Culture

Men with a history of obesity in their late teens are, in adult life, more at risk of a blood clot (thrombus) in a leg or lung, according to a study from the University of Gothenburg study shows. The risk rises successively and is highest in those who were severely obese in adolescence.

A thrombus in the leg or lung is known as venous thromboembolism (VTE). This is one of our most common cardiovascular diseases. Risk increases with advancing age and, overall, 5-10 percent of the population are affected at some time during their lives. The disease is potentially fatal, but its degree of severity varies.

The current study, published in Journal of Internal Medicine, is based on data on 1,639,838 men who enlisted for military service in Sweden in the years 1969-2005. Their average age on enlistment was just over 18 years. These individuals were followed up using patient and cause-of-death registers.

During the follow-up period, with a median duration of 28 years, a blood clot in the leg or lung was registered among just over 1 percent (n=18,665) of the study participants. A clear association was found between body mass index (BMI) at the time of enlistment and subsequent thrombus risk.

A successive rise in VTE risk was also observed in the group in the middle and the upper part of the normal BMI range (20-25), compared with the lower part of the normal range (18.5-20).

The risk then continued to rise in the two higher BMI groups, those with obesity and severe obesity, to which more than 36,000 of the study participants belonged.

In the group with obesity (BMI 30-35), the relative risk was 2.93 compared with the reference group in the study -- over twice as high. For those with severe obesity, the corresponding relative risk was 4.95, i.e. a nearly fivefold risk for blood clots in the leg or lung during the follow-up period.

Katarina Glise Sandblad is a PhD student at Sahlgrenska Academy, University of Gothenburg, a resident physician specializing in internal medicine at Sahlgrenska University Hospital and the first author of the study.

"Up to now, the association between VTE and obesity has been studied mainly in populations where BMI is measured relatively late in life. By then, the study participants may have developed obesity-related diseases, such as certain forms of cancer, that also affect their thrombus risk. Consequently, there's a danger of underestimating the risk from obesity. As obesity and severe obesity become more prevalent among children and adolescents, it's increasingly important to study the long-term risks involved," Dr Glise Sandblad says.

Although the current study covers men only, the patterns and associations found are probably similar for women, in the research group's opinion. Heading the group is Annika Rosengren, Professor of Medicine at the University of Gothenburg.
The group has previously conducted studies of obesity and outcomes other than VTE, such as heart attack, stroke, heart failure and cardiomyopathy, where similar patterns in both men and women have been observed.

A research team including research scientist Atsuko Kobayashi from the Earth-Life Science Institute (ELSI) at Tokyo Institute of Technology, Japan and research scientist Mizuho Koike from the Institute of Space and Astronautical Science at Japan Aerospace Exploration Agency, have found nitrogen-bearing organic material in carbonate minerals in a Martian meteorite. This organic material has most likely been preserved for 4 billion years since Mars' Noachian age. Because carbonate minerals typically precipitate from the groundwater, this finding suggests a wet and organic-rich early Mars, which could have been habitable and favourable for life to start.

For decades, scientists have tried to understand whether there are organic compounds on Mars and if so, what their source is. Although recent studies from rover-based Mars exploration have detected strong evidence for Martian organics, little is known about where they came from, how old they are, how widely distributed and preserved they may be, or what their possible relationship with biochemical activity could be.

Martian meteorites are pieces of Mars' surface that were themselves blasted into space by meteor impacts, and which ultimately landed on Earth. They provide important insights into Martian history. One meteorite in particular, named Allan Hills (ALH) 84001, named for the region in Antarctica it was found in 1984, is especially important. It contains orange-coloured carbonate minerals, which precipitated from salty liquid water on Mars' near-surface 4 billion years ago. As these minerals record Mars' early aqueous environment, many studies have tried to understand their unique chemistry and whether they might provide evidence for ancient life on Mars. However, previous analyses suffered from contamination with terrestrial material from Antarctic snow and ice, making it difficult to say how much of the organic material in the meteorite were truly Martian. In addition to carbon, nitrogen (N) is an essential element for terrestrial life and a useful tracer for planetary system evolution. However, due to previous technical limitations, nitrogen had not yet been measured in ALH84001.

This new research conducted by the joint ELSI-JAXA team used state-of-the-art analytical techniques to study the nitrogen content of the ALH84001 carbonates, and the team is now confident they have found the first solid evidence for 4-billion-year-old Martian organics containing nitrogen.

Terrestrial contamination is a serious problem for studies of extraterrestrial materials. To avoid such contamination, the team developed new techniques to prepare the samples with. For example, they used silver tape in an ELSI clean lab to pluck off the tiny carbonate grains, which are about the width of a human hair, from the host meteorite. The team then prepared these grains further to remove possible surface contaminants with a scanning electron microscope-focused ion beam instrument at JAXA. They also used a technique called Nitrogen K-edge micro X-ray Absorption Near Edge Structure (μ-XANES) spectroscopy, which allowed them to detect nitrogen present in very small amounts and to determine what chemical form that nitrogen was in. Control samples from nearby igneous minerals gave no detectable nitrogen, showing the organic molecules were only in the carbonate.

After the careful contamination checks, the team determined the detected organics were most likely truly Martian. They also determined the contribution of nitrogen in the form of nitrate, one of the strong oxidants on current Mars, was insignificant, suggesting the early Mars probably did not contain strong oxidants, and as scientists have suspected, it was less-oxidizing than it is today.

Mars' present surface is too harsh for most organics to survive. However, scientists predict that organic compounds could be preserved in near-surface settings for billions of years. This seems to be the case for the nitrogen-bearing organic compounds the team found in the ALH84001 carbonates, which appear to have been trapped in the minerals 4 billion years ago and preserved for long periods before finally being delivered to Earth.

The team agrees that there are many important open questions, such as where did these nitrogen-containing organics come from? Kobayashi explains, 'There are two main possibilities: either they came from outside Mars, or they formed on Mars. Early in the Solar System's history, Mars was likely showered with significant amounts of organic matter, for example from carbon-rich meteorites, comets and dust particles. Some of them may have dissolved in the brine and been trapped inside the carbonates.' The research team lead, Koike adds that alternatively, chemical reactions on early Mars may have produced the N-bearing organics on-site. Either way, they say, these findings show there was organic nitrogen on Mars before it became the red planet we know today; early Mars may have been more 'Earth-like', less oxidising, wetter, and organic-rich. Perhaps it was 'blue.'

Last year, the 18th International Congress of Myriapodology brought together 92 of the world's top experts on the curious, yet still largely unknown multi-legged centipedes, millipedes, pauropods, symphylans (collectively referred to as myriapods) and velvet worms (onychophorans).

Held between 25th and 31st August 2019 at the Hungarian Natural History Museum in Budapest and co-organised by the Hungarian Biological Society, the biennial event saw the announcement of the latest findings related to the diversity, distribution and biology of these creatures. Now, the public gets the chance to learn about a good part of the research presented there on the pages of the open-access scholarly journal ZooKeys.

The special issue in ZooKeys, "Proceedings of the 18th International Congress of Myriapodology (25-31 August 2019, Budapest, Hungary)", features a total of 11 research articles reporting on species new to science, updates on the distribution and conservation of already known myriapods and discoveries about the biology, ecology and evolution of individual species. Together, the publications reveal new insights into the myriapod life on four continents: Europe, Asia, Africa and Australia.

Amongst the published research outputs worth mentioning is the comparison between regional and global Red Listings of Threatened Species that worryingly identifies a missing overlap between the myriapod species included in the global IUCN Red List and the regional ones. This first-of-its-kind overview of the current conservation statuses of myriapods from around the world highlights the lack of dedicated funding for the conservation of hundreds of threatened myriapods. As a result, the scientists behind the study urge for the establishment of a Myriapoda Specialist Group in the Species Survival Commission of the IUCN.

Meanwhile, to give us a hint about how many millipedes are out there unbeknownst to the world and any conservation authorities, at the congress, three research teams revealed a total of seven new to science species: three giant pill-millipedes from Vietnam, another three from the biodiversity hotspot Madagascar and a spirostreptid millipede inhabiting Sao Tome and Principe.

Amongst the rest of the papers is the curious discovery of two Tasmanian species of flat-backed millipedes of the genus Tasmaniosoma whose neighbouring populations have seemingly come to their own terms to keep distance between each other, save for a little stretch of land, for no obvious reason. Not a single site where both species occur together was found by Dr Bob Mesibov, the millipede expert behind the study. How is the parapatric boundary maintained? How, when and where did the parapatry originate? These are the big mysteries that the already retired Australian scientist leaves for his successors to resolve.

Results from a first-of-its-kind study of a multicancer blood test in more than 9,900 women with no evidence or history of cancer showed the liquid biopsy test safely detected 26 undiagnosed cancers, enabling potentially curative treatment.

Overall, 26 cancers were detected by the blood test while an additional 24 cancers were detected by standard screening such as mammography or colonoscopy. Together, screen-detected cancers (those detected by either blood testing or standard screening), accounted for more than half of the 96 cancers detected during the study period. Cancers detected by the blood test were most often localized by diagnostic PET-CT. Twelve of the cancers detected by the blood test were able to be surgically removed.

Researchers at the Ludwig Center at the Johns Hopkins Kimmel Cancer Center, who developed the blood test, say the study, called DETECT-A (Detecting cancers Earlier Through Elective mutation-based blood Collection and Testing) represents the first time any liquid biopsy blood test was used clinically to screen for cancer in a population without previously detected cancer for the purpose of diagnosis and intervention -- specifically treatment with the intent to cure cancer.

A report on the work will be published April 28 in Science and presented the same day at the virtual annual meeting of the American Association for Cancer Research. "This study suggests that a multicancer blood test can be complementary and additive to standard of care screening and may be a good strategy for increasing early detection of cancer," says Anne Marie Lennon, M.B.B.Ch., Ph.D., professor of medicine, interim director of the Division of Gastroenterology and Hepatology, and lead author of the published report.

The multicancer blood test detects the presence of cancer gene mutations in circulating DNA and blood levels of specific cancer proteins. This test, called the DETECT-A blood test, was originally designed in 2016 by the research team. A more advanced version of the test, called CancerSEEK, was first reported in Science in January 2018. Improvements continue to be made to the test, such as those reported in the March 3 issue of the Proceedings of the National Academy of Sciences. The DETECT-A study was initiated before these advances were made, says Lennon.

"The DETECT-A study incorporated PET-CT imaging to provide independent confirmation of the existence of a cancer and to precisely localize its site," says Nickolas Papadopoulos, Ph.D., senior author and professor of oncology and pathology. "For example, we could detect a lung cancer, tell in which lobe of which lung the cancer was located, the size of the cancer and if there were metastatic lesions present. Blood tests alone are not able to provide this type of precise information."

In the DETECT-A study, the blood test followed by PET-CT imaging was 99.6% specific for cancer. The researchers also confirmed that the genetic mutations picked up by the blood test that led to a positive test were present in the cancer 100% of the time.

"Our primary goal was to demonstrate reliability and safety -- to show the blood test could lead to the diagnosis of cancers and get patients to treatment aimed at curing them," says Kenneth Kinzler, Ph.D., professor of oncology and co-director of the Ludwig Center at Johns Hopkins.

A secondary goal was to show that blood testing could be integrated with conventional screening methods for detecting breast, colon and lung tumors.

Papadopoulos says it was encouraging that the DETECT study found combining standard of care screening with the blood test augmented the benefit of standard of care screening for these three cancer types, improving sensitivity from 47% to 71%. Blood testing also allowed the detection of seven other cancer types (lymphoma, appendix, uterine, thyroid, kidney, ovary and cancers arising from an unknown primary site) that cannot be screened now, with a sensitivity of 31%. "This underscores the value of blood-based multicancer screening as both complementary and additive to standard of care screening," he explains.

Only women were chosen for the DETECT study because ovarian cancer -- one of the cancers the test detects -- occurs only in women, and the investigators wanted to have consistent comparisons.

Of the 10,006 female patients initially enrolled between September 2017 and May 2019, 9,911 completed the study. Of the 95 people excluded from the study, 73 voluntarily withdrew, 12 were found to have a history of cancer and 10 did not complete the necessary clinical workup.

Because study participants were all members of a managed health care system, all had access to standard of care cancer screening guidance, including recommendations for mammography to detect breast cancer and colonoscopy to detect colon cancer.

The blood tests were performed and results were generated in a Clinical Laboratory Improvement Amendments (CLIA)-approved lab operated by Thrive Earlier Detection. (CLIA establish quality standards for clinical laboratory testing.) Cancers initially detected by the blood test included cancers in 10 different organs: lymphomas (2), colorectal (2), appendix (1), uterine (2), thyroid (1), kidney (1), lung (9), breast (1), ovary (6) and unknown primary (1).

Importantly, 17 cancers (65%) first detected by the blood test were diagnosed at an early stage, when the cancer was still localized or regional to the area it originated. Twelve surgeries were performed with intent to cure. Of the 26 patients first detected by blood testing, 12 remain in remission and eight remain in treatment or have stable disease approximately nine months past diagnosis.

The investigators plan to continue to follow all 9,911 participants, including those with positive and negative test results, for five years. It is likely that other cancers that were too small to be detected by imaging or were not detected by the blood test will arise in these individuals.

Surveys conducted after the study showed that blood testing did not discourage participants from engaging in standard screening. Moreover, these surveys showed high satisfaction with the study. Specifically, among 6,874 participants who completed a survey 12 months post-enrollment, only 0.3% reported feeling they made the wrong decision by participating in the study. Similar responses were obtained from participants who received true positive and true negative test results and from those who received false positive or false negative results. Only 1% of respondents said they would be unwilling to join a similar subsequent study.

The investigators say additional studies reflecting an optimized version of the blood test are in planning. "We believe that more than two-thirds of cancers that occur in the U.S. can eventually be screen-detected, either by blood testing or standard screening, before they cause symptoms of disease. Such earlier detection has the capacity to substantially reduce suffering and death from many cancer types," says Bert Vogelstein, M.D., Clayton Professor of Oncology, co-director of the Ludwig Center at Johns Hopkins and a Howard Hughes Medical Institute investigator. The test remains in research and is not currently available to the general public.

A protein known to expand blood vessels -- key to controlling conditions like high blood pressure -- actually has different functions in males and females, new UC Davis Health research shows.

Conducted using arterial cells from mice, the study is the first to identify sex-based distinctions in how the protein --Kv2.1 -- works.

Kv2.1 is generally known to form calcium channels that dilate blood vessels. In arterial cells from female mice, however, it contracted blood vessels.

The research was led by Luis Fernando Santana, professor and chair of physiology and membrane biology, and graduate student Samantha O'Dwyer. It is published in the Proceedings of the National Academy of Sciences.

"We were shocked at the difference and the strength of that difference," Santana said. "We think we've found the physiological explanation for what some of our clinical colleagues are seeing in patients ? some high blood pressure medications tend to work better for men, while others work better for women."

Santana and his team study calcium channels, their effects on heart muscle cells and how to alter that process to improve treatments for cardiovascular disease. They are especially interested in finding new treatments for hypertension, because it affects 45% of adults in the U.S. and is linked with serious conditions such as stroke, heart failure and aneurysm.

The current study focused on how Kv2.1 changes calcium channel organization and function. The investigators found that Kv2.1 promotes tight clustering of calcium channels. Kv2.1 expression is higher in cells from female mice, leading to larger clusters. This caused higher calcium levels in arterial cells and vasoconstriction. In arterial cells from male mice, Kv2.1 expression was not as high and calcium channel clusters were much smaller, causing vasodilation.

"This difference can only be attributed to the sex of the research mice," Santana said.

The next step, Santana said, is to determine what causes the different roles of Kv2.1. He plans to investigate the potential that sex hormones regulate the protein in arterial cells. His ultimate goal is tailored treatment strategies for hypertension for men and women.

"Until recently, the research community only used male mice to investigate heart disease," Santana said. "Our study proves what a major oversight that has been."

When people behave selfishly, they have a reliable ally to keep their self-image well-polished -- their own memory.

When asked to recall how generous they were in the past, selfish people tend to remember being more benevolent than they actually were, according to a series of experiments by Yale psychologists and economists at University of Zurich published April 29 in the journal Nature Communications.

"When people behave in ways that fall short of their personal standards, one way they maintain their moral self-image is by misremembering their ethical lapses," said Yale's Molly Crockett, assistant professor of psychology and senior author of the study.

Psychologists have long been interested in how people balance their self-interest with their desire to be viewed as moral. To justify self-serving behaviors to themselves and others, people engage in a process called motivated reasoning -- for example, when leaving a stingy tip, customers might convince themselves that their server didn't deserve any more.

But a team of researchers led by Crockett and Ryan Carlson, a Ph.D. student at Yale and first author of the study, wanted to explore whether people's memories of their behaviors help them preserve their moral self-image, perhaps even negating the need to employ motivated reasoning.

Instead of convincing themselves their server didn't deserve a better tip, for example, a customer might misremember tipping more generously than they actually did.

In their first lab experiment, conducted at the University of Zurich with economists Michel Maréchal and Ernst Fehr, the researchers presented subjects with a pot of money and asked them to decide how much to keep and how much to give to anonymous strangers. After answering some intervening survey questions, participants then were asked to recall how much they had given to the anonymous strangers. Crucially, participants received bonus money if they recalled their decisions accurately.

Even with a financial incentive, stingier subjects tended to recall giving more money than they actually did.

In another pair of experiments conducted in the lab and online, the researchers asked subjects what they thought was a fair distribution of money before asking them to divide the pot. The researchers found that only those subjects who had given less than what they personally deemed fair recalled being more generous than they actually were.

A final pair of online studies showed that subjects only misremembered their stinginess when they felt personally responsible for their decisions. When participants were explicitly instructed by the experimenters to give lower amounts, and so felt no responsibility for their actions, they remembered their giving behavior accurately.

"Most people strive to behave ethically, but people sometimes fail to uphold their ideals," Carlson said. "In such cases, the desire to preserve a moral self-image can be a powerful force and not only motivate us to rationalize our unethical actions, but also 'revise' such actions in our memory."

Crockett cautioned that because the experiments were conducted in Switzerland and the USA, it is not yet clear whether the results will generalize across different cultures.

She also stressed that this tendency for faulty recall only applied to the selfish. The majority of people behaved generously toward their anonymous strangers, and remembered their behavior accurately.

Researchers in South Korea have developed ultra-fast transmitting/receiving optical engine that can provide stable and improved data transfer speed for data centers.

The Electronics and Telecommunications Research Institute (ETRI) in South Korea has succeeded to develop a world's top-class 400-Gbps transmitting/receiving optical engine. It enables real-time high definition video streaming for 100,000 viewers simultaneously. Thus the optical engine can be applied for data centers that accommodate thousands of servers.

The developed technology sends eight times as much data than conventional methods in each linecard/server. It is expected to contribute to solving data traffic congestion in data centers where the demand for fast data speed has increased due to high-definition video content and services using artificial intelligence and cloud computing. The global market for hyper-scale data centers is expected to grow due to high demands from various sectors.

Conventional 100-Gbps transmitting/receiving modules split data speed into four channels of 25-Gbps (gigabits per second). ETRI said its researchers have succeeded in developing high-speed optical devices/components that can provide 100-Gbps per channel which is four times the previous speed.

Moreover, the new technology not only improved the data transfer speed but also data processing capacity. An existing linecard of telecommunication equipments consists of 32 optical transceivers. The new technology developed by ETRI enables 64 optical engines to be mounted on the linecard of the telecommunication equipments.

As a result, by mounting twice as much optical engines with 4 times the speed, the total data processing capacity has been increased up to 8 times. The research outcome was presented in the '2020 Optical Fiber Communication Conference (OFC)'.

In adult tissue, the number of cells in each tissues and organs remains constant, and any new cells produced by cell division need to be compensated by the loss of other cells. In contrast, during postnatal growth, an excess of cell production over cell loss is required to generate the excess of cells that ensure tissue expansion while maintaining tissue function. Very little is known about the mechanisms that ensure the postnatal growth from birth until adulthood.

In this new study led by Pr Cédric Blanpain, Université libre de Bruxelles-ULB, Director of the laboratory of Stem Cells and Cancer and Welbio investigator, that makes the cover of this issue of Cell, Sophie Dekoninck and colleagues unravel the mechanisms that mediate postnatal skin expansion. This study was performed in collaboration with the University of Cambridge, UK (Pr B. Simons and E. Hannezo) and KU Leuven, Belgium (Pr T. Voet and A. Sifrim). Using multidisciplinary approaches combining lineage tracing, cell proliferation kinetics, single cell transcriptomics, and mathematical modeling, the researchers define the design principles underlying postnatal tissue expansion.

By performing morphometric studies of postnatal skin expansion combined with genetic lineage tracing clonal analysis, they demonstrated that the mouse tail skin expanded by 15-fold from birth to the adult size and they recorded the behaviour of many individual developmental progenitors overtime during postnatal development.

Cell proliferation measurements indicated that cell division progressively decreased over time during postnatal growth. "It was very surprising to see that the tissue growth is achieved through a constant gain of new cells by self-duplication over cell lost and through a gradual decrease in cell division rate throughout the postnatal development" commented Sophie Dekoninck, the first author of the study. The researchers suggest that this design principle allows optimal tissue growth, meaning that the skin grows robustly and linearly, but also maintains constant the proportion of stem cells and differentiated cells ensuring the integrity of the skin barrier function.

To probe further the molecular mechanisms beyond the observed heterogeneity of the developmental progenitor behavior, the researchers performed single-cell RNA sequencing of skin cells on mice of different ages and analysed developmental progenitors, adult stem cells and their more differentiated progeny. "These data reveal the molecular features of developmental progenitors, which consist of a very homogenous population that actively proliferate and expand whereas the transition from tissue growth to adult life was associated with increased stem cell and progenitor heterogeneity, shaping the final architecture and function of the adult skin. These data pave the way for new fascinating projects in the future" comments Cédric Blanpain, the senior author of the study.

Finally, the researchers found that the orientation of the cell divisions of the developmental progenitors correlate with the orientation of the extracellular matrix of the underlying tissue. These data show that the extracellular microenvironment influence the orientation of cell division of developmental progenitors, which ultimately control the shape of the tissue.

In conclusion, this new study unravels the mechanisms that mediate postnatal tissue expansion, and show that developmental progenitors control the optimality of postnatal growth by maintaining a constant density between progenitor and differentiated cells, which allows harmonious tissue expansion while maintaining tissue function.

A new study is among the first to trace the molecular connections between genetics, the gut microbiome and memory in a mouse model bred to resemble the diversity of the human population.

While tantalizing links between the gut microbiome and brain have previously been found, a team of researchers from two U.S. Department of Energy national laboratories found new evidence of tangible connections between the gut and the brain. The team identified lactate, a molecule produced by all species of one gut microbe, as a key memory-boosting molecular messenger. The work was published April 17 in the journal BMC Microbiome.

"Our study shows that the microbiome might partner with genetics to affect memory," said Janet Jansson, a microbial ecologist at Pacific Northwest National Laboratory and a corresponding author of the study.

Scientists know that mice which have been fed microbes that benefit health, called probiotics, experience several positive benefits. Scientists also know that microbes produce molecules that travel through the blood and act as chemical messengers that influence other parts of the body, including the brain. However, it wasn't clear which specific microorganisms and microbial molecular messengers might influence memory until now.

"The challenge is that a mouse's unique genetic makeup and environmental conditions also impact its memory and microbiome," said Antoine Snijders, a bioscientist at Lawrence Berkeley National Laboratory (Berkeley Lab) and co-corresponding author. "To know if a microbial molecule influenced memory, we needed to understand the interaction between genetics and the microbiome."

The microbiome's impact on memory is a very active research area now, he added, with more than 100 papers published in the last five years on links between common probiotics and memory.

Mouse genetics influence memory and gut microbiome

Before they could start hunting for molecules that might be involved with memory improvement, Jansson, Snijders and their colleagues needed to determine how genetics influence memory.

The researchers started with a collection of mice called the Collaborative Cross. They bred 29 different strains of mice to mimic the genetic and physical diversity of a human population. It includes mice of different sizes, coat colors and disposition (e.g., timid or bold). Researchers also know the genome sequences of each strain.

First, the team gave each strain of mice a memory test. Then they screened each strain for genetic variations and correlated these variations to the memory results. They found two sets of genes associated with memory. One was a set of new candidate genes for influencing cognition, while the other set of genes was already known.

Next, the researchers analyzed the gut microbiome of each strain so they could make microbial connections to the genetics and memory links they already had. They identified four families of microbes that were associated with improved memory. The most common of those was a species of Lactobacillus, L. reuteri.

To test this association, the researchers fed L. reuteri to germ-free mice without any gut microbes and then tested the mice's memory. They saw a significant improvement relative to germ-free mice not fed microbes. They also found the same improvement when they fed germ-free mice one of two other Lactobacillus species.

"While a link between Lactobacillus and memory was previously reported, we also found it independently in this unbiased genetic screen," Snijders said. "These results suggest that genetic variation in large part controls memory, as well as the differences in the composition of the gut microbiome across strains."

Diet and probiotics boost memory

Finally, the researchers wanted to identify which microbe-related molecules might be involved with memory enhancement. They analyzed stool, blood and brain tissue from germ-free mice each fed a specific species of Lactobacillus. Lactate was one of the common metabolic molecular byproducts; it is also a molecule that all Lactobacillus strains produce.

The team fed lactate to mice previously identified to have poor memory and noticed that their memory improved. Mice fed lactate or Lactobacillus microbes also had increased levels of gamma-aminobutyric acid (GABA), a molecular messenger linked to memory formation in their brains.

To see if the same molecular mechanism might apply in humans too, the researchers contacted Paul Wilmes, at the University of Luxembourg, who developed a tiny chip that mimics where microbes interact with human intestinal tissue. When Wilmes and his colleagues tested L. reuteri in this chip, they saw that lactate produced by the microbes traveled through the human gut tissue, indicating that it could enter the bloodstream and potentially travel to the brain.

"While this research strengthens the idea that diet, genetics, and behaviors--like memory--are connected, further work is needed to show if Lactobacillus can improve memory in humans," Jansson said.

Snijders agreed, adding that it might be possible one day to use probiotics to improve memory in targeted populations, such as people with learning disabilities and neurodegenerative disorders.

Researchers at the Radboud university medical center seem to have found an essential mechanism in the disease process of COVID-19, which has so far been overlooked. If the insight is correct, it probably has important consequences for the treatment of the disease. In an international collaborative effort it is now being investigated whether the new insights and treatments do indeed have an effect in practice.

An infection with the coronavirus COVID-19 is different from the flu or other more common viral diseases. Radboudumc researchers wondered what exactly happens in the case of a severe infection. Doctors recognize three clear phases. In the beginning, patients quickly become short of breath because of fluid in the lungs. About nine days after the infection an inflammatory reaction occurs in the lungs; the patient's antibodies might attack the virus in the lungs, which can further aggravate the situation in the lung. Some of the patients who recover after a stay in the ICU develop thrombosis and scarring in the lungs due to the long-standing fluid, which makes recovery difficult. In short: it all begins with a fluid problem.

Vanishing ACE2 receptors

"We have been closely monitoring the COVID patients," says Frank van de Veerdonk. "That first phase, during which the lungs fill up with fluid, CT scans of the lungs look bad and patients quickly experience shortness of breath due to the administration of fluid, is very characteristic. This image cannot be explained solely by the infection of the lungs. So we got the idea that the capillaries, which are the very small blood vessels, start to leak into the lungs during this process. That leakage causes the lungs problems, because they partly fill up."

This observation was already made with SARS (a previous coronavirus infection that occurred in 2003), but no good explanation was available. Researchers from the Radboudumc now come up with a hypothesis, a theoretical explanation that makes the leakage plausible. Van de Veerdonk: "COVID-19 enters the lungs via the ACE2 receptor. The virus binds to the receptor, which then pulls it into the lung cell where the virus can multiply. In case of a massive infection, this process makes the ACE2 receptors disappear from the outside of the cell. With that, their function also disappears."

Bradykinine makes blood vessels leak

ACE2 (angiotensin-converting enzyme 2) is known to play a role in maintaining blood pressure throughout the body, which is regulated by the RAAS, the renin-angiotensin-aldosterone system. The RAAS system, and thus ACE2, controls blood pressure by regulating vasodilatation and vasoconstriction. But ACE2 has another function, which up until now has remained out of the picture in coronavirus infections. Van de Veerdonk: "ACE2 keeps the substance bradykinin under control. Bradykinin makes blood vessels leak. We have good reason to believe that with COVID-19 infections we see exactly this effect: when the virus is introduced, ACE2 receptors disappear from the lung cells, giving bradykinine free rein in causing the small blood vessels to leak massively at the site of infection."

Van de Veerdonk and colleagues recognize this phenomenon from another very rare disease: hereditary angioedema. People with this disease can suddenly develop swelling of, for example, hands, feet, abdomen or face. These swellings can persist for several hours, sometimes even days, after which they disappear just as quickly as they have developed. The cause of these swellings: leaking blood vessels due to too much bradykinin. Some side effects of ACE inhibitors, which are used against high blood pressure, are also very similar to symptoms seen with COVID-19. The dry cough, for example. And in rare cases, angioedema can also occur with ACE inhibitors.

Quick sharing and testing of the insights

The problems of vascular leakage can be aggravated by an inflammatory phase. This causes even more leakage and damage to the lungs. Anti-inflammatory drugs can have a potentially dampening effect here, and doctors and researchers all over the world are doing their best to select the most optimal drugs for this stage. In addition the long lasting vascular leakage and inflammation of the blood vessels will trigger the coagulation cascade leading to thrombosis and eventually scarring of the lungs. Interventions that are started early to treat this leakage have the capacity to prevent these serious complications and might be effective in keeping patients out of the ICU.

Researchers from the Radboudumc have published their insights in an article published on Preprints. Articles on Preprints have not been reviewed and commented on by colleagues, but can therefore be published very quickly. "The latter is very important, because we want to share our vision with everyone as soon as possible," says Van de Veerdonk. "The so-called peer review by colleagues is in full swing anyway. The article on Preprints has already been viewed over 1800 times and downloaded more than 900 times. Based on this shared knowledge, we are now working on the first treatments with Icatibant, a product that can inhibit the effects of bradykinine. Because for every good idea the corresponding proof must first be provided. At the Dutch national level we are collaborating with the UMC Utrecht, and on an international level with, among others, Remap-Cap. We hope that this will quickly provide us with conclusive information about the insights we have now launched".

For people with allergies, contact with pollen leads to symptoms such as sneezing, rhinitis and watery eyes. This may sound trivial, but is in fact a complex correlation of physiological processes. As these have not yet been fully understood, we do not know exactly yet how allergies develop and how the symptoms are triggered.

Symptoms can be predicted in advance

A research group led by the Institute of Environmental Medicine at Helmholtz Zentrum München and Technical University of Munich (Research Association UNIKA-T), examined patients with pollen-induced allergic rhinitis and people without allergy over a period of one year. In addition to a digital symptom diary kept daily by the study participants, the researchers took samples of blood and nasal secretion. They then compared the immune variables (cytokines, chemokines and pollen-specific immunoglobulins) in these samples during and after the pollen season. As a result, they identified the endogenous messenger substances IL-8 and IL-33 as well as the antibodies sIgG4 and sIgE as biomarkers (= measurable characteristics with relevance for biological processes). These biomarkers show a significant correlation with pollen-specific nasal symptoms (proven by Spearman's rank correlation coefficient). The researchers were now able to predict the severity of the symptoms even before the start of the pollen season based on the expression rate of these biomarkers in people with and without allergy, independent of their individual genetic disposition.

Multiple applications for biomarkers

Mehmet Gökkaya, researcher at UNIKA-T and first author of the study: "The identification of biomarkers helps us in three ways. Firstly, by predicting the severity of nasal symptoms we can better identify the patients who benefit the most from therapeutic treatment. Secondly, biomarkers can help us understand the processes at work during the development of allergies in non-allergic patients and so help us to be ultimately able to prevent them. And thirdly, biomarkers can be used to identify the physiological processes that originally cause these symptoms. Possibly this could be a new starting point for the development of novel therapeutics."

An article published in the Journal of General Internal Medicine looks at the relationship between burnout and depressive symptoms in medical interns.

The article is authored by Constance Guille, M.D., an associate professor in the Department of Psychiatry and Behavioral Sciences at the Medical University of South Carolina, and Lisa Rotenstein, M.D., an internal medicine resident at Harvard Medical School/Brigham and Women's Hospital, among others.

According to Rotenstein, these findings help correct a long-held misconception about burnout and depression.

"There is a long-standing thought that burnout is associated with workplace factors and that depressive symptoms are associated with workplace factors but also heavily influenced by personal factors," explained Rotenstein. "We found that the factors that drive burnout are much more closely related to the factors that drive depressive symptoms than previously realized."

In this study, Rotenstein and Guille uncover that there is substantial overlap between the factors that predict burnout and depressive symptoms. The study surveyed 1,552 medical interns entering residency programs at 68 different institutions about depressive symptoms, emotional exhaustion and depersonalization, as well as about potential contributing factors. Depressive symptoms were measured by a standard 9-item Patient Health Questionnaire, while emotional exhaustion and depersonalization were measured with a 9-item abbreviated Maslach Burnout Inventory. Workload and learning environment satisfaction were assessed with a standardized instrument. Personal factors assessed included age, gender, ethnicity, relationship status, sexual orientation, parenting status, specialty, self-reported history of depression, early life stress and neuroticism score.

The study found significant overlap between factors that contribute to depressive symptoms and those that contribute to burnout, with about two-thirds of variance in both depressive symptoms and burnout attributable to personal factors, and one-third of the variance in these measures attributable to workplace factors.

With more than 142 definitions circulating in the literature, the definition of burnout has historically been unclear. This lack of clear definition has led to highly variable rates of burnout being reported among medical interns, residents and attending physicians. In contrast, depressive symptoms are well-defined and have been clinically validated. The results of this study suggest that assessing for depressive symptoms may be a validated, standardized alternative to assessing for burnout among medical personnel. They also underscore that interventions that help address burnout may be effective in addressing depressive symptoms and vice versa. Examples of such interventions include leveraging resources such as scribes to address documentation burdens, time banking for physician service and resources such as childcare to take stress off those physicians with familial obligations.

For Guille, the takeaway message from this study is clear.

"Previous to this work, depression and burnout were conceptualized as separate entities with different factors contributing to these outcomes," explained Guille. "This work suggests there is substantial overlap between both workplace and personal factors that contribute to an increase in both depressive symptoms and burnout."

Maunakea, Hawaii - Our solar system has a king. The planet Jupiter, named for the most powerful god in the Greek pantheon, has bossed around the other planets through its gravitational influence. With twice the mass of Saturn, and 300 times that of Earth, Jupiter's slightest movement is felt by all the other planets. Jupiter is thought to be responsible for the small size of Mars, the presence of the asteroid belt, and a cascade of comets that delivered water to young Earth.

Do other planetary systems have gravitational gods like Jupiter?

A team of astronomers led by the University of Hawaii Institute for Astronomy (UH IfA) has discovered a planet three times the mass of Jupiter in a distant planetary system.

The discovery is based on six years of data taken at W. M. Keck Observatory on Maunakea in Hawaii. Using the High-Resolution Echelle Spectrometer (HIRES) instrument on the 10-meter Keck I telescope, the team confirmed that the planet, named Kepler-88 d, orbits its star every four years, and its orbit is not circular, but elliptical. At three times the mass of Jupiter, Kepler-88 d is the most massive planet in this system.

The system, Kepler-88, was already famous among astronomers for two planets that orbit much closer to the star, Kepler-88 b and c (planets are typically named alphabetically in the order of their discovery).

Those two planets have a bizarre and striking dynamic called mean motion resonance. The sub-Neptune sized planet b orbits the star in just 11 days, which is almost exactly half the 22-day orbital period of planet c, a Jupiter-mass planet. The clockwork-like nature of their orbits is energetically efficient, like a parent pushing a child on a swing. Every two laps planet b makes around the star, it gets pumped. The outer planet, Kepler-88 c, is twenty times more massive than planet b, and so its force results in dramatic changes in the orbital timing of the inner planet.

Astronomers observed these changes, called transit timing variations, with the NASA Kepler space telescope, which detected the precise times when Kepler-88 b crossed (or transited) between the star and the telescope. Although transit timing variations (TTVs for short) have been detected in a few dozen planetary systems, Kepler-88 b has some of the largest timing variations. With transits arriving up to half a day early or late, the system is known as "the King of TTVs."

The newly discovered planet adds another dimension to astronomers' understanding of the system.

"At three times the mass of Jupiter, Kepler-88 d has likely been even more influential in the history of the Kepler-88 system than the so-called King, Kepler-88 c, which is only one Jupiter mass," says Dr. Lauren Weiss, Beatrice Watson Parrent Postdoctoral Fellow at UH IfA and lead author on the discovery team. "So maybe Kepler-88 d is the new supreme monarch of this planetary empire - the empress."

Perhaps these extrasolar sovereign leaders have had as much influence as Jupiter did for our solar system. Such planets might have promoted the development of rocky planets and directed water-bearing comets toward them. Dr. Weiss and colleagues are searching for similar royal planets in other planetary systems with small planets.

Their paper announcing the discovery of Kepler-88 d is published in the April 29th issue of the Astronomical Journal.

An international team of researchers, led by Professor Margaret Rayman at the University of Surrey, has identified a link between the COVID-19 cure rate and regional selenium status in China.

Publishing their findings in the American Journal of Clinical Nutrition, researchers using data (up to 18 February), investigated possible links between selenium levels in the body and cure or death rates of those with the COVID-19 virus in China.

Selenium is an essential trace element obtained from the diet (i.e. fish, meat and cereals) which has been found to affect the severity of a number of viral diseases in animals and humans. For example selenium status in those with HIV has been shown to be an important factor in the progression of the virus to AIDs and death from the condition. China is known to have populations that have both the lowest and highest selenium status in the world, due to geographical differences in the soil which affects how much of the trace element gets into the food chain.

Margaret Rayman, Professor of Nutritional Medicine at the University of Surrey, said; "Given the history of viral infections associated with selenium deficiency, we wondered whether the appearance of COVID-19 in China could possibly be linked to the belt of selenium deficiency that runs from the north-east to the south-west of the country."

Examining data from provinces and municipalities with more than 200 cases and cities with more than 40 cases, researchers found that areas with high levels of selenium were more likely to recover from the virus. For example, in the city of Enshi in Hubei Province, which has the highest selenium intake in China, the cure rate (percentage of COVID-19 patients declared 'cured') was almost three-times higher than the average for all the other cities in Hubei Province. By contrast, in Heilongjiang Province, where selenium intake is among the lowest in the world, the death rate from COVID-19 was almost five-times as high as the average of all the other provinces outside of Hubei.

Most convincingly, the researchers found that the COVID-19 cure rate was significantly associated with selenium status, as measured by the amount of selenium in hair, in 17 cities outside of Hubei.

Kate Bennett, a medical statistician at the University of Surrey, said; "There is a significant link between selenium status and COVID-19 cure rate, however it is important not to overstate this finding; we have not been able to work with individual level data and have not been able to take account of other possible factors such as age and underlying disease."

Ramy Saad, a doctor at Royal Sussex County Hospital, Brighton, currently taking an MSc degree in Nutritional Medicine at the Department of Nutritional Sciences at Surrey, commented; "The correlation we have identified is compelling, particularly given previous research on selenium and infectious diseases. As such, a careful and thorough assessment of the role selenium may play in COVID-19 is certainly justified and may help to guide ongoing public-health decisions".

When a natural disaster like an earthquake strikes, a community can literally be shaken to its core. One way to assess how well and how quickly that community recovers is to measure how, and how quickly, its hospitals and wider healthcare systems can become fully functional again and take care of its patients. Predicting the trajectory of that recovery is no easy task.

That's because the resilience measures of a healthcare system are dizzyingly complex. They span everything from the availability of hospital staff, to the protection of critical equipment, to the state of the roads for ambulances to travel on, to the efficiency by which hospitals can transfer critically ill patients to different hospitals.

Hussam Mahmoud, an associate professor in the Department of Civil and Environmental Engineering at Colorado State University, and his students spend a lot of time thinking about how to define and describe "community resilience." Mahmoud and graduate student Emad Hassan have created a modeling tool that could help city planners and emergency managers understand the full functionality and recovery of a healthcare system, in the wake of a natural disaster.

"We set out to develop models allowing us to understand, what is the demand on a hospital healthcare facility after an event like an earthquake," Mahmoud said. "When we started looking into this, we were shocked to learn that there are no models currently that allow you to understand, what is the demand on the hospital, how is the hospital being impacted by the natural disaster, how is that going to impact demand and capacity, and how will that change over time?"

Their model, described in a forthcoming issue of the journal Reliability Engineering and System Safety, has wider implications for use in other disasters, including pandemics, like the one the world is experiencing now with COVID-19.

Healthcare as a complex network

In their paper, Mahmoud and Hassan seek to understand healthcare systems as complex networks that can be visualized as nodes of different functionalities. These include number of staffed beds, hospital staff availability, housing functionality, patient waiting time for treatment, and even things like the probability of patient X going to healthcare facility Y. The availability of water, power, transportation and telecommunication also support hospital operation and factor into the model. And the researchers define healthcare not just by physical metrics, but also by quality metrics, like the level of customer satisfaction - measured by things like patient wait time.

To develop and test their framework, the researchers applied it to a virtual community called Centerville, which was developed as a research tool by researchers at the CSU Center for Risk-Based Community Resilience, a National Institute of Standards and Technology Center of Excellence of which Mahmoud and Hassan are contributing members. The researchers applied an earthquake scenario to Centerville - an imagined mid-sized U.S. community of 50,000 residents with commercial and industrial zones, schools, fire stations and hospitals - to see how it would fare. Using the virtual environment helped them highlight the capabilities of their model and the impact of decisions made as the community recovered.

Pandemic applications

The purpose of Mahmoud and Hassan's work is to define the parameters needed to be measured by communities to assess how prepared they are for natural disasters. In the wake of COVID-19, Mahmoud said, they have begun using their model to theorize and predict how hospital networks can better manage pandemics by identifying gaps in resources and potential bottlenecks according to different worst-case scenarios. They are now working with the National Center for Disaster Medicine and Public Health to further refine the model and apply it to pandemic planning.