Culture

A recent study of more than 2,000 companies finds that corporations feeling the pinch of financial constraints can benefit significantly from taking a more aggressive stance in their tax planning strategies. One takeaway of the finding is that tax authorities should look closely at the activities of companies facing financial constraints to make sure their tax activities don't become too aggressive.

Financial constraints aren't unusual and occur when a company can't afford to fund a project that would increase its value. Sometimes the constraints are caused by an external event - like a pandemic - that leaves companies with less income than they were anticipating. Sometimes the factors causing a constraint are specific to a single company, such as corporate mismanagement.

"Business researchers are interested in how companies respond to sudden changes in their financial constraints," says Nathan Goldman, co-author of the study and an assistant professor of accounting in the Poole College of Management at North Carolina State University. "But it's difficult to separate various confounding variables from the financial constraints that companies are facing. However, my co-authors and I realized that the Pension Protection Act of 2006 (PPA) gave us a great opportunity to examine financial constraints."

The PPA increased pension funding requirements by almost 500% for all companies that had defined-benefit pension plans. For example, before the PPA, if a company had $400 million in pension obligations, and $100 million in pension assets, it would have 30 years to fund 90% of its obligations. In other words, it could set aside an additional $9 million per year for 30 years. But the PPA changed that, and the same company would have been required to fund 100% of its obligations within seven years - or an additional $43 million per year.

"The PPA imposed new demands on the financial resources of these 'pension firms' - and that means many were suddenly facing financial constraints," Goldman says.

To assess the impact of these financial constraints, the researchers looked at data from 2,647 publicly traded companies: 730 pension firms and 1,907 companies that did not provide defined-benefit pension plans to their employees.

"We found that pension firms were able to recoup 19% of their investment shortfall by modifying their tax strategies," Goldman says. "That is a significant amount of money."

The benefits of the tax strategies can vary in terms of whether they are one-time benefits - such as R&D expenses - or recurring savings - such as relocating operations to locations with lower taxes.

Ultimately, the researchers found that there were three key takeaway messages for the business community.

"One: firms facing financing constraints should consider turning to tax planning as a way of generating capital without increasing debt or equity," Goldman says. "Two: tax planning alone cannot solve liquidity demands. However, the average firm generated a significant amount of cash to offset investment that would otherwise be lost. And, lastly, the taxing authority should more carefully scrutinize tax positions of financially constrained firms - since these firms are more likely to be increasing the aggressiveness of their deductions, and thus have a higher likelihood of being overturned."

A comprehensive assessment of 12 different strategies for reducing beef production emissions worldwide found that industry can reduce greenhouse gas (GHG) emissions by as much as 50% in certain regions, with the most potential in the United States and Brazil. The study, "Reducing Climate Impacts of Beef Production: A synthesis of life cycle assessments across management systems and global regions," is published April 5 in Global Change Biology.

A research team led by Colorado State University (CSU) found that widespread use of improved ranching management practices in two distinct areas of beef production would lead to substantial emissions reductions. This includes increased efficiency to produce more beef per unit of GHG emitted - growing bigger cows at a faster rate - and enhanced land management strategies to increase soil and plant carbon sequestration on grazed lands.

Globally, cattle produce about 78% of total livestock GHG emissions. Yet, there are many known management solutions that, if adopted broadly, can reduce, but not totally eliminate, the beef industry's climate change footprint, according to lead author Daniela Cusack, an assistant professor in the Department of Ecosystem Science and Sustainability at CSU.

Overall, the research team found a 46% reduction in net GHG emissions per unit of beef was achieved at sites using carbon sequestration management strategies on grazed lands, including using organic soil amendments and restoring trees and perennial vegetation to areas of degraded forests, woodlands and riverbanks. Additionally, researchers found an overall 8% reduction in net GHGs was achieved at sites using growth efficiency strategies. Net-zero emissions, however, were only achieved in 2% of studies.

"Our analysis shows that we can improve the efficiency and sustainability of beef production, which would significantly reduce the industry's climate impact," said Cusack, also a research associate at the Smithsonian Tropical Research Institute in Panama. "But at the same time, we will never reach net-zero emissions without further innovation and strategies beyond land management and increased growth efficiency. There's a lot of room, globally, for improvement."

Global analysis

Researchers analyzed 292 comparisons of "improved" versus "conventional" beef production systems across Asia, Australia, Brazil, Canada, Latin America and the U.S. The analysis revealed that Brazilian beef production holds the most potential for emissions reductions.

In the studies analyzed, researchers found a 57% GHG emission reduction through improved management strategies for both carbon sequestration and production efficiency in Brazil. Specific strategies include improved feed quality, better breed selections and enhanced fertilizer management.

The biggest impact was found in integrated field management, including intensive rotational grazing schemes, adding soil compost, reforestation of degraded areas and selectively planting forage plants bred for sequestering carbon in soils.

"My home country of Brazil has more than 52 million hectares of degraded pastureland - larger than the state of California," said Amanda Cordeiro, co-author and a graduate student at CSU. "If we can aim for a large-scale regeneration of degraded pastures, implementation of silvo-agro-forestry systems and adoption of other diversified local management strategies to cattle production, Brazil can drastically decrease carbon emissions."

In the U.S., researchers found that carbon sequestration strategies such as integrated field management and intensive rotational grazing reduced beef GHG emissions by more than 100% - or net-zero emissions - in a few grazing systems. But efficiency strategies were not as successful in the U.S. studies, possibly because of a high use of the strategies in the region already.

"Our research shows the important role that ranchers can play in combatting the global climate crisis, while ensuring their livelihoods and way of life," said Clare Kazanski, co-author and North America region scientist with The Nature Conservancy. "By analyzing management strategies in the U.S. and around the world, our research reinforces that ranchers are in a key position to reduce emissions in beef production through various management strategies tailored to their local conditions."

Darrell Wood, a northern California rancher, is an example of a producer leading the way on climate-friendly practices. Wood's family participates in the California Healthy Soils program, which incentivizes practices with a demonstrated climate benefit.

"As a sixth-generation cattle rancher, I see nothing but upside potential from using our cattle as a tool for reducing greenhouse gas emissions," Wood said. "Taking good care of our grasslands not only benefits climate, but also wildlife and the whole ecosystem that generates clean air and water. It'll help the next generation continue our business, too."

Next steps

Although the research shows a significant reduction in the GHG footprints of beef production using improved management strategies, scientists don't yet know the full potential of shifting to these emission-reducing practices because there are very few data on practice adoption levels around the world.

"Asia, for example, is one of the most rapidly growing beef markets, but there is an imbalance between the amount of research focus on improving beef production and the growing demand for beef," Cusack said. "We know with the right land management and efficiency strategies in place, it's possible to have large reductions in emissions across geographic regions, but we need to keep pushing for additional innovations to create a truly transformation shift in the way the global beef system operates to ensure a secure food supply and a healthy environment."

Syracuse, N.Y. - Emergency medical service (EMS) workers face triple the risk for significant mental health problems such as depression and posttraumatic stress disorder compared to the general population, according to a recently published study by researchers from Syracuse University.

The study also showed that daily mental health symptoms for EMS workers can be reduced through recovery activities such as exercising, socializing with other people, and finding meaning in the day's challenges.

The study, "Dynamic psychosocial risk and protective factors associated with mental health in Emergency Medical Service (EMS) personnel," was published recently by the Journal of Affective Disorders. The study is also summarized in the Lerner Center for Public Health Promotion research brief "How Do Emergency Medical Service Workers Cope with Daily Stressors?"

The COVID-19 pandemic has underscored the significant mental health burden experienced by EMS workers. The researchers surveyed EMS workers at American Medical Response in Syracuse, N.Y., for eight consecutive days in 2019 to better understand their mental health symptoms related to daily occupational stressors. These stressors can take the form of routine work demands, critical incidents involving serious harm or death, and social conflicts.

"Together, these occupational stressors negatively impacted mental health each day that they occurred," said researcher Bryce Hruska. "Each additional work demand or critical event that an EMS worker encountered on a given workday was associated with a 5% increase in their PTSD symptom severity levels that day, while each social conflict was associated with a 12% increase in their depression symptom severity levels."

The research team was led by Hruska, a Lerner Faculty Affiliate and assistant professor of public health at Syracuse University's David B. Falk College of Sport and Human Dynamics. Here are the team's key findings:

EMS workers experience a diverse array of occupational stressors each day.

These stressors are associated with an elevation in mental health symptoms each day that they occur.

Recovery activities (like exercising or socializing with other people) and looking for meaning in the day's stressors may protect mental health.

The study found that on workdays, the EMS workers engage in approximately three recovery activities during non-work hours, mostly visiting with friends and family, eating a meal with others, and spending quiet time alone.

"These activities had a beneficial impact on mental health; each additional recovery activity in which a worker engaged was associated with a 5% decrease in their depression symptom severity levels that day," Hruska said. "The social nature of the reported recovery activities is notable, given that healthy relationships can alleviate the negative impact of stress on mental health by assisting with coping efforts and helping to reframe the day's stressors.

"Perhaps demonstrating this latter effect, we also found that EMS workers who looked for lessons to learn from the day's challenges experienced a 3% decrease in their daily depression symptoms," Hruska added.

The researchers identified several actionable strategies that build upon the protective behaviors in which the EMS workers naturally engaged and could make some work events less stressful. Here are some instances noted in the study:

Developing or refining communications strategies may be helpful for alleviating the stress associated with managing patients' family and friends and interacting with co-workers.

Recognizing conflicts as an opportunity for learning and growing may be a useful tactic for effectively resolving the situation with fewer negative mental health effects.

Taking time to recharge after a particularly demanding shift offers an opportunity to let emotions cool. For example, when EMS workers respond to a critical event, scheduled downtime may offer an opportunity for recovery and processing of the day's events.

BATON ROUGE, La. (March 2021) - Without restoration efforts in coastal Louisiana, marshes in the state could lose half of their current ability to store carbon in the soil over a period of 50 years, according to a new paper published in American Geophysical Union Journal of Geophysical Research Biogeosciences.

"This reduction in capacity could significantly alter the global carbon budget, given that Louisiana's marsh soils account for between 5 and 21 percent of the global soil carbon storage in tidally influenced wetlands," said Melissa Baustian, lead author and coastal ecologist at The Water Institute of the Gulf.

The article, "Long-term carbon sinks in marsh soils of coastal Louisiana are at risk to wetland loss" examined 24 south Louisiana sites located within four marsh habitats defined by the amount of saltwater influence - fresh, intermediate, brackish, and saline. Carbon sink is a reservoir that stores more carbon than it releases.

By working with colleagues from U.S. Geological Survey, Vernadero Group, Abt Associates, and Tulane University the team used marsh habitat maps from 1949 to 2013, deep soil cores, soil carbon accumulation rates, and maps of future marsh area, to confirm the importance of considering historical habitats when evaluating a coastal areas' long-term ability to store carbon in the soil. Due to the evolving nature of coastal wetland habitats, simply looking at current conditions might not reflect how much carbon was buried historically or how much carbon can be buried in the future, especially in Louisiana where land loss is a continuing concern.

"Protection and restoration of these marshes is vital to help protect the pool of buried carbon in the soils, and to prevent release of carbon to the atmosphere from soil oxidation," Baustian said.

As Louisiana continues to build projects contained with its 50-year Coastal Master Plan, Gov. John Bel Edwards announced in August that the Institute, led by Baustian, will be working with the state to quantify the carbon sink potential of coastal Louisiana with and without restoration projects in the state's 2017 Coastal Master Plan to examine how these potential coastal carbon sinks could help reach the Governor's greenhouse gas emissions goals of 2025, 2030, and 2050.

Tokyo, Japan - Researchers from Tokyo Metropolitan University have shown that skeletal muscle satellite cells, key players in muscle repair, proliferate better in low glucose environments. This is contrary to conventional wisdom that says mammalian cells fare better when there is more sugar to fuel their activities. Because ultra-low glucose environments do not allow other cell types to proliferate, the team could produce pure cultures of satellite cells, potentially a significant boost for biomedical research.

Healthy muscles are an important part of a healthy life. With the wear and tear of everyday use, our muscles continuously repair themselves to keep them in top condition. In recent years, scientists have begun to understand how muscle repair works at the cellular level. Skeletal muscle satellite cells have been found to be particularly important, a special type of stem cell that resides between the two layers of sheathing, the sarcolemma and basal lamina, that envelopes myofiber cells in individual muscle fibers. When myofiber cells get damaged, the satellite cells go into overdrive, multiplying and finally fusing with myofiber cells. This not only helps repair damage, but also maintains muscle mass. To understand how we lose muscles due to illness, inactivity, or age, getting to grips with the specific mechanisms involved is a key challenge for medical science.

A team of scientists from Tokyo Metropolitan University led by Assistant Professor Yasuro Furuichi, Associate Professor Yasuko Manabe and Professor Nobuharu L Fujii have been studying how skeletal muscle satellite cells multiply outside the body. Looking at cells multiplying in petri dishes in a growth medium, they noticed that higher levels of glucose had an adverse effect on the rate at which they grew. This is counterintuitive; glucose is considered to be essential for cellular growth. It is converted into ATP, the fuel that drives a lot of cellular activity. Yet, the team confirmed that lower glucose media led to a larger number of cells, with all the biochemical markers expected for greater degrees of cell proliferation.

They also confirmed that this doesn't apply to all cells, something they successfully managed to use to their advantage. In experiments in high glucose media, cultures of satellite cells always ended up as a mixture, simply due to other cell types in the original sample also multiplying. By keeping the glucose levels low, they were able to create a situation where satellite cells could proliferate, but other cell types could not, giving a very pure culture of skeletal muscle satellite cells. This is a key prerequisite for studying these cells in a variety of settings, including regenerative medicine. So, was the amount of glucose in their original experiment somehow "just right"? The team added glucose oxidase, a glucose digesting enzyme, to get to even lower levels of glucose, and grew the satellite cells in this glucose-depleted medium. Shockingly, the cells seemed to fare just fine, and proliferated normally. The conclusion is that these particular stem cells seem to derive their energy from a completely different source. Work is ongoing to try to pin down what this is.

The team notes that the sugar levels used in previous experiments matched those found in diabetics. This might explain why loss of muscle mass is seen in diabetic patients, and may have significant implications for how we might keep our muscles healthier for longer.

The neurons in our nervous system "talk" to each other by sending and receiving chemical messages called neurotransmitters. This communication is facilitated by cell membrane proteins called receptors, which pick up neurotransmitters and relay them across cells. In a recent study published in Nature Communications, scientists from Japan report their findings on the dynamics of receptors, which can enable understanding of the processes of memory formation and learning.

The regulation of receptor movement and localization within the neuron is important for synaptic plasticity, an important process in the central nervous system. A specific type of glutamate receptor, known as AMPA-type glutamate receptor (AMPAR), undergoes a constant cycle of "trafficking", being cycled in and out of the neuronal membrane. "A precise regulation of this 'trafficking' process is associated with learning, memory formation, and development in neural circuits," says Professor Shigeki Kiyonaka from Nagoya University, Japan, who led the aforementioned study.

While methods to analyze the trafficking of AMPARs are available aplenty, each has its limitations. Biochemical approaches include "tagging" a receptor protein with biotin (a B vitamin). However, this requires purification of the proteins after tagging, hindering quantitative analysis. Another method which involves producing "fusion" receptor proteins labelled with a fluorescent protein may interfere with the trafficking process itself. "In most cases, these methods largely rely on the overexpression of target subunits. However, the overexpression of a single receptor subunit may interfere with the localization and/or trafficking of native receptors in neurons", explains Prof. Kiyonaka.

To that end, researchers from Nagoya University, Kyoto University, and Keio University developed an AMPAR-selective reagent (a chemical agent that causes reactions) that allowed them to label AMPARs with chemical probes in cultured neurons in a two-step manner, combining affinity-based labeling with a biocompatible reaction. The new method, as anticipated by Prof. Kiyonaka, proved to be superior to the conventional ones: it allowed scientists to analyze receptor trafficking over both shorter as well as much longer periods (over 120 hours) and did not require extra purification steps after labeling.

The team's analyses showed a three-fold higher concentration of AMPARs at synapses compared with dendrites as well as a half-life of 33 hours in neurons. Additionally, scientists used this technique to label and analyze the trafficking of NMDA-type glutamate receptors (NMDARs), and obtained a half-life of 22 hours in neurons. Interestingly, both half-life values were significantly longer than those reported in HEK293T (a kidney cell line). The researchers attributed this to the formation of large glutamate receptor protein complexes and -- in the case of AMPARs -- a difference in phosphorylation levels.

The team is excited by potential implications of their findings. "Our method can contribute to our understanding of the physiological and pathophysiological roles of glutamate receptor trafficking in neurons. This, in turn, can help us understand the molecular mechanism underlying memory formation and the process of learning," says Prof. Kiyonaka.

The study provides a closer look at -- and brings us a step closer to deciphering -- the processes of memory and learning at the molecular level.

Gasoline, the primary transportation fuel, contains hydrocarbons with 5-11 carbons (C5-11) and is almost derived from petroleum at present.

Gasoline can also be produced from non-petroleum syngas. Nonetheless, achieving high conversions of syngas to C5-11 with excellent selectivity and stability remains a challenge.

A research group led by Prof. LIU Zhongmin and Prof. ZHU Wenliang from the Dalian Institute of Chemical Physics (DICP) of the Chinese Academy of Sciences realized highly efficient and selective conversion of syngas to gasoline-range liquid hydrocarbons over a dual-bed catalyst.

The study was published in Chem Catalysis on April 2.

This dual-bed catalyst, (CZA +Al2O3)/N-ZSM-5(97), consists of the conventional syngas-to-dimethyl ether catalyst CZA + Al2O3 in the upper bed and a dimethyl ether-to-gasoline catalyst N-ZSM-5(97) in the lower bed.

The selectivity of C5-11 and C3-11 in the hydrocarbon products reached 80.6% and 98.2%, respectively, along with 86.3% CO conversion.

The catalyst exhibited excellent stability, and the iso/n-paraffin ratio in the C5-11 products was up to 18. The nano-sized structure of N-ZSM-5(97) was beneficial for reducing coke and prolonging the lifetime; meanwhile, the low acid content of N-ZSM-5(97) was advantageous for increasing the C5-11 selectivity.

Compared with the Fischer-Tropsch synthesis process, this dual-bed syngas-to-gasoline (STG) process was more suitable for producing high-quality gasoline, along with the co-production of aromatic hydrocarbons.

ANN ARBOR--We are made of stardust, the saying goes, and a pair of studies including University of Michigan research finds that may be more true than we previously thought.

The first study, led by U-M researcher Jie (Jackie) Li and published in Science Advances, finds that most of the carbon on Earth was likely delivered from the interstellar medium, the material that exists in space between stars in a galaxy. This likely happened well after the protoplanetary disk, the cloud of dust and gas that circled our young sun and contained the building blocks of the planets, formed and warmed up.

Carbon was also likely sequestered into solids within one million years of the sun's birth--which means that carbon, the backbone of life on earth, survived an interstellar journey to our planet.

Previously, researchers thought carbon in the Earth came from molecules that were initially present in nebular gas, which then accreted into a rocky planet when the gases were cool enough for the molecules to precipitate. Li and her team, which includes U-M astronomer Edwin Bergin, Geoffrey Blake of the California Institute of Technology, Fred Ciesla of the University of Chicago and Marc Hirschmann of the University of Minnesota, point out in this study that the gas molecules that carry carbon wouldn't be available to build the Earth because once carbon vaporizes, it does not condense back into a solid.

"The condensation model has been widely used for decades. It assumes that during the formation of the sun, all of the planet's elements got vaporized, and as the disk cooled, some of these gases condensed and supplied chemical ingredients to solid bodies. But that doesn't work for carbon," said Li, a professor in the U-M Department of Earth and Environmental Sciences.

Much of carbon was delivered to the disk in the form of organic molecules. However, when carbon is vaporized, it produces much more volatile species that require very low temperatures to form solids. More importantly, carbon does not condense back again into an organic form. Because of this, Li and her team inferred most of Earth's carbon was likely inherited directly from the interstellar medium, avoiding vaporization entirely.

To better understand how Earth acquired its carbon, Li estimated the maximum amount of carbon Earth could contain. To do this, she compared how quickly a seismic wave travels through the core to the known sound velocities of the core. This told the researchers that carbon likely makes up less than half a percent of Earth's mass. Understanding the upper bounds of how much carbon the Earth might contain tells the researchers information about when the carbon might have been delivered here.

"We asked a different question: We asked how much carbon could you stuff in the Earth's core and still be consistent with all the constraints," Bergin said, professor and chair of the U-M Department of Astronomy. "There's uncertainty here. Let's embrace the uncertainty to ask what are the true upper bounds for how much carbon is very deep in the Earth, and that will tell us the true landscape we're within."

A planet's carbon must exist in the right proportion to support life as we know it. Too much carbon, and the Earth's atmosphere would be like Venus, trapping heat from the sun and maintaining a temperature of about 880 degrees Fahrenheit. Too little carbon, and Earth would resemble Mars: an inhospitable place unable to support water-based life, with temperatures around minus 60.

In a second study by the same group of authors, but led by Hirschmann of the University of Minnesota, the researchers looked at how carbon is processed when the small precursors of planets, known as planetesimals, retain carbon during their early formation. By examining the metallic cores of these bodies, now preserved as iron meteorites, they found that during this key step of planetary origin, much of the carbon must be lost as the planetesimals melt, form cores and lose gas. This upends previous thinking, Hirschmann says.

"Most models have the carbon and other life-essential materials such as water and nitrogen going from the nebula into primitive rocky bodies, and these are then delivered to growing planets such as Earth or Mars," said Hirschmann, professor of earth and environmental sciences. "But this skips a key step, in which the planetesimals lose much of their carbon before they accrete to the planets."

Hirschmann's study was recently published in Proceedings of the National Academy of Sciences.

"The planet needs carbon to regulate its climate and allow life to exist, but it's a very delicate thing," Bergin said. "You don't want to have too little, but you don't want to have too much."

Bergin says the two studies both describe two different aspects of carbon loss--and suggest that carbon loss appears to be a central aspect in constructing the Earth as a habitable planet.

"Answering whether or not Earth-like planets exist elsewhere can only be achieved by working at the intersection of disciplines like astronomy and geochemistry," said Ciesla, a U. of C. professor of geophysical sciences. "While approaches and the specific questions that researchers work to answer differ across the fields, building a coherent story requires identifying topics of mutual interest and finding ways to bridge the intellectual gaps between them. Doing so is challenging, but the effort is both stimulating and rewarding."

Blake, a co-author on both studies and a Caltech professor of cosmochemistry and planetary science, and of chemistry, says this kind of interdisciplinary work is critical.

"Over the history of our galaxy alone, rocky planets like the Earth or a bit larger have been assembled hundreds of millions of times around stars like the Sun," he said. "Can we extend this work to examine carbon loss in planetary systems more broadly? Such research will take a diverse community of scholars."

WEHI researchers have discovered a key differentiation process that provides an essential immune function in helping to control cancer and infectious diseases.

The research, published in Science Immunology, is the first to show a new factor - DC-SCRIPT - is required for the function a particular type of dendritic cell - called cDC1 - that is essential in controlling the immune response to infection.

Led by WEHI Professor Stephen Nutt, Dr Michael Chopin and Mr Shengbo Zhang, it defines the role for a new regulatory protein - DC-SCRIPT - in producing dendritic cells.

At a glance

WEHI researchers have uncovered a key step in the formation of a particular type of dendritic cell - called cDC1 - in controlling the immune response to infection.

The research highlights the importance of DC-SCRIPT in the production of effective dendritic cells.

Through gaining a better understanding of how dendritic cells are produced, researchers hope to be able to determine a way of directing the body to produce large numbers of dendritic cells, to enable it to better fight off cancer and infections.

DC-SCRIPT essential in the production of cancer-fighting cells

Dendritic cells are immune cells that activate 'killer' T cells, which are vital for clearing viral infections and for triggering a response to cancer tumours.

Through gaining a better understanding of how this process works, researchers hope to be able to determine a way of directing the body to produce large numbers of dendritic cells, to enable it to better fight off cancer and infections.

Professor Nutt said the research paper highlighted the importance of DC-SCRIPT in the production of effective dendritic cells.

"What we found, is that without this new factor, the cells develop poorly, and their capacity to fight infection and cancer, or to clear a parasite, is diminished," he said.

"The next stage of our research is to try and work out how we can get the body to produce these particular dendritic cells, cDC1s, in large volumes in order to boost the body's natural tumour response."

Harnessing the body's natural response to infection

Dr Chopin said he was confident cDC1s held the clues to improving immunity to viruses and tumours.

"This paper clearly shows DC-SCRIPT is one of the regulators of dendritic cell production. As a result of this study, we're now focussed on ways we could harness this to increase dendritic cell production," he said.

"We now have a biomarker to follow when we expand this elusive cell type, which we will continue to test in pre-clinical models."

This research lays the foundation for future studies into dendritic cell production and their clinical applications in response to tumours.

"We have generated new tools, allowing us to trace these cells within the tumour and observe how they behave in the tumour environment," Dr Chopin said.
This work was made possible with funding from the National Health and Medical Research Council and the Victorian Government.

What The Study Did: This survey study examined the career development, productivity, childcare needs and likelihood of leaving the workforce among employees at an academic medical center during the COVID-19 pandemic.

Authors: Angela Fagerlin, Ph.D., of the University of Utah in Salt Lake City, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamanetworkopen.2021.3997)

Editor's Note: The article includes conflicts of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

Extended surges in the South and West in the summer and early winter of 2020 resulted in regional increases in excess death rates, both from COVID-19 and from other causes, a 50-state analysis of excess death trends has found. Virginia Commonwealth University researchers' latest study notes that Black Americans had the highest excess death rates per capita of any racial or ethnic group in 2020.

The research, publishing Friday in the Journal of the American Medical Association, offers new data from the last 10 months of 2020 on how many Americans died during 2020 as a result of the effects of the pandemic -- beyond the number of COVID-19 deaths alone -- and which states and racial groups were hit hardest.

The rate of excess deaths -- or deaths above the number that would be expected based on averages from the previous five years -- is usually consistent, fluctuating 1% to 2% from year to year, said Steven Woolf, M.D., the study's lead author and director emeritus of VCU's Center on Society and Health. From March 1, 2020, to Jan. 2, 2021, excess deaths rose a staggering 22.9% nationally, fueled by COVID-19 and deaths from other causes, with regions experiencing surges at different times.

"COVID-19 accounted for roughly 72% of the excess deaths we're calculating, and that's similar to what our earlier studies showed. There is a sizable gap between the number of publicly reported COVID-19 deaths and the sum total of excess deaths the country has actually experienced," Woolf said.

For the other 28% of the nation's 522,368 excess deaths during that period, some may actually have been from COVID-19, even if the virus was not listed on the death certificates due to reporting issues.

But Woolf said disruptions caused by the pandemic were another cause of the 28% of excess deaths not attributed to COVID-19. Examples might include deaths resulting from not seeking or finding adequate care in an emergency such as a heart attack, experiencing fatal complications from a chronic disease such as diabetes, or facing a behavioral health crisis that led to suicide or drug overdose.

"All three of those categories could have contributed to an increase in deaths among people who did not have COVID-19 but whose lives were essentially taken by the pandemic," said Woolf, a professor in the Department of Family Medicine and Population Health at the VCU School of Medicine.

The percentage of excess deaths among non-Hispanic Black individuals (16.9%) exceeded their share of the U.S. population (12.5%), reflecting racial disparities in mortality due to COVID-19 and other causes of death in the pandemic, Woolf and his co-authors write in the paper. The excess death rate among Black Americans was higher than rates of excess deaths among non-Hispanic white or Hispanic populations.

Woolf said his team was motivated to break down this information by race and ethnicity due to mounting evidence that people of color have experienced an increased risk of death from COVID-19.

"We found a disproportionate number of excess deaths among the Black population in the United States," said Woolf, VCU's C. Kenneth and Dianne Wright Distinguished Chair in Population Health and Health Equity. "This, of course, is consistent with the evidence about COVID-19 but also indicates that excess deaths from some conditions other than COVID-19 are also occurring at higher rates in the African American population."

Surges in excess deaths varied across regions of the United States. Northeastern states, such as New York and New Jersey, were among the first hit by the pandemic. Their pandemic curves looked like a capital "A," Woolf said, peaking in April and returning rapidly to baseline within eight weeks because strict restrictions were put in place. But the increase in excess deaths lasted much longer in other states that lifted restrictions early and were hit hard later in the year. Woolf cited economic or political reasons for decisions by some governors to weakly embrace, or discourage, pandemic control measures such as wearing masks.

"They said they were opening early to rescue the economy. The tragedy is that policy not only cost more lives, but actually hurt their economy by extending the length of the pandemic," Woolf said. "One of the big lessons our nation must learn from COVID-19 is that our health and our economy are tied together. You can't really rescue one without the other."

According to the study's data, the 10 states with the highest per capita rate of excess deaths were Mississippi, New Jersey, New York, Arizona, Alabama, Louisiana, South Dakota, New Mexico, North Dakota and Ohio.

Nationally, Woolf expects the U.S. will see consequences of the pandemic long after this year. For example, cancer mortality rates may increase in the coming years if the pandemic forced people to delay screening or chemotherapy.

Woolf said future illness and deaths from the downstream consequences of the devastated economy could be addressed now by "bringing help to families, expanding access to health care, improving behavioral health services and trying to bring economic stability to a large part of the population that was already living on the edge before the pandemic." Among other research, his team's 2019 JAMA study of working-age mortality underscores the importance of prioritizing public health measures like these, he said.

"American workers are sicker and dying earlier than workers in businesses in other countries that are competing against America," Woolf said. "So investments to help with health are important for the U.S. economy in that context just as they are with COVID-19."

Derek Chapman, Ph.D., Roy Sabo, Ph.D., and Emily Zimmerman, Ph.D., of VCU's Center on Society and Health and the School of Medicine joined Woolf as co-authors on the paper published Friday, "Excess Deaths From COVID-19 and Other Causes in the United States, March 1, 2020, to January 2, 2021."

Their study also confirms a trend Woolf's team noted in an earlier 2020 study: Death rates from several non-COVID-19 conditions, such as heart disease, Alzheimer's disease and diabetes, increased during surges.

"This country has experienced profound loss of life due to the pandemic and its consequences, especially in communities of color," said Peter Buckley, M.D., dean of the VCU School of Medicine. "While we must remain vigilant with social distancing and mask-wearing behaviors for the duration of this pandemic, we must also make efforts to ensure the equitable distribution of care if we are to reduce the likelihood of further loss of life."

Based on current trends, Woolf said the surges the U.S. has seen might not be over, even with vaccinations underway.

"We're not out of the woods yet because we're in a race with the COVID-19 variants. If we let up too soon and don't maintain public health restrictions, the vaccine may not win out over the variants," Woolf said. "Unfortunately, what we're seeing is that many states have not learned the lesson of 2020. Once again, they are lifting restrictions, opening businesses back up, and now seeing the COVID-19 variants spread through their population.

"To prevent more excess deaths, we need to hold our horses and maintain the public health restrictions that we have in place so the vaccine can do its work and get the case numbers under control."

What The Study Did: This study updates an analysis of deaths in the United States in 2020, including deaths due to COVID-19 as well as all other causes.

Authors: Steven H. Woolf, M.D., M.P.H., of the Virginia Commonwealth University School of Medicine in Richmond, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jama.2021.5199)

Editor's Note: The article includes funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

People who radicalize to extremist ideologies often are triggered by negative life events or exposure to propaganda, and those who escape from extreme groups frequently are aided by an individual or group that intervenes to help them reject the philosophy, according to a new RAND Corporation study.

Expanding access to mental health care, creating opportunities for exposure to diverse cultural groups and media literacy education all are important strategies that may aid the battle against extremism, according to researchers. However, harsh law enforcement actions often are unproductive in changing people's extremist beliefs.

The RAND study describes personal accounts based on interviews with more than two dozen former white supremacists, Islamic extremists and their family members about what leads people to join extremist groups and, at least in some cases, leave these groups and their radical ideologies.

"Terrorism and ideologically-inspired violence represent persistent and serious threats to the security of the United States," said Ryan Andrew Brown, the study's lead author and a senior social scientist at RAND, a nonprofit research organization. "By better understanding the pathways individuals take to radicalization, we can improve our prevention and deradicalization strategies."

The study is one of the first public reports to incorporate the experiences of white supremacists, Islamic extremists and their family members to look for common factors and signs along the pathway to radicalization.

Events such as the Jan. 6 attack on the U.S. Capitol underscore a growing threat to America's national security posed by homegrown terrorism and ideologically inspired violence. Domestic attacks have maintained a steady and growing pace in recent years, foreshadowing recent events.

The RAND study is based on interviews about 32 people who became radicalized -- 24 white supremacists and 8 Islamic extremists. Those interviewed included 24 former extremists, 10 family members and two friends. To recruit study participants, the team worked with Parents for Peace and Beyond Barriers, two organizations that work with former members of radical extremist organizations and family members who have assisted with deradicalization efforts.

The study provides findings across four areas: background characteristics of radical extremists, pathways to radicalization, deradicalizing and leaving organizations, and participant perspectives on mitigation strategies.

The RAND interviews highlight several factors that may contribute to individuals becoming radicalized, including facing financial instability, mental health challenges such as trauma and PTSD, and social factors such as victimization and marginalization.

In more than half of the cases, a "re-orienting" event was described that prompted an individual to reconsider previously accepted views and embrace extremist ideologies. These events included a gun possession charge, rejection by the military, a friend's suicide and an extended period of unemployment.

In a majority of cases, individuals described consuming propaganda during radicalization, especially online materials, but also music and books.

In seven cases (4 white supremacist, 3 Islamic extremist), recruitment involved top-down action by recruiters from radical organizations. In 18 cases (15 white supremacist, 3 Islamic extremist), recruitment involved "bottom-up" entry in which individuals radicalize on their own and then sought membership in extremist organizations.

"It may be difficult to observe noticeable changes in individuals until they are radicalized and those changes often are a surprise to their family," Brown said. "It is only after the radicalization takes place that family members and friends may understand what has happened."

Individuals in the RAND study said they also benefited socially while participating in extremist groups, most notably finding friends and developing a sense of camaraderie and friendship that was previously missing in their lives. Some noted a new sense of power.

The most commonly mentioned factor for exiting a group was a sense of disillusionment and burnout. Hypocrisy or other negative behaviors by group members were often cited as reasons for these feelings.

Individuals or groups helped 22 of the individuals in the RAND sample to exit extremist groups, with such interventions most often conducted intentionally. The interventions included diverse cultural and demographic exposures, providing emotional support, and providing pathways to financial and/or domestic stability.

In half of those cases, the intervention was orchestrated and conducted by an institution, including religious groups, law enforcement, and secular nonprofits. Twenty-two of the 32 cases also described processes of self-driven exit from extremism, in which former extremists sought their own paths out of groups and ideologies.

A majority of the study participants also indicated that they experienced interventions that had failed, most often efforts that had been initiated by family members. Punitive interventions by law enforcement also often led to paradoxical effects of increased extremism.

"Our work suggests that the punitive approach should be used sparingly because it seldom ends radicalization and frequently has negative consequences for community members," Brown said.

The RAND study provides recommendations that community organizations and researchers should pursue in the future to strengthen both practice and understanding of what works.

Those recommendations include expanding community based mental health services in areas at risk for radicalization and exploring whether interventions based on an addiction treatment model can help deter radicalization.

Community organizations also should consider ways to expand exposure to diverse populations, help at-risk families recognize and react to signs of extremism, and improve ways to present deradicalization messages at the right time and place.

Researchers should work to better identify geographic and demographic hot spots for radicalization, develop educational and outreach efforts to help recognize and address the signs of radicalization, and explore social network approaches to deradicalization.

ITHACA, NY, April 2, 2021 - A team of researchers from the Boyce Thompson Institute (BTI) has discovered a distinct group of bacteria that may help fungi and plants acquire soil nutrients. The findings could point the way to cost-effective and eco-friendly methods of enriching soil and improving crop yields, reducing farmers' reliance on conventional fertilizers.

Researchers know that arbuscular mycorrhizal (AM) fungi establish symbiotic relationships with the roots of 70% of all land plants. In this relationship, plants trade fatty acids for the fungi's nitrogen and phosphorus. However, AM fungi lack the enzymes needed to free nitrogen and phosphorus from complex organic molecules.

A trio of BTI scientists led by Maria Harrison, the William H. Crocker Professor at BTI, wondered whether other soil microbes might help the fungi access those nutrients. In a first step towards examining that possibility, the team investigated whether AM fungi associate with a specific community of bacteria. The research was described in a paper published in The ISME Journal on March 1.

The team examined bacteria living on the surfaces of long filament-like structures called hyphae, which the fungi extend into the soil far from their host plant. On hyphae from two species of fungi, the team discovered highly similar bacterial communities whose composition was distinct from those in the surrounding soil.

"This tells us that, just like the human gut or plant roots, the hyphae of AM fungi have their own unique microbiomes," said Harrison, who is also an adjunct professor in Cornell University's School of Integrative Plant Science. "We're already testing a few interesting predictions as to what these bacteria might do, such as helping with phosphate acquisition."

"If we're right, then enriching the soil for some of these bacteria could increase crop yields and, ultimately, reduce the need for conventional fertilizers along with their associated costs and environmental impacts," she added.
Her co-researchers on the study were former BTI scientists Bryan Emmett and Véronique Lévesque-Tremblay.

Among the fungi

In the study, the team used two species of AM fungi, Glomus versiforme and Rhizophagus irregularis, and grew them in three different types of soil in symbiosis with Brachypodium distachyon, a grass species related to wheat. After letting the fungus grow with the grass for up to 65 days, the researchers used gene sequencing to identify bacteria sticking to the hyphae surfaces.

The team found remarkable consistency in the makeup of bacterial communities from the two fungal species. Those communities were similar in all three soil types, but very different from those found in soil away from the filaments.
The function of these bacteria is not yet clear, but their composition has already sparked some interesting possibilities, Harrison said.

"We predict that some of these bacteria liberate phosphorus ions in the immediate vicinity of the filaments, giving the fungus the best chance to capture those ions," Harrison said. "Learning which bacteria have this function could be key to enhancing the fungi's phosphate acquisition process to benefit plants."

Harrison's group is investigating the factors that control which bacteria assemble on the filaments. Harrison thinks the AM fungi may secrete molecules that attract these bacteria, and in turn, the bacterial communities may influence which molecules the fungus secretes.

Highway patrol

Among the hyphae microbiomes were members of Myxococcales and other taxa that include "bacterial predators" that kill and eat other bacteria by causing them to burst and release their contents.

These predators move by gliding along surfaces so "the fungal filaments could serve as linear feeding lanes," said Emmett, who is currently a research microbiologist for the U.S. Department of Agriculture's Agricultural Research Service in Ames, Iowa. "Many soil bacteria appear to travel along fungal hyphae in soil, and these predators may make it a more perilous journey."
While not every member of those taxa on the filaments may be predatory, Harrison's group plans to investigate how and why those putative predators assemble there. "It's possible that the actions of predatory bacteria make mineral nutrients available to everyone in the surrounding soil - predators and fungi alike," she said.

Infectious diseases are a leading cause of global mortality. During an infection, bacteria experience many different stresses -- some from the host itself, some from co-colonizing microbes and others from therapies employed to treat the infection. In this arms race to outwit their competition, bacteria have evolved mechanisms to stay alive in the face of adversities. One such mechanism is the stringent response pathway. Understanding how the activation of the stringent response pathway is controlled can provide clues to treat infection.

In new research published this week online in the journal Proceedings of the National Academy of Sciences, former Carnegie Mellon University graduate student Surya D. Aggarwal and his advisor, Associate Professor of Biological Sciences Luisa Hiller, observed that the deletion of a gene involved in surface remodeling caused a stress-dependent growth defect in a human pathogen that could not easily be explained. Deciphering the biological mechanism underlying this defect led to an international collaboration between Carnegie Mellon, the Universidade NOVA de Lisboa (Portugal) and the University of Warwick (UK). The joint effort combined the Carnegie Mellon team's expertise in pathogenesis with that of Assistant Professor Sergio Filipe of the Universidade NOVA de Lisboa and the University of Warwick Associate Professor Adrian Lloyd's work in the composition and biosynthesis of bacterial cell walls and associated biochemical processes.

"This has been one of the most fun and exciting projects in my career," said Hiller.

The joint project established that transfer RNAs (tRNAs) serve as a crucial component in the control of the activation of the stringent response pathway. tRNAs play a critical role in translation: they help to decode the genetic information into amino acids, the building blocks of proteins.

However, sometimes they can make a mistake, where the tRNA carrier and the amino acid building block are mismatched, rendering the combination toxic. In stressful conditions, tRNAs make more errors and accumulation of these errors is a trigger for the stringent response. This biological process is akin to the malfunction of a machine in an assembly line that results in flaws in the final manufactured product.

Many bacteria display a thick cell wall on their surface. Amino acids are a key component of this structure, and this research revealed that a protein involved in the addition of amino acids to this cell wall, the MurM enzyme, displays a strong preference for the tRNA loaded with mismatched building blocks. By diverting these toxic blocks towards cell wall synthesis and away from translation, MurM serves as a quality control manager who ensures that the flow line remains error-free and the manufacturing process can continue unabated.

In the absence of MurM, cells under stress activate the stringent response more easily than the parental strain. These findings suggested that MurM serves as a gatekeeper of this stress response pathway.

"It is highly rewarding when suddenly intriguing observations are explained by a simple and clear model," Filipe said. "The proposal that the cell wall can be used to divert the accumulation of toxic compounds is quite exciting. I wonder what other surprises will come from the study of the bacterial cell surface".

"To explore this further, we drew parallels between the bacteria we study and other species that do not encode MurM", said Aggarwal, who is now a postdoctoral fellow at NYU Langone Medical Center. In most domains of life, including human cells, the pathological consequences of these toxic tRNAs are mitigated by AlaXp, an enzyme that also corrects the defect by decoupling the tRNA from the incorrectly coupled building block.

However, Streptococcus pneumoniae, the bacteria in this study, as well as multiple other bacteria with thick cell walls, do not encode AlaXp. Aggarwal adds, "We wanted to test whether artificially introducing an additional gatekeeper in the form of AlaXp to pneumococcal cellular machinery would allow the flow line to remain functional even in the absence of MurM. This line of investigation set us on a road to test whether the stress-dependent growth defects we observed were attributable to the protein's role in preventing accumulation of toxic tRNAs."

The validation was a joint effort. The research at CMU employed genetic tools to decouple the role of the MurM in the architecture of the cell wall from its role in correcting toxic carrier-building block pairs. The work at Warwick made use of biochemical tools to reveal the underlying processes that render MurM optimal to correct the toxic molecules, while studies in Lisbon captured how the correction activity of the MurM enzyme impacts cell wall architecture. To quote Lloyd: "This international consortium was able to focus disparate yet connected areas of expertise to determine how previously considered disparate areas of microbial biochemistry collaborate to enable a crucial pathogen to navigate the stresses it endures during infection. This work provides a step change in our understanding of the resilience of bacteria as they cause infection."

The study suggests that MurM is an alternative evolutionary solution to the challenge of these toxic tRNAs. These findings implicate cell wall synthesis in the survival of bacteria as they encounter unpredictable and hostile conditions in the host. The association between cell wall synthesis and translational fidelity is likely to be active in many other pathogens, implicating these findings in the biology of many other pathogens.

This collaborative work sets the framework for future work exploring the molecular connection between two fundamental cell processes, translation and cell wall synthesis, and stress responses. Moreover, the pivotal position of the stringent response in survival to stresses and to antibiotics, suggests these findings will also shed light on pathways associated with bacterial drug resistance, a major challenge for this century.