame."

Natural experiment

Darling wants to change that--in this case, with a little help from PSR J1745-2900.

This magnetar orbits the supermassive black hole at the center of the Milky Way Galaxy from a distance of less than a light-year away. And it's a force of nature: PSR J1745-2900 generates a magnetic field that is roughly a billion times more powerful than the most powerful magnet on Earth.

"Magnetars have all of the magnetic field that a star has, but it's been crunched down into an area about 20 kilometers across," Darling said.

And it's where Darling has gone fishing for dark matter.

He explained that scientists have yet to locate a single axion, a theoretical particle first proposed in the 1970s. Physicists, however, predict that these ephemeral bits of matter may have been created in monumental numbers during the early life of the universe--and in large enough quantities to explain the cosmos' extra mass from dark matter. According to theory, axions are billions or even trillions of times lighter than electrons and would interact only rarely with their surroundings.

That makes them almost impossible to observe, with one big exception: If an axion passes through a strong magnetic field, it can transform into light that researchers could, theoretically, detect.

Scientists, including a team at JILA on the CU Boulder campus, have used lab-generated magnetic fields to try to capture that transition in action. Darling and other scientists had a different idea: Why not try the same search but on a much bigger scale?

"Magnetars are the most magnetic objects we know of in the universe," he said. "There's no way we could get close to that strength in the lab."

Narrowing in

To make use of that natural magnetic field, Darling drew on observations of PSR J1745-2900 taken by the Karl G. Jansky Very Large Array, an observatory in New Mexico. If the magnetar was, indeed, transforming axions into light, that metamorphosis might show up in the radiation emerging from the collapsed star.

The effort is a bit like looking for a single needle in a really, really big haystack. Darling said that while theorists have put limits on how heavy axions might be, these particles could still have a wide range of possible masses. Each of those masses, in turn, would produce light with a specific wavelength, almost like a fingerprint left behind by dark matter.

Darling hasn't yet spotted any of those distinct wavelengths in the light coming from the magnetar. But he has been able to use the observations to probe the possible existence of axions across the widest range of masses yet--not bad for his first attempt. He added that such surveys can complement the work happening in Earth-based experiments.

Konrad Lehnert agreed. He's part of an experiment led by Yale University--called, not surprisingly, HAYSTAC--that is seeking out axions using magnetic fields created in labs across the country.

Lehnert explained that astrophysical studies like Darling's could act as a sort of scout in the hunt for axions--identifying interesting signals in the light of magnetars, which laboratory researchers could then dig into with much greater precision.

"These well-controlled experiments would be able to sort out which of the astrophysical signals might have a dark matter origin," said Lehnert, a fellow at JILA, a joint research institute between CU Boulder and the National Institute of Standards and Technology (NIST).

Darling plans to continue his own search, which means looking even closer at the magnetar at the center of our galaxy: "We need to fill in those gaps and go even deeper."

Worldwide, otherwise healthy adolescents and young people without underlying conditions are sometimes severely affected by COVID-19, with the viral infection in the worst cases quickly becoming life-threatening. But why is this happening?

A world-wide consortium of researchers is determined to investigate this - and they have now made so much progress that Science has just published two scientific articles describing some of their results.

Professor Trine Mogensen from the Department of Biomedicine at Aarhus University is co-author on the two research articles in Science. She conducts research into rare immunodeficiencies that lead to increased susceptibility to viral infections and, together with her research group, participates in the steering committee of the research consortium Covid human genetic effort (covidhge) as the only Danish representativ.

She explains that in the vast majority of people, infection with the COVID-19 causing coronavirus leads to an anti-viral response in which interferon plays a crucial role. Interferon is an importantimmune signaling hormone that slows the division of the virus and prevents it from penetrating the surrounding cells. In the event of a viral infection, the body normally quickly begins producing interferon, and the virus can be brought under control withing a few hours. In popular terms, interferon is our first safeguard against an infection.

"However, if there are defects in the interferon signalling pathways, there is nothing to inhibit the virus dividing, and while the coronavirus usually remains in the cells in the throat, it can in this case also infect other parts of the body such as the lungs, kidneys and perhaps even the brain," explains Trine Mogensen, who also is Medical Specialist at the Department of Infectious Diseases, Aarhus University Hospital, Denmark

Genetic and immunological analyses of blood samples from 650 patients from all over the world with severe COVID-19 show that some of these patients have an inherited immunodeficiency which leads to the anti-viral interferon either not being produced or not working on the body's cells. Blood samples from 1,226 healthy individuals have functioned as a control group - with all of the samples being taken prior to the COVID-19 pandemic.

The researchers have obtained consent to collect blood samples and carry out a genetic analysis from hospitalized and severely ill COVID-19 patients. From the blood samples, the researchers have purified immune cells from the 650 patients and subsequently infected these immune cells with coronavirus, which enabled them to ascertain that the immune system was not properly activated. In addition, a genetic sequencing of DNA from the 650 patients has been carried out, with some of this work being carried out at Aarhus University Hospital.

"Our DNA consists of approximately 20,000 genes, and we have found defects in thirteen different genes. This means that the proteins which the genes encode become defective and therefore cannot perform their role in the immune system. We're already aware of some of these genetic defects from patients affected by severe influenza, but some are new and specific to COVID-19," says Trine Mogensen.

The next task for the international research consortium is to translate - i.e. transfer - the basic immunological findings to the treatment of patients, and the first clinical trials are on the way. Medical doctors will be able to measure whether the patients have autoantibodies in their blood as these are relatively easy to measure, and if they are, they can be filtered from the blood. It will also be possible to screen for the thirteen critical genes identified and in this way have the ability to identify particularly vulnerable individuals. This group will then be able to receive preventative medical treatment and a vaccine once this is available.

"The goal is to prevent the very severe cases of COVID-19 with high mortality rates," summarizes Trine Mogensen, who is optimistic and hopes that the clinical trials will demonstrate positive results - perhaps already within a year.

She does not only base her optimism on the unique international collaboration which exists in the COVID Human Genetic Effort, as the international research consortium is named.

"I've never experienced anything like it before in my field of immunology and infectious diseases. We share knowledge and work together in a very altruistic spirit," she adds. The consortium comprises more than 250 researchers under the overall leadership of Professor Jean-Laurent Casanova from The Rockefeller University in the United States - with the professor also serving as an Honorary Skou professor at Aarhus University since 2019.

Earth could have lost anywhere between ten and 60 per cent of its atmosphere in the collision that is thought to have formed the Moon.

New research led by Durham University, UK, shows how the extent of atmospheric loss depends upon the type of giant impact with the Earth.

Researchers ran more than 300 supercomputer simulations to study the consequences that different huge collisions have on rocky planets with thin atmospheres.

Their findings have led to the development of a new way to predict the atmospheric loss from any collision across a wide range of rocky planet impacts that could be used by scientists who are investigating the Moon's origins or other giant impacts.

They also found that slow giant impacts between young planets and massive objects could add significant atmosphere to a planet if the impactor also has a lot of atmosphere.

The findings are published in the Astrophysical Journal Letters.

The Moon is believed to have formed about 4.5 billion years ago following a collision between the early Earth and a giant impactor possibly the size of Mars.

Research lead author Dr Jacob Kegerreis, in the Institute for Computational Cosmology, Durham University, said: "The puzzle about how the Moon formed and the other consequences of a giant collision with the early Earth is something that scientists are working hard to unravel.

"We ran hundreds of different scenarios for many different colliding planets, showing the varying impacts and effects on a planet's atmosphere depending upon a number of factors such as the angle, speed of impact or the sizes of the planets.

"While these computer simulations don't directly tell us how the Moon came to be, the effects on the Earth's atmosphere could be used to narrow down the different ways it might have been formed and lead us closer to understanding the origin of our nearest celestial neighbour."

Earlier this year, an initial study by Durham University reported that giant impacts which dominate the late stages of planet formation can have a wide range of consequences for young planets and their atmospheres.

That study examined the ways that thin atmospheres could be removed by objects impacting at different angles and speeds.

The researchers' latest paper looks at the effects across a much wider variety of impacts adjusting for size, mass, speed and angle of the impacting object. They also changed the density of the impactor and if it was made of iron, rock or both.

The simulations revealed the different outcomes when one or more of these variables are changed, leading to atmospheric loss or gain, or sometimes the complete obliteration of the impacted planet.

The research team also included scientists at the BAERI/NASA Ames Research Centre and the University of Washington, USA, and the University of Glasgow, UK.

Co-author Dr Luis Teodoro, in the School of Physics and Astronomy, University of Glasgow, and the BAERI/NASA Ames Research Centre, said: "This major suite of planetary simulations also sheds light on the role of impacts in the evolution earth like exoplanets."

In a paper published in Molecular Frontiers Journal, researchers from Cambridge, Massachusetts have discovered a more effective way of eliminating airborne particles from airways using nasal calcium-rich salts called FEND, which have potential applications in the fight against Covid-19.

Sensory Cloud, creators of FEND and a Boston-based technology startup that designs solutions to problems of human wellbeing and healthcare through pioneering discoveries at the frontiers of olfaction and respiratory biology, studied the effectiveness of nasal administration of physiological salts at reducing airborne particles from exhaled breath including the sub-micron aerosolized particles that are ineffectively filtered by cloth face masks. Lead authors of the paper are Dr. David Edwards (John A. Paulson School of Engineering, Harvard University) and Dr. Robert Langer (Department of Chemical Engineering, MIT),

Ninety-two men, women and children were observed in three separate studies showcasing the use of FEND in various situations: in the workplace, quarantining at home, and in comparison to cloth face masks. The studies assessed how FEND, a drug-free calcium-enriched nasal salt, would interact with airway lining mucus to cleanse the airways of bioaerosols. The results showed a reduction of exhaled aerosol particles of up to 99%, with an overall reduction of exhaled particles in the largest cohort of human subjects (76 workers) of around 75%.

"The findings, which build on an earlier study this summer, suggest that we can provide what is, in effect, a nasal filter to protect at-risk populations from viral carrying aerosols," said Sensory Cloud founder Edwards. "Access to a new hygiene protocol for reducing the spread of these smallest particles, which can otherwise be dispersed into indoor air and enter deep into our lungs, can be an important intervention as we head back to work and school, as winter approaches, and as troubling data about rates of infection continue to emerge."

In the first study, 76 COVID-negative volunteers (including 74 workers and two children) from No Evil Foods in Asheville, NC, ages 15-66, were recruited. Prior to the nasal hygiene intervention, exhaled aerosol from the 76 workers followed a classical "super spreading" distribution, with 20% of participants accounting for 80% of the overall exhaled aerosol. Within the "super spreader" group, half of the individuals (or the top 10% of exhaled particle producers) were found to be responsible for 80% of the super spreader production - or 64% of the overall production. The 76 volunteers then received FEND, a drug-free nasal saline hygiene formulation comprised of calcium chloride and sodium chloride in distilled water and administered via a mist of 9-10 micron diameter droplets by a hand-held mister. The FEND intervention suppressed 84% of exhaled aerosols for the highest producing super-spreaders and 78% overall for all super-spreaders. Overall, exhaled aerosols among all participants did not change after a nasal saline control intervention, Simply Saline from Arm & Hammer, a nasal spray of isotonic sodium chloride.

"Health and safety is a huge priority at No Evil Foods," said Sadrah Schadel, co-founder and Chief Creative Officer of No Evil Foods. "Having the chance to actually see FEND work, clearing particles from our exhaled breath, was an overwhelmingly positive experience for our team."

The second study evaluated the exhaled aerosols of a volunteer family of four in quarantine with one COVID-positive mother. The study followed the family for five days starting at eight days post-symptoms for the mother. The mother's exhaled aerosols showed extremely high output on days eight and nine. After receiving the FEND intervention, her levels decreased to average baseline levels for a COVID-negative patient, with suppression lasting several hours following the intervention.

The final study compared the use of FEND to surgical mask use in 12 children and adults. The surgical masks reduced overall exhaled particles by around 34% for the group, while FEND reduced overall exhaled particles by 46% -- with one individual showing no statistical difference on using the mask or FEND, possibly for failure to administer properly. Excluding the outlier subject, exhaled aerosols were reduced by 59% when wearing masks and 87% following the FEND intervention. The differential benefit of FEND was due to its more effective reduction in sub-micron aerosol particles, given that most exhaled aerosol particles for all individuals are sub-micron.

The paper concludes that FEND can be an important addition to current COVID-19 hygiene protocols of mask wearing, hand washing, and social distancing. FEND adds to the efficacy of masks at reducing the penetration of respiratory droplets into the lungs or back into the environment and provides an added layer of defense for when mask wearing is not a possibility.

"We continue to support human volunteer studies in the USA and overseas, exploring unique hygiene protocols for collaborative teams, and deepening our understanding of nasal salt hygiene among those infected with COVID-19," said Edwards. "As FEND comes to market in coming weeks, we will prioritize distribution to healthcare professionals, and other essential workers in the USA and in countries around the world that are hardest hit by the COVID-19 pandemic. As we scale up production, we hope also to be helpful to clearing the air for children and teachers in public schools around the world."

Pamplona (Spain), September 29th, 2020. Researchers at Cima and the Clinica Universidad de Navarra (Spain) have led an international study identifying the cardiac cells responsible for repairing the damage to this organ after infarction. These "restorative" cells are a subpopulation of cardiac fibroblasts that play a fundamental role in the creation of the collagen scar needed to avoid the rupture of the ventricular wall. The research also reveals the molecular mechanisms involved in the activation of these cells and the regulation of their function.

This finding, in which basic and clinical researchers have participated, will permit the identification of new therapeutic targets and the development of targeted therapies which will control the healing process of the heart after infarction.

The study has been published in the latest issue of the journal Circulation, the leading scientific journal of the American Heart Association.

Characterization of the reparative cardiac fibroblasts

Cardiac fibroblasts are one of the fundamental components of the heart. These cells play an essential role in maintaining the structure and mechanism of this vital organ. "Recent studies have shown that fibroblasts do not respond homogeneously to heart injury. Therefore the object of our study was to determine their heterogeneity during the remodeling of the injured ventricle and to understand the mechanisms that regulate the function of these cells", said Dr Felipe Prósper, a researcher at Cima and the Clinica Universidad de Navarra, the leader of the study.

"Using single-cell transcription analysis techniques (single-cell RNA-seq), we identified a subpopulation within the cardiac fibroblasts, which we have named Reparative Cardiac Fibroblasts (RCF) due to their role after the cardiac injury. We have found that, when a patient has a heart attack, these RCF are activated and offer a fibrotic response due to which a collagen scar is generated to avoid the rupture of the cardiac tissue", stated Dr Prósper, who is also a member of the Red de Terapia Celular (TerCel) and the Instituto de Investigación Sanitaria de Navarra (IdiSNA).

CTHRC1, a protein related to collagen and essential for the regenerative process

In the detailed molecular study, the researchers have found that the RCF have a unique transcriptional profile, that is to say, a specific information pattern for the expression of the genes involved in their cardiac function. "Among the main differential markers of the transcriptome of these cells, we have identified the CTHRC1 protein (Collagen Triple Helix Repeat Containing 1), a molecule with a fundamental role in the fibrotic response after myocardial infarction. Specifically, this protein participates in the collagen synthesis of the extracellular cardiac matrix and is crucial for the process of ventricular remodeling", in the words of Adrián Ruiz-Villalba, a researcher on the Regenerative Medicine Program at Cima and first author of the article.

These results "suggest that the RCF activates the healing scar process of the cardiac lesion by secreting the CTHRC1 protein. Thus, this molecule may be considered as a biomarker associated with the physiological condition of the injured heart and a potential therapeutic target for patients who have suffered a heart attack or have dilated cardiomyopathy", stated Ruiz-Villalba, who is also a researcher at IdiSNA. In addition to Cima and the Clinica Universidad de Navarra, basic and clinical researchers from the United States, Belgium and Austria have taken part in this research.

This work falls within the framework of the Cell Therapy and Regenerative Medicine research line being carried out at Cima and the Clinica Universidad de Navarra, aimed at understanding the regenerative potential of stem cells and their therapeutic application in different diseases such as cardiovascular ones. Specifically, this study is linked to the BRAV? project, an international research project combining bioengineering and cardiac stem cells to restore the function of an infarcted heart. BRAV? is an H2020 funded program by the European Union (H2020-SC1-BHC-07-2019-874827).

In a proof-of-concept study, North Carolina State University researchers reported promising preclinical findings for a prototype of a vascular graft designed as a replacement for a damaged or blocked coronary artery, which supplies blood to the heart.

The findings, which were made in partnership with researchers from Case Western Reserve University, are part of an effort to develop a synthetic graft that could replace a damaged or blocked coronary artery when a patient's own vessels are not available as viable replacements after a heart attack. Ultimately, the graft is designed as a scaffold to aid in regeneration of the patient's own blood vessels. And while their work is still in early stages, the researchers said their design will help to move the field forward.

In the journal Materials Science and Engineering: C, researchers reported they made their prototype vascular graft by knitting a collagen material with a synthetic yarn. They found their design showed improved strength compared to a model that used the collagen material alone, and flexibility that compared to the human coronary artery. Also, in studies with human endothelial cells, they saw increased growth and adhesion of cells on the graft, indicating it could aid in the regeneration of the coronary artery lining.

"We see this as a new direction for research into coronary artery replacement grafts," said the study's senior author Martin King, professor of biotextiles and textile technology at NC State. "The use of collagen yarns is very new. We relied not just on one material, but we mixed the materials together and showed the two yarns can provide both mechanical strength and the biological response that we're looking for."

Currently, researchers said the "gold standard" is to use a patient's own blood vessel, such as a vein from the leg or the mammary artery, to replace the coronary artery, but some patients do not have viable blood vessels that can be harvested and used.

"There is a need to find an alternative solution for this kind of patient," said Fan Zhang, the study's first author and graduate student at NC State. "That's why we're looking to use tissue-engineered vascular grafts."

There are multiple challenges to designing a synthetic vascular graft that could replace a coronary artery, the researchers said. Some models have failed due to problems with clotting and narrowing of the arteries. Meanwhile, other models aren't able to stretch and relax with the beating heart.

"The coronary artery is only about three to four millimeters in diameter so it's a very fine artery, and it's very easy for it to get blocked," King said. "The question is: Do we have materials that will serve as a conduit without provoking this clotting on the arterial wall? That is one of the challenges. The other is that the heart is continually expanding and contracting, so we need a structure that can stretch and relax with every heart beat."

To develop their design, the NC State investigators collaborated with researchers at Case Western Reserve who have designed a biological yarn made of collagen. They combined that collagen yarn with a synthetic fiber made of polylactic acid, which is "biocompatible." When it degrades, it forms lactic acid, researchers said, which is easily tolerated because the muscles in our bodies continuously generate lactic acid.

Researchers said their model is designed to form a temporary scaffold that can regenerate a cell lining similar to the patient's own blood vessels.

"We're not designing a prototype that is a 'final product,' we're putting in the ingredients that will allow the patient to heal, and use this construct to heal and function as a coronary artery," King said. "The fibers would eventually degrade and be absorbed into the body."

Researchers found that by knitting the collagen fibers together with the synthetic PLA yarn, human endothelial cells stuck to the scaffold 10 times as much as to the synthetic yarn alone. The experiment also showed three times greater cell growth after adhesion.

Also, they found it had "excellent" bursting strength and compliance, which are the properties that will allow it to expand and contract with each heart beat - similar to a healthy coronary artery.

"We were able to mimic the compliance of the coronary artery," Zhang said. "This is the most important finding. In addition, with the addition of the collagen yarn component, we were able to promote endothelial cells to grow faster within this structure. That is very important for recovery of the endothelium."

Their work is still at a preclinical stage and has yet to be tested in a living animal. They still have work to improve their prototype to overcome additional design challenges, including how to reduce the porous nature of the hybrid graft.

However, they believe their findings show it is possible to combine both biological and synthetic materials in the design of a synthetic coronary artery graft. They are working on solutions to prevent blood leakage.

"With this combination of materials, we have been able to balance the mechanical performance with the biological response," King said. "We were also able to manufacture the prototype graft using high speed textile production machinery, which will facilitate future manufacturing scale-up and translation to a commercial graft and the clinic."

Scientists have challenged a popular theory behind the evolution of similar traits in island lizards, in a study published recently in eLife.

The findings in Greater Antillean Anolis lizards provide insights on why creatures often evolve similar physical features independently when living in similar habitats. They suggest that the role of developmental plasticity in shaping adaptive evolution may be less important than commonly thought.

Developmental plasticity refers to how development responds to the environment, in particular the way that an organism's genetic constitution (or genotype) interacts with its environment during development to produce a particular set of characteristics (or phenotype).

"Anolis lizards that live on all four of the Greater Antillean islands have independently and repeatedly evolved six different body types for maneuvering through their given habitat," says lead author Nathalie Feiner, Researcher at the Department of Biology, Lund University, Sweden. "As a result, they make a great model for studying why evolution often repeats itself."

To address this question, Feiner and the team used micro computed tomography scans to measure the shoulder, hip and leg bones of 95 species of anoles that live on the Greater Antillean islands. Their work revealed that several of the species' body shapes evolved along similar trajectories.

"These body shapes are adapted by natural selection, but several different shapes could in principle perform equally well in a given habitat," says senior author Tobias Uller, Professor of Evolutionary Biology at the Department of Biology, Lund University. "As a result, repeated evolution is more likely to occur when species share a developmental biology that makes some characteristics appear readily, while others are rare or even impossible."

One source of these developmental biases can be found in how individuals respond to different environments, a hypothesis known as plasticity-led evolution. The researchers tested how the anoles' bones responded to stresses induced by climbing and running to see if these changes directly matched the skeletal structure (or morphology) of those specialised to a given habitat.

To do this, they raised two groups of anoles - some that typically perch on narrow twigs, and others that typically run and climb on tree trunks - on two different types of surfaces, which changed the way the animals moved or perched, as well as their morphology. However, these changes were poorly matched to the evolutionary divergence between habitat specialists that evolved repeatedly on different islands.

"The responsiveness of bone to mechanical stress is a good candidate for plasticity-led evolution," Feiner explains. "But this responsiveness does not seem to have channelled the evolution of the locomotor skeleton in Anolis lizards. Instead, our findings suggest that the morphologies that evolved again and again in these lizards are likely due to simple genetic changes."

Women who have suffered unexplained repeated pregnancy loss (uRPL) have altered perceptions and brain responses to male body odours, in comparison to those with no history of uRPL, suggests a new study published today in eLife.

The results could lead to urgently needed answers for many women who experience repeat miscarriage with no clear underlying explanation.

Around 50% of human conceptions and 15% of human pregnancies result in miscarriage, but only a limited number of these can be explained. Body odour has been linked to many aspects of healthy human reproduction - such as synchrony of menstruation between women who live together, and the influence of body odours of breast-feeding women on the timing of ovulation and menstruation in others.

"Given that sense of smell is associated with human reproduction, we hypothesised that it may also be related to disorders of human reproduction," explains lead author Liron Rozenkrantz, who was a graduate student at the Azrieli National Institute for Human Brain Imaging and Research, and the Weizmann Institute of Science, Israel, and is now a Postdoctoral Fellow at the Massachusetts Institute of Technology (MIT), Cambridge, US. "We set out to test the hypothesis that perception of smell - known as olfaction - is altered in unexplained pregnancy loss, specifically the smell of body odours."

The team started by testing a key olfactory function important in reproduction: the ability to identify mates by smell. They offered 33 women with uRPL and the same number of women with no history of uRPL (controls) three body odour sniff jars, containing body odour from their spouse, a non-spouse male and one with no odor. They found that the women with a history of uRPL were twice as likely to correctly identify their spouse than the control women.

To see whether this was because the women with a history of uRPL had a better sense of smell, the team compared their ability to smell a range of different odours, such as peanuts and soap. The women with experience of uRPL were also better at discriminating between the smells, but only marginally.

The researchers next asked whether it was the characteristics of the men's body odours that made the women who have had uRPL better at identifying their spouse by smell. They asked 36 women (18 who have experienced uRPL) to rate men's body odours based on intensity, pleasantness, sexual attraction and fertility. Based on these criteria, the uRPL group rated non-spouse body odours lower when compared with the control group.

To look at how these perceptions might be controlled, the team used MRI scans to look at brain structure and function. They found that women with a history of uRPL had smaller olfactory bulbs, which was surprising given their apparent greater ability to perceive and discriminate between different smells. When they measured brain activity while the women watched an emotional film clip, with or without the subliminal presence of a non-spouse male body odour, they found a remarkable response in the hypothalamus region: while body odour increased the hypothalamus activity in women with history of uRPL, it decreased this activity in the control group.

"We have found that women who experience unexplained pregnancy loss are much more likely to recognise their spouse by smell and rate men's body odour differently than other women," concludes senior author Noam Sobel, Professor in Neurobiology at the Azrieli National Institute for Human Brain Imaging and Research, and the Weizmann Institute of Science. "We have also found differences in structural and functional brain patterns, which have not been previously associated with unexplained repeat pregnancy loss. We hope our findings will help direct further thinking and research on this condition, which is currently not well understood or managed."

Scientists have built a computer 'brain circuit', or artificial neural network, that mirrors human decision-making processes and sheds light on how circuits might be altered in psychiatric diseases, a new study published today in eLife reports.

The model identifies a potential mechanism for the impaired decision making that is commonly seen in schizophrenia, involving the reduced activity of molecules in the brain called NDMA receptors. These results provide new insight that may inform the development of future treatments for neuropsychiatric conditions.

"A major challenge in psychiatry is to relate changes that occur at nerve synapses in the brain to the cognitive processes that cause symptoms of disorders such as schizophrenia," explains lead author Dr. Sean Cavanagh, who is an MBPhD student at the UCL Queen Square Institute of Neurology, London, UK. "Computational modelling of brain circuits can fill in these gaps. By altering the circuit model at the synapse level, you can make predictions of nerve activity and behaviours, and then test these experimentally."

The team built a model that reproduces how the brain accumulates evidence and makes a decision. The types of decisions they were interested in were those that involve combining multiple pieces of information. For example, when deciding about where to go on holiday, we must combine information about many factors including the cost, weather and cultural experience. Initially, the team wanted to see whether their computer model showed the same decision-making bias that healthy humans show on these sorts of choices, called the 'pro-variance bias'. This describes how humans tend to choose options with more variable evidence. For example, when planning a holiday and facing two options, people generally tend to prefer a holiday which is very appealing in one attribute but less so in another (expensive price, but excellent weather), when compared with another holiday which is mediocre in all attributes (acceptable price and acceptable weather).

The researchers began by setting a decision-making task for two macaque monkeys and recording the pattern of their behaviours. The monkeys were presented with two series of eight bars, one on either side of a computer screen, and they had to decide which side had the taller average height. The monkeys made decisions based on nearly 30,000 sets of information, and the researchers studied the effect of timing and variability of the evidence on the monkeys' choices. They found that, as with humans, the monkeys generally preferred to choose options with greater variability across the evidence.

To explore the brain processes that underlie this preference, the team built a computer-based circuit model. This model includes two groups of excitatory nerve cells (neurons) assigned to either the right or left option, such that high activity in one group signals a decision towards that option. Both groups of neurons are also connected to inhibitory neurons, which counteract and balance the activity of the excitatory neurons. The circuit was then tested with the same decision tasks as the monkeys and was shown to be able to reproduce the same bias that the monkeys used (and which humans use) to make their decisions.

To understand how these decision processes may be impaired in neuropsychiatric diseases such as schizophrenia, the team reduced the activity of synaptic NMDA receptors that connect the neurons in each excitatory and inhibitory group. They found that the decision-making performance in the model was dependent on the balance between excitation and inhibition, which in turn was influenced by the relative changes to NDMA receptors on the two groups of neurons.

The drug ketamine is known to block NDMA receptors and is used as an experimental model of schizophrenia, as it temporarily reproduces many of the symptoms of schizophrenia in healthy humans. To test if the predictions from the model were consistent with behavioural changes, the team studied the effects of ketamine on the monkeys' decision making. Although the monkeys became less accurate in their decision making after ketamine, they retained the same pro-variance bias. In the computer model, this change in decision-making behaviour was consistent with lowered excitation/inhibition balance.

Taken together, this suggests that the changes in decision-making behaviour seen in schizophrenia and other disorders could arise from reduced activity at the NMDA receptors present on excitatory neurons. The team hopes this insight could pave the way for the development of new treatments.

"Decision-making biases can be features of normal behaviour or deficits underlying neuropsychiatric symptoms," concludes senior author Steve Kennerley, Professor of Cognitive Neuroscience at the UCL Queen Square Institute of Neurology. "Developing mechanistic accounts of neurological disease is very challenging, requiring well-designed experimental tasks, normal versus abnormal neurological groups, and computational modelling. This study was only possible with collaborations with Oxford University (Dr. Laurence Hunt) and Yale University (Dr. Norman Lam; Professor John Murray). Our results provide a circuit-level mechanism that bridges from the synaptic to behavioural level in neuropsychiatric disorders where decision-making biases are prominent."

HAMILTON, ON, Sept. 29, 2020 -- An international team led by current and former McMaster University researchers has developed an artificial lung to support pre-term and other newborn babies in respiratory distress.

The group has proven the concept using a live piglet, a major step along the route toward approval for use in humans, where the portable device could save many lives and prevent catastrophic damage by taking up some of the placenta's role in oxygenating the blood until babies are able to breathe independently.

"This technology, which is complicated to create but simple to use, is going to create a situation where more and more of these babies can be saved, and that is what is driving all of us to do this," says Ravi Selvaganapathy, a professor of Mechanical and Biomedical Engineering at McMaster who holds the Canada Research Chair in Biomicrofluidics.

The device, designed to be connected to a newborn's umbilical cord, uses the existing power of the heart to drive blood through channels of a fine membrane whose structure resembles the lining of the lungs, allowing the release of carbon dioxide and the uptake of oxygen while protecting the blood from outside infection.

The membrane is only 35 to 50 microns thick - about half the thickness of a human hair - permitting natural diffusion of carbon dioxide and oxygen. The baby's own heart beats at a rate to regulate the supply of oxygen.

Independent breathing is a particular obstacle to the survival of pre-term babies, since the lungs are not fully formed in many pre-term infants, placing them in respiratory distress from the moment they are born because they cannot take up enough oxygen on their own.

"Typically, a newborn immediately takes over breathing, feeding, and other organ functions that have been provided in utero via the placenta," says Christoph Fusch, a McMaster faculty member in Pediatrics and Chief of Pediatrics at Nuremberg General Hospital in Germany, which is affiliated with Paracelsus Medical School.

"When this transition is disturbed due to disease or immaturity, our device will enable neonatal caregivers to mimic the intrauterine supply. It will improve survival, reduce brain damage and improve long-term health in pre-term and term newborns with life-threatening postnatal lung failure."

Though the design of the artificial lung is complex, the device itself operates without external power and is simple to deploy - compared to existing technology which is much riskier and far more expensive - making it a promising contender for use in developing countries, where the risk of death among pre-term babies is greatest.

"Our research takes Mother Nature as a blueprint," says Niels Rochow, a former fellow in Neonatology at McMaster and now a staff neonatologist working with Fusch at the Nuremberg General Hospital. "The artificial placenta will allow gentle and efficient care in newborn babies with life-threatening postnatal lung failure. Families will benefit having babies with better chances for a normal life."

The device would ideally be paired with still-developing technology to supply pre-term babies with nutrition, also through the umbilical cord, thereby replacing the major functions of the placenta long enough for vulnerable pre-term babies to finish developing safely outside the womb.

"Developing this device seemed like an impossible mission in so many ways," says Mohammadhossein Dabaghi, who earned his PhD in Biomedical Engineering at McMaster and is now a post-doctoral fellow in the university's Department of Medicine. "A pumpless device that is capable of gas exchange in ambient air is something that one would expect to be bulky, but we were able to keep it compact and by using microfabrication technologies we developed in our group."

The proof-of-concept research is published today in the journal Advanced Science. The nine-person research team showed that the device worked in a live newborn piglet, restoring its reduced blood-oxygen levels to normal. Piglets are close in weight to human babies and are very similar physiologically.

Subject to successful larger-scale animal trials and regulatory approvals, Selvaganapathy says the new device could become available for clinical use within the next six to eight years.

A team of researchers found out that children with autistic spectrum disorder (ASD) have increased levels of the amino acid hydroxyproline. According to the medics, this may be associated with joint hypermobility, a common symptom in ASD patients. This information can help improve anti-ASD therapy. The work was published in the Research in Autism Spectrum Disorders journal.

Amino acids are the building blocks of proteins, and proteins are what our muscles, internal organs, and also enzymes and hormones are made of. They control our daily functioning and secure healthy growth and development of our bodies. Both lack and excess of amino acids can cause health issues. One of the factors that can have a negative impact on the balance of amino acids is autistic spectrum disorder or ASD. It manifests itself in a patient's early childhood and remains with them for the rest of their life. It is still unknown how exactly ASD affects a patient's amino acid profile and what effects it has on their body. However, a team of researchers found out that children with ASD have increased levels of the amino acid hydroxyproline. This may be associated with joint hypermobility, a common symptom in ASD patients.

"The available data about the amino acid profile of ASD patients is quite contradictory which may be due to age and gender differences, specifics of clinical treatment, and other parameters. Information about the levels of several amino acids at a given time can help better understand the specifics of metabolism in ASD patients. That is why in our work we focused on studying the levels of amino acids in children's blood serum," said Alexey Tinkov, a Candidate of Medical Sciences, and a lecturer at the Department of Elementology at RUDN University and Yaroslavl State University.

The participants of the study were 97 boys from 3 to 14 years of age, of which 64 were diagnosed with ASD. The levels of amino acids in their blood serum were measured using high-efficiency liquid chromatography with UV detection. This method allowed the researchers to break the samples down to their components and measure their concentrations.

Four amino acids (leucine, serine, tyrosine, and hydroxyproline) turned out to be associated with ASD. Hydroxyproline is a component of collagen, the basis of all connective tissues: tendons, bones, and cartilages. Therefore, the team assumed that increased hydroxyproline levels might be the cause of joint hypermobility. By various estimates, this disorder is found in 15% to 50% of young ASD patients. The level of hydroxyproline in the blood of healthy children amounted to 0.87 mg per liter, while in ASD patients it reached 1.7 mg/l. The team also found out that the levels of arginine, glutamine, histidine, leucine, lysine, phenylalanine, serine, taurine, tryptophan, and threonine in the blood of children with ASD were 15% to 28% lower than in healthy ones. Among other things, these amino acids regulate the growth and reconstruction of body tissues. According to the researchers, their deficiency can negatively affect a child's psychomotor development.

"We assumed that increased hydroxyproline levels might be associated with joint hypermobility, and the deficiency of other amino acids might affect the neuronal dysfunction. Further studies may identify potential targets for proactive treatment. Theoretically, the normalization of amino acid balance can become an additional tool for ASD therapy," added Prof. Anatoly Skalny, MD, the head of the Department of Medical Elementology at RUDN University.

By examining preexisting research for other conditions, researchers at the University of Cincinnati have found a potential treatment that could be applied to COVID-19.

The findings, published in the Journal of Biological Chemistry, established that a lipid found in the human body could be used to prevent or treat infections with SARS-CoV-2, the virus that causes COVID-19. That lipid, called sphingosine, is a natural element taken from the body and is important in the lipid metabolism of all cells and the local immune defense in epithelial cells, a type of cell that lines the surfaces of the body including skin, blood vessels, urinary tract and organs. They serve as a barrier between the inside and outside of your body and protect it from viruses.

"We investigated whether a specific lipid is able to interfere with the binding of SARS-CoV-2 to human epithelial cells," says corresponding author Erich Gulbins, MD, a visiting professor in UC's Department of Surgery. He is also chair of the Department of Molecular Biology at the University of Duisburg-Essen, Germany.

"Sphingosine has been shown in past studies to prevent and eliminate bacterial infections of the respiratory tract, but it is unknown if it can be used to prevent viral infections. The coronavirus needs to bind to specific molecules on the surface of human cells as a prerequisite to infect them," Gulbins says. "This is similar to the key and lock principle of a door: To open the door you must insert the key into the lock. We show that the lipid sphingosine binds into the cellular 'lock,' the receptor ACE2, for SARS-CoV-2 and thereby prevents binding of the virus to and infection of human cells."

Researchers in this study analyzed the use of this lipid in regulating infection in cultured human cells with SARS-CoV-2 particles added.

"We showed that sphingosine prevented cellular infection in these cultures, and pretreatment of cultured cells or freshly obtained human nasal epithelial cells with low concentrations of sphingosine prevented adhesion of and infection with the virus," says Gulbins.

"These findings indicate that sphingosine prevents at least some viral infection by interfering with the interaction of the virus with its receptor; it could be used as a nasal spray to prevent or treat infections with SARS-CoV-2," he adds. "The nasal spray must be developed, but sphingosine is a natural product. More research is needed to see if this could be a treatment for COVID-19."

Co-author Syed Ahmad, MD, co-director of the UC Cancer Center, professor and chief of the division of surgical oncology at UC and a UC Health surgeon, says this collaboration is particularly fascinating because it takes medical research from other areas of study and applies it to a timely public health issue.

"The ACE2 receptor has been studied and identified as a treatment target in pancreatic cancer," says Ahmad, the Hayden Family Endowed Chair for Cancer Research. "This is an example of taking existing research and applying it to COVID-19 science in order to make progress in the field. This is how translational science works."

ROCHESTER, Minn. -- Patients with large polycystic kidneys in need of a kidney transplant can have their diseased kidneys safely removed laparoscopically at the same time as their transplant surgery. That is the finding of a Mayo Clinic study recently published in the American Journal of Transplantation.

Mikel Prieto, M.D., a transplant surgeon and the study's senior author, began offering this dual laparoscopic procedure to polycystic kidney disease patients six years ago. The study results confirm that this all-in-one surgical approach is a safe and viable option for these patients.

"Some patients with polycystic kidney disease have two big problems. The first one is that their kidneys do not work and they need a kidney transplant. The other one is that they have very large kidneys that can cause pain and other problems," Dr. Prieto says. "If you fix one problem with the transplant, you still have the other problem to fix. It's very unsatisfying for patients who can be miserable with these kidneys to be told they will need to wait six months after the transplant to have them removed."

Polycystic kidney disease is an inherited disorder that causes clusters of cysts to develop primarily within the kidneys. As these fluid-filled cysts grow larger, they damage the kidneys, which can ultimately lead to kidney failure. These kidneys can sometimes reach a very large size significantly impairing a patient's quality of life. An estimated 600,000 people in the U.S. have polycystic kidney disease, according to the National Kidney Foundation.

The study compared the results of 51 transplant patients who had the dual surgery versus 97 patients who had only a living donor kidney transplant between January 2014 and October 2019. Researchers discovered that the kidney function for both groups of patients after undergoing surgery was the same. The risk of complications for both groups was also the same at 2%.

Patients who had the dual surgery needed to be hospitalized an average of four days post-surgery versus three days for those who had the kidney transplant alone. Researchers found that patients who had the dual surgery were more likely to need additional care immediately after the surgery. However, the long-term outcomes for both sets of patients were comparable.

"This study shows that the removal of both kidneys laparoscopically and a living donor transplant at the same time can be done successfully and safely without a significant effect on kidney function," Dr. Prieto says.

Using a zebrafish model, researchers from North Carolina State University have found that vitamin D deficiency during early development can disrupt the metabolic balance between growth and fat accumulation. The results suggest a linkage between vitamin D and metabolic homeostasis, or equilibrium.

The research team, led by Seth Kullman, professor of biological sciences at NC State, looked at groups of post-juvenile zebrafish on one of three diets: no vitamin D (or vitamin D null), vitamin D enriched and control. The zebrafish spent four months on their particular diet, then the researchers looked at their growth, bone density, triglyceride, lipid, cholesterol and vitamin D levels. They also examined key metabolic pathways associated with fat production, storage and mobilization and growth promotion.

The zebrafish in the vitamin D deficient group were, on average, 50% smaller than those in the other two groups, and they had significantly more fat reserves.

"The vitamin D deficient zebrafish exhibited both hypertrophy and hyperplasia - an increase in both the size and number of fat cells," Kullman says. "They also had higher triglycerides and cholesterol, which are hallmarks of metabolic imbalance that can lead to cardio-metabolic disease. This, combined with the stunted growth, indicates that vitamin D plays an important role in the ability to channel energy into growth versus into fat storage."

After the initial testing, the vitamin D deficient zebrafish were given a vitamin D enriched diet for an additional six months, to see if the results could be reversed. While the fish did continue to grow and begin to utilize fat reserves, they never caught up in size with the other cohorts and they retained residual fat deposits.

"This work shows that vitamin D deficiency can influence metabolic health by disrupting the normal balance between growth and fat accumulation," Kullman says. "Somehow the energy that should be going toward growth is getting shunted into creating fat and lipids, and this occurrence cannot be easily reversed. While we don't yet understand the mechanism, we are beginning to tease that out."

Future work will involve looking at the offspring of vitamin D deficient mothers, to determine whether this vitamin deficiency has epigenetic effects that can be passed down.

Jizhong Zhou, the Director of the Institute for Environmental Genomics, a George Lynn Cross Research Professor in the OU College of Arts and Sciences and the lead for the study, tackles a problem that has challenged scientists for more than a decade.

"Soil microbial respiration, which is the carbon dioxide flux from the soil to the atmosphere, is an important source of uncertainty in projecting future climate and carbon cycle feedbacks," said Zhou. "Our study illustrates that warming-induced respiratory adaptation is subject to the adaptive changes in microbial community functional structure, so that the positive feedback of soil microbial respiration in response to climate warming may be less than previously expected."

He adds that this study is also unique in its approach to integrate omics data, the term for the comprehensive approach for analysis of complete genetic profiles of organisms and communities, into ecosystem models for better predictions.

"Integrating microbial omics information to inform global climate change models is extremely challenging," Zhou said. "The findings from this study have important implications for understanding and predicting the ecological consequences of climate warming."