Brain

Researchers at Nagoya University have discovered a neural circuit that drives physical responses to emotional stress. The circuit begins in deep brain areas, called the dorsal peduncular cortex and the dorsal tenia tecta (DP/DTT), that send stress signals to the hypothalamus, a small region in the brain that controls the body's vital functions. The findings were recently published in the journal Science.

Emotional stress activates the sympathetic nervous system, which leads to physical responses, such as a rise in blood pressure and body temperature, and a faster heart rate. Such responses are thought to be coping mechanisms in humans and many other mammals to boost physical performance in fight-or-flight situations. But nowadays, when most people rarely encounter such situations, these responses could perhaps have an adverse effect on their health. Excessive stress may cause symptoms such as psychogenic fever, a condition of abnormally high body temperature.

To develop strategies for treating stress-induced symptoms, the neural mechanism underlying physical responses to stress had first to be understood. To this end, a research team led by Professor Kazuhiro Nakamura and Designated Assistant Professor Naoya Kataoka, of the Nagoya University Graduate School of Medicine, conducted a study in which tracers were injected into the brains of a group of rats and the rats were subjected to a stressful event (rat bullying by a dominant rat).

The tracers showed that specifically the DP/DTT brain areas were highly active when exposed to stress. To further examine the role these brain areas have in stress response, the researchers impaired the areas' connections to the hypothalamus and again exposed the rats to the same stress. Now the rats did not exhibit any stress-induced physical response, neither a rise in blood pressure nor body temperature, nor a faster heart rate.

This study demonstrates that the DP/DTT areas together are responsible for sending stress signals to the hypothalamus, and thus that blocking the DP/DTT-to-hypothalamus circuit can result in a reduction of stress symptoms in rats.

Professor Nakamura sums up the research result like this: "The DP/DTT are parts of the brain that are involved in processing emotion and stress. The DP/DTT-to-hypothalamus pathway we discovered, therefore, represents a brain mechanism for a 'mind-body connection,' which can be a potential target for treating stress-related disorders such as panic disorder, post-traumatic stress disorder (PTSD), and psychogenic fever."

The first step in many light-driven chemical reactions, like the ones that power photosynthesis and human vision, is a shift in the arrangement of a molecule's electrons as they absorb the light's energy. This subtle rearrangement paves the way for everything that follows and determines how the reaction proceeds.

Now scientists have seen this first step directly for the first time, observing how the molecule's electron cloud balloons out before any of the atomic nuclei in the molecule respond.

While this response has been predicted theoretically and detected indirectly, this is the first time it's been directly imaged with X-rays in a process known as molecular movie-making, whose ultimate goal is to observe how both electrons and nuclei act in real time when chemical bonds form or break.

Researchers from Brown University, the University of Edinburgh and the Department of Energy's SLAC National Accelerator Laboratory reported their findings in Nature Communications today.

"In past molecular movies, we have been able to see how atomic nuclei move during a chemical reaction," said Peter Weber, a chemistry professor at Brown and senior author of the report. "But the chemical bonding itself, which is a result of the redistribution of electrons, was invisible. Now the door is open to watching the chemical bonds change during reactions."

A model for important biological reactions

This was the latest in a series of molecular movies starring 1,3-cyclohexadiene, or CHD, a ring-shaped molecule derived from pine oil. In a low-pressure gas its molecules float freely and are easy to study, and it serves as an important model for more complex biological reactions like the one that produces vitamin D when sunlight hits your skin.

In studies going back almost 20 years, scientists have studied how CHD's ring breaks apart when light hits it - first with electron diffraction techniques, and more recently with SLAC's "electron camera," MeV-UED, and X-ray free-electron laser, the Linac Coherent Light Source (LCLS). These and other studies around the world have revealed how the reaction proceeds in finer and finer detail.

Four years ago, researchers from Brown, SLAC and Edinburgh used LCLS to make a molecular movie of the CHD ring flying apart, - the first-ever molecular movie recorded using X-rays. This achievement was listed as one of the 75 most important scientific breakthroughs to emerge from a DOE national laboratory, alongside discoveries such as the decoding of DNA and the detection of neutrinos.

But none of those previous experiments were able to observe the initial electron-shuffling step, because there was no way to tease it apart from the much larger movements of the molecule's atomic nuclei.

Electrons in the spotlight

For this study, an experimental team led by Weber took a slightly different approach: They hit samples of CHD gas with a wavelength of laser light that excited the molecules into a state that lives for a relatively long period of time - 200 femtoseconds, or millionths of a billionth of a second - so their electronic structure could be probed with LCLS X-ray laser pulses.

"X-ray scattering has been used to determine the structure of matter for more than 100 years," said Adam Kirrander, a senior lecturer at Edinburgh and senior co-author of the study, "but this is the first time the electronic structure of an excited state has been directly observed."

The technique used, called non-resonant X-ray scattering, measures the arrangement of electrons in a sample, and the team hoped to capture changes in the distribution of electrons as the molecule absorbed the light. Their measurement bore out that expectation: While the signal from the electrons was weak, the researchers were able to unambiguously capture how the electron cloud deformed into a larger, more diffuse cloud corresponding to an excited electronic state.

It was critical to observe these electronic changes before the nuclei started moving.

"In a chemical reaction, the atomic nuclei move and it's difficult to disentangle that signal from the other parts that belong to chemical bonds forming or breaking," said Haiwang Yong, a PhD student at Brown University and lead author of the report. "In this study, the change in the positions of atomic nuclei is comparatively small on that timescale, so we were able to see the motions of electrons right after the molecule absorbs light."

SLAC senior staff scientist Michael Minitti added, "We're imaging these electrons as they move and shift around. This paves the way to watching electron motions in and around bond breaking and bond formation directly and in real time; in that sense it's similar to photography."

The growth, death, and diseases of complex organisms rely on the flow of information -- from genes in DNA, through their transcription into RNA, and then translation of that transcript into proteins, which in turn build much of the living organism.

Proteins that control this whole process are themselves subject to this overarching information flow for survival. Researchers have now discovered a previously unknown function of a group of proteins, called the Ccr4-Not complex, that may shed light on the development of diseases like Alzheimer's.

The findings were published in Science on 17-Apr-2020.

"The Ccr4-Not complex is involved in so many aspects of gene expression that we might as well call it the 'Swiss Army Knife' of protein production," says Toshifumi Inada, a professor from the Graduate School of Pharmaceutical Sciences at Tohoku University, who led the research.

The best understood aspect of Ccr4-Not's role is its involvement in the destruction of the messenger RNA (mRNA). The mRNA molecules are like instruction manuals that tell the ribosomes, the cell's protein-making machinery, how to construct proteins.

The amount of proteins produced by the ribosomes is crucial, and so is the speed of that production. You don't want too many or too few, too fast or too slow. In turn, these protein levels depend on the amount of mRNA. Thus control of mRNA destruction--especially when these instruction manuals have mistakes in them--is critical in controlling protein production.

"But until now, how Ccr4-Not did this has remained elusive," Inada adds.

The mRNA instruction manuals are composed of multiple three-unit codes called 'codons' that tell the ribosomes which amino acids to use. Amino acids are the building blocks of proteins.

But even with this error-tolerant redundancy, there can still be a preference, or to use the formal term, bias, toward a particular synonym codon, because it speeds up the process. If an instruction manual for some reason doesn't have this codon bias, the system is not working at the speed it should.

The researchers found that the Ccr4-Not complex is always on the hunt for slow-poke mRNA that don't have this codon bias. They discovered that when the complex spots one, a part of it attaches itself to the ribosome, in turn triggering a degradation of the faulty mRNA.

But if the Ccr4-Not complex itself is faulty, missing the part that would attach to the ribosome reading the faulty mRNA, then the complex loses this crucial ability to sense and destroy these mRNA that are manufacturing proteins at the wrong speed.

Protein production that happens at the wrong speed can result in incorrect protein concentration, location or shape, all of which have been associated with a wide variety of diseases including Huntington's and Alzheimer's. The research offers insight into how Ccr4-Not abnormalities contribute to such illnesses via insufficient control of the rate of protein synthesis.

The researchers now want to investigate whether a normally functioning Ccr4-Not complex's management of this rate also enables it to control protein folding and transport of proteins to their appropriate destination in the body.

Acoustic tweezers are a powerful tool for contactless manipulation of particles and cells using acoustic radiation forces (ARF) generated by the transfer of acoustic wave momentum. They play an important role in display technology, biomedical sensors, imaging devices and diagnostic tools, etc.

Although standing waves or sound beams have been used in acoustic tweezer devices to trap particles, a huge phased array or a displacement platform is needed to shift the wave phase or move the sound source for dynamic manipulation requiring time-variant acoustic fields.
Currently, it's still a challenge to achieve dynamic manipulation in a tiny microchannel with a simple, flexible, low-cost and disposable method.

A research team led by Prof. ZHENG Hairong from the Shenzhen Institutes of Advanced Technology (SIAT) of the Chinese Academy of Sciences has addressed the challenge of comprehensive, dynamic manipulation of particles and cells in a microchannel by integrating acoustofluidics, physics and fabrication of phononic crystals on the microscale.

In this study, a phononic crystal plate (PCP) fabricated by chemical etching and located in the microchannel created a tunable and time-variant sound field that generated a nonisotropic and reversible ARF that could be adjusted in real time.

The ARF originated from the interaction of the incident sound waves with the resonant excitation of two different modes in the phononic crystal plate.

These specific modes could be flexibly switched by simply changing the driving frequency. This change in frequency induced a highly localized acoustic field that generated a negative ARF to trap particles, along with a leaky field that caused a positive ARF to levitate particles, respectively.

In conjunction with an offset sound source setting for the PCP location, a radiation force induced by the field gradient along the channel could further transport levitated microparticles or cells toward the source along a certain predefined trajectory, such as a straight line, polyline line, arc line or loop line based on the straight line and arc line.

An arbitrary stop-and-go motion, namely, trapping and transportation, of particles and cells along a predefined path in the channel was achieved by switching the frequency so as to change the PCP' s resonant modes and by designing patterns on the phononic crystal plates in order to construct routes.

"By carefully designing and engineering acoustic fields using phononic crystals or metamaterials in microfluidic devices, a wide range of materials, particles, cells and organisms can be acoustically manipulated in a tunable and multifunctional manner for biomedical applications," said Prof. ZHENG.

By analyzing the brightness variations of 369 solar-like stars, researchers have concluded that the Sun is less magnetically active and shows less variability in its brightness than similar stars in the Galaxy. "Why does the Sun seem to differ so much from other stars that appear to be the most similar to it?" asks a related Perspective from Angela Santos and Savita Mathur. Like other main-sequence stars, the Sun possesses a powerful magnetic field that generates dark sunspots, bright solar flares, and other visible features. These magnetic imprints vary over time and temporarily affect the variability of the star's light output, causing the Sun to go through an 11-year cycle of higher and lower activity. Understanding the Sun's magnetic field is critical for predicting the star's future, but scientists debate whether the Sun's activity will diminish or may still become more magnetically active. Timo Reinhold and colleagues compared the Sun's brightness variations to observations of 369 stars with similar masses, temperatures, compositions and rotational properties, which they selected from four years of observations from the Kepler space telescope and combined with data from the Gaia spacecraft. By quantifying the brightness variations of the stars, the authors found that most were more active than the Sun, often being five times more variable than the Sun was over the last 140 years. Reinhold et al. discuss several potential explanations for their observations, including possibilities that the Sun can have higher variability over long timescales, or differs from similar stars in ways that haven't yet been recognized. Santos and Mathur also discuss how stellar variability has implications for the operation of satellites in orbit around E

A new study from University of Michigan climate researchers concludes that some of the latest-generation climate models may be overly sensitive to carbon dioxide increases and therefore project future warming that is unrealistically high.

In a letter scheduled for publication April 30 in the journal Nature Climate Change, the researchers say that projections from one of the leading models, known as CESM2, are not supported by geological evidence from a previous warming period roughly 50 million years ago.

The researchers used the CESM2 model to simulate temperatures during the Early Eocene, a time when rainforests thrived in the tropics of the New World, according to fossil evidence.

But the CESM2 model projected Early Eocene land temperatures exceeding 55 degrees Celsius (131 F) in the tropics, which is much higher than the temperature tolerance of plant photosynthesis--conflicting with the fossil evidence. On average across the globe, the model projected surface temperatures at least 6 C (11 F) warmer than estimates based on geological evidence.

"Some of the newest models used to make future predictions may be too sensitive to increases in atmospheric carbon dioxide and thus predict too much warming," said U-M's Chris Poulsen, a professor in the U-M Department of Earth and Environmental Sciences and one of the study's three authors.

The other authors are U-M postdoctoral researcher Jiang Zhu and Bette Otto-Bliesner of the National Center for Atmospheric Research. They say their study shows how geological evidence can be used to benchmark climate models and predictions of future warming.

The new study focuses on a key climate parameter called equilibrium climate sensitivity, or ECS. ECS refers to the long-term change in global temperature that would result from a sustained doubling--lasting hundreds to thousands of years--of heat-trapping carbon dioxide above the preindustrial baseline level of 285 parts per million.

The present-day CO2 level is about 410 ppm, and climate scientists say atmospheric concentrations could hit 1,000 ppm by the year 2100 if nothing is done to limit carbon emissions from the burning of fossil fuels.

For decades, most of the top climate models predicted an equilibrium climate sensitivity of around 3 degrees Celsius (5.4 F), with a range of 1.5 to 4.5 C (2.7 to 8.1 F).

But that changed recently with some of the newest climate models participating in CMIP6. The Coupled Model Intercomparison Project (CMIP) is an internationally coordinated effort between climate-science institutions, and it is now in its sixth phase. The next assessment report from the authoritative Intergovernmental Panel on Climate Change, which is due next year, will rely on CMIP6 models.

Ten of the 27 CMIP6 models have an equilibrium climate sensitivity higher than 4.5 C (8.1 F), meaning that they are more sensitive to CO2 increases than most previous-generation models. The CESM2 model (Community Earth System Model, version 2) tested by the U-M-led research team is one of those CMIP6 models and has an equilibrium climate sensitivity of 5.3 C (9.5 F).

The predecessor to CESM2, the CESM1.2 model, did a remarkably good job of simulating temperatures during the Early Eocene, according to the researchers. It has an equilibrium climate sensitivity of 4.2 C (7.6 F).

"Our study implies that CESM2's climate sensitivity of 5.3 C is likely too high. This means that its prediction of future warming under a high-CO2 scenario would be too high as well," said Zhu, first author of the Nature Climate Change letter.

"Figuring out whether the high climate sensitivity in CMIP6 models is realistic is of tremendous importance for us to anticipate future warming and to make adaptation plans," said NCAR's Otto-Bliesner.

The team's simulations of the Early Eocene incorporated the latest paleoclimate reconstructions and included data about paleogeography, vegetation cover and land surface properties. Reconstructions of atmospheric carbon dioxide levels from that time predate ice-core records and rely on geochemical and paleobotanical proxies.

The Intergovernmental Panel on Climate Change's Fifth Assessment Report, finalized in 2014, said the global surface temperature increase by the end of the 21st century is likely to exceed 1.5 C relative to the 1850 to 1900 period for most emissions scenarios, and is likely to exceed 2.0 C for some emissions scenarios.

The projections in that assessment were based on the previous generation of CMIP models, known as CMIP5 models. The newer CMIP6 models will likely lead to projections of even greater warming.
The Paris climate accord's long-term temperature goal is to keep the increase in global average temperature to well below 2 C above preindustrial levels and to pursue efforts to limit the increase to 1.5 C.

Researchers from Peter the Great St.Petersburg Polytechnic University (SPbPU) in collaboration with colleagues from Southern Federal University and Indian Institute of Technology-Madras (IIT Madras) suggested using machine learning methods to predict the properties of artificial sapphire crystals. It is a unique material widely used in microelectronics, optics and electronics. The results of the study were published in the Journal of Electronic Science and Technology and the illustration from the article hit the coverpage of the journal.

Machine learning methods are becoming increasingly popular in accelerating the design of new materials by predicting material properties. The minimization of various defects in the crystal structure is extremely important for the improvement and development of modern technologies for the artificial sapphire crystal growth.

Scientists note that the purpose of the study is to reduce various defects in sapphire crystals, improve and develop modern technologies for growing artificial crystals.

"Our research team obtained the models of crystal growth parameters' influence on sapphire crystal growth. We developed the software which is considered to be a universal tool for studying the influence of various parameters on the quality of crystals. It can be widely used to assess and predict the defects in a growing crystal," said Alexey Filimonov, Professor of the Higher Engineering Physics School at Peter the Great St. Petersburg Polytechnic University (SPbPU).

Julia Klunnikova, Associate Professor at Southern Federal University (SFU), adds: "We use the scheme where the predictive modules are developed separately using the Orange Canvas data mining tool. For the decision support system, our group developed a special software for analyzing the quality of the resulting crystals, which allows optimizing the process of crystal growth".

Ravi Kumar, Head of the Laboratory for High Performance Ceramics & Professor in the Dept of Metallurgical and Materials Engg.,at the Indian Institute of Technology-Madras (IIT Madras), is confident that the industrial application of such methods will heighten the automatization level of production of crystals with a predefined combination of properties that can be important for a particular application in micro- and nanoelectronics. The solution of these scientific and engineering problems assumes the use of information technologies in production of crystals at a new level.

Currently, the team of authors is working to increase the number of experimental data, which will provide new opportunities for prediction and increase its accuracy. It is planned to recognize crystal images from the furnace chamber and to forecast the conditions' influence on the crystal quality.

BINGHAMTON, NY -- Research into mass trauma events, like the 9/11 terror attacks, suggests effective ways to cope during the current COVID-19 crisis, according to research led by faculty at Binghamton University, State University of New York.

Binghamton University Distinguished Professor of Psychology Steven Jay Lynn, doctoral student Craig Polizzi and Andrew Perry explored these techniques in "Stress and Coping in the time of COVID-19: Pathways to Resilience and Recovery," an article published in a special issue of the academic journal Clinical Neuropsychiatry. Lynn is the director of the Laboratory of Consciousness, Cognition and Psychopathology at Binghamton University.

The lab has studied coping techniques that can potentially promote resilience to and recovery from stress, including acceptance-based coping, mindfulness and lovingkindness meditation, Polizzi explained.
"We also drew inspiration from our previous work with clients who have experienced traumas and how they have coped with traumatic events," he said.

In the article, the authors draw on studies of the New York metropolitan area following the Sept. 11, 2001, terrorist attacks, another incident of mass trauma marked by intense fear with the potential to produce psychological problems such as posttraumatic stress, anxiety and depression. Additionally, 9/11 has been heavily studied in terms of coping, resilience and trauma, providing a strong scientific foundation for evaluating the efficacy of coping strategies, Polizzi said.

Of course, there are significant differences. While natural disasters and terror events can bring people together in response or recovery, the pandemic requires a level of social isolation not seen since the 1918 Spanish flu. People also respond to trauma differently, which led the authors to suggest a variety of coping techniques.

"People are unique and the way they cope should be consistent with their needs and values," Polizzi said.

Coping activities -- also called behavioral activation -- can increase the ability to bounce back from negative events, and free up mental resources to deal with ongoing stressors and changing situations. At the heart of these coping activities are the three Cs of control, coherence and connectedness.

You can get a sense of control by planning your daily activities, checking in on friends and loved ones, adjusting your news intake, keeping a journal or preparing for your post-pandemic future. Connection, which fulfills the need for human contact and support, can be achieved even in times of social distancing through telephone calls, videoconferencing and social media, or even the purely internal practice of lovingkindness meditation, which directs positive emotions toward the self, loved ones, all humans and eventually all sentient beings.

Coherence "is founded in the deeply human desire to make sense and meaning of the world," according to the article. One starting point is "acceptance-based coping," observing our fears, anxieties and emotional responses without judgment -- a practice commonly known as mindfulness. You can practice mindfulness not only through meditation and focusing on the breath, but by giving an activity -- such as eating or walking -- your full and unhurried attention.

Looking ahead, the pandemic will give rise to additional research. Lynn's laboratory is planning to evaluate how mindfulness and emotion regulation promote resilience during the pandemic by defending against post-traumatic stress and dissociation.

"It is also important to test the coping strategies we proposed in our article to see if people did use them to reduce distress during the pandemic, as well identify additional techniques individuals used to cope with stress to enhance recommendations for coping during future mass traumas," Polizzi said.

Chinese researchers are using big data to help identify trauma patients who could experience potential adverse health events in the emergency department through the aid of a clinical decision support system. It was developed using a novel real-world evidence mining and evidence-based inference method, driven by improved information storage and electronic medical records.

The researchers, from Peking University People's Hospital and National Institute of Health Data Science at Peking University, published their results online on February 7 in IEEE Transactions on Systems, Man, and Cybernetics: Systems, a journal of the Institute of Electrical and Electronics Engineers.

Clinical decision support systems have been in use for nearly 50 years, but this is the first one developed using evidential reasoning in an emergency department setting.

"Appropriate use of information technologies, particularly clinical decision support systems, may aid clinicians to make better clinical decisions and reduce the rate of medical errors," said first author Guilan Kong, associate research professor at the National Institute of Health Data Science at Peking University. "By inputting clinical data of a patient, combined with available historical data, our proposed clinical decision support system outputs a predicted belief degree of severe trauma, including ICU admission and in-hospital death."

In the proposed clinical decision support system, the emergency room physician supplies information about the patient, including blood pressure, pulse rate, respiration rate, consciousness level, body temperature, age, comorbidities, mechanism and location of injury. These clinical signs and symptoms are then processed using an evidential reasoning rule, which compares each piece against the evidence mined from real-world data to predict the probability of adverse events.

"The clinical variable signs and symptoms may be interrelated and lead to a clinical outcome," said Kong, who is also appointed at the Center for Data Science in Health and Medicine.

For example, a patient may have low level of consciousness because of the location of the injury, or it might be related to the high body temperature. The degree of interdependence between clinical signs and symptoms can be calculated from historical patient data.

"To optimally manage trauma patients and help them achieve ideal outcomes, trauma patients with a high probability of being admitted to the intensive care unit or dying in hospital need to be identified quickly and accurately upon their arrival at a hospital," Kong said.

In developing their clinical decision support system, the researchers used a trauma dataset from the emergency department at Kailuan Hospital in China, a hospital that has a close research collaboration with the Trauma Center at Peking University People's Hospital. Through the dataset, the researchers obtained the data of 1,299 trauma patients.

The team found that not only did their model prove especially useful in cases without prior expert knowledge or clinical experiences, but that the clinical decision support system also allowed for more accurate identification of trauma patients with adverse events compared to other systems with traditional machine learning models.

Furthermore, the clinical decision support system works in a real-time fashion. From a physician's input of a patient's data to generating appropriate advices, the system works almost without any delay, which in turn helps buy trauma patients valuable time.

Next, the researchers plan to finetune their system and to generalize it for use in other clinical areas and non-emergent department settings.

University of Sheffield scientists have produced the first high resolution images of the cell wall of the deadly bacterium Staphylococcus aureus, better known as its antibiotic resistant form, MRSA

Research will help scientists combat antibiotic resistance

Findings overturn previous theories about the structure of these outer bacterial layers

Scientists from the University of Sheffield have produced the first high-resolution images of the structure of the cell wall of bacteria, in a study that could further understanding of antimicrobial resistance.

The research, published in Nature, revealed a new and unexpected structure of the outer bacterial layers of the bacterium Staphylococcus aureus.

The findings set a new framework for understanding how bacteria grow and how antibiotics work, overturning previous theories about the structure of the outer bacterial layers.

The images give unprecedented insight into the composition of the bacterial cell wall and will inform new approaches to developing antibiotics in order to combat antibiotic resistance. There are no other examples of studies of the cell wall in any organism at comparable resolution, down to the molecular scale.

Laia Pasquina Lemonche, a PhD Researcher from the University of Sheffield's Department of Physics and Astronomy, said: "Many antibiotics work by inhibiting the bacteria's production of a cell wall, a strong but permeable skin around the bacteria which is critical for its survival.

"We still don't understand how antibiotics like penicillin kill bacteria, but this isn't surprising because until now we had remarkably little information about the actual organisation of the bacterial cell wall. This study provides that essential stepping stone which we hope will lead to both a better understanding of how antibiotics work and to the future development of new approaches to combat antimicrobial resistance."

The team used an advanced microscopy technique called Atomic Force Microscopy (AFM), which works by using a sharp needle to feel the shape of a surface and build an image similar to a contour map, but at the scale of individual molecules.

Professor Jamie Hobbs, Professor of Physics at the University of Sheffield, said: "It is by physicists and biologists working together that we've been able to make these breakthroughs in our understanding of the bacterial cell wall."

The researchers are now using the same techniques to understand how antibiotics change the architecture of the cell wall and also how changes in the cell wall are important in antimicrobial resistance.

Stony Brook, Long Island, April 29, 2020: In evolutionary terms, islands are the stuff of weirdness. It is on islands where animals evolve in isolation, often for millions of years, with different food sources, competitors, predators, and parasites...indeed, different everything compared to mainland species. As a result, they develop into different shapes and sizes and evolve into new species that, given enough time, spawn yet more new species.

Such is the case with the discovery of a new, bizarre 66-million-old mammal in Madagascar by a team of international researchers led by Dr. David Krause, senior curator of vertebrate paleontology at the Denver Museum of Nature & Science and professor emeritus at Stony Brook University, where part of the research was done. The discovery of this opossum-sized mammal that lived among dinosaurs and massive crocodiles on the fourth largest island on Earth was announced today in the journal Nature. Dr. James B. Rossie of Stony Brook University is one of the study's co-authors. The late Yaoming Hu of Stony Brook University was also a co-author.

The finding of the new mammal, called Adalatherium, which is translated from the Malagasy and Greek languages and means "crazy beast," is based on a nearly complete skeleton that is astoundingly well preserved. The skeleton is the most complete for any Mesozoic mammal yet discovered in the southern hemisphere.

Krause said that, "knowing what we know about the skeletal anatomy of all living and extinct mammals, it is difficult to imagine that a mammal like Adalatherium could have evolved; it bends and even breaks a lot of rules."

In fact, although a life-like reconstruction might lead one to think that Adalatherium was a run-of-the-mill badger, its "normality" is literally only skin deep. Below the surface, its skeleton is nothing short of "outlandish." It has primitive features in its snout region (like a septomaxilla bone) that hadn't been seen for a hundred million years in the lineage leading to modern mammals.

"Its nasal cavity exhibits an amazing mosaic of features, some of which are very standard for a mammal, but some that I've never seen in anything before," Rossie declared.

Adalatherium had more holes (foramina) on its face than any known mammal, holes that served as passageways for nerves and blood vessels supplying a very sensitive snout that was covered with whiskers. And there is one very large hole on the top of its snout for which there is just no parallel in any known mammal, living or extinct.

The teeth of Adalatherium are vastly different in construction than any known mammal. Its backbone had more vertebrae than any Mesozoic mammal and one of its leg bones was strangely curved.

About the size of a Virginia opossum, Adalatherium was also unusual in that it was very large for its day; most mammals that lived alongside dinosaurs were much smaller, mouse-sized on average.

Adalatherium belongs to an extinct group of mammals called gondwanatherians because they are only known from the ancient southern supercontinent of Gondwana. Gondwanatherian fossils were first found in Argentina in the 1980s but have since also been found in Africa, India, the Antarctic Peninsula, and Madagascar. Gondwanatherians were first thought to be related to modern-day sloths, anteaters, and armadillos but "now are known to have been part of a grand evolutionary experiment, doing their own thing, an experiment that failed and was snuffed out in the Eocene, about 45 million years ago," Krause explained.

Prior to the discovery of the nearly complete skeleton of Adalatherium, gondwanatherians were only known from isolated teeth and jaw fragments, with the exception of a cranium from Madagascar described by Krause and his team in 2014.

The completeness and excellent preservation of the skeleton of Adalatherium potentially opens up new windows into what gondwanatherians looked like and how they lived, but the bizarre features still have the scientific team guessing.

As Krause's primary collaborator Simone Hoffmann of the New York Institute of Technology put it, "Adalatherium is the oddest of oddballs. Trying to figure out how it moved is nearly impossible because, for instance, its front end is telling us a different story than its back end." The research team is still uncovering clues but thinks that, although Adalatherium might have been a powerful digging animal, it was also capable of running and potentially even had other forms of locomotion.

The plate tectonic history of Gondwana provides independent evidence for why Adalatherium is so bizarre. Adalatherium was found in rocks dated to near the end of the Cretaceous, at 66 million years ago. Madagascar, with the Indian subcontinent attached to the east, separated from Africa over a hundred million years before and finally became isolated as an island in the Indian Ocean when the Indian subcontinent detached at approximately 88 million years ago and drifted northward. That left the lineage that ultimately resulted in Adalatherium to evolve, isolated from mainland populations, for over 20 million years - "ample time to develop its many ludicrous features," said Krause.

The fossil record of early mammals from the northern hemisphere is roughly an order of magnitude better than from the south.

"Adalatherium is just one piece, but an important piece, in a very large puzzle on early mammalian evolution in the southern hemisphere," Krause noted. "Unfortunately, most of the pieces are still missing."

More than anything, this discovery underscores to the researchers how much more remains to be learned by making new discoveries of early mammals in Madagascar and other parts of the former Gondwana.

In addition to Krause, Hoffmann, and Rossie, other researchers involved in the new discovery - which was funded by the National Science Foundation and National Geographic Society -- were: the late Yaoming Hu of Stony Brook University; John R. Wible of Carnegie Museum of Natural History; Guillermo W. Rougier of University of Louisville; E. Christopher Kirk of University of Texas at Austin; Joseph R. Groenke of Stony Brook University and Ohio University; Raymond R. Rogers of Macalester College; Julia A. Schultz of Institut für Geowissenschaften der Universität Bonn, Alistair R. Evans of Monash University and Museums Victoria; Wighart von Koenigswald of Institut für Geowissenschaften der Universität Bonn; and Lydia J. Rahantarisoa of Université d'Antananarivo.

The new Adalatherium mammal is just the latest of a series of bizarre back-boned animals discovered by Krause and his research team on Madagascar over the past 25 years. Earlier discoveries have included a giant, armored, predatory frog (Beelzebufo), a pug-nosed, vegetarian crocodile (Simosuchus), and a small, buck-toothed dinosaur (Masiakasaurus).

The island itself is filled with animals (and plants) found nowhere else on the planet, including hissing cockroaches, giraffe weevils, tomato frogs, Satanic leaf-tailed geckos, panther chameleons, and streaked tenrecs to name a few. And, of course, there is the signature group of mammals - lemurs - made famous in the animated "Madagascar" movies. Only a few thousand years ago, the Madagascar fauna also included 1400-pound elephant birds, gorilla-sized lemurs, and pygmy hippopotamuses.

The near-shore habitats of Bahia Las Minas in the central Caribbean coast of Panama became heavily contaminated after a refinery accident in 1986. Over the next five years, there was a significant decline in the numbers and diversity of corals. Thirty years later, researchers from the Smithsonian Tropical Research Institute (STRI) and collaborating institutions report on the long-term changes of the oil spill on coral communities. Their findings were published in the journal Marine Biodiversity.

Oil pollution is known to cause lethal and sublethal responses on coral communities in the short-term, but its long-term effects have not been widely studied. The Bahia Las Minas oil spill, which contaminated about 40 square kilometers (about 15 square miles) near the Smithsonian's Galeta Point Marine Laboratory in Colon and became the largest recorded near coastal habitats in Panama, served as an opportunity to understand how coral reefs in tropical ecosystems recover from acute contamination over time.

"Monitoring these coral reefs was complex, exhausting and intense due to the large spatial scale of the project," said Héctor M. Guzmán, STRI marine ecologist. "Originally, we compared the contaminated refinery area with uncontaminated reef systems about 50 kilometers to the east between Portobelo and Isla Grande."

After the first five years, the team found that the abundance and diversity of most hard corals (Scleractinia), some branching and massive corals, and fire corals (Millepora) had decreased in the affected area. Other organisms, such as crustose coralline algae, an encrusting stony kind of seaweed that grows in the gaps between coral reefs, and Agaricia tenuifolia, a lettuce type of hard coral, had increased.

"Oil residues from the spill on the sediment surface were quickly degraded through natural weathering processes," said Stefanie Kaiser, a marine biologist at the University of Lodz. "However, a large amount of oil has been trapped in deeper layers where weathering processes are strongly hampered. The chronic effects of this reoccurring oil leaking from sediments could have been by far worse for affected coral communities than the acute effects of the spill."

A similar phenomenon occurred after the Deepwater Horizon oil spill in the Gulf of Mexico in April 2010, the largest in United States history. Ten years later, high levels of oil pollution continue to be found in organisms inhabiting the seafloor. However, as sea currents stir up these polluted sediments, they also contaminate species living at shallower waters.

Thirty years after the Bahia Las Minas spill, there were no longer any significant differences between the area near the oil refinery and the area the original team used for comparison. Since the mid-1990s, this area was affected by coastal development and deforestation. In both areas, the number and diversity of species had declined and the number of juvenile colonies was low. That is, the younger corals and associated organisms were not enough to regenerate healthy coral communities.

The similarities between both areas had more to do with the sustained deterioration of the Portobelo-Isla Grande coastal area than with an improvement in the conditions of Bahia Las Minas after the oil spill. These effects were related to coastal development and other human-related impacts on the reefs, such as rising sea temperatures, coral diseases, overfishing and aquatic pollution and sedimentation.

"The initial impact on the reef community was clear and somewhat predictable, a gradual recovery and an increase in the more resistant coral species," Guzmán said. "Nevertheless, we did not expect to see a similar response in our 'control' reefs where the long-term impact of coastal development was equal to or greater than the initial oil spill."

Although the long-term consequences of oil pollution on reef communities could not be determined, scientists worry about the way these external factors are contributing to the deterioration of marine ecosystems in previously healthy areas and preventing recovery in areas affected by oil contamination.

"The coral reefs along Panama's central Caribbean coast are practically doomed by coastal development," Guzmán said. "If unplanned development continues on the rise, they may continue to survive, but without any substantial recovery."

Members of the research team are affiliated with the Smithsonian Tropical Research Institute, the Universität Hamburg, the University of ?o?dz? and the University of Puerto Rico. Researchers involved were funded by the Smithsonian Tropical Research Institute, the Smithsonian Institution Environmental Science Program, the U.S. Mineral Management Service and the Secretaria Nacional de Ciencia, Tecnología e Innovación of Panama (SENACYT).

The Smithsonian Tropical Research Institute, headquartered in Panama City, Panama, is a unit of the Smithsonian Institution. The institute furthers the understanding of tropical biodiversity and its importance to human welfare, trains students to conduct research in the tropics and promotes conservation by increasing public awareness of the beauty and importance of tropical ecosystems.

New Rochelle, NY, April 28, 2020--In the quest to engineer replacement tissues and organs for improving human health, biofabrication has emerged as a crucial set of technologies that enable the control of precise architecture and organization. A new article reviews the impacts of biofabrication in tissue engineering and regenerative medicine over the previous year. The article is reported in Tissue Engineering, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. Click to read the article for free on the Tissue Engineering website through May 28, 2020.

In "Tissue Engineering and Regenerative Medicine 2019: the Role of Biofabrication--A Year in Review", Tiago Ramos, University College of London, UK, and Lorenzo Moroni, Maastricht University, the Netherlands, discuss the growing field of biofabrication and its recent impacts on tissue engineering and other disciplines. The authors first clarify terminology, including the concepts of bioassembly, bioprinting, and bioinks. They then catalog and highlight the developments in the 3D bioprinting of several specific tissue models, discussing both the extrusion-based methods and the newer optical fabrication techniques of stereolithography, laser-induced forward transfer, and two-photon lithography. Finally, developments are explored in the area of 4D bioprinting--the time-dependent modification of fabricated constructs.

"Drs. Ramos and Moroni, both leaders in the field of bioprinting and biofabrication, brilliantly detail the rising impact of printing on the tissue engineering community," says Tissue Engineering Co-Editor-in-Chief John P. Fisher, PhD, Fischell Family Distinguished Professor & Department Chair, and Director of the NIH Center for Engineering Complex Tissues at the University of Maryland. "The unique capabilities 3D printing--precision, flexibility, and personalization--have driven its growth in medicine, and the critical, recent success are nicely detailed in this review."

Nonverbal learning disability (NVLD), a poorly understood and often-overlooked disorder that causes problems with visual-spatial processing, may affect nearly 3 million children in the United States, making it one of the most common learning disorders, according to a new study by led by Columbia University Irving Medical Center.

The study, the first to estimate the prevalence of NVLD in the general population, was published online today in JAMA Network Open.

"NVLD is a huge and hidden public health burden," said Jeffrey Lieberman, Chair of Psychiatry at the Columbia University Vagelos College of Physicians and Surgeons and Director of the New York State Psychiatric Institute. "This important work might never have come to light if not for the support of dedicated advocate and their philanthropic support. We hope that these findings raise awareness of the disorder and lead to an understanding of its neurobiology and better treatments."

The name of this neurodevelopmental disorder may be part of the problem: children with NVLD are not nonverbal, as the name suggests, and have no difficulty reading. Instead, children with NVLD have difficulty processing visual-spatial sensory information, which can cause problems with math, executive function, and fine motor and social skills. "Children with this disorder might shy away from doing jigsaw puzzles or playing with Legos," says lead author Amy E. Margolis, PhD, assistant professor of medical psychology at Columbia University Vagelos College of Physicians and Surgeons. "They may have trouble tying their shoes, using scissors, or learning routes or schedules."

NVLD was first described in 1967, but compared with other learning disorders it has received little attention. There's little consensus among physicians on how to diagnose the disorder, and it is not included in the current edition of the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM). The cause of NVLD is not known and there are no treatments.

Few parents have heard of NVLD. "Most parents recognize that a child who isn't talking by age two should be evaluated for a learning disorder. But no one thinks twice about kids who have problems with visual-spatial tasks," says Margolis.

To see how common the disorder is, the researchers analyzed three independent samples of children (ages 6 to 19) in the U.S. and Canada, including a total of 2,596 individuals. Any child with a deficit in spatial reasoning and impairment in two of four domains (fine motor skills, math calculation, visual executive functioning, and social skills) was considered to have NLVD.

The researchers found that 3 to 4 percent of children in each sample met the criteria for NLVD. "When applied to the U.S. population under 18, this translates to approximately 2.2 to 2.9 million children having NVLD," says co-author Katherine Keyes, PhD, MPH, associate professor of epidemiology at the Columbia Mailman School of Public Health.

Many of the children in the study who were identified as having NVLD had been diagnosed with attention-deficit hyperactivity disorder (ADHD) or anxiety disorder. "While there is some overlap in symptoms between the two disorders, it's important to distinguish between them so we can begin to develop interventions for NVLD," says Margolis.

The researchers plan to submit an application to the American Psychiatric Association to include the disorder in the next (sixth) edition of the DSM. They also plan to propose a new name--developmental visual spatial disorder--to improve understanding and recognition of the disorder.

Margolis advises parents to seek evaluation for children with symptoms of NVLD. "Diagnosis can be accomplished using basic assessment tools," says Margolis. "It doesn't have to involve complex and costly neuropsychological testing. We envision that all clinicians who use DSM5 will be able to use our new criteria to determine who may meet criteria. They can then send patients for basic psychological testing that is always available through schools to identify/quantify a problem with visual-spatial processing."

DALLAS, April 28, 2020 -- People who reported work-related stress were more likely to be hospitalized for peripheral artery disease compared to those who did not report work-related stress, according to new research published today in the Journal of the American Heart Association, an open access journal of the American Heart Association. The article appears in a special spotlight issue exploring different aspects of the complex relationships between psychosocial factors and cardiovascular health.

Peripheral artery disease, or PAD, is a cardiovascular disease that occurs when cholesterol or other fatty substances in the blood build up in the blood vessels away from the heart, usually the legs, impeding blood flow. Symptoms often include leg pain while walking. Left untreated, peripheral artery disease increases the likelihood of heart disease and stroke. Worldwide, peripheral artery disease affects more than 200 million people, including more than 8.5 million in the United States. Despite the considerable burden of peripheral artery disease, the evidence on specific risk factors, including potential primary preventive targets, for this disease is scarce, according to researchers.

Work-related stress, or job strain, refers to psychological and social stress at work, often from high expectations combined with lower levels of personal control. Previous studies have linked work-related stress to other forms of atherosclerotic disease; however, few have specifically analyzed its effects on peripheral artery disease. This study focused on the relationship between work-related stress and hospital treatment for peripheral artery disease.

The researchers evaluated the records of 139,000 men and women (36.4% men; average age of study participants range 39-49) participating in 11 separate studies from 1985-2008 in Finland, Sweden, Denmark and the United Kingdom. Participants included in the analysis had no previous history of peripheral artery disease when the respective studies began. Individual information for each participant included age, sex, BMI, smoker or nonsmoker, alcohol consumption, physical activity level, diabetes status, socioeconomic position, data on hospitalizations and the questionnaire on work-related stress.

During an average 12.8 years of follow up, 667 people (0.2 to 1.8% of participants) were hospitalized for peripheral artery disease. Researchers found that people with work-related stress were 1.4 times as likely as those without work-related stress to have a record of peripheral artery disease in the hospitalization register, after adjusting for age, sex and lifestyle variables.

"Our findings suggest that work-related stress may be a risk factor for peripheral artery disease in a similar way as it is for heart disease and stroke," said lead study author Katriina Heikkilä, Ph.D., senior researcher at the Karolinska Institute, Stockholm.

Stress is associated with increased inflammation and higher blood glucose levels. So, although there is limited evidence linking work-related stress to heart disease, stress could be contributing to complications and exacerbations of peripheral artery disease.

The investigators measured work-related stress based on participants' ratings of statements to describe psychosocial aspects of their job. This information was compared to records on peripheral artery disease hospitalizations across nearly 13 years of hospital records.

Overall, nearly one-fourth of participants with no previous hospitalization for peripheral artery disease reported work-related stress at the beginning of the 11 studies.

Researchers noted increased risk among men, those with high socioeconomic position and smokers, but noted such subgroup analysis was limited by the small number of people with peripheral artery disease.

Limitations of this study are that it included hospital-treated peripheral artery disease only, which means that the results cannot be generalized to less severe forms of the disease. Also, certain health information, such as blood pressure and cholesterol levels, was unavailable.

Co-authors are Jaana Pentti, M.Sc.; Ida E.H. Madsen, Ph.D.; Tea Lallukka, Ph.D.; Marianna Virtanen, Ph.D.; Lars Alfredsson, M.D., Ph.D.; Jakob Bjorner, Ph.D.; Marianne Borritz, M.D.; Eric Brunner, Ph.D.; Hermann Burr, Ph.D.; Jane E. Ferrie, Ph.D.; Anders Knutsson, M.D.; Aki Koskinen, M.S.; Constanze Leineweber, Ph.D.; Linda L. Magnusson Hanson, Ph.D.; Martin L. Nielsen, M.D.; Solja T. Nyberg, Ph.D.; Tuula Oksanen, M.D.; Jan H. Pejtersen, Ph.D; Olli Pietiläinen, M.Sc.; Ossi Rahkonen, Ph.D.; Reiner Rugulies, Ph.D.; Archana Singh-Manoux, Ph.D.; Andrew Steptoe, D.Sci.; Sakari Suominen, M.D.; Töres Theorell, Ph.D.; Jussi Vahtera, M.D., Ph.D.; Ari Väänänen, Ph.D.; Hugo Westerlund, Ph.D.; and Mika Kivimäki, Ph.D. Author disclosures are in the manuscript.

NordForsk (the Nordic Research Programme on Health and Welfare), the United Kingdom Medical Research Council, the Academy of Finland and the Helsinki Institute of Life Sciences funded the study.

Additional original articles published in JAHA's spotlight issue on psychosocial risk factors in cardiovascular disease include:

Youth Who Achieve Upward Socioeconomic Mobility Display Lower Psychological Distress But Higher Metabolic Syndrome Rates as Adults: Prospective Evidence from the National Study of Adolescent Health and The Midlife in the United States Study

Sleep characteristics and measures of glucose metabolism in African Americans: The Jackson Heart Study

An Analysis of Post-Traumatic Stress Disorder (PTSD), Depression, Anxiety and Resiliency within the Unique Population of Spontaneous Coronary Artery Dissection Survivors

Association of Childhood Psychosocial Environment with 30-year Cardiovascular Disease Incidence and Mortality in Middle Age

From Tear to Fear: Posttraumatic Stress Disorder in Patients with Acute Type A Aortic Dissection

Prevalence and Prognostic Association of a Clinical Diagnosis of Depression in Adult Congenital Heart Disease: Results of the Boston Adult Congenital Heart Disease Biobank

Cardiovascular Risk and Resilience among Blacks: Rationale and Design of the Morehouse-Emory Center (MECA) for Health Equity

Greater Daily Psychosocial Stress Exposure is Associated with Increased Norepinephrine-Induced Vasoconstriction in Young Adults

Goal-Striving Stress and Incident Cardiovascular Disease in African Americans: The Jackson Heart Study

Positive Health Beliefs and Blood Pressure Reduction in the Discharge Educational Strategies for Reduction of Vascular Events (DESERVE) Study

Exploring the spatial patterning in racial differences in cardiovascular health between blacks and whites across the United States: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study