Brain

DALLAS – April 23, 2020 – A combination of immunotherapy agents that encourages some immune cells to eat cancer cells and alert others to attack tumors put mice with a deadly type of brain cancer called glioblastoma into long-term remission, a new study led by UT Southwestern scientists suggests. The finding, published online March 20, 2020, in Nature Communications, could lead to new therapies that may significantly extend survival for human glioblastoma patients, which stands at an average of 15 months after diagnosis even with current state-of-the-art therapies.

The immune system has two branches: innate immunity, an evolutionarily older system that continually scans the body and removes foreign invaders such as bacteria or viruses often by “eating” them in a process called phagocytosis; and adaptive immunity, which provides a more targeted and stronger response based on memory acquired from previous exposure to a pathogen. These branches overlap somewhat: For example, the innate immune system trains the adaptive one on where to focus its efforts using the potential pathogens it encounters.

In recent years, researchers have had considerable success in harnessing the immune system to fight some cancers, developing several drugs that have vastly extended survival. However, explains study leader Wen Jiang, M.D., Ph.D., assistant professor of radiation oncology at UT Southwestern Medical Center, these efforts have mostly focused on adaptive immunity.

Some pharmaceuticals in development aim to boost the innate immune system’s action against cancer by blocking CD47, a protein that many cancer cells display on their surfaces that functions as a “don’t eat me” signal. Glioblastoma (GBM) – the most common primary central nervous system malignancy in adults and a cancer that Jiang frequently treats in clinic – often displays substantially elevated amounts of CD47 on its tumor cell surfaces, with higher amounts generally suggesting worse outcomes for patients. But these drugs have had mixed results in clinical trials, Jiang says; although they’ve shown promise for blood cancers, such as leukemias, their performance for solid tumors has been disappointing.

Seeking to boost survival for GBM patients, Jiang and his colleagues searched for ways to encourage innate immune cells to eat GBM cells, which not only destroys these cells directly but also helps train the adaptive immune system to continue the attack.

The researchers first tested how well CD47 monoclonal antibodies – proteins that stick to and mask CD47 – work on GBM cells grown with innate immune cells called phagocytes in petri dishes. Although this agent did boost the phagocytes’ consumption of the cancer cells, “the activity wasn’t too striking,” Jiang says. “It was nothing to brag about.”

Next, he and his colleagues tested increasing the cancer cells’ “eat me” signal by administering a drug called temozolomide (TMZ), a decade-old pharmaceutical that’s a mainstay for most GBM treatment protocols. The drug activates stress responses in cancer cells that make the immune system more likely to eliminate them. Although this drug also increased phagocyte consumption of the cancer cells, these results were also lackluster, says Jiang, also a member of UT Southwestern’s Harold C. Simmons Comprehensive Cancer Center.

Jiang and his colleagues then reasoned that because these two pharmaceuticals operate using completely different mechanisms, they might get more of a response combined. Sure enough, when they administered both agents together, they appeared to work in synergy, prompting phagocytes to eat many more GBM cells than either drug alone. Further experiments showed that once phagocytes had eaten their cancerous prey, they used components from these tumor cells to prime the immune system’s T cells – the primary adaptive immune cells that fight cancers – to kill more GBM cells.

When the researchers tested this combination therapy in a mouse model of GBM, it successfully shrank tumors and extended life. However, in time, the tumor cells developed a different way to evade the immune system by boosting their production of a protein called PD-L1, which shields them from T cell attack. Thwarting this move, the researchers added an antibody against this protein called anti-PD-1. Together, this three-part regimen – anti-CD47 antibodies, TMZ, and anti-PD-1 antibodies – dramatically extended survival. About 55 percent of these animals did not die over the course of the study, a scenario akin to long-term remission in patients, Jiang says. He and his colleagues hope to test this approach in humans soon in a clinical trial, he adds.

“If a new therapy extends survival by even one to two months, it’s considered a blockbuster drug,” Jiang says. “Here, we’re talking potentially about a significant proportion of patients who could be cured. Bridging the innate and adaptive immune systems could prove to be a major advance for GBM.”

Current regulatory standards regarding the dissolved oxygen and pH levels of coastal waters have not kept pace with the scientific understanding of hypoxia and acidification, nor with the mounting evidence of their negative impact on coastal marine life. In light of these shortcomings, a Policy Forum by Stephen Tomasetti and Christopher Gobler argues the need for new approaches to coastal policy that account for new knowledge, and ultimately, that lead to improved protection of important coastal fisheries worldwide. Coastal hypoxia, or the depletion of dissolved oxygen (DO) in near-shore marine ecosystems, is often caused by runoff pollution from agricultural fertilizers. The overabundance of nitrogen and phosphorus nutrients induces the excessive growth of algal blooms, which use the water's DO, converting it into acidic carbon dioxide molecules and hydrogen ions. The process can quickly turn warm, poorly mixed coastal waters acidic and starved of oxygen. While recent research has demonstrated the concurrent effects of low DO and low pH are more severe for marine life than either effect individually, Tomasetti and Gobler discuss how aging water policies do not account for their combined effects. What's more, current Environmental Protection Agency pH standards allow for levels now known to impact coastal marine life negatively. According to the authors, these regulatory criteria put many coastal fisheries at risk, and this risk will likely intensify as climate change-induced reductions in ocean pH and DO accelerate into the coming century.

Many organizations arrange employees into groups, and research has recognized the importance of groups having access to resources (e.g., labor, knowledge, raw materials, technology, financial capital), as well as how they use those resources to ensure optimal performance. These studies have shown that groups with the same resources vary in how they use what is available, suggesting that the same resources can have different effects across groups.

A new study looked at more than 1,300 retail banking sales teams in a large regional bank to explore whether groups vary in how they convert resources into performance. The study found that resources are generally helpful, but groups differ in the results they achieve. The variation is also largely associated with the group's coordinated attention--specifically, their patterns of email communication. The findings have implications for how firms can operate more efficiently.

The study, by researchers at Carnegie Mellon University and Johns Hopkins University, is published in Academy of Management Discoveries.

"We looked at how the effects of knowledge-related resources vary from team to team to determine how certain groups benefit more than others," explains Anna Mayo, Postdoctoral Fellow in the Carey Business School at Johns Hopkins University, who coauthored the study.

The researchers used a dataset from a U.S. retail banking sales group to examine whether teams varied in how they converted resources into performance (i.e., monthly sales). Sales groups consisted of two to 17 retail sales personnel that were co-located. The primary measure of performance was sales revenue generated, including the services employees provided (e.g., checking and savings accounts, credit cards, mortgages) to both new and current customers. Researchers also interviewed key sales personnel.

The study controlled for a variety of factors related to each group's composition, including the ages and genders of members, the average number of months members had worked for the bank, members' experience working together, and their salaries. It also controlled for prior performance (the average individual sales from the month prior to the study), turnover, evaluated ability, and market factors.

In all groups, functional diversity, or having members with different types of roles and organizational functions, as well as the number of team members working together were linked to better performance. However, the study found that some branches generated even greater returns on these resources than others. It also found an association between branches that were more successful in converting resources into results and how well employees at those branches coordinated their resources across tasks to avoid delays and missed opportunities.

Coordinated attention allowed relevant information to be shared quickly so members could act on it and complete work efficiently.

Specifically, researchers identified email activity as an indicator of coordination among groups because employees used email to share referrals, inquire or share information about the bank's products and services, and transfer information. Using archival data on email activity among sales group members, the researchers measured the burstiness of emails--that is, how the emails were clustered in time as opposed to being distributed uniformly across time. They found that groups that sent emails in bursts had greater success capitalizing on available resources.

"The ability to determine variations in how groups use resources has practical implications," suggests Anita Williams Woolley, Associate Professor of Organizational Behavior and Theory at Carnegie Mellon University's Tepper School of Business, who coauthored the study. "In organizations with many teams working on the same or similar tasks, it may be prudent to identify which groups are most likely to communicate in ways that capitalize on firms' resources.

Understanding what allows some teams to reap greater returns can shed light on how to allocate resources and facilitate more efficient work across all groups."

A new way to deliver therapeutic proteins inside the body uses an acoustically sensitive carrier to encapsulate the proteins and ultrasound to image and guide the package to the exact location required, according to Penn State researchers. Ultrasound then breaks the capsule, allowing the protein to enter the cell.

"When you expose the particle to ultrasound it opens a hole in the cell membrane that lasts for a couple of microseconds," said Scott Medina, assistant professor of biomedical engineering, Penn State. "We can use this temporary opening to deliver antibodies, which are attractive therapeutic molecules in precision medicine that cannot otherwise get inside cells."

These antibodies are emerging therapeutics for cancers, infectious diseases and rheumatoid arthritis, he said.

But getting the protein inside the nanoparticle carrier was not easy, which is why other researchers have had to resort to complicated and often poorly performing methods, such as attaching the cargo to the exterior of nanoparticles, resulting in inefficient protein release and off-target delivery.

The challenge with the new method was that the protein did not want to interact with the interior of the particle, which is made of a fluorous liquid, similar to liquid Teflon. Medina's doctoral student, Janna Sloand, came up with a creative work around -- a fluorous mask. These chemical masks have a counterbalance of polarity and fluorine content that allows the protein to interact with the fluorous liquid medium while maintaining the protein's folded state and bioactivity.

"We had a lot of challenges developing this new method," said Sloand, first author on the paper published recently in ACS Nano. "The most difficult was figuring out what kind of chemicals could mask the protein. That was definitely my eureka moment when I saw that it worked."

In future work, the team will explore the use of their ultrasound-programmable material as a platform for image-guided delivery of therapeutic proteins and gene editing tools.

In related therapeutic applications, they are leveraging this technology to deliver antibodies that can alter abnormal signaling pathways in tumor cells to effectively 'turn-off' their malignant traits. In other work they are delivering gene editing tools, like CRISPR constructs, to enable ultrasound-controlled genome engineering of cells in complex 3D tissue microenvironments.

Importantly, these delivery applications can all be performed using ultrasound techniques already employed in hospitals, which they hope will enable the rapid translation of this technology for precision healthcare.

Current marine protected areas in the Southern Ocean need to be at least doubled to adequately safeguard the biodiversity of the Antarctic, according to a new CU Boulder study published today, Earth Day, in the journal PLOS ONE.

Proposals under consideration by an international council this year would significantly improve the variety of habitats protected, sustain fish populations and enhance the region's resilience to the effects of climate change, the authors say.

"Compared to the rest of the world's oceans, we have some of the healthiest marine systems left in the world in Antarctica," said Cassandra Brooks, author of the new paper and assistant professor in the Environmental Studies Program. "But there are vast areas of the Southern Ocean that are left completely unprotected."

Many international targets suggest that 10 to 30 percent of the world's combined oceans should be protected. The Southern Ocean, which surrounds Antarctica, comprises about 10 percent of the world's oceans, and its protection can play a large role in accomplishing this goal.

At present, almost 12 percent of the Southern Ocean is designated as part of marine protected areas, or MPAs. MPAs - especially "no-take" MPAs, or marine reserves which do not allow any fishing - have been shown to support the abundance and diversity of species.

"But percentages aren't enough," said Brooks. "You want protected areas to be representative of all the different life that's in the Southern Ocean."

The Antarctic region is home to as many as 10,000 species - including whales, seals, penguins, fish, corals and giant Antarctic sea spiders - many of which are found nowhere else in the world. And as far as scientists know, none of them have yet gone extinct from climate change or other human actions.

If additional marine protected areas currently under negotiation by the Convention on the Conservation of Antarctic Marine Living Resources (CCAMLR) are implemented, they would encompass almost 22 percent of the Southern Ocean and achieve at least 10 percent representation of its over 40 unique habitats.

"As marine scientists, it's important we have places left that we can actually study as healthy systems that are undergoing climate stress," said Brooks.

But the Southern Ocean supports international commercial fisheries for Patagonian and Antarctic toothfish, sold as Chilean sea bass, as well as krill, which is farmed for fish meal and omega-3 fatty acid pills. Less than 5 percent of the Southern Ocean's protection bans fishing.

Pressure on these fisheries has increased in recent years and is likely to continue, due to the popularity of omega-3 pills and demand for fish meal - which is fed to pigs, chickens, and other farmed fish. At the same time, climate change pressures on Southern Ocean ecosystems are also increasing.

To help boost the resilience of these ecosystems, "we really need large areas that are off limits to extraction," said Brooks. "Antarctica is a global commons that belongs to all of us."

A system in flux

The importance of the Antarctic cannot be understated. The Southern Ocean stores 90 percent of the world's freshwater, drives global ocean circulation and regulates our entire climate.

"At its most basic level, all Earth's systems depend on the Southern Ocean," said Brooks. "And Antarctica is one of the fastest changing places in the whole world due to climate change. It is impacting the entire ecosystem in ways that we really don't understand yet."

Populations of phytoplankton communities and krill - at the bottom of the food chain - to penguins and toothfish - at the very top - are changing. The whole system is in flux.

Most of these animals cannot migrate or relocate. They're already as far south as they can go.

Building on work from previous studies, Brooks and her co-authors wanted to know: Are we protecting the right areas that actually will conserve biodiversity?

So they looked at the variety of Antarctic ocean habitats, from the seafloor to the open water, and examined what percentage of them rest within existing and proposed protected areas and which ones do not.

They found that for protections to be fully representative of the biodiversity in the Southern Ocean, and better protect many ocean birds and mammals, they would need to be increased even more than protections currently proposed by CCAMLR. This international treaty group of 26 member states is next scheduled to meet in October of 2020.

Adopting these protections would be an important milestone in the right direction, said Brooks.

Over 6,000 languages are currently spoken worldwide, but a substantial minority - well over 5% - are in danger of dying out. It is perhaps surprising that this fraction is no higher, as most models have so far predicted that a minority language will be doomed to extinction once contacts with speakers of the majority language reach a certain level. Statistical physicists Jean-Marc Luck from Université Paris-Saclay, Paris, France and Anita Mehta from the University of Oxford, UK have described, using mathematical modelling, two mechanisms through which this doomsday scenario does not occur, i.e. several languages come to coexist in the same area. This work is now published in EPJ B.

Clearly, some languages will be more popular than others, because, for example, of their universal utility: Luck and Mehta parametrised this by 'attractiveness', which was a key variable in the coupled differential equations they devised to model language competition. Their equations turned out to belong to the class of Lotka-Volterra equations describing the dynamic relationship between predators and their prey.

The authors outlined two possible scenarios leading to language coexistence. The first of these concerns linguistic diversity: in a nation such as India, a regional language can, in a given state, coexist with the national languages spoken by the majority of the country. The second scenario is more subtle, where the coexistence of two or more languages is determined by the internal dynamics of the population of speakers in a given region. The simplest way of explaining this is to say that the dynamics between two competing languages in a single geographical area depends on the degree to which their speakers are mixed.

Luck and Mehta now intend to extend this model to explore the synchronous competition between different forms of past participles and the eventual survival of one, which is an important open problem in linguistics. They continue also to work on other problems in linguistics using the methods of statistical physics, such as the perception of speech.

The mollusc Leptogyra bujnitzkii appeared in a biological collection in Russia thanks to the legendary Arctic drift that began on 23 October 1937. Three icebreaking steamers - Georgiy Sedov, Malygin and Sadko - were beset and drifting in the ice following the sea current in the area of the New Siberian Islands. The same current transports drift-wood from the Siberian rivers towards Greenland. In August 1938, the veteran icebreaker Yermak freed the Sadko and Malygin. However, the Sedov, whose rudder was badly damaged, had to be left in the ice 'as a drifting high-latitude station'. This enforced wintering in the Arctic resulted in many scientific discoveries, included the debunking of the myth about the Sannikov Land.

The discoveries, however, continue to be made today. The last among them has been the discovery of sea snails from the subclass Neomphaliones among the exhibits in the collection compiled by the research expedition of the Sadko. The species description was based on only two specimens raised from a depth of about 3800 metres north of the Laptev Sea. Initially, in 1946, the Russian hydrobiologist Grigory Gorbunov assigned it to the genus Ganesa. Then, in 2003, the mollusc was assigned to the genus Skenea. However, in 2020, the experts' opinion about the rare sea snail unexpectedly changed.

'Last autumn, I wrote a conference paper on small molluscs from the genus Skenea,' recalls Ekaterina Krol. ''Our' mollusc was reiterated as a representative of this genus as well, which appeared questionable to me from the very beginning. The day before my presentation at the conference, when I was finishing the paper, it became clear to me that the shell sculpture does not belong to the genus Ganesa. I started searching for more information about similar molluscs and came across representatives of the Leptogyra genus. Our specimens looked very similar. Then we had to prove their kinship.'

Both syntypes at the disposal of Ekaterina Krol were initially studied with a stereo microscope. After that, one of specimens was coated with silver and studied using a scanning electronic microscope at the Interdisciplinary Resource Centre for Nanotechnology at the St Petersburg University Research Park. The research findings confirmed the hypothesis that the mollusc belongs to the genus Leptogyra.

'Unfortunately, knowledge gaps are a common problem in biology,' notes Ekaterina Krol. 'Besides, we are dealing with extremely small snails - representatives of micromolluscs. Their shells are only about 5 to 6 mm in adult size. Previously, such snails were often mistaken for larval shells. Another reason why the error had occurred is insufficient knowledge of the subclass Neomphaliones at the time of its initial description.'

Interestingly, representatives of the genus Leptogyra inhabit extremely unusual environments. For instance, they live in a type of hydrothermal vents, often referred to as 'black smokers', which are found along the mid-ocean ridges. Another habitat of such molluscs is sunken wood. It must have been there that our two specimens were discovered during the expedition.

'The Leptogyra molluscs use decomposing wood as an energy source. Notably, the decaying wood habitat is a very aggressive environment. It is unsafe for living organisms that are not adapted to it. It would be interesting to find out how closely the organisms living on sunken wood are related to species associated with 'black smokers', because these habitats are very different. Getting the specimens from such depths is a challenge, indeed. Hence, there are very few of them at the researchers' disposal,' explains Ekaterina Krol.

According to the researcher, the study findings can indicate the presence of sunken wood biocenoses in the Arctic Ocean. In other words, there may exist a previously unknown type of marine communities using decaying wood as the main source of energy. The closest communities of this type were previously reported in the northern Atlantic Ocean in the Iceland region.

DALLAS - April 21, 2020 - Immunotherapy drugs that target a protein called programmed death ligand 1 (PD-L1) on the surface of cancer cells have quickly become a mainstay to treat many forms of cancer, often with dramatic results. But exactly how cancer cells turn on this protein was not completely understood. New research by UT Southwestern Medical Center scientists, published online today in Nature Cancer, lays out key pieces of this mechanism. The findings could offer new targets that may further improve how well current cancer immunotherapies work.

Nearly a decade ago, the Food and Drug Administration approved the first drug in a new class of pharmaceuticals called checkpoint inhibitors. These drugs reverse a cloaking mechanism that many types of cancer cells use to avoid being discovered by the immune system, allowing cancer-fighting immune cells called T cells to attack tumors. Blocking the interaction between one of these cloaking proteins, PD-L1, and its receptor on T cell surfaces forms the basis of several pharmaceuticals currently on the market, including nivolumab, pembrolizumab, and atezolizumab.

Although these drugs have made headway in several types of cancer, notably non-small cell lung cancer (NSCLC) - the leading cause of cancer-associated deaths worldwide - how cancer cells overexpress PD-L1 to shield themselves from immune system attack has been a mystery.

To help answer that question, Kathryn A. O’Donnell, Ph.D., an associate professor of molecular biology at UT Southwestern, and her colleagues started by looking broadly at which genes might serve as regulators for manufacturing PD-L1 in NSCLC. Using CRISPR, which acts as molecular scissors to remove specific genes, the researchers individually removed 19,000 genes in a human NSCLC cell line. Then, they used a fluorescent PD-L1 antibody to see which cells had more or less PD-L1. This allowed them to identify genes that normally encourage PD-L1 production, or positive regulators, and those that stymie PD-L1 production, or negative regulators.

Surprisingly, they found that a potent inhibitor for the manufacture of PD-L1 is a gene called UROD, which plays a key role in producing heme. This iron-containing chemical is pivotal for carrying oxygen in red blood cells, but is also broadly necessary in other cells for maintaining normal balance, or homeostasis. To confirm these findings, the researchers used other methods to remove heme in NSCLC cells, which also triggered the lung cancer cells to make more PD-L1 protein. When tumors in which UROD was depleted were implanted into healthy mice, they grew significantly faster than those in mice lacking working immune systems. These findings suggest that by activating PD-L1 production, this gene accelerates cancer by suppressing anti-tumor immunity, O'Donnell says.

Further experiments showed that hampering heme production turned on a pathway called the integrated stress response (ISR) that cells broadly use to deal with diverse stress conditions such as low oxygen, toxins, or nutrient starvation. Under these conditions, NSCLC cells used a specialized mechanism, relying on a protein known as eIF5B, to increase PD-L1 production. Just stimulating cells with this single protein could turn up PD-L1 production, the researchers found, even without tampering with heme synthesis.

By examining a database of genes that are over- or underproduced in various cancers, O'Donnell and her team found that the gene encoding eIF5B is frequently overproduced in lung cancers, and that this overproduction in lung cancer patients was a marker for poor prognosis. "Developing new drugs that specifically target this protein, or other proteins involved in making PD-L1, could help improve the success of immunotherapy drugs currently in use," says O'Donnell, also a member of UT Southwestern's Harold C. Simmons Comprehensive Cancer Center.

"Investigating the relationship between stress responses and immune evasion in cancer will be an important priority for future work," says Shruthy Suresh, Ph.D., a former graduate student researcher and first author of this study.

Other UTSW researchers who contributed to this study include Vanessa Schmid, Sojeong Jun, Michael Peyton, Adwait Amod Sathe, Chao Xing, John D. Minna, Joshua T. Mendell, Yang-Xin Fu, Yang Xie, Guanghua Xiao, Shruthy Suresh, BeiBei Chen, Jingfei Zhu, Changzheng Lu, Xiaowei Zhan, Chelsea M. Karacz, Lin Zhong, Zhuoyu Wen, Ryan Golden, and Bret Evers, plus graduate students Bethany Smith and Nicole Novaresi. Mendell and Golden collaborated with the team on the CRISPR screen.

This research was supported by funding from NCI (R01 CA207763 and P50CA70907, R35CA19731104), Sidney Kimmel Foundation (SKF-15-067), Cancer Prevention and Research Institute of Texas (CPRIT) (R1101 and RP150676), Welch Foundation (I-1881-20180324 and I-1961-20180324), LUNGevity Foundation (2015-03), UTSW Friends of the Comprehensive Cancer Center, and the Howard Hughes Medical Institute.

About UT Southwestern Medical Center

UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution's faculty has received six Nobel Prizes, and includes 22 members of the National Academy of Sciences, 17 members of the National Academy of Medicine, and 14 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 2,500 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in about 80 specialties to more than 105,000 hospitalized patients, nearly 370,000 emergency room cases, and oversee approximately 3 million outpatient visits a year.

Graphene Flagship researchers at RWTH Aachen University, Germany and ONERA-CNRS, France, in collaboration with researchers at the Peter Grunberg Institute, Germany, the University of Versailles, France, and Kansas State University, US, have reported a significant step forward in growing monoisotopic hexagonal boron nitride at atmospheric pressure for the production of large and very high-quality crystals.

Hexagonal boron nitride (hBN) is the unsung hero of graphene-based devices. Much progress over the last decade was enabled by the realisation that 'sandwiching' graphene between two hBN crystals can significantly improve the quality and performance of the resulting devices. This finding paved the way to a series of exciting developments, including the discoveries of exotic effects such as magic-angle superconductivity and proof-of-concept demonstrations of sensors with unrivalled sensitivity.

Until now, the most widely used hBN crystals came from the National Institute of Material Science in Tsukuba, Japan. These crystals are grown using a process at high temperatures (over 1500°C) and extremely high pressures (over 40,000 times atmospheric pressure). "The pioneering contribution by the Japanase researchers Taniguchi and Watanabe to graphene research is invaluable", begins Christoph Stampfer from Graphene Flagship Partner RWTH Aachen University, Germany. "They provide hundreds of labs around the world with ultra-pure hBN at no charge. Without their contribution, a lot of what we are doing today would not be possible."

However, this hBN growth method comes with some limitations. Among them is the small crystal size, which is limited to a few 100 μm, and the complexity of the growth process. This is suitable for fundamental research, but beyond this, a method with better scalability is needed. Now Graphene Flagship researchers tested hBN crystals grown with a new methodology that works at atmospheric pressure, developed by a team of researchers led by James Edgar at Kansas State University, US. This new approach shows great promise for more demanding research and production.

"I was very excited when Edgar proposed that we test the quality of his hBN", says Stampfer. "His growth method could be suitable for large-scale production". The method for growing hBN at atmospheric pressure is indeed much simpler and cheaper than previous alternatives and allows for the isotopic concentration to be controlled.

"The hBN crystals we received were the largest I have ever seen, and they were all based either on isotopically pure boron-10 or boron-11" says Jens Sonntag, a graduate student at Graphene Flagship Partner RWTH Aachen University. Sonntag tested the quality of the flakes first using confocal Raman spectroscopy. In addition, Graphene Flagship partners in ONERA-CNRS, France, led by Annick Loiseau, carried out advanced luminescence measurements. Both measurements indicated high isotope purity and high crystal quality.

However, the strongest evidence for the high hBN qualitycame from transport measurements performed on devices containing graphene sandwiched between monoisotopic hBN. They showed equivalent performance to a state-of-the-art device based on hBN from Japan, with better performance in some areas.

"This is a clear indication of the extremely high quality of these hBN crystals," says Stampfer. "This is great news for the whole graphene community, because it shows that it is, in principle, possible to produce high quality hBN on a large scale, bringing us one step closer to real applications based on high-performance graphene electronics and optoelectronics. Furthermore, the possibility of controlling the isotopic concentration of the crystals opens the door to experiments that were not possible before."

Mar García-Hernández, Work Package Leader for Enabling Materials, adds: "Free-standing graphene, being the thinnest material known, exhibits a large surface area and, therefore, is extremely sensitive to its surrounding environment, which, in turn, results in substantial degradation of its exceptional properties. However, there is a clear strategy to avoid these deleterious effects: encapsulating graphene between two protective layers."

García-Hernández continues: "When graphene is encapsulated by hBN, it reveals its intrinsic properties. This makes hBN an essential material to integrate graphene into current technologies and demonstrates the importance of devising new scalable synthetic routes for large-scale hBN production. This work not only provides a new and simpler path to produce high-quality hBN crystals on a large scale, but it also enables the production of monoisotopic material, which further reduces the degradation of graphene when encapsulated by two layers."

Andrea C. Ferrari, Science and Technology Officer of the Graphene Flagship and Chair of its Management Panel, adds: "This is a nice example of collaboration between the EU and the US, which we fostered via numerous bilateral workshops. Devising alternative approaches to produce high-quality hBN crystals is crucial to enable us to exploit the ultimate properties of graphene in opto-electronics applications. Furthermore, this work will lead to significant progress in fundamental research."

Experts have predicted that the COVID-19 pandemic will result in the worst financial crisis in the United States since the Great Depression. While the full scope of the financial fallout remains to be seen, furloughs, job losses and pay cuts resulting from the outbreak have already hit many people hard, and such financial challenges can put a significant strain on romantic relationships.

Some couples may be better equipped to manage that kind of stress than others, suggests research by Ashley LeBaron, a doctoral student in the University of Arizona Norton School of Family and Consumer Sciences in the College of Agriculture and Life Sciences.

LeBaron, whose research was conducted prior to the COVID-19 pandemic, has studied how financial stress impacts married and unmarried couples from different socioeconomic backgrounds. Her findings provide insight into what might make some couples more resilient.

In 2018, as a student at Brigham Young University, LeBaron co-authored a paper in the Journal of Family and Economic Issues that focused on married couples affected by financial stress during the 2008 recession. She found that some couples reported that their relationships grew stronger not just in spite of, but because of, the financial challenges they had endured together.

However, most of the couples in that study were white, middle- or upper-class married couples.

Now a doctoral student at the University of Arizona, LeBaron set out in a more recent study to see if her previous findings would hold true for people for whom financial stress might have higher stakes - unmarried, low-income couples expecting their first child together.

Most of the couples in the new study, also published in the Journal of Family and Economic Issues, were low-income and black. All of them had experienced at least one of three financial stressors in the year prior: the inability to pay rent or a mortgage in full, having their utilities shut off or eviction.

"Financial stress isn't good for anyone, but for lower-income couples, it can really affect the time and energy and focus they can put on relationships," LeBaron said.

In both of her studies, LeBaron zoomed in on the relationships in which partners remained highly committed to one another after financial hardship.

In both studies, she found that the strongest relationships were those in which partners remembered to practice "relationship maintenance behaviors," including respecting one another, being there for one another, and showing love and affection for one another.

"A big take-home message is the importance of these relationship maintenance behaviors, especially when you're experiencing financial stress," LeBaron said. "It's hard to remember to do that when you're in the middle of financial stress. But making sure that your partner knows that you're there for them, and doing things that show love and affection for them is really important."

LeBaron also found that receiving financial support from family and friends was associated with higher levels of commitment for the couples in both of her studies.

In her second study, LeBaron measured the success of the unmarried, low-income, expectant couples not only by how committed they reported being to their relationship, but also by how well they reported co-parenting.

Some additional factors emerged as important for the low-income unmarried couples that LeBaron didn't see in the married couples. Those factors included having health insurance, having a support network and having children with no more than one partner.

"It can be stressful and financially demanding to have kids with multiple partners," LeBaron said. She added that health insurance didn't emerge as a factor, and wasn't asked about, in the study of married couples.

LeBaron's findings suggest that there may not be a one-size-fits-all approach to maintaining a strong relationship in times of financial stress.

"One of the takeaways for policymakers or therapists is that it really depends on the context of the couple you're trying to help, because something that works for one couple might not work for the other one," she said.

However, it seems that practicing relationship maintenance behaviors can go a long way for any couple, regardless of marital status and financial standing. And it's possible that some romantic relationships may grow stronger not just in spite of, but because of, financial challenges, LeBaron said.

"Financial stressors happen to everyone. They happen more often and to a greater extent to some people than others, but everyone experiences financial stress," LeBaron said. "If they use that stress as a catalyst to make positive changes in the relationship, it can be an opportunity to grow closer together, instead of having that stress tear you apart."

A new green pit viper species of the genus Trimeresurus was discovered during the herpetological expedition to Arunachal Pradesh in India, part of the Himalayan biodiversity hotspot. The scientists named the newly-discovered snake Trimeresurus salazar after a Parselmouth (able to talk with serpents) wizard, co-founder of Hogwarts School of Witchcraft and Wizardry and the founder of the House of Slytherin - Salazar Slytherin, the fictional character of J.K. Rowling's saga "Harry Potter". The discovery, authored by Zeeshan Mirza of the National Centre for Biological Sciences, Bengaluru, Mr. Harshal and Mr. Mandar of the Bombay Natural History Society, Mumbai, Mr. Gowande of Pune's Fergusson College and Mr. Phansalkar of the Wildlife Institute of India, Dehradun, is published in the open-access journal Zoosystematics and Evolution.

The pit vipers in the genus Trimeresurus are charismatic venomous serpents, distributed widely across east and southeast Asia. In total, the genus includes at least 48 species, with fifteen representatives occurring in India. The species belonging to the genus are morphologically cryptic, which makes it difficult to distinguish them in the field. As a result, their real diversity could be underestimated.

Arunachal Pradesh, where the new species was found, belongs to the Himalayan biodiversity hotspot, which explains the diverse flora and fauna being continuously discovered there.

The new green pit viper demonstrates a unique orange to reddish stripe, present on the head and body in males.

Explaining the name of the new species, the scientists suggest that it is colloquially referred to as the Salazar's pit viper.

This is already the second species discovered within the course of the expedition to Arunachal Pradesh, which reflects the poor nature of biodiversity documentation across north-eastern India.

"Future dedicated surveys conducted across northeastern India will help document biodiversity, which is under threat from numerous development activities that include road widening, agriculture, and hydro-electric projects", shares the lead researcher Dr. Zeeshan A. Mirza from National Centre for Biological Science of Bangalore, India.

When looking at a left hand in the mirror, it looks like a right hand. However, the left hand never overlaps the right hand. Such a geometrical relationship that an image of the object in a plane mirror cannot be brought to coincide with itself is called chirality. A clockwise or counterclockwise helical staircase is an example of a chiral structure. On the other hand, a round ball is not chiral since its image in a mirror overlaps the original shape.

The structure of a material which consists of atoms and/or molecules may exhibit chirality. It is known that chiral molecules or chiral crystals show a chiral structure, as exemplified by deoxyribonucleic acid (DNA), amino acids, and sugars. Such chiral substances are inevitable in living activity. However, their electrical and magnetic characteristics have attracted little attention so far.

Recently, it was found by Ron Naaman et al. in Israel that electron spins orient in the same direction when electrons pass through chiral molecules such as DNA. Because the direction of spins depends on the handedness of a chiral molecule structure, this phenomenon is called chirality-induced spin selectivity (CISS).

CISS research clarified that non-magnetic chiral molecules make electrons spin polarized. This phenomenon is very puzzling and its mechanism remains to be clarified. To produce a spin-polarized state in a non-magnetic material is an important research target to promote the next generation electronics and quantum science. It is very interesting to investigate how universal the spin-polarized phenomena are in chiral materials widely found in molecules and crystals.

In this study, the researchers at Osaka Prefecture University, Institute for Molecular Science, The Open University of Japan, and Toho University focused not a chiral molecule but a 'chiral crystal'. The chiral crystal that the researchers have investigated possesses a helical arrangement of atoms twisting in one direction. Such a helical structure appears all over the chiral crystal, as shown in upper panel of Figure. Although molecules are very tiny invisible entities, crystals are large enough to be handled. The crystals also exhibit fabrication feasibility and material stability in usual cases.

A chiral crystal CrNb3S6 used in this study is a metal that conducts electricity well but exhibits no magnetism at room temperature in the absence of magnetic field. However, the experiments clarified that electrons flowing in CrNb3S6 are spin polarized. Namely, the chiral crystal plays a role to make the spins of flowing electrons aligned in the same direction spontaneously.

Applying an electrical current into the coil found in our daily life induces magnetic fields in the coil. This is a macroscopic electromagnet generating macroscopic magnetic fields. A helical atomic configuration found in the crystals plays a role to generate polarized spins. Namely, it behaves as a 'microscopic' electromagnet generating polarized spin in the microscopic tiny world.

This study clarified that spin-polarized phenomena initially found in chiral molecules occur even in chiral solid crystals, suggesting that such phenomena appear universally in a wide range of chiral materials from chiral molecules to chiral crystals. The study made a fundamental and significant contribution to the research field of spin manipulation and detection in combination with chiral systems.

A new study from psychologists at the University of Bath highlights the true impact of heavy drinking on our ability to plan, set goals and make decisions the following day. Published in the Journal of Clinical Medicine, the study provides new evidence as to why hangovers cost the wider economy so much.

A recent report, which involved the same team, found that hangovers cost the UK economy £1.4 billion a year in wasted productivity, including people working while hungover.

The latest study involved thirty-five 18 to 30-year-olds who had reported experiencing a hangover at least once in the past month. Individuals completed measures which assessed their ability to switch attention between tasks, to update and process information from multiple sources and to guide and plan behaviour, whilst experiencing a hangover.

Their findings show how, when hungover, individuals have a reduced ability to retain information in their short-term memory - for example retaining a telephone number whilst taking a message at the same time. They also highlight impairments when it comes to individuals' ability to switch attention between tasks and focus on a goal.

Few studies have explored how hangover effects key cognitive processes, the so-called 'core executive functions', which we use in daily life to plan, set goals and make decisions.

Lead author Craig Gunn of Bath's Department of Psychology explained: "We know that hangovers can have a big economic cost, but we did not know how hangover affects our ability to switch attention from one task to another, update information in our mind, and maintain focus on set goals. Our study asked participants to complete tasks measuring these processes when they had a hangover and again when they had not consumed alcohol. The results suggest that all of these processes are impaired by a hangover, which could have consequences for other aspects of our lives."

Senior author, Dr Sally Adams from the Addiction & Mental Health Group at the University of Bath added: "Anecdotally, we may experience reduced performance of daily tasks when we are hungover such as planning activities and dividing our attention between several tasks. Our data show that this impairment is likely the result of reduced capability in several core executive functions, which are important for tasks such as workplace performance and driving."

The authors suggest these findings could also have important implications during the current lockdown situation. Earlier this month, Alcohol Change UK estimated that 8.6 million adults in the UK were drinking more frequently. Those drinking heavily at home are at increased risk of experiencing a hangover the next day, which may impact their ability and productivity when working at home.

Virtual reality activates brain networks that increase your ability to identify with other people, according to new research published in eNeuro. The technology could become a tool in the treatment of violent offenders to empathize more with others.

Understanding someone's point of view is crucial for successful relationships. When this doesn't come naturally, virtual reality technology may be able to help the process. A first-person perspective virtual reality experience providing multi-sensory feedback can coax the brain into thinking a virtual body is its own body. This causes the brain to react to virtual events as if they are happening in the real world.

de Borst et al. used functional magnetic resonance imaging to monitor the brain activity of participants while they experienced a virtual reality animation of a man verbally abusing a woman, from the perspective of the woman. Before watching the scene, the participants went through virtual reality training embodied as the woman or as a bystander watching the woman. People experiencing the first-person embodiment identified the woman's body as their own and demonstrated synchronized brain activity in the personal space and body ownership networks. They also showed strong synchronized activity in parts of the brain processing threat perception when the man got close.

INDIANAPOLIS -- Putting together research for publication can be a challenging and time-consuming process, heightened even further because of the current COVID-19 situation, during which non-essential labs have been hibernated and many researchers are now working separately and remotely, instead of collaborating within the same space.

Despite those obstacles, Indiana University School of Medicine faculty and Regenstrief Institute research scientists had their research published in Nature Communications on April 14, which is an even more significant feat considering one of the leading authors has been quarantined in Wuhan, China for the last two months of their work.

The team consists of Affiliated Scientist Jie Zhang, PhD, Regenstrief Institute Research Scientist Kun Huang, PhD, both Indiana University School of Medicine faculty members, Jun Cheng, PhD, of Shenzhen University and colleagues including Liang Cheng, M.D. of IU School of Medicine.

The study was led by Dr. Zhang, an assistant professor of medical and molecular genetics at IU School of Medicine. The work focuses on the application of machine learning and image analysis to help researchers distinguish a rare subtype of kidney cancer (translocational renal cell carcinoma, or tRCC) from other subtypes by examining the features of cells and tissues on a microscopic level. Dr. Zhang said the structural similarities have caused a high rate of misdiagnosis. Within this publication, the researchers studied 74 tRCC samples, which constitutes the largest tRCC collection in the world.

"The phenotype of this tRCC looks very much like clear cell renal cell carcinoma, or ccRCC, the most common type of renal cell carcinoma, so it's kind of difficult for pathologists to distinguish between the two," said Dr. Zhang. "To improve that, we tried to use the machine-learning technique, feeding in the digitized pathological image data to the analysis pipeline to train the computer to extract the features related to tRCC. This will help pathologists confirm the case, instead of just relying on their eyes."

The first author of this paper, Dr. Jun Cheng started working with Drs. Zhang and Huang in 2016, while Dr. Jun Cheng was a visiting PhD student from China. He visited for the first time when Drs. Zhang and Huang were researchers at Ohio State University, before they joined IU School of Medicine and Regenstrief Institute, and has also visited them since they transitioned to their current roles. Dr. Jun Cheng is currently an assistant professor at Shenzhen University and had traveled to his hometown of Wuhan for winter vacation.

"I was planning to stay at home for 10 days," said Dr. Jun Cheng. "Three days later, the whole city of Wuhan was in lockdown (due to concerns of COVID-19) and the lockdown lasted for over two months."

The city of Wuhan became the epicenter of the pandemic, with more than 50,000 confirmed cases of COVID-19 among the population of 11 million people. As he was working to revise their publication, Dr. Cheng could not return to his lab at Shenzhen University, since teachers and students who left for vacation weren't allowed to go back due to the pandemic. He only had a laptop at his home, but needed a high-performance computer to conduct data analyses.

"Fortunately, one student in my lab didn't go home and stayed in school during winter vacation," said Dr. Jun Cheng. "She helped boot the computer in my lab and then I did all the experiments on it remotely."

Dr. Jun Cheng also needed to repeat some of the analysis for the revised manuscript, which required a transfer of previously downloaded public data to China from Dr. Huang's lab in Indiana, and it took a week to complete the data transfer.

"It was quite stressful to revise the publication during the quarantine, but finally we made it," said Dr. Jun Cheng.

Dr. Huang described this publication as a true team science effort, involving both internal and international collaborations, both of which he said are essential. Liang Cheng, MD, Virgil Moon Professor of Pathology from IU School of Medicine and one of the corresponding authors in the paper, was able to collect additional tRCC and ccRCC samples within two weeks from a collaborator in Michigan for the additional analysis, which he described as an amazing accomplishment.

"In many cases, we collaborate internationally because there is a huge innovation base that can help with our research," said Dr. Huang, who is also the Director of Data Sciences and Informatics for the IU Precision Health Initiative. "Even in difficult times, as long as we have enough resources and means of communication, we can still carry out collaborative research."

This research focuses on renal cancer based on genetic markers rather than location of the disease. This study was supported in part by the IU Precision Health Initiative.

The city of Wuhan was reopened earlier this month.