Culture

Volcanoes on Mars could be active

image: Recent explosive volcanic deposit around a fissure of the Cerberus Fossae system.

Image: 
NASA/JPL/MSSS/The Murray Lab

Evidence of recent volcanic activity on Mars shows that eruptions could have taken place in the past 50,000 years, according to new study by researchers at the University of Arizona's Lunar and Planetary Laboratory and the Planetary Science Institute.

Most volcanism on the Red Planet occurred between 3 and 4 billion years ago, with smaller eruptions in isolated locations continuing perhaps as recently as 3 million years ago. But, until now, there was no evidence to indicate Mars could still be volcanically active.

Using data from satellites orbiting Mars, researchers discovered a previously unknown volcanic deposit. They detail their findings in the paper "Evidence for geologically recent explosive volcanism in Elysium Planitia, Mars," published in the journal Icarus.

"This may be the youngest volcanic deposit yet documented on Mars," said lead study author David Horvath, who did the research as a postdoctoral researcher at UArizona and is now a research scientist at the Planetary Science Institute. "If we were to compress Mars' geologic history into a single day, this would have occurred in the very last second."

The volcanic eruption produced an 8-mile-wide, smooth, dark deposit surrounding a 20-mile-long volcanic fissure.

"When we first noticed this deposit, we knew it was something special," said study co-author Jeff Andrews-Hanna, an associate professor at the UArizona Lunar and Planetary Laboratory and the senior author on the study. "The deposit was unlike anything else found in the region, or indeed on all of Mars, and more closely resembled features created by older volcanic eruptions on the Moon and Mercury."

Further investigation showed that the properties, composition and distribution of material match what would be expected for a pyroclastic eruption - an explosive eruption of magma driven by expanding gasses, not unlike the opening of a shaken can of soda.

The majority of volcanism in the Elysium Planitia region and elsewhere on Mars consists of lava flowing across the surface, similar to recent eruptions in Iceland being studied by co-author Christopher Hamilton, a UArizona associate professor of lunar and planetary sciences. Although there are numerous examples of explosive volcanism on Mars, they occurred long ago. However, this deposit appears to be different.

"This feature overlies the surrounding lava flows and appears to be a relatively fresh and thin deposit of ash and rock, representing a different style of eruption than previously identified pyroclastic features," Horvath said. "This eruption could have spewed ash as high as 6 miles into Mars' atmosphere. It is possible that these sorts of deposits were more common but have been eroded or buried."

The site of the recent eruption is about 1,000 miles (1,600 kilometers) from NASA's InSight lander, which has been studying seismic activity on Mars since 2018. Two Marsquakes, the Martian equivalent of earthquakes, were found to originate in the region around the Cerberus Fossae, and recent work has suggested the possibility that these could be due to the movement of magma deep underground.

"The young age of this deposit absolutely raises the possibility that there could still be volcanic activity on Mars, and it is intriguing that recent Marsquakes detected by the InSight mission are sourced from the Cerberus Fossae," Horvath said. In fact, the team of researchers predicted this to be a likely location for Marsquakes several months before NASA's InSight lander touched down on Mars.

A volcanic deposit such as this one also raises the possibility for habitable conditions below the surface of Mars in recent history, Horvath said.

"The interaction of ascending magma and the icy substrate of this region could have provided favorable conditions for microbial life fairly recently and raises the possibility of extant life in this region," he said.

Similar volcanic fissures in this region were the source of enormous floods, perhaps as recently as 20 million years ago, as groundwater erupted out onto the surface.

Andrews-Hanna's research group continues to investigate the causes of the eruption. Pranabendu Moitra, a research scientist in the UArizona Department of Geosciences, has been probing the mechanism behind the eruption.

An expert in similar explosive eruptions on Earth, Moitra developed models to look at the possible cause of the Martian eruption. In a forthcoming paper in the journal Earth and Planetary Science Letters, he suggests that the explosion either could have been a result of gases already present in the Martian magma, or it could have happened when the magma came into contact with Martian permafrost.

"The ice melts to water, mixes with the magma and vaporizes, forcing a violent explosion of the mixture," Moitra said. "When water mixes with magma, it's like pouring gasoline on a fire."

He also points out that the youngest volcanic eruption on Mars happened only 6 miles (10 kilometers) from the youngest large-impact crater on the planet - a 6-mile-wide crater named Zunil.

"The ages of the eruption and the impact are indistinguishable, which raises the possibility, however speculative, that the impact actually triggered the volcanic eruption," Moitra said.

Several studies have found evidence that large quakes on Earth can cause magma stored beneath the surface to erupt. The impact that formed the Zunil crater on Mars would have shaken the Red Planet just like an earthquake, Moitra explained.

While the more dramatic giant volcanoes elsewhere on Mars - such as Olympus Mons, the tallest mountain in the solar system - tell a story of the planet's ancient dynamics, the current hotspot of Martian activity seems to be in the relatively featureless plains of the planet's Elysium region.

Andrews-Hanna said it's remarkable that one region hosts the epicenters of present-day earthquakes, the most recent floods of water, the most recent lava flows, and now an even more recent explosive volcanic eruption.

"This may be the most recent volcanic eruption on Mars," he said, "but I think we can rest assured that it won't be the last."

The volcanic deposit described in this study, along with ongoing seismic rumbling in the planet's interior detected by InSight and possible evidence for releases of methane plumes into the atmosphere detected by NASA's MAVEN orbiter, suggest that Mars is far from a cold, inactive world, Andrews-Hanna said.

"All these data seem to be telling the same story," he said. "Mars isn't dead."

Credit: 
University of Arizona

CHEST releases updated guidelines to diagnose and evaluate hypersensitivity pneumonitis

The American College of Chest Physicians® (CHEST) recently released new clinical guidelines on the Diagnosis and Evaluation of Hypersensitivity Pneumonitis (HP). The guidelines contain 14 evidence-based recommendations to improve individual diagnostic decision-making and to decrease diagnostic practice variability.

Occurring at any age, HP is an immunologically mediated form of lung disease resulting from inhalational exposure to a large variety of environmental and/or occupational inciting antigens (typically fungal, bacterial, avian). Over the years, the categorization of HP based on clinical features and disease duration coupled with traditional diagnostic criteria has been unhelpful, even when accurate, when separated from a probabilistic diagnostic reasoning approach and multidisciplinary consensus.

By outlining a patient-centered and interdisciplinary diagnostic approach to a confident or working HP diagnosis, these guidelines will serve as a central source to help optimize diagnostic consistency and decision-making in HP across multidisciplinary teams and among clinicians.

"Guidelines for medical diagnoses are fundamental to better align diagnostic approaches across practicing institutions," says Evans Fernández, MD, MS, a pulmonologist at National Jewish Health. "Along with streamlining the approach to diagnosing HP, the guidelines also provide a diagnostic algorithm incorporating the evidence and informed by expert consensus, to aid physicians in gauging the probability of HP."

Several of the guidelines presented in the report include the following recommendations:

In patients with suspected HP, the panel suggests:

Classifying patients based on the likelihood of occupational or environmental inciting antigen exposure and as fibrotic or nonfibrotic based on the presence or absence of fibrosis on high-resolution CT of the chest.

Against performing bronchoalveolar lavage fluid analysis in patients who have a compelling exposure history within the appropriate clinical context and a pattern typical for HP on high-resolution CT of the chest.

Considering histological lung biopsy for additional diagnostic evaluation when all available data such as clinical, laboratory and radiologic findings (along with bronchoscopic results) do not yield a confident diagnosis, and results may help guide management.

The full list of recommendations and an explanation of the methodology applied is available on the journal CHEST® website.

"Along with the physician's diagnosis, it is important for patients to understand their disease," says Dr. Fernández. "To assist those diagnosed with an interstitial lung disease, like HP, there are resources available on the CHEST Foundation website."

Credit: 
American College of Chest Physicians

Researchers use arcuate organoids to study development and disease of the hypothalamus

PHILADELPHIA-- Human brain organoids are remarkable platforms for modeling features of human brain development and diseases. Building on methods to generate organoids to model different brain regions such as the cortex and the midbrain, researchers at the Perelman School of Medicine at the University of Pennsylvania have generated the first organoids of the arcuate nucleus (ARC), an essential structure in the hypothalamus that sends signals of hunger and feeling full. This part of the hypothalamus exhibits a tremendous amount of cell diversity, and is far more complex than previously modeled parts of the brain.

In a paper published today in Cell Stem Cell, researchers at Penn report generating arcuate organoids (ARCOs) that model the ARC of the hypothalamus. Previous studies have generated 2D hypothalamic-like neurons and 3D hypothalamic organoids from human induced pluripotent stem cells (iPSCs). However, no protocols previously existed to generate hypothalamus nucleus-specific organoids.

Researchers applied a machine learning approach and used published mouse data to predict ARC populations in the human hypothalamus at the single-cell level. Researchers then compared individual clusters of cells from the ARCO dataset with the predicted human ARC cells in the neonatal human hypothalamus. Using this approach, they determined that the ARCOs exhibit very similar cell type diversity and molecular signatures to those of human ARCs.

"This model provides opportunities to examine the previously inaccessible human fetal development of the hypothalamic arcuate nucleus," says senior author Guo-li Ming, MD, PhD, a professor of Neuroscience at Penn. "For the first time, we have an atlas of cell types in the human hypothalamus, which will be a blueprint to further understanding the development of brain disorders, such as certain causes of obesity and autism."

Knowing that a dysfunction within the hypothalamus can lead to disorders such as Prader-Willi syndrome (PWS) - a genetic disorder caused by a loss of function of specific genes on chromosome 15, in which patients become constantly hungry, often leading to obesity and other complications - researchers generated iPSCs from two patients with known genetic mutations that cause PWS, and used those to derive ARCOs. They showed that ARCOs derived from patients with PWS maintain disease- and patient-specific gene signatures. For example, one of the cell types within the ARC is responsible for regulating the leptin response, which regulates food intake, and it is known that this pathway malfunctions in patients with PWS. Researchers found that indeed there is also a dysfunction in leptin response and the signaling pathways in the PWS ARCO, suggesting that not only can the ARCOs recapitulate single nuclei in terms of their cell type diversity and molecular signatures, but the patient-derived ARCOs can recapitulate certain disease signatures.

"Our study provides a scalable, efficient, and robust protocol to generate ARC-specific organoids, which can be used to model early hypothalamic developmental processes and related brain diseases," Ming says. "I look forward to future studies with a larger cohort of Prader-Willi syndrome donors to help us better model PWS in ARCOs and further understand the potential pathology of the disorder at the cellular and molecular levels."

Credit: 
University of Pennsylvania School of Medicine

New mapping technique reveals epigenetic drivers of cancers

Scientists have made major advances in understanding and developing treatments for many cancers by identifying genetic mutations that drive the disease. Now a team led by researchers at Weill Cornell Medicine, NewYork-Presbyterian and the New York Genome Center (NYGC) has developed a machine learning technique for detecting other modifications to DNA that have a similar effect.

The study, published May 10 in Cancer Discovery, a journal of the American Association for Cancer Research, focuses on a type of chemical modification to DNA, called methylation, that typically silences nearby genes. The new technique can analyze the thousands of DNA methylation changes detected in tumor cells and infer which ones are likely driving tumor growth.

Methylation is an "epigenetic" process that normally regulates gene activity across the genome by altering the structure of DNA without changing the information contained in the genes. Occasionally, though, excessive methylation, called hypermethylation, occurs near a tumor suppressor gene, silencing the gene and helping to trigger or drive the runaway cell division of cancer.

"If we can profile a large number of tumors with techniques like this, we can map the epigenetic changes that are contributing to tumor growth in certain cancers," said senior author Dr. Dan Landau, an associate professor of medicine in the Division of Hematology and Medical Oncology and a member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine. "Then we can use that information to improve our understanding of cancer origins, as well as to optimize treatments for individual patients."

The challenge addressed by the new technique is similar to the one cancer researchers have faced regarding DNA mutations--how to distinguish "driver" mutations from more abundant "passenger" mutations that have no effect on cancer. Though there are now sophisticated methods for making the distinction among genetic mutations, techniques for distinguishing driver methylation changes from passenger methylation changes have not been nearly as sophisticated, said Dr. Landau, who is also a core member of the NYGC and an oncologist at NewYork-Presbyterian/Weill Cornell Medical Center.

The new algorithm developed by Dr. Landau's team is called MethSig. It uses available information, such as the background rate of methylation in a particular area of the genome, to estimate when a given methylation change is likely to be a cancer driver.

The researchers applied the algorithm to DNA methylation maps from different tumor types and found that it inferred a small number of cancer-driver events--a median of a dozen or so, in each tumor--compared to thousands of passenger methylation changes. The patterns of inferred driver methylation were consistent across patients and tumor types, as well as other statistical features suggesting the algorithm's non-incremental increase in performance compared to existing methods.

The team further validated several of the most strongly inferred DNA methylation cancer drivers by knocking out the affected gene in chronic lymphocytic leukemia (CLL) cells, and showing that the gene's absence enhanced cell growth when the cells were untreated, and also in the presence of some standard CLL treatments. Overall, the researchers concluded that their algorithm detects likely cancer-driving methylation changes much more sensitively and selectively than current methods.

In a demonstration of the algorithm's potential for improving cancer prognosis and treatment, the researchers applied MethSig to another set of CLL samples and used its inferences to predict the aggressiveness of individual patients' cancers.

"The classifier we developed using MethSig produced estimated risks for each patient, and we found that patients with higher estimated risks were more likely to have had worse outcomes," said first author Dr. Heng Pan, a senior research associate in the HRH Prince Alwaleed Bin Talal Bin Abdulaziz Al?Saud Institute for Computational Biomedicine at Weill Cornell Medicine, who performed most of the experiments in the study.

The researchers plan to continue using and improving the MethSig algorithm with more cancer datasets and more comprehensive genomic information.

"Ultimately we envision being able to map the entire landscape of cancer-driving DNA methylation changes, for different tumor types and in the contexts of different treatments, so that we can expand the scope of precision medicine beyond genetics to include also the critical dimension of epigenetic changes in cancer " Dr. Landau said.

Credit: 
Weill Cornell Medicine

Undetected early heart damage raises risk of death in hospitalized COVID-19 patients

DALLAS, May 10, 2021— Hospitalized COVID-19 patients with impaired first-phase ejection fraction were nearly 5 times more likely to die compared to patients with healthier measures of this early, often undetected sign of heart failure, according to new research published today in Hypertension, an American Heart Association journal. First-phase ejection fraction is a measure of the left ventricular ejection fraction until the time of maximal ventricular contraction.

Cardiovascular risk factors and/or disease have been recognized as COVID-19 risk factors that have a high negative impact on patient outcomes, since early in the SARS-CoV-2 pandemic. Researchers hypothesized that predisposition to heart failure would be associated with more severe cases of COVID-19 in hospitalized patients.

“Traditionally, heart function is measured by ejection fraction, or how much blood the left ventricle pumps out with each contraction of the heart,” said study author Phil Chowienczyk, M.B.B.S., B.Sc., professor of cardiovascular clinical pharmacology at St. Thomas' Hospital, in London. “First-phase ejection fraction is a new measure of the heart’s function that seems to be much more sensitive of early, undetected damage to the heart than traditional ejection fraction measures.”

To determine if first-phase ejection fraction predicted adverse patient outcomes, researchers analyzed mortality rates for 129 hospitalized COVID-19 patients in Wuhan, China, and 251 hospitalized COVID-19 patients in South London, treated between February and May 2020, were analyzed. All patients had echocardiography upon hospital admission, and the average patient age was 58 years. Researchers compared echocardiography results of COVID-19 patients to adult patients with otherwise similar health profiles who had an echocardiography test before the pandemic.

First-phase ejection fraction was measured with conventional echocardiography imaging conducted at hospitalized patients’ bedsides. Researchers note that there is not a universally established ‘normal’ value for first-phase ejection fraction.  Based on previous research, they estimated that the normal first-phase ejection fraction value should be above 25%. When first-phase ejection fraction was less than 25%, researchers referred to it as ‘impaired,’ suggesting relatively subtle signs of heart damage.

The authors found that COVID-19 patients with a first-phase ejection fraction of less than 25% had a nearly five-fold higher risk of death than those with an ejection fraction of 25% or higher. They also found that a similar proportion of people with similar risk factors who did not have COVID-19 had low values of first-phase ejection fraction. This suggests that the damage to the heart may be due to chronic pre-existing conditions and was not the result of COVID-19 infection.

“Patients with impaired first-phase ejection fraction could be prioritized for vaccines and, if they get COVID-19, monitored closely at the early stages of their illness to prevent deterioration,” Chowienczyk said. “The findings suggest that if we can prevent the very early chronic damage to the heart detected using first-phase ejection fraction imaging, then people will be much more likely to survive respiratory infections like COVID-19. Healthy lifestyle choices, better treatments and adherence to treatments for high blood pressure and high cholesterol are also important.”

Researchers note that this is a relatively small study, so the findings need to be confirmed in larger studies with more patients. If the results are confirmed, first-phase ejection fraction could be a new way to identify patients at elevated risk of dying from COVID-19 and possibly other types of pneumonia.

Credit: 
American Heart Association

Small study shows heart damage after COVID-19 uncommon in college athletes

DALLAS, May 10, 2021 — In a small study, researchers found college athletes who contracted COVID-19 rarely had cardiac complications. Most had mild COVID symptoms that did not require treatment, and in a small percentage of those with abnormal cardiac testing, there was no evidence of heart damage on special imaging tests. All athletes returned to sports without any health concerns, according to new research published today in the American Heart Association’s flagship journal Circulation.

In spring 2020, concerns about heart damage, especially inflammation, among athletes with COVID-19 led to recommendations for cardiac screening based on symptom severity before resuming training and competition. The preferred diagnostic test for heart inflammation is an MRI of the heart, or cardiac magnetic resonance imaging. The American College of Cardiology’s Sports & Exercise Cardiology Council’s standard recommendations, issued in May 2020, do not advise cardiac MRI as an initial screening test based on COVID symptoms alone, so researchers investigated if symptom severity was associated with heart inflammation or poor recovery after COVID-19.

“Our study results support an approach to cardiac screening guided by patient symptoms and severity of COVID illness in line with current recommendations from sports-cardiology groups before resuming exercise or sports,” said senior study author Ranjit R. Philip, M.D., pediatric cardiologist at Le Bonheur Children’s Hospital and assistant professor in pediatric cardiology at the University of Tennessee Health Science Center in Memphis.

From July 9, 2020 to October 21, 2020, researchers at the University of Tennessee Health Sciences Center reviewed health records to identify 137 college athletes (average age of 20, 68% male) who were referred for cardiac screening to return to play after testing positive for COVID-19. On average, the athletes were evaluated 16 days after testing positive for the COVID-19 virus. Nearly half of the participants were African American students, nearly half were white students, and 7% were Hispanic students. Of the 11 sports represented at three universities, more than a third of the athletes were football players, followed by dance, basketball, baseball, softball, tennis, soccer, cheer, track, volleyball and golf athletes.

Most (82%) of the athletes had COVID-19 symptoms; the symptoms were mild for the majority (68%); and none required treatment or hospitalization. The most frequent symptoms were the loss of smell/taste (58%), fever (less than 2 days, 42%), headache (41%) and fatigue (40%). Less frequently reported symptoms were shortness of breath (12%) and chest pain/tightness (11%). African American and Hispanic athletes were more often symptomatic compared to white athletes (86% and 100% vs. 75%, respectively). No differences in symptoms or severity were found based on gender or sport.

All of the athletes underwent initial heart imaging tests, including ultrasound of the heart and electrocardiogram to screen for possible heart damage, and received a blood test (troponin level). Troponin is a protein that is released in the blood and found in the muscles of the heart when there is heart damage. Only participants who had abnormal test results received a cardiac MRI.

Researchers found:

Less than 4% (5) of the 137 athletes showed heart abnormalities on initial screening tests.
Further screening via cardiac MRI of the 5 athletes identified found no heart damage or inflammation.
After COVID-19 recovery, all athletes were able to resume their full training and competition regimens without any complications.

“We were encouraged to find so few abnormal tests in these athletes as well as negative cardiac MRIs in those who did have an abnormal test during the initial screening, and no athlete had any problems after returning to exercise and sport,” said Benjamin S. Hendrickson, M.D., co-author and pediatric and congenital cardiologist with Le Bonheur Children’s Hospital and assistant professor of pediatrics (cardiology) at the University of Tennessee Health Science Center.

“Our findings may offer reassurance to high school athletes, coaches and parents where resources for testing can be limited,” Philip added.

Limitations that could have affected the study’s results include the lack of a control group without COVID-19 and the use of a regular as opposed to the high-sensitivity troponin test.

The new study by Dr. Philip and colleagues also confirms recent research published April 17 in Circulation, that found no adverse cardiac events related to SARS-CoV-2 infections observed among more than 3,000 collegiate athletes during short-term clinical surveillance. Findings also suggested a safe return-to-play without cardiac testing for asymptomatic or mildly symptomatic athletes.

Other efforts to track how COVID-19 impacts college athletes includes an initiative from the American Heart Association and the American Medical Society for Sports Medicine (AMSSM) to accelerate a critical new research initiative studying cardiac conditions in athletes. The collaborative data registry, started in January 2021, aids research on COVID-19 and, long-term, it will develop a deep knowledge base on cardiac disease in athletes beyond the pandemic.

Credit: 
American Heart Association

Could wider use of gene reserves protect rare species?

image: Mountain Ringlet butterfly

Image: 
Melissa Minter, University of York

UK landowners and conservationists welcome wider-spread use of Gene Conservation Units (GCUs) to help protect some of the rarest plants and insects, research at the University of York has shown.

In particular the Great Yellow Bumblebee and the Mountain Ringlet Butterfly, which are at risk of further population decline, would benefit from Gene Conservation Units, currently only employed for forest trees and agricultural species or their relatives.

Genetic diversity in these species is essential if they are to adapt to new, and often challenging, environmental conditions. Gene Conservation Units are areas of land managed to allow the recovery of species, and maintain evolutionary processes to enable them to adapt to environmental change.

For tree species, this means promoting natural regeneration, and for others, it means ensuring that the breeding population is large enough, and diverse enough, to be able to weather the changes ahead. Habitat management may achieve this, as well as population monitoring to ensure a large population is sustained.

PhD researcher Melissa Minter, from the Department of Biology at the University of York, said: "In investigating whether landowners would be interested in adopting a system of GCUs, we looked at the potential benefits these might bring to some species of insects and plants.

"We have shown that the genetic diversity of cold-adapted butterflies, such as the Mountain Ringlet, is at high risk of local extinction in a warming climate and so conservation measures are needed to secure the survival of threatened populations.

"Similarly, the Great Yellow Bumblebee now only survives on a few Scottish islands and the northern tip of mainland Scotland, which means that any changes in our climate could negatively impact their already depleted population.

"We wanted to know if GCUs could provide a solution to some of these issues and whether this concept could be applied to other species, in addition to forest trees."

The research involved a survey questionnaire of conservationists and land managers to gather opinions on adopting a system of GCUs to protect biodiversity. The survey results showed that if GCUs could be co-developed with stakeholders, then a GCU approach is more likely to appeal to land managers.

Specifically, landowners would benefit from setting-up GCUs on their land as recognition of best practice in conserving species and genetic diversity, and supporting evolutionary processes to help species cope with environmental change. A working group has now been established to look at how the first non-tree GCU could be developed.

NatureScot's Beinn Eighe National Nature Reserve (NNR) was registered as the UK's first GCU in recognition of its ancient Caledonian pine forest in 2019. Since then, the Woodland Trust have registered several more sites across the UK, including three more in Scotland, for six tree species.

NatureScot Woodlands Officer and research co-author Jeanette Hall said: "We have seen first-hand how successful the Gene Conservation Unit approach can be with the registration of our Beinn Eighe NNR and this research shows the exciting potential for working with land managers to expand this work to cover many more plant, animals and wild species.

"Conserving genetic diversity remains an international biodiversity priority so in what will be an important year for nature and tackling climate change, it's great to see partnership working across the UK leading the way in this field."

Genetic diversity was the focus of one of the international Aichi 2020 biodiversity targets. This year new global targets to improve nature will be agreed at a Conference of the Parties in Kunming, China (COP15), followed by the COP26 on climate change in Glasgow.

Credit: 
University of York

Serotonin transporters increase when depression fades, study shows

image: Jonas Svensson, postdoc researcher
Center for Psychiatry Research
Department of Clinical Neuroscience, Karolinska Institutet

Image: 
Lou Almskog

Low levels of serotonin in the brain are seen as a possible cause of depression and many antidepressants act by blocking a protein that transports serotonin away from the nerve cells. A brain imaging study at Karolinska Institutet now shows that the average level of the serotonin transporter increased in a group of 17 individuals who recovered from depression after cognitive behavioural therapy. The results are published in the journal Translational Psychiatry.

"Our results suggest that changes to the serotonin system are part of the biology of depression and that this change is related to the episode rather than a static feature - a state rather than a trait," says the study's last author Johan Lundberg, researcher at the Department of Clinical Neuroscience, Karolinska Institutet. "The finding raises many questions about the function of the serotonin system in depression and opens up for lines of research that could challenge the prevailing concept of serotonin and depression."

Serotonin is a neurotransmitter that affects, amongst other things, mood and emotion. Its transporter protein, 5-HTT, is considered to play a critical part in depression, as it pumps serotonin away from the cerebral neuron synapses, thus regulating the amount of active serotonin the brain.

Many modern antidepressant drugs inhibit this transporter, which increases the concentration of serotonin in the synapses. However, the effect of these drugs can be delayed by several weeks and in certain cases they have no effect at all, so the need for new or improved drug therapies is pressing. To achieve this, more knowledge is needed about the biological causes of the disease.

Earlier studies have shown that depressed individuals have lower levels of 5-HTT in the brain than healthy individuals. This finding is somewhat surprising given the dominant theory of serotonin function in depression, "the serotonin hypothesis." This theory dictates that low levels of synaptic serotonin causes depressive symptoms, and since the function of 5-HTT is to reduce the concentration of serotonin, high levels of the protein could be expected in depressed individuals. To better understand these findings a longitudinal or post-treatment study design can be used to answer the question of whether 5-HTT is temporarily or chronically low in people with depression.

In this study, the researchers sought to investigate how the serotonin transporter changes when a depressed person is successfully treated. To do this, they measured levels of 5-HTT in 17 individuals with depression before and after a course of internet-based cognitive behavioural therapy. The measurements were achieved with positron emission tomography (PET), a brain imaging technique in which scientists can gauge levels of different substances in the brain using radioactive tracers.

The researchers found that levels of 5-HTT were on average 10 percent higher after three months' treatment, when 13 of the 17 patients reported a significant improvement in their symptoms. Prior to treatment, the individuals with depression had roughly the same average level of 5-HTT as a control group of 17 healthy individuals.

"Instead of lower levels of serotonin transporter when depression had been treated, we found the opposite - more transporter after improved symptoms," says Jonas Svensson, postdoc researcher in Dr Lundberg's group. "One possible interpretation is that the serotonin system doesn't cause depression but is part of the brain's defence mechanism for protecting itself against depression. One might hypothesize, for example, that the level of 5-HTT drops when an individual is subjected to stress, such as during a depressive state, and that the level rises or normalises when this stress goes away. It's important to point out, however, that even if these ideas are raised by our study, its design doesn't allow us to draw any conclusions about why levels of 5-HTT change."

The study had some limitations, such as that it only included 17 individuals with depression, which is a heterogeneous state, and that the control group was examined only once.
The researchers are now designing new studies to test whether the dynamic function of the serotonin system can be part of a stress-defence system.

Credit: 
Karolinska Institutet

Parallel universes cross in Flatland

image: 2D sheets intersect and twist on top of each other, modifying the energy landscape of the materials

Image: 
Ventsislav Valev

In 1884, Edwin Abbott wrote the novel Flatland: A Romance in Many Dimensions as a satire of Victorian hierarchy. He imagined a world that existed only in two dimensions, where the beings are 2D geometric figures. The physics of such a world is somewhat akin to that of modern 2D materials, such as graphene and transition metal dichalcogenides, which include tungsten disulfide (WS2), tungsten diselenide (WSe2), molybdenum disulfide (MoS2) and molybdenum diselenide (MoSe2).

Modern 2D materials consist of single-atom layers, where electrons can move in two dimensions but their motion in the third dimension is restricted. Due to this 'squeeze', 2D materials have enhanced optical and electronic properties that show great promise as next-generation, ultrathin devices in the fields of energy, communications, imaging and quantum computing, among others.

Typically, for all these applications, the 2D materials are envisioned in flat-lying arrangements. Unfortunately, however, the strength of these materials is also their greatest weakness - they are extremely thin. This means that when they are illuminated, light can interact with them only over a tiny thickness, which limits their usefulness. To overcome this shortcoming, researchers are starting to look for new ways to fold the 2D materials into complex 3D shapes.

In our 3D universe, 2D materials can be arranged on top of each other. To extend the Flatland metaphor, such an arrangement would quite literally represent parallel worlds inhabited by people who are destined to never meet.

Now, scientists from the Department of Physics at the University of Bath in the UK have found a way to arrange 2D sheets of WS2 (previously created in their lab) into a 3D configuration, resulting in an energy landscape that is strongly modified when compared to that of the flat-laying WS2 sheets. This particular 3D arrangement is known as a 'nanomesh': a webbed network of densely-packed, randomly distributed stacks, containing twisted and/or fused WS2 sheets.

Modifications of this kind in Flatland would allow people to step into each other's worlds. "We didn't set out to distress the inhabitants of Flatland," said Professor Ventsislav Valev who led the research, "But because of the many defects that we nanoengineered in the 2D materials, these hypothetical inhabitants would find their world quite strange indeed.

"First, our WS2 sheets have finite dimensions with irregular edges, so their world would have a strangely shaped end. Also, some of the sulphur atoms have been replaced by oxygen, which would feel just wrong to any inhabitant. Most importantly, our sheets intersect and fuse together, and even twist on top of each other, which modifies the energy landscape of the materials. For the Flatlanders, such an effect would look like the laws of the universe had suddenly changed across their entire landscape."

Dr Adelina Ilie, who developed the new material together with her former PhD student and post-doc Zichen Liu, said: "The modified energy landscape is a key point for our study. It is proof that assembling 2D materials into a 3D arrangement does not just result in 'thicker' 2D materials - it produces entirely new materials. Our nanomesh is technologically simple to produce, and it offers tunable material properties to meet the demands of future applications."

Professor Valev added: "The nanomesh has very strong nonlinear optical properties - it efficiently converts one laser colour into another over a broad palette of colours. Our next goal is to use it on Si waveguides for developing quantum optical communications."

PhD student Alexander Murphy, also involved in the research, said: "In order to reveal the modified energy landscape, we devised new characterisation methods and I look forward to applying these to other materials. Who knows what else we could discover?"

Credit: 
University of Bath

Study indicates São Tomé island has two species of caecilians found nowhere else on Earth

image: The caecilians found on the southern part of the island are typically yellow with brown splotches.

Image: 
© Andrew Stanbridge

SAN FRANCISCO, CA (May 10, 2021) -- The Gulf of Guinea islands harbor an abundance of species found nowhere else on Earth. But for over 100 years, scientists have wondered whether or not a population of limbless, burrowing amphibians--known as caecilians--found on one of the islands is a single or multiple species. Now, a team of researchers from the California Academy of Sciences and the Smithsonian National Museum of Natural History has contributed the strongest evidence to date that there is not one, but two different species of caecilians on São Tomé island. Their findings, published today in Molecular Ecology, also suggest that volcanic activity may have led to the divergence of the species.

"To judge whether one species is in fact composed of multiple lineages, scientists have to build a case," says senior author and Academy Curator of Herpetology Rayna Bell. "By conducting a population level genomic study of these amphibians across the entire island, we are adding a crucial line of evidence that the São Tomé caecilian is actually two unique species."

Initially described by Portuguese scientists during colonial times, the São Tomé caecilians were later split into two distinct species based on their variation in color and location on the island--solid lemon yellow in the north and yellow with brown splotches to the south. Since then, subsequent research has bounced back and forth, grouping the species together then separating them out again, based on the best available evidence.

Then, in 2014, a study by former Academy Curator of Herpetology Robert Drewes and graduate student Ricka Stoelting using mitochondrial DNA indicated that not only were there likely two unique species, but they might be interbreeding. Bell and her colleagues build upon those previous findings by sampling 85 caecilians from 21 locations across the island for genome-wide genetic markers that more accurately confirm the presence--and interbreeding--of the two species.

"That earlier study was the first clue towards unraveling the mystery of the São Tomé caecilians," Bell says. "Our study provides further proof of the presence of two separate, interbreeding species and quantifies how much overlap--or hybridization--is occurring between them."

Once the research team confirmed the existence of two different but interbreeding species, they started to work backward through time to try to determine how the species diverged.

"It's pretty remarkable that there are two unique species on such a small island," says Academy collections manager and study co-author Lauren Scheinberg. "It really makes you wonder how natural selection is acting to drive speciation."

Through their analysis, the researchers found that the two species diverged around 300,000 years ago, a time period that coincides with a burst of volcanic activity on the island. The researchers suggest that lava flows during this period may have led to the speciation of the caecilians by dividing the island into a patchwork of smaller habitats with unique environmental pressures. As the lava flows eroded, resulting in suitable habitat for caecilians, the two species came back into contact and started to hybridize, obscuring the evidence of their separation.

"These findings are an important reminder that islands are not static," Bell says. "Even though they can be small and isolated, they are dynamic systems that are actively accumulating new species. It's also an important consideration for the conservation of São Tomé caecilians to know that we have two, genetically and morphologically unique species."

Though the picture of their past is becoming clearer, there is still much to learn about these enigmatic amphibians. For example, while most caecilians spend a majority of their time underground, the São Tomé caecilians can be readily found on the forest floor, raising questions about how the bright yellow amphibians avoid predation.

While one century-long mystery is nearing a resolution, it seems more are taking its place. But Bell is looking forward to the challenge. "These are perhaps the most well-studied caecilians on Earth because of their accessibility and how long ago they were described to science. Yet there is still so much to learn about them, from their mating behavior to how they deter predators," Bell says. "For a biologist, what could be more exciting than that?"

Credit: 
California Academy of Sciences

Male infertility scoring using AI-assisted image classification requiring no programming

image: All images are X400 magnification. Algorithm performance using Google Cloud AutoML Vision, Average precision recall curve for image dataset, magnification X400.

Image: 
Hideyuki Kobayashi

Infertility affects females and males equally. In male infertility, azoospermia (a medical condition with no sperm in semen) is a major problem that prevents a couple from having a child. For the treatment of patients with azoospermia, testicular sperm extraction (TESE) is required to obtain mature sperms. When examined, histological specimens are typically given a score, called the Johnsen score, on a scale of 1 to 10, based on the histopathological features of the testis.

"The Johnsen score has been widely used in urology since it was first reported 50 years ago. However, histopathological evaluation of the testis is not an easy task and takes much time due to the complexity of testicular tissue arising from the multiple, highly specialized steps in spermatogenesis. Our goal was to simplify this time consuming step of diagnosis by taking advantage of AI technology. To do this, we chose Google's automated machine learning (AutoML) Vision, which requires no programming, to create an AI model for individual patient data sets. With AutoML Vision, clinicians with no programming skills can use deep learning in building their own models without help from data scientists," said Dr. Hideyuki Kobayashi, Associate Professor of Urology department at Toho University School of Medicine (Fig. 1).

"The model we created can classify histological images of the testis without help from pathologists. I hope that our approach will enable clinicians in any field of medicine to build AI-based models which can be used in their daily clinical practice", he said.

To simplify the use of Johnsen scores in clinical practice, Dr. Kobayashi defined four labels: Johnsen score 1-3, 4-5, 6-7, and 8-10 (Fig. 2). He and his co-researchers obtained a dataset of 7155 images at magnification X400. All images were uploaded to the Google Cloud AutoML Vision platform. For the X400 magnification image dataset, the average precision (positive predictive value) of the algorithm was 82.6%, precision was 80.31%, and recall was 60.96% (Fig. 3).

AI has become popular and is being applied in all fields of medicine. However, the use of AI by clinicians in hospitals is still hampered by the need of help from data scientists in the proper use of AI. "The cloud-based machine learning framework we used is for everyone. It can become such a powerful tool in medicine that, in the near future, doctors in hospitals will be using AI-based medical image classifiers with ease, in the same way they use Microsoft PowerPoint or Excel now", Dr. Kobayashi said. He added, "The most difficult part was taking images of testis pathology and it was very time consuming. Two colleagues worked very hard to obtain all the images used in the study. I really appreciate their dedicated efforts."

Dr. Kobayashi's group has described the development of an AI-based algorithm for evaluating Johnsen scores combining original images (X400), which achieved high accuracy. This is the first report of an algorithm that can be used for predicting Johnsen scores without having to rely on pathologists and data science experts.

Credit: 
Toho University

In soil, high microbial fluctuation leads to more carbon emissions

image: San Diego State University ecologists found that seasonal fluctuations in temperature lead to a corresponding fluctuation in soil microbial populations, and increased carbon emissions.

Image: 
SDSU

As humans, the weather where we live influences our energy consumption. In climates where weather shifts from hot summers to very cold winters, humans consume more energy since the body has to work harder to maintain temperature.

In much the same way, weather influences microbes such as bacteria and fungi in the soil. Seasonal fluctuations in soil temperature and moisture impact microbial activities that in turn impact soil carbon emissions and nutrient cycles.

Microbes consume carbon as the source of energy. As microbes increase in quantity and activities, they consume more carbon which results in more carbon emissions and vice versa.

In a modeling study published in Global Change Biology on May 10, San Diego State University ecologists found that this microbial seasonality has a significant impact on global carbon emissions and acts as a fundamental mechanism that regulates terrestrial-climate interactions and below ground soil biogeochemistry.

"When microbial colonies in the soil are in a productive phase, increasing in numbers and size, they will need more carbon to fuel their growth," said Xiaofeng Xu, global change ecologist and lead author. "When we manipulated the quantities and activities of soil microbes in simulations and observed the reciprocal changes in soil carbon, we found that when seasonal variation was removed, microbial respiratory rates went down."

By keeping the microbial population at a constant average level, carbon emissions can be reduced.

Stewards of the land could look at reducing fluctuation in soil microbial population by reducing tillage and other management practices in order to reduce soil carbon emissions, the researchers said. It can also help agricultural scientists and growers to sustain soil fertility

Using a microbial modeling framework -- CLM-Microbe (Community Land Model) -- developed in the Ecological Modeling and Integration Lab at SDSU where he studies how climate change impacts the terrestrial carbon cycle -- Xu and colleagues deployed the model on an SDSU supercomputer to reach this conclusion.

"We know soil microbes drive carbon flux -- the amount of carbon exchanged between land, ocean and atmosphere -- by producing enzymes that impact carbon flux," Xu said. "Soil carbon completes its cycle with the help of these microbes which have a hand in ultimate control of the carbon."

Different soil microbial groups play distinct roles in the carbon cycle.

"The model's ability to simulate bacterial and fungal dynamics improves our understanding of the soil microbial community's impact on the carbon cycle," said Liyuan He, first author and doctoral student at SDSU.

The finding advances soil microbial ecology and shows the ecological significance of microbial seasonality and our understanding of soil carbon storage under changing climate conditions.

The authors modeled and validated carbon fluxes observed at an individual plot scale in nine natural biomes including tropical/subtropical forest, temperate coniferous forest, temperate broadleaf forest, boreal forest, shrubland, grassland, desert, tundra, and wetland.

"This study demonstrates the need to incorporate microbial seasonality in earth system models so we can better predict climate-carbon interactions," said Chun-Ta Lai, co-author and an ecosystem ecologist at SDSU.

Next, the researchers will explore microbial seasonality and its impact on global carbon balance, given the dynamics of land use change around the world.

Credit: 
San Diego State University

Molecular tweezers that attack antibiotic resistant bacteria developed by Ben-Gurion U.

image: Top: Prof. Raz Jelinek (left) and his student Ravit Malishev

Image: 
Dani Machlis/BGU

BEER-SHEVA, Israel May 10, 2021 - Researchers from Ben-Gurion University (BGU), together with American and German colleagues, have developed new "molecular tweezers" to combat antibiotic-resistant bacteria. Their recently announced findings were published in Cell Chemical Biology.

For years, medical professionals have struggled with bacterial infections becoming increasingly resistant to antibiotics. These molecular tweezers may be the key to battling one of greatest public health issues of the 21st century.

"Our discovery prevents infection without building up antibiotic resistance, and it might even be preferable to develop treatments based on molecular tweezers rather than antibiotics," said BGU Department of Chemistry Prof. Raz Jelinek.

The research team, led by Prof. Jelinek and his Ph.D. student Ravit Malishev, tested their molecular tweezers on the Staphylococcus aureus (Staph) bacteria. In the U.S. staph infections have an estimated mortality rate of over 25%, and 40% for drug-resistant strains.

The tweezers target biofilm, a thin layer of fibers that protects the bacteria. By gripping the fibers and destroying the protective layer, the tweezers impair the bacteria without directly attacking it, which prevents resistance from occurring.

Prof. Jelinek, who is also BGUs vice president of Research & Development and a member of the Ilse Katz Institute for Nanoscale Science and Technology explained, "The tweezers are just like your home tweezers but a million times smaller, and instead of plucking hairs they attack fibers of the bacteria's biofilm." By doing that they break the biofilm, making it more vulnerable to human immune defenses and external substances that are used against bacteria like antibiotics."

“The success of the study indicates an innovative direction of antibiotic treatments against pathogenic bacteria. We found that binding the tweezers to the biofilm disrupts its protective capabilities. Consequently, the bacterial pathogens become, less virulent to the human body, and, more vulnerable to elimination by the immune system. This breakthrough may open up new ways to fight antibiotic-resistant bacteria.” Prof. Jelinek hopes that following further testing, a pill containing millions of “swallowable tweezers” could identify biofilms in the body and break them apart.

Credit: 
American Associates, Ben-Gurion University of the Negev

Wastewater treatment system recovers electricity, filters water

Whether wastewater is full of "waste" is a matter of perspective.

"Why is it waste?" asked Zhen (Jason) He, professor in the Department of Energy, Environmental & Chemical Engineering in the McKelvey School of Engineering at Washington University in St. Louis.

"It's organic materials," He said, and those can provide energy in a number of ways. Then there's the other valuable resource in wastewater.

Water.

He's lab has developed one system that recovers both, filtering wastewater while creating electricity. Results from bench-scale trials were published May 6 and featured as a front cover article in the journal Environmental Science: Water Research & Technology.

The waste materials in wastewater are full of organic materials which, to bacteria, are food.

"Bacteria love them and can convert them into things we can use," He said. "Biogas is the primary source of energy we can recover from wastewater; the other is bioelectricity."

There already exist ways to capitalize on bacteria to produce energy from wastewater, but such methods often do so at the expense of the water, which could be filtered and otherwise be used -- if not for drinking -- for "grey water" purposes such as irrigation and toilet flushing.

He's lab took the two processes -- filtration and energy production -- and combined them, integrating the filtration system into the anode electrode of a microbial electrochemical system.

The system is set up like a typical microbial fuel cell, a bacterial battery that uses electrochemically active bacteria as a catalyst where a traditional fuel cell would use platinum. In this type of system, the bacteria are attached to the electrode. When wastewater is pumped into the anode, the bacteria "eat" the organic materials and release electrons, creating electricity.

To filter that same water, however, requires a different system.

He's lab combined the systems, developing a permeable anode that acts as a filter.

The anode is a dynamic membrane, made of conductive, carbon cloth. Together, the bacteria and membrane filter out 80% to 90% of organic materials -- that leaves water clean enough to be released into nature or further treated for non-potable water uses.

He used a mixed culture of bacteria, but they had to share one feature -- the bacteria had to be able to survive in a zero-oxygen environment.

"If there was oxygen, bacteria would just dump electrons to the oxygen not the electrode," He said. "If you cannot respire with the electrode, you'll perish."

To find the correct bacteria, He mostly defers to nature.

"It's not 100 percent natural, but we select those that can survive in this condition," He said. "It's more like 'engineered selection,'" the bacteria that did survive and respire with the electrode were selected for the system.

The amount of electricity created is not enough to, say, power a city, but it is in theory enough to help to offset the substantial amount of energy used in a typical U.S. water treatment plant.

"In the U.S., about 3% to 5% of electricity is used for water and wastewater activity," He said. Considering the usage by a local municipal plant, He believes his system can reduce energy consumption significantly.

"Typically, the process consumes about 0.5 KWH of electricity per cubic meter," He said. Based on bench scale experiments, "We can reduce it by half, or more of that."

But the primary goal of He's system isn't electricity production, it's wastewater treatment and nutrient recovery.

"Bacteria can convert those organic materials into things we can use," He said. "We can also recover nutrients like nitrogen or phosphorus for fertilizer. We can use it to feed plants. It's only when we don't use it, then it becomes waste.

"Wastewater is a resource in the wrong location."

Credit: 
Washington University in St. Louis

Researchers achieve 50dB noiseless at all optical isolation

image: Diagram of experimental device

Image: 
HU Xinxin et al.

Chinese researchers achieved 51.5dB nonreciprocal isolation in the atomic ensemble, which is the highest isolation ratio in the non-magnetic nonreciprocal field. They discussed the quantum noise problem in nonreciprocal devices for the first time.

The result was published on Nature Communications on April 22, 2021.

Nonreciprocity is an important basic concept in the optical field. The isolators and circulators derived from it are all indispensable components in the optical path. Faraday isolator based on circular birefringence of magneto-optical effect is widely used because of its easy construction, high isolation and low loss.

However, in the integrated optical path, the traditional faraday isolator is subject to various limitations. On one hand, it is difficult to prepare high-performance magneto-optical media on chip. On the other hand, the required strong magnetic field will interfere with the surrounding devices. Realizing the integrated non-magnetic nonreciprocal has attracted much attention in recent years. The research team led by Academician GUO Guangcan from University of Science and Technology of China (USTC) of CAS has investigated on nonreciprocal photonic devices for several years.

In this work, Prof. ZOU Changling from the research team, cooperating with researchers from Shanxi University, has achieved an isolation ratio of 30dB first. They took use of circularly polarized pump light to polarize the atoms in the gas chamber to a specific magnetic spin state, achieving different absorptions and dispersions for different polarized lights. Based on this, they further added a traveling wave cavity which greatly enhanced the interaction between light and atoms. The isolation ratio was finally increased to 51.5dB and the nonreciprocal medium was prepared based on atomic ensemble.

The system has good robustness and is insensitive to the interference of external weak magnetic field. The fluctuation of pump frequency and power and considered has practical application value.

In addition, the team has proved that non-reciprocal devices don't produce noisy photons in the non-reciprocal field with a confidence level of 99.7%.

This achievement has opened up a new direction in the field of non-reciprocity and is of great significance in practical application. The reviewers praised highly on this work as "The results are very impressive and seem encouraging toward realizing non reciprocal devices".

Credit: 
University of Science and Technology of China