Culture

Washington, DC - March 23, 2020 - The number of potential therapeutic options for treatment of COVID-19 is growing. Approaches include blocking SARS-CoV-2 from entering cells, disrupting the virus' replication, antivirals, vaccines, and suppressing overactive immune response.

The research was published in a minireview, and in a short article in Antimicrobial Agents and Chemotherapy, a journal of the American Society for Microbiology. The authors of the former suggest that therapeutic drugs directly targeting SARS-CoV-2 will be most effective.

SARS-CoV-2 is easily transmissible because spike proteins on the virus' surface bind exceptionally efficiently to "angiotensin-converting enzyme 2" (ACE2) on the surfaces of human cells. A pilot clinical trial is underway in patients with severe COVID-19, investigating use of recombinant human ACE2 to act as "decoys" that would attach to spike proteins, disabling SARS-CoV-2's mechanism for entry into human cells.

The most promising antiviral for fighting SARS-CoV-2 is remdesivir. It gets incorporated into nascent viral RNA, where it prevents RNA synthesis, and in turn, further viral replication. Remdesivir inhibited SARS-CoV-2 replication in laboratory studies, and the clinical condition of the first confirmed case of COVID-19 in the U.S. improved following intravenous remdesivir administration. But more data is needed.

Tilarone, a broad spectrum antiviral, may also be active against SARS-CoV-2. This 50-year-old synthetic small molecule is used in some Russian Federation countries and neighboring countries against multiple viruses, including acute respiratory viral infection, influenza and hepatitis. Recent observations suggest tilarone is active against chikungunya virus and MERS-CoV.

While tilarone is approved in Russian Federation countries, it has not been tested for safety and efficacy in studies that meet U.S. Food and Drug Administration standards.

Another approach being researched is the transfusion of blood from recovered patients--which contain antibodies against the virus--into current patients. Due to lack of high quality randomized clinical trials and knowledge of the precise mechanism of action, it is not clear how effective this therapy is. It is used mainly in patients in critical condition. Several clinical trials investigating its effectiveness and safety against COVID-19 are now in progress.

More than fifteen vaccine candidates are being developed around the world, which take different approaches to vaccine design. Experts say vaccine development will take approximately 12-18 months.

Shorter and warmer winters lead to an increase in emissions of methane from northern lakes, according to a new study by scientists in Finland and the US. Longer ice-free periods contribute to increased methane emissions. In Finland, emissions of methane from lakes could go up by as much as 60%.

An international study by scientists from Purdue University in the US, the University of Eastern Finland, the Finnish Environment Institute and the University of Helsinki published in Environmental Research Letters significantly enhances our current knowledge of methane emissions from boreal lakes. The backbone of the study is a large dataset on the distribution and characteristics of lakes and their methane emissions in Finland. Using this dataset and modelling tools, the scientists aimed to find out how methane emissions from northern lakes will change towards the end of this century as a result of global warming.

Lakes account for about 10% of the boreal landscape and are, globally, responsible for approximately 30% of biogenic methane emissions that have been found to increase under changing climate conditions. However, the quantification of this climate-sensitive methane source is fraught with large uncertainty under warming climate conditions. Only a few studies have addressed the mechanisms of climate impact on methane emissions from northern lakes.

The authors estimated that the total current diffusive emission from Finnish lakes is 0.12±0.03 Tg CH4 yr-1 and will increase by 26-59% by the end of this century, depending on the warming scenario used. The study showed that while the warming of lake water and sediments plays a vital role, the increase in the length of the ice-free period is a key factor increasing methane emissions in the future.

"The boreal lakes remain a significant methane source under the warming climate within this century, and the increase in methane emissions depends on latitude: the increase is greater from the lower latitude northern lakes," Dr Narasinha Shurpali from the University of Eastern Finland and Dr Pirkko Kortelainen from the Finnish Environment Institute point out.

"The study shows the importance of co-operation between modellers and experimentalists. Here the representative dataset on lakes and their methane emissions was produced by the Finnish Environment Institute and the universities, enabling biogeochemical modelling to estimate the present and future methane emissions from lakes," Professor Pertti Martikainen from the University of Eastern Finland notes.

COLUMBUS, Ohio - Scientists have found a way in the laboratory to shorten the time it takes to create a key chemical used to synthesize a variety of medications, fertilizers and other important substances.

The finding could make a number of industrial manufacturing processes cheaper and more efficient. And all it takes, essentially, is electrifying an aluminum container that includes the right chemicals.

In a study recently published in the Journal of the American Chemical Society, the research team described how to shorten a process to turn one chemical - triphenylphosphine oxide - into another chemical - triphenylphosphine. Triphenylphosphine is an important chemical for the manufacturing of materials that improve farming or can be used as pharmaceuticals.

"It might make it easier or cheaper to produce certain medications, materials, agrochemicals - essentially all organic synthesis," said Christo Sevov, an assistant professor of chemistry at The Ohio State University and senior author of the study.

Manufacturers already are making this conversion happen, but the process by which they do it is lengthy and expensive. The process also uses a substance, phosgene, that is toxic to humans.

"Nobody wants to use phosgene - it's incredibly toxic - but you need to use it in order to reactivate the chemicals - and you need a lot of it," Sevov said. Phosgene is a high-energy chemical; that high energy is necessary to convert triphenylphosphine oxide to triphenylphosphine, he said.

The current conversion process also produces carbon dioxide - something chemists have been trying to figure out how to limit.

The study published by Sevov and his research group shows that the energy needed to allow that conversion can happen by sending an electrical charge through an aluminum container. Doing so provides enough energy to allow aluminum to break one of the chemical bonds in triphenylphosphine oxide - essentially, to strip oxygen away from that molecule - and to leave behind just triphenylphosphine.

"We just cut the top off an aluminum soda can and poured everything we needed in there. Then we clipped a couple of electrical leads to the wall of the can and then that was the electricity we needed to make the conversions," Sevov said.

Chemists have been trying for decades to shorten this conversion process and to find a way to achieve the conversion without using toxic chemicals. Sevov's research group, which studies the interactions between electricity and chemicals, discovered this shortcut almost by accident, while working on another experiment.

Shuhei Manabe, a researcher in Sevov's lab, noted that introducing aluminum and electricity allowed the team to convert one chemical to the other with very little waste.

Sevov said the simplicity of that process was surprising to the whole research team.

"Usually, you get a whole mess of byproducts when you convert one to the other - that's why nobody does this in a single step," he said. "And it's really the steps in the conversion process that make things expensive. If you can cut steps, that makes the final product much cheaper."

As cities physically expanded worldwide between 1970 and 2010, the population in those cities became less dense, according to a study led by a Texas A&M university professor.

Researchers found the trend was driven by small- and medium-sized cities, particularly in India, China, North America and Europe. Burak Güneralp, assistant professor in the Department of Geography at Texas A&M, Billy Hales, a doctoral student in the same department, and colleagues from Yale University and Arizona State University examined these changes in a study published in Environmental Research Letters.

More than 60 percent of the reported urban expansion was formerly agricultural land, the researchers estimated.

"If urban population densities had remained unchanged since 1970, more than 48,000 square miles (roughly the size of North Carolina) would have been saved from conversion to urban and instead could have remained in cultivation or as natural vegetation," Güneralp said.

He said decreases in urban population densities present several problems. Loss of fertile lands at the outskirts of growing cities caused by decreasing urban population densities is of serious concern in China, India and Nigeria, Güneralp said.

"These three countries are expected to account for more than a third of the projected increase in the world's urban population by 2050," he said. "They also still have many millions of small farmers earning their livelihoods working fertile lands on the outskirts of cities. Thus, any loss of these high-quality lands to urban expansion has huge implications for the livelihoods of these farmers."

This is "especially disconcerting" for India, he said, with about half of its land classified as "degraded" while the country had the steepest decreases in urban land-use efficiency from 1970 to 2010. India has the world's largest rural population.

"Our findings suggest that decreasing urban population densities in India and Nigeria since 1970 caused 85 percent and 30 percent more land, respectively, to be converted to urban," Güneralp said.

A decrease in density as cities grow outward also puts pressure on local and regional governments to provide adequate infrastructure such as water, transportation and housing to formerly rural areas, he said.

The researchers found that these trends are the strongest in small- and medium-sized urban centers, defined in the study as those with fewer than 2 million people.

"Furthermore, small-medium cities in India, China, Southeast Asia, Africa and Europe are following in the footsteps of the United States in declines in urban population densities," he said. "These findings are important because, globally, it is these small-medium sized cities with limited institutional and financial capacity that are growing the fastest."

The U.S. had the lowest urban population densities across all four decades the researchers looked at, which led to many of the same problems seen in other countries.

"Such low density development whether in the U.S. or anywhere else generally means inefficient use of resources," Güneralp said.

Güneralp said the findings are relevant to one of the Sustainable Development Goals of the United Nations', SDG11, which was established specifically to measure progress around the world toward making cities and communities more sustainable.

"It is important for urban areas to attain densities that would both improve living conditions in urban landscapes and promote efficient use of resources including land," he said.

(Boston)--Physician gender pay gaps continue to persist in the U.S. despite an impressive body of research spanning more than 25 years. While men have a larger representation within academic medical leadership, a new study publish in JAMA Network Open has found that women are significantly overrepresented as the authors and disseminators of physician compensation studies and this research is largely unfunded.

A multidisciplinary team of researchers led by Boston University School of Medicine (BUSM) and Harvard University examined multiple areas of medicine including surgery, critical care and infectious disease, physical medicine and rehabilitation, dermatology, psychiatry, interventional radiology and pediatric emergency medicine.

"If compensation studies are unfunded and if women are more engaged than men in the pay equity issue, these factors may contribute to slow progress in addressing compensation disparities," explained corresponding author Allison R. Larson, MD, MS, associate professor of dermatology at BUSM.

"This study supports the idea that women physicians and scientists may be considerably more knowledgeable about and engaged in solving gender disparities than male colleagues, but because of a dearth of women in top leadership roles they have less power to do so," added senior author, Julie K. Silver, MD, associate professor and associate chair of the department of physical medicine and rehabilitation at Harvard Medical School.

In 2019, the average male doctor made $258,000 per year, while the average female physician earned $207,000--25 percent less. The pay gap among specialists was larger, but narrowed slightly, from 36 percent in 2018 to 33 percent in 2019.

Researchers searched the literature for physician compensation studies (including salary, income, industry payments and Medicare reimbursements) that included data on gender differences. They then analyzed the genders of the authors of these studies as well as the genders of authors of articles citing these studies and individuals who disseminated the studies on Twitter. They found that women made up the majority of study authors, citation authors and Twitter disseminators. In terms of funding, more than half of these studies were unfunded.

According to the researchers, equity and diversity in the physician workforce are a priority as they have implications for patient care. "Based on our findings, women may be more engaged and knowledgeable about pay disparities while men are disproportionately represented in medical school and hospital leadership, and thus are better positioned to fix disparities.

Additionally, if women are primarily producing this mostly unfunded research, they are doing so largely at the expense of additional income in the form of clinical revenue and without appropriate academic credit for promotions in the form of grant funding," added Larson, a dermatologist at Boston Medical Center.

The researchers believe all healthcare leaders need to actively engage in fixing pay disparities and grant funding organizations should make these studies a priority.

A global research effort

'There is broad agreement on the importance of academic freedom, yet we have strikingly little knowledge about global or country-level trends,' says Prof. Kinzelbach, Professor for International Politics of Human Rights. 'This is why we decided to assess academic freedom worldwide and across time.'

The Academic Freedom Index (AFi) attempts to fill an important gap in knowledge and promote academic freedom as a fundamental principle of higher education and scientific research. Prof. Kinzelbach developed the project and a series of indicators in close coordination with the Global Public Policy Institute in Berlin and with the Scholars at Risk Network in New York. The V-Dem Institute in Gothenburg managed the data collection. '1810 scholars from around the globe contributed to the new index by answering an expert survey, spanning the years 1900-2019,' explains Prof. Dr. Anna Lührmann, who is deputy director of the V-Dem Institute. 'We vetted and aggregated this data using our tested and award-winning statistical model.'

Indicators of academic freedom

AFi provides near global, time-series data on national levels of academic freedom. It includes five indicators, each measuring a different dimension of academic freedom: freedom to research and teach, freedom of academic exchange and dissemination, institutional autonomy, campus integrity, and freedom of academic and cultural expression. An online tool hosted by the V-Dem Institute provides easy access to the data. The tool allows researchers, policy-makers, advocates, students or others to analyse the various indicators, and compare trends across states and regions. The AFi opens up a wide variety of opportunities for research as well as for informing debates and enhancing decision-making by key stakeholders in both higher education and government.

'The new data not only helps us to examine where and why infringements of academic freedom occur, but also ways of strengthening academic freedom,' explains Prof. Kinzelbach. 'For example, we can show that countries where universities enjoy high institutional autonomy also tend to respect the freedom to research and teach. Further research into the data can open important doors for advocates of academic freedom around the world.'

Challenging university rankings

AFi is the result of a unique collaboration between scholars, an advocacy organisation and a think tank. 'Our aim is to modify incentive structures for universities and governments to make genuine respect for academic freedom a priority,' says Janika Spannagel from the Global Public Policy Institute (GPPi) in Berlin. 'By providing data on the state of academic freedom worldwide, we aim to bring a rights and freedoms perspective into international debates on the quality, reputation and governance of higher education.' This should also call into question existing university rankings, which purport to measure 'excellence', without adequately considering academic freedom. 'We hope that academics, students, university management, research funders, governments, and other higher education stakeholders will use the Academic Freedom Index to enhance monitoring systems, make better informed decisions, and to strengthen concrete safeguards for academic freedom,' adds her colleague Ilyas Saliba, also from GPPi. For example, funders and universities could require the submission of risk mitigation strategies with research and partnership proposals that foresee activities in repressive settings.

Robert Quinn, Executive Director of the Scholars at Risk Network, agrees that the AFi data demands international attention and calls for better safeguards. 'We need an Academic Freedom Index to understand trends over time and we must act on the findings. For too long now, governments and universities have lacked the data to measure and promote academic freedom,' says Quinn. 'I am extremely pleased that we now have a global dataset, which was produced by academics themselves in a collaborative, international effort,' says Quinn. 'We must now use it to defend historical advances, push back against contemporary pressures on free academia, and nurture higher education values. The Academic Freedom Index will help us to do so.'

The index and all disaggregated indicators will be updated annually.

Full global coverage will be reached by spring 2021.

Ithaca, NY--According to a new study, Zebra Finches exposed to low levels of environmental PCBs as nestlings show changes in breeding behavior as adults. The study published in the journal PLoS ONE was conducted by scientists at the Cornell Lab of Ornithology. Though polychlorinated biphenyls, or PCBs, were banned in 1979, they still contaminate the environment because of improper disposal.

"Decades of work has shown that high levels of PCB-exposure can be toxic and carcinogenic, but less is known about low levels of PCB exposure," explains lead author Sara DeLeon, who conducted the research as part of her doctoral studies at Cornell University. "PCBs are endocrine disruptors, meaning that even very low levels could be mimicking the effects of hormones, and potentially influencing behavior."

The researchers investigated the effects of two kinds of PCBs used by industry. Nestling Zebra Finches were exposed to low levels of PCBs for seven days to mimic exposure to contaminated food that parent birds in the wild would deliver to their young.

"Our results show that this level of PCB exposure during nestling development does have consequences on adult reproductive behavior," says DeLeon. "Male Zebra Finches exposed to PCBs during development sang fewer syllables as adults. Depending on the type of PCB treatment, some finches made more nesting attempts and also abandoned nests more often."

Some young fledged significantly earlier than normal. DeLeon says these results are likely the result of increased aggression between males.

"Our findings suggest that sub-lethal PCB-exposure during development can change key reproductive characteristics of adult Zebra Finches, likely reducing fitness in the wild," concludes DeLeon.

Washington, DC - March 20, 2020 - SARS-CoV-2, the virus that causes COVID-19 disease is more transmissible, but has a lower mortality rate than its sibling, SARS-CoV, according to a review article published this week in Antimicrobial Agents and Chemotherapy, a journal of the American Society for Microbiology.

In humans, coronaviruses cause mainly respiratory infections. Individuals with SARS-CoV-2 may remain asymptomatic for 2 to 14 days post-infection and some individuals likely transmit the virus without developing disease symptoms.

So far, the most promising compound for treating COVID-19 is the antiviral, remdesivir. It is currently in clinical trials for treating Ebola virus infections.

Remdesivir was recently tested in a non-human primate model of MERS-CoV infection. Prophylactic treatment 24 hours prior to inoculation prevented MERS-CoV from causing clinical disease and inhibited viral replication in lung tissues, preventing formation of lung lesions. Initiation of treatment 12 hours after virus inoculation was similarly effective.

Remdesivir has also shown effectiveness against a wide range of coronaviruses. It has already undergone safety testing in clinical trials for Ebola, thereby reducing the time that would be necessary for conducting clinical trials for SARS-CoV-2.

Nonetheless, much work needs to be done to gain a better understanding of the mechanics of SARS-CoV-2. For example, understanding how SARS-CoV-2 interacts with the host ACE2 receptor--by which SARS-CoV-2 gains entry into the host (whether human or animal)--might reveal how this virus overcame the species barrier between animals and humans. This could also lead to design of new antivirals.

Although coronaviruses are common in bats, no direct animal source of the epidemic has been identified to date, according to the report. "It is critical to identify the intermediate species to stop the current spread and to prevent future human SARS-related coronavirus epidemics," the researchers write.

Research published in the journal Microbiology has found that a unique type of algae, usually only seen on the shells of turtles, affects the surrounding microbial communities.

It is hoped that these findings can be applied to support the conservation of turtles. Previous research has shown that a diverse microbiome can protect animals against infections.

The research aimed to understand how the microbiome - a complex community of micro-organisms - varies around the body of Krefft's river turtles. Samples were assessed from inside the mouth, the top of the head and parts of the shells of six turtles collected from Ross River in Queensland, Australia.

The research team, based at the University of New England and James Cook University, then used a technique called high-throughput sequencingto identify which micro-organisms were present on the turtles, using DNA sequencing to determine which bacteria are present, and their abundance.

Previous research has shown that animals in captivity often have less diverse microbiomes, which could affect their long-term health. Dr Donald McKnight, who led the research, said: "Successful conservation efforts inherently require a thorough understanding of an organism's ecology, and we are increasingly realising that microbiomes are a really important part of host ecology. So, filling that gap in our knowledge is important, particularly for animals like turtles.

"Turtles are one of the most imperilled groups of animals. Nearly two-thirds of all turtle species are either threatened or endangered, and efforts to conserve them often involve breeding turtles in captivity or collecting eggs from wild turtles and raising them in captivity until they are large enough to be released. Studies on other animals have, however, shown that captivity can alter the microbiome."

The results showed that the microbiome of the turtles' shells varied, depending on whether algae was present. "It is really interesting that even something like the presence of algae can affect the microbiome" said Dr McKnight. "The algae on turtle's shells is fascinating. It's actually a unique genus that grows almost exclusively on turtles."

The algae seen on turtles' shells has many important roles, including providing camouflage and acting as a home for small crustaceans and dispersing seeds. "Our study adds to those roles by showing that algae also affects the microbiome. The mechanism through which it affects the microbiome isn't clear yet, but there are several possibilities. For example, it might compete with some bacteria in order to access the turtles' shells. It may also provide a habitat for bacteria that don't grow well on just the shell itself. Another possibility is that it could retain moisture while turtles bask, and that could affect which species of bacteria grow well. Our study is just an early step in understanding turtle microbiomes, but hopefully future work will build on it and test some of these possibilities." said Dr McKnight.

It is important to understand what the microbiome looks like on all parts of the turtle, according to Dr McKnight. He said, "Studies on other animals, including humans, have often found that different parts of the body have different microbiomes. So, it makes sense that this would be true for turtles as well, but it is still really important to test these things rather making assumptions

"We don't really know how this affects the success of efforts to conserve turtles by raising them in captivity and releasing them, but it could be an important part of the puzzle. Our study contributes to this by documenting the microbiomes of wild turtles, so that we have a baseline to compare to. More studies are needed to look at whether captivity affects microbiomes in turtles and how those shifts affect conservation."

Dr McKnight hopes to continue to research turtle microbiomes: "We are in the early stages of looking at how various environmental and demographic factors affect turtle microbiomes. For example, we want to see if they shift seasonally, if diet affects them, and if different ages and sexes have different microbiomes."

As scientists scramble to learn more about the SARS-CoV-2 coronavirus, two recent studies of the virus' genome reached controversial conclusions: namely, that snakes are intermediate hosts of the new virus, and that a key coronavirus protein shares "uncanny similarities" with an HIV-1 protein. Now, a study in ACS' Journal of Proteome Research refutes both ideas and suggests that scaly, anteater-like animals called pangolins are the missing link for SARS-CoV-2 transmission between bats and humans.

Understanding where SARS-CoV-2 -- the virus that caused the COVID-19 pandemic ¬-- came from and how it spreads is important for its control and treatment. Most experts agree that bats are a natural reservoir of SARS-CoV-2, but an intermediate host was needed for it to jump from bats to humans. A recent study that analyzed the new virus' genome suggested snakes as this host, despite the fact that coronaviruses are only known to infect mammals and birds. Meanwhile, an unrelated study compared the sequence of the spike protein -- a key protein responsible for getting the virus into mammalian cells -- of the new coronavirus to that of HIV-1, noting unexpected similarities. Although the authors withdrew this preprint manuscript after scientific criticism, it spawned rumors and conspiracy theories that the new coronavirus could have been engineered in a lab. Yang Zhang and colleagues wanted to conduct a more careful and complete analysis of SARS-CoV-2 DNA and protein sequences to resolve these issues.

Compared to the previous studies, the researchers used larger data sets and newer, more accurate bioinformatics methods and databases to analyze the SARS-CoV-2 genome. They found that, in contrast to the claim that four regions of the spike protein were uniquely shared between SARS-CoV-2 and HIV-1, the four sequence segments could be found in other viruses, including bat coronavirus. After uncovering an error in the analysis that suggested snakes as an intermediate host, the team searched DNA and protein sequences isolated from pangolin tissues for ones similar to SARS-CoV-2. The researchers identified protein sequences in sick animals' lungs that were 91% identical to the human virus' proteins. Moreover, the receptor binding domain of the spike protein from the pangolin coronavirus had only five amino acid differences from SARS-CoV-2, compared with 19 differences between the human and bat viral proteins. This evidence points to the pangolin as the most likely intermediate host for the new coronavirus, but additional intermediate hosts could be possible, the researchers say.

Maintaining vitamin D receptor (VDR) levels in pancreatic cells that synthesize and secrete insulin (β cells) could contribute to protecting against the development of diabetes and counteract pancreatic cell damage caused by the progression of the disease. This is suggested by a study conducted by researchers of the CIBER's area of Diabetes and Associated Metabolic Diseases (CIBERDEM) at the Universitat Autònoma de Barcelona (UAB), which points to this receptor as a potential therapeutic target in the prevention and treatment of the disease.

Vitamin D deficiency has been associated with a greater prevalence of both type 1 (T1D) and type 2 (T2D) diabetes, and the relation of this disease with variations in the vitamin D receptor gene has also been described. Nevertheless, the specific participation of this vitamin receptor in the development of the disease, specifically in the β cells, continues to be unknown. That is why this new study has focused its efforts on understanding the role played by the VDR of these pancreatic cells in the development of diabetes, by analyzing its behavior in mice.

Decreased VDR Expression in Diabetics

Researchers observed lower VDR expression in the pancreatic islets of mice with both type 1 and type 2 diabetes. In addition, they also demonstrated that the overexpression of VDR in β cells of diabetic mice counteracted the disease, while at the same time proving that sustained levels of vitamin D receptors in these cells could preserve their mass and function and protect against diabetes.

These results suggest that maintaining VDR expression could be essential in counteracting damage to β cells and protect against the development of the disease. "Sustained VDR levels protected transgenic mice from developing severe hyperglycemia, partially preserving the mass of β cells, thereby reducing local inflammation and diabetes", explains Alba Casellas, CIBERDEM researcher at the Centre for Animal Biotechnology and Gene Therapy (CBATEG) at the Universitat Autònoma de Barcelona and coordinator of the study. She goes on to say that, "all of this reveals an unprecedented role of the vitamin D receptor in the pathophysiology of diabetes".

Glucose Stimulates the Vitamin D Receptor

The researchers also confirmed that VDR expression was negatively correlated with circulating sugar levels, i.e., glucose stimulates VDR: "Unexpectedly, we demonstrated that the vitamin D receptor decreases when circulating glucose levels are physiologically low, such as after fasting". In relating this to the characteristics of pancreatic cells in diabetic individuals, what stood out was that "these results could be explained due to the fact that diabetes is associated with low intracellular glucose levels".

Usefulness of Vitamin D in Treating Diabetes

Although the benefits of supplementing with vitamin D as a way to prevent diabetes have been widely reported, clinical data on its effectiveness in improving the state of diabetes are controversial. "Discrepancies in the effectiveness of vitamin D supplements can be due to the negative regulation of the VDR during diabetes", Dr Casellas points out in view of these results.

Therefore, the authors suggest that to achieve positive results, the dosage regimen of vitamin D supplementation must be scheduled in the absence of VDR expression decrease. "Therefore, future strategies for the treatment of diabetes should be based on better knowledge of the mechanisms subjacent to the negative regulation of VDR during diabetes and focus on restoring VDR levels", they conclude.

Most ovarian cancer starts in fallopian tubes. Then it sloughs from its site of origin and floats around in fluid until finding new sites of attachment. It's not easy for cancer cells to survive away from their moorings. Observations by ovarian cancer doctors at University of Colorado Cancer Center and elsewhere hint at how they might do it: These doctors have seen that ovarian cancer cells often collect in tissues with high fat content. Could these cells be somehow using fat to survive the journey from their point of origin to their sites of growth?

Benjamin Bitler, PhD, and CU Cancer Center colleagues asked this question at a molecular level. The work now results in a study published in the journal Molecular Cancer Research showing that when these ovarian cancer cells become detached from their point of origin, they shift to using fats as an energy source. Bitler and colleagues also show how these cells make the shift: The enzyme CPT1A may control how much fat these cancer cells can burn, suggesting that limiting these cells' access to CPT1A may starve them of the resources they need to spread.

"When they break off, they metabolically shift to use fats more - it allows these cells to survive and then they seek out or are able to colonize fatty tissue. It looked like CPT1A was the rate-limiting step in their ability to do this," says Bitler, who is also an assistant professor in the CU School of Medicine Department of Obstetrics & Gynecology.

Interestingly, Bitler was in a serendipitous position to delve deeper into the role of CPT1A in ovarian cancer dissemination. That's because one of the world's experts on this enzyme happens to work on the same campus. The laboratory of Isabel Schlaepfer, PhD, had been working with funding from the American Cancer Society to explore the role of CPT1A in the progression of prostate cancer.

"With Isabel's lab, we were able to demonstrate that, yes, the cells become more dependent on fatty acids to survive the attachment-free environment. For example, we showed that by adding fatty acids to a model of ovarian cancer cells in suspension, we could prevent these cells from dying," Bitler says.

Likewise (and oppositely), the group was also able to show that by knocking down CPT1A, they could keep ovarian cancer cells from spreading in cell-culture studies and slow the spread of human cancer cells grown in mouse models.

"It didn't completely abolish ovarian cancer cells' capacity to go to fat-rich sites, but it reduced it pretty dramatically," he says.

Not only was Bitler able to work with Schlaepfer on better understanding the role of CPT1A on the spread of ovarian cancer cells, but he is now working with another on-campus collaborator, Brad Corr, MD, to bring this strategy to patients who need it.

"There's a drug called etomoxir that inhibits CPT1A and has been tested as a preventative for congestive heart failure," Bitler says. Clinical trials of preventive medicines have a very low tolerance for side-effects, and in the case of etomoxir with congestive heart failure, the risks outweighed the benefits. But in the context of treating cancer, Bitler suggests that the drug's risk would be well within (and even much less than) risks of existing medicines.

"We are working with Brad [Corr] to move forward with this. The question is where exactly to put etomoxir with respect to patient treatment," Bitler says. He explains that a major issue in the treatment of ovarian cancer is the disease's ability to resist chemotherapy. "The cells we've been studying resist cell death because they need to disseminate. Avoiding cell death is at the heart of chemoresistance as well," he says.

The funding from the American Cancer Society to first author, Brandon Sawyer, MD, played an important role in the development of this study and has resulted in additional grants submitted to the National Institutes of Health with the goal of bringing this promising strategy from the laboratory to the clinic.

"Our hope is that we could use etomoxir to treat chemo-resistant disease," Bitler says.

ITHACA, N.Y. - Cornell University astronomers have created five models representing key points from our planet's evolution, like chemical snapshots through Earth's own geologic epochs.

The models will be spectral templates for astronomers to use in the approaching new era of powerful telescopes, and in the hunt for Earth-like planets in distant solar systems.

"These new generation of space- and ground-based telescopes coupled with our models will allow us to identify planets like our Earth out to about 50 to 100 light-years away," said Lisa Kaltenegger, associate professor of astronomy and director of the Carl Sagan Institute.

For the research and model development, Kaltenegger, doctoral student Jack Madden and Zifan Lin authored "High-Resolution Transmission Spectra of Earth through Geological Time," published in Astrophysical Journal Letters.

"Using our own Earth as the key, we modeled five distinct Earth epochs to provide a template for how we can characterize a potential exo-Earth - from a young, prebiotic Earth to our modern world," she said. "The models also allow us to explore at what point in Earth's evolution a distant observer could identify life on the universe's 'pale blue dots' and other worlds like them."

Kaltenegger and her team created atmospheric models that match the Earth of 3.9 billion years ago, a prebiotic Earth, when carbon dioxide densely cloaked the young planet. A second throwback model chemically depicts a planet free of oxygen, an anoxic Earth, going back 3.5 billion years. Three other models reveal the rise of oxygen in the atmosphere from a 0.2% concentration to modern-day levels of 21%.

"Our Earth and the air we breathe have changed drastically since Earth formed 4.5 billions years ago," Kaltenegger said, "and for the first time, this paper addresses how astronomers trying to find worlds like ours, could spot young to modern Earth-like planets in transit, using our own Earth's history as a template."

In Earth's history, the timeline of the rise of oxygen and its abundancy is not clear, Kaltenegger said. But, if astronomers can find exoplanets with nearly 1% of Earth's current oxygen levels, those scientists will begin to find emerging biology, ozone and methane - and can match it to ages of the Earth templates.

"Our transmission spectra show atmospheric features, which would show a remote observer that Earth had a biosphere as early as about 2 billion years ago," Kaltenegger said.

Using forthcoming telescopes like NASA's James Webb Space Telescope, scheduled to launch in March 2021, or the Extremely Large Telescope in Antofagasta, Chile, scheduled for first light in 2025, astronomers could watch as an exoplanet transits in front of its host star, revealing the planet's atmosphere.

"Once the exoplanet transits and blocks out part of its host star, we can decipher its atmospheric spectral signatures," Kaltenegger said. "Using Earth's geologic history as a key, we can more easily spot the chemical signs of life on the distant exoplanets."

The cerebral cortex is the relatively thin, folded, outer "gray matter" layer of the brain crucial for thinking, information processing, memory, and attention. Not much has been revealed about the genetic underpinnings that influence the size of the cortex's surface area and its thickness, both of which have previously been linked to various psychiatric traits, including schizophrenia, bipolar disorder, depression, attention deficit hyperactivity disorder (ADHD), and autism.

Now, for the first time, more 360 scientists from 184 different institutions - including UNC-Chapel Hill - have contributed to a global effort to find more than 200 regions of the genome and more than 300 specific genetic variations that affect the structure of the cerebral cortex and likely play important roles in psychiatric and neurological conditions.

The study, published in Science, was led by co-senior authors Jason Stein, PhD, assistant professor in the Department of Genetics at the UNC School of Medicine; Sarah Medland, PhD, senior research fellow at the QIMR Berghofer Medical Research Institute in Australia; and Paul Thompson, PhD, associate director of the Mark and Mary Stevens Neuroimaging and Informatics Institute at the University of Southern California. Ten years ago, these scientists cofounded the ENIGMA Consortium, an international research network that has brought together hundreds of imaging genomics researchers to understand brain structure, function, and disease based on brain imaging and genetic data.

"This study was only possible due to a huge scientific collaboration of more than 60 sites involved in MRI scanning and genotyping participants," Stein said. "This study is the crown jewel of the ENIGMA Consortium, so far."

The researchers studied MRI scans and DNA from more than 50,000 people to identify 306 genetic variants that influence brain structure in order to shed light on how genetics contribute to differences in the cerebral cortex of individuals. Genetic variants or variations are simply the slight genetic differences that make us unique. Generally speaking, some variants contribute to differences such as hair color or blood type. Some are involved in diseases. Most of the millions of genetic variants, though, have no known significance. This is why pinpointing genetic variants associated with cortex size and structure is a big deal. Stein and colleagues consider their new genetic roadmap of the brain a sort of "Rosetta stone" that will help translate how some genes impact physical brain structure and neurological consequences for individuals.

Among the findings of the research published in Science:

Some genetic variants are associated with cortical folding, measured as surface area, while other genetic variants are associated with the thickness of the cortex.

Genes that determine surface area are related to very early development in the fetal cortex, while thickness appears to be driven by genes active in the adult cortex.

People at genetic risk for depression or insomnia are genetically inclined toward having lower surface area, while people with a genetic risk for Parkinson's disease tend to have higher surface area.

The vast scale of the project allowed the discovery of specific genes that drive brain development and aging in people worldwide.

"Most of our previous understanding of genes affecting the brain are from model systems, like mice," Stein said. "With mice, we can find genes, knock out genes, or over express genes to see how they influence the structure or function of the brain. But there are a couple of problems with this."

One problem is, quite simply, a mouse is not a human. There are many human-specific features that scientists can only study in the human brain.

"The genetic basis for a mouse is very different than the genetic basis for humans," Stein said, "especially in in the noncoding regions of the genome."

Genes contain DNA, the basic human code that, when translated into action, creates proteins that "do" things, such as help your finger muscles type or your heart beat or your liver process toxins. But only about 3 percent of the human genome codes for proteins. The vast majority of the human genome is called the noncoding genome. Much of this region is not shared between mice and humans. This noncoding genome consists of tiny molecular switches that can modulate the expression of other genes. These switches don't directly alter the function of a protein, but they can affect the amounts of a protein that is expressed. Turns out, most genetic variants associated with psychiatric disorders are found in the noncoding region of the genome.

These findings can now be a resource for scientists to help answer important questions about the genetic influences on the brain and how they relate to numerous conditions.

AURORA, Colo. (March 26, 2020) - Assessing adverse childhood experiences and current anxiety and depression symptoms may help ease cognitive distress in women who have undergone a surgical menopause for cancer risk-reduction, or RRSO, according to a new study published in Menopause.

Researchers, including Dr. Neill Epperson of the University of Colorado Anschutz Medical Campus, remotely collected extensive cognitive data from women across the nation. 552 women who are BRCA1 and BRCA2 mutation carriers and have undergone RRSO completed the assessments, which measured executive function (a cognitive process that allows individuals to manage information in a planful versus reactive manner), exposure to early life stress, and mood symptoms.

Results show that adverse childhood experiences (ACE) were associated with more severe symptoms of executive dysfunction and worse performances on cognitive tasks post-surgical menopause. Changes in mood, such as anxiety and depressive symptoms, partially mediated ACE associations on subjective and objective measures of executive function. These findings indicate that assessing history of childhood adversity and current anxiety and depression symptoms may help to identify women who will experience executive cognitive complaints after surgical menopause.

This research emphasizes the importance of considering psychological state during other medical procedures. "We can't change the past for women who have experienced serious childhood adversities such as abuse, neglect, divorce, parental substance abuse, or exposure to domestic violence, but we can identify a patient population that is easily assessed for these ACEs as well as current negative mood symptoms," said Epperson, study lead investigator and professor and Chair of psychiatry at the University of Colorado School of Medicine. "Our hope is that assessment of childhood adversity and history of depression and anxiety would become part of the pre-surgical risk-benefit discussion between patients and their doctors."

"Many women have told me over the years that their doctor did not warn them about the potential brain effects of undergoing a surgical menopause. While these women may have made the same decision regarding surgery given its life preserving benefits, they indicated that they wish they had been informed about the potential cognitive and mood effects so that they could be prepared and seek treatment sooner", says Epperson.