Culture

NUI Galway study establishes how cognitive intelligence is a whole brain phenomenon

An international collaborative study led by researchers from the NUI Galway provides findings on the neural basis of intelligence, otherwise known as general cognitive ability (IQ).

This new research uses an imaging technique called diffusion tensor imaging (DTI) to provide an insight into how small variations in this wiring system is associated with differences in IQ in both the general population and how disorders such as schizophrenia manifest.

Over 40 scientists from around the world were involved in analysing brain MRI scans and measures of cognitive function of 1,717 participants, with both healthy functions and patients with schizophrenia. This resulted in a new method to harmonise data collection and analysis as part of the Enhancing Neuroimaging Genetics through Meta-Analysis project (ENIGMA), Schizophrenia Working Group. The study, published in The American Journal of Psychiatry, was led by Dr Laurena Holleran, Lecturer in Clinical Neuroscience and Professor Gary Donohoe, Established Professor at NUI Galway's School of Psychology and Centre for Neuroimaging Cognition and Genomics.

Commenting on the findings, lead author Dr Laurena Holleran, stated that: "To date, this is the largest meta-analysis study of brain structure and cognitive function in schizophrenia. Understanding the neural basis of cognitive function is essential so that effective therapies that address difficulties associated with disorders like schizophrenia, which aren't targeted by current treatments. This is important because cognitive deficits associated with the disorder strongly predict social and functional outcomes, such as employment or social relationships.

"Previous literature suggested that general intelligence relies on specific grey matter areas of the brain, including temporal, parietal and frontal regions. However, the results from this study indicate that efficient connection pathways across the entire brain provide a neural network that supports general cognitive function."

According to the study's senior author Professor Gary Donohoe: "These results advance our knowledge in a number of ways. Firstly, we have demonstrated that the relationship between brain structure and intelligence not only involves grey matter, but also white matter - the brain's wiring system. Secondly, it's not just one part of this wiring system that is important for intelligence, but rather the wiring system as a whole. And finally, the relationship between intelligence and the brain's wiring system is basically the same in patients with schizophrenia and healthy people, in that the lack of pattern explains their cognitive abilities. This suggests that cognitive function in patients is the same as the general population, at least as far as white matter is concerned."

Credit: 
University of Galway

Why you should say 'thank you' and not 'sorry' after most service failures

Chicago, March 26, 2020 -- Researchers from New Mexico State University, University of South Carolina, Zhejiang University (China), and The Ohio State University published a new paper in the Journal of Marketing, which examines strategies for restoring customer satisfication.

The study forthcoming in the March issue of the Journal of Marketing is titled "When and Why Saying "Thank You" Is Better Than Saying "Sorry" in Redressing Service Failures: The Role of Self-Esteem" and is authored by Yanfen You, Xiaojing Yang, Lili Wang, and Xiaoyan Deng.

Business leaders worldwide report that consumers' expectations of service quality are higher than ever. It is therefore not surprising that consumers report interactions with service providers as often rife with service failures. Consider restaurant service. A high proportion of U.S. consumers are dissatisfied with various aspects of their dining experience, with 60.8% complaining about slow services, 29.4% about inadequate food and beverage quality, and 21.6% about inefficient staff. In general, service failure consequences to businesses include considerable financial loss and negative word of mouth (WOM). For example, U.S. companies lost $1.6 trillion in 2016 from customer switching caused by poor service with 44% of unsatisfied customers venting their frustrations on social media.

In their initial recovery efforts after a service failure, service providers need to decide what to communicate to consumers to restore their satisfaction. A new study in the Journal of Marketing focuses on two symbolic recovery communications commonly utilized by service providers--appreciation (saying "thank you") versus apology (saying "sorry"). For example, when there is a service delay (e.g., a plumber shows up later than the scheduled time), the service provider could either say, "Thank you for your patience," or "I am sorry for the wait."

This research suggests that appreciation (saying "thank you") is often a more effective strategy than apology (saying "sorry") at restoring consumer satisfaction. That is, in the case of service failures, when service providers redress such failures with the appreciation (vs. apology) recovery communication strategy, consumers are more satisfied with the way service providers redress the failure, report higher overall satisfaction, form higher repatronage intentions, are more likely to recommend the service provider to other consumers, and are less likely to complain.

The researchers reason that a shift of focus in the interaction between service provider and consumer--from emphasizing the service provider's fault and accountability (apology) to spotlighting the consumer's merits and contributions (appreciation)--can increase consumer self-esteem and, in turn, enhance post recovery satisfaction.

The study also identifies situations in which the superiority effect of appreciation (vs. apology) holds or disappears. For example, the superiority of appreciation over apology is more likely to be observed among consumers who are narcissistic and when recovery communications are communicated after (vs. before) the service failure. The appreciation strategy is as effective as recovery messages that combine appreciation and apology, too. The appreciation strategy's superiority over apology also holds when material recovery needs to be provided in severe failures (e.g., a server provides a free drink in addition to expressing appreciation or apology).

These findings have substantial implications for service providers about how to effectively recover from service failures. As an initial step, service providers need to decide what to say to consumers to redress the failure and restore satisfaction. Despite abundant guidance on whether and when to redress a service failure, researchers have offered little advice on what service providers should say, except for recommending that they apologize for the service failure. This study suggests that saying "thank you" is more effective at restoring consumer satisfaction than saying "sorry."

What service providers ultimately say--"thank you" or "sorry"--should be tailored to certain situational factors (i.e., timing of the recovery, severity of failure, and presence of utilitarian recovery) and individual traits (e.g., consumers' narcissism). For example, the superior effect of appreciation disappears if service providers redress potential failures in advance. Furthermore, when the service failure is severe, utilitarian recovery or material compensation is a prerequisite for the superior effect of appreciation. Service providers should use appreciation in their service recovery for consumers with a higher narcissistic tendency (e.g., those who use social networks more, are younger), but should be aware that appreciation is not necessarily better than apology for those low in narcissism.

Credit: 
American Marketing Association

Bricks can act as 'cameras' for characterizing past presence of radioactive materials

Researchers from North Carolina State University have developed a new technique for determining the historical location and distribution of radioactive materials, such as weapons grade plutonium. The technique may allow them to use common building materials, such as bricks, as a three-dimensional "camera," relying on residual gamma radiation signatures to take a snapshot of radioactive materials even after they've been removed from a location.

"This research builds on our previous work, which was an empirical demonstration that we could turn a brick into a gamma ray spectrometer - characterizing the energy distribution of a radiation source," says Robert Hayes, an associate professor of nuclear engineering at NC State and first author of a paper on the work.

"Our new work effectively shows that we could take an array of bricks and turn them into a gamma ray camera, characterizing the location and distribution of a radiation source," Hayes says. "Although this time we did not use bricks, instead relying on commercial dosimeters, since it's a proof of concept study. Also, the radiation source we imaged this time was 4.5 kilograms of weapons grade plutonium, whereas we previously used a commercial americium source for the spectrometry demonstration. In this most recent study, we were able to rather accurately predict not only the location of the weapons grade plutonium, but even the radius of the source, just with passive dosimeters.

"Even though we used commercial dosimeters here, our findings strongly suggest that we could do the same using building materials, such as brick," Hayes says. "That's because the silicates in brick - such as quartz, feldspars, zircons, and so on - are all individual dosimeters. It is a tedious process to remove those grains from the brick for measurements, but we have done it multiple times. For the goals of this new research, it wasn't necessary to use brick - we've already shown we can do that. This was simply a question of determining how much information we could glean from this approach. And the answer is that we could learn a lot - about the size and shape of the radiation source, as well as the nature of the radioactive material itself."

"This ability for three-dimensional imaging is a novel capability, meaning we can basically see into history in terms of what nuclear material was where or when," says Ryan O'Mara, a Ph.D. student at NC State and coauthor of the work.

Credit: 
North Carolina State University

Researchers investigate potential treatments for COVID-19

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.

Credit: 
American Society for Microbiology

Less ice, more methane from northern lakes: A result from global warming

image: Shorter and warmer winters lead to an increase in emissions of methane from northern lakes.

Image: 
Kristiina Martikainen

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.

Credit: 
University of Eastern Finland

Scientists electrify aluminum to speed up important process

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."

Credit: 
Ohio State University

Worldwide urban expansion causing problems

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.

Credit: 
Texas A&M University

Female physicians drive unfunded research on pay disparity

(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.

Credit: 
Boston University School of Medicine

New index challenges university rankings

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.

Credit: 
Friedrich-Alexander-Universität Erlangen-Nürnberg

Birds exposed to PCBs as nestlings show behavior changes as adults

image: Zebra Finch

Image: 
Terence Alexander/Macaulay Library

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.

Credit: 
Cornell University

A possible treatment for COVID-19 and an approach for developing others

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.

Credit: 
American Society for Microbiology

What can be learned from the microbes on a turtle's shell?

image: A Krefft's river turtle

Image: 
Dr Donald McKnight

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."

Credit: 
Microbiology Society

Missing link in coronavirus jump from bats to humans could be pangolins, not snakes

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.

Credit: 
American Chemical Society

New therapeutic strategy against diabetes

image: Researchers at the CEBATEG - Universitat Autònoma de Barcelona

Image: 
CBATEG-UAB

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.

Credit: 
Universitat Autonoma de Barcelona

Experimental medication to prevent heart disease may treat chemo-resistant ovarian cancer

image: Benjamin Bitler, PhD, and colleagues from many fields of cancer research collaborate to show CPT1A may be necessary for ovarian cancer dissemination, chemo-resistance.

Image: 
University of Colorado Cancer Center

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.

Credit: 
University of Colorado Anschutz Medical Campus