Culture

Researchers from the Hubrecht Institute in Utrecht (The Netherlands) and the Max Planck Institute for Molecular Biomedicine in Münster (Germany) used computer simulations to reveal in atomic detail how a short piece of DNA opens while it is tightly wrapped around the proteins that package our genome. These simulations provide unprecedented insights into the mechanisms that regulate gene expression. The results were published in PLOS Computational Biology on the 3rd of June, 2021.

Every cell in the body contains two meters of DNA. In order to fit all the DNA in the cell's small nucleus, the DNA is tightly packed in a structure known as chromatin. Chromatin is an array of identical smaller structures named nucleosomes. In a single nucleosome, DNA is wrapped around 8 proteins called histones. Chromatin is not uniformly compact across the genome. The tightness of the packaging is important in regulating which genes are expressed and therefore which proteins are produced by a cell.

Transitions from tightly to loosely packed DNA - from closed to open chromatin - are essential for cells to convert to another cell type. These cell conversions are hallmarks of development and disease, but are also often used in regenerative therapies. Understanding how such transitions occur may contribute to understanding diseases and optimizing therapeutical cell type conversions.

Computational nanoscope

One step in the opening of chromatin is the motion of DNA while wrapped in nucleosomes. Like all molecular structures in our cells, nucleosomes are dynamic. They move, twist, breathe, unwrap and wrap again. Visualizing these motions using experimental methods is often very challenging. One alternative is to use the so-called "computational nanoscope".

Researchers use the term computational nanoscope to refer to a set of computer simulation methods. These methods enable them to visualize the movements of molecules over time. Over the past years, the methods have become so accurate that researchers started referring to them as a computational nanoscope; observing the molecules moving on the computer is similar to observing them under a very high resolution nanoscope.

Nucleosomes breathing

Jan Huertas and Vlad Cojocaru, supported by Hans Schöler from the Max Planck Institute for Molecular Biomedicine (Münster, Germany), generated multiple real-time movies of the movements of nucleosomes, each covering one microsecond from the nucleosome lifetime. Using these movies, they monitored how the nucleosomes open and close in a motion known as nucleosome breathing.

In their new paper, published in PLOS Computational Biology, Huertas and Cojocaru describe what causes nucleosome breathing. First, they found that the order in which the building blocks of DNA are arranged - the DNA sequence - is important for nucleosome breathing. Second, the dynamics of histone tails are essential for this process. These histone tails are flexible regions in the histones that play a role in the regulation of gene expression. While the role of histone tails has been studied intensively, little is known about how they influence the motions of single nucleosomes. With their simulations, Huertas and Cojocaru described the relationship between histone tails and nucleosome breathing in atomic detail.

Histone modifications

"Being able to observe the breathing of nucleosomes in computer simulations is very challenging. The fact that we have now been able to visualize this represents a major step towards simulating the complete spectrum of nucleosome dynamics, from breathing to unwrapping. It also allows us to study how these motions are affected by modifications of the histones, which occur in different cells and regions of our DNA. Our simulations revealed that two histone tails are responsible for keeping the nucleosome closed. Only when these flexible tails moved away from particular regions of DNA, the nucleosome was able to open," says the research leader, Vlad Cojocaru.

Jan Huertas, first author in the publication and recent PhD-graduate, adds: "Active (open) and inactive (closed) chromatin contain different modifications of histone tails. The next step is to perform simulations with such modifications. The atomic resolution of the simulations would allow us to pinpoint how each modification affects nucleosomes and chromatin dynamics."

Towards understanding epigenetics

All three researchers are excited about the future of the use of atomistic computer simulations in understanding gene expression mechanisms in development and disease. "With the further increase of computational power available in the world, we will soon be able to simulate milliseconds of a nucleosome lifetime with all its atoms included. Furthermore, we will be able to routinely simulate multiple nucleosomes to study the effect of different modifications of histones on gene expression. This will give unprecedented insights into the mechanisms that regulate gene expression," Cojocaru concludes.

Oncotarget published "Characterization of the inflammatory microenvironment and hepatic macrophage subsets in experimental hepatocellular carcinoma models" which reported that HCC typically develops on a background of chronic inflammation and fibrosis with tumor associated macrophages playing an important role in chronic inflammation-induced HCC and progression.

However, the liver harbors unique macrophages, resident liver Kupffer cells and monocyte-derived macrophages, and their contribution to HCC and to the population of TAMs is incompletely known.

Here, the authors characterized the tumor microenvironment and the proportion and transcriptional profile of hepatic macrophages in two commonly used HCC mouse models.

A gradually increased expression of inflammatory, immune regulatory, fibrotic and cell proliferation pathways and markers was observed during diethylnitrosamine - and non-alcoholic steatohepatitis -induced HCC development.

These insights are useful to further unravel sequential pathogenic events during hepatocarcinogenesis and direct future development of new treatment strategies for HCC.

Dr. Lindsey Devisscher from The Ghent University said, "The incidence of hepatocellular carcinoma (HCC) is increasing worldwide, and HCC is amongst the leading causes of cancer death globally."

"The incidence of hepatocellular carcinoma (HCC) is increasing worldwide, and HCC is amongst the leading causes of cancer death globally."

HCC is considered a classic inflammation-related cancer, whereby inflammation drives carcinogenesis by inducing continuous cycles of tissue damage, necrosis with regeneration and subsequent fibrosis, cell dysplasia and ultimately HCC lesions.

The observations that there were at least 4 nodules with an average tumor growth rate of 150% from 16 to 20 weeks of age, no visible metastasis and preserved liver function suggested that HCC induced in this model is equivalent to more advanced stages B to C of the Barcelona Clinic Liver Cancer staging system for patients.

The liver tumor microenvironment consists of cancer cells surrounded by extracellular matrix elements and different stromal cells such as fibroblasts, endothelial cells and inflammatory cells which secrete a variety of growth factors, cytokines or matrix remodeling enzymes.

Indeed, they previously reported that in models of DEN- and NASH-induced HCC, Mo massively infiltrate the liver KCs, whereas KC are partially depleted during chronic liver injury, including end-stage HCC.

This study assessed the time-dependent characteristics of the inflammatory micro-environment in the two aforementioned HCC mouse models, with an emphasis on the differential transcriptional profile of liver M/Users/anxiolydiot/Desktop/press-formatting-html.html subsets and the sequential changes in phenotype during the progression of HCC.

The Devisscher Research Team concluded in their Oncotarget Research Output, "HCC is an inflammation driven tumor, in which hepatic macrophage populations play a central role. KCs, Mo and Mo-M/Users/anxiolydiot/Desktop/press-formatting-html.html have divergent phenotypes that change with disease progression and these cell populations contribute to the population of TAMs in HCC. The knowledge that KCs also express typical TAM markers further contributes to the understanding of hepatocarcinogenesis in two different frequently used experimental mouse HCC models."

A growing number of people use they/them pronouns to signal their gender identity, but for many people, use of "they" to refer to a single individual takes some getting used to.

Results of a recent University of North Carolina at Chapel Hill study showed the social trend of announcing preferred pronouns, which is often seen in email signatures, Twitter bios and Zoom settings, improves how pronouns are understood.

"Announcing one's pronouns matters, and explicitly saying that someone uses they/them pronouns increases the chance that others will successfully interpret the pronoun in this way in the future," said Jennifer Arnold, a UNC-Chapel Hill professor of psychology and neuroscience who led the study published in Psychonomic Bulletin & Review.

There is a psychology of language and Arnold studies the mental steps that underlie the way we process language.

Singular "they" has been around for centuries. But its frequency and range of uses is expanding to those who identify as non-binary, that is, those who do not exclusively identify as male or female. Using the pronouns that a person goes by is considered a sign of respect.

Still sometimes people can use the wrong pronoun without realizing it or meaning any harm.

For the recent study Arnold worked with undergraduate students Heather Mayo and Lisa Dong to test the impact of explicitly discussing pronouns. For example, saying "Alex uses they/them pronouns."

During experiments, 184 participants from the United States, United Kingdom and Australia read short stories such as "Alex went running with Liz. They fell down." Answers to "Who fell down?" indicated whether the participants interpreted they as Alex or Alex and Liz.

Singular responses were found more often when Alex was either the only person in the story or when Alex was mentioned first. When Alex was listed as second, the rate of assigning singular interpretations was very low, occurring about 20 percent of the time. It was especially hard to get without instruction about preferred pronouns.

The singular interpretation was stronger - in some experiments doubling the chance of getting pronouns right -- when participants heard explicit instructions that Alex uses they/them pronouns. However, participants in all experiments had the opportunity to learn this through observation and illustrations.

"We found that people adopted the singular interpretation more often when they had been explicitly told a person uses they/them pronouns in comparison with people who just figured it out from the context of a conversation," Arnold said.

(Geneva, 5 June 2021) Mass screening of school age children has led to significantly higher numbers of coeliac disease cases being diagnosed, according to a new study presented today at the 6th World Congress of Paediatric Gastroenterology, Hepatology and Nutrition.

Researchers in Italy found double the number of cases of the autoimmune disease - where the body produces antibodies to gluten, a protein found in wheat, barley, and rye - in school children compared to a similar study by the same group 25 years ago.

A new screening programme of 7,760 children aged from five to 11 in eight provinces of Italy found that the overall prevalence of coeliac disease was 1.6%, much higher than the approximate 1% of the global population thought to be currently affected by the condition. The children were screened with a finger-tip blood test for Human Leukocyte Antigens (HLA) gene mutations which predisposes a child to developing coeliac disease. If they tested positive the children were then checked for antibodies to gluten. Diagnosis was then confirmed using the ESPGHAN (European Society for Paediatric, Gastroenterology, Hepatology and Nutrition) criteria.

Lead author of the CELI SCREEN multi-centre trial,i Prof. Elena Lionetti, says the study showed that screening in childhood leads to more cases of coeliac disease being diagnosed than in standard care (where children are tested if they present with symptoms, or are screened because of a family history of the disease).

'Our study showed that prevalence of coeliac disease in schoolchildren has doubled over the past 25 years when compared to figures reported by our team in a similar school age group,' says Prof. Lionetti. 'Our sentiment is that there are more cases of coeliac disease than in the past, and that we could not discover them without a screening strategy.'

'At the moment 70% of coeliac disease patients are going undiagnosed and this study shows that significantly more could be identified, and at an earlier stage, if screening were carried out in childhood with non-invasive screening tests. Diagnosis and avoiding gluten could potentially prevent damage to the villi (finger-like projections that line the gut), which can lead to malabsorption of nutrients and long-term conditions such as growth problems, fatigue and osteoporosis (a fragile bone condition).'

'The study has shown that screening is an effective tool for diagnosing coeliac disease in children which could potentially help avoid a lot of unnecessary suffering from what can be a hard-to-detect condition.'

Commenting on the research, Tunde Koltai, who is Chair of AOECS (Association of European Coeliac Societies) and Patient Representative of the ESPGHAN Public Affairs Committee, added: 'This new study adds to the growing evidence base that the number of people in Europe with coeliac disease is rising, yet many still remain undiagnosed. It is essential that we adopt an effective screening strategy for coeliac disease across Europe to ensure children and the wider population are diagnosed as early as possible so that they can have the best possible quality of life'.

Coeliac disease is caused by the body producing antibodies to gluten, a protein found in wheat, barley, and rye and used to make foods including bread, pasta, biscuits, cake, and some breakfast cereals. The antibodies damage the gut lining causing symptoms such as bloating, pain, diarrhoea, anaemia, and other conditions connected to malabsorption of nutrients, including fatigue, anaemia, osteoporosis, and fertility problems. In infants and children, coeliac disease can cause abdominal pain, bloating, and vomiting, as well as lead to poor growth and delay puberty.

Coeliac disease is one of the most common lifelong conditions in European countries. Following a strict gluten-free diet is an effective treatment, causing symptoms to disappear and gut damage to gradually heal.

The melodic and diverse songs of birds frequently inspire pop songs and poems, and have been for centuries, all the way back to Shakespeare's "Romeo and Juliet" or "The Nightingale" by H.C. Andersen.

Despite our fascination with birdsong, we are only beginning to figure out how this complicated behavior is being produced and which extraordinary specializations enabled songbirds to develop the diverse sound scape we can listen to every morning.

Songbirds produce their beautiful songs using a special vocal organ unique to birds, the syrinx. It is surrounded by muscles that contract with superfast speed, two orders of magnitude faster than e.g. human leg muscles.

"We found that songbirds have incredible fine control of their song, including frequency control below one Hertz", says Iris Adam, lead author on the study and Assistant Professor at Department of Biology, University of Southern Denmark.

A motor unit is the fundamental contraction unit of muscle and consists of a motor neuron and the number of muscle fibers it connects to and activates. Combining tissue preparations to count muscle and nerve fibers and mathematical models the researchers could show that a large portion of the motor units must be very small and even as small as single muscle fiber.

"Motor units vary in size from several hundreds or thousands of muscle fibers in our leg muscles down to only 5-10 in the muscles controlling eye position and the muscles in the larynx", says Dr. Coen Elemans, senior author on the study and head of the Sound Communication and Behavior group at the University of Southern Denmark.

"In zebra finch song muscles our models predicted that 13-17% of the motor neurons innervates a single muscle fiber."

This was such an extraordinary claim that the researchers developed a new technique that can measure the activity of all muscle fibers within a small muscle.

"Our new method allowed us for the first time to activate single motor neurons and visualize and record the activity of all responding muscle fibers simultaneously.", Adam says.

"Like this we were able to show that the song muscles of zebra finches indeed contain motor units a s small as one muscle fiber.", Adam adds.

To be able to understand what the effect such small motor units can have on song the researchers also measured the amount of stress the muscles can make and how such stress changes the frequency of the sound.

Adam: "Next to small motor units, we discovered that songbird vocal muscles have the lowest stress measured in any vertebrate."

"To be able to study how changes in muscle force alter the sound made by the birds' vocal organ, the syrinx, we had to invent a new setup" Elemans adds.

"This setup blows air through the syrinx while we can control the muscles with small motors".

Songbird vocal muscles certainly pack a lot of extremes. "They are among the fastest muscles known, and now we show that they are also the weakest with the highest level of control possible", says Adam.

This fine control is important. Previous research has shown that females can detect these small changes and use it to decide whether they are attracted to a male or not.

Songbirds evolved about 40 million years ago and quickly radiated into the speciose group of birds we know today. Song is crucial for females to find and judge males and can even drive speciation. A few important special features are thought to have been important for their success. Just as humans, songbirds need to learn their song from a tutor by imitation.

Adam: "We think that next to a special syrinx and their amazing ability to imitate sounds, the fine gradation of the song features such as pitch has increased the amount of different sounds a bird can make."

"We suggest that the fine graduation of sound has contributed to the radiated of songbirds", Elemans concludes.

link to Coen Elemans Lab at University of Southern Denmark: http://www.celemans.com/index.html

What The Study Did: This survey study in California assesses what the public knows about extreme risk protection orders and if people are willing to use them to prevent firearm-related harm, both in general and when a family member is at risk, and if not, why not. The orders temporarily suspend firearm and ammunition access by individuals a judge has deemed to be at substantial risk of harming themselves or others.

Authors: Nicole Kravitz-Wirtz, Ph.D., M.P.H., of the University of California Davis School of Medicine in Sacramento, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamahealthforum.2021.0975)

Editor's Note: The article includes funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

Accurate soft tissue measurements are critical when making reconstructions of human ancestors, a new study from the University of Adelaide and Arizona State University has found.

"Reconstructing extinct members of the Hominidae, or hominids, including their facial soft tissue, has become increasingly popular with many approximations of their faces presented in museum exhibitions, popular science publications and at conference presentations worldwide," said lead author PhD student Ryan M. Campbell from the University of Adelaide.

"It is essential that accurate facial soft tissue thickness measurements are used when reconstructing the faces of hominids to reduce the variability exhibited in reconstructions of the same individuals."

Hominids have been readily accepted to line the halls of even the most trusted institutions. They are predominantly used for disseminating scientific information to the public in museum displays and students in university courses, which will influence the way humanity is perceived and defined more generally.

"Up until now soft tissue reconstruction has been based on mean tissue depth measurements which does not take into account variation in tissue depths between individuals," says Mr Campbell.

In this study, published in the journal PLOS ONE, the authors have formulated a facial soft tissue thickness dataset for adult chimpanzees, and a set of regression equations that can be used to reconstruct the soft tissues for ancient hominids, such as those dated from 4.0 to 1.2 million years ago.

The study was co-authored by Gabriel Vinas, a Master of Fine Arts candidate at Arizona State University who handles the sculpting in the lab.

"Correlations have been found and multiple regression models have been used to generate equations for improving estimations of soft tissue thickness from craniometrics in modern humans," he said.

"We looked at tissue depths in present day chimpanzees to identify correlations in skin and bone."

This article represents the first time that such a collection of tissue depth data has been collected and presented for chimpanzees in a systematic manner.

"The soft tissue thickness data for chimpanzees are freely available for anyone to download on Figshare.

"The equations, which resulted directly from this research, are also included and can be implemented in future practitioners' reconstructions," said Mr Campbell.

"This research is invaluable for future efforts reconstructing ancient hominids, as well as for comparative studies within and outside the discipline of biological/physical anthropology."

(SACRAMENTO, Calif.) -- Extreme risk protection orders, also known as gun violence restraining orders (GVROs) or "red flag" orders, exist in 19 states and the District of Columbia.

The laws allow law enforcement, family and household members, some co-workers, employers and teachers to work with a judge to temporarily remove access to firearms and ammunition from people at significant risk of self-harm or harming others.

But an obstacle to implementing these preventive measures has been revealed in a new study from the Violence Prevention Research Program at UC Davis Health. Although GVROs have been available in California for five years, two-thirds of the Californians surveyed for the study had never heard of them.

"Firearm violence is preventable, not inevitable. Raising public awareness about proactive ways for people to intervene can be crucial for preventing violence before it occurs," said Nicole Kravitz-Wirtz, lead author of the study and an assistant professor with the Violence Prevention Research Program.

GVROs are only available if an individual has or could get a gun, and other options to protect against harm have failed or are not appropriate.

The study appears June 4 in JAMA Health Forum.

Majority, including gun owners, would be somewhat or very willing to use a GVRO

The survey was completed in July 2020 by 2,870 adults statistically representative of the adult population in California. It also assessed personal willingness to use a GVRO when a family member was at risk.

After reading a brief description of California's GVRO law, more than 80% of the respondents said they would be somewhat or very willing to ask a judge to issue a GVRO if a family member had threatened to physically hurt themselves, someone else or a group of people.

Respondents who lived in homes with gun owners expressed the highest levels of willingness to ask a judge for a GVRO. The responses ranged from 84% who were somewhat or very willing if a family member were experiencing an emotional crisis to 95% if a family member had threatened to physically hurt someone else.

The study included five risk scenarios of a person who has or could get a gun and:

was experiencing an emotional crisis;

has severe dementia or similar condition;

has threatened to physically hurt themselves;

has threatened to physically hurt someone else; or

has threatened to physically hurt a group of people.

A majority of respondents who identified as gun owners -- 70% to 86%, depending on the described risk scenario -- said they would be somewhat or very willing to ask a judge for a GVRO if a family member had threatened to harm themselves or others.

About 30% of the respondents reported they were unwilling to ask a judge for a GVRO for a family member in at least one of the described risk scenarios. The most frequently cited reason for being unwilling was not knowing enough about GVROs. The second most common reason was the belief that the described risk scenarios are personal or family matters.

GVROs can be effective tools for preventing violence. They leverage the knowledge of those who are often the first to recognize someone they care about is in crisis or behaving dangerously and provide a tool for proactive intervention.

"Given the evidence of this and prior studies, the take-home message is clear: 'If you see or hear something, please say something,'" said Garen Wintemute, director of the UC Davis Violence Prevention Research Program and professor of emergency medicine at UC Davis Health.

Prevention measures gaining traction in United States

Firearms are involved in half of suicides and three-quarters of homicides in the United States, accounting for nearly 39,000 violent deaths in 2019, the most recent year in which data are available from the Centers for Disease Control and Prevention.

In California, as in many other states, GVRO legislation was passed in the wake of a public mass shooting. Past research suggests that GVROs have been used successfully to prevent mass harm and that these orders are particularly effective for suicide prevention. But the use of GVROs remains relatively uncommon.

In California, the use of GVROs has grown from 70 orders in 2016, the year the law went into effect, to 700 in 2019. However, overall uptake of the law has been slow, possibly due to a lack of awareness. Given high levels of personal willingness to use a GVRO, including among gun owners and non-owners who live with owners, the current study indicates that improved knowledge of GVROs may lead to increased usage to prevent firearm injury and death in California and other parts of the country.

"GVROs are promising tools for preventing firearm-related harm. Our findings are consistent with national studies indicating that many firearm violence prevention policies have widespread public support and that general consensus exists between firearm owners and non-owners," Kravitz-Wirtz says.

Fukuoka, Japan--According to the Global Burden of Disease Study 2017, close to nine percent of the global population lives with some form of chronic kidney disease, or CKD. Not only does the condition affect renal function, CKD has long been associated with increased risk of cardiovascular disease.

Now, in a new study that could aid the development of therapeutic drugs to reduce these cardiac complications, researchers led by Kyushu University have found an underlying molecular pathway that can explain how chronic kidney disease induces heart failure.

Studying mice, the researchers found that a key driver is the dysfunction of a type of white blood cell called a monocyte. The dysfunction is caused by increased levels of vitamin A and its binding protein--a common symptom of chronic kidney disease--breaking a well-known genetic pathway: the circadian clock.

The circadian clock is one of the most indispensable biological functions in living organisms. Common understanding of the pathway is that it controls our sleep patterns. However, the circadian clock plays a much larger role, affecting blood pressure, metabolic rate, and even hormone levels. In fact, nearly 10% of our genes are directly influenced by the circadian clock.

These properties made it a natural target for Shigehiro Ohdo, professor of Kyushu University's Faculty of Pharmaceutical Sciences, and his team for investigating the causes of chronic kidney disease-induced heart inflammation and fibrosis.

"We found that mice with a mutated Clock gene--one of the main regulators of the circadian clock--have decreased symptoms of heart problems related to chronic kidney disease, despite having high blood pressure," explains Yuya Yoshida, one of the first authors of the study published in the journal Nature Communications.

To search for the underlying cause of this protective effect, the team looked for abnormalities in genes that connect Clock and kidney dysfunction.

"Our investigation led us to find that a protein called 'G protein-coupled receptor 68,' or GPR68, produced in monocytes was playing a key role. GPR68 is known to increase the production of proteins that cause inflammation, and more importantly, it is regulated by the Clock gene," states Naoya Matsunaga, another author of the study.

One sign of kidney dysfunction is elevated levels of vitamin A and its binding protein, two molecules that are usually carefully controlled. The researchers found that this elevation disrupts the normal activity of the circadian clock in monocytes, which in turn over-express GPR68.

These high-GPR68-expressing monocytes then infiltrate the heart and cause inflammation and fibrosis. This explains why mice with defective Clock genes have less severe CKD-induced heart problems: there is no Clock gene to produce GPR68.

"Our study reveals a previously unknown role of monocytic clock genes in CKD-induced heart failure," concludes Ohdo. "The findings will help us develop therapeutic drugs such as ones targeting GPR68. We also can investigate better treatments for abnormal vitamin A accumulation in the blood."

Coral insights into 1,000 years of seasonal changes in the Arabian Sea warn of significant impacts caused by global warming.

Every year, the southwesterly winds of the summer monsoon sweep down the Arabian Peninsula, pushing the surface waters of the Arabian Sea away from the coast and driving an upwelling of deep waters to the surface. This rising seawater is colder and less saline than the surface water and is rich in nutrients, providing energy for the various organisms living in the Arabian Sea and Indian Ocean.

Scientists from Japan, Taiwan and Germany, including coral reef scientist Dr. Tsuyoshi Watanabe of Hokkaido University, have uncovered evidence from corals off the coast of Oman suggesting that global warming is causing changes to the Arabian Sea that could impact the climate, ecosystems and socioeconomics of the densely populated areas surrounding the Indian Ocean. The findings were published in the journal Geophysical Research Letters.

Stronger summer monsoon winds lead to a stronger upwelling in the Arabian Sea. Stronger winds form when the air over the Indian subcontinent warms more rapidly than the air over the Indian Ocean. Recently, however, the opposite has been happening. Scientists wanted to know how this change affects the Arabian Sea upwelling, but the phenomenon has not been monitored continuously, so available measurements aren't enough to tell the whole story.

Watanabe and his colleagues analysed fossil and modern corals off an Omani island in the Arabian Sea. They identified the ages of the corals they collected and established a correlation between coral data and seawater temperature changes over a very fine timescale, and used that information to extrapolate salinity changes. The four fossil corals they used dated to approximately 1167 CE, 1624 CE, 1703 CE and 1968 CE, respectively. They took samples from the corals at different depths towards their cores, and then analysed the ratio of strontium to calcium in the samples, as well as the amounts of oxygen and carbon isotopes. The growth rate of the corals is steady over centuries, and the skeletons contain a record of the changes in elements. Generally, as water temperatures rise, the strontium-to-calcium ratio and isotope oxygen-18 in coral decrease.

The results showed that the summer Arabian Sea upwelling was relatively stable through the warmer period of the medieval climate anomaly in the 12th century; the cooler little ice age, which extended between the 14th and 19th centuries AD; and up until the mid-20th century. After this period, however, the scientists observed a clear weakening of the Arabian Sea upwelling. They reason this can most likely be explained by faster warming of the northern Indian Ocean, caused by greenhouse gases, and slowed warming of the Indian subcontinent, caused by the absorption of sunrays by aerosol emissions over South Asia. This then weakens the summer monsoon winds, impacting the strength of the Arabian Sea upwelling.

"The seasonal upwelling is vital for commercial fishing and has significant impacts on the regional climate, ecosystems and socioeconomics," says Tsuyoshi Watanabe. "Our findings imply that weakening of the Arabian Sea upwelling is likely to continue along with global warming, impacting monsoon rainfalls, sea levels, fisheries and even agricultural production."

Delicious to some, but a bitter bane to others' taste buds, vegetables like broccoli rabe, bok choy and turnips are a dinner staple ---and picky eater conflict --- around the world.

It all likely started in the mountains near present-day Afghanistan, where humans first domesticated turnips 3,500 to 6,000 years ago, according to a new study recently published in the journal Molecular Biology and Evolution. University of Wisconsin-Madison Professor of Botany Eve Emshwiller and her former graduate student Alex McAlvay (now an assistant curator assistant curator of economic botany at The New York Botanical Garden) led the research.

To identify the genetic root of it all, the research team reconstructed an evolutionary tree from a comparative DNA sequences analysis of more than 400 different varieties of the species Brassica rapa from around the world.

Just as varieties of ancient corn look very different than the hybrid crops of today's farms, Brassica revealed a similar past.

From this tree, they discovered that Central Asian turnips were the most genetically diverse crops. That in turn suggested that humans in the region may have valued most the fatter, starch-rich taproots that became turnips several thousand years ago, as agriculture took root around the world.

The research team identified both the Hindu Kush mountains as the epicenter of domestication, and weeds from the Caucasus region as among the most likely wild relatives of the species' vegetable crops. Turnips then spread west to Europe and east to East Asia, where farmers later selected for larger leaves. These leafy versions became bok choy, napa cabbage and broccoli rabe, among other vegetables found in today's grocery stores.

Interestingly, ancient cultures also pointed to evidence that matched the genetic analysis. Ancient literary references to turnips in the region, and the apparent existence of the word for "turnip" in the ancestor of languages from the region, also supported the turnip as the original domesticated form.

"It's important to know where your crops are from," said McAlvay. "In this work, we had a broader data set than had been used previously. And we also had more wild collections than had been used previously. Having enough of those non-cultivated forms allowed us to distinguish between those feral or escaped weeds and the ones that are likely truly wild."

Before the study, it remained unclear if turnips or oilseeds were the first tamed varieties.

This confusion has stemmed from the ubiquity of Brassica rapa and its many weedy forms, which could be truly wild or merely escaped crops turned feral. While wild and feral forms look similar, their genetic histories are vastly different.

"That parallel selection for leafy forms is interesting and gives us an evolutionary system to compare how this leafiness trait can arise," said McAlvay. Other farmers selected other lineages for their oil-rich seeds.

The true identities of these wild relatives -- which have been hidden for years because of the tangled web of family relationships in the species -- also provides valuable information to evolutionary biologists and crop breeders alike.

"We might want this information in order to conserve those wild relatives, so they don't disappear in the course of habitats being lost," said Emshwiller. Wild plants can confer valuable traits when crossed with crops, which typically lose their hardiness during domestication.

"And domestication is a good way to study evolution in general," Emshwiller adds. "If we understand how crops evolved under human influence, that can help us extrapolate to how wild plants might evolve under different kinds of selection."

For their next steps, the researchers want to include more weedy samples mainly from the original site of domestication, the Hindu Kush region. The region should be host to many different wild versions of Brassica rapa.

The study may also provide important information for this worldwide important crop and preserve important genetic resources to make brassica varieties more resilient as climate change and new pests may threaten some crops in the future.

Proteins are the key players in our cellular processes. Their generation follows principles called transcription and translation. First, DNA copies its genetic information to messenger RNA (mRNA), which then determines the sequence in a chain of amino acids, which finally fold into a protein. The reality, however, is more complex: More than 90 per cent of our genes do not result in only one mRNA and then one protein, but a process called alternative splicing produces several mRNA variants, only some of which are then translated into a specific protein isoform in a specific cell at a given time. Conventional techniques to detect alternative splicing are mostly single time-point measurements that are work-intense and cannot reliably monitor over time which protein isoforms are actually translated in the cell.

Researchers at Helmholtz Zentrum München and the Technical University of Munich (TUM) thus developed a new bioengineered reporter system called EXSISERS. The idea behind it is to generate a signal such as light as soon as a specific protein isoform is being translated. "This is possible via designer reporter proteins that can cut themselves out of the nascent amino acid chain- they are self-excising," says Dong-Jiunn Jeffery Truong. "In analogy to the famous cut and restore rope trick in magic performances, the excision of the reporter leaves no scar in the natural protein isoforms." The researchers have already applied this method to human cells in culture. One of their aims was to analyze the expression of isoforms of a protein called Tau, which is associated with neurodegenerative diseases such as Parkinson's. This makes Tau isoforms a potential target for future molecular therapies.

"Bioengineering inspired by natural biomolecular processes will make it possible to observe many other fundamental cellular processes non-invasively," says Gil Gregor Westmeyer. "The more cellular parameters we can monitor, the better we can develop targeted molecular interventions for future cellular therapies, for example, to treat neurodegenerative diseases." Westmeyer and his team are already collaborating with several academic laboratories that use the new reporter system to obtain a more comprehensive understanding of isoform expression in cells and its implication in diseases.

The first evidence of a genetic link explaining why some people who catch Covid-19 don't become sick has been discovered

A scientific and medical team led by Newcastle University, UK, has demonstrated that the gene, HLA-DRB1*04:01, is found three times as often in people who are asymptomatic. This suggests that people with this gene have some level of protection from severe Covid.

The study, funded by Innovate UK, the UK's innovation agency, compared asymptomatic people to patients from the same community who developed severe Covid but had no underlying illnesses, and is published in the HLA journal.

The study team believe this is the first clear evidence of genetic resistance because this study compared severely affected people with an asymptomatic COVID group and used next generation sequencing to focus in detail and at scale on the HLA genes which are packed together on chromosome 6. Other studies have scanned the whole genome but that approach is less effective in the tissue typing complex.

Genome wide studies can be likened to a satellite image. The high density and complexity of the histocompatibility complex and variation in different populations means significant variation can be overlooked. For example, different alleles or versions of the same gene could have opposite effects on the immune response. This study was much more focused and compared symptomatic to asymptomatic in the same population revealing the "protective" qualities of the allele.

It is known that the human leukocyte antigen gene identified, HLA-DRB1*04:01, is directly correlated to latitude and longitude. This means more people in the North and West of Europe are likely to have this gene.

This suggests that populations of European descent will be more likely to remain asymptomatic but still transmit the disease to susceptible populations.

Dr Carlos Echevarria from the Translational and Clinical Research Institute, Newcastle University who also works as a Respiratory Consultant in the Newcastle Hospitals NHS Foundation Trust and is a co-author of the paper says: "This is an important finding as it may explain why some people catch Covid but don't get sick.

"It could lead us to a genetic test which may indicate who we need to prioritise for future vaccinations."

"At a population level, this is important for us to know because when we have lots of people who are resistant, so they catch Covid but don't show symptoms, then they risk spreading the virus while asymptomatic."

The effect of genes being linked to geolocation is an accepted scientific concept and it is well known that HLA genes develop over generations in reaction to disease-causing pathogens.

Study author, David Langton, whose company ExplantLab helped fund the study through an Innovate UK research award, added: "Some of the most interesting findings were the relationships between longitude and latitude and HLA gene frequency. It has long been known that the incidence of multiple sclerosis increases with increasing latitude. This has been put down in part to reduced UV exposure and therefore lower vitamin D levels. We weren't aware, however, that one of the main risk genes for MS, that is DRB1*15:01, directly correlates to latitude.

"This highlights the complex interaction between environment, genetics and disease. We know some HLA genes are vitamin D responsive, and that low vitamin D levels are a risk factor for severe COVID and we are doing further work in this area."

The study used samples from 49 patients with severe Covid who had been hospitalised with respiratory failure, samples from an asymptomatic group of 69 hospital workers who had tested positive through routine blood antibody testing and a control group from a study into the relationship between HLA genotypes and the outcomes of joint replacement surgery.

The research used next generation sequencing machines to study the different versions, or alleles, of the HLA genes in depth which was combined with a variety of expertise and modelling. The work was limited to samples from North East England during the first lockdown, this reduced variation in the study groups but more studies will be needed in the UK and other populations as there may be different copies of the HLA genes providing resistance in other populations.

They recently published their findings in the renowned journal "Advanced Materials". Cells are not only our biological building blocks, but also highly dynamic, active systems. The research group led by Professor Käs has succeeded in significantly reducing these dynamics with heavy water, without damaging the cells.

"Generally, a lot of people know heavy water for its important technical use in nuclear power plants. We took a different approach here and were able to show that for cells, time - or, more specifically, their dynamics - can be significantly slowed down in the presence of heavy water," said Käs, who has devoted himself to researching the physical properties of cells and tissue. The research showed on various biological levels that the movement of cells and their dynamics was only taking place in slow motion. "It is very intriguing that cellular dynamics can be slowed down at the same temperature. So far, only the theory of relativity has offered such possibilities in the physical context," explained Käs. He added that the results form the basis of a method to offer cells and organs longer-lasting protection against degeneration.

The researchers confirmed this effect with a variety of complementary methods and attributed the observations to an increased interaction between the structural proteins. "Heavy water also forms hydrogen bonds, but these are stronger than in normal aqueous environments. As a result, structural proteins such as actin seem to interact more strongly with one another and briefly stick together. What is spectacular here is that the effects are reversible, with cells showing their native properties again as soon as they are transferred into a normal aqueous medium," said Dr Jörg Schnauß. "What is even more astonishing is that these changes show the fingerprint of a passive material. However, cells are highly active and far from thermodynamic equilibrium. If they behave like a passive material, they are usually dead," added Käs.

However, as the researchers were able to show, this was not the case in their experiments. They now hope to be able to use the knowledge gained to keep cells or even tissue vital for longer. If this approach is confirmed, heavy water could be used for longer storage times, for example during organ transplants.

Graphene may be among the most exciting scientific discoveries of the last century. While it is strikingly familiar to us--graphene is considered an allotrope of carbon, meaning that it essentially the same substance as graphite but in a different atomic structure--graphene also opened up a new world of possibilities for designing and building new technologies.

The material is two-dimensional, meaning that each "sheet" of graphene is only 1 atom thick, but its bonds make it as strong as some of the world's hardest metal alloys while remaining lightweight and flexible. This valuable, unique mix of properties have piqued the interest of scientists from a wide range of fields, leading to research in using graphene for next-generation electronics, new coatings on industrial instruments and tools, and new biomedical technologies.

It is perhaps graphene's immense potential that has consequently caused one of its biggest challenges--graphene is difficult to produce in large volumes, and demand for the material is continually growing. Recent research indicates that using a liquid copper catalyst may be a fast, efficient way for producing graphene, but researchers only have a limited understanding of molecular interactions happening during these brief, chaotic moments that lead to graphene formation, meaning they cannot yet use the method to reliably produce flawless graphene sheets.

In order to address these challenges and help develop methods for quicker graphene production, a team of researchers at the Technical University of Munich (TUM) has been using the JUWELS and SuperMUC-NG high-performance computing (HPC) systems at the Jülich Supercomputing Centre (JSC) and Leibniz Supercomputing Centre (LRZ) to run high-resolution simulations of graphene formation on liquid copper.

A window into experiment

Graphene's appeal primarily stems from the material's perfectly uniform crystal structure, meaning that producing graphene with impurities is wasted effort. For laboratory settings or circumstances where only a small amount of graphene is needed, researchers can place a piece of scotch tape onto a graphite crystal and "peel" away atomic layers of the graphite using a technique that resembles how one would use tape or another adhesive to help remove pet hair from clothing. While this reliably produces flawless graphene layers, the process is slow and impractical for creating graphene for large-scale applications.

Industry requires methods that could reliably produce high-quality graphene cheaper and faster. One of the more promising methods being investigated involves using a liquid metal catalyst to facilitate the self-assembly of carbon atoms from molecular precursors into a single graphene sheet growing on top of the liquid metal. While the liquid offers the ability to scale up graphene production efficiently, it also introduces a host of complications, such as the high temperatures required to melt the typical metals used, such as copper. When designing new materials, researchers use experiments to see how atoms interact under a variety of conditions. While technological advances have opened up new ways for gaining insight into atomic-scale behavior even under extreme conditions such as very high temperatures, experimental techniques do not always allow researchers to observe the ultra-fast reactions that facilitate the correct changes to a material's atomic structure (or what aspects of the reaction may have introduced impurities). This is where computer simulations can be of help, however, simulating the behavior of a dynamic system such as a liquid is not without its own set of complications.

"The problem describing anything like this is you need to apply molecular dynamics (MD) simulations to get the right sampling," Andersen said. "Then, of course, there is the system size--you need to have a large enough system to accurately simulate the behavior of the liquid." Unlike experiments, molecular dynamics simulations offer researchers the ability to look at events happening on the atomic scale from a variety of different angles or pause the simulation to focus on different aspects.

While MD simulations offer researchers insights into the movement of individual atoms and chemical reactions that could not be observed during experiments, they do have their own challenges. Chief among them is the compromise between accuracy and cost--when relying on accurate ab initio methods to drive the MD simulations, it is extremely computationally expensive to get simulations that are large enough and last long enough to accurately model these reactions in a meaningful way.

Andersen and her colleagues used about 2,500 cores on JUWELS in periods stretching over more than one month for the recent simulations. Despite the massive computational effort, the team could still only simulate around 1,500 atoms over picoseconds of time. While these may sound like modest numbers, these simulations were among the largest done of ab initio MD simulations of graphene on liquid copper. The team uses these highly accurate simulations to help develop cheaper methods to drive the MD simulations so that it becomes possible to simulate larger systems and longer timescales without compromising the accuracy.

Strengthening links in the chain

The team published its record-breaking simulation work in the Journal of Chemical Physics, then used those simulations to compare with experimental data obtained in their most recent paper, which appeared in ACS Nano.

Andersen indicated that current-generation supercomputers, such as JUWELS and SuperMUC-NG, enabled the team to run its simulation. Next generation machines, however, would open up even more possibilities, as researchers could more rapidly simulate larger numbers or systems over longer periods of time.

Andersen received her PhD in 2014, and indicated that graphene research has exploded during the same period. "It is fascinating that the material is such a recent research focus--it is almost encapsulated in my own scientific career that people have looked closely at it," she said. Despite the need for more research into using liquid catalysts to produce graphene, Andersen indicated that the two-pronged approach of using both HPC and experiment would be essential to further graphene's development and, in turn, use in commercial and industrial applications. "In this research, there is a great interplay between theory and experiment, and I have been on both sides of this research," she said.