Culture

Researchers outline adapted health communications principles for the COVID-19 pandemic

The COVID-19 pandemic has introduced unique challenges for public health practitioners and health communicators that warrant an expansion of existing health communication principles to take into consideration.

In an article published Tuesday in Public Health Research & Practice, CUNY SPH Distinguished Lecturer Scott C. Ratzan and colleagues outline a checklist for the implementation of COVID-19 communication strategies to move from the acute phase of the pandemic to the "next normal."

One of the major challenges that has emerged during the COVID-19 pandemic is the increasing amount of false content circulating on social media platforms. The spread of misinformation relating to a potential vaccine for the disease, even well before a vaccine is available for public use, is particularly concerning, the authors say. Rumours of safety scares and conspiracies relating to a COVID-19 vaccine have swirled throughout social media, leading to social media outlets taking active measures to limit misinformation. These measures, although important, have not prevented a saturated information system nor blocked harmful misinformation from undermining science-backed sources. These features of the media environment and the way people engage with the news call for a revision of the risk communication guidance during a public health crisis.

Ratzan and colleagues identified three general areas of capacity building for health communication during the pandemic: the need for communicators to be proactive and to take preventive actions at times; the importance of planning ahead while also acknowledging the unpredictability of the situation; and the call to focus on people.

The checklist for health communicators is made up of five objectives: set shared goals, establish coordinated response, devise a communication strategy, implement the communication plan, and be ready to adapt.

"We are trying to advance public health with simple innovations to promote evidence-based approaches to stem the COVID-19 pandemic," says Ratzan. "While we are pleased to publish and disseminate widely, we implore political leaders and governmental officials to adapt these checklists for a healthier populace and COVID-19 recovery."

It is critical that health communicators worldwide are more proactive in tackling risk communication challenges related to COVID-19, with likely prevention achieved through vaccination and societal COVID-19 resilience, Ratzan says.

Credit: 
CUNY Graduate School of Public Health and Health Policy

How does our brain fold? Study reveals new genetic insights

image: Grey matter neurons in the outward folds (left) and inward folds (right), with differences highlighted in red. The study found that variations in neuron shape in these regions during the folding process correlate with genetic differences.

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RMIT University

New research is helping unlock the mystery of how the brain folds as a baby develops in the womb - a process critical to healthy brain function.

Misfolding of the brain is linked with many neurological conditions including autism, anorexia, epilepsy and schizophrenia.

Premature birth and foetal growth restriction, major risk factors for cerebral palsy, can also affect brain folding and lead to cognitive deficits.

While we know folds are essential to how a healthy human brain works, scientists are only beginning to understand what drives the folding process and why it goes wrong.

A new pre-clinical study by Australian and Swiss researchers has for the first time identified the genes linked with the development of the two types of brain folds - inward and outward - in the grey matter of the brain.

Using animal models that closely resemble human brain development, the study found differences in both genetic expression and neuron shape during the folding process.

Co-chief investigator Associate Professor Mary Tolcos said there were currently no therapies for the prevention or treatment of brain misfolding and no early test to detect problems before folding begins.

"We know folding happens in the second and third trimester of pregnancy and that all human brains fold along largely the same patterns," said Tolcos, an Australian Research Council Future Fellow at RMIT.

"This suggests the process is heavily controlled by our genes but we're only starting to understand how - it's like having an intricately folded piece of origami that's missing the instructions.

"Our study is a critical step towards fully understanding those genetic instructions, by pinpointing which genes are linked with fold development.

"The next step is to determine the precise role these genes play in the process, so we can work towards identifying potential therapeutic targets and develop interventions to prevent and fix misfolding in the brain."

Folding fundamentals

Previous brain folding studies have focused on white matter or looked at animals with smooth brains rather than folded ones, but have largely overlooked grey matter.

Grey matter is made up of neuron bodies and their connecting arms, while white matter is composed of the neurons' long nerve fibres and their protective layer of fat.

While the science of folding is still unclear, the latest evidence suggests grey matter in the developing brain expands faster than white matter, creating mechanical instability that leads to brain folding.

But the resulting "hill" and "valley" folds are not random - they follow a similar pattern in all folded brains of the same species.

The new study focused on sheep brains, which fold in the womb like the human brain.

Researchers investigated the genetic and microstructural differences in future grey matter, the cortical plate, in the parts of the brain just beneath the "hills" and "valleys".

The areas were analysed at three points of development - when the brain was smooth, semi-folded and fully folded.

Postdoctoral researcher Dr Sebastian Quezada Rojas said it was the first study to look at the genetics of folding of the future grey matter, as the folding process develops over time.

"Understanding the changes in the cortical plate during brain folding is paramount since this region changes so dramatically during this process," he said.

"We found some genes have higher expression in regions that fold outward and lower expression in regions that fold inwards. Other genes reverse this pattern.

"Together, these genetic expression patterns might explain why the cortical folding pattern is so consistent between individuals of the same species."

These genetic differences are also correlated with changes in grey matter neurons, with the study finding variations in the number of arms - or dendrites - that neurons grow in these regions during the folding process.

"We believe the regions that fold outward and inward are programmed to behave differently, and the shape of the neurons affects the way these areas fold. Untangling these connections will be focus of the next stage of this research," Quezada Rojas said.

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RMIT University

Lifetime discrimination may increase risk of hypertension among African Americans

DALLAS, July 1, 2020 -- Lifetime discrimination is a chronic stressor that may increase the risk for hypertension also known as high blood pressure, in African Americans, according to new research published today in Hypertension, an American Heart Association journal.

"Previous studies have shown that discrimination affects African Americans' health; however, this research is one of the first large, community-based studies to suggest an association between discrimination over a lifetime and the development of hypertension among a large sample of African American men and women," said Allana T. Forde, Ph.D., M.P.H., the study's first author and a postdoctoral research fellow at the Urban Health Collaborative at Drexel University in Philadelphia, Pennsylvania.

"African Americans continue to be disproportionately affected by hypertension, making it imperative to identify the drivers of hypertension in this population," Forde said. "Greater lifetime discrimination was associated with an increased risk for hypertension among African Americans in this study, which reflects the impact of cumulative exposure to stressors over one's lifetime and the physiological reactions to stress that contribute to deleterious health outcomes."

Researchers reviewed data on 1,845 African Americans, ages 21 to 85, enrolled in The Jackson Heart Study, which focused on cardiovascular disease among African Americans in the tri-county areas of Jackson, Mississippi. The study participants did not have hypertension during the first visit in 2000 through 2004. Patients completed two follow-up study visits: one in 2005 through 2008, and the second between 2009 through 2013. Participants self-reported their discrimination experiences through in-home interviews, questionnaires and in-clinic examinations.

Participants were defined as having hypertension if they said they were taking blood pressure-lowering medication, or had a systolic blood pressure of 140 mm Hg or above or diastolic blood pressure higher than 90 mm Hg at follow-up visits.

During the follow-up period, more than half of the participants (954 or 52%) developed hypertension. Participants who reported medium levels compared to low levels of lifetime discrimination had a 49% increased risk for hypertension after accounting for other risk factors.

"The study has important implications for patient care and population health," Forde said. "Traditional risk factors, such as diet and physical activity, have been strongly correlated with hypertension, yet important psychosocial factors like discrimination, which also have the potential to negatively impact health, are rarely considered when evaluating the risk for hypertension among African Americans in health care settings."

"Our findings highlight the need for health care professionals to recognize discrimination as a social determinant of health. Health care professionals who understand the importance of unique stressors like discrimination that impact the health of African Americans will be better equipped to provide optimal patient care to this population."

"However, medical care is not enough. More broadly, our results suggest how social determinants such as racism and discrimination affect health in measurable ways. Addressing these factors is critical to reducing rates of chronic diseases."

The researchers note that although the study included experiences of discrimination among a large sample of African Americans, discrimination was measured at a single point in time, which limited the researchers' ability to capture changes in discrimination experiences over the entire follow-up period.

Researchers said additional studies with African Americans in other regions of the U.S. are warranted to confirm the findings of this study. However, these results add to a large body of work documenting the impact of discrimination on the health of African Americans. Strategies to reduce health inequities and improve health are needed to address these broader social determinants.

Credit: 
American Heart Association

School absenteeism has surprising consequences for adults

COLUMBUS, Ohio -- Kids who miss a lot of school from kindergarten to eighth grade may suffer unexpected costs as young adults, a new study finds.

Researchers found that those who were more regularly absent in these early years of school were less likely to vote, reported having greater economic difficulties and had poorer educational outcomes when they were 22 to 23 years old.

The results suggest early school absenteeism should be taken more seriously, said Arya Ansari, lead author of the study and assistant professor of human sciences at The Ohio State University.

"There's this misconception, especially among parents, that it doesn't matter as much if kids miss school early on - that it only becomes important when they get to middle or high school," said Ansari, who is also a researcher at Ohio State's Crane Center for Early Childhood Research and Policy.

"This study shows that those early absences do matter, and in ways that many people don't consider."

The study was published online recently in the Journal of Youth and Adolescence.

Ansari and his colleagues used data from the Study of Early Child Care and Youth Development, which is run by the National Institute of Child Health and Human Development.

This study included data on 648 students from 10 cities across the United States who were followed from birth through young adulthood. Researchers had information on the number of days the children were absent from school between kindergarten and eighth grade.

In 2013 and 2014, when the participants were 22 or 23 years old, they reported on a variety of outcomes, from criminal or deviant behavior to parenthood, political participation and economic hardship.

Results showed that school absenteeism didn't have any relation with criminal, risky or deviant behavior, Ansari said. But it was linked to political engagement and educational and economic success.

Students who were more frequently absent from school were 4.7 percentage points less likely to have voted in the 2012 election.

They also reported experiencing greater economic hardship (such as difficulty paying bills), were more likely to say they used government assistance such as food stamps, were less likely to have a job and reported poorer educational outcomes, such as a lower high school GPA and a lower likelihood of going to college.

"Absenteeism in those early years of school has pretty far-reaching consequences," Ansari said. "It goes beyond just affecting your education and how well you do in high school."

Ansari said showing up less to school in those early years may set dangerous precedents.

"If you start out being disengaged with school, you may end up being less engaged with society more broadly. You're less likely to vote, less likely to go to college, less likely to be employed," he said.

"We believe disengagement may be one of the key mechanisms linking early school absences to poorer outcomes in early adulthood."

Ansari said the participants in this study were mostly from middle-class families, so results may be different for those from a more disadvantaged background.

"If we're seeing these negative outcomes of absenteeism in this largely middle-class sample, the associations may be even more pronounced among disadvantaged families," he said.

In 2020, parents may be wondering how widespread school closings during the pandemic may be affecting their children. Ansari said this situation is different from what they studied here.

"These really are unprecedented times. All kids are absent. With that said, the differential access to supports and resources will likely result in even greater variability in outcomes when students return to school after the pandemic."

Ansari said he hopes this study will make parents more aware of the importance of school attendance, even for young children.

"What this work suggests is that we should take absenteeism and its consequences more seriously."

Credit: 
Ohio State University

A shake-up in cell culturing: Flame sterilization may affect the culture

image: Researchers from the University of Tsukuba have found that flame-sterilizing shake-flasks, to avoid introducing microbial contaminants, considerably increases the carbon dioxide concentration in the flasks. This enhanced carbon dioxide concentration affects the growth of some microbial species, which may affect the quantity of vaccines or other valuable substances produced by the microbes.

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University of Tsukuba

Tsukuba, Japan - Researchers commonly culture bacteria for many purposes, such as to screen pharmaceuticals and manufacture vaccines. In these cases, shake flasks have been commonly and generally used for over 90 years to cultivate microbes.

To keep track of what's going on in the shake flask, researchers must use stringent sterilization techniques while extracting a sample of cells. A common sterilization technique is to expose the plug and flask to a flame at several time points during cell extraction. However, if this sterilization affects the cell culture in any way, you may inadvertently hinder production of the vaccine or whatever substance you want from the culture.

In a study recently published in Scientific Reports, researchers from the University of Tsukuba have shown that flame sterilization introduces carbon dioxide into shake flasks. This excess carbon dioxide can considerably affect cell growth.

Carbon dioxide is a product of methane combustion in the flame. The researchers found that flaming the flask for even a few extra seconds, or tilting the flask a few extra degrees, considerably increased the carbon dioxide concentration in the flask.

"For example, at a flame exposure time of only 5 s, increasing the inclination angle from 15° to 25° increased the carbon dioxide concentration in the headspace by approximately 50%," says Professor Hideki Aoyagi, senior author of the study. "Computational modeling confirmed our findings."

These increases in carbon dioxide concentration are induced over the course of only a few seconds of flame sterilization. But do they substantially affect cell growth? To test this hypothesis, the researchers needed to add excess carbon dioxide while keeping the flasks shaking, because interrupting the shaking can itself affect cell growth.

"We introduced intermittent carbon dioxide at concentrations similar to those expected by flame sterilization," explains Professor Aoyagi. "The ultimate oxygen demand of Acetobacter pasteurianus--known to spoil wine-- increased by up to 70%. Pelomonas saccharophila increased by up to 35%, whereas the other two microbes were not clearly affected in terms of growth."

The researchers do not yet know how common it is for flaming a shake-flask to alter cell culture growth. Nevertheless, seemingly minor experimental sterilization variables--too subtle for most researchers to even notice at first glance--may actually be pertinent. Culturing microbes in shake flasks and producing valuable products in the culture--perhaps relevant to COVID-19 research--may be substantially more complicated than previously appreciated.

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University of Tsukuba

Traffic data show drastic changes in Floridians' behavior at onset of the pandemic

image: Using same-day traffic volumes for March 2019 and March 2020 across Florida, researchers examined the relationship of key governmental requests for public isolation and travel limitations.

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Florida Atlantic University

It's not just health, social and economic consequences from COVID-19 that have impacted the world. Travel behavior also has been significantly affected. Using statewide traffic data from the Florida Department of Transportation (FDOT), a study demonstrates the drastic changes in human behavior during the onset of the pandemic. With more than 20 million residents, Florida was selected because of its enormous diversity and unique demographic and commercial characteristics.

Researchers from Florida Atlantic University; Embry-Riddle Aeronautical University; Louisiana State University, and the University of Hawaii, analyzed highway volume data as a representation of personal activity and interaction. For the study, published in the journal National Hazards Review, they used same-day traffic volumes for March 2019 and March 2020 across Florida to examine the chronological relationship of key governmental requests for public isolation and travel limitations in both time and space. They looked at differences in urban versus rural regions of the state over time as well as on different road functional classifications.

Analyzing same-day traffic volumes for 2019 and 2020 across Florida, results showed that traffic volumes by March 22, 2020, dropped by 47.5 percent compared to that same point in 2019. Moreover, traffic declined in March 2020 corresponding with the governor's state of emergency declaration and school, restaurant, and bar closures. During the study period, the traffic decline followed similarly shaped trends with the increase in confirmed COVID-19 cases throughout Florida. Traffic decline outside of South Florida was statistically noticeable before that of South Florida. This finding indicates that people in the epicenter in South Florida continued to travel more early on despite being at a higher threat. However, traffic both inside and outside South Florida noticeably dropped after schools closed.

"In Florida, issuing the emergency declaration started the reductions in travel, but other actions such as school closings, shutdown of theme park operations, and the shuttering of bars and restaurants were associated with increased travel reductions," said John Renne, Ph.D., co-author, professor, and director of FAU's Department of Urban and Regional Planning within FAU's Charles E. Schmidt College of Science. "Whether the reduction in travel demand was attributable to the closure of activities and trip generators or a function of increased fear arising from the increased lethality of COVID-19 requires further exploration."

Findings also showed that urban areas across the state experienced significant decline several days before rural areas. Traffic on highways accounted for about two-thirds of the total volume and corresponding decline, but traffic decline on arterials was not consistently different until five days after freeways. This may indicate that people reduced travel for longer trip purposes, such as work trips, but continued to make local trips for nearly an extra week. Urban arterials experienced consistently different volumes a day after urban freeways and rural arterials had a four-day lag compared to urban arterials.

"Our analysis demonstrates that overall traffic volumes decreased significantly over the period with the greatest declines occurring later in the study period, suggesting that many factors including the start of spring break and decisions by local governments and employers contributed to the changes in travel behavior," said Renne.

Data from this study support greater understanding of how to implement quarantine and isolation controls, adding to research on slowing movement of infectious disease. If the duration of the pandemic is long, there may be need for other operational strategies, such as the prepositioning of supplies, including equipment and other goods necessary for response and relief efforts or to ensure populations can comply with stay-at-home orders. Data on travel behavior also are relevant to recovery efforts and planning for the return to normalcy, training and overall preparedness, and longer-term community resilience.

"It would be interesting to determine if starting some of the actions earlier such as closing restaurants and bars would have resulted in steeper increases in trip reduction," said Renne. "Clearly there was a lag between urban and rural areas and more investigation into reasons and motivations for the slower reaction is warranted. This knowledge could be useful in messaging especially if the protective action decision-making is transferable to other hazards and threats."

Among the most important unanswered questions of this research pertain to the ultimate effect of reduced travel: was it successful in reducing sickness and fatalities from COVID-19? The researchers say, "Time will tell." This will require more direct correlation between trip reduction and reduction in infection, transmission, and lethality for COVID-19.

The FDOT Transportation Data and Analytics Office gathers roadway data from across the state. Volume, speed, and vehicle classification are collected hourly using telemetric monitoring stations that transmit these data through telephone or wireless communications. For the study, bidirectional hourly traffic counts were collected, cataloged, and processed from 262 telemetric monitoring stations.

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Florida Atlantic University

Research shows telehealth is an important tool for rural hospitals in treating COVID-19

image: Neeraj Puro, Ph.D., co-author and an assistant professor, management programs/health administration in FAU's College of Business.

Image: 
Florida Atlantic University

Rural hospitals are more likely than urban facilities to have access to telehealth, a once-underused service that now is playing a key role in treating coronavirus patients, according to research by two health administration professors in Florida Atlantic University's College of Business.

Neeraj Puro, Ph.D., and Scott Feyereisen, Ph.D., say the research can help U.S. hospitals understand the extent to which they are prepared for another wave of the pandemic. The work has been published in The Journal of Rural Health, one of the leading peer-reviewed publications on rural health issues.

Telehealth connects patients with doctors by computer or telephone when in-person appointments are not possible or safe from disease transmission.

"It's a relatively easy way to expand access," Feyereisen said. "More health care access is good. It's one of the goals of the system."

Having telehealth provides hospitals the ability to expand their service offerings in multiple ways, according to the report. For example, telehealth services have the potential to improve outcomes for high-risk obstetric patients in rural communities, while telehealth facilitated the use of anti-microbials in rural areas where infectious disease physicians were not available. Still, barriers such as insurance restrictions and technology limitations remain in place, preventing the widespread use of the service.

Puro and Feyereisen concluded that talking with doctors remotely is an important part of improving rural health care. The odds of hospitals to provide telehealth services vary, with Minnesota, Iowa, South Dakota, North Dakota, Nebraska, Missouri and Kansas leading the way among the nine regions designated by the U.S. Census.

What's more, coastal states, including New York, Florida, California and Washington, generally lacked the capability to provide e-services in rural areas, with telehealth specifically in short supply. In addition, telehealth capabilities are more common in hospitals that belong to a system and benefit from the economies of scale.

"Not only are rural populations some of the most vulnerable to diseases such as COVID-19, they might be called upon to provide back-up service to overflowing urban hospitals in the event such systems are overwhelmed," the report stated. "Going forward, telehealth is likely to play a large role in diagnosing patients, particularly in coming months as long as social distancing is a preferred strategy for preventing the spread of COVID-19. This virus might also become seasonal, and until a vaccine is introduced, telehealth will likely be increasingly integral to diagnosis and treatment."

The research also found that telehealth capabilities are predictably available in larger hospitals as well as teaching hospitals, and the professors say policymakers would be wise to provide support to smaller facilities.

The study of 3,268 hospitals is based on 2017 data from the American Hospital Association survey, Area Health Resource Files and Medicare cost reports.

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Florida Atlantic University

Is not helping a bad person good or bad?

image: The scores were calculated by simply adding together the scores of three statements on a 5-point scale, so it has minimum and maximum values of 3 and 15. The vertical axis shows the density of kernel density estimation. The solid black line, dotted red line, and dotted green line represent Experiments 1, 2, and 3, respectively.

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PLOS ONE

People can engage in cooperative behavior even among strangers with no direct expectation of personal benefit. For such cooperative behavior to be sustained, a mechanism needs to be in place to ensure that benefits are returned to the individuals who cooperate. As the proverb goes, "One good turn deserves another." This mechanism is generally referred to as indirect reciprocity.

Indirect reciprocity relies on social norms that distinguish the good from the bad. Many game theoretical researches have searched for norms that discourage cooperation directed toward the bad. Previous theoretical studies have predicted that the evaluation rule that "not cooperating with bad people is a good thing (justified defection)" is necessary to stabilize cooperative behavior. This is because if defection against a bad person is not justified, those who have not cooperated with an uncooperative person (a bad person) will be assessed as bad, thus a chain of non-cooperation emerges.

The research team conducted several online experiments to answer whether "justified defection" is justified and analyzed the norms that people adopt in their daily lives. The results show that, contrary to previous theoretical predictions, people have a neutral attitude toward justified defection, avoiding judging it as good or bad. On the other hand, they judged "cooperation with a bad person (unjustified cooperation)" to be good.

Yamamoto says, "Our results indicate the necessity to reconsider the justification of "justified defection" in the evolution of cooperation."

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Rissho University

Why do arteries age? Study explores link to gut bacteria, diet

A compound produced in the gut when we eat red meat damages our arteries and may play a key role in boosting risk of heart disease as we get older, according to new University of Colorado Boulder research.

The study, published this month in the American Heart Association journal Hypertension, also suggests that people may be able to prevent or even reverse such age-related decline via dietary changes and targeted therapies, like novel nutritional supplements.

"Our work shows for the first time that not only is this compound directly impairing artery function, it may also help explain the damage to the cardiovascular system that naturally occurs with age," said first author Vienna Brunt, a postdoctoral researcher in the Department of Integrative Physiology.

Eat a slab of steak or a plate of scrambled eggs, and your resident gut bacteria get to work immediately to break it down. As they metabolize the amino acids L-carnitine and choline, they churn out a metabolic byproduct called trimethylamine, which the liver converts to trimethylamine-N-Oxide (TMAO) and sends coursing through your bloodstream.

Previous studies have shown that people with higher blood levels of TMAO are more than twice as likely to have a heart attack or stroke and tend to die earlier.

But to date, scientists haven't completely understood why.

Drawing on animal and human experiments, Brunt and her team set out to answer three questions: Does TMAO somehow damage our vascular system? If so, how? And could it be one reason why cardiovascular health gets worse--even among people who exercise and don't smoke--as we get older?

The researchers measured the blood and arterial health of 101 older adults and 22 young adults and found that TMAO levels significantly rise with age. (This falls in line with a previous study in mice, showing the gut microbiome--or your collection of intestinal bacteria--changes with age, breeding more bacteria that help produce TMAO).

Adults with higher blood levels of TMAO had significantly worse artery function, the new study found, and showed greater signs of oxidative stress, or tissue damage, in the lining of their blood vessels.

When the researchers fed TMAO directly to young mice, their blood vessels swiftly aged.

"Just putting it in their diet made them look like old mice," said Brunt. She noted that 12-month-old mice (the equivalent of humans about 35 years old) looked more like 27-month-old mice (age 80 in people) after eating TMAO for several months.

Preliminary data also show that mice with higher levels of TMAO exhibit decreases in learning and memory, suggesting the compound could also play a role in age-related cognitive decline.

On the flip side, old mice that ate a compound called dimethyl butanol, (found in trace amounts in olive oil, vinegar and red wine) saw their vascular dysfunction reverse. Scientists believe that this compound prevents the production of TMAO.

Brunt notes that everyone--even a young vegan--produces some TMAO. But over time, eating a lot of animal products may take a toll.

"The more red meat you eat, the more you are feeding those bacteria that produce it," she said.

Senior author Doug Seals, director of the Integrative Physiology of Aging Laboratory, said the study is an important breakthrough because it sheds light on why our arteries erode with age, even in the healthiest people.

"Aging is the single greatest risk factor for cardiovascular disease, primarily as a result of oxidative stress to our arteries," said Seals. "But what causes oxidative stress to develop in our arteries as we age? That has been the big unkown. This study identifies what could be a very important driver."

The research team is now further exploring compounds that might block production of TMAO to prevent age-related vascular decline.

For now, they said, a plant-based diet may also keep levels in check.

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University of Colorado at Boulder

Identified the genetic landscape of myelodysplastic/myeloproliferative neoplasms

image: Visual abstract of the molecular landscape and clonal architecture of adult myelodysplastic/ myeloproliferative neoplasms.

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Laura Palomo

Myelodysplastic/myeloproliferative neoplasms (MDS/MPN) is a group of rare malignancies with overlapping features from myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN), that include a variety of diseases depending on their phenotype (hematological and morphological characteristics). Adult MSD/MPN include Chronic Myelomonocytic Leukaemia (CMML), atypical chronic myeloid leukemia (aCML), MDS/MPN with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T) and MDS/MPN unclassifiable (MDS/MPN-U).

Due to overlap features among these diseases, as well as with MDS and MPN, differential diagnosis remains a challenge. For hematologists, deciding a diagnosis of these rare malignancies is a broad process that involves the use of different tests and techniques, a long way of analyses, tests, prognosis evaluation, and decision making. In the end, the lack of knowledge that could allow a more precise and fast diagnosis to decide the best treatment and enhance good prognosis prolongs the patient's pain.

Laura Palomo and her colleagues from the MDS Group coordinated by Francesc Solé, from the Josep Carreras Leukaemia Research Institute, in a study led by Torsten Haferlach and his team from the Munich Leukemia Laboratory (MLL), have recently published a study in the Journal Blood that reveals the molecular landscape of these diseases and the combination of genes exclusively mutated in each of these rare neoplasms. These findings provide a useful tool to complement current diagnostic workup in MDS/MPN patients.

"In previous studies, over 90% of MDS/MPN harbored somatic mutations in a group of known genes, which are related to their pathophysiological features and play a role in their clinical heterogeneity, but none of them was specific of MDS/MPN. In our study, made with whole-genome data from a cohort of 367 patients with MDS/MPN, we identified genotype-phenotype associations and potential diagnostic and prognostic molecular markers that could translate to medical practice. We also wanted to provide novel insights into the clonal hierarchy of mutations of MDS/MPN." Says Laura Palomo.

Researchers found recurrent combinations of mutations exclusive to some extent to CMML, aCML, and MDS/MPN-RS-T, while MDS/MPN-U show heterogeneous features that overlap with the other MDS/MPN, but that can be classified according to their molecular profile. For Palomo, "It is imperative to include targeted DNA sequencing techniques in clinical hematology laboratories to improve the diagnosis and risk stratification of these hematological malignancies."

This project is part of an international effort from the MLL, the 5000 Genomes Project. This project includes whole-genome and transcriptome sequencing of 5000 patients with hematological neoplasms and is funded by the Torsten Haferlach Leukämie Diagnostikstiftung.

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Josep Carreras Leukaemia Research Institute

High-end microscopy refined

image: Left two sperm-forming cells expanded with ExM-SIM and imaged with a diffraction limited microscope. On the right, a detailed 3D image of a single synaptonemal complex. The 3D information is colour-coded, the measuring bar on the left corresponds to 25 micrometres, the bar on the right to three micrometres.

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(Picture: Working groups Benavente and Sauer / University of Wuerzburg)

The synaptonemal complex is a ladder-like cell structure that plays a major role in the development of egg and sperm cells in humans and other mammals. "The structure of this complex has hardly been changed in evolution, but its protein components vary greatly from organism to organism," says Professor Ricardo Benavente, cell and developmental biologist at the Biocenter of Julius-Maximilians-Universität (JMU) Würzburg in Bavaria, Germany.

This points to the fact that the structure is crucial for the undisturbed function of the complex. Benavente is investigating the synaptonemal complex together with Markus Sauer, Professor of Biotechnology and Biophysics at the JMU Biocenter. The latest findings of the two research groups have been published in the journal Nature Communications.

The data indicate, among other things, that the synaptonemal complex in the case of the mouse is not, as previously assumed, double-layered, but far more complex.

Sophisticated combination of microscopy techniques

"In our study, we combined structured illumination microscopy SIM with various methods of expansion microscopy ExM," explains Sauer, who is an expert in high-resolution microscopy. The ExM enables greater resolution by embedding the target structures into a swellable polymer which can be physically ~ 4fold expanded.

ExM in combination with SIM enabled the researchers for the first time to visualize the three-dimensional ultrastructure of the synaptonemal complex by multicolour imaging with a spatial resolution of 20 to 30 nanometres.

"If immunolabeling is performed after expansion of the complex, the antibody accessibility can be improved compared to other high-resolution methods. This has enabled us to decipher details of the molecular organisation that were previously hidden," said Benavente and Sauer. In addition, the images can now be taken with almost molecular resolution on a standard light microscope.

With the combination of ExM-SIM, the JMU teams are now looking to discover further details of the synaptonemal complex and other multi-protein complexes.

Info box: Synaptonemal complex

The synaptonemal complex is ultimately responsible for the individuality of the human being. It occurs exclusively in the cells from which the egg and sperm cells of humans and other mammals develop. The complex ensures that the chromosomes exchange genetic material with each other. Thus, a subsequent cell division results in the formation of individual egg or sperm cells.

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University of Würzburg

The mystery of pollen sterility and its reversion in pigeon pea revealed in a new study

image: The Vienna Metabolomics Centre (VIME), University of Vienna, in collaboration with International Crops Research Institute for the Semi-Arid Tropics (ICRISAT), based in India has made a breakthrough in pigeonpea by resolving the mystery behind fertility-sterility transition in pigeonpea.

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CC BY-SA 4.0

This work has been published in The Plant Genome very recently. This study has analyzed one environment-sensitive genic male sterile (EGMS) line that exhibited fertility transition under specified environmental conditions. Fertility transition here refers to the reversion of male sterile condition producing viable pollen to become male fertile plant and vice-versa. An EGMS line, if understood better, could be used together with any elite line for hybrid seed production. Such a system is popular in rice, where the two-line based hybrid rice occupies about 30% of the total hybrid rice growing areas with up to 5-10% higher yield than the three-line hybrids. This new study has dissected unique phenomenon of fertility-sterility transition at molecular level using the systems biology approach.

Prof. Wolfram Weckwerth, Director of VIME and co-leader of this study highlights the importance, "This study is a result of our collaboration over several years with the ICRISAT Center of Excellence in Genomics & Systems Biology." He added, "We are very much hopeful that this study will be hihgly useful to enhance a hybrid breeding system in pigeonpea and help the farming community in developing countries."

Pigeonpea is a key staple crop, highly resistant against drought and extremely important to smallholder farmers in India and many developing countries such as Myanmar, Nepal, Tanzania, Kenya etc. Several years back ICRISAT together with their partners developed cytoplastic male sterility (CMS)-based three-lines hybrid breeding system in pigeonpea. These hybrids have demonstrated upto 30-40% yield advantage over popular varieties. The current hybrid breeding system needs three lines- A- cytoplasmic sterile line, R- fertility restorer line, and B- sterility maintainer line. As a result, the hybrid seed production system is technically demanding and resource intensive. To make the current hybrid breeding system simple and cost effective, CEGSB has been working with VIME for the last years to dissect a suitable EGMS line.

Prof. Rajeev K Varshney, Director, CEGSB at ICRISAT and co-leader of the study on completion of this study said, "It has been privilege for us to work with VIME for using a systems biology approach that combines transcriptomics, proteomics, metabolomics and computational genomics for dissecting fertility-sterility transiation mechanism in the EGMS line." He added, "This study has identified a transcription factor called REVEILLE1 to regulate auxin levels that explains the fertility transition in response to day temperature, especially morning hours."

Dr Rachit Saxena, co-leader and Senior Scientist at ICRISAT told, "Our study had revealed the role of disturbed auxin levels for causing pollen wall thickening and responsible for inhibiting nutrient uptake leading to starvation of pollen grain and subsequent sterility."

In summary, the precise day temperatures could be utilized for hybrid seed production (sterility condition) and multiplication of the TGMS line (fertility condition). Accordingly, any fluctuation in the environmental condition could be monitored for critical temperatures. Further, the exogenous application of auxin could be useful for multiplication of the male sterile line under unfavorable conditions (e.g. higher day temperatures). In the tropical regions, thermosensitive genic male sterility is considered more appropriate for two-line hybrid breeding over photo-sensitive genic male sterility as photoperiod differences are marginal. TGMS line identified from this study looks at a promising future that could ensure a successful hybrid seed production methodology for development of a two-line based hybrid pigeonpea for the semi-arid tropics.

Credit: 
University of Vienna

B-cell protectors

image: The protein Pdap1 (red) is located in the cytoplasm of B cells.

Image: 
Di Virgilio, MDC

Whenever a germ gets into the human body, the immune system usually responds immediately to fight off the enemy attacker. One of our defense system's most important strategies involves B lymphocytes, also known as B cells, which produce antibodies that target and neutralize pathogens. B cells play a central role in adaptive immunity and, together with T cells and components of the innate system, they protect the body against foreign pathogens, allergens and toxins.

Many Berlin researchers involved in the study

A team led by Dr. Michela Di Virgilio, head of the Genome Diversification & Integrity Lab at the Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), has now identified a protein called Pdap1 that supports B cells in this important task while simultaneously protecting them from stress-induced cell death.

The lead authors of the study, which was published in the Journal of Experimental Medicine, are the two doctoral students Verónica Delgado-Benito and Maria Berruezo-Llacuna - both members of Di Virgilio's lab. Researchers from the MDC's Berlin Institute of Medical Systems Biology (BIMSB) and the Experimental and Clinical Research Center (ECRC) were also involved. The ECRC is a joint institution of the MDC and Charité - Universitätsmedizin Berlin.

B cells must continuously adapt

"A successful humoral immune response, which is mediated by antibodies, is dependent on several factors," explains Di Virgilio. Mature B cells have to modify their genes (i.e., building instructions) in order to create antibodies that better match the distinguishing features on the surface of the invading pathogen. This is known as the lock-and-key principle and is achieved by somatic hypermutation, which mutates the pathogen-recognizing portion of the antibody molecule after the encounter and B cell activation.

Over the course of the humoral immune response, another part of the antibodies is transformed in a process known as class-switch recombination (CSR). Here, B cells change the isotype of the antibodies they produce. Instead of immunoglobulins of the isotype IgM, which are predominantly produced at the start of an infection, they may produce, for example, IgG antibodies, which have a different effector function. This process potentiates the ability of antibodies to effectively dispose of the pathogen.

The protein was found with the help of "gene scissors"

"In the beginning, we primarily wanted to understand how class switching works," says Delgado-Benito. "So we genetically modified a mouse B cell line using the CRISPR-Cas9 gene scissors to prevent them from producing certain proteins." In this way, she and the team discovered that without PDGFA associated protein 1 (Pdap1), less class switching occurs.

"In the next step, we generated mice where the gene for Pdap1 was switched off specifically in B cells," reports Berruezo-Llacuna. "This showed us that the protein is also crucial for somatic hypermutation." Without the protein, fewer such mutations occurred in the pathogen-recognizing part of the antibody, thus reducing the possibility to generate highly-specific variants.

B cells die more easily without Pdap1

"A particularly surprising finding to come out of our in vivo experiments, however, was that mouse B cells that are unable to produce Pdap1 die far more easily than is normally the case," adds Di Virgilio. Her team discovered that the protein protects B lymphocytes from stress-induced cell death. "Mature B cells experience cellular stressors particularly when they begin to grow and proliferate rapidly after contact with the pathogen," explains the researcher.

It seems that in unmodified animals, Pdap1 helps B cells to cope with this stress. Without the protein, however, a program is started that ultimately leads to cell death. "So Pdap1 not only helps the B lymphocytes to consistently produce the effective antibodies," says Di Virgilio. "It can also be seen as their protector."

Credit: 
Max Delbrück Center for Molecular Medicine in the Helmholtz Association

Age research: A low level of the stress hormone cortisol contributes to the ageing process

image: Why do we age? What exactly is happening in our bodies? And can we do anything about it? Mankind has sought answers to these questions since time immemorial. While the pharmaceutical scientists Alexandra K. Kiemer (Photo) and Jessica Hoppstädter from Saarland University are not claiming to have solved this ancient problem, they have uncovered processes within our immune system that contribute to ageing. Kiemer and Hoppstädter have shown that low levels of the hormone cortisol and the protein known as GILZ can trigger chronic inflammatory responses in the body.

Image: 
Iris Maurer

Why do we age? What exactly is happening in our bodies? And can we do anything about it? Mankind has sought answers to these questions since time immemorial. While the pharmaceutical scientists Alexandra K. Kiemer and Jessica Hoppstädter from Saarland University are not claiming to have solved this ancient problem, they have uncovered processes within our immune system that contribute to ageing. Kiemer and Hoppstädter have shown that low levels of the hormone cortisol and the protein known as GILZ can trigger chronic inflammatory responses in the body. The results have been published in the journal Aging Cell, doi: https://doi.org/10.1111/acel.13156

The phenomenon of human ageing is the result of a complex interaction between numerous factors, with our own immune system playing a critical role. As we get older, our body's own defence mechanisms age, too. The adaptive or specific immune system that each of us acquires over the course of our lives and that protects us from the pathogens that we came into contact with gradually deteriorates as we age. In contrast, however, our innate or non-specific immune system, which is the first line of defence towards a wide variety of pathogens, becomes overactive. The result is chronic inflammation.

A persistent state of inflammation can cause serious damage to our bodies. One consequence is that chronic inflammatory diseases, such as atherosclerosis or arthritis, are far more prevalent in older patients. 'This has been well-known for a long time. In fact, the scientific community refers to this phenomenon as "inflamm-ageing" - a portmanteau word that combines the two inseparably linked processes of inflammation and ageing,' explains Alexandra K. Kiemer, Professor of Pharmaceutical Biology at Saarland University.

What was uncertain up until now was what actually caused these inflammatory responses to flare up. Kiemer and her research group have now provided some important insight. According to research results from Jessica Hoppstädter, a lead researcher in Kiemer's team, the inflammatory process is linked to the fact that the amount of cortisol generated in the body decreases as we get older.

Cortisol and its inactive form cortisone, commonly referred to as stress hormones, are released by the adrenal gland. The hormone cortisol acts as a biochemical signalling molecule and is involved in numerous metabolic processes in the body. Cortisol deficiency in the body leads to an inflammatory response. 'The serum level of cortisol in the body is lower in the elderly. Moreover, macrophages, an important type of immune cells, can convert inactive cortisone to active cortisol, but this ability declines with increasing age. What we observe is what we could call "macroph-ageing" - the age-induced disruption of macrophage functions,' says Dr. Hoppstädter.

Macrophages are important cells within the immune system that use signalling molecules to control other immune cells. They play a critical role in determining the extent of our body's inflammatory response. However, macrophage function becomes impaired with increasing age. This can lead to an increase in the quantities of pro-inflammatory signalling molecules, which in turn drives the activity of other inflammatory cells of the body's immune system.

The studies conducted by the pharmaceutical research team in Saarbrücken indicate that one particular protein is implicated in the malfunctioning of macrophages in the elderly. The protein is known as GILZ and its levels are regulated in part by cortisol. 'The acronym GILZ stands for glucocorticoid-induced leucine zipper,' explains Professor Kiemer. Kiemer's research group has been conducting experimental studies on the GILZ protein for many years and has discovered that it plays a critical role in many important processes in the human body. But GILZ can have a beneficial or a detrimental effect depending on the specific metabolic conditions.

'We know that GILZ plays a key role in our immune system, for example it's involved in switching off the macrophage inflammatory response. So we put forward the hypothesis that loss of GILZ contributes to macrophage-mediated inflammation in older individuals,' explains Jessica Hoppstädter. Her data shows that a lower cortisol level causes macrophages to produce less GILZ, which in turn means that the macrophages simply continue to release inflammatory signalling molecules. The team found that GILZ levels are indeed lower in older subjects. To find out whether that in itself was enough to cause an inflammatory response, Hoppstädter genetically deactivated the GILZ protein. The data confirmed Hoppstädter's conjecture: the macrophages were activated and there was a resulting increase in chronic inflammatory processes.

Professor Kiemer's research group is involved in a number of studies examining the activity of the GILZ protein, including the search for new active compounds that are capable of boosting GILZ levels in the human body. However, a substance able to arrest the progress of age-related inflammatory processes or impede macrophage ageing is still a long way off. 'All of these projects are still very much in the realm of basic research. The GILZ protein operates within an extensive network of complex biochemical interrelationships and it can have both beneficial and deleterious effects. A huge amount of work still needs to be done before we have a medically effective drug,' says Alexandra K. Kiemer. The phenomenon of human ageing remains immensely complex, but the work of the Saarbrücken scientists has moved us one small step further to a better understanding of why and how we age.

Credit: 
Saarland University

Role models have major influence on female university choices

Women exposed to successful and charismatic role models are more likely to follow them in choosing a university major.

An experiment with undergraduates studying introductory economics classes at Southern Methodist University (SMU) in the USA, published in the American Economic Journal: Applied Economics, revealed that female students were hugely more likely to study the subject further having encountered successful female graduates of the same course.

Researchers from Texas A&M University and Lancaster University engaged two role models - chosen with the help of two current female economics majors - to speak with classes of undergraduates studying principles of economics classes about how their choice of major contributed to their success. They measured the uptake of future economics classes among that group when compared with those studying the same course who had no such interaction with the successful women.

Female students' enrolment in further economics classes almost doubled following the role models encounter, going against general patterns in recent years showing little progress in attracting women to the field.

"Our results show that role model intervention had a significant impact on all outcomes for female students," said report co-author Associate Professor Danila Serra, of Texas A&M University. "Being in a class that received the role model visits increased the likelihood that a female student would major in economics by almost 100 per cent. The probability of them taking intermediate or any other economics classes also increased by large margins.

"There is strong evidence of the impact of female role models on female students moving into fields of study in which men are traditionally over-represented, and that the encounters served as an inspiration."

Principles of economics classes at SMU are typically gender-balanced, with between 44 and 47 per cent of students female. In contrast, for the next step up, only 26 per cent of students are women, and the gender imbalance worsens by graduation, with less than a quarter of economics degrees awarded to women.

"Due to historical gender imbalances in some subjects, such as economics, it is difficult for young women to come into direct contact with successful women who have majored in these fields and who can inspire them to do the same," said report co-author Dr Catherine Porter, of Lancaster University Management School. "Our study suggests that role model intervention could have a significant impact on the treated women's lifetime income streams.

"Our research shows that the long-term goal of moving towards gender parity in the economics profession at all levels could be achieved simply and at a relatively low cost by exposing students enrolled in principles classes to successful and inspiring alumnae."

The researchers' data shows the majority of those women impacted were previously planning to major in lower-earning humanities fields, and the effect did not decrease the number of them majoring in male-dominated, higher-paying fields such as STEM and finance. Those women who swayed towards economics also performed as well, if not better, in exams as the control students, showing the attraction towards the change affected seemingly qualified women who were not previously pursuing economics. Thus, there could be a positive impact on their potential future earnings.

While the effect on female students in the role model classes was marked, there was no effect on the male students in the same groups.

Credit: 
Lancaster University