Culture

AMHERST, Mass. - Over the last 20 years, many academic institutions have conducted surveys in STEM disciplines, seeking ways to address and increase awareness of discrimination and racism that are major obstacles to attracting and retaining women - particularly underrepresented minority women - to diversify the STEM workforce.

Now results of a new experiment by researchers at the University of Massachusetts Amherst suggest that an online mutual-mentoring model called "Amplifying Voices" can create "trusting and supportive environments" among underrepresented minority women in STEM across academic institutions. Details were published online by the journal Innovative Higher Education.

Lead author Sandra Petersen, professor of veterinary and animal sciences, says, "Our research suggests that combining career-focused mentoring found in most academic institutions with empathetic psychosocial mentoring achieved through Amplifying Voices is a more effective strategy for supporting underrepresented minority women in STEM than either strategy alone."

She and co-authors Barbara Pearson, retired from the Office of Research Development, with Mary Moriarty of Research and Evaluation Associates, Northampton, point out that underrepresented minority women women make up nearly 18% of the population, but only 3% of STEM tenure-track faculty members in four-year colleges and universities.

Mentoring is the most commonly cited intervention to help faculty achieve success in higher education, and is especially important for those from underrepresented groups.

However, they are less likely to receive effective mentoring, Petersen and colleagues add. Empathetic mentoring is best provided by colleagues who understand intersecting racial and gender stereotypes, but empathetic mentoring relationships may be difficult to establish when mentor and mentee are in the same institution, they note.

To investigate the effectiveness of the Amplifying Voices approach, the researchers adapted the in-person mutual-mentoring model from the book,"Every Other Thursday" by Ellen Daniell. The new goal was to determine the feasibility and effectiveness of adapting it to an online format linking women STEM faculty at many institutions.

For this two-year study, Petersen and her colleagues recruited four groups of five to seven women from similar disciplines, but at 20 different institutions that collaborate in the Northeast Alliance for Graduate Education and the Professoriate, a National Science Foundation program to diversify STEM Ph.D. programs and the professoriate.

Groups included 16 African Americans, one Asian, five Hispanics or Latinas, one American Indian, and one White.

Each group selected a facilitator for the 60- to 90-minute every-other-week Zoom meetings. An anonymous eight-question pre-survey and the same post-survey 14 months later was used to assess changes in support level and effectiveness of the process. Of the 24 participants, 14 (58%) completed the post-survey.

Petersen and colleagues report, "Results of the post-survey showed that participants generally agreed that the components of the mutual mentoring model, as well as the way it was instituted and supported, were effective. Eighty-six percent agreed or strongly agreed that the format met mentoring needs and provided an effective platform for discussing challenges faced in their institutions; 92% indicated that it was also a good place for discussing solutions to those challenges. Importantly, 93% agreed or strongly agreed that the virtual environment was an effective way to conduct a mentoring group."

Participants also indicated that groups made up of mostly underrepresented racial/ethnic groups created an environment where people understood stereotype threat and implicit bias without having to educate colleagues about these issues.

Facilitators also said their groups worked because "they understood each other's struggles," they "felt relieved to know that they were not alone," and "often came to new insights by sharing professional experiences, achievements and challenges."

The researchers state, "Given the relatively low cost of program coordination and the capacity to network individuals across institutions with available technologies, we believe that the Amplifying Voices program is an attractive model for providing a mentoring community for URM women."

Most traditional cancer therapies target either the tumor cells themselves or indiscriminately kill any rapidly dividing cell. New findings by researchers at University of California San Diego School of Medicine indicate that manipulating macrophages, a type of immune cell found abundantly in the tissues surrounding a tumor, could also be a viable strategy for treating cancer.

The study, published June 10, 2020 in PLoS Biology, is the first to uncover the role a molecule called IRE1α plays in determining whether macrophages promote inflammation in the tissues surrounding cancer cells -- a region known as the tumor microenvironment -- and throw off the ability of other immune cells to fight cancer. Inflammation is known to promote tumor growth, making IRE1α an attractive target for future study and drug development.

"We've known that it takes a toll on a person's ability to fight cancer when the tumor microenvironment is not properly regulated, when there's a mix of pro-and anti-inflammatory macrophages," said senior author Maurizio Zanetti, MD, professor of medicine at UC San Diego School of Medicine and head of the Laboratory of Immunology at UC San Diego Moores Cancer Center. "What we discovered here is how that happens, and a potential way to reverse it."

IRE1α is a key regulator of the unfolded protein response, a cellular process that mammalian cells use to deal with stress. Life in the tumor microenvironment is stressful for immune and cancer cells, where they may be cut off from oxygen and nutrients. IRE1α and the unfolded protein response can often determine whether a cell survives under these conditions.

In the new study, Zanetti and team show for the first time that IRE1α and the unfolded protein response are also responsible for immune cell malfunction in the tumor microenvironment. The researchers found that IRE1α regulates macrophage activation, determining whether these abundant immune cells secrete molecules that increase inflammation and at the same time produce signals that suppress the immune system. They also discovered that IRE1α boosts levels of PD-L1, a molecule that inhibits other immune cells.

To corroborate their findings in mice, Zanetti and team looked for IRE1α patterns in genomic data available in The Cancer Genome Atlas (TCGA), the National Institutes of Health's database of genomic information from thousands of human tumors. They found that in human breast and cervical cancers, the presence of macrophage IRE1α predicts the presence of PD-L1.

IRE1α's newly discovered role in regulating PD-L1 is significant because the interaction between PD-L1 on tumor cells and its receptor on immune cells tells the immune system to leave tumor cells alone. Checkpoint inhibitors, a type of cancer immunotherapy, treat cancer by blocking that interaction, and thus boosting the immune system's ability to fight off cancer. Other recent studies have shown that a person's response to anti-PD-L1 immunotherapy depends on the PD-L1 present on their macrophages, not on their tumor cells.

What this means, Zanetti said, is that a therapeutic drug that inhibits macrophage IRE1α might work indirectly as a checkpoint inhibitor -- less IRE1α could mean less PD-L1, removing the brake and allowing a person's immune system to better attack tumor cells on its own.

To test this approach, the team engineered mice that lack the IRE1α gene in their macrophages. These IRE1α-deficient mice survived melanoma better than control mice.

"The implication for therapy is that, down the line, we might be able to locally inhibit IRE1α to specifically prevent the mis-regulation of the macrophages that infiltrate tumors and thus tip the balance in favor of the immune system rather than the tumor," Zanetti said. "There is an urgent need to develop IRE1α inhibitors as therapeutics for humans."

New research indicates that taking vitamin D supplements may help prevent a potentially serious side effect of a revolutionary form of anti-cancer therapy. The findings are published early online in CANCER, a peer-reviewed journal of the American Cancer Society (ACS).

Immune checkpoint inhibitors help the immune system recognize and combat cancer cells, and although these treatments have helped many patients and have prolonged lives, they can cause side effects such as colitis, an inflammatory reaction in the colon. "Immune checkpoint inhibitor-induced colitis can limit the use of such life-saving drugs leading to discontinuation of treatment. While it is one of the most common and severe adverse events of immunotherapy, there is a lack of understanding of the risk factors that could be modified to prevent colitis," said Osama Rahma, MD, of the Dana-Farber Cancer Institute and Harvard Medical School, in Boston.

Dr. Rahma and his colleagues conducted a study that examined whether taking vitamin D supplements might reduce the risk of colitis in patients receiving immune checkpoint inhibitors to treat their cancer. The team chose this strategy because previous studies have found that vitamin D may affect the immune system in cases of autoimmune disorders and inflammatory bowel disease.

The study included information on 213 patients with melanoma who received immune checkpoint inhibitors between 2011 and 2017. Thirty-seven (17 percent) of these patients developed colitis. Sixty-six patients in the study (31 percent) took vitamin D supplements before starting treatment with immune checkpoint inhibitors.

Patients who took vitamin D had 65 percent lower odds of developing colitis, after adjustments for confounding factors. These findings were validated in another group of 169 patients, of whom 49 (29 percent) developed colitis. In this validation group, use of vitamin D was linked with 54 percent lower odds of developing colitis.

"Our findings of a link between vitamin D intake and reduced risk for colitis could potentially impact practice if validated in future prospective studies," said Dr. Rahma. "Vitamin D supplementation should be tested further to determine if it could be a safe, easily accessible, and cost-effective approach towards preventing immunotherapy's gastrointestinal toxicity and extending the effectiveness of immune checkpoint inhibitor treatment in cancer patients."

Capital funding of health care, used to build new hospitals, redesign or upgrade existing facilities and invest in new technologies, has declined in Canada over the last 20 years, according to an analysis in CMAJ (Canadian Medical Association Journal).

"Despite increases in total health care spending in Canada, capital investment in Canadian health care has seen a substantial decline in recent years, contributing to Canada's high hospital occupancy rates, hallway health care problem and operating inefficiencies," writes Dr. David Klein, Dalla Lana School of Public Health and St. Michael's Hospital, Unity Health, Toronto, Ontario, with coauthors.

Without adequate capital funding, health care systems are unable to adopt new technologies for diagnosis and patient care or upgrade aging buildings and equipment, which can affect patient care and efficient health care delivery.

"Capital funding to support infrastructure is largely neglected in discussions about annual funding, yet inadequate or uncertain capital investment may threaten the sustainability and equity of the Canadian health care system even more than the variable disbursement of operational funding," says Dr. Klein.

The authors argue that Canada and its provinces and territories should prioritize capital funding by

encouraging innovative funding models, such as public-private partnerships with strong regulatory oversight

pursuing partnerships with strategic investors

improving tax breaks to encourage charitable giving

supporting better tools for decision-making

engaging community stakeholders in capital projects

Expert leadership to oversee investment and project execution is critical.

"More capital alone will not solve the problem," they write. "Capital investment must also be overseen and managed by expert leadership, fairly, transparently and ethically, to protect the public's interest and trust. The challenges underpinning the current level and effectiveness of our health care system will not be solved with one method alone."

TALLAHASSEE, Fla. -- Social distancing during the COVID-19 pandemic has not led to an overall increase in loneliness among Americans.

That's the takeaway from a comprehensive, nationwide study by Florida State University College of Medicine researchers who surveyed more than 2,000 people before and during the enactment of stay-at-home policies in response to the COVID-19 pandemic.

The study on how loneliness and perceived support has changed from before to during the pandemic is published in American Psychologist.

"There has been a lot of worry that loneliness would increase dramatically because of the social distancing guidelines and restrictions," said lead author Martina Luchetti, an assistant professor at the College of Medicine. "Contrary to this fear, we found that overall loneliness did not increase. Instead, people felt more supported by others than before the pandemic. Even while physically isolated, the feeling of increased social support and of being in this together may help limit increases in loneliness."

The paper is part of a larger study College of Medicine researchers are doing on COVID-19 to look at changes in mental health during the COVID-19 crisis and how psychological factors contribute to various aspects of response to the pandemic.

The study involved a nationwide panel of adults ages 18 to 98. Participants first completed a survey in early February unrelated to COVID-19, before the virus was widely known to be a threat to the U.S.

As the threat was being realized, researchers contacted participants again for two more surveys -- one in mid-March during the 15-day period to slow the spread based on White House guidelines and another in late April as the guidelines were about to expire. More than 2,000 responses to the surveys were included in the findings.

The study also looked for increased loneliness in specific at-risk groups, finding only modest evidence of a small increase in loneliness among older adults. Older adults reported less loneliness overall compared to younger age groups, despite an increase in loneliness during the acute phase of the outbreak. That increase in feelings of loneliness among older adults was temporary, leveling off after the issuance of stay-at-home orders.

Individuals living alone and those with at least one chronic condition reported feeling lonelier at the outset but did not increase in loneliness after social-distancing measures were implemented.

"Despite a small increase among some individuals, we found overall remarkable resilience in response to COVID-19," said Angelina Sutin, associate professor of Behavioral Sciences and Social Medicine and senior author.

Loneliness already was a known health risk before the pandemic, and it has been linked to increased risks of morbidity and mortality. Surveys have found that 35 percent of adults 45 and older report feeling lonely and 43 percent of those over 60 report experiencing loneliness at least some of the time.

Some studies suggest that loneliness is even more pervasive among younger adults.

"In the context of the coronavirus pandemic, it may be particularly difficult to reconnect with others given the restrictions on in-person social gatherings," Luchetti said. "Even these transient feelings of loneliness can have a negative effect on health, meaning there could be dangerous unintended consequences if loneliness increases in response to the restrictive measures taken as a result of the pandemic."

Yet from the start of the pandemic, there have been anecdotal reports of people calling their family and friends more often and finding creative ways to stay connected. This outpouring of support may have shielded them from potential increases in loneliness.

The pandemic is also something that everybody is going through.

"Just knowing that you are not alone and that everyone is going through the same restrictions and difficulties may be enough in the short term to keep feelings of loneliness down," Sutin said.

*CORRECTION, 6/22/20, 3 p.m. CT: The estimated number of cardiovascular events that could be prevented with an absolute sugar content tax is 1.8 million.

DALLAS, June 22, 2020 -- A simulation model of different designs of taxes on sugary drinks, which are linked to obesity, cardiovascular disease and diabetes, suggests that all tax designs would generate substantial health gains as well as lower health costs in the U.S., according to new research published today in the American Heart Association's flagship journal Circulation. However, some of the models perform better than others.

Frequent consumption of sugary drinks is strongly linked to weight gain, Type 2 diabetes and cardiovascular disease. Sugary drinks remain the largest source of added sugars intake in the U.S., with about 60% of children and half of adults consuming sugary drinks every day.

Boston researchers created a nationally representative microsimulation model to test three types of taxation on sugary drinks: a flat "volume tax" by drink volume ($0.01 per ounce), the only type used in U.S. cities to-date; a "tiered sugar content tax" by 3 levels of sugar content (ranging from $0.00 for less than 5 grams of added sugars per 8 ounces, to $0.02 per ounce of added sugars for more than 20 grams of added sugars per 8 ounces); and a "fixed sugar content tax" by absolute sugar content ($0.01 per teaspoon of added sugars, regardless of the number of ounces).

Under the simulation scenario, the researchers found all three tax structures would generate tax revenue, lower health care costs and prevent cardiovascular disease events and diabetes cases. However, the tiered tax and sugar content tax could generate the largest health gains and cost savings. Any of the tax designs could be effective public health policy tools that may be able to reduce consumption of sugary drinks, and thus improve health and overall well-being, the researchers noted.

Younger adults (ages 35 to 44 years), blacks and Hispanics, and adults with lower incomes were estimated to experience the largest health gains. Thus, the research suggested that all three sugary drink tax designs may reduce health disparities, particularly among these subgroups.

"Overwhelming evidence confirms that food prices have a big impact on purchasing decisions. Taxing sugary drinks influences consumer choices, reducing consumption," said Yujin Lee, Ph.D., a postdoctoral fellow of the Friedman School of Nutrition Science and Policy at Tufts University in Boston and the co-lead study author. "U.S. cities have introduced volume taxes on sugary drinks. But our findings suggest that a tiered fixed sugar content tax would be best, reducing consumer intakes while also encouraging manufacturer reformulations to reduce the sugar content of their products."

Researchers estimated the potential health impact, quality-adjusted life-years (a measure of disease burden) costs and cost-effectiveness of volume-based and sugar content-based (tiered, fixed) sugary drinks taxes in the U.S. They used nationally representative data and a validated computer simulation model that incorporated data on adults ages 35 to 80 across three National Health and Nutrition Examination Survey cycles (2009 to 2014) to derive sociodemographics, cardiometabolic risk factors and lifestyle habits. Net costs were calculated from adding the expense of the government's implementation of tax collection plus the industry's compliance and reformulation costs, then subtracting health care savings from fewer medical screenings, treatments, medications, surgeries and supplies, discounted at 3% annually.

In the U.S., seven cities (Philadelphia; Seattle; Boulder, Colorado; and Berkeley, Albany, Oakland and San Francisco, California) currently have volume-based taxes for sugary drinks as does Mexico, Belgium, Brunei, Norway and the Philippines. The American Heart Association currently advocates for a tiered sugar content tax as an effective approach to achieve better health and expand healthier options. The Association has also supported volume-based sugar taxes, which were able to be passed in those seven cities. Taxing sugary drinks based on sugar content (i.e., tiered or fixed tax) has been implemented in other countries, including Chile, Ireland, the United Kingdom, France, Portugal and South Africa.

The simulation found that, compared to the status quo, over a lifetime, a volume-based tax could:

prevent 850,000 cardiovascular (CVD) events;

prevent 269,000 cases of diabetes;

gain 2.44 million quality-adjusted life years across the population;

generate $80.4 billion in federal tax revenue; and

save $53.2 billion net health care costs.

However, the tiered- and absolute-sugar content tax structures could double those gains.

In the simulation model, a tiered tax would:

prevent 1.67 million CVD events;

prevent 531,000 diabetes cases;

generate $142 billion in tax revenue;

gain 4.85 million quality-adjusted life years across the population; and

save $105 billion in net health care costs.

Similarly, the simulation estimated that an absolute content tax would:

*prevent 1.8 million CVD events;

prevent 550,000 diabetes cases;

generate about $42 billion in tax revenue;

gain 5 million quality-adjusted life years across the population; and

save $105 billion in net health care costs.

For this study, the researchers defined sugary drinks as soft drinks/sodas, juice drinks, sports drinks, pre-sweetened iced tea or coffee, and electrolyte replacement drinks with 5 or more grams of added sugars per 12 ounces. Consumption of sugary drinks, including their added sugars content for each person, was derived from two, 24-hour dietary recalls per person.

Given that the projections and modeling are based on observational data, the study does not establish a causal link between the health and cost effects of these sugary drink tax designs in U.S. adults. Rather, the estimates provide evidence that can be considered and incorporated into the design, implementation and evaluation plans of potential taxes, including at local, state or federal levels. The model's population also did not include children, adolescents or adults under age 35.

"Our study underscores the importance of considering different sugary drink tax designs in any new local, state and federal efforts to improve health outcomes and save health care costs," Lee said.

Researchers behind the report - Uncharted Territory: Universal Credit, Couples and Money [released Monday 22 June, 00.01] - say the way Universal Credit is designed and delivered does not fit the way modern couples and families live their lives.

Based on interviews with nearly 100 participants in more than 50 claimant households across England and Scotland, the research finds that, for some, the transition to Universal Credit has proved relatively easy. But, for many others, it has exacerbated financial strains and created additional difficulties with which they must grapple on a daily basis.

The staged rollout of Universal Credit, which replaces most means-tested benefits and tax credits for people on low incomes both in and out of work, meant that single people without children moved on to it first. This is the first independent research to focus on couples claiming Universal Credit and was carried out by researchers from the Universities of Bath and Oxford, funded by the ESRC.

Whilst previous studies often focused on the poorest and most vulnerable groups, participants in this research were a much broader cross-section of claimants, making their experiences more relevant to the current crisis.

In their report, the researchers highlight how someone claiming Universal Credit in a couple might not realise that how much benefit they receive, or whether they receive any at all, depends on both partners' income and needs.

Some claimants found as well that they had inherited debts from their partner, sometimes from a period long before the couple had even met. Repayments were automatically deducted from the couple's Universal Credit.

The study found that couples often struggled with the unpredictability of the Universal Credit payment, which could vary significantly from month to month, especially for dual-earner couples with two wages paid at different times. The automated nature of the calculation and payment process transfers the risk and onus on to claimants - and in particular women, who mainly dealt with the risk and uncertainty and the resulting administrative burden, described by some as a 'nightmare'.

The fact that Universal Credit is a single payment between the partners in a couple was a design feature that some couples found difficult. Women in particular were not keen on joint accounts and the amalgamation of different benefits into one could upset the delicate balance of both partners having some income of their own. Some women had suffered from financial coercion and control in previous relationships, which had been one reason for them breaking up.

But the payment of the whole monthly lump sum to the woman was not a solution either. The research found that the woman was already more likely to take on the burden of managing the entire household budget, as well as the Universal Credit claim itself.

Dr Rita Griffiths, lead author of the report, from the IPR at the University of Bath, said: "Having to decide who should get the Universal Credit and how the money should be distributed and managed was particularly hard for couples who had no other source of income. It sometimes obliged one partner to go 'cap in hand' to the other to ask for a share of the money. It could also allow one partner to take control of the household's entire monthly income.

"Because most of the couples we interviewed were in committed relationships and trusted each other, this generally didn't happen. However, many felt that a single payment harked back to a bygone era of male breadwinners, and was out of step with modern relationships in which both partners go out to work, manage their own money and contribute to the household finances."

Co-author Fran Bennett, from the Department of Social Policy and Intervention at the University of Oxford, added: "With an unprecedented number of additional Universal Credit claims brought about by the Covid-19 pandemic, policy makers need urgently to learn from these findings so others do not find themselves in the same boat as our participants.

"We are calling on the Government to give more priority to reconsidering how couples are treated in the Universal Credit system. In the first instance, giving access to some income for both partners would be safer and fairer. The government needs to create more security for claimants by tackling the reimbursement of childcare costs in arrears, and the unpredictability of Universal Credit payments, which can affect two-earner families the most. Policy changes more widely should ensure some financial independence for both partners as the best basis for modern relationships and how families live their lives today."

The report will be officially launched at an online event taking place at 2.30pm on Monday 22 June https://www.eventbrite.co.uk/e/uncharted-territory-universal-credit-couples-and-money-tickets-107675038940 .

When cells don't divide into proper copies of themselves, living things fail to grow as they should. For the first time, scientists now understand how a protein called TANGLED1 can lead to accurate cell division in plants.

Inside cells are structures called microtubules, which act like highways for moving proteins and organelles. They're also critical for separating DNA after it has been duplicated to eventually make two cells from one.

"You can't live without microtubules, and plants can't either," said Carolyn Rasmussen, an assistant professor of plant cell biology at UC Riveride. "Because they're so important, where they go and how they move has to be carefully controlled."

Rasmussen and colleagues discovered that the TANGLED1 protein performs this microtubule controlling function by binding the microtubules together like glue. Their description of how TANGLED1 operates was published today in the Journal of Cell Biology.

By adding together microtubules and TANGLED1 in a test tube, the team saw surprising interactions between them. Often, proteins can only bundle microtubules at very specific angles -- 40 degrees or less. TANGLED1 can grab microtubules from any angle and link them together.

"To the best of my knowledge, this is the first plant protein observed in vitro with this characteristic," Rasmussen said.

The protein's ability to capture and stabilize microtubules is likely critical for being able to separate daughter cells properly. Cell divisions at the wrong angle lead to big problems such as the formation of tumors.

Animal cells normally need to remain attached to a surface, and their division is controlled to ensure the cells remain there. If a cell becomes unattached to the surface after division, that could mark the beginning of a tumor.

Rasmussen's team included Pablo Martinez, Sean O'Leary, and Antonia Zhang from UC Riverside; biochemists Ram Dixit and Rachappa Balkunde from Washington University; and mathematician Kenneth Brakke from Susquehanna University.

Now that the team has seen TANGLED1 at work in vitro, the next step is to observe it in a living cell. If they can gain a deeper understanding of the genes that control plant cell division, these genes might be manipulated to produce higher yield crops, such as bigger ears of corn or more grain.

An additional benefit of this research is the insight it could yield into human cellular processes. When there are defects in the cell's ability to move material around on microtubules, diseases such as Alzheimer's disease or cancer could follow.

Research on these diseases is often conducted on human cell lines or animal models. However, there are similarities between the microtubule bundling behavior of TANGLED1 in plants and microtubule binding proteins in humans, making it easier to learn more by characterizing both at the same time.

"People say plants don't get cancer, which is generally true," Rasmussen said. "But sometimes when you have a different perspective on a related question -- in this case, what controls the spatial positioning of cell division -- you can see things that are hard to see in other model systems."

The virus SARS coronavirus 2 (SARS-CoV-2) is the known cause of coronavirus disease 2019 (COVID-19). The "spike" or S protein facilitates viral entry into host cells.

Now a group of researchers from Seoul National University in South Korea, University of Cambridge in UK, and Lehigh University in USA, have worked together to produce the first open-source all-atom models of a full-length S protein. The researchers say this is of particular importance because the S protein plays a central role in viral entry into cells, making it a main target for vaccine and antiviral drug development.

The details can be found in a paper , "Developing a Fully-glycosylated Full-length SARS-CoV-2 Spike Protein Model in a Viral Membrane" just published online in The Journal of Physical Chemistry B.

This video demo illustrates how to build this membrane system from their SARS-CoV-2 S protein models. The model-building program is open access and can be found from the home page of CHARMM-GUI by clicking on the COVID-19 Archive link , or by clicking the archive link in the header, then the COVID-19 Proteins link in the left sidebar.

Developed by Wonpil Im , a professor in Lehigh University's Department of Biological Sciences and Bioengineering Department, CHARMM-GUI (GUI = graphical user interface) is a program that simulates complex biomolecular systems simply, precisely and quickly. Im describes it as a "computational microscope" that enables scientists to understand molecular-level interactions that cannot be observed any other way. More information about CHARMM-GUI can be found in this video .

"Our models are the first fully-glycosylated full-length SARS-CoV-2 spike (S) protein models that are available to other scientists," says Im. "I was fortunate to collaborate with Dr. Chaok Seok from Seoul National University in Korea and Dr. Tristan Croll from University of Cambridge in the U.K. Our team spent days and nights to build these models very carefully from the known cryo-EM structure portions. Modeling was very challenging because there were many regions where simple modeling failed to provide high-quality models."

Scientists can use the models to conduct innovative and novel simulation research for the prevention and treatment of COVID-19, according to Im.

The S protein structure was determined with cryo-EM with the RBD up (PDB ID: 6VSB), and with the RBD down (PDB ID: 6VXX). But, this model has many missing residues. So, they first modeled the missing amino acid residues, and then other missing domains. In addition, they modeled all potential glycans (or carbohydrates) attached to the S protein. These glycans prevent antibody recognition, which makes it difficult to develop a vaccine. They also built a viral membrane system of an S protein for molecular dynamics simulation.

June 22, 2020-- In a new article, scientists provide an exhaustive, evidence-based review of how COVID-19 droplets from infected patients spread through the air and describe how health care professionals can protect themselves. This Pulmonary Perspective is published online in the American Thoracic Society's American Journal of Respiratory and Critical Care Medicine.

In "Coughs and Sneezes: Their Role in Transmission of Respiratory Viral Infections, Including SARS-CoV-2," Rajiv Dhand, MD, professor and chair, Department of Medicine and associate dean of clinical affairs, University of Tennessee Graduate School of Medicine, along with Jie Li, PhD, RRT, associate professor, Department of Cardiopulmonary Services, Division of Respiratory Care, Rush University Medical Center, describe the various types and sizes of virus-containing droplets present in sneezes and coughs, the locations in the respiratory systems where they deposit, and how certain medical procedures and devices may spread these droplets and the risks for health care professionals.

"The apprehension about the use of aerosolized therapies in COVID-19 patients relates to their potential to spread infectious aerosols," said Dr. Dhand. "Our recommendations offer a balanced, scientific perspective on the use of such aerosolized therapies in patients infected with SARS-CoV-2, the virus that causes COVID-19."

Airborne particles may be produced by various aerosol generating procedures (AGPs), such as suctioning or tracheal intubation, as well as by aerosol generators, especially jet nebulizers.

"AGPs such as intubation, bronchoscopy, physiotherapy and suctioning generate potential infectious bioaerosols by provoking coughs and are associated with increased infection rates among employees working in health care," stated the authors. "In contrast, AGPs such as oxygen therapy, use of humidified high-flow nasal cannula, non-invasive ventilation and manual ventilation via mask are less about 'generating' bioaerosols and more about 'dispersing' aerosols further away from the patient."

Drs. Dhand and Li noted that the evidence linking AGPs to spread of viral infections is limited by the low quality of studies on this topic. They also noted that aerosols produced by medical aerosol generators do not contain pathogens unless the aerosol device is contaminated.

The authors make a number of recommendations for reducing the transmission of respiratory tract infections, which are consistent with guidelines from the Centers for Disease Control and Prevention. They include (please see the article for more detail):

Avoid procedures that irritate airways and provoke violent coughing and try to reduce exposure to infectious aerosol.

If possible, health care providers should stay six feet away from infected patients, especially when the patient is coughing or sneezing.

When using a mechanical ventilator, institute barriers to filter the virus or reduce virus dispersion by placing a filter at the exhalation port of the ventilator or connecting a filter to the oxygen mask.

For spontaneously breathing patients, placing a surgical mask on the patient's face or using tissue to cover his or her mouth, especially during coughing, sneezing or talking, may reduce the dispersion distance or viral load.

Employ PPE for health care providers.

While, ideally, infected patients should be in single rooms to prevent droplet dispersion, it is acceptable for two patients with the same infection that is spread by respiratory droplets to be in the same room.

Dr. Dhand concluded, "Coughs and sneezes create respiratory droplets of variable size that spread respiratory viral infections. Because these droplets are forcefully expelled, they are dispersed in the environment and can be exhaled by a susceptible host. While most respiratory droplets are filtered by the nose or deposit in the oropharynx, the smaller droplet nuclei become suspended in room air and individuals farther away from the patient may inhale them.

These finer particles are carried by the airstream into the lungs, where their site of deposition depends on their size and shape and is governed by various mechanisms. The respiratory transmission of the SARS-CoV-2 virus that causes COVID-19 is mainly by respiratory droplets. Appropriate protective measures are necessary to prevent virus transmission in various settings."

Adolescents and young adults (AYA) who have survived cancer often continue to suffer from insomnia long after treatment ends, interfering with a range of daily activities. In a study published today by Pediatric Blood and Cancer, researchers at Dana-Farber Cancer Institute show that an online program developed specifically for AYA cancer survivors can significantly alleviate insomnia and improve overall quality of life.

The program, which consists of six, 20-30 minute sessions, shows how sleep habits that may have helped patients cope with their intensive cancer treatments can become obstacles to healthy sleep as survivors move beyond treatment. Its automated format makes it particularly well-suited to the moment, as telehealth and online programs that are already adopted by many hospitals and clinics, are becoming even more widely used as a result of the COVID-19 crisis.

"Cognitive-behavioral therapy for insomnia (CBT-I), which helps patients understand the behavioral and thought patterns that lead to long-term troubles with falling or staying asleep, has been shown to be very effective in adult cancer survivors. However, it has not been widely tested in the AYA survivor group. We wanted to explore whether a CBT-I program, specifically tailored to AYA survivors and available online, could be helpful in this population," said Eric Zhou, PhD, who conducted the study with Dana-Farber colleague Christopher Recklitis, PhD, MPH.

"People who survived cancer as adolescents or young adults face a variety of sleep-related issues unique to their age group," Zhou commented. "These include the constraints placed on young people's sleep schedules by their parents or disruptive roommates. Teens and young adults also undergo normal developmental changes in circadian timing, naturally going to bed later and sleeping later than younger children and older adults. Insomnia treatments for AYA cancer survivors need to take account of these factors, as well as addressing their long-term cancer-related issues such as pain or fatigue."

The insomnia intervention tested in the study is known as SHUTi (Sleep Healthy Using the Internet) was developed by researchers at the University of Virginia and adapted for AYA cancer survivors by Zhou and Recklitis. The interactive program uses text, images, and video to explain how insomnia develops and how it can be overcome. In adapting the program, Dana-Farber researchers replaced vignettes - brief stories of individuals struggling with insomnia - from the original version with ones more relatable to young people.

The program discusses how sleep behaviors that helped patients weather cancer treatment can become maladaptive when they return to normal life. "During treatment, people may stay in bed because they're not feeling well or haven't gotten enough sleep. They may take naps and their sleep at night can be fragmented," said Zhou. As people move into recovery, these habits can make it difficult to resume healthy sleep patterns.

"SHUTi trains people to recalibrate their sleep so their sleep habits are no longer addressing the problems they experienced during treatment and are, instead, focused on improving long-term sleep," Zhou remarked.

In the study, 22 AYA cancer survivors - mean age 20.4 years - with insomnia enrolled to use the specially adapted SHUTi. As part of the program, participants kept a sleep diary, tracking when they slept, and entered the information into SHUTi, which adjusted its sleep recommendations accordingly.

At eight and 16 weeks after starting to use SHUTi, participants reported a significant lessening in insomnia severity, daytime sleepiness, and fatigue, and an overall improvement in quality of life.

"Our results demonstrate that an internet-delivered CBT-I program targeting AYA cancer survivors reduced their insomnia and improved their quality of life," Recklitis remarked. "Notably, our participants' insomnia severity continued to get better after the intervention had ended, suggesting that the continued to make sleep-related decisions that helped their sleep even after they had finished using the program."

Sometimes, when something is broken, the first step to fixing it is to break it even more.

In a recent example, scientists seeking to understand the mechanism of a DNA-repairing enzyme have discovered that the molecule performs its functions by first marking and then further breaking damaged DNA. The team's surprising findings on the protein, called XPG, have provided much-needed insight into how DNA repair works in healthy cells, as well as how different mutations can translate into different diseases and cancer.

"We saw that XPG makes a beeline for discontinuous DNA - places where the hydrogen bonds between bases on each strand of the helix have been disrupted - and then it very dramatically bends the strand at that exact location, breaking the interface that connects bases stacked on top of each other," said Susan Tsutakawa, a structural biologist in the Biosciences Area at Lawrence Berkeley National Laboratory (Berkeley Lab) and first author on the work, published this month in PNAS. "The bending activity adds to an already impressive arsenal, as XPG was first identified as a DNA chopping enzyme, responsible for cutting out nucleotide bases with chemical and UV radiation damage."

Yet despite this knack for destruction, the team notes that XPG is more like a master sculptor than a demolition crew.

"An unexpected finding from our imaging data is that the flexible parts of the protein - which were previously impossible to examine - have the ability to recognize perturbations associated with many different types of DNA damage," said co-author Priscilla Cooper, a biochemist senior scientist in the Biosciences Area. "XPG then uses its sculpting properties to bend the DNA in order to recruit and load into place the proteins that can fix that type of damage."

A protein with many jobs

Although the extent of what XPG does in human cells is still only partially understood, scientists have long known that the protein is essential to human health by observing the devastating symptoms that occur when it is missing or not functioning normally. Cockayne syndrome, a disease characterized by a progressive and ultimately fatal neurological decline that begins in infancy, and xeroderma pigmentosum, a condition of varying severity characterized by extreme sun sensitivity and greatly elevated risk of skin cancer, are both known to be caused by mutations in the gene that encodes XPG.

Fascinated by its many roles, Tsutakawa, Cooper, and John Tainer, the director of structural biology at the University of Texas MD Anderson Cancer Center and visiting faculty in the Biosciences Area, have been collaborating on studies of XPG for 20 years. The trio, and their many colleagues, pool their expertise in structural biology, molecular imaging, biochemistry, and cell biology so that they can map the protein's structure and interpret how its three-dimensional form interacts with DNA and other proteins. They had previously discovered that XPG often binds to damaged DNA without engaging its DNA cutting activity, but could not examine the protein in great enough detail to find out what it actually does in these instances.

After many years spent developing technology that could catch up with their ambitions, the team was finally able to build a precise model of XPG's catalytic core - the region responsible for the DNA cutting activity - and produce images of the large, multiple-unit molecule's overall structure using a trifecta of cutting-edge imaging technology.

They performed X-ray crystallography at Stanford Synchrotron Radiation Laboratory, and small angle X-ray scattering (SAXS) at the SIBYLS beamline of Berkeley Lab's Advanced Light Source. SAXS is a technique that has recently evolved to allow scientists to analyze flexible molecules moving freely between their natural states rather than in static or frozen conformations, as necessitated by crystallography. Such an approach is sorely needed for a protein like XPG, whose catalytic core is only one-quarter of the total structure and the rest is made of highly flexible "disordered" regions with no default shape.

To visualize the XPG-bound DNA, the scientists recruited Jack Griffith, a pioneer of rotary shadowing electron microscopy at the Lineberger Comprehensive Cancer Center at UNC Chapel Hill. Rotary shadowing electron microscopy allows direct visualization of individual DNA molecules with proteins bound to them, including how they were bent by XPG.

"The ability to see the shapes of individual DNA molecules gave us an essential clue as to how XPG works to identify and process damaged DNA," said Griffith, a professor of biochemistry and biophysics and expert in protein-DNA interactions.

The electron microscopy imaging also provided visual evidence supporting the scientists' previous surprising finding that XPG plays a role in homologous recombination - a DNA repair process frequently used by cells to fix dangerous double-strand breaks before replication. This means that XPG could be at the right place to help known homologous recombination proteins such as BRCA1 and BRCA2, defects in which are known to cause cancer.

Meanwhile, crystallography performed on the catalytic core shed light on how inherited patient mutations in the gene for XPG can translate into severe protein dysfunction and different diseases. The team made and tested catalytic core proteins having each of the 15 known point mutations that cause either xeroderma pigmentosum or Cockayne syndrome, and found that these single amino acid substitutions can destabilize the entire protein, but to different extents. The properties of the residual mutant protein will determine which disease results. "This structure helps us understand the distinction between the two diseases," said Cooper, "and it reinforces how complex the protein is."

Invigorated by the new information, the team has already begun a study looking at XPG's role in different cancers, as well as a follow-up structural study of the protein's disordered regions to learn more about its DNA sculpting properties.

"The superb technical and collaborative strengths of Berkeley Lab and our partners made this multi-disciplinary breakthrough feasible," noted Tainer.

"But we would also like to highlight the contribution of patients and patients' families," added Tsutakawa. "So much of what we have discovered was made possible by them choosing to share their DNA sequences with the scientific community."

The severity of knee joints damage in soccer players depends on their age and career duration, and the condition of articular cartilage and meniscus of the dominant (which has a higher mechanical load) and the non-dominant leg does not differ. However, even pronounced changes can be asymptomatic and do not impair knee joint mobility, as shown by a group of scientists, which included researchers from the Sechenov University. The findings which will help interpret the results of players clinical examination more accurately, were published in Sports Medicine - Open.

Regular strenuous training is not harmless for professional athletes. They often get injured and, as previous research shows, pathological joint changes are more common than among people of the same age who are not active in sports. Legs experience the major mechanical load in soccer. The dominant, kicking leg is particularly subject to uneven strain and, thus, injuries.

The authors of the study evaluated whether the prevalence and severity of joint damage depends on the age and experience of athletes, as well as if there is any difference in knee injuries between the dominant and the non-dominant leg. They examined 47 professional soccer players aged 19-31. The sample did not include goalkeepers, athletes who previously underwent knee surgery or those who suffered a knee injury in the past three months or were experiencing joint pain at the time of the examination.

Participants were divided into two groups: one included athletes who played soccer for more than 20 years (including sports schools and groups), and the other comprised less experienced players. MRI was used to examine the joints and allowed to obtain the high-resolution images of the joint structures and evaluate the changes in bone and cartilage tissues.

The imaging showed that absolutely all patients had asymptomatic cartilage or meniscus damages. Certain tissue changes were significantly more common in experienced athletes, the others were observed more often in younger players. The condition of the joint was identical in the dominant and non-dominant legs.

Coauthors of the paper included researchers from Sechenov University: Alexey Lychagin, the head of the Department of Traumatology and Orthopaedic Surgery, Eduard Bezuglov, assistant professor of the Department of Sport Medicine and Medical Rehabilitation and the chief doctor of the Russian national football team, and Artemii Lazarev, a 6th-year student of the Faculty of Medicine.

'In my view, the most significant finding of our study is that the vast majority of professional soccer players have asymptomatic cartilage or meniscus damages of the knee joint. These changes are often rather pronounced. For instance, 12.7% of knee joints have grade 4 cartilage damage, and 13.8% have grade 3 meniscus damage. This data can be extrapolated to almost all professional athletes from game sports; it should be considered by doctors when interpreting MRI data after an acute injury and choosing treatment tactics. All studies conducted in this group of players have shown that the surgery negatively affects professional performance and the progression of osteoarthritis. No wonder many well-known sports medicine specialists say that the best surgery is the surgery that did not take place,' said Artemii Lazarev.

The study will help to assess the impact of athletes' experience and leg dominance on the condition of the knee joints, and allow to develop injury prevention programmes and make injuries diagnostics more accurately.

Forest conservation areas in oil palm plantations play a vital role in storing carbon and boosting rainforest biodiversity, a new study on palm oil agriculture in Borneo has revealed.

The study, led by the University of York, found that patches of protected forest play an important role in helping to conserve endangered species including hornbill birds and dipterocarp trees.

The study revealed that plantations, where a tenth of the land is protected as natural forest, store up to 20% more carbon than plantations with no protected forest.

Oil palm agriculture is a key driver of deforestation, causing widespread biodiversity loss and carbon emissions - particularly in Indonesia and Malaysia, where 85% of the world's palm oil is produced.

Lead author of the study, Susannah Fleiss, a PhD student in the Department of Biology at the University of York, said: "Our study found that these forest areas do increase carbon stored in oil palm plantations, helping to mitigate the carbon emissions associated with oil palm agriculture.

"We also found that the protected forest sites which stored the most carbon also contained the highest plant diversity, so by choosing to protect forest areas with high carbon stocks, oil palm plantations will also protect rainforest biodiversity."

For the study, the researchers measured trees and other vegetation in 14 forest areas protected in Roundtable on Sustainable Palm Oil (RSPO)-certified oil palm plantations in Malaysian Borneo.

A key requirement for oil palm plantations to be certified as sustainable, under the RSPO certification scheme, is that the plantations must protect areas of natural forest within their land.

The researchers found that, in comparison to primary rainforest, the forest areas protected within oil palm plantations had low numbers of tree seedlings, meaning they may contain fewer trees in the years to come.

Oil palm plantation owners must act to manage protected areas of forest in order to conserve them for the future, the researchers urge.

Susannah Fleiss added: "We recommend that oil palm plantations manage their protected forest to improve the potential for the trees to produce seedlings and for the seedlings to survive. This could include planting additional seedlings or cutting back vines."

Professor Jane Hill, who co-supervised the project added: "Palm oil is a key ingredient in many supermarket products and it is crucial that it comes from sustainable sources. Our study highlights the importance of retaining forest patches in sustainable cultivation practices."

'Conservation set-asides improve carbon storage and support associated plant diversity in certified sustainable oil palm plantations' is published in Biological Conservation. The research was jointly funded by Unilever and the University of York.

How do plants know when it is time to flower? Researchers at Martin Luther University Halle-Wittenberg (MLU) have studied this question and identified two genes that are key to this process. They were able to show that the ELF3 and GI genes control the internal clock of the plants that monitors the length of daylight and determine when it is the right time to flower. The findings could help to breed plants that are better adapted to their environments. The study was published in The Plant Journal.

Plants also have an internal clock that prepares internal cellular mechanisms in anticipation of the upcoming environmental changes. This ensures that plants only perform specific tasks at the most suitable time of the day. For instance, during the day they carry out photosynthesis, extracting energy from sunlight. However, completely different processes occur at night when the sun is no longer shining. Many plants grow significantly more than during the day. So, in order to tell the difference between day and night, plants have special receptors in their cells that can sense sunlight and start and stop different processes as needed.

"Just like humans, plants also have a so-called circadian clock. This is a complex network of genes and proteins that enables plants to control different processes in relation to time so that their biorhythm is perfectly synchronised to the day-night cycle," explains Dr Usman Anwer from the Institute for Agricultural and Nutritional Sciences at MLU. Like humans, plants react to more than just external influences; the circadian clock regulates metabolism and other processes in the plant cells so that they take place at the right time throughout the day and year. That means plants are able to anticipate certain regularities in their environment, such as the alternation of day and night, and adjust accordingly. This also includes the ability by the plants to begin flowering at the right time. "Plant orient themselves to the ratio between the hours of sunlight and darkness. Some plants only flower when the days are particularly long. Others only flower when the nights exceed a certain length of time," explains the plant scientist. This is not surprising; after all, different plant species flower at different times of the year when the days have different lengths.

In this new study, the MLU researchers wanted to understand which genes control a plant's internal clock, thereby influencing the flowering process. They did this by investigating two genes that were already known to play a crucial role in the circadian clock: ELF3 and GI. "These two genes have always been studied separately. Our goal was to understand how the two genes work together and how they jointly influence the circadian clock, for example by regulating when a plant flowers," says Anwer. The team investigated how the two genes functioned in the model plant, the thale cress, also known as the Arabidopsis thaliana. The scientists bred plants that had various genetic defects. In one group, the ELF3 gene was defective, in the second group it was the GI gene. In the third group, both genes were switched off. The researchers then observed how the plants reacted to different periods of light. They found that when one of the two genes was defective, the plants' circadian clock still functioned on a rudimentary basis. When both genes were switched off, the plant no longer reacted at all. "The plants could still perceive the light, but they could no longer tell how long the light lasted. This explains why the mutants with the double gene defect produced flowers at the same time under different lengths of light period ," Answer concludes.

However, light is not the only external source of information for the circadian clock, says the researcher. The ambient temperature also changes during the course of the day and year. In a follow-up project, the scientists want to understand how temperature influences plant flowering and whether temperature can compensate for the lack of information about light. The findings could also be important for plant breeding. Most plants have adapted to their original environment in such a way that they require a specific ratio between hours of sunlight and darkness in order to flower. The new findings could allow plants to be bred that can also flower in other places and produce good yields.