Culture

Greenville, SC - March 11, 2021 - KIYATEC, Inc researchers demonstrated that their immune-modified ex vivo platform can measure treatment response through direct interaction between a patient's cancer and infiltrating immune cells, and immuno-oncology agents. This work, published in the March 2021 issue of Cancer Immunology, Immunotherapy, validates the use of this platform in a pre-clinical setting to demonstrate tumor sensitivity to immune checkpoint inhibitors alone or in combination with other drugs.

Immunotherapy agents, although a potentially promising cancer treatment option, cost a premium and in many cases only 10-30% of patients respond to treatment. Currently, there is a great need and opportunity to better predict which patients will respond to immunotherapies. Patient selection is a challenge; the magnitude of this challenge has been validated by the recent withdrawal of approval of four immunotherapies for more than one cancer indication.

This study, which demonstrated that clinically relevant biological changes in immune cells and ovarian cancer cells could be detected in KIYATEC's platform after treatment with immune checkpoint inhibitors, marks significant progress towards successfully predicting immunotherapy response in the clinic.

Tessa DesRochers, PhD, KIYATEC Chief Scientific Officer said, "This paper highlights our ability to model the immune microenvironment of a patient, and then measure checkpoint inhibitor response alone or in combination with PARP inhibitors. Most checkpoint inhibitors are used in combination with other drugs and the PARP inhibitor combination is particularly relevant in ovarian cancer."

Past clinical studies demonstrated that the presence of immune cells in ovarian tumors generally leads to improved patient survival. However, the use of checkpoint inhibitors such as pembrolizumab, which blocks the PD-1 receptor thus allowing immune cells to attack cancer cells, has not been successful in clinical trials.

In this study, primary ovarian cancer tissue was used to generate 3D spheroids, containing both tumor cells and infiltrating immune cells. Before applying drug treatments, the researchers validated infiltrating immune cell function in the co-culture platform. The spheroids were then treated with the checkpoint inhibitors durvalumab or pembrolizumab alone or in combination with olaparib, a PARP inhibitor.

Cancer treatment success is measured by tumor cell death. Strikingly, KIYATEC's platform showed that tumor cell death was due to the anti-cancer activity of the immune cells within the spheroids. While these findings highlight the synergy between pembrolizumab and olaparib in ovarian cancer tumors that contain immune cells, the overarching excitement is the potential for platform use for the personalized, clinical prediction of immune checkpoint inhibitor response.

KIYATEC's platform is already predictive for chemotherapy and targeted agents. While studies will be performed to correlate the test results with patient immunotherapy endpoints in the clinic, today, pharmaceutical companies can use KIYATEC's platform to aid decision-making during drug lifecycles.

"Our platform has demonstrated the ability to generate responses across multiple therapies, including chemotherapies, targeted agents, and immuno-oncology agents. Also, the platform can tease out intricate biological interactions between tumor cells, immune cells, and therapeutics in ways that are not possible in patients. We believe that a test predicting patient-specific response with clinically meaningful accuracy reflects a multi-billion-dollar market opportunity," said Matthew Gevaert, PhD, CEO and Founder of KIYATEC.

URBANA, Ill. ¬- As the global population grows, the demand for food increases while arable land shrinks. A new University of Illinois study investigates how rice production in India can meet future needs by adapting to changing climate conditions and water availability.

"Rice is the primary crop in India, China, and other countries in Southeast Asia. Rice consumption is also growing in the U.S. and elsewhere in the world," says Prasanta Kalita, professor in the Department of Agricultural and Biological Engineering at U of I and lead author on the study.

"If you look at where they traditionally grow rice, it is countries that have plenty of water, or at least they used to. They have tropical weather with heavy rainfall they depend on for rice production. Overall, about 4,000 liters of water go into production and processing per kilogram of rice," he states.

Climate change is likely to affect future water availability, and rice farmers must implement new management practices to sustain production and increase yield, Kalita says.

The United Nations' Food and Agriculture Organization (FAO) estimates the world population will grow by two billion people by 2050, and food demand will increase by 60%.

"We will need multiple efforts to meet that demand," Kalita states. "And with two billion more people, we will also need more water for crop production, drinking water, and industrial use."

Kalita and his colleagues conducted the study at the Borlaug Institute for South Asia's research farm in Bihar, India. Farmers in the region grow rice during the monsoon season, when heavy rainfall sustains the crop.

The researchers collected data on rice yield and climate conditions, then used computer simulations to model future scenarios based on four global climate models. The purpose of the study was to estimate rice yield and water demand by 2050, and evaluate how farmers can adapt to the effects of climate change.

"As the weather changes, it affects temperature, rainfall, and carbon dioxide concentration. These are essential ingredients for crop growth, especially for rice. It's a complicated system, and effects are difficult to evaluate and manage," Kalita states.

"Our modeling results show the crop growth stage is shrinking. The time for total maturity from the day you plant to the day you harvest is getting shorter. The crops are maturing faster, and as a result, you don't get the full potential of the yield."

If farmers maintain current practices, rice yield will decrease substantially by 2050, the study shows. But various management strategies can mitigate the effects of climate change, and the researchers provide a series of recommendations.

Traditional rice farming involves flooding the fields with water. Rice transplants need about six inches of standing water. If fields aren't level, it requires even more water to cover the crops, Kalita says. However, if farmers use direct-seeded rice instead of transplants, they can increase production while using significantly less water.

Another practice involves soil conservation technology. "The soil surface continuously loses water because of temperature, humidity, and wind. If you keep crop residue on the ground, it reduces the evaporation and preserves water. Furthermore, when the crop residue decomposes, it will help increase soil quality," Kalita explains.

The researchers also suggest implementing strategies to prevent post-harvest crop losses. FAO estimates about 30% of crops are lost or wasted after harvest, so efforts to reduce those losses can further increase crop availability and food security.

Overall, the best approach to achieve a 60% increase in rice production while minimizing additional irrigation needs is a combination of conservation strategies and a 30% reduction in post-harvest loss, the researchers conclude.

LOS ALAMOS, N.M., March 11, 2021--A long-time question in astrophysics appears to finally be answered, thanks to a collection of large, high-tech water tanks on a mountainside in Mexico. The High-Altitude Water Cherenkov (HAWC) data shows that the highest-energy cosmic rays come not from supernovae, but from star clusters.

"The origin of the highest-energy cosmic rays in the galaxy has been an open question in astrophysics for more than 60 years," said Patrick Harding, a Los Alamos National Laboratory astrophysicist doing research using HAWC. "Very few regions of the galaxy have both the power to produce high-energy particles and the necessary environments to boost those particles to the petaelectronVolt (PeV) energies that are seen in the highest-energy cosmic rays. And most of the expected regions to produce the particles have been ruled out in recent years by high-energy observatories."

"In this paper, we discover high-energy gamma rays coming from Cygnus OB2, a birthplace of massive stars located inside the 'Cygnus Cocoon' superbubble, meaning it is likely the source of these highest-energy galactic cosmic rays," Harding said.

The cosmic rays have been observed striking Earth's atmosphere at PeV energies by the detection tanks at the HAWC observatory near Puebla, Mexico. Instead of supernovae, this work shows that star clusters such as the Cygnus Cocoon serve as "PeVatrons" -- PeV accelerators capable of creating high-energy particles that travel across the galaxy.

The algorithms used to analyze the highest-energy HAWC photons, which were used in a paper published today in Nature Astronomy, were developed by Los Alamos postdoctoral researcher Kelly Malone. Additionally, the paper which first identified the Cocoon as a significant emitter of high-energy gamma-rays using the HAWC high-energy catalog, was also led by Malone, who is the leader of the Galactic Science Working Group within HAWC.

"HAWC is the first observatory to detect gamma rays from across the sky with energies above 100 TeV. This high-energy reach allows us to answer fundamental questions about our galaxy," said Malone.

The consequences of this result are relevant for several areas of Los Alamos astrophysics study: The transport of cosmic rays and their interactions with the surrounding medium are of interest at the Laboratory, and in particular, Los Alamos studies which types of astronomical sources can efficiently accelerate cosmic rays to high energy, and which acceleration mechanism enables it. Identifying a source of these high-energy cosmic rays will lead to greater theoretical understanding of these mechanisms.

A recent study on spectacular fossil plants preserved in a volcanic ash fall deposit--known as China's "vegetational Pompeii," in Inner Mongolia, China--has resolved a mystery that puzzled palaeontology for over a century: What are Noeggerathiales?

The study, published in PNAS on March 8, was led by Prof. WANG Jun from the Nanjing Institute of Geology and Palaeontology of the Chinese Academy of Sciences (NIGPAS) and by Prof. David Dilcher from Indiana University (USA). Researchers from the UK, Czech Republic and Austria were also involved.

The researchers confirmed that Noeggerathiales had the spore propagation mode of ferns and the vascular tissue of seed plants. They belonged to a sister group of seed plants, the former gymnosperm.

Noeggerathiales were important peat-forming plants that lived approximately 325-251 million years ago. Although they were first recognized as a distinct plant group in the 1930s, scientists have long argued over their relationships with other plant groups. As a result, they were considered an evolutionary dead end.

The researchers studied complete plants preserved in a 66-cm-thick bed of volcanic ash that fell 298 million years ago and smothered all the plants growing in a swamp. The ash prevented the fossils from being consumed by other organisms or decaying and thus preserved many complete individuals.

From these complete plants, the scientists reconstructed a new species of Noeggerathiales named Paratingia wuhaia that finally allowed the groups affinity and evolutionary importance to be determined.

These results show for the first time that Noeggerathiales were advanced members of the evolutionary lineage from which seed plants evolved. This is important as it shows Noeggerathiales are more closely related to seed plants than they are to other fern groups, and Noeggerathiales can no longer be considered an evolutionary dead end.

The study also shows that the ancestral lineage from which seed plants evolved diversified alongside the earliest seed plant radiation during the Devonian, Carboniferous and Permian periods and did not rapidly die out as previously thought.

Noeggerathiales are now recognized as an advanced group of spore plant that evolved complex cone-like structures from modified leaves. Despite their reproductive sophistication, however, they were victims of profound environmental and climate changes during the Permian-Triassic mass extinction approximately 251 million years ago that destroyed swamp ecosystems globally.

The "vegetational Pompeii" is certainly a fossil Lagerstätte, preserving a large number of materials that have huge potential for resolving mysteries in the area of palaeobotany.

"The whole-plant Paratingia wuhaia reconstructed here represents a tip of the iceberg. The ongoing research based on the fossils from the 'vegetational Pompeii' may bring about more and more reconstruction of ancient plants," said Prof. WANG.

The fossil collection from the "vegetational Pompeii" represents the largest number of plant fossils describing a coal-forming forest. Meanwhile, the research group has conducted the largest actual reconstruction of an ancient peat-forming swamp in the world.

Adolescents and young adults may be more susceptible to COVID-19 than previously believed, according to analysis of cases in six U.S. states experiencing surges.

Individuals' willingness to engage in COVID-19 control measures is associated with their trust in the government, other citizens, and in particular science, according to a new study published this week in the open-access journal PLOS ONE by Stefano Pagliaro of University of Chieti-Pescara, Italy, and colleagues.

The spread of SARS-CoV-2 since December 2019 has posed a severe public health threat to people around the world. As vaccines are being rolled out, behavioral changes are also necessary to counter the spread of the virus. These actions include both prescribed behaviors such as wearing masks, social distancing, and quarantining, as well as discretionary prosocial behaviors like donating to charities and buying supplies for people in quarantine. The willingness of citizens to engage in such behaviors varies greatly.

In the new study, researchers examined factors that may account for these differences in behavior. They collected data on 6,948 people from 23 countries using an online survey in April and May of 2020. Participants provided sociodemographic information and details about their COVID-19 experiences, and answered questions about their moral principles, trust in their government, other citizens, and science and feelings on the importance of adhering to COVID-19 prevention measures.

The results revealed that the country in which people lived accounted for less than 10% of the variance in predicting engagement in prescribed and discretionary behaviors, and the publicized number of infections was not significantly related to individual intentions to engage in either type of behavior. Instead, behavior was largely predicted by individual differences in trust in their government, other citizens, and in particular science. Moreover, the more people endorsed moral principles of fairness and care, the more inclined they were to trust in science and the more likely they were to carry out both prescribed and discretionary behaviors related to COVID-19. Interestingly, factors such as age, gender, and education did not change the overall pattern of results. The authors conclude that communication strategies to encourage behaviors that limit the spread of COVID-19 should be tailored to the broader moral codes of given countries and subgroups of the population.

The authors add: "We considered individuals' intentions to comply with prescribed and discretionary behaviors to manage the spread of COVID-19 in 23 countries and examined the factors that might drive such behavioral intentions. We showed that the publicized statistics of the pandemic in terms of infections and deaths in each country does not represent the only, or even the most important antecedent of individual reactions, as a threat account of the health emergency would suggest. [...] Instead, considering psychological differences in terms of trust toward different agents - governments, citizens, and science - provide a more informative picture of individuals' reactions to COVID-19. " In particular, "[...] The present research further showed that trust in science represents a crucial factor in shaping individuals' behavior in response to the COVID-19 pandemic."

Blood pressure measurements in children and adolescents should be taken from both arms after new research showed substantial differences could be seen depending on which arm was used.

The study, led by the Murdoch Children's Research Institute (MCRI) and published in the Journal of Hypertension, found even a small difference in blood pressure measurements between arms could lead to a wrong diagnosis.

MCRI PhD candidate and study lead author Melanie Clarke said this was the first study worldwide to determine the size and frequency of inter-arm blood pressure differences in children and adolescents.

The study involved 118 participants, aged 7-18 years, recruited from a cardiology day clinic in Melbourne. It found in healthy children one in four had an inter-arm difference that could lead to misdiagnosis. This figure doubled in those with a history of aortic surgery, which is often performed in infants with congenital heart disease.

Ms Clarke said the high rates of misclassification occurred because the difference between a normal and hypertensive recording was so small.

"Misdiagnosis could occur when the blood pressure difference is greater than about 5 mmHg, but one in seven healthy children had a difference greater than 10 mmHg, which could lead to a failure to identify stage one or two hypertension," she said.

"Given blood pressure measured in a child's right and left arm are often different, it's important to take measurements in both arms to make a correct diagnosis. Accurate blood pressure assessment in kids is critical for identifying the potential risk for damage to the heart and blood vessels, which can lead to early-onset cardiovascular disease."

High blood pressure is one of the primary risk factors for heart disease and stroke, the leading causes of death worldwide. Globally, an average of three children per school classroom have elevated blood pressure or hypertension (almost 14 per cent).

MCRI Associate Professor Jonathan Mynard said children with high blood pressure were more likely to develop hypertension as adults at a relatively young age, and the damage it caused to the heart and blood vessels started silently in childhood.

"Children with high blood pressure, many of whom appear to be healthy, have a greater risk of developing hypertension in adulthood, a major risk factor for cardiovascular disease," he said.

The European Society of Hypertension and the American Academy of Pediatrics recommend blood pressure be measured in children and adolescents at least once a year. However, Associate Professor Mynard said in Australia it wasn't common practice for GPs to measure blood pressure in children or in both arms.

"We know high blood pressure is common in adults but many people don't realise how common it is in kids too," he said. Parents can help by encouraging their kids to eat a healthy diet that is low in salt and sugary drinks, and high in fruit, vegetables, and whole grains, and to engage in lots of physical activity.

"More work needs to be done to draw attention to the problem of childhood hypertension and its long-term consequences. Australia would benefit from having its own set of clinical guidelines addressing high blood pressure in children, including how to obtain accurate measurements and avoid misclassification."

Heart Foundation Chief Medical Advisor and cardiologist Professor Garry Jennings said: "There are good clinical reasons for measuring blood pressure in both arms in children and adolescents in the evaluation of hypertension and this study provides clear support for this approach."
Researchers from the University of Melbourne, The Royal Children's Hospital and the Slippery Rock University in Pennsylvania also contributed to the findings.

Recently, Prof. ZHU Shu from University of Science and Technology of China (USTC) of CAS and Prof. Richard A. Flavell from Yale University were invited to publish a review article in Nature Reviews Gastroenterology and Hepatology. They systematically summarized the gastrointestinal manifestations in patients with COVID-19 and explored the possible mechanisms of intestinal symptoms caused by COVID-19 infection.

Although the clinical manifestations of COVID-19 are primarily fever, cough, and pulmonary imaging, gastrointestinal symptoms have also been reported. About 50% of COVID-19 patients have shown detectable SARS-CoV-2 RNA in their faecal samples. Evidence of SARS-CoV-2 intestinal infection has also been reported based on multiple in vitro and in vivo animal studies.

Existing evidence of intestinal infection in COVID-19 were summarized. Intestinal expression of SARS-CoV-2 receptor and serine protease remain relatively high level. Virus particles and intestinal inflammation were detected at autopsy and biopsy of the patient's intestines. In vitro intestinal cell lines and intestinal organs were identified as susceptible to SARS-CoV-2. The mouse, hamster, ferret, rhesus monkey and other animal models that can be used to investigate the intestinal infection of SARS-CoV-2 were also summarized and compared

The risk of potential faecal-oral transmission of SARS-CoV-2 was discussed. A rigorous and systematic determination of whether the virus titre in faecal fomites can exceed the minimum infection dose is essential to accurately quantify the true risk of SARS-CoV-2 transmission through a faecal-oral route.

This work deepened the understanding of COVID-19 gastrointestinal manifestations and suggest a potential relation between intestinal infections and disease severity. It is important for understanding the pathogenicity and transmission mechanism of the virus and developing scientific prevention and control strategies.

As countries around the world race to mitigate global warming by limiting carbon dioxide emissions, an unlikely source could be making climate goals harder to achieve without even deeper cuts in greenhouse gas production: reductions in air pollution.

New modeling experiments from Kyushu University in Japan of the long-term effects of reductions in pollutants known as sulfate aerosols predicts further increases in surface air temperature at current and increased carbon dioxide levels because of the loss of an overall cooling effect caused by the light-scattering particles.

"Air pollution causes an estimated seven million premature deaths per year worldwide, so action is essential, especially in emerging and developing countries, which tend to be most affected," says Toshihiko Takemura, professor at Kyushu University's Research Institute for Applied Mechanics and author of the study.

"However, reductions in air pollutants must come hand in hand with reductions in greenhouse gases to avoid accelerating global warming."

To analyze how sulfate aerosols--small particles of sulfur-containing compounds often produced by burning fossil fuels or biomass--influence climate, Takemura used a combination of models known as MIROC-SPRINTARS.

MIROC is a general circulation model taking into account many key aspects of the atmosphere and oceans along with their interactions, while SPRINTARS, which is widely used by news outlets for air pollution forecasts, is capable of predicting the mixing of aerosols in the atmosphere.

Combining the two models allows for effects such as the scattering and absorption of light by aerosols and the interaction of aerosols with clouds to be included in the climate projection.

Looking at the immediate changes to the atmosphere in the case of reduced emission of SO2--a precursor of sulfate aerosols--from fuel sources, Takemura found that changes such as in light scattering and cloud formation by the sulfate aerosols lead to more energy overall entering the atmosphere, though the increase is similar regardless of whether the atmospheric carbon dioxide concentration is the same as present levels or doubled.

However, considering changes in the climate and surface temperatures over longer time scales showed that not only does the surface air temperature increase with a reduction in sulfate aerosols but this increase is even larger when carbon dioxide levels double.

"Although the fast response is similar for both situations, long-term changes caused by more slowly responding factors related to interactions with the oceans and subsequent changes, such as in clouds and precipitation, eventually leads to a bigger temperature increase," explains Takemura.

"Thus, global warming will accelerate unless increases in greenhouse gas concentrations are suppressed as air pollution control measures decrease sulfate aerosol concentrations, further emphasizing the urgency for reducing carbon dioxide in the atmosphere," he concludes.

The unpredictable nature of life during the coronavirus pandemic is particularly challenging for many people. Not everyone can cope equally well with the uncertainty and loss of control. Research has shown that while a large segment of the population turns out to be resilient in times of stress and potentially traumatic events, others are less robust and develop stress-related illnesses. Events that some people experience as draining seem to be a source of motivation and creativity for others.

These differing degrees of resilience demonstrate that people recover from stressful events at different rates, with psychosocial factors such as positivity, optimism, the ability to self-regulate, social skills, problem-solving skills and social support playing a role. A team from the Department of Psychology and the University Hospital of Psychiatry Zurich teamed up with researchers from New York to investigate how people can strengthen their psychological resilience when facing adversity.

Importance of believing in your own power

"Self-efficacy is a key element of resilience," explains Birgit Kleim, professor of psychology at UZH and director of the study. "By self-efficacy, I mean the belief that we have the ability to influence things to at least a small degree, even if some things are unchangeable." A self-efficacious person is convinced that they can draw on their own powers to overcome difficult and challenging situations. It doesn't matter whether this is actually the case, as Kleim explains: "Without believing in your own capabilities, you wouldn't take on any challenges in the first place." Self-efficacious people have stronger problem-solving abilities and a higher level of persistence. They also show changes in brain activation in regions linked to emotional regulation.

How might it be possible, then, to boost people's self-efficacy so that they can harness its positive powers in the coronavirus era? For the resilience study, a team of researchers examined 75 people who were distressed by a negative emotional memory. Before recalling and reassessing this distressing memory, one group of subjects was instructed to vividly recall a positive event such as a beautiful experience in nature or a joyful encounter with others. The others were instructed to think of a time in which they felt they were particularly self-efficacious: situations such as having a successful conversation, passing a difficult exam or giving a presentation. In many cases, doing this exercise just once was already enough to achieve a positive effect.

Recalling autobiographical self-efficacy yields dramatic effects

"Recalling a specific instance of one's own self-efficacy proved to have a far greater impact than recalling a positive event," says Kleim. People who actively recalled their own self-efficacious behavior found it easier to reassess a negative situation and view it in a different light. They perceived the negative experience as less distressing than the subjects who were instructed to reflect on a positive memory unconnected to self-efficacy.

"Our study shows that recalling self-efficacious autobiographical events can be used as a tool both in everyday life and in clinical settings to boost personal resilience," explains the research team. It may be possible to strategically use memories of overcoming past challenges as a way of coping with crisis situations. This also applies to the coronavirus crisis, where these memories can be used to shield against the negative impacts of the pandemic.

In a study recently published in Nature Communications, scientists from The Novo Nordisk Foundation Center for Biosustainability (DTU) and Yale University have investigated how bacteria that are commonly found in sugarcane ethanol fermentation affect the industrial process. By closely studying the interactions between yeast and bacteria, it is suggested that the industry could improve both its total yield and the cost of the fermentation processes by paying more attention to the diversity of the microbial communities and choosing between good and bad bacteria.

The scientists dissected yeast-bacteria interactions in sugarcane ethanol fermentation by reconstituting every possible combination of the microbial community structure, covering approximately 80% of the biodiversity found in industrial processes, and especially one bacterium deserves extra attention: Lactobacillus amylovorus. But how come exactly this one doesn't fall into the category of "the bad guys"? The main reason is that it produces a lot of the molecule acetaldehyde, which is used to feed yeast and thus helps it to grow. You could say that Lactobacillus amylovorus is more generous by nature and shares the meal, whereas many other bacteria involved in these processes prefer simply to steal the food.

"It works almost in the same way as a probiotic that shields the bad bacteria from entering into the system. And when this bacterium grows, it will grow in a way that is almost symbiotic with the yeast which is very beneficial for the industrial process", says Felipe Lino, former PhD Student at The Novo Nordisk Foundation Center for Biosustainability and Global R & D Manager at Anheuser-Busch InBev.

Significant improvement of yield

Thus, companies could take advantage of selecting not only for an ideal yeast strain for production, as they started doing already in the 90's, but to select for the best-suited bacteria as well, since it is completely impossible to get rid of bacteria that are hanging around no matter what. An effort that could turn out to pay dividends already in a short-term perspective.

By using this probiotic in a sugarcane ethanol fermentation, it is estimated that the fermentation yield could increase by three percent. While three percent can sound like a rather low number this is definitely not the case. According to Brazil's Biofuels Annual 2019, Brazil's total ethanol production in 2019 was 34.5 billion liters with domestic demand for 34 billion liters making the country the home to the largest fleet of cars that use ethanol derived from sugarcane as an alternative fuel to fossil fuel-based petroleum.

These numbers indicate that optimised fermentation processes hold great potential. One way to start ensuring more efficient industrial production of ethanol would be to apply more targeted approaches and shift away from a "one-size fits all" strategy where sulfuric acid treatment is used without further consideration to lower the pH and kill the bacteria to keep the population under a certain threshold. This would be beneficial both economically and environmentally, says Morten Sommer, Professor and Group Leader at The Novo Nordisk Foundation Center for Biosustainability.

"Instead of using a broad range of antibiotics, one should go for a more specific solution where you keep the good bacteria inside the fermenter. This is definitely a paradigm shift because you are not per definition fighting against all bacteria, since some of the bacteria are actually good and improve your final output significantly while also having a positive effect on production costs and the environmental footprint."

Italian and Russian researchers confirmed the hypothesis that the self-maintaining order in eukaryotic cells (cells with nuclei) is a result of two spontaneous mechanisms' collaboration. Similar molecules gather into 'drops' on the membrane and then leave it as tiny vesicles enriched by the collected molecules. The paper with the research results was published in the journal Physical Review Letters.

The research was carried out by an international interdisciplinary team of biologists (from Polytechnic University of Turin, Italian Institute for Genomic Medicine of the University of Turin and Candiolo Cancer Institute) and physicists (from Landau Institute for Theoretical Physics and HSE University Faculty of Physics).

'Participation of physics theoreticians in biological studies can be rather important, when in the investigated phenomena, we can detect a universal structure, which is poorly sensitive to chemical and other detail,' believes HSE Professor Igor Kolokolov, Director of the Landau Institute for Theoretical Physics (RAS) and Head of the HSE Department for Theoretical Physics. 'Of course, the biology problem setting is primary, and without our colleagues, biologists, there would be no such study. But generally speaking, such collaboration of biologists, oncologists and physics theoreticians comprises a modern swiftly developing scientific area - physical biology.'

A eukaryotic cell has a nucleus and is the main structural unit of all animals and plants. With a microscope, one can see that it is a complicated structure consisting of many compartments divided by membranes. Each compartment plays its role in cell functioning and is occupied by certain molecules. The cell preserves this internal order when it interacts with the environment, and, if no pathologies interfere, it does not degrade to a shapeless gathering of molecules. An important role in a eukaryotic cell's sustainability is played by the process of spatial re-ordering and molecule delivery to correct destinations.

'This process is reminiscent of a daily cleaning in a big and crowded house. But this house doesn't have an obvious housekeeper, and it looks like this important work happens by itself, with unclear rules,' commented Vladimir Lebedev, Professor at the HSE Joint Department for Theoretical Physics with the Landau Institute for Theoretical Physics.

In their paper Optimality in Self-Organized Molecular Sorting, the researchers proposed, analysed and experimentally tested the hypothesis that such self-maintaining order in eukaryotic cells is a result of joint action of two spontaneous mechanisms. First, similar molecules aggregate on the membrane into clusters, similarly to water drops that aggregate in a subcooled cloud and make up a fog. Second, these 'drops' induce a local membrane curvature, and, in the end, form tiny vesicles. Enriched with the gathered molecules, these vesicles detach from the membrane and start they journey in the cell. That's why many internal membranes of a eukaryotic cell are natural distillers, with ready-made production delivered to the end consumer (in another cell compartment) in a 'bottle'.

The published paper suggests a mathematical apparatus that allows universal features in the kinetics of such distillation to be detected. Its adequacy has been tested by direct quantitative modelling. The researchers discovered that for each sort of molecules, there are optimal indicators of parameters, such as cluster appearance frequency, with which the whole distillation process is maximally effective. In particular, if the frequency is too low, distillation is too slow. If it is too high, many small drops quickly evolve and cover a considerable area on the membrane, but none of them reaches the critical size within reasonable time, which is needed to form a vesicle.

'In terms of physics, molecule movement on the membrane follows the laws of diffusion (chaotic, irreversible movement) and the structure of these molecules and the membrane determine only one parameter - the coefficient of this diffusion. The laws of diffusion mean that on a 2D surface, which is a membrane, the probability of molecule arriving in the determined area poorly depends on the size of this area. It is a key thing, which looks to be the main reason that many vital cell processes take place on internal membranes, which are two-dimensional, and intermembrane volume serves mostly as a warehouse for the mix of necessary substances,' said Prof. Kolokolov.

The paper also includes the results of experimental observation of distillation processes in cells taken from blood vessels in human umbilical tissue. The experimental data confirm the theoretical construction, including such an important feature as distribution of growing enriched clusters by size.

'Our paper uses the nucleus growth law, which can be illustrated as follows: if in a boiling pot you see a centimetre-sized bubble, that means that a split second ago, it still existed but was the size of a millimetre, it was not born centimetre-sized,' explained Igor Kolokolov. 'These concepts, brilliantly used decades ago by Ilya Lifshitz and Vitaly Slezov in the kinetics of first?order phase transitions, turned out to be very useful in our research, too.'

The paper allows us to conclude that in evolutionary terms, live cells 'work' with optimal parameters that provide maximum efficiency in the process of molecular reorganization.

The study results are interesting for medical applications, since the defects in the process of molecular re-ordering are related to many serious diseases, including cancer. Creating a universal and clear description that helps determine the parameters of this process management is an important first step, which is essential for the search of treatment opportunities.

Women of the ruling class may have played an important role in the governance of El Argar, a society which flourished in the southeast of the Iberian Peninsula between 2200 and 1550 BCE, and which in the last two centuries of its existence, developed into the first state organisation of the western Mediterranean.

These are the conclusions reached by researchers from the Universitat Autònoma de Barcelona (UAB) who led a study analysing the contents of a princely tomb (Grave 38), containing two individuals and a large amount of valuable items. The tomb was discovered in 2014 at the archaeological site of La Almoloya in Pliego, Murcia, beneath what was later identified to be the governing hall of a palatial building.

"La Almoloya and the princely grave 38 belong to these exceptional archaeological finds, which from time to time provide a glimpse into the ruling subjects and the emblematic objects of the first state societies emerging in Europe during the Bronze Age", states Vicente Lull, one of the study's coordinators. Published in Antiquity, this research has given archaeologists an insight into the political and economic power of the ruling class in El Argar.

The burial, located in a large ceramic jar, featured two individuals: a man aged 35 to 40, and a woman aged 25 to 30. Next to them was a range of some 30 valuable and prestigious objects, many of which were made or embellished with silver and almost all belonging to the female. There was a very complete repertoire of jewels and personal objects: bracelets, earlobe plugs, necklaces, spirals and containers with animal offerings. The most outstanding item was a silver diadem found on the head of the female.

A detailed study of the diadem found in La Almoloya and its comparison to four others found in the 19th century in the tombs of rich women at the site of El Argar, which gives name to the Argaric society and culture, points to the fact that all of them, despite being remarkedly uniform, were highly exclusive pieces. They were created in a silversmith workshop such as the one recently discovered in Tira del Lienzo, another Argaric site excavated by the same UAB team a few years ago.

"The singularity of these diadems is extraordinary. They were symbolic objects made for these women, thus transforming them into emblematic subjects of the dominant ruling class", explains Cristina Rihuete, who also took part in the study. "Each piece is unique, comparable to funerary objects pertaining to the ruling class of other regions, such as Brittany, Wessex and Unetice, or in the eastern Mediterranean of the 17th century BCE, contemporary to our Grave 38".

According to researchers, the opulence of the funerary goods found in the tombs of the elite women of El Argar, in which the diadems are of particular importance, is an indication of the distinguished role played by these women in the governance of some of these settlements. This is the case in La Almoloya, birthplace of the Argar society and centre of the most relevant political and economic power within the region.

Were the women rulers, or were the emblems of power worn by them merely of symbolic value? This is the question the research team is interested in. And their answer is that most probably they were the rulers: "In the Argaric society, women of the dominant classes were buried with diadems, while the men were buried with a sword and dagger. The funerary goods buried with these men were of lesser quantity and quality. As swords represent the most effective instrument for reinforcing political decisions, El Argar dominant men might have played an executive role, even though the ideological legitimation as well as, perhaps, the government, had lain in some women's hands", they argue.

Biologically unrelated, but with shared offspring

According to the genetic analyses conducted at the Max Planck Institute, the individuals buried in Grave 38 were contemporaneous, and died simultaneously or close together in the mid-17th century BCE. They were unrelated, but did have a daughter, who was found buried near them. The woman had several congenital abnormalities, along with markings on the ribs that could indicate she had a pulmonary infection at the time of death. Meanwhile, the male also had wear and tear on his bones indicative of extensive physical activity, possibly horse riding.

A value of 900 daily wages

The metal objects of Grave 38 also stand out in quantitative terms. The total weight of the silver is approximately 230 gr, which is equivalent to 27.5 shekels, a currency used during the time of Hammurabi, the ruler of Babylon, in the first half of the 18th century BCE (contemporaneous with El Argar), and adapted by other Near Eastern and Aegean economies. Hence, the silver found in La Almoloya would be enough to pay around 938 daily wages or buy 3350 kg of barley.

Notably, the mean weight of the three medium-sized silver spirals worn by both individuals is 8.44 g, which matches the weight of the Mesopotamian shekel (8.33 g). Furthermore, the weights of other silver spirals found in Grave 38 are practically fractions or multiplications of that figure. "This may be a random distribution or it may indicate a standardised system of weights and measures mirroring contemporaneous Eastern examples. Further research is required to determine this, but the possibility of detecting a metric system behind the silver spirals is a further indication of the extent of the economic control exercised by the dominant class in El Argar", Roberto Risch, co-author of the study, points out.

Political unity among Argaric regions

Contrary to the tombs found in El Argar, where there is no knowledge of the space in which they were placed, the funerary goods in Grave 38 and the diadem did offer the possibility of interpreting their location within an architectural setting. "The presence of emblematic objects buried in such an important place as is the "parliament" of La Almoloya could represent political unity among the Argaric regions during the last period of this society, in the 17th century BCE. The building was destroyed in a fire shortly after the burials took place", explains Rafael Micó, also co-director of the project.

The El Argar society and the importance of La Almoloya

The El Argar society flourished from 2200 to 1550 BCE in the southeast of the Iberian Peninsula (Murcia and Almería), and represents an early Bronze Age society with urban centres and monumental constructions, a developed division of labour, intramural burials with marked asymmetries in funerary expenditure between individuals, political boundaries and institutionalized violence in the context of a class-based state society. The most important settlements are El Argar, La Bastida and La Almoloya.

The discovery of Grave 38 in La Almoloya, excavated in 2014 by researchers from the ASOME (Arqueoecologia Social Mediterrània) research group, affiliated to the UAB Department of Prehistory, pointed out the unique archaeological wealth of the site. A privileged, strategic location which helped this society thrive for over six centuries. The discoveries made, including a building with political functions and Grave 38, confirmed its importance as a centre of political and economic relevance within the political territory of El Argar. The diadem found in La Almoloya is the only one to be preserved in Spain.

Almost 60% of frontline health and social care workers (HSCWs) experienced a mental health disorder during the first COVID-19 lockdown, with many suffering "very high rates of distress", suggests a new study led by researchers at UCL and the University of Haifa, Israel.

Given the significantly high levels of mental health disorders across all HSCWs, the researchers (part of the UCL-led COVID Trauma Response Working Group*), are now calling for long-term planning to meet the needs of staff from across health and social care, including specialist trauma services to be set up for healthcare workers, similar to the specialist commissioned NHS psychological trauma services for military veterans.

The 'Frontline-COVID study', published in the European Journal of Psychotraumatology, surveyed 1,194 HSCWs, who worked in UK hospitals, nursing or care homes and other community settings, to identify and compare the rates of mental health disorder across different job roles and places of work.

The study, carried out just after the first wave of COVID in the UK between 27 May and 23 July, 2020, found that 58% of HSCWs met the threshold for any mental health disorder; 22% met criteria for post-traumatic stress disorder (PTSD); 47% had clinically significant anxiety and 47% had depression. Symptom levels were high across all job roles and settings.

Importantly, the study found that it was not just doctors and nurses who were experiencing clinically significant distress, but all staff from across health and care.

Furthermore, the research also identified some specific mental health risk factors, principally: concern about infecting others with COVID; being unable to talk with their managers about how they were coping; feeling stigmatised (about their role); and not having had reliable access to personal protective equipment (PPE). Key predictors for PTSD included staff being redeployed to other teams and having had COVID themselves.

The research was conducted by the COVID Trauma Response Working Group, formed by UCL psychiatrists and psychologists, who are calling for immediate additional mental health support for HSCWs. This is the first UK study to assess mental health disorders across all health and social care settings during COVID-19.

Lead author, Dr Talya Greene (UCL Psychiatry and University of Haifa), said: "Our study shows that more than half of health and social care staff surveyed met criteria for a mental disorder following the first wave of COVID-19 in the UK. Importantly, we found that rates of distress were high, not only among doctors and nurses, but across a wide range of health and social care roles, such as allied health professionals, ambulance workers, hospital porters, pharmacists, and care home staff.

"Let's be clear: we may be on the verge of a mental health crisis across the health and social care sector. So we need to make sure that specialist help is offered and accessible across all the different roles and settings.

"It is important that this support (for those that need it) is planned for the long-term. Our findings highlight the urgency for immediate long-term funding for specialist mental health services for health and social care workers."

Co-author, Dr Jo Billings (UCL Psychiatry), said: "A really important finding from our study is that it showed that, in addition to doctors and nurses, all staff across the health and social care sector need to be offered help. This study also highlights the need for reliable access to PPE for all staff working in health and social care roles, and further investigation of barriers to communication between managers and staff. Our findings also highlight that staff redeployed into new frontline roles are at particular risk of being traumatised and are likely to require additional support during redeployment."

Nearly 100 percent of the red snapper sampled in the Gulf of Mexico over a six-year period by University of South Florida (USF) marine scientists showed evidence of liver damage, according to a study reported in Aquatic Toxicology.

The study is the first to correlate the concentration of crude oil found in the workhorses of the digestive system -- the liver, gall bladder, and bile - with microscopic indicators of disease, such as inflammation, degenerative lesions, and the presence of parasites. The team sampled nearly 570 fish from 72 Gulf locations between 2011 to 2017 in the wake of the historic 2010 Deepwater Horizon oil spill.

"The results add to the list of other species we've analyzed indicating early warning signs of a compromised ecosystem," said Erin Pulster, PhD, first author of the study and researcher at the USF College of Marine Science.

Pulster and the team of researchers studying oil pollution in Gulf of Mexico fishes have previously reported high levels of oil exposure in yellowfin tuna, golden tilefish, and red drum as well.

The Gulf of Mexico not only experiences hundreds of annual oil spills with long-lasting effects such as the historic Deepwater Horizon spill in 2010 but is routinely subject to intense shipping traffic and collects pollutants from faraway places that flow in from coastlines and rivers like the Mighty Mississippi and the Rio Grande.

In this study Pulster and the team looked specifically at the most toxic component of crude oil called polycyclic aromatic compounds, or PAHs. PAH sources include old oil and gas rigs, fuel from boats and airplanes, and natural oil seeps, which are fractures on the seafloor that can add millions of barrels of oil to the Gulf every year.

The presence of PAHs in the bile, which is produced by the liver to aid in digestion, indicates relatively recent oil exposure (days to weeks). The team found that the PAH concentration in the bile declined and remained relatively stable after 2011 but they noted a sharp increase in 2017.

Overall, the bile PAH "hot spots" were on the West Florida Shelf (WFS) and in the vicinity of the Deepwater Horizon spill, off the mouth of the Mississippi River. This is the site of the 2004 Taylor oil platform collapse off Louisiana, the longest oil spill in history, which continues to leak oil today. The hotspot west of Tampa on the WFS could be due to shipping traffic or submarine groundwater discharge, Pulster said.

PAH found in the liver indicates the fish has been chronically exposed to oil (months to years). The team found the liver PAH "hot spots" in the northwest Gulf of Mexico, where a considerable number inactive oil and gas platforms exist.

While the PAH concentrations in the liver remained relatively stable throughout the study, indicating that the red snapper are physically managing the oil exposure, there is a tipping point, Pulster said. Red snapper can live upwards of 40 years but fish manage oil toxins, similar to the way humans manage exposure to greasy burgers and alcohol.

Repeated exposure to oil in fish can lead to cancer and eventually to death, but it can also result in sublethal impacts. Virtually all (99 percent) of the red snapper sampled had an average of five physical signs of liver damage. The observed changes can result from natural causes but are also well documented secondary responses to stress which, could potentially signal disease progression.

"We just don't know when we will tip the scale," said Pulster. There was literally one red snapper in the bunch with PAHs but no physical signs of damage when viewed under the microscope, said Pulster.

It's a good thing that humans only eat the muscle of the fish, not the liver. Red snapper remain safe to eat but Pulster stressed the need for continued monitoring. Only then can scientists keep their finger on the pulse of fish health and know what the impacts of additional oil spills may be - especially in species like snapper that are so critical to the Gulf economy, she said.

"This is a unique study. Most investigations of oil spill effects only last a year or two, and this study gives us both a wide scale of reference across the Gulf and also long-term monitoring, which we lacked prior to Deepwater Horizon," said Steve Murawski, PhD, senior author on the study. Murawski, a professor and the St. Petersburg Downtown Partnership Peter R. Betzer Endowed Chair at the USF College of Marine Science, led the 10-year research effort in response to the Deepwater Horizon oil spill (C-IMAGE (usf.edu).

"There is a story we can tease out of the data," Murawski said. "The observed decline in oil exposure in red snapper in the few years following the Deepwater Horizon accident suggests the high levels measured in earlier years were a direct impact from the spill. Its legacy continues, and we'd be wise to continue the critical research ironically made possible by long-term monitoring post-disaster."