Culture

When Rebecca Acabchuk was studying mild traumatic brain injuries while working on her doctorate in physiology and neurobiology at UConn, she met a student athlete who had suffered multiple concussions.

"When I started doing research on concussions, people just started coming to me," Acabchuk says. "Families at my daughter's school, anytime somebody had a concussion, I would hear about it - I would hear these personal stories and all the struggles of people who had concussions and their symptoms just didn't resolve."

So it was for the student athlete, who told Acabchuk that she would experience seizures when a smoke alarm went off in her dormitory.

"All of these symptoms she would have to struggle with - really profound symptoms - are an invisible injury," says Acabchuk, who earned her PhD in 2016 and is now a post-doctoral fellow with UConn's Institute for Collaboration on Health, Intervention, and Policy, or InCHIP. "People think you should be better, the injury happened so long ago. Why aren't you better? And then more frustration comes in when your doctor says just to rest, there's nothing else that can be done, but you're still getting headaches or feeling fatigued or depressed."

Chronic concussion symptoms are notoriously difficult to treat. But Acabchuk - who is also a yoga instructor in Hebron, and has been teaching yoga for 17 years - is hoping that a recently published InCHIP study, the first-ever meta-analysis looking at the use of yoga, meditation, and mindfulness-based interventions for the effective treatment of chronic concussion symptoms, will offer hope to those still struggling with their symptoms. The study was recently published in the journal Applied Psychology: Health and Well-being.

"This was really a passion project for me in the sense that it combines these two areas of interest, concussion work with yoga and meditation," says Acabchuk, who is the study's lead author. "We know from other studies that yoga and meditation may be helpful for reducing systemic inflammation, and we know that they are helpful for increasing self-compassion and reducing rumination if people are dealing with symptoms of depression."

Most studies looking at the effectiveness of yoga, meditation, and mindfulness on concussions have been small. For their meta-analysis, Acabchuk and her team pulled together data from 22 different studies, including both published and unpublished work, that all together included a total of 539 study participants, and looked at the impact of the three interventions on outcome categories - including mental health, physical health, cognitive performance, quality of life, and social/occupational performance - and on specific health outcomes, like depression, attention, anxiety, and fatigue. The team then applied advanced meta-analytical methods to compile and assess the results of those studies.

"The main results that we saw were significant reductions in depression and fatigue," Acabchuk says. "Especially with fatigue, it was a large effect size, which is impressive in the sense that fatigue is a difficult symptom for patients to deal with."

The meta-analysis found that mind-body interventions consistently provided symptom improvement across nearly all measured outcomes. The trends were remarkable, the researchers noted, because of the variety of patients enrolled in the studies, and the known difficulty of relieving chronic concussion symptoms.

Acabchuk says more and larger studies are needed to further investigate the benefits of yoga, meditation, and mindfulness in concussion treatment plans. She also says that more study is needed to help researchers and the general public understand the mechanisms by which these types of interventions promote healing and reduce concussion symptoms.

But importantly, including some sort of yoga, meditation, or mindfulness practice as part of a treatment plan for a mild traumatic brain injury appears to involve no adverse effects for the patient, she says - so there's little downside to giving it a try.

"Think of the brain almost like an ACL - if you tear your ACL, you're going to rest it, but you're also going to take steps to rehabilitate it," Acabchuk says. "If you think of the brain in that sense, a concussion is also like a rehabilitation injury in that, through rehabilitation, you can strengthen certain pathways in the brain. And we think the tools to help do that are breath-work, meditation, and mindful movement through poses from yoga."

She continues, "Maybe starting with a meditation app or online meditation group to learn the basics, and setting aside time to meditate 10 minutes a day. If you're a person who can't sit still, maybe yoga is better for you. If you're too tired at the end of the day, maybe a simple body scan with deep breathing exercises would be better for you. It's not going to be a miracle cure, but more of something that can provide benefits over time by incorporating these tools into daily life. I really do hope that this helps empower people who are struggling with their symptoms."

BOSTON - A combination cancer therapy that is effective against treatment-resistant hepatocellular carcinoma (HCC) by inhibiting tumor growth and increasing survival has been identified by researchers at Massachusetts General Hospital (MGH). In a paper published in the Journal for ImmunoTherapy of Cancer, the investigators describe how the dual therapy -- which combines the multikinase inhibitor drug regorafenib to "reprogram" the tumor immune microenvironment, and programmed cell death 1 (PD1) antibodies to stimulate anti-tumor immunity -- improved survival in mouse models of HCC beyond what each therapy could have achieved alone.

"The holy grail of immunotherapy in treating solid cancers like HCC is to draw cancer-fighting T-cells inside the tumor," explains Dan G. Duda, DMD, PhD, director of translational research in GI Radiation Oncology at MGH and senior author of the study. "We found that regorafenib delivered at the right intermediate dose tricks cancer cells into expressing a chemokine known as CXCL10 which, in turn, triggers intratumoral T-cell infiltration."

HCC, the most common form of liver cancer, is an aggressive gastrointestinal disease that is increasing globally at more than 3% a year. It is the second deadliest form of cancer, responsible for more than 700,000 deaths annually. The encouraging news for patients is the emergence in recent years of combination therapies of anti-vascular endothelial growth factor receptor (anti-VEGFR) inhibitors along with PD1 pathway blockades.

This type of cancer develops a rich new vasculature that feeds tumor progression. This vasculature is highly abnormal, which limits the recruitment and activity of effector T-cells. Anti-VEGFR inhibitors work to control that growth in part by normalizing tumor vasculature and increasing T-cell infiltration into tumors. This concept was first advanced by study co-author Rakesh K. Jain, PhD, director of Steele Laboratories for Tumor Biology at MGH, and a pioneer in the fields of vascular biology and cancer therapy. PD1 inhibitors, for their part, restore the immune system's ability to become activated and kill cancer cells by inhibiting the interaction between PD-L1, a protein on the surface of some of the malignant and non-malignant cells in HCC, and the protein PD1 on the surface of T-cells. This dual treatment strategy has shown in some clinical trials of HCC patients response rates nearly double the 15% to 20% who typically respond to anti-PD1 treatment alone.

"Combination therapy has been a major advance for the field, but it still has limitations in treating liver cancer, as evidenced by the fact so many patients experience recurrence of the disease, even as they are living longer," says Jain. "To address treatment resistance, we suggested that an inhibitor that can target multiple kinases beyond VEGF receptors could be particularly effective. Our research teams were able to show that regorafenib has that unique capability when used at doses that induce both vascular normalization and increased expression of the chemokine CXCL10 in cancer cells. These intratumoral changes induce infiltration of T-cells into tumors where they can more effectively do their job."

Findings from the MGH study are directly informing ongoing clinical trials of regorafenib in cancer patients. Indeed, this work is highly relevant to the future development of treatments for HCC as well as other cancers that metastasize to the liver, according to Duda. "Now that our preclinical study has shown the effectiveness of dual therapy, we need to understand how to combine its components in ways that produce maximum benefit in patients," he says. "Our work has taken a major step in that direction by demonstrating the importance of targeting the immune microenvironment of HCC while using immunotherapy against this deadly cancer."

In recent decades, researchers have found that most mammals' guts are surprisingly complex environments - home to a variety of microbial ecosystems that can profoundly affect an animal's well-being. Scientists have now learned that the bear appears to be an exception, with its gut playing host to a microbial population that varies little across the intestinal tract.

"It's the first mammal species where we've looked at two separate locations in the gut and found microbial communities that are essentially indistinguishable from each other," says Sierra Gillman, first author of a paper on the work and a Ph.D. student at the University of Washington. Gillman did the work while a grad student at Northern Michigan University (NMU).

"Bears have really simple guts - pretty much a garden hose - so they can't regulate their gut microbes to the extent that animals with longer, more complex guts can," says Erin McKenney, co-author of the paper and an assistant professor of applied ecology at North Carolina State University. "Without that control, the bears' diet and environment may play a greater role in shaping the gut microbiome. It raises some interesting evolutionary questions about the relationship between the shape of an animal's gut, its gut microbiome, and the relationship between the microbiome and the animal's health and behavior."

The researchers set out to learn more about the gut microbiome of American black bears (Ursus americanus) with little idea of what to expect. Not much research has been done on microbial ecosystems in the species, and what work has been done has focused on animals in captivity. Since animals in captivity and animals in the wild often have very different gut microbiomes, the researchers were curious as to what they'd find. One major challenge was obtaining samples in the first place.

To that end, the researchers worked with guides who lead scheduled trips with hunters in the Upper Peninsula of Michigan. Gillman developed a detailed set of protocols and conducted training sessions with the guides on how to collect samples from bears that were harvested when the guides went on their regularly scheduled trips with hunters. Specifically, Gillman taught the guides how to retrieve samples from both the jejunum, which is the middle section of the small intestine, and the colon, which is also called the large intestine.

Ultimately, the researchers obtained 31 useable jejunum samples and 30 useable colon samples. They then analyzed the samples to identify which microbial species were present.

The researchers expected to see more, and different, species of microbes in the colon. The colon is often where digestion slows down, enabling gut microbes to break down fiber in the diet - which normally fosters microbial diversity. But not, apparently, in the black bears of Michigan.

Why are bear gut microbiomes different from the microbiomes of other omnivores scientists have looked at? In a word, it's probably the cecum.

Omnivores with more complex guts have a small pouch - called the cecum - between the small and large intestine. The cecum helps slow down the rate at which food passes through the gut, like an oxbow in a river, and likely serves as a reservoir for microbial populations in the gut, allowing animals to replenish the diversity of their microbiomes, even as their diets and health change.

"Bears don't have a cecum," Gillman says. "That makes their gut microbiomes more vulnerable to systemic change due to diet, health or other factors."

This finding has an immediate practical application for wildlife researchers.

"In many animal species, a fecal sample can tell you what the microbial diversity of the colon was like - but it doesn't tell you much about what's happening in other parts of the gut," says Diana Lafferty, co-author of the paper and an assistant professor of wildlife ecology at NMU. "Our work suggests that a fecal sample offers insight into the microbial community across the entire gut for black bears - and possibly for other carnivores and omnivores that have simple gut morphologies."

In other words, they can learn more from wild animal poop than they previously thought.

The researchers are currently in the process of comparing the samples collected in Michigan to samples from black bears harvested by hunters in North Carolina, in order to determine if the findings are consistent across geographic regions.

"We are also looking at carnivore species that also lack a cecum to see if they have a similar lack of microbial diversity across the gut," Gillman says.

"And we are working on a project that will help us better identify and understand the connections between the gut microbiome and bear health," says Lafferty.

"One of the things we're curious about is weight gain," McKenney says. "We know that specific shifts in the microbiome can lead to weight gain and obesity in other species, which is usually viewed as a negative. But for species that hibernate, like bears, that could actually be advantageous."

Researchers at the University of Gothenburg in Sweden, together with their colleagues at the Barcelona Beta Research Centre in Spain, the University Medical Centre in Ljubljana, Slovenia, and the University of Paris, have found new forms of tau protein that become abnormal in the very early stages of Alzheimer's disease before cognitive problems develop. The scientists developed new tools to detect these subtle changes and confirmed their results in human samples.

At a time when the incidence and social costs of dementia and Alzheimer's disease in particular continue to rise, this breakthrough is very timely as it could enable the detection of the disease much earlier than current approaches. The findings are also important for the testing of therapies against this devastating disease.

Alzheimer's disease is characterized by two pathological changes in brain tissue. One is a protein called tau while the other involves the amyloid beta peptide. Both can form clumps of aggregates that progressively accumulate in specific areas of the brain. For tau, individual units of the protein can aggregate into finely-ordered fibrillar structures facilitated by a biochemical process called phosphorylation. Throughout the disease process, amyloid beta and phosphorylated tau (p-tau) are released from the brain into cerebrospinal fluid; the amount of the released proteins are used as reliable surrogate markers for clinical diagnoses of Alzheimer's disease.

Normally, amyloid beta levels in cerebrospinal fluid become abnormal several years before p-tau. The current clinical tests for p-tau become abnormal when memory failings develop. This makes it difficult to identify people with the disease at the very early stages before it is too late. How can we, therefore, reliably detect these sub-threshold disease changes?

To address these challenges, the scientists discovered that there are specific forms of p-tau that undergo very minute increases in cerebrospinal fluid and blood in people with emerging Alzheimer pathology. Consequently, the researchers developed highly sensitive techniques to measure these biological markers that precede clinical signs by several years.

In the first study, conducted in the Alfa parent cohort study at the Barcelona Beta Research Centre (BBRC), with the support of "la Caixa" Foundation, about a third of the 381 people evaluated had brain evidence of Alzheimer pathology but without any cognitive problems, meaning that these changes could not be detected in the clinic by memory assessments. Remarkably, the new p-tau markers correctly identified these emerging abnormalities measured in cerebrospinal fluid and regular blood samples.

Subsequent studies performed in Gothenburg, Paris and Ljubljana revealed that these new markers continue to increase from the preclinical stage through the onset of cognitive problems to the late dementia stages. For this reason, progressive increases in p-tau could provide insights into the biological and clinical development of Alzheimer's disease. The studies are now published in the leading journals EMBO Molecular Medicine and Alzheimer's & Dementia: The Journal of the Alzheimer's Association.

Kaj Blennow, professor of neurochemistry at the University of Gothenburg, who directed the work said "A possible way to improve the chances of future therapies is to test them on people in the very early stages of the disease with elusive biological changes but lacking clinical symptoms including memory failings. Candidate drug trials have not been too successful." He added that: "The practical challenge, however, is that these very tiny initial changes are incredibly difficult to measure reliably. This compromises our chances to identify and recruit preclinical AD patients for clinical trials."

Dr. Thomas Karikari, an assistant professor at the University of Gothenburg, who co-led the discovery commented: "The remarkable findings reported in these publications show that the new highly sensitive tools capture the earliest Alzheimer disease changes in the brain in clinically normal people. These tools therefore have the potential to advance population screening and clinical trials."

According to Dr. Marc Suárez-Calvet, neurologist and ERC researcher at BBRC, "the biomarker detected in blood may change clinical practice in the coming years, since it will improve the diagnosis of patients with Alzheimer's disease, both in its asymptomatic and symptomatic phases".

Inside every cell, thousands of different proteins form the machinery that keeps all living things - from humans and plants to microscopic bacteria - alive and well. Almost all diseases, including cancer, dementia and even infectious diseases such as COVID-19, are related to the way these proteins function. Because each protein's function is directly related to its three-dimensional shape, scientists around the world have strived for half a century to find an accurate and fast method to enable them to discover the shape of any protein.

Today (Monday) researchers at the 14th Community Wide Experiment on the Critical Assessment of Techniques for Protein Structure Prediction (CASP14) will announce that an artificial intelligence (AI) solution to the challenge has been found.

Building on the work of hundreds of researchers across the globe, an AI program called AlphaFold, created by London-based AI lab DeepMind, has proved capable of determining the shape of many proteins. It has done so to a level of accuracy comparable to that achieved with expensive and time-consuming lab experiments.

CASP14 is organised by Dr John Moult (chair), University of Maryland, USA; Dr Krzysztof Fidelis, UC Davis, USA; Dr Andriy Kryshtafovych, UC Davis, USA; Dr Torsten Schwede, University of Basel and SIB Swiss Institute of Bioinformatics, Switzerland; and Dr Maya Topf, Birkbeck, University of London, UK and CSSB (HPI and UKE) Hamburg, Germany.

Dr Moult said: "Proteins are extremely complicated molecules, and their precise three-dimensional structure is key to the many roles they perform, for example the insulin that regulates sugar levels in our blood and the antibodies that help us fight infections. Even tiny rearrangements of these vital molecules can have catastrophic effects on our health, so one of the most efficient ways to understand disease and find new treatments is to study the proteins involved.

"There are tens of thousands of human proteins and many billions in other species, including bacteria and viruses, but working out the shape of just one requires expensive equipment and can take years.

"Nearly 50 years ago, Christian Anfinsen was awarded a Nobel Prize for showing that it should be possible to determine the shape of proteins based on their sequence of amino acids - the individual building blocks that make up proteins. That's why our community of scientists have been working on the biennial CASP challenge."

Teams taking part in the CASP challenge are given the amino acid sequences for a set of around 100 proteins. While scientists study the proteins in the lab to determine their shape experimentally, about a 100 participating CASP teams from more than 20 countries will try to do the same thing using computers. The results are assessed by independent scientists.

Dr Fidelis said: "The CASP approach has created intense collaboration between researchers working in this field of science and we have seen how it has accelerated scientific developments.

"Since we first ran the challenge back in 1994, we have seen a succession of discoveries, each solving an aspect of this problem, so that computed models of protein structures have become progressively more useful in medical research."

During the latest round of the challenge, DeepMind's AlphaFold program has determined the shape of around two thirds of the proteins with accuracy comparable to laboratory experiments*. AlphaFold's accuracy with most of the other proteins was also high, though not quite at that level.

The CASP organisers say that this success builds on achievements made in previous CASP rounds, both by the DeepMind team and other participants, and that other teams taking part in CASP14 have also produced some highly accurate structures during this round.

Dr Kryshtafovych said: "What AlphaFold has achieved is truly remarkable and today's announcement is a win for DeepMind, but it's also a triumph for team science. The unique and intense way we collaborate with researchers around the world through CASP, and the contributions from many teams of scientists over the years, have brought us to this breakthrough."

He adds: "Being able to investigate the shape of proteins quickly and accurately has the potential to revolutionise life sciences. Now that the problem has been largely solved for single proteins, the way is open for development of new methods for determining the shape of protein complexes - collections of proteins that work together to form much of the machinery of life, and for other applications."

Professor Dame Janet Thornton, Director Emeritus of EMBL's European Bioinformatics Institute (EMBL-EBI), who is not affiliated with CASP or DeepMind, said: "One of biology's biggest mysteries is how proteins fold to create exquisitely unique three-dimensional structures. Every living thing - from the smallest bacteria to plants, animals and humans - is defined and powered by the proteins that help it function at the molecular level.

"So far, this mystery remained unsolved, and determining a single protein structure often required years of experimental effort. It's tremendous to see the triumph of human curiosity, endeavour and intelligence in solving this problem. A better understanding of protein structures and the ability to predict them using a computer means a better understanding of life, evolution and, of course, human health and disease."

OAK BROOK, Ill. - Up to one-third of adult women who sustain a non-displaced fracture to the ulna bone of the forearm may be victims of intimate partner violence, according to a study being presented at the annual meeting of the Radiological Society of North America (RSNA). The findings underscore the need to screen for intimate partner violence in women with these types of injuries, researchers said.

Fractures to the ulna, the bone on the pinkie side of the forearm, often occur when people hold up their hands to protect their faces from being struck with an object. These breaks are referred to as "nightstick fractures," because they are frequently seen in people who try to block blows from nightsticks wielded by police officers.

Bharti Khurana, M.D., a radiologist at Brigham and Women's Hospital in Boston and senior author of the study, had observed these fractures in her practice for years, mostly in men. But it was the occasional woman she saw that raised questions.

"I would see these types of injuries in men, but once in a while I would see them in women," Dr. Khurana said. "I never correlated it with intimate partner violence until recently. I shared my thoughts with our orthopedic surgeons and, with their interest and support, decided to pursue the study."

For the study, Dr. Khurana and colleagues searched electronic medical records from six hospitals for isolated ulnar fractures in women ages 18 to 50. They identified 62 patients, average age 31. Of those, 12 were confirmed for intimate partner violence and another eight were suspected of intimate partner violence.

Analysis of the radiographs demonstrated that intimate partner violence was strongly associated with minimally displaced fractures.

"The radiological characteristics we were looking at were the location of the fracture, the pattern of the fracture in terms of how it broke, and the displacement of the fracture," said study lead author David Sing, M.D., an orthopedic surgery resident at Boston Medical Center. "Out of all those things, what we usually saw was a minimally displaced fracture, meaning the bone is broken all the way through but has not shifted significantly."

Confirmed cases were also linked with homelessness and previous visits to the emergency department with musculoskeletal injuries.

Women with ulnar fractures from intimate partner violence who are reluctant to report the crime will often attribute their injuries to a fall, Dr. Khurana said. However, she noted, falls are much more likely to result in a fracture of the radius, the other bone of the forearm.

This observation was supported by the study, as all the patients who were not victims of intimate partner violence had ulnar fractures from motor vehicle accidents or accidental striking, such as from crashing into a tree while skiing. Of the eight patients where intimate partner violence was suspected, four reported a fall.

"It's actually rare to break your ulna in a fall," Dr. Khurana said. "If a radiologist is seeing an ulnar fracture that is non-displaced, and the woman says she had a fall, it's actually quite concerning for intimate partner violence."

The study results suggest that intimate partner violence screening may be underutilized. Formal documentation of intimate partner violence evaluation or screening was completed in only 40% of confirmed/suspected intimate partner violence cases in the study. According to the researchers, radiologists who observe non-displaced ulnar fractures can help close that shortfall by letting the emergency department physician or orthopedic surgeon know that the fracture is often seen in intimate partner violence. The ordering physician can then look at the patient's clinical history to see if there is anything suspicious.

"Careful analysis of previous imaging exams may also help radiologists confirm their suspicion of intimate partner violence," said study co-author Rahul Gujrathi, M.D., a radiology fellow at Brigham and Women's Hospital.

In the study, for instance, historical imaging analysis alone was able to raise suspicion in 75% of clinically confirmed intimate partner violence patients.

"We have resources that we can provide to the patients who are stuck in that situation," Dr. Sing said. "It's especially important during COVID-19, where we've seen the rate of intimate partner violence go up with people trapped at home with their abusers."

Dr. Khurana, who devotes much of her research to identifying radiological signs of intimate partner violence, believes that a more widespread awareness of the association between ulnar fractures and intimate partner violence will help provide earlier detection and intervention.

"The sooner we can address and change the behavior, the better," she said. "Just like radiologists want to diagnose cancer as early as possible, it's the same thing with this. If we diagnose early, we have a better chance to break the cycle of violence."

Researchers from Bochum, Göttingen, Duisburg and Cologne have developed a new method for detecting bacteria and infections. They use fluorescent nanosensors to track down pathogens faster and more easily than with established methods. A team headed by Professor Sebastian Kruß, formerly at Universität Göttingen, now at Ruhr-Universität Bochum (RUB), describes the results in the journal Nature Communications, published online on 25 November 2020.

Traditional methods of detecting bacteria require tissue samples to be taken and analysed. Sebastian Kruß and his team hope to eliminate the need to take samples by using tiny optical sensors to visualise pathogens directly at the site of infection.

Fluorescence changes in the presence of bacterial molecules

The sensors are based on modified carbon nanotubes with a diameter of less than one nanometre. If they are irradiated with visible light, they emit light in the near-infrared range (wavelength of 1,000 nanometres and more), which is not visible to humans. The fluorescence behaviour changes when the nanotubes collide with certain molecules in their environment. Since bacteria secrete a characteristic mix of molecules, the light emitted by the sensors can thus indicate the presence of certain pathogens. In the current paper, the research team describes sensors that detect and differentiate harmful pathogens that are associated with, for example, implant infections.

"The fact that the sensors work in the near-infrared range is particularly relevant for optical imaging, because in this range there are far fewer background signals that can corrupt the results," says Sebastian Kruß, who heads the Functional Interfaces and Biosystems Group at RUB and is a member of the Ruhr Explores Solvation Cluster of Excellence (Resolv). Since light of this wavelength penetrates deeper into human tissue than visible light, this could enable bacteria sensors read out even under wound dressings or on implants.

Additional areas of application are conceivable

"In the future, this could constitute the foundation for optical detection of infections on intelligent implants, as sampling would no longer be required. It would thus allow the healing process or a possible infection to be detected quickly, resulting in improved patient care," says Robert Nißler from the University of Göttingen, lead author of the study. "The possible areas of application are not limited to this," adds Kruß. "For example, improved rapid diagnosis of blood cultures in the context of sepsis is also conceivable in the future."

Researchers created a new astronomical instrument that has successfully aided in estimating the abundance of metals in the early universe. The WINERED instrument allows for better observations of astronomical bodies like quasars in the early universe, billions of years ago. Researchers hope this deeper level of exploration could help answer questions about the origins not only of metals in the universe but also of the stars themselves.

Iron is one of the most important elements for life as we know it, and for the technology, both primitive and modern, that has shaped human history. But details of the exact origin of iron and other important metals such as magnesium remain elusive. Exploration of this is important in the field of astronomy as it also connected to the origins of the first stars that would have begun to shine several hundred million years after the Big Bang.

Project Research Associate Hiroaki Sameshima from the Institute of Astronomy at the University of Tokyo and his team decided a new instrument was needed to study these matters. Due to limited instrumentation, previous observations to collect data for the study of metals' origins mainly looked at old stars nearby. But this only gave astronomers information about our own unique galaxy. A new instrument with enhanced sensitivity to near-infrared light could push the boundary and open up observations of distant quasars, ferociously energetic ancient galactic cores that emitted light when the universe was only 2.4 billion years old.

"By mounting the WINERED instrument on a large telescope, we can see further back in time as we can observe bodies more distant, or more ancient, than those from previous studies. We can now see details of quasars over 10 billion years old," said Sameshima. "WINERED is a special kind of spectrograph, which can read the chemical signatures present in the light from distant bodies. It revealed to us the fingerprints of iron and magnesium in the light from these quasars, and this allowed us to calculate the abundance of these elements when the universe was much younger than previous studies allowed."

Now that the researchers have established a new method to directly examine the abundance of metals in the early universe, the challenge becomes one of refining the technique and broadening its scope to collect more data. With improved data, astronomers can build on this study and create theories to explain the origins of metals including the iron in your blood.

Research findings by a KAIST team provide insight into the complex mechanism of cellular senescence and present a potential therapeutic strategy for reducing age-related diseases associated with the accumulation of senescent cells.

Simulations that model molecular interactions have identified an enzyme that could be targeted to reverse a natural aging process called cellular senescence. The findings were validated with laboratory experiments on skin cells and skin equivalent tissues, and published in the Proceedings of the National Academy of Sciences (PNAS).

"Our research opens the door for a new generation that perceives aging as a reversible biological phenomenon," says Professor Kwang-Hyun Cho of the Department of Bio and Brain engineering at the Korea Advanced Institute of Science and Technology (KAIST), who led the research with colleagues from KAIST and Amorepacific Corporation in Korea.

Cells respond to a variety of factors, such as oxidative stress, DNA damage, and shortening of the telomeres capping the ends of chromosomes, by entering a stable and persistent exit from the cell cycle. This process, called cellular senescence, is important, as it prevents damaged cells from proliferating and turning into cancer cells. But it is also a natural process that contributes to aging and age-related diseases. Recent research has shown that cellular senescence can be reversed. But the laboratory approaches used thus far also impair tissue regeneration or have the potential to trigger malignant transformations.

Professor Cho and his colleagues used an innovative strategy to identify molecules that could be targeted for reversing cellular senescence. The team pooled together information from the literature and databases about the molecular processes involved in cellular senescence. To this, they added results from their own research on the molecular processes involved in the proliferation, quiescence (a non-dividing cell that can re-enter the cell cycle) and senescence of skin fibroblasts, a cell type well known for repairing wounds. Using algorithms, they developed a model that simulates the interactions between these molecules. Their analyses allowed them to predict which molecules could be targeted to reverse cell senescence.

They then investigated one of the molecules, an enzyme called PDK1, in incubated senescent skin fibroblasts and three-dimensional skin equivalent tissue models. They found that blocking PDK1 led to the inhibition of two downstream signalling molecules, which in turn restored the cells' ability to enter back into the cell cycle. Notably, the cells retained their capacity to regenerate wounded skin without proliferating in a way that could lead to malignant transformation.

The scientists recommend investigations are next done in organs and organisms to determine the full effect of PDK1 inhibition. Since the gene that codes for PDK1 is overexpressed in some cancers, the scientists expect that inhibiting it will have both anti-aging and anti-cancer effects.

Earth just got 7 km/s faster and about 2000 light-years closer to the supermassive black hole in the center of the Milky Way Galaxy. But don't worry, this doesn't mean that our planet is plunging towards the black hole. Instead the changes are results of a better model of the Milky Way Galaxy based on new observation data, including a catalog of objects observed over the course of more than 15 years by the Japanese radio astronomy project VERA.

VERA (VLBI Exploration of Radio Astrometry, by the way "VLBI" stands for Very Long Baseline Interferometry) started in 2000 to map three-dimensional velocity and spatial structures in the Milky Way. VERA uses a technique known as interferometry to combine data from radio telescopes scattered across the Japanese archipelago in order to achieve the same resolution as a 2300 km diameter telescope would have. Measurement accuracy achieved with this resolution, 10 micro-arcseconds, is sharp enough in theory to resolve a United States penny placed on the surface of the Moon.

Because Earth is located inside the Milky Way Galaxy, we can't step back and see what the Galaxy looks like from the outside. Astrometry, accurate measurement of the positions and motions of objects, is a vital tool to understand the overall structure of the Galaxy and our place in it. This year, the First VERA Astrometry Catalog was published containing data for 99 objects.

Based on the VERA Astrometry Catalog and recent observations by other groups, astronomers constructed a position and velocity map. From this map they calculated the center of the Galaxy, the point that everything revolves around. The map suggests that the center of the Galaxy, and the supermassive black hole which resides there, is located 25800 light-years from Earth. This is closer than the official value of 27700 light-years adopted by the International Astronomical Union in 1985. The velocity component of the map indicates that Earth is travelling at 227 km/s as it orbits around the Galactic Center. This is faster than the official value of 220 km/s.

Now VERA hopes to observe more objects, particularly ones close to the central supermassive black hole, to better characterizes the structure and motion of the Galaxy. As part of these efforts VERA will participate in EAVN (East Asian VLBI Network) comprised of radio telescope located in Japan, South Korea, and China. By increasing the number of telescopes and the maximum separation between telescopes, EAVN can achieve even higher accuracy.

Portland State University researchers and their collaborators at the Quinault Indian Nation and Oregon State University found microplastics in Pacific razor clams on Washington's sparsely populated Olympic Coast -- proof, they say, that even in more remote regions, coastal organisms can't escape plastic contamination.

Microplastics are pieces of plastic smaller than 5 millimeters that are either intentionally produced at that size, or break down from synthetic clothing, single-use plastic items, or other products. These particles enter the environment and pervade freshwater and marine environments, soils and even the air we breathe.

Britta Baechler, the study's lead author and a recent graduate of PSU's Earth, Environment and Society doctoral program, analyzed the concentrations of microplastics in razor clams collected from eight beaches along the Washington coast and, after surveying recreational clam harvesters,estimated the annual microplastic exposure of those who eat them.

The Pacific razor clam is one of the most sought-after shellfish in Washington. The state's Department of Fish and Wildlife said that during a recent season, the recreational razor clam fishery saw more than 280,000 digger trips with diggers harvesting 4 million clams for the season. It's also a key first food, cultural resource, and vital source of income for members of the Quinault Indian Nation.

During the study, a total of 799 suspected microplastics were found in the 138 clam samples, 99% of which were microfibers. On average, clams had seven pieces of plastic each.

Clams from Kalaloch Beach, the northernmost site near the mouth of Puget Sound, contained significantly more microplastics than clams from the other seven sites. Though the study did not explore the reasons behind this, Baechler noted that there were no major differences in land cover types between Kalaloch and the other sites, but Kalaloch is the closest in proximity of all sites to the densely populated Seattle metro area.

Baechler's team compared whole clams -- minimally processed as if being consumed by an animal predator -- and cleaned clams -- gutted, cleaned of sand debris and grit, and prepared as if being eaten by a person. They found that in thoroughly cleaned clams, the amount of microplastics was reduced by half.

Baechler said this bodes better for people -- 88% percent of the survey respondents reported cleaning clams before eating them -- than for ocean predators that aren't afforded the luxury of cleaning clams prior to consumption.

Surveys of 107 recreational harvesters determined the average number of razor clams consumed per meal and the number of meals containing clams each year. Combining consumption information with the average number of microplastics per clam, the researchers estimated Olympic Coast razor clam harvester-consumers were exposed to between 60 and 3,070 microplastics per year from razor clams for those who thoroughly cleaned their clams before eating them, or between 120 and 6,020 microplastics a year for those who ate them whole without removing the guts, gills or other organs.

"We don't know the exact human health impacts of microplastics we inevitably ingest through food and beverages," said Baechler, who now works as an ocean plastics researcher at Ocean Conservancy. "Our estimates of microplastic exposure from this single seafood item are, for context, far lower than what we likely take in from inhalation, drinking bottled water and other sources, but no amount of plastic in our marine species or seafood items is desirable."

Baechler and Elise Granek, a professor of environmental science at PSU, said that everyone has a role to play in reducing plastic pollution in the marine environment -- from plastic producers and product designers who can develop effective upstream pollution control solutions to consumers who can make substitutions in their daily lives to reduce their plastic footprints.

"We all have become dependent on plastics for our clothing and packaging, and the more plastic we use, the more likely it's going to end up in our drinking water, our food and our air," Granek said. "All of us have a responsibility to do what we can to limit the amount of plastic that we're using."

Computer simulations explain how electrons with wide-ranging energies rain into Earth's upper and middle atmosphere during a phenomenon known as the pulsating aurora. The findings, published in the journal Geophysical Research Letters, suggest that the higher-energy electrons resulting from this process could cause destruction of the part of the ozone in the mesosphere, about 60 kilometres above Earth's surface. The study was a collaboration between scientists in Japan, including at Nagoya University, and colleagues in the US, including from NASA.

The northern and southern lights that people are typically aware of, called the aurora borealis and australis, look like coloured curtains of reds, greens, and purples spreading across the night skies. But there is another kind of aurora that is less frequently seen. The pulsating aurora looks more like indistinct wisps of cloud strumming across the sky.

Scientists have only recently developed the technologies enabling them to understand how the pulsating aurora forms. Now, an international research team, led by Yoshizumi Miyoshi of Nagoya University's Institute for Space-Earth Environmental Research, has developed a theory to explain the wide-energy electron precipitations of pulsating auroras and conducted computer simulations that validate their theory.

Their findings suggest that both low- and high-energy electrons originate simultaneously from interactions between chorus waves and electrons in the Earth's magnetosphere.

Chorus waves are plasma waves generated near the magnetic equator. Once formed, they travel northwards and southwards, interacting with electrons in Earth's magnetosphere. This interaction energizes the electrons, scattering them down into the upper atmosphere, where they release the light energy that appears as a pulsating aurora.

The electrons that result from these interactions range from lower-energy ones, of only a few hundred kiloelectron volts, to very high-energy ones, of several thousand kiloelectron volts, or 'megaelectron' volts.

Miyoshi and his team suggest that the high-energy electrons of pulsating auroras are 'relativistic' electrons, otherwise known as killer electrons, because of the damage they can cause when they penetrate satellites.

"Our theory indicates that so-called killer electrons that precipitate into the middle atmosphere are associated with the pulsating aurora, and could be involved in ozone destruction," says Miyoshi.

The team next plans to test their theory by studying measurements taken during a space rocket mission called 'loss through auroral microburst pulsations' (LAMP), which is due to launch in December 2021. LAMP is a collaboration between NASA, the Japan Aerospace Exploration Agency (JAXA), Nagoya University, and other institutions. LAMP experiments will be able to observe the killer electrons associated with the pulsating aurora.

Newly published research carried out at the University of Guam has used a critically endangered species to show how trees modify leaf function to best exploit prevailing light conditions. The findings revealed numerous leaf traits that change depending on the light levels during leaf construction.

"The list of ways a leaf can modify its shape and structure is lengthy, and past research has not adequately looked at that entire list," said Benjamin Deloso, lead author of the study.

The results appear in the October issue of the journal Biology (doi:10.3390/biology9100333).

Terrestrial plants are unable to move after they find their permanent home, so they employ methods to maximize their growth potential under prevailing conditions by modifying their structure and behavior. The environmental factor that has been most studied in this line of botany research is the availability of light, as many trees begin their life in deep shade but eventually grow tall to position their leaves in full sun when they are old. These changes in prevailing light require the tree to modify the manner in which their leaves are constructed to capitalize on the light that is available at the time of leaf construction.

"One size does not fit all," Deloso said. "A leaf designed to perform in deep shade would try to use every bit of the limited light energy, but a leaf grown under full sun needs to refrain from being damaged by excessive energy."

The research team used Guam's critically endangered Serianthes nelsonii tree as the model species because of the complexity of its leaf design. This tree's leaf is classified as a bi-pinnate compound leaf, a designation that means a single leaf is comprised of many smaller leaflets that are arranged on linear structures that have a stem-like appearance. The primary outcome of the work was to show that this type of leaf modifies many whole-leaf traits in response to prevailing light conditions. Most literature on this subject has not completely considered many of these whole-leaf traits, and may have under-estimated the diversity of skills that compound leaves can benefit from while achieving the greatest growth potential.

This study provides an example of how plant species that are federally listed as endangered can be exploited for non-destructive research, helping to highlight the value of conserving the world's threatened biodiversity while demonstrating a universal concept.

The study was a continuation of several years of research at the University of Guam designed to understand the ecology of the species. The research program has identified recruitment as the greatest limitation of species survival. Recruitment is what botanists use to describe the transition of seedlings into larger juvenile plants that are better able to remain viable. Considerable seed germination and seedling establishment occur in Guam's habitat, but 100% of the seedlings die. Extreme shade is one of the possible stress factors that generate the seedling mortality. Testing this possibility by providing outplanted seedlings with a greater range of sunlight transmission than the 6% recorded in this study may provide answers to the extreme shade stress hypothesis.

The latest results have augmented the team's earlier research that demonstrated how a specialized leaf gland enables rapid leaflet movement when the light energy is excessive. This skill of being able to change the leaflet's orientation is an instantaneous behavior that mitigates the damage that may result from excessive sunlight exposure.

"Just because the tree can't move itself, that doesn't mean it can't move its leaves to avoid stress," Deloso said.

Serianthes nelsonii was listed on the Endangered Species Act in 1987. A formal plan to recover the species was published in 1994 and called for research to more fully understand the factors that limit success of the species. This latest publication adds to the expanding knowledge that the University of Guam is generating to inform conservation decisions into the future.

A Nagoya University-led research team in Japan has found a new neural pathway that links the circadian clock, stress, and wakefulness in mammals. The team identified a neuron, called the corticotropin-releasing factor (CRF) neuron, that becomes excessively active when the mammal is under stress, which could trigger insomnia and other sleep disorders. Their findings were recently published in the journal Science Advances.

Living organisms exhibit a 24-hour oscillation called the circadian rhythm. In mammals, the central circadian clock, located in the brain's suprachiasmatic nucleus (SCN) neurons, regulates the sleep-wake cycle. However, in the event of life-threatening situations, the circadian rhythm signal is shut off to keep the animal awake so that it can escape from danger even when it would normally be time to sleep. Although the temporary shutoff of the sleep-wake cycle is necessary for survival, excessive or prolonged stress caused by such dangers can trigger insomnia and other sleep disorders.

"It is well-known that the circadian clock and stress have an effect on sleep, but it was unclear which neural pathway is crucial for the circadian regulation of sleep and wakefulness," says Dr. Daisuke Ono of the Research Institute of Environmental Medicine at Nagoya University. To determine the pathway, a Nagoya University research team led by Prof. Akihiro Yamanaka and Dr. Ono, in collaboration with Takashi Sugiyama at Olympus Corporation in Japan, conducted a study using mice.

The researchers focused on CRF neurons -- which are known to play a role in stress response -- that are located in the paraventricular nucleus of the hypothalamus. They investigated how sleep and wakefulness in mice would be affected when the CRF neurons were activated. The results showed that the activated CRF neurons kept the animals awake and made them move around vigorously, indicating that their wakefulness was promoted. The researchers also observed that CRF neurons remained active when the mice were awake, and that when the neurons' activity was suppressed, the animals' wakefulness and locomotor activities were reduced.

Further investigations also showed that inhibitory neurons in the SCN, called GABAergic neurons, play a significant role in regulating the activity of CRF neurons, and that the activation of CRF neurons stimulates orexin neurons in the lateral hypothalamus, which results in the promotion of wakefulness.

The team thus concluded that GABAergic neurons in the SCN control the activity of CRF neurons, which ultimately regulates the sleep-wake cycle. "We identified this neural pathway in mice, which are nocturnal animals. Further studies are required to elucidate how the nocturnal and diurnal difference is regulated in the brain," says Dr. Ono.

"In today's society, sleep disorders are a serious problem. We hope our finding will contribute to the development of new therapies for insomnia and other sleep disorders caused by stress or a disturbed circadian rhythm."

Tsukuba, Japan -- With fall and winter holidays coming up, many will be pondering the relationship between food and sleep. Researchers led by Professor Masashi Yanagisawa at the University of Tsukuba in Japan hope they can focus people on the important middlemen in the equation: bacterial microbes in the gut. Their detailed study in mice revealed the extent to which bacteria can change the environment and contents of the intestines, which ultimately impacts behaviors like sleep.

The experiment itself was fairly simple. The researchers gave a group of mice a powerful cocktail of antibiotics for four weeks, which depleted them of intestinal microorganisms. Then, they compared intestinal contents between these mice and control mice who had the same diet. Digestion breaks food down into bits and pieces called metabolites. The research team found significant differences between metabolites in the microbiota-depleted mice and the control mice. As Professor Yanagisawa explains, "we found more than 200 metabolite differences between mouse groups. About 60 normal metabolites were missing in the microbiota-depleted mice, and the others differed in the amount, some more and some less than in the control mice."

The team next set out to determine what these metabolites normally do. Using metabolome set enrichment analysis, they found that the biological pathways most affected by the antibiotic treatment were those involved in making neurotransmitters, the molecules that cells in the brain use to communicate with each other. For example, the tryptophan-serotonin pathway was almost totally shut down; the microbiota-depleted mice had more tryptophan than controls, but almost zero serotonin. This shows that without important gut microbes, the mice could not make any serotonin from the tryptophan they were eating. The team also found that the mice were deficient in vitamin B6 metabolites, which accelerate production of the neurotransmitters serotonin and dopamine.

The team also analyzed how the mice slept by looking at brain activity in EEGs. They found that compared with the control mice, the microbiota-depleted mice had more REM and non-REM sleep at night--when mice are supposed to be active--and less non-REM sleep during the day--when mice should be mostly sleeping. The number of REM sleep episodes was higher both during the day and at night, whereas the number of non-REM episodes was higher during the day. In other words, the microbiota-depleted mice switched between sleep/wake stages more frequently than the controls.

Professor Yanagisawa speculates that the lack of serotonin was responsible for the sleep abnormalities; however, the exact mechanism still needs to be worked out. "We found that microbe depletion eliminated serotonin in the gut, and we know that serotonin levels in the brain can affect sleep/wake cycles," he says. "Thus, changing which microbes are in the gut by altering diet has the potential to help those who have trouble sleeping."

So, this holiday season, when you're feeling sleepy after eating tryptophan-stuffed turkey, please don't forget to thank your gut microbes!