Earth

Spearheaded by earth scientists of the University of Cologne, an international team of geologists has found evidence that a large proportion of the elements that are important for the formation of oceans and life, such as water, carbon and nitrogen, were delivered to Earth very late in its history. Previously, many scientists believed that these elements were already present when the Earth began to form. However, geological investigations have now shown that most of the water in fact was only delivered to Earth when its formation was almost complete.

The new findings, which are a result of collaboration among scientists from Germany, Denmark, Wales, Australia and Japan, will be published in Nature under the title 'Ruthenium isotope vestige of Earth's pre-late veneer mantle preserved in Archean rocks' on 11 March 2020.

It is a generally accepted fact that volatile elements such as water originate from asteroids, the 'planetary building blocks' that formed in the outer solar system. However, there is ongoing discussion among experts as to when precisely they came to Earth. 'We have now been able to narrow down the timeframe much more precisely', said first author Dr. Mario Fischer-Gödde from the Institute of Geology and Mineralogy at the University of Cologne. 'To do so, we compared the composition of the oldest, approximately 3.8 billion-year-old mantle rocks from the Archean Eon with the composition of the asteroids from which they may have formed, and with the present-day composition of the Earth's mantle.'

To constrain the delivery of the so-called 'volatile' elements to Earth, the researchers measured the isotope abundances of a very rare platinum metal called ruthenium, which was already present in Earth's mantle by Archean time. Like a genetic fingerprint, this rare platinum metal is an indicator for the late growth phase of the Earth. 'Platinum group metals like ruthenium have an extremely high tendency to combine with iron. Therefore, when the Earth formed all ruthenium must have been completely sequestered into the Earth's metallic core', said Fischer-Gödde.

Professor Dr. Carsten Münker added: 'If we still find traces of the rare platinum metals in the Earth's mantle, we can assume that they were only added after the formation of the core was completed. They were certainly added during later collisions of the Earth with asteroids or smaller protoplanets, so called planetesimals.'

Scientists refer to these very late building blocks of the Earth, which were delivered by these collisions, as the 'late veneer'. If ruthenium was added during this stage, it is distributed and well mixed into Earth's mantle by now. The old Archean mantle relics in Greenland, on the other hand, have still preserved Earth's pristine composition.

'The up to 3.8 billion-year-old rocks from Greenland are the oldest preserved mantle rocks. They allow us a glimpse into the early history of the Earth as if through a window', Fischer-Gödde said. Interestingly, Earth's oldest mantle is openly accessible in surface outcrops in southwest Greenland, allowing the geologists to easily collect rock samples.

The pristine ruthenium preserved in the old mantle rocks most likely originates from the inner part of the solar system, the two Cologne-based geologists report. It is presumably the same material that - for the most part - also formed Mercury and Venus. The reference values for the asteroidal ruthenium were previously obtained from meteorites found on Earth.

'Our findings suggest that water and other volatile elements such as carbon and nitrogen did indeed arrive on Earth very late, during the "late veneer" phase', Fischer-Gödde concluded. This result is surprising because the scientific community had previously assumed that water-bearing planetary building blocks were already delivered to Earth during the early stages of its formation.

The scientists are planning further field trips to India and Greenland to investigate more rock samples. Their work is being supported by the German Research Foundation's Priority Programme 1833 'Building a Habitable Earth', which is coordinated in Cologne, as well as Professor Münker's ERC grant 'Infant Earth' by the European Union.

Alzheimer's disease, the main cause of dementia in the elderly, is a neurodegenerative disease caused by the irreversible destruction of neuronal networks in certain brain structures affecting memory. While some risk factors are known, such as hypertension or diabetes, the potential role of non-biological factors begins to be discovered. Scientists from the University of Geneva (UNIGE) and the University Hospitals of Geneva (HUG), Switzerland, demonstrated, through brain imaging and psycho-cognitive evaluations conducted over several years on a community-based cohort of elderly people, that certain personality traits protect brain structures against neuro-degeneration. Among them, people who are less agreeable but with a natural curiosity and little conformism show better preservation of the brain regions that tend to lose volume, both in normal aging and in Alzheimer's disease. These results, to be discovered in the journal Neurobiology of Aging, highlight the importance of taking personality into account in neuropsychiatric disorders and pave the way for more precise prevention strategies against neurodegeneration.

For several decades, Alzheimer's disease specialists have been trying unsuccessfully to develop therapeutic vaccines that could repair brain damage caused by the accumulation of amyloid - a small protein that, in large numbers, is harmful to the central nervous system - and the resulting destruction of neurons. Today, a new avenue of study is beginning to be explored: would it be possible to limit the damage by acting on non-biological factors? Are some individuals more protected than others because of their personality or way of life? "Between the destruction of the first neurons and the appearance of the first symptoms, 10 to 12 years elapse", says Professor Panteleimon Giannakopoulos, a psychiatrist at the UNIGE Faculty of Medicine and Head of the Division of Institutional Measures at the HUG, who has directed this work. "For a long time, the brain is able to compensate by activating alternative networks; when the first clinical signs appear, however, it is unfortunately often too late. The identification of early biomarkers is therefore essential for an effective disease management."

A follow-up of several years

To this end, the specialists recruited a large cohort of people over 65 years of age in a longitudinal study. Various methodologies were used, including functional and structural brain imaging, to assess amyloid accumulation and brain volume. Atrophy of certain brain regions is indeed one of the major features preceding memory loss and Alzheimer's disease. "In order to get as complete a picture as possible, we decided to look at the non-lesional determinants of brain damage, i.e. the environment, lifestyle and psychology," says Professor Giannakopoulos. "So we conducted cognitive and personality assessments." To ensure the statistical validity of their work, they used a restrictive model to control for possible demographic, socio-economic or psychiatric bias. In the end, 65 people - men and women - were examined several times over a five-year period.

A plea for selfishness?

The results are surprising: people who are unpleasant, who are not afraid of conflicts and who show a certain anti-conformity have better protected brains. In addition, this protection takes place precisely in the memory circuits that are damaged by Alzheimer's disease. "A high level of agreeableness characterizes highly adaptive personalities, who want above all to be in line with the wishes of others, to avoid conflict, and to seek cooperation", notes the specialist. "This differs from extraversion. You can be very extroverted and not very pleasant, as are narcissistic personalities, for example. The important determinant is the relationship to the other: do we adapt to others at our own expenses?"

Open-mindedness is also important

Another personality trait seems to have a protective effect, but in a less clear-cut way: openness to experience. "This is less surprising, as we already knew that the desire to learn and interest in the world around us protects against cerebral ageing." But why? What are the biological mechanisms at work? For the moment, this remains a mystery, which the Geneva team would like to decipher, as does the stability of their observations. Indeed, does the phenomenon last for decades? And how can these results be used for prevention purposes? "If it seems difficult to profoundly change one's personality, especially at an advanced age, taking this into account in a personalized medicine perspective is essential in order to weigh up all the protective and risk factors of Alzheimer's disease. It is an important part of a complex puzzle," the authors conclude.

Launching a two-pronged attack on cancer's ability to safeguard its DNA could offer an effective new way of treating the disease, a new study reports.

Scientists have found that small molecules that stop cancer cells from copying their DNA can boost the effectiveness of drugs called CHK1 inhibitors, which are designed to stop cells from patching up their genomes.

CHK1 inhibitors weaken the ability of cancer cells to cope with DNA damage. The researchers discovered that when another set of genes involved in accurately copying genetic material are also blocked, this leads to catastrophic levels of DNA damage and 'replicative stress' - causing cancer cells to die.

They hope that a combination strategy that attacks DNA repair by inhibiting CHK1 and blocking accurate DNA replication at the same time could be effective against lung, bowel and other cancers - including ones that are resistant to current treatments.

Scientists at The Institute of Cancer Research, London, and the University of Kent treated lung and bowel cancer cells in the lab with a new experimental drug called SRA737, which blocks CHK1, and screened thousands of genes for targets that could be inhibited to increase cancer cell killing.

Using this approach, the researchers discovered that inhibiting a family of proteins known as B-family DNA polymerases - which are involved in the accurate replication of DNA - was highly effective in combination of SRA737.

Their study is published in Cancer Research, a journal of the American Association for Cancer Research. It was funded by Wellcome, with additional support from other organisations, including The Institute of Cancer Research (ICR) itself.

The researchers found that when they targeted the B-family DNA polymerases, cancer cells became more vulnerable to treatment with SRA737. Combined treatment with SRA737 and an experimental inhibitor of B-family DNA polymerases called aphidicolin stripped cancer cells of their ability to cope with DNA damage, and was more effective at killing them in eight of the nine cancer cell lines tested.

The researchers at the ICR - a charity and research institute - and the University of Kent believe that blocking both CHK1 and B-family DNA polymerases using a future combination of drugs could potentially be an effective cancer treatment.

This is an example of the kind of approach the ICR plans to take within its pioneering Centre for Cancer Drug Discovery, which aims to combat the central challenge of cancer evolution and drug resistance. The ICR has less than £10 million left to raise of the £75 million cost to create and equip the new building.

The researchers also found that low levels of the B-family DNA polymerases within tumours could be used as an indicator to pick out patients who may be more likely to respond to treatment with a CHK1 inhibitor when used on its own. More research will be needed, but this could bring CHK1 inhibitors a step closer to clinical use.

Combination approaches that use CHK1 inhibitors alongside other drugs, like the chemotherapy drug gemcitabine, have already shown promise in previous studies - including early clinical trials in cancers of the anus and genitals.

The new findings suggest the combination of SRA737 alongside an inhibitor of B-family DNA polymerases such as aphidicolin is also promising. However, aphidicolin is no longer being developed as it was found to be toxic.

Instead, the next step will be to discover suitable B-family DNA polymerase drug candidates, so the benefit of combination treatment with CHK1 inhibitors like SRA737 can be investigated in animals.

Study co-leader Professor Paul Workman, Chief Executive of The Institute of Cancer Research, London, said:

"Our new study establishes the basis for a potentially exciting new approach to treatment involving a two-pronged attack on cancer. We found that doubling up on drugs that target the systems for repairing DNA could be effective even against cancers that do not respond to single-drug treatment.

"Our findings also provide us with a way of picking out which patients are most likely to benefit from existing CHK1 inhibitors like SRA737 - a highly innovative drug discovered at the ICR and currently in clinical development.

"At the ICR, we believe that combinations of targeted drugs will be critical as we aim to overcome the major challenge of cancer evolution and drug resistance - just as they have been in other diseases such as HIV."

Study co-leader Professor Michelle Garrett, previously a Team Leader at The Institute of Cancer Research, London, and currently Professor of Cancer Therapeutics at the University of Kent, said:

"Our study shows the potential of targeting DNA replication for adding to the effect of an existing drug that blocks a system that helps respond to DNA damage.

"It's exciting too that detecting tumours with low levels of B-family DNA polymerases could be used to identify patients most likely to respond to a CHK1 inhibitor, presumably because of natural weaknesses in DNA repair within these cancers.

"The next step is to develop new drug candidates that could be used to target B-family DNA polymerases in combination with the CHK1 inhibitor SRA737, as we have shown that this could open up a potential new therapeutic approach."

Researchers at the University of Bristol are pioneering the use of virtual reality (VR) as a tool to design the next generation of drug treatments.

The findings, published in the journal PLOS ONE describe how researchers used VR to understand how common medications work on a molecular level.

Many drugs are small molecules, and discovering new drugs involves finding molecules that bind to biological targets like proteins.

In the study, users were able to use VR to 'step inside' proteins and manipulate them, and the drugs binding to them, in atomic detail, using interactive molecular dynamics simulations in VR (iMD-VR).

Using this iMD-VR approach, researchers 'docked' drug molecules into proteins and were able to predict accurately how the drugs bind. Among the systems studied were drugs for flu and HIV.

Professor Adrian Mulholland, from the University of Bristol's Centre for Computational Chemistry, and co-lead of the work, said: "Many drugs work by binding to proteins and stopping them working. For example, by binding to a particular virus protein, a drug can stop the virus from reproducing.

"To bind well, a small molecule drug needs to fit snugly in the protein. An important part of drug discovery is finding small molecules that bind tightly to specific proteins, and understanding what makes them bind tightly, which helps to design better drugs.

"To design new therapies, researchers need to understand how drug molecules fit into their biological targets. To do this, we use VR to represent them as fully three-dimensional objects. Users can then fit a drug within the 'keyhole' of a protein binding site to discover how they fit together."

In the study, users were set the task of binding drugs to protein targets such as influenza neuraminidase and HIV protease.

Tests showed that users were able to predict correctly how the drugs bind to their protein targets. By pulling the drug into the protein, they could build structures that are very similar to the structures of the drug complexes found from experiments.

Even non-experts were able to dock drugs into the proteins effectively. This shows that interactive VR can be used to predict accurately how new potential drugs bind to their targets.

The study shows how VR can be used effectively in structure-based drug design, even by non-experts. It uses readily available VR equipment and an open source software framework, so can be applied by anyone.

Professor Mulholland added: "An important aspect of the work is that the drugs, and their protein targets, are fully flexible: we model their structural changes and dynamics, and users can manipulate them interactively to find how drugs interact with their biological targets. This is a really exciting and powerful way to model drug binding. We have shown in this work that it gives accurate results. These tools will be useful in the design and development of new drugs."

Dr David Glowacki, Royal Society Senior Research Fellow in Bristol's School of Chemistry and Department of Computer Science, said: "Our results show that it is possible to unbind and rebind drugs from protein targets on a simulation timescale significantly shorter than the timescale of similar events observed using non-interactive molecular dynamics engines.

"It is also important to note that the full unbinding and rebinding events generated using iMD-VR were achieved by the users in less than five minutes of real time.

"Where non-expert users had trace atoms showing them the correct pose, all participants were able to establish a docking pose which was close enough to the starting structure to be scientifically considered redocked.

"Where no trace atoms were present, binding poses understandably had more variation, but users were still able to get within the same range of the accepted bound position for all three systems. These results were achieved within a single hour-long training session with each participant, demonstrating the usability of this VR framework."

Researchers at Louisiana State University have discovered a new species of shrew, which they have named the hairy-tailed shrew, or Crocidura caudipilosa.

"There was no doubt that this was a new species," said LSU Museum of Natural Science Mammal Curator Jake Esselstyn whose work on Sulawesi Island in Indonesia led to the discovery published in the Journal of Mammalogy. "There isn't another species on the island that has as much hair on its tail, in terms of shrews."

The newly discovered shrew is slender with gray-brown fur on its back and silver-gray fur on its belly. Its tail is slightly longer than the combined length of its head and body and is covered with long bristles and hair, which make the distinctive tail very hirsute. In fact, no other shrew species in Indonesia, Malaysia or the Philippines is known to have such thick, long hair on its tail; however, some shrew species in Africa have very hairy tails. The scientists were also surprised to discover that this shrew climbs trees whereas most shrews live primarily on the ground, as far as anyone knows.

The Sulawesi hairy-tailed shrew was found on nine mountains across Sulawesi at various elevations from 1,500 feet to 4,800 feet.

"Tropical diversity is still not well documented even for mammals with a wide distribution on this island. This discovery shows how little we still know about mammal diversity," Esselstyn said.

Puzzling pieces

The real challenge was figuring out which shrew is its closest relative and how this new species fits into the shrew family tree. Shrews' features do not change very much over time, which means closely related species tend to look very similar and are hard to distinguish from each other. This has posed a challenge for mammalogists in the past to discover new shrew species.

"Genetic data have revolutionized what we can distinguish between shrews. A lot of species are first recognized as being genetically distinct, then we look at its morphology, or physical features," Esselstyn said.

Deforestation and degradation of natural habitats have also posed a challenge for discovering new species. For example, a few shrew specimens were collected in the early 20th century, but when scientists return to the same location where the early specimens were collected, the habitat is no longer a forest. It is a farm.

Despite these challenges, Esselstyn and his colleagues and students have also discovered several new mammals in Indonesia including the hog-nosed rat, the Sulawesi water rat and the slender root rat as well as the sky island moss shrew in the Philippines.

Meanwhile at the LSU Museum of Natural Science, they continue to search and analyze specimens for more new species and to help put the pieces of the large tree of life puzzle together.

DALLAS (SMU) - "Even if she doesn't say it, I know it's my fault that my mother gets sad."

Kids who believe comments like this - assuming blame for their mom's sadness or depression - are more likely to face depression and anxiety themselves, a new study led by SMU has found.

"Although mothers with higher levels of depressive symptoms face increased risk that their children will also experience symptoms of depression and anxiety, our study showed that this was not the case for all children," said SMU family psychologist and lead author Chrystyna Kouros. "Rather, it was those children who felt they were to blame for their mother's sadness or depression...that had higher levels of internalizing symptoms."

In light of the findings, Kouros said it's critical that parents and others who regularly interact with children pay close attention to the kinds of comments that kids make about their mom's symptoms and to intervene if children incorrectly think that it's their fault that their mom is depressed. Children who take on this blame can benefit from therapies and interventions that target negative thoughts, said Kouros, SMU associate professor of psychology.

Sharyl E. Wee and Chelsea N. Carson, graduate students at SMU, and Naomi Ekas, an associate professor of psychology at Texas Christian University, also contributed to the study, which was published in the Journal of Family Psychology. 

The study is based on surveys taken by 129 mothers and their children, who were recruited from the Dallas-Fort Worth community through schools, flyers and online advertisements. On average, children included in the study were 13 years old. 

Moms were asked to agree or disagree to 20 statements like "I could not shake off the blues" and "I lost interest in my usual activities" to assess if they had depressive symptoms, even if they had not actually been diagnosed with depression. Nearly 12 percent of the women surveyed were found to have potential clinical levels of depressive symptoms.

The moms were also asked to assess whether they felt their children had symptoms of depression and anxiety.

Kids, meanwhile, were asked to complete a total of four surveys to see if they were dealing with any anxiety or depression and whether they blamed themselves for any signs of depression in their mothers.

Kouros said there are two likely explanations for the linkage between mothers' depressive symptoms and kids' own mental health issues:

"If children blame themselves for their mothers' depressive symptoms, then they may be more likely to brood about their mother's symptoms. And we know from an extensive body of research that rumination over stressors - especially ones that are uncontrollable - is linked with depression and anxiety," Kouros said. "Also, if children feel personally responsible for their mothers' symptoms, they may try to 'make it better' and use ineffective coping strategies. This could lead to a sense of helplessness, failure, and low self-worth in the child, since ultimately the child was misattributing the cause of their mothers' depressive symptoms."

More studies are needed to see if depressed dads have the same effect on their children, Kouros said.

Scientists agree that sea levels will continue to rise this century, but projections beyond 2050 are much more uncertain regarding exactly how much higher ocean levels will be by 2100. While actions to protect against 2050 sea-level rise have a secure scientific basis, this range in late-century estimates makes it difficult for coastal communities to plan their long-term adaptation strategies.

Princeton University researchers at the Center for Policy Research on Energy and the Environment have developed a new framework allowing urban planners and policymakers to consider a combination of responses to sea-level rise (e.g., levees, storm surge barriers, elevating buildings, retreat) and, if hard structures, how high these protections should be built, depending on their tolerance for risk and the projected financial losses to a particular area due to flooding. The paper was published in Earth's Future.

Over the past 100 years, relative sea level measured at The Battery, the historic park at the southernmost tip of Manhattan Island, New York, has increased by 0.285 meters or just under 1 foot, according to the National Oceanic and Atmospheric Administration. Because of global warming, scientists expect this rate of sea-level rise to accelerate in the coming decades. However, there is uncertainty regarding how much greenhouse gas emissions will change and how much of Antarctica will melt in response to a warming climate.

Scientific perspectives on these issues result in different projections of global average sea-level rise. For example, local sea levels at the Battery are expected to rise between 0.6 m and 1.8 m from the beginning of this century to 2100. "We will be contending with more frequent, extreme flooding from coastal storms and high tides. These '100-year floods' will become much more frequent - in some places, as often as once per year," added co-author and leading climate scientist, Michael Oppenheimer.

Existing frameworks for calculating how high to elevate structures to avoid future floods only consider extreme water levels, not the damages that flooding can cause. This may lead to under- or over-estimates in terms of how high to raise a structure.

The authors introduce a new "flood damage allowance" approach that connects extreme water levels with projected damages, incorporating both uncertainty regarding sea-level rise, as well as people's individual tolerance of risk.

"Our approach allows decision-makers to specify their own acceptable level of risk, a protection strategy type - such as elevation, storm surge barrier, or coastal retreat - and their assumptions about how much the Antarctic Ice Sheet will melt," said D.J. Rasmussen, lead author and a Ph.D. candidate at the Woodrow Wilson School of Public and International Affairs at Princeton. "Our framework could help inform the Army Corps of Engineers' efforts to design climate change adaptation projects."

The authors use Manhattan as an example to illustrate their framework. New York City has experienced tremendous losses due to flooding, as it is among the top global cities exposed to coastal flood threats; just in Manhattan, there are over $50 billion of assets are currently within the 100-year flood plain. Some of the key responses the flood damage allowances approach explores are:

While planners will still need to do more detailed assessments of the feasibility of various sea defense models in a particular location, this simpler model can identify promising strategies before planners invest in further, more complex engineering and financial models. Because of the study's modeling simplifications, the authors do not propose specific recommendations for how NYC should respond; rather, the framework illustrates that under different circumstances, some approaches may have certain advantages over others.

For example, in the wake of Hurricane Sandy, the Army Corps of Engineers is currently exploring the use of storm surge barriers to protect New York City from future sea-level rise and more frequent coastal floods. A key question is, "How high to build the barriers?" The answer depends on input from the engineers and expert judgments about how much and how quickly Antarctica will melt. The authors' framework can facilitate estimates of how high to build the storm surge barriers and allow planners to explore the impact of different factors on recommended surge barrier heights.

"As coastal cities and communities prepare for a changing coastline and climate in the coming decades, tools like this one that incorporate uncertainty and integrate oceanographic and financial information will help planners develop a more thorough analysis of their best defense options," the researchers said; "In the end, a variety of strategies will be needed to protect most coastal cities."

Scientists from China and Russia found a new way of searching for new drug candidates by inactivating the molecular structure of the human muscarinic receptor and applying screening to find drugs that it responds to. The results of their study were published in IUCrJ.

The membrane receptors which ensure that human cells function properly count among the most sought after drug targets. Scientists and pharmacologists alike are busy testing thousands of molecules to find drugs with the desired pharmacological effect, that is, receptor activation or inactivation. A member of the important class of G protein-coupled receptors (GPCR), the human muscarinic receptor is a drug target for many disorders, including Alzheimer's disease, Parkinson's disease, and schizophrenia.

A group of scientists from ShanghaiTech University in collaboration with a professor from the Skoltech Center for Computational and Data-Intensive Science and Engineering, Petr Popov, inactivated the human muscarinic receptor's structure so as to enable binding between the receptor and the drugs, primarily the receptor blockers, which is a great convenience in screening for the optimal drug.

Inactivation became possible thanks to the artificial intelligence (AI) and molecular modeling algorithms. First, the inactivated 3D structure and mutations in the protein structure were modeled and then the inactivated receptor was synthesized in the lab.

"This study shows that machine learning and molecular modeling methods hold tremendous hands-on potential for biotechnology tools. We tested several thousand modifications of the receptor in silico in search of its most stable inactive form. Our approach has been successfully used for other drug targets, too," -- says Popov

Scientists from Woods Hole Oceanographic Institution reveal how microorganisms could survive in rocks nestled thousands of feet beneath the ocean floor in the lower oceanic crust, in a study published on March 11 in Nature. The first analysis of messenger RNA -- genetic material containing instructions for making different proteins -- from this remote region of Earth, coupled with measurements of enzyme activities, microscopy, cultures, and biomarker analyses provides evidence of a low biomass, but diverse community of microbes that includes heterotrophs that obtain their carbon from other living (or dead) organisms.

"Organisms eking out an existence far beneath the seafloor live in a hostile environment," says Dr. Paraskevi (Vivian) Mara, a WHOI biochemist and one of the lead authors of the paper. Scarce resources find their way into the seabed through seawater and subsurface fluids that circulate through fractures in the rock and carry inorganic and organic compounds.

To see what kinds of microbes live at these extremes and what they do to survive, researchers collected rock samples from the lower oceanic crust over three months aboard the International Ocean Discovery Program Expedition 360. The research vessel traveled to an underwater ridge called Atlantis Bank that cuts across the Southern Indian Ocean. There, tectonic activity exposes the lower oceanic crust at the seafloor, "providing convenient access to an otherwise largely inaccessible realm," write the authors.

Researchers combed the rocks for genetic material and other organic molecules, performed cell counts, and cultured samples in the lab to aid in their search for life. "We applied a completely new cocktail of methods to really try to explore these precious samples as intensively as we could," says Dr. Virginia Edgcomb, a microbiologist at WHOI, the lead PI of the project, and a co-author of the paper. "All together, the data start to paint a story."

By isolating messenger RNA and analyzing the expression of genes -- the instructions for different metabolic processes -- researchers showed evidence that microorganisms far beneath the ocean express genes for a diverse array. Some microbes appeared to have the ability to store carbon in their cells, so they could stockpile for times of shortage. Others had indications they could process nitrogen and sulfur to generate energy, produce Vitamin E and B12, recycle amino acids, and pluck out carbon from hard-to-breakdown compounds called polyaromatic hydrocarbons. "They seem very frugal," says Edgcomb.

This rare view of life in the far reaches of the earth extends our view of carbon cycling beneath the seafloor, Edgcomb says. "If you look at the volume of the deep biosphere, including the lower oceanic crust, even at a very slow metabolic rate, it could equate to significant amounts of carbon."

Tumors have figured out various ways to prevent the immune system from attacking them. Medicine, for its part, has fought back with cancer immunotherapies. The major approach uses checkpoint inhibitors, drugs that help the immune system recognize cancer cells as foreign. Another method, CAR T-cell therapy, directly engineers peoples' T cells to efficiently recognize cancer cells and kill them.

But not all patients benefit from these approaches, which work for just a minority of cancer types, and CAR T-cell therapy carries significant risks. New research from Boston Children's Hospital, published March 11 in Nature, adds another strategy to the arsenal, one that could potentially work in more types of cancer. It reactivates a gene called gasdermin E, harnessing an immune response we already have but that is suppressed in many types of cancer.

"Gasdermin E is a very potent tumor suppressor gene, but in most tumor tissues, it's either not expressed or it's mutated," says Judy Lieberman, MD, PhD, of the Program in Cellular and Molecular Medicine (PCMM), the study's principal investigator. "When you reactivate gasdermin E in a tumor, it can convert an immunologically 'cold' tumor -- not recognized by the immune system -- into a 'hot' tumor that the immune system can control."

In the study, Lieberman and colleagues showed that 20 of 22 cancer-associated mutations they tested led to reduced gasdermin E function. When they re-introduced gasdermin E in a mouse model, they were able to trigger pyroptosis and suppress growth of variety of tumors (triple-negative breast tumors, colorectal tumors, and melanoma).

Heating up the immune response

The team also showed, in mouse tumor cell lines, how gasdermin E works. Normally, when cells die, including most cancerous cells, it's through a process called apoptosis, a quiet, orderly death. But if gasdermin E is present and working, cancer cells go down in flames, through a highly inflammatory form of cell death called pyroptosis.

As Lieberman's team showed in live mice, pyroptosis sounds a potent immune alarm that recruits killer T cells to suppress the tumor. The team is now investigating therapeutic strategies for inducing gasdermin E to rally that anti-tumor immune response.

"What we're suggesting is that if we can turn on the danger signal, which is inflammation, we can activate lymphocytes more fully than with other immunotherapy approaches, and have immunity that is potentially much broader," says Lieberman. "Combining activation of inflammation in the tumor with approved checkpoint inhibitor drugs could work better than either strategy on its own."

The next wave of quantum, optical and electronic devices will be built from powerful two-dimensional materials. These materials can host room temperature qubits thereby enabling solid-state quantum technologies that are inherently more powerful than their classical counterparts.

But, they have a weakness. Unlike 3-D systems, where almost all of the atoms are protected from the environment, 2-D materials are exposed to the elements and susceptible to outside interactions from nearby materials or chemicals in the air. These interactions can actually change the atomic arrangement of the system.

If researchers are going to build new devices out of 2-D materials, they need to understand where their atoms are and how tiny imperfections change their material and electronic properties.

Now, researchers at the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS), the University of California, Los Angeles, and the Oak Ridge National Laboratory have combined experimental and theoretical techniques to measure atomic positions of all the atoms in a 2D material and calculate how the arrangement impacts the electronic properties of various regions of the system.

The research is published in Nature Materials.

The researchers found that materials were far from perfect, with atoms constantly misaligned, missing, or replaced with something else.

"While it makes sense that missing atoms and substituted atoms would change the local interactions and atomic configuration, it's not easy to answer the question by how much," said Christopher Ciccarino, a graduate student in the NarangLab at SEAS and co-author of the paper.

In collaboration with John Miao, professor at UCLA's Department of Physics and Astronomy, the researchers used a high-powered scanning electron microscope to measure the precise location of individual atoms and image atomic configurations at different angles relative to the 2D sheet.

After mapping out these positions, the research team analyzed the lattice to see how imperfections play a role in its properties.

"Defects within the lattice created local disorder and irregularities," said Prineha Narang, Assistant Professor of Computational Materials Science at SEAS and co-author of the paper. "Even when zoomed out, the collection of vacancies and defects seemed to contribute to disorder. In particular, the 2D sheet wasn't really 2D, but instead had long range ripples in the third dimension."

"What we saw were these supposedly 2D sheets preferring to use this third dimension instead of remaining perfectly flat," said Ciccarino. "It is interesting then to think about how this would play into the observed properties of the material." The researchers found that local disorder can have significant effects on electronic and optical properties of 2D materials, including huge effects in how efficiently the material emitted light.

"Theorists usually have to make some assumptions about their system in order to compare with experiment," said Narang. "Here we were in a unique and exciting situation where we could directly intersect our methods with experimentally computed coordinates. Direct quantification of atomic disorder and interactions with environment could be an invaluable technique for fully understanding the nature and potential of these materials."

Factoring in the total number of days that extremely preterm infants require supplemental oxygen and tracking this metric for weeks longer than usual improves clinicians' ability to predict respiratory outcomes according to bronchopulmonary dysplasia (BPD) severity, a research team led by Children's National Hospital writes in Scientific Reports. What's more, the researchers defined a brand-new category (level IV) for newborns who receive supplemental oxygen more than 120 days as a reliable way to predict which infants are at the highest risk of returning to the hospital due to respiratory distress after discharge.

About 1 in 10 U.S. infants are born preterm, before 37 weeks gestation, according to the Centers for Disease Control and Prevention. That includes extremely preterm infants who weigh about 1 lb. at birth. These very low birthweight newborns have paper thin skin, frail hearts and lungs that are not yet mature enough to deliver oxygen throughout the body as needed. Thanks to advances in neocritical care, an increasing number of them survive prematurity, and many develop BPD, a chronic lung disease characterized by abnormal development of the lungs and pulmonary vasculature.

"About half of the babies born prematurely will come back to the hospital within the first year of life with a respiratory infection. The key is identifying them and, potentially, preventing complications in this high-risk population," says Gustavo Nino, M.D., a Children's National pulmonologist and the study's lead author.

For decades, the most common way to stratify BPD risk in these vulnerable newborns has been to see if they require supplemental oxygen at 36 weeks corrected gestational age.

"The problem with this classification is it doesn't take into account the very premature babies who are on oxygen for much longer than other babies. So, we asked the question: Can we continue risk stratification beyond 36 weeks in order to identify a subset of babies who are at much higher risk of complications," Dr. Nino says.

The longitudinal cohort study enrolled 188 infants born extremely preterm who were admitted to the neonatal intensive care unit (NICU) at Children's National and tracked their data for at least 12 months after discharge. The team used a multidimensional approach that tracked duration of supplemental oxygen during the newborns' NICU stay as well as scoring lung imaging as an independent marker of BPD severity. To validate the findings, these U.S.-born newborns were matched with 130 infants who were born preterm and hospitalized at two NICUs located in Bogotá, Colombia.

"Babies who are born very preterm and require oxygen beyond 120 days should have expanded ventilation of the lungs and cardiovascular pulmonary system before going home," he notes. "We need to identify these newborns and optimize their management before they are discharged."

And, the babies with level IV BPD risk need a different type of evaluation because the complications they experience - including pulmonary hypertension - place them at the highest risk of developing sleep apnea and severe respiratory infection, especially during the first year of life.

"The earlier we identify them, the better their outcome is likely to be," Dr. Nino says. "We really need to change the risk stratification so we don't call them all 'severe' and treat them the same when there is a subset of newborns who clearly are at a much higher risk for experiencing respiratory complications after hospital discharge."

MINNEAPOLIS, MN- March 11, 2020 - A team of researchers at the University of Minnesota Medical School recently proved the ability to grow human-derived blood vessels in a pig--a novel approach that has the potential for providing unlimited human vessels for transplant purposes. Because these vessels were made with patient-derived skin cells, they are less likely to be rejected by the recipient, helping patients potentially avoid the need for life-long, anti-rejection drugs.

Daniel Garry, MD, PhD, and Mary Garry, PhD, both professors in the Department of Medicine at the U of M Medical School, co-led the research team and published their findings in Nature Biotechnology last week.

"There's so many chronic and terminal diseases, and many people are not able to participate in organ transplantation," said Daniel, who is also a heart failure and transplant cardiologist. "About 98 percent of people are not going to be eligible for a heart transplant, so there's been a huge effort in trying to come up with strategies to increase the donor pool. Our approach looked at a pig."

Because of similarities between human and pig physiology, scientists have historically studied pigs to discover treatments for health issues, including diabetes. Before researchers engineered human insulin, doctors treated patients with pig insulin.

"Our discovery has made a platform for making human blood vessels in a pig," said Daniel. "This could allow us to make organs with human blood vessels that would be less apt to be rejected and could be used in patients in need of a transplant. That's what typically causes rejection--the lining of the blood vessels in the organs."

The blood vessels created by the Garry duo will avoid rejection because of the method by which they are made. The team injects human-induced pluripotent stem cells--taken from mature cells scraped from a patient's skin and reprogrammed to a stem cell state--into a pig embryo, which is then placed into a surrogate pig. In the future, viable piglets, with blood vessels that will be an exact match to the patient, will ensure a successful transplant and the ability to live without the need for immunosuppression, or anti-rejection, drugs.

"There's hundreds of thousands of patients that have peripheral artery disease, either because of smoking or diabetes or any number of causes, and they have limb amputations," Mary said. "These blood vessels would be engineered and could be utilized in these patients to prevent those kinds of life-long handicaps, if you will."

The first phase of their study, approved by the U of M's Stem Cell Research Oversight committee, brought the first embryo to a 27-day term. Because of the success of this phase, Daniel and Mary are currently seeking the committee's approval to advance the research further into the later gestational period.

"We're trying to take it in a phased approach," Daniel said. "We want to be sure we address all of the possible issues--whether human cells go where we want them to go."

"While it is a first phase, there's pretty solid proof of concept," Mary said. "We believe that we've proven that there's no off-target effects of these cells, so we're ready to move forward to later gestational stages."

This exoplanet, 390 light years away towards the constellation Pisces, has days when its surface temperatures exceed 2,400 Celsius, sufficiently hot to evaporate metals. Its nights, with strong winds, cool down the iron vapour so that it condenses into drops of iron. This is the first result with the high resolution spectrograph ESPRESSO, an instrument co-directed by the IAC and installed on teh Very Large Telescope (VLT) of ESO, in Chile.

With ESPRESSO (Echelle SPectrograph for Rocky Exoplanets and Stable Spectroscopic Observations), astrophysicists have identified chemical variations between day and night on the planet: they detected the trace of iron vapour just at the division between the daytime and the night-time sector of the planet. It is the first time that chemical variations have been detected in a giant ultra-hot planet. "However, suprisingly we do not see this iron vapour at dawn. The only explanation possible for this phenomenon is that it rains iron on the dark side of this exoplanet with extreme conditions" says David Ehrenreich, a researcher at the University of Geneva and the first author of the article.

"The observations" reports María Rosa Zapatero Osorio, researcher at the del Centre for Astrobiology of the CSIC and coordinator of the ESPRESSO science team, "show a huge quantity of iron in the daytime atmosphere of the giant planet WASP-76b. A part of this iron is transported to the dark side of the planet due to its rotation and the atmospheric winds. There in the cooler environment of the dark side of the planet, the iron condenses and precipitates".

"Just like the Moon around the Earth, this planet always keeps the same face towards its star as it rotates around it, which causes this extreme difference in temperature between day and night on the planet" explains Jonay I. Gonzálezz Hernández, Ramón y Cajal researcher at the IAC and a member of the science team of ESPRESSO. WASP-76b receives thousands of times more radiation from its central star than arrives at the Earth from the Sun. Its daytime face is so hot that the molecules split into atoms, and metals such as iron evaporate into the atmosphere. The difference of more than a thousand degrees between night and day produce strong winds which take the iron vapour into the coolest part of the exoplanet.

"Ultrahot giant planets are the best laboratories we have for studying extreme climates on exoplanets. If we observe an exoplanet during its transit across the disc of its star we can study the part of its atmosphere through which the light from the star passes. With ESPRESSO it has been possible to detect chemical variations using analysis of the small part of the atmosphere we can observe", adds Núria Casasayas Barris, researcher at the IAC and PhD student of the University of La Laguna (ULL).

A pioneer instrument

The results on WASP-76b were obtained during the first observations made with ESPRESSO in September 2018 by the consortium that built the instrument, in Chile, Portugal, Italy, Switzerland, Spain, and the European Southern Observatory (ESO). ESPRESSO was designed from the beginning to "hunt" exoplanets similar to the Earth in orbit around stars similar to the Sun, but it has turned out to be much more versatile. "The great stability of ESPRESSO, without precedent anywhere in the world, together with the potential of the telescopes in the VLT makes ESPRESSO a fundamental tool in the search for Earths, and to study the atmospheres of exoplanets in general" we are assured by Rafael Rebolo, Director of the IAC, winner of the National Prize for Science, and one of the co-directors of ESPRESSO. This instrument will measure with high precision the radial velocities of rocky planets and the possible time variation of the constants of physics, as well as analyzing in great detail the chemical composition of stars. "This work also shows that we have a new way to track the climate of the most extreme exoplanets" concludes Ehrenreich.

March 11, 2020 (Toronto) - Publicly-funded physician psychotherapy is only available to a fraction of those with urgent mental health needs in Ontario, according to a joint study by the Centre for Addiction and Mental Health (CAMH) and ICES published today in CMAJ Open.

The study confirms that there are far too few physicians providing publicly-funded psychotherapy in Ontario to meet the demand for it, and those physicians are concentrated in large urban areas and are rarely able to take on new patients with urgent mental health needs.

"The need for innovations in mental health to improve access and quality of care is urgent," said lead author Dr. Paul Kurdyak, Director of Health Outcomes and Performance Evaluation in the Institute for Mental Health Policy Research at CAMH and lead of the Mental Health and Addictions Research Program at ICES. "But increasing the number of physicians who provide psychotherapy alone will not solve the existing problem of poor access to psychotherapy in a publicly-funded system."

The study focused on the availability of publicly-funded psychotherapy provided by physicians in Ontario. Psychotherapy is an evidence-based treatment for conditions like depression and anxiety, two of the most common psychiatric disorders. Treatment guidelines suggest that structured, evidence-based therapies like Cognitive Behavioural Therapy (CBT) should be a front-line treatment option for patients with mild to moderate depression or anxiety.

Historically, most access to publicly-funded psychotherapy in Ontario has been provided by psychiatrists or family physician psychotherapists. But there are less than 1,000 of them in Ontario (out of a total physician population of over 12,000) and they see a much smaller number of patients on average.

While access to urgent care was low in general (more than half of all patients who sought care for mental health including addictions issues at an Emergency Department did not see any physicians within a month of the visit) access to psychotherapist physicians was even lower. Only two to three per cent of patients with urgent need were able to access psychotherapist physicians.

One part of the solution according to the study is to allow psychotherapists and other clinicians who are not physicians to provide publicly-funded CBT. It points to a program initiated in England that involved training non-physicians to provide publicly-funded CBT as one model for Ontario to consider.

CAMH has been one of four mental health hospitals in Ontario taking part in a three-year pilot project based on the England model, and last week the Ontario government announced it was expanding that program under the name Mindability to provide publicly-funded CBT to an additional 80,000 patients a year. But the study estimates that more than ten times that amount of patients--up to 900,000 a year in Ontario--could benefit from psychotherapy.

"Evidence-based psychotherapy should be available to all patients suffering from the most prevalent mental disorders," said Dr. Kurdyak. "Our study suggests that there are far too few publicly-funded physician psychotherapists to meet the needs of these patients."