Culture

You can have too much of a good thing, says study financial analysts' work-life balance

image: Ole-Kristian Hope is the Deloitte Professor of Accounting at the Rotman School of Management. He has broad research interests in financial disclosure, financial reporting quality, corporate governance, analysts, valuation, auditing, private firms, corporate finance, and international business issues. He has published extensively in The Accounting Review, Journal of Accounting Research, Journal of Accounting and Economics, Accounting, Organizations, and Society, Contemporary Accounting Research, Review of Accounting Studies, and several other journals.

Image: 
Rotman School.

Toronto - Last winter, Goldman Sachs reported it was working to make things better after a group of junior analysts revolted against 100-hour work weeks.

That's a smart thing to do, suggests a new study from the University of Toronto's Rotman School of Management. Drawing from more than 6,000 employee reviews of their workplaces and data on their firms' forecasting accuracy, the research shows that making improvements to hardworking analysts' work-life balance produces dividends for the company and for the analysts' careers.

"There is a lot of anecdotal evidence, but here we provide large-scale evidence that supports the recent push to grant these employees at least some reprieve from the extremes of their jobs," said Ole-Kristian Hope, who is the Deloitte Professor of Accounting at the Rotman School, and worked on the research with three colleagues.

Too much of a good thing is possible, however. The study found there was a limit to the positive performance impact of improving work-life balance.

An analyst's forecast accuracy -- that is, how correct their forecasts are about a company's future earnings and whether it's a recommended stock pick -- maxed out once analysts' work-life balance hit about 3.5, or "okay," on a 5-point review scale.

Investment returns based on those stock recommendations showed a similar effect, with returns maxing out when work-life balance reached about 3 out of 5 points. It's thought that this is because people need a certain amount of mental stimulation and demand to process information efficiently.

"If you have too much work-life balance, that means you're not focusing enough on work," said Prof. Hope. "A little bit of stress is probably a good thing but if it's too much then the pressure becomes daunting and you can't do anything."

Optimized work-life balance was also found to support analysts' career advancement, based on job mobility and promotion data and information from a recognized industry awards recognition program. Such awards influence analysts' compensation and career opportunities.

This is the first study to examine the role of work-life balance in financial analysts' performance and career advancement. It was made possible by the availability of employee reviews about the companies they work for via a social media platform called Glassdoor.

The researchers chose these employees to measure the impacts of work-life balance because of their reputation for being more professionally aggressive, career-oriented and having a higher tolerance for stress. Financial analysts can put in as much as 70 to 110 hours a week during quarterly earnings seasons, when companies are issuing their reports. "They're not your typical animals," said Prof. Hope, making it less obvious that work-life balance would affect them the same as it does other workers.

Financial analysts are also important to study because the information they provide contributes significantly to the operation of capital markets. "Learning about the source of variations in their work performance is important by itself," said Prof. Hope.

Credit: 
University of Toronto, Rotman School of Management

GSA's journal's add seven articles on COVID-19 and aging

The Gerontological Society of America's highly cited, peer-reviewed journals are continuing to publish scientific articles on COVID-19. The following were published between May 4 and June 14; all are free to access:

Cardiometabolic therapy and mortality in very old patients with diabetes hospitalized due to COVID-19: Research article in The Journals of Gerontology, Series A: Biological Sciences and Medical Sciences by Jose Manuel Ramos-Rincón, MD, PhD, Luis M. Pérez-Belmonte, MD, PhD, Francisco Javier Carrasco-Sánchez, MD, PhD, Sergio Jansen-Chaparro, MD, PhD, Mercedes De-Sousa-Baena, MD, José Bueno-Fonseca, MD, Maria Pérez-Aguilar, MD, Coral Arévalo-Cañas, MD, Marta Bacete Cebrian, MD, Manuel Méndez-Bailón, MD, PhD, Isabel Fiteni Mera, MD, PhD, Andrés González García, MD, PhD, Francisco Navarro Romero, MD, PhD, Carlota Tuñón de Almeida, MD, Gemma Muñiz Nicolás, MD, Amara González Noya, MD, Almudena Hernández Milian, MD, Gema María García García, MD, José Nicolás Alcalá Pedrajas, MD, Virginia Herrero García, MD, Luis Corral-Gudino, MD, PhD, Pere Comas Casanova, MD, Héctor Meijide Míguez, MD, PhD, José Manuel Casas-Rojo, MD, Ricardo Gómez-Huelgas, MD, PhD, and the SEMI-COVID-19 Network
The Role of Media Sources for COVID-19 Information on Engaging in Recommended Preventive Behaviors among Medicare Beneficiaries Aged ≥ 65 Years: Research article in The Journals of Gerontology, Series B: Psychological Sciences and Social Sciences by Boon Peng Ng, PhD, and Chanhyun Park, PhD
Impact of Negative and Positive Age Stereotypes in Media on Older Individuals’ Mental Health during the COVID-19 Pandemic: Article in The Journals of Gerontology, Series B: Psychological Sciences and Social Sciences by Becca R. Levy, PhD, E-Shien Chang, MA, Sarah Lowe, PhD, Natalia Provolo, BA, and Martin D Slade, MPH
Network-exposure severity and self-protective behaviors: The case of COVID-19: Original research article in Innovation in Aging by Howard Litwin, PhD, and Michal Levinsky, MA
COVID-19 and its Impacts on Older Adults: Global Perspectives: Editorial in The Journals of Gerontology, Series B: Psychological Sciences and Social Sciences by Danan Gu and Qiushi Feng
The Lived Experience of Already-Lonely Older Adults During COVID-19: Research article in The Gerontologist by Henry Bundy, PhD, Heather M. Lee, BSW, CCM, Kim N. Sturkey, BA, ACM-SW, CCM, CMC, and Anthony J. Caprio, MD
Purpose in life, loneliness, and protective health behaviors during the COVID-19 pandemic: Research article in The Gerontologist by Yoona Kang, PhD, Danielle Cosme, PhD, Rui Pei, PhD, Prateekshit Pandey, MA, José Carreras-Tartak, BA, and Emily B. Falk, PhD

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The Gerontological Society of America

US beekeepers continue to report high colony loss rates, no clear improvement

image: Honey bees

Image: 
Damien Tupinier

Beekeepers across the United States lost 45.5% of their managed honey bee colonies from April 2020 to April 2021, according to preliminary results of the 15th annual nationwide survey conducted by the nonprofit Bee Informed Partnership (BIP). These losses mark the second highest loss rate the survey has recorded since it began in 2006 (6.1 percentage points higher than the average annual loss rate of 39.4%). The survey results highlight the continuing high rates of honey bee colony turnover. The high loss rate was driven by both elevated summer and winter losses this year, with no clear progression toward improvement for beekeepers and their colonies. BIP hopes to use the survey results to better understand how colony losses are experienced by beekeepers, and what can be done to reduce losses in future seasons.

Since beekeepers began noticing higher losses in their colonies in the early 2000s, agricultural agencies, researchers, and the beekeeping industry have been working together to understand why and develop best management practices to reduce their losses. The BIP annual colony loss survey, which has been conducted since 2006, has been integral to that process.

"This year's survey results show that colony losses are still high," says Nathalie Steinhauer, BIP's science coordinator and a post-doctoral researcher in the University of Maryland Department of Entomology. "Not all beekeepers are affected at the same intensity, but the turnover rate of colonies is still overall higher than beekeepers deem acceptable [normal or acceptable turnover is defined at about 20%]. We should remember, however, that loss rates are not the same as population decline. The recent numbers of honey bee colonies in the U.S. are relatively stable despite those high losses, but that's because beekeepers invest a lot of time and effort to increase their operation size to mitigate their losses."

Commercial honey bee operations are essential to agricultural production in the U.S., pollinating $15 billion worth of food crops each year. Honey bee colonies are moved around the country to pollinate important agricultural crops such as almonds, blueberries, and apples. Minimizing their losses and ensuring the health of both commercial and backyard colonies is critical to food production and supply.

"Beekeepers of all types consistently lose a high number of colonies each year, which puts a heavy burden on many of them to recoup those losses in time for major pollination events like California almonds," says Geoffrey Williams, assistant professor of entomology at Auburn University and co-author of the survey. "Colony losses remain elevated, and this year's annual and summer loss rates are among the highest recorded."

This past year, winter losses were reported at 32.2%, which is 9.6 percentage points higher than last year and 3.9 points higher than the survey average. Summer losses were some of the highest ever reported again this year at 31.1%, which is 0.9 percentage points lower than last year, but 8.6 points higher than the survey average.

The survey asks beekeeping operations of all sizes to track the survival or turnover rates of their honey bee colonies. This year, 3,347 beekeepers managing 192,384 colonies across the country responded to the survey, representing about 7% of the nation's estimated 2.71 million managed colonies. This effort helps to keep a finger on the pulse of what is going on with beekeepers to identify why high losses are persisting.

"Though we see fluctuations from year to year, the worrisome part is we see no progression towards a reduction of losses," says Steinhauer.

"The long-term efforts of the BIP's annual survey are so important to monitoring honey bee colony losses and beekeeper management over time, and hopefully to identifying key practices that are protective for colonies," stresses Williams. "Because of the close connection of honey bees to the environment, the survey's long-term data may lend itself to insights into how changes in land-use and weather impact the beekeeping industry too. These are really understudied areas at the moment."

This year, to get a better understanding of different management practices that may lead to loss fluctuations, the BIP team delivered two versions of the survey to cater to different beekeepers. The two surveys found that backyard (managing 50 or fewer colonies) and sideliner (managing 51-500 colonies) beekeeping operations face both similar and distinct challenges to commercial beekeepers managing more than 500 colonies. While parasitic varroa mites continue to be a major issue for beekeepers regardless of operation size, queen management might be a factor that can lead to variation in seasonal colony losses.

"A colony needs a healthy, fully functioning queen before major pollination events to be productive," explains Williams. "A preliminary look into survey data reveals that commercial beekeepers almost always replace old queens with new ones during the summer, whereas only about half of backyard beekeepers do. Could this explain why commercial beekeepers lose fewer colonies in the subsequent winter than backyard beekeepers? Perhaps, but we need to dig deeper and possibly perform experiments to shed more light on this."

While the survey suggests that beekeepers are remaining responsive to the current best management practices and health concerns of their colonies, the loss data shows little progress.

"We see in the survey signs that beekeepers are adjusting their practices over time," says Steinhauer. "We also see that their perception of risk is changing. The level of acceptable loss, which was originally around 15% in earlier years of the survey, has crept up to 23% this year. So that tells us beekeepers are thinking about those factors that affect honey bee health more actively. We also see some beneficial changes in agricultural practices that could affect honey bee health, like changes in spray recommendations. But there are still a lot of issues that are left unaddressed. It seems we're running to stand still because beekeepers are changing their practices, and yet we still don't see a clear improvement in their loss rates."

BIP stresses that the lack of improvement in losses is a clear call for more attention and efforts to be paid on finding solutions, especially concerning varroa mites. The BIP annual loss survey continues to be an important part of documenting the data necessary to drive future research, best management practice recommendations, and support for honey bee health.

"We hope to continue BIP's survey effort to record colony losses experienced by U.S. beekeepers and explore beekeepers' management practices," ensures Steinhauer. "We have a general idea of what practices are associated with higher success, but the devil is in the details, and we need to understand why the implementation of some practices are more successful in some cases than others. Of course beekeepers also need the support of the public and political sectors. We need to recreate environments that are conducive to healthy bees, and that will benefit both honey bees and native bees or other wild pollinators."

The survey is conducted by the Bee Informed Partnership with data collected and analyzed by the University of Maryland and Auburn University. Survey results are available here on the Bee Informed Partnership website, with a summary provided below.

Winter Loss Estimates:

1 October 2020 - 1 April 2021: 32.2% losses

9.6 percentage points higher than winter 2019-2020: 22.6%

3.9 percentage points higher than average winter loss (2006-2021): 28.3%

Summer Loss Estimates:

1 April 2020 - 1 October 2020: 31.1% losses

0.9 percentage points lower than summer 2019: 32.1%

8.6 percentage points higher than average summer loss (2010-2020): 22.8%

Total Annual Loss Estimates:

1 April 2020 - 1 April 2021: 45.5% losses

1.8 percentage points higher than 2019-2020: 43.7%

6.1 percentage points higher than average annual loss (2010-2021): 39.4%

Loss Comparison by Beekeeper Category:

Backyard beekeepers (manage 50 or fewer colonies): 27.0% summer vs. 42.0% winter losses

Sideliner (manage 51-500 colonies): 19.5% summer vs. 31.9% winter losses

Commercial (manage more than 500 colonies): 30.9% summer vs. 32.9% winter losses

Credit: 
University of Maryland

New class of compounds found to block coronavirus reproduction

A human genetic mechanism hijacked by SARS-CoV-2, the coronavirus behind the COVID-19 pandemic, to help it spread also makes it vulnerable to a new class of drug candidates, a new study finds.

Led by researchers at NYU Grossman School of Medicine, a research team showed that coronavirus reproduction in infected human cells requires chemical changes made by the human protein METTL3 to RNA, a key form of genetic material. Additional human proteins involved in the recognition of modified RNA, YTHDF1 and YTHDF3, were also found to be important to the process.

Published online in Genes and Development on June 24, the study showed for the first time that a molecular inhibitor of METTL3, designed by Storm Therapeutics Ltd and called STM2457, dramatically reduced in cell cultures the replication of both pandemic SARS-CoV-2 and, a less severe, seasonal coronavirus, HCoV-OC43, one cause of the common cold.

"Our results represent the first time a chemical inhibitor of METTL3 has been shown to have an anti-viral effect for coronaviruses, or any virus," says senior study author Ian Mohr, PhD, professor in the Department of Microbiology at NYU Langone Health. "This represents a necessary step in drug development, identifies new targets, and reveals an unexpected strategy to halt the coronavirus lifecycle."

Turning Virus' Weaknesses Against Them

The current study builds on a growing understanding of gene regulation. It has long been established that sequences of As, Gs, Cs and Ts, the molecular letters in the DNA code of genes, are copied into messenger RNA (mRNA) molecules that carry the information to the machinery that determines which proteins are made. Only recently has the importance of chemical modification to mRNAs become apparent in the control of protein production. In some instances this process is controlled by the attachment of a methyl group (one carbon and three hydrogens) to an RNA chain, which turns that genetic message off.

Crucially, coronaviruses that replicate inside human cells are known to encode the complete set of their genetic instructions (their genomes) in RNA chains, raising the question of whether human RNA modification enzymes, including those that attach methyl groups, could impact the production of viral proteins that enable them to multiply.

Past work in Mohr's lab had revealed the enzymes that determine whether an A (adenosine), one of the chemical "letters" making up mRNA, is methylated at the N6 position (m6A) is important for replication of human cytomegalovirus (HCMV), with regulation by human m6A enzymes of mRNAs shaping the immune response to that virus.

In the current study, the research team showed for the first time that the reproduction of SARS-CoV-2 and HCoV-OC43 requires the action, not only of the human enzyme that installs the m6A methylation on RNA, METTL3, but human proteins that bind to this unusual arrangement of methylated RNA, YTHDF1 and YTHDF3. Remarkably, the researchers also found that the RNA genomes of both study coronaviruses contained this m6A modification.

For the next step, the NYU Langone team partnered with the UK-based Storm Therapeutics, which had run a medicinal chemistry program to develop a compound that best inhibited the action of METTL3. The current study compared the effects of the METTL3 inhibitor STM2457 and an inactive control compound, STM2120, on cultures of human lung cells infected with the seasonal coronavirus or SARS-CoV-2. The researchers then used an imaging technology to track viral infection in thousands of cells treated with different doses of STM2457.

Compared with the same concentration of the inactive control compound, the highest dose of STM2457 reduced the number of HCoV-OC43 infected cells in culture by more than 80 percent, while the same dose of STM2457 reduced SARS-CoV-2 reproduction by more than 90 percent. Further experiments revealed that STM2457 reduced viral RNA and protein levels, but not by affecting the same human immune response mRNAs previously found to be important for HCMV.

"The inhibition of coronaviruses by this molecule is really encouraging but understanding exactly why coronaviruses need m6A RNA modification is important and might enable the design of compounds that work even better," says study first author Hannah Burgess, PhD, an assistant research scientist in the Department of Microbiology at NYU Langone Health.

Moving forward, the research team plans to further investigate precisely how m6A modification influences virus and host gene expression in cells infected with pandemic or seasonal coronaviruses and whether STM2457 can interfere with coronavirus replication and prevent severe disease outcomes in non-human animals.

"We went into it hoping to learn about the differences between the biology of innocuous and pandemic coronavirus infections," says co-corresponding author Angus Wilson, PhD, associate professor in the Department of Microbiology at NYU Langone Health. "If anything we found that both share a dependence upon the m6A methylation machinery. That creates the hope that inhibiting METTL3 may also be useful against future pandemic coronaviruses."

Credit: 
NYU Langone Health / NYU Grossman School of Medicine

Powerful people are less likely to be understanding when mistakes are made

Those with power, such as the wealthy are more likely to blame others for having shortcomings and they are also less troubled by reports of inequality, according to recent research from the University of California San Diego's Rady School of Management.

The study published in Social Psychological and Personality Science defines power as control over valuable resources. The paper finds that people in positions of power are more likely to adopt a "choice-mindset," which means that although they have more choices (the definition of power in many cases) they still see others with less power as having lots of choice, regardless of their situation. Consequently, high-power individuals are more likely to blame others if they perform poorly and they are also more likely to punish them.

"Being in a choice-mindset changes how individuals think, feel and behave," said Yidan Yin, the first author of the paper and recent PhD graduate from the Rady School. "Compared to low-power people, high-power people are less likely to be aware of others' constraints. As a result they assign more blame when people make mistakes or have shortcomings. Thus, they see the current hierarchy as more justified."

The results from the research were derived from three different studies the authors conducted to replicate the findings in different settings.

Research findings hold up in three robust study settings

The first study was conducted via a survey in which the researchers measured the sense of power of 363 members of the general public recruited through the platform Prolific. They also asked the participants to complete a separate survey, claiming it was unrelated, in which they were crowdsourcing how to resolve a human resources issue at the university. The survey explained that their academic department was weighing whether to give an administrative assistant a bonus though they had missed a deadline on a big project due to conflicting priorities. The survey participants who measured as having a greater sense of power overwhelming responded the administrative assistant did not deserve the bonus and that their excuses were without merit.

The second study was conducted with the platform Amazon Mechanical Turk involving 393 members of the general public who were randomly assigned to roles as supervisors and subordinates in completing various tasks. Though the assigned ranks were random, supervisors were told they earned the role for their proficiencies and subordinates were told they were designated as such because they were outperformed by supervisors.

The two groups had to judge the performance of an anonymous individual, who by design, made mistakes in completing their tasks. Once again, the researchers found that those with a greater sense of power (supervisors) were harsher, less understanding with their judgment and recommended punishment more than subordinates.

The third study was done in a lab with UC San Diego undergraduates and mirrored the second experiment. The main difference was that both supervisors and subordinates knew that the target person they had to judge had the rank of a subordinate and therefore less choices. The results from the first two studies held up with subjects that had more power assigning more blame and recommending more punishment.

"Each study was designed to build on the others," Yidan and co-author Pamela K. Smith, associate professor of economics and strategic management at the Rady School write. "In study one, we were measuring power, in study two, we manipulated power and in study three, we created a world in which the judges knew the target person had less power and less choices. We wanted to see if the perceptions remained consistent in all three settings. It was a combination of replication and adding these additional twists and turns."

Implications for more equitable public policy and workplace environments

The results from the study have significant implications for public policy, according to the authors.

"Policymakers are in a position of power and privilege and may be less sensitive to the disadvantages of their constituents," the authors write. "This is especially important as we come out of the pandemic when there are big discussions in the political domain on pulling back on unemployment benefits, or rent assistance. If you are in a position of power, you may assume people are choosing to stay home and not work and they can make better choices. However, you may need to think much more carefully about how many choices citizens have and if you are missing constraints they face."

In addition, the implications are far-reaching for the workplace.

"Mangers should be aware of how many more choices they have than their subordinates and their tendency to project their own choices onto others, especially when employees make mistakes." Yin said.

Smith added, "It might require having more discussion with employees and being cognizant of their situation because sometimes lack of choice and constraints can be invisible to someone from the outside."

Credit: 
University of California - San Diego

Study finds abnormal response to cellular stress is associated with Huntington's disease

image: Shown is a surface rendering of G3BP1 granules (in green) detected by immunofluorescence in the HD mouse model cortex.

Image: 
UCI School of Medicine

Irvine, CA - June 23, 2021 - A new University of California, Irvine-led study finds that the persistence of a marker of chronic cellular stress, previously associated with neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), also takes place in the brains of Huntington's disease (HD) patients.

Chronic cellular stress results in the abnormal accumulation of stress granules (SGs), which are clumps of protein and RNAs that gather in the cell. Prior to this study, published in the Journal of Clinical Investigation, it was not known if these types of granules were a pathological feature of HD, an inherited and progressive neurodegenerative disorder that typically strikes in the prime of life.

In addition to identifying SGs as a pathological feature of HD, researchers made several other discoveries including that extracellular vesicles, which float in cerebrospinal fluid (CSF) and act as a messaging system between cells in the brain, can potentially alter the behavior of other cells and impact the abnormal accumulation of the granules. They also found that TAR DNA-binding protein 43 (TDP43) is mislocalized, which has emerged as a critical feature of multiple neurodegenerative diseases.

"We were initially interested in whether the profile of these messages could serve as a biomarker for HD and investigated whether the vesicles from HD patients contain messages that are different from those of unaffected individuals," said first author Isabella I. Sanchez, PhD, from the Thompson Laboratory at UCI School of Medicine.

Researchers found that the CSF of HD patients carried messages in the form of small non-coding RNAs (miRNAs) that did were predicted to alter the production of proteins that are indispensable for SG formation. They soon identified a key player in SG dynamics, GTPase-activating protein-binding protein 1 (G3BP1), as a predicted target.

"This finding regarding the miRNAs was very exciting, as we had simultaneously started investigations to characterize SGs in HD brain tissues. SGs can be very difficult to detect in brain tissues, and it just so happened that we had narrowed down the adequate conditions and were ready to being characterizing G3BP1 SGs in HD mouse and HD patient brains," said Leslie M. Thompson, PhD, Donald Bren and UCI Chancellor's professor in the Departments of Psychiatry & Human Behavior and Biological Chemistry at the UCI School of Medicine, and Neurobiology and Behavior at the UCI School of Biological Sciences.

While SG formation is a normal physiological process that enables cells to overcome stressful conditions, the SG pathology in HD may result from an accumulation G3BP1 SGs that initially served a protective function, but develop into hyper-stable structures over time.

"We hope that our findings will inform future studies aimed at understanding how SG accumulation affects HD progression, and whether targeting SG pathology is a viable therapeutic avenue in the fight against HD," said Robert Spitale, PhD, professor in the Department of Pharmaceutical Sciences and also a lead author of the study.

Credit: 
University of California - Irvine

Research provides a roadmap to HIV eradication via stem cell therapy

image: HIV disrupts the lymphoid immune battleground

Image: 
UC Regents

In a groundbreaking study, a team of UC Davis researchers has discovered a special type of stem cell that can reduce the amount of the virus causing AIDS, boosting the body's antiviral immunity and repairing and restoring the gut's lymphoid follicles damaged by the simian immunodeficiency virus (SIV), the equivalent of the human immunodeficiency virus (HIV) in non-human primates.

The study, published June 22 in JCI Insight, showed the mechanism through which mesenchymal stem/stromal cells (MSCs) enhance the body's immune response to the virus. It also provides a roadmap for developing multi-pronged HIV eradication strategies.

"Impaired immune functions in HIV infection and incomplete immune recovery pose obstacles for eradicating HIV," said Satya Dandekar, senior author of this paper. "Our objective was to develop strategies to boost immunity against the virus and empower the host immune system to eradicate the virus. We sought to repair, regenerate and restore the lymphoid follicles that are damaged by the viral infection."

The lymphoid tissue in the gut is an early site for viral replication and the establishment of viral reservoirs. Dandekar's group has previously shown that an HIV infection causes severe loss of gut mucosal T immune cells and disrupts the gut epithelial barrier lining, leading to a leaky gut.

"The lymphoid follicles are organized structures where the long-term immune attack is launched against pathogens by generating antibody response targeting the virus. These important regions are functionally impaired very early following HIV infection," Dandekar said.

While antiretroviral drugs effectively suppress viral replication, they do not repair the damage caused by the virus to the immune system. On their own, these drugs cannot restore the functionality of the lymphoid follicles damaged by HIV infection.

Can stem cells counteract the gut damage caused by HIV?

The researchers administered bone marrow-derived MSC in a rhesus macaque model of AIDS that had impaired immunity and disrupted gut functions due to the viral infection.

"We are starting to recognize the great potential of these stem cells in the context of infectious diseases. We have yet to discover how these stem cells can impact chronic viral infections such as AIDS," Dandekar said. She is a professor at and the chairperson of the Department of Medical Microbiology and Immunology at UC Davis and affiliated with the California National Primate Research Center.

The study found that the MSCs can modulate, alter and remodel the damaged mucosal site. There were immediate benefits, with a rapid rise in antibodies and T-immune cells targeting the virus. The stem cells were instrumental in the recovery and restoration of these lymphoid follicles.

MSCs also offer an opportunity for an innovative, multi-pronged HIV cure strategy by complementing current HIV treatments.

"Stem cells are good synergistic partner components with drugs. The antiretroviral drugs can stop the fire of the viral infection but cannot restore the forest of the lymphoid tissue compartment. The MSCs would rejuvenate the field and bring back immune vitality," Dandekar said.

Even without the use of antiviral drugs, MSCs were able to increase the host's antiviral response by repairing the lymphoid follicles, restoring the mucosal immunity and reviving what has been targeted by the virus very early on.

MSC treatments

MSC treatments require well defined cell quality controls and specific delivery mechanisms. The UC Davis Stem Cell Program, a center for excellence for stem cell research, is leading multiple clinical trials on MSC use in treating diseases such as spina bifida and Huntington's disease. Findings from this study provide a scientific basis for investigating MSC in treating HIV and other infectious diseases in the clinical setting.

Credit: 
University of California - Davis Health

Coral offspring physiology impacted by parental exposure to intense environmental stresses

image: A recent publication in the journal Global Change Biology documents the results of two years of experiments conducted at BIOS by a team of researchers including Kevin Wong (shown here), a doctoral student at the University of Rhode Island. The results of the experiments provide insight into coral resilience, demonstrating that adult corals that survive high-intensity environmental stresses can produce offspring better suited to survive in new environments.

Image: 
Kevin Wong

Adult corals that survive high-intensity environmental stresses, such as bleaching events, can produce offspring that are better suited to survive in new environments. These results from a series of experiments conducted at the Bermuda Institute of Ocean Sciences (BIOS) in 2017 and 2018 are deepening scientists' understanding of how the gradual increase of sea surface temperatures and other environmental disturbances may influence future coral generations.

Researchers on the project included BIOS marine ecologists Samantha de Putron and Gretchen Goodbody-Gringley (now with the Central Caribbean Marine Institute), ecophysiologist Hollie Putnam at the University of Rhode Island (URI), and Kevin Wong, then a first-year doctoral student at URI. Primary funding came from the Heising-Simons Foundation International, Ltd. with additional funding from the National Geographic Society and the Canadian Associates of BIOS (CABIOS).

The team spent last year working the data into a manuscript, which was published this month in the journal Global Change Biology and listed Wong as the first author. Wong, now nearing the end of his fourth year of studies at URI under the mentorship of Putnam, plans to graduate in May 2022.

"We know parental history influences the characteristics of offspring in corals, however the experimental design used in this study provides us with a unique perspective on how multiple types of thermal events can accumulate over time and have lasting consequences across generations," Wong said.

Coral Collection and Study
The multi-year field and lab-based study began in the summer of 2017. Departing from BIOS on a small boat with diving gear, the team collected 40 adult Porites astreoides (mustard hill) corals from two different reef sites northwest of Bermuda: a patch reef (Crescent Reef), which is located in a shallower lagoon environment, and a rim reef (Hog Reef) which is a barrier reef more exposed to open ocean conditions.

They next placed the live corals in the then newly-constructed BIOS mesocosm facility, where large outdoor aquaria "flow-through" seawater systems allowed researchers to control and adjust water temperature in the tanks for completing the study.

A variety of baseline data were collected on the corals in each colony, such as metabolic rates and the density of Symbiodinaceae, the symbiotic algae that live within the coral tissues. To simulate a thermal stress event, the adult corals were exposed to two different temperature treatments--ambient (84°F or 29°C) or heated (88°F or 31°C)--for a period of 21 days over their reproductive period. Afterward, the team assessed the physiology of the adult corals, looking at key functions such as respiration and photosynthetic rates. They also monitored the release of coral larvae and assessed its physiology, measuring the larval size and density of Symbiodinaceae within each larva, among other factors.

Upon completion of the experiment, the adult corals were divided in half and reciprocally transplanted, with half of the fragments positioned in the new environments and half returned to their originating environments. All of the fragments remained in place until the summer of 2018, when they were re-collected, and the physiologies of both adult corals and coral larvae were assessed in the same manner as in 2017.

A Stronger Coral Generation
The results of this two-year investigation showed that adult corals that experienced the thermal stress event produced offspring more capable of thriving in their current environment. This means that parent corals that experience stressors may be able to "pre-condition" their offspring to survive in new environments in the following year. The results also indicate that high-intensity environmental stress events, such as bleaching, can have lasting impacts on adult colonies and how they produce their offspring.

"The coral used in this study is a notoriously resilient coral and these findings potentially demonstrate how this species is so persistent across the Caribbean," Putnam said. "Not all coral species are this robust to environmental stressors. However, this system allows us to unravel the mechanisms leading to resilience and identify which corals are most sensitive to climate change."

Long-time Member of BIOS Community
Wong, 27, is a familiar face at BIOS, having first arrived on campus in the summer of 2014 as a CABIOS intern when he spent 12 weeks working with de Putron on a research project investigating the role of temperature and light on the growth and survivorship of juvenile mustard hill corals from two different reef zones. The following year, he received CABIOS funding to work with then-faculty member Gretchen Goodbody-Gringley on a project focused on the reproductive ecology of corals from mesophotic reef ecosystems, deeper-water reefs which typically extend from 100 to almost 500 feet (30 to 150 meters) in depth.

While presenting the results of his research at the 2016 International Coral Reef Symposium meeting in Hawaii, he had the opportunity to interview with Putnam for URI's Biological and Environmental Sciences doctoral program. Wong then returned to BIOS to spend six months in 2016 as a teaching assistant for several summer and fall courses. He also received BIOS Grants-in-Aid funding for a research project with Goodbody-Gringley and de Putron focused on the reproductive ecology of mustard hill coral from various reef sites around Bermuda, resulting in a publication in the journal Coral Reefs.

"It is wonderful to see an undergraduate intern progress to a successful graduate student who is publishing manuscripts," de Putron said. "Many years of hard work and plenty of exhausting, yet fun, days in the field and laboratory all culminated in interesting and critically relevant discoveries that further our understanding of coral resilience."

Now, a year from graduation, Wong is diving deeper into the mechanisms that drive environmental memory within and across coral generations at a molecular level. By using approaches such as metabolomics (the identification and quantification of metabolic by-products), transcriptomics (quantification of gene expression), and epigenetics (features that regulate gene expression), Wong aims to determine the key linkages between metabolism and coral bleaching phenotypes at a cellular level.

Credit: 
Bermuda Institute of Ocean Sciences

Smoother silicone breast implants may reduce severity of immune system reactions

image: Scanning electron microscope image of a silicone breast implant.

Image: 
Josh Doloff

FOR IMMEDIATE RELEASE

STUDY SUGGESTS THAT SMOOTHER SILICONE BREAST IMPLANTS REDUCE SEVERITY OF IMMUNE SYSTEM REACTIONS

According to researchers at Johns Hopkins Medicine, the Massachusetts Institute of Technology (MIT) and Rice University in Houston, silicone breast implants with a smoother surface design have less risk of producing inflammation and other immune system reactions than those with more roughly textured coatings. Results of the experiments using mice, rabbits and samples of human breast tissue advance knowledge of how the body responds to such implants, providing new information to physicians and affirming the benefits of certain smoother surfaces, the researchers say.

A summary of the experiments, funded by an implant manufacturer, are published June 21 in Nature Biomedical Engineering.

Breast implants, surgically inserted following mastectomies or to augment breast size, can be filled with either saline or silicone, but both types have a silicone outer shell. Previous studies showed that most of the 400,000 women each year in the U.S. who receive silicone implants will need to have them replaced within 10 years because of pain and shape shifting of the implant caused by immune system cells that contribute to scarring and fibrous tissue.

"Our aim is to provide patients with as much information as possible so they can make informed decisions to guide their own personal health," says Joshua Doloff, Ph.D., assistant professor of biomedical engineering at The Johns Hopkins University and a first author of the research, which began during his postdoctoral training at MIT.

Doloff, whose research overall focuses on the interface between implantable devices and the human body, says scientists have long known that the immune system biologically walls off foreign objects in the body by creating inflammation and scarring that can be disfiguring and painful.

For the past decade, scientists have been examining how to design implant surfaces in ways that reduce such effects.

Previous studies found that implants with absolutely smooth coatings produce strong immune rejection responses over time, and according to Doloff, they may also more easily "flip" inside the body and contribute to a higher rate of replacement. So, manufacturers also marketed implants with textured surfaces to try to address immune system rejection and to "stick" like Velcro to human tissue, enabling better and more stable positioning in the body. More than 90% of breast implants used in the U.S. are characterized as smooth, according to the researchers, whereas most implants used outside of the U.S. .

An implant with the highest degree of textured surface was taken off the U.S. market in 2019 because of its links to higher rates of a type of cancer called breast implant-associated anaplastic large cell lymphoma among patients with these "macrotextured" implants.

In the current study, the researchers analyzed outcomes of placing in mice tiny versions of implants with five different surface designs. The implants included one with a completely smooth surface, one slightly contoured at the level of an individual human cell, as well as others with different surfaces. Of note, they also implanted one with the 90-micron macrotextured surface like the implants taken off the market.

Establishment Labs helped manufacture the mini-implants, using similar manufacturing methods used in the market. Two of the full scale commercial implants, including one with a surface design that includes a roughness of approximately 4 microns on average as well as other characteristics including skewness and the number, distribution and size of contact points, are also manufactured by Establishment Labs, which funded the research.

Among human-scale size implants used in rabbits, the implant with design features that include a 4 micron surface roughness resulted in the least fibrous tissue surrounding it -- about 10 times less -- at three weeks and six months post-implantation when compared with the 90 micron implant.

Tissue surrounding implants in mice and rabbits with the specific design that includes a 4 micron roughness had the highest activity of the gene FOXP3, suggesting the production of more immune cells called Tregs, which act as traffic police to reduce the amount of inflammation and fibrous tissue created by immune system cells.

The research team also sequenced genetic expression levels from specific cell types in the tissue surrounding implants in mice to find that genes associated with pro-inflammatory responses, including STAT1 and CXCL10, increase about fivefold to tenfold with more highly textured implants.

Among tissue collected from implants removed from 15 healthy patients at the University of Texas MD Anderson Cancer Center in Houston and the Costa Rican Institute for Research and Teaching on Nutrition and Health Foundation, patients with implants with design features that include a 4 micron surface roughness had the most significantly reduced fibrous tissue formation surrounding the implants compared to the more heavily textured devices or to completely smooth ones.

Doloff says other areas of active research for implantable devices include development of biosensors that can detect rupture, leakage or inflammation of surrounding tissue. He says the surface design that includes roughness of 4 microns may be worth studying in biomaterials other than breast implants. He also plans to study the amount of immune response, inflammation and fibrous tissue among implants in women following cancer diagnosis and treatment.

"Engineers should know how something works, not just that it works, so we can improve on existing technologies, says Doloff.

Credit: 
Johns Hopkins Medicine

Food protein can eliminate pungency and bitterness of extra virgin olive oil

PHILADELPHIA - Researchers have been investigating the potential health-promoting qualities of extra virgin olive oil (EVOO) for decades, including its possible medicinal value for preventing cancer, Alzheimer's, and cardiovascular disease, as part of the well-known Mediterranean diet. However, consumers in the U.S. have been slow to embrace it as a staple in their diet. This reluctance, say scientists, might be in part due to EVOO's bitter taste and pungency, which is caused by the presence of substances known as phenolic compounds, the very ones believed to contribute to EVOO health benefits. In 2005, researchers from the Monell Chemical Senses Center identified one of these compounds as an anti-inflammatory that they named oleocanthal and is mostly responsible for the oil's strong, pungent sensation localized to the throat.

Now, another team from Monell has shown that the presence of certain food proteins, such as those in egg yolk, suppresses EVOO's purported less desirable sensory qualities. The team published their findings in Scientific Reports.

"Knowing that the oil can be consumed without bitterness or stinging sensation might increase the popularity of this healthy food," said first author Catherine Peyrot des Gachons, PhD, a Monell senior research associate. "Our findings show that, in many cases, people are not going to perceive the bitterness and pungency once mixed in food."

While experimenting in the laboratory, investigators put the EVOO into a mayonnaise-like material that would be easier for sensory study participants to assess, rather than drinking unadulterated EVOO from a drinking glass, as is commonly done for EVOO tasting. They discovered that after several hours the oil-mayo mixture was much less pungent and bitter. Even a small amount of egg yolk in the mixture was sufficient to cause this reduction.

"This was a big surprise to us," said coauthor Gary Beauchamp, PhD, Distinguished Member of Monell. "But it probably would not be a surprise to people from the Mediterranean area who are much more familiar with consuming extra virgin olive oil in foods and even neat."

The team showed that proteins in the egg yolk were responsible for eliminating EVOO pungency and bitterness. Others such as whey protein yielded similar sensory suppression. The researchers hypothesize that eliminating bitterness and pungency in EVOO happens when proteins interact with oleocanthal and the bitter-tasting phenolic compounds.

The possibility that oleocanthal could be bound by food protein raises a significant conundrum for scientists. For example, the authors ask, could this binding reduce oleocanthal's medicinal effects in the human body? Or, to the contrary, might it make oleocanthal more available in the human body compared to oleocanthal alone? "We don't know the answer to those questions, but it certainly raises some interesting and important issues of bioavailability of this compound," said Beauchamp.

Knowing definitively that EVOO can be comfortably consumed when mixed with other foods might encourage people to consume more, say the researchers, thereby gaining from its medicinal and culinary benefits. However, consumers need to know that only high quality EVOOs contain enough oleocanthal to impart putative health advantages. Olive oil is more expensive than other forms of fat, but there may be a major payoff - the potential for health benefits that other cooking oils do not possess, say the study's authors.

Credit: 
Monell Chemical Senses Center

Combining three techniques boosts brain-imaging precision

image: A new approach to brain imaging combines functional MRI, electroencephalography and a technique known as EROS, which shines near-infrared light on the scalp to capture brain activity. (A young woman inside an MRI suite wears an imaging cap with many sensors attached.)

Image: 
Photo by L. Brian Stauffer

CHAMPAIGN, Ill. -- Researchers report that they have developed a method to combine three brain-imaging techniques to more precisely capture the timing and location of brain responses to a stimulus. Their study is the first to combine the three widely used technologies for simultaneous imaging of brain activity. The work is reported in the journal Human Brain Mapping.

The new "trimodal" approach combines functional MRI, electroencephalography and a third technique, called EROS, that tracks the activity of neurons near the surface of the brain using near-infrared light.

"We know that fMRI is very good at telling us where in the brain things are happening, but the signal is quite slow," said postdoctoral researcher Matthew Moore, the first author of the study, which was conducted at the University of Illinois Urbana-Champaign's Beckman Institute for Advanced Science and Technology. "And when we measure electrical activity through EEG, it is very good at telling us when things happen in the brain - but it's less precise about where."

The third method, called event-related optical signal, provides a measure of spatial information that is similar to fMRI but, like EEG, can more accurately assess the timing of brain responses. This helps researchers fill in the blanks left by the other two technologies, Moore said. The result is a clearer picture of how different parts of the brain are activated and communicate with one another when an individual engages in a cognitive task and is distracted - in this case, by emotionally challenging information.

Functional MRI captures a signal from the flow of oxygenated blood in the brain when a person sees or responds to a stimulus. This signal is very useful for determining which brain structures are being activated, Moore said.

"Changes in blood oxygenation levels occur over a period of seconds, but the brain actually responds within hundreds of milliseconds," he said. This lag between brain activity and oxygenation signals means fMRI is unable to detect changes occurring faster than seconds.

"On the other hand, EEG is very good at telling us when things happen," Moore said. "But we're collecting from sensors placed on the scalp, and we're getting a summation of activity, so really, we're blurring across centimeters of the scalp."

The third technique, EROS, was developed by two co-authors of the new report, U. of I. psychology professors Monica Fabiani and Gabriele Gratton. This method shines near-infrared light into the brain and measures changes in how the light scatters, a reflection of neural activity. EROS provides precise information about where and when the brain responds, but it can only penetrate a few centimeters below the scalp, so it cannot detect events occurring deeper in the brain, as fMRI can, the researchers said.

Combining the three techniques was no easy task. There is limited space available on the scalp for various electrodes and sensors, and the EEG and EROS equipment had to fit within an fMRI coil and could not contain any magnetic metals, the researchers said. Over a period of years, the researchers found a way to include EROS patches that could share space with EEG electrodes on the scalp. They tested different combinations of the three techniques to determine how to intertwine them and how to interpret the information coming through the different channels.

To study how the brain behaves when an individual tries to focus on a task but is distracted by emotional information, the researchers gave study participants a goal of quickly picking out circles from a series of squares and other images that had either emotionally neutral or negative content.

The imaging results revealed that various brain regions responded rapidly to the stimuli. The signals cycled back and forth between locations over parts of the prefrontal and parietal cortices, brain areas that work together to maintain attention and process distractions. This switching occurred on a time scale of hundreds of milliseconds, the researchers found.

The ability to switch attention from a distraction and get back on task is highly relevant to normal cognitive function, said study leader Florin Dolcos, a professor of psychology at Illinois who studies emotional regulation and cognition.

"Sometimes people with depression or anxiety are not able to switch away from emotional distractions and focus," he said. "Better imaging studies will make it easier to test individuals who have been trained in specific emotion-regulation strategies to see if those strategies are working to improve their cognition. And now we can image this with precision in real time, at the mind's speed," he said.

The trimodal approach will provide better answers to other questions about how the brain operates, the researchers said.

"In previous work, these three technologies were applied on the same individuals at different times," Gratton said. "But we gain a lot from measuring these things together."

"This new approach could have a profound effect on neuroscience theory in general, on human neuroscience," Fabiani said. "Because now we don't have to guess about how these different signals align."

Credit: 
University of Illinois at Urbana-Champaign, News Bureau

Mining precious rare-earth elements from coal fly ash with a reusable ionic liquid

Rare-earth elements are in many everyday products, such as smart phones, LED lights and batteries. However, only a few locations have large enough deposits worth mining, resulting in global supply chain tensions. So, there's a push toward recycling them from non-traditional sources, such as waste from burning coal -- fly ash. Now, researchers in ACS' Environmental Science & Technology report a simple method for recovering these elements from coal fly ash using an ionic liquid.

While rare-earth elements aren't as scarce as their name implies, major reserves are either in politically sensitive locations, or they are widely dispersed, which makes mining them challenging. So, to ensure their supply, some people have turned to processing other enriched resources. For instance, the ash byproduct from coal-fired power plants has similar elemental concentrations to raw ores. Yet, current methods to extract these precious materials from coal fly ash are hazardous and require several purification steps to get a usable product. A potential solution could be ionic liquids, which are considered to be environmentally benign and are reusable. One in particular, betainium bis(trifluoromethylsulfonyl)imide or [Hbet][Tf2N], selectively dissolves rare-earth oxides over other metal oxides. This ionic liquid also uniquely dissolves into water when heated and then separates into two phases when cooled. So, Ching-Hua Huang, Laura Stoy and colleagues at Georgia Tech wanted to see if it would efficiently and preferentially pull the desired elements out of coal fly ash and whether it could be effectively cleaned, creating a process that is safe and generates little waste.

The researchers pretreated coal fly with an alkaline solution and dried it. Then, they heated ash suspended in water with [Hbet][Tf2N], creating a single phase. When cooled, the solutions separated. The ionic liquid extracted more than 77% of the rare-earth elements from fresh material, and it extracted an even higher percentage (97%) from weathered ash that had spent years in a storage pond. Finally, rare-earth elements were stripped from the ionic liquid with dilute acid. The researchers found that adding betaine during the leaching step increased the amounts of rare-earth elements extracted. The team tested the ionic liquid's reusability by rinsing it with cold water to remove excess acid, finding no change in its extraction efficiency through three leaching-cleaning cycles. The researchers say that this low-waste approach produces a solution rich in rare-earth elements, with limited impurities, and could be used to recycle precious materials from the abundance of coal fly ash held in storage ponds.

Credit: 
American Chemical Society

Climate change makes arctic ozone loss worse

Results of the MOSAiC expedition show: the expected recovery of the ozone layer may fail to happen anytime soon, if global warming is not slowed down

In spring 2020, the MOSAiC expedition documented an unparalleled loss of ozone in the Arctic stratosphere. As an evaluation of meteorological data and model-based simulations by the Alfred Wegener Institute, Helmholtz Centre for Polar and Marine Research (AWI) now indicates, ozone depletion in the Arctic polar vortex could intensify by the end of the century unless global greenhouse gases are rapidly and systematically reduced. In the future, this could also mean more UV radiation exposure in Europe, North America and Asia when parts of the polar vortex drift south. With their new findings, the experts call into question the commonly held assumption that, thanks to the ban on the production of chlorofluorocarbons (-CFCs), ozone loss would grind to a halt in just a few decades. The AWI study was jointly conducted with the University of Maryland and the Finnish Meteorological Institute, and has now been published online in the science magazine Nature Communications.

On 12 October 2020, when Polarstern returned to Bremerhaven from MOSAiC - the largest Arctic expedition in history - she brought with her troubling news: broad expanses of open water to the north of Greenland, and sea ice riddled with meltwater pools at the North Pole, bore witness to the dramatic effects of global warming that could already be seen in the Arctic. But the rapid melting wasn't the only thing that worried Expedition Leader Markus Rex: "Readings taken during the expedition showed that the chemical loss of ozone over the Arctic in the spring of 2020 was worse than ever before. A comprehensive analysis has now determined that this was also due to climate change. Unfortunately, our work indicates that, if climate change continues unchecked, loss of ozone over the Arctic will likely continue to worsen through the end of the 21st century, despite the global ban on ozone-destroying substances." During MOSAiC, at the altitude range of maximum ozone concentration, approx. 95% of the ozone had been destroyed. As a result, the thickness of the ozone layer was reduced by more than half, even though the concentration of ozone-destroying substances has declined since the turn of the millennium - a success of the international efforts to protect the ozone layer.

Does that mean the ozone layer - a protective barrier against harmful UV radiation - over the Arctic is increasingly at risk?

To find the answer, a team led by the AWI experts Peter von der Gathen and Markus Rex, and by Ross Salawitch from the University of Maryland, compared the data from 53 computer models created in the context of the international "Coupled Model Intercomparison Project Phases 5 and 6" (CMIP5, CMIP6). Working from this basis, the researchers then projected the ozone depletion in the Arctic polar vortex up to the year 2100. The vortex, a relatively self-contained low-pressure system in the stratosphere at an altitude of 15 to 50 kilometres, forms over the Arctic every autumn and stays for varying durations throughout winter and spring. "For ozone to be depleted in the Arctic, the stratosphere must cool down considerably at the altitude where the ozone layer is," says Peter von der Gathen, first author of the study. "Chlorine, which is normally bound in harmless substances, is released at low temperatures. Subsequently, chlorine together with bromine destroy ozone when exposed to sunlight. However, this only takes place when temperatures sink low enough during winter. Accordingly, in our study we estimated the ozone loss in the next few decades on the basis of the long-term temperature trend in the polar vortex and the expected decline in chlorine and bromine compounds."

Despite the production ban issued in the 1987 Montreal Protocol, substances like chlorofluorocarbons (CFCs) and halons, which contain ozone-destroying chlorine and bromine atoms, are still abundant in the atmosphere, because they break down only very slowly. "The concentrations of these substances in the polar vortex continued to rise until the year 2000," says Peter von der Gathen. "Since then, they've been on decline and are currently at roughly 90 percent of the maximum. Only by the end of the century they will have fallen below 50 percent, according to an assessment of the World Meteorological Organization. Since the pattern of warm and cold stratospheric winters in the polar vortex is very irregular, the degree of ozone depletion varies accordingly. Superimposed on this, however, our analysis of meteorological data from the past 56 years shows a significant trend toward lower temperatures in the cold stratospheric winters and associated increases in ozone losses. In addition, the analysis of the climate models clearly shows that this trend is part of climate change and therefore the product of global greenhouse-gas emissions."

The complex underlying mechanism is at least partly understood: the same gases that result in global warming at the Earth's surface (like CO2) also promote cooling of higher atmospheric layers in the stratosphere, where the ozone layer is located. "In addition, due to climate change we notice changes in the prevailing wind systems. We suppose that these changes also contribute to lower temperatures in the polar vortex. Up to now, the trend towards colder winters in the Arctic stratosphere was debated among researchers. Even when assuming such a trend it was believed that climate change would, in the worst case, prolong the recurring ozone depletion over the Arctic by a few years," Peter von der Gathen explains. "By then at the latest - that's what we assumed, too - the falling concentrations of CFCs would become such a dominating factor that the ozone loss would continually fade. But, according to our new calculations, things could also turn out very differently in the Arctic."

The team's analysis shows that the future chemical loss of ozone in the Arctic will greatly depend on the amount of greenhouse gases emitted by the end of the century. If emissions are substantially reduced in the coming decades, the study actually predicts an early and then steady decline in the degree of ozone loss; but for less optimistic scenarios characterised by rising greenhouse-gas emissions, the opposite could happen. "If we don't reduce our greenhouse-gas emissions rapidly and decisively, loss of ozone in the Arctic stratosphere could, despite the great success of the Montreal Protocol, continue to worsen through the end of this century, instead of following the generally expected path towards a full recovery of the ozone layer" explains Markus Rex. "This represents a fundamental paradigm shift in our assessment of the future of the Arctic ozone layer. And the future of the Arctic ozone layer is relevant for life in Europe, North America and Asia: the Arctic polar vortex occasionally drifts south, which can lead to a few days with a reduced ozone layer over populated areas in spring, increasing levels of UV radiation and ultimately a greater risk of sunburn and acquiring skin cancer during these periods."

For Markus Rex, the message from the Arctic is clear: "There are plenty of good reasons to quickly and comprehensively reduce greenhouse-gas emissions. Now we can add the risk of intensified ozone depletion over the Arctic to the list."

Credit: 
Alfred Wegener Institute, Helmholtz Centre for Polar and Marine Research

Low-cost method for finding new coronavirus variants

image: Nicola Crosetto, senior researcher at the Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Sweden.

Image: 
Stefan Zimmerman

Researchers at Karolinska Institutet in Sweden have developed a technology for cost-effective surveillance of the global spread of new SARS-CoV-2 variants. The technique is presented in the scientific journal Nature Communications.

Since the onset of the pandemic, thousands of viral genomes have been sequenced to reconstruct the evolution and global spread of the coronavirus. This is important for the identification of particularly concerning variants that are more contagious, pathogenic, or resistant to the existing vaccines.

For global surveillance of the SARS-CoV-2 genome, it is crucial to sequence and analyse many samples in a cost-effective way. Therefore, researchers in the Bienko-Crosetto laboratory at Karolinska Institutet and Science for Life Laboratory (SciLifeLab) in Sweden have developed a new method, named COVseq, that can be used for surveillance of the viral genome on a massive scale at a low cost.

First, many copies of the viral genome are created using so-called multiplex PCR (polymerase chain reaction). The samples are then labelled and pooled together in the same sequencing library, using a previous method developed in the Bienko-Crosetto laboratory and now adapted for SARS-CoV-2 analysis.

"By performing reactions in very small volumes and pooling together hundreds of samples into the same sequencing library, we can sequence potentially thousands of viral genomes per week at a cost of less than 15 dollars per sample," says Ning Zhang, postdoctoral researcher at the Department of Medical Biochemistry and Biophysics, Karolinska Institutet and co-first author together with PhD students Michele Simonetti and Luuk Harbers at the same department.

Comparative analyses of 29 SARS-CoV-2 positive samples revealed that COVseq had a similar ability as the standard method to identify small changes in the genome. Analyses of 245 additional samples showed that COVseq also had a high ability to detect emergent coronavirus variants of potential concern. The key advantage of COVseq over existing methods is cost-effectiveness.

"Our inexpensive method could immediately be used for SARS-CoV-2 genomic surveillance by public health agencies and could also be easily adapted to other RNA viruses, such as influenza and dengue viruses," says Nicola Crosetto, senior researcher at the Department of Medical Biochemistry and Biophysics, Karolinska Institutet, and last author of the paper.

Credit: 
Karolinska Institutet

Cellular signatures of kidney tumours discovered

The origins of seven types of kidney cancer, including several rare subtypes, have been identified by researchers at the Wellcome Sanger Institute, Great Ormond Street Hospital (GOSH), the Princess Máxima Center for Pediatric Oncology and Oncode Institute. The findings confirm that these cancers have their origin in specific forms of developmental cells present in the maturing fetus.

The study, published today (23 June) in Nature Communications, used computational methods to analyse existing datasets and pinpoint the 'cellular signals' given off by different cancers as they emerge. This method holds promise as a tool for diagnosing patients with rare cancers - in the study, one patient's cryptic kidney cancer was identified as a Wilms-like tumour by looking at its cellular signals.

All cancers are derived from normal cells that have started to multiply uncontrollably. By comparing patterns of gene expression in cancer and normal cells, it is possible to learn about aspects of each tumour's origin and behaviour. This type of analysis has been made possible by the advent of single-cell mRNA sequencing, a high-resolution technology that can identify different cell types present in a tissue according to the genes expressed by individual cells.

Previous studies have used these techniques to compare normal and diseased tissue in some of the most common kidney cancers, but to conduct single-cell sequencing on many hundreds of tumours would not be achievable.

In this study, researchers at the Wellcome Sanger Institute and their collaborators turned to computational techniques to mine Human Cell Atlas (HCA) reference data* and databases of tumour gene expression. They assessed mRNA signals in 1,300 childhood and adult renal tumours, spanning seven different tumour types, in order to investigate the origins of these cancers**.

The results confirmed that these childhood cancers are developmental in origin, occurring after errors in a particular developmental cell type's journey to maturity. In contrast, adult kidney cancers emerged from mature cell types and do not revert to a developmental pattern of gene expression in the vast majority of cases.

Each cancer type was also found to exhibit unique 'cellular signals', or patterns of gene expression, that could be used to classify them in future.

Dr Matthew Young, first author of the study from the Wellcome Sanger Institute, said: "It has long been assumed that childhood tumours have 'fetal' origins. Now we can replace that loose definition with a precise, quantitative measurement of the cellular signals that different tumour types exhibit. Our analysis also refutes the theory that adult tumours revert to a developmental state, unless they are a highly lethal subtype of adult kidney cancer."

The study sheds light on the behaviour and origins of some kidney tumour subtypes whose rarity would have made it difficult to examine otherwise. These were congenital mesoblastic nephroma, clear cell sarcoma of the kidney, malignant rhabdoid tumour of the kidney, and chromophobe renal cell carcinoma.

The method pioneered in the study also helped to classify one patient's tumour, which clinicians had been unable to diagnose fully.

Dr Karin Straathof, a senior author of the study from Great Ormond Street Hospital, said: "Sometimes it is not possible to fully diagnose childhood kidney cancers via the usual methods, which can impact our ability to adopt the best course of treatment. One of the samples used in this study was from a child with one of these undiagnosed tumours. But by analysing the genes expressed by the tumour cells, we were able to recognise it as Wilms' tumour. My hope is that this approach can be used in such cases in future."

In recent studies, researchers have identified the origins of individual childhood cancers, such as neuroblastoma, using mRNA single-cell sequencing on small numbers of tumours. Here, computational analysis of existing data has been used to determine the origin of a larger groups of childhood cancers.

Dr Sam Behjati, a senior author of the study from the Wellcome Sanger Institute, said: "Not only does this computational approach using existing datasets validate previous results on the origins of childhood kidney cancers, it provides a new way of expanding this research to much larger numbers of tumours and rare cancer types. I believe that the success of this approach could act as a blueprint for investigating the behaviour and origins of the entire spectrum of human cancer."

Credit: 
Wellcome Trust Sanger Institute