Culture

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."

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.

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.

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.

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.

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."

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.

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.

CLEVELAND, Ohio (July 1, 2020)--Depression has been shown to be prevalent during menopause, affecting as many as 70% of women transitioning into menopause. A new study not only confirms the high prevalence of depression but also the greatest risk factors for it in postmenopausal women, as well as any relationships with anxiety and fear of death. Study results are published online today in Menopause, the journal of The North American Menopause Society (NAMS).

With the decrease in hormone production during menopause, women are more prone to a number of psychological problems, including depression, anxiety, irritability, nervousness, sadness, restlessness, memory problems, lack of confidence and concentration, and a loss of libido. At the same time, as women age, the fear of death becomes more pronounced. Depression and anxiety, which are the most common psychological problems that occur during the menopause transition, likely increase that fear.

In this new study involving 485 postmenopausal Turkish women aged between 35 and 78 years, researchers sought to determine the frequency of depressive symptoms in postmenopausal women, the variables affecting it, and the levels of anxiety and fear of death. They then evaluated the relationship between all these variables and postmenopausal depression. They found that depression in postmenopausal women is a common and important health problem that requires further study. In this specific study, 41% of the participants were confirmed to experience some form of depression, although it is theorized that this rate was lower than in some previous studies because of the somewhat lower age of participants (average age, 56.3 y).

In addition, the researchers identified those risk factors that most affected depression in postmenopause. These included being a widow or separated from one's spouse, alcohol consumption, any medical history requiring continuous medication, the presence of any physical disability, physician-diagnosed mental illness, and having four or more living children. They did not, however, confirm any relationship between depression and the fear of death, although the somewhat younger age of the study group may have influenced this lack of association.

Study results appear in the article "Depression, anxiety and fear of death in postmenopausal women."

"The findings of this study involving postmenopausal Turkish women are consistent with existing literature and emphasize the high prevalence of depressive symptoms in midlife women, particularly those with a history of depression or anxiety, chronic health conditions, and psychosocial factors such as major stressful life events. Women and the clinicians who care for them need to be aware that the menopause transition is a period of vulnerability in terms of mood," says Dr. Stephanie Faubion, NAMS medical director.

A treasure trove of information relevant to human and environmental health is hiding in an unexpected place. Samples of wastewater from homes, institutions, towns and cities around the world can now be probed for valuable data concerning community well-being, antibiotic use and resistance, recreational substance consumption and abuse, biomarkers of disease as well as environmental hazards and degradation.

This rapidly emerging health surveillance technique, termed wastewater-based epidemiology (WBE), is an economical and powerful tool. It can teach us much about large populations contributing into a centralized­­ sewerage system during the course of a full 24-hour cycle.

In a pair of new studies, Rolf Halden, director of the ASU Biodesign Center for Environmental Health Engineering and author for the 2020 Book Environment, describes the process and highlights important new findings extracted from the municipal wastewater most of us contribute to on a daily basis. Halden is also a professor at ASU's School of Sustainable Engineering and the Built Environment.

"After being around for more than 15 years, wastewater-based epidemiology is finally getting the attention it deserves, thanks in no small part to the challenges brought about by the COVID-19 pandemic," says Halden, a pioneer and champion of WBE whose team has built the largest single monitoring network and sample archiv­­­­e in the U.S. and around the world.

Data-rich waste

Advances in WBE technologies and applications are progressing rapidly. The method offers a low-cost strategy for obtaining health and environmental data on a local, regional, national and even continental scale. It can provide valuable information with acute spatial and temporal resolution. Because the method aggregates community-wide data, it is non-invasive and ensures the privacy of the population under study.

In addition to its ability to measure ingestion rates of drugs including cocaine and opioids, WBE has been proposed as a means of identifying exposure to agents including pesticides, personal care products, infectious pathogens, persistent organic pollutants, as well as for tracking community-wide incidence of illnesses including diabetes, allergies, stress-induced disorders and cancer.

In the first of two current studies, with Biodesign Institute research scientist Erin Driver as lead author, wastewater samples from a large university in the American Southwest were analyzed for the presence of caffeine, tobacco and alcohol. This study monitored the presence of these substances during the 2017-18 academic year. It is the first U.S. study to focus on these common psychotropic compounds, aimed at comparing data output from WBE to that of conventional methods, namely the use of questionnaires.

Alcohol, nicotine and caffeine use are significant public health concerns, claiming some 550,000 lives annually. Data suggest college-aged students are particularly vulnerable to overconsumption of these substances, often resulting in behaviors that last their lifetimes, which create poorer health outcomes. This work shows the utility of monitoring this particular subset of a population and illustrates the prospective benefit of long-term monitoring networks on college campuses to improve student health and promote future success.

Efficient, near real-time monitoring

WBE represents an attractive alternative to community-wide monitoring through self-reported surveys, which may introduce sampling and reporting biases and are often comparatively costly to administer; how much more expensive, was one of the questions investigated in the study.

In addition to measurements of the quantities of stimulants consumed, the study revealed strong positive correlations for the consumption of alcohol and nicotine as well as between nicotine and caffeine, but not between alcohol and caffeine.

Temporal information was also tracked, indicating that caffeine consumption was highest during the week, while nicotine and alcohol consumption peaked on the weekends, as anticipated. The study demonstrated the practicality and reliability of campus-wide longitudinal tracking of some 60,000 students directly and inexpensively.

In addition to monitoring health indices related to behavior, WBE could ultimately provide a low-cost means of carrying out infectious disease surveillance across populations, providing an early-warning system to alert researchers to disease outbreaks in near real time, within as little as 24 hours.

Halden hopes to leverage the power of WBE technology, ultimately combining a broad range of human health indicators present in wastewater into a comprehensive system he calls the Human Health Observatory (HHO). Currently, ASU's HHO gathers data from over 350 cities representing around 32 million people or roughly 10% of the U.S. population and a quarter billion people globally.

Data streams

Strategies for extracting information on particular target substances vary, often using sophisticated methods such as liquid chromatography tandem mass spectroscopy, which can fingerprint chemical traces based on their differing molecular weights and characteristic ionization and fragmentation behavior. But the basic process used for WBE is simple.

Samples of raw wastewater--sewage entering a water reclamation facility, are typically collected over a 24-hour period and then shipped to the laboratory to determine the average concentration of chemicals or their biological metabolites. The concentration value is then multiplied with the flow volume of sewage during the sampling period, to provide a more meaningful unit of a quantity of a substance per 1,000 people per day. Combining this information with estimates of average excretion rates of target metabolites permits researchers to determine the quantity of consumption of a given substance, be it cups of coffee, number of alcoholic beverages or cigarettes smoked.

The final data in the university study showed levels of alcohol consumption to be consistent with quantities observed in self-reported surveys. But whereas both study methods were shown to yield similar findings, Driver summed up the big news as follows: "In this study, use of WBE was over 200-times cheaper than conventional methods, yielding data at more frequent intervals throughout the academic year. Costs were reduced from an estimated $127 to only $0.58 per person when using wastewater analytics."

The researchers are now measuring how the COVID-19 epidemic and the associated stay-at-home orders are impacting substance use in the university's home city.

Health surveillance refined

In the other new study, lead authors Professors Olga Hart and Rolf Halden of the Biodesign Center for Environmental Health Engineering report on a modeling study that considered all 13,940 major sewage treatment plants in the U.S. and demographic information collected by the U.S. Census during the 2017 American Community Survey.

The aim of the study was to investigate and understand potential biases in WBE studies by examining variations in data collected due to temperature, seasonal variations and rates of biomarker decay. To do this, the researchers assumed stable consumption in the population over one calendar year and computed how the community contributing to the chemical signal detectable at a given wastewater treatment plant would change as a function of the changes induced by seasonally variable temperatures and biomarker decay rates.

The study also found intriguing correlations between seasonal temperatures and the size and distance a population can be observed by wastewater analytics. In general, during the colder months of the year the "visibility down the pipe" is better, leading to a larger population captured that resides farther away from the plant, and a more even representation of all people served by the treatment plant.

In contrast, in-sewer degradation during the summer months reduced the observable population and the detectable chemistry was composed primarily of communities closer to the treatment. This finding gained great significance when census data showed considerable differences in demographic indicators exist as a function of the distance of residence from a plant. Compared to the cold winter season, observations in the summer were more likely to capture households with lower income, less educational attainment, more prevalent military service, higher unemployment, and greater lack of health insurance. Hart summed up the findings:

"If not taken into account, this uneven distribution of populations within urban environments could lead to skewed data from wastewater sampling, or to attributing to seasonal change, patterns that are actually of demographic origin. Just like in traditional human subject studies, whether we are trying to better understand the health status of communities by passive monitoring or testing the impact of proactive interventions, it's critical to understand if our study population significantly changes from observation to observation."

Halden agreed and added: "This study challenges WBE researchers to reassess their data in the context of temperature changes. Regardless of whether we are monitoring chemicals or biological agents in wastewater, our research community will have to pay more attention to ambient air temperatures in order to get the most robust information from wastewater analysis."

WASHINGTON, June 30, 2020 -- It is well established that the SARS-CoV-2 virus responsible for the COVID-19 disease is transmitted via respiratory droplets that infected people eject when they cough, sneeze or talk. Consequently, much research targets better understanding droplet motion and evaporation to understand transmission more deeply.

In a paper in Physics of Fluids, by AIP Publishing, researchers developed a mathematical model, proceeding from first principles, for the early phases of a COVID-19-like pandemic using the aerodynamics and evaporation characteristics of respiratory droplets.

The researchers modeled the pandemic dynamics with a reaction mechanism, where each reaction has a rate constant obtained by calculating the frequency of collisions between the infectious droplet cloud ejected by an infected person and a healthy person.

"The size of the droplet cloud, the distance it travels, and the droplet lifetimes are, therefore, all important factors that we calculated using conservation of mass, momentum, energy and species," said Swetaprovo Chaudhuri, one of the authors.

The model could be used to estimate approximately how long droplets can survive, how far they can travel, and which size of droplet survives for how long. Though, as Chaudhuri adds, "The actual situation could be complicated by wind, turbulence, air-recirculation or many other effects."

"Without wind and depending on the ambient condition, we found droplets travel between 8 to 13 feet before they evaporate or escape," said Abhishek Saha, a co-author.

This finding implies that social distancing at perhaps greater than 6 feet is essential.

Furthermore, the initial size of the longest surviving droplets is in the range of 18-50 microns, meaning masks can indeed help. These findings could help inform reopening measures for schools and offices looking at student or employee density.

"This model is not claiming to predict the exact spread of COVID-19," said Saptarshi Basu, another author. "But, our work shows that droplet evaporation or desiccation time is highly sensitive to the ambient temperature and relative humidity."

More broadly, this multiscale model and the firm theoretical underpinning that connects the two scales -- macroscale pandemic dynamics and the microscale droplet physics -- could emerge as a powerful tool in clarifying the role of environment on infection spread through respiratory droplets.

The revolution in our understanding of the night sky and our place in the universe began when we transitioned from using the naked eye to a telescope in 1609. Four centuries later, scientists are experiencing a similar transition in their knowledge of black holes by searching for gravitational waves.

In the search for previously undetected black holes that are billions of times more massive than the sun, Stephen Taylor, assistant professor of physics and astronomy and former astronomer at NASA's Jet Propulsion Laboratory (JPL) together with the North American Nanohertz Observatory for Gravitational Waves (NANOGrav) collaboration has moved the field of research forward by finding the precise location - the center of gravity of our solar system - with which to measure the gravitational waves that signal the existence of these black holes.

The potential presented by this advancement, co-authored by Taylor, was published in the journal the Astrophysical Journal in April 2020.

Black holes are regions of pure gravity formed from extremely warped spacetime. Finding the most titanic black holes in the Universe that lurk at the heart of galaxies will help us understand how such galaxies (including our own) have grown and evolved over the billions of years since their formation. These black holes are also unrivaled laboratories for testing fundamental assumptions about physics.

Gravitational waves are ripples in spacetime predicted by Einstein's general theory of relativity. When black holes orbit each other in pairs, they radiate gravitational waves that deform spacetime, stretching and squeezing space. Gravitational waves were first detected by the Laser Interferometer Gravitational-Wave Observatory (LIGO) in 2015, opening new vistas on the most extreme objects in the universe. Whereas LIGO observes relatively short gravitational waves by looking for changes in the shape of a 4-km long detector, NANOGrav, a National Science Foundation (NSF) Physics Frontiers Center, looks for changes in the shape of our entire galaxy.

Taylor and his team are searching for changes to the arrival rate of regular flashes of radio waves from pulsars. These pulsars are rapidly spinning neutron stars, some going as fast as a kitchen blender. They also send out beams of radio waves, appearing like interstellar lighthouses when these beams sweep over Earth. Over 15 years of data have shown that these pulsars are extremely reliable in their pulse arrival rates, acting as outstanding galactic clocks. Any timing deviations that are correlated across lots of these pulsars could signal the influence of gravitational waves warping our galaxy.

"Using the pulsars we observe across the Milky Way galaxy, we are trying to be like a spider sitting in stillness in the middle of her web," explains Taylor. "How well we understand the solar system barycenter is critical as we attempt to sense even the smallest tingle to the web." The solar system barycenter, its center of gravity, is the location where the masses of all planets, moons, and asteroids balance out.

Where is the center of our web, the location of absolute stillness in our solar system? Not in the center of the sun as many might assume, rather it is closer to the surface of the star. This is due to Jupiter's mass and our imperfect knowledge of its orbit. It takes 12 years for Jupiter to orbit the sun, just shy of the 15 years that NANOGrav has been collecting data. JPL's Galileo probe (named for the famed scientist that used a telescope to observe the moons of Jupiter) studied Jupiter between 1995 and 2003, but experienced technical maladies that impacted the quality of the measurements taken during the mission.

Identifying the center of the solar system's gravity has long been calculated with data from Doppler tracking to get an estimate of the location and trajectories of bodies orbiting the sun. "The catch is that errors in the masses and orbits will translate to pulsar-timing artifacts that may well look like gravitational waves," explains JPL astronomer and co-author Joe Simon.

Taylor and his collaborators were finding that working with existing solar system models to analyze NANOGrav data gave inconsistent results. "We weren't detecting anything significant in our gravitational wave searches between solar system models, but we were getting large systematic differences in our calculations," notes JPL astronomer and the paper's lead author Michele Vallisneri. "Typically, more data delivers a more precise result, but there was always an offset in our calculations."

The group decided to search for the center of gravity of the solar system at the same time as sleuthing for gravitational waves. The researchers got more robust answers to finding gravitational waves and were able to more accurately localize the center of the solar system's gravity to within 100 meters. To understand that scale, if the sun were the size of a football field, 100 meters would be the diameter of a strand of hair. "Our precise observation of pulsars scattered across the galaxy has localized ourselves in the cosmos better than we ever could before," said Taylor. "By finding gravitational waves this way, in addition to other experiments, we gain a more holistic overview of all different kinds of black holes in the Universe."

As NANOGrav continues to collect ever more abundant and precise pulsar timing data, astronomers are confident that massive black holes will show up soon and unequivocally in the data.

What The Editorial Says: The term "cytokine storm" and its relevance to COVID-19 are examined in this editorial.

Authors: Pratik Sinha, M.B., Ch.B., of the University of California, San Francisco, 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/jamainternmed.2020.3313)

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

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Ischemic heart disease (IHD) has maintained its rank as one of the worldwide leading causes of mortality outweighing the burden from all malignancies combined.

When IHD develops, chronic myocardial ischemia, aggravated in some instances by periods of acute ischemia in the form of myocardial infarction, ensue. Damaged myocardium is replaced with a fibrotic scar that over-activates physiologic compensatory mechanisms with challenging sequalae, such as myocardial rigidity and eventually, over time, heart failure.

A research collaboration team at University of Helsinki together with a State Key Laboratory of Cardiovascular Disease (FuWai Hospital, Beijing, China) has investigated in a mouse model of artificial myocardial infarction, the molecular mechanisms underlying novel, easily clinically implementable tissue-engineered approach for stimulating the myocardial regeneration.

The tissue-engineered approach relies on a local transplantation of minute pieces of autologous atrial appendage tissue, termed atrial appendage micrografts (AAMs), to the surface of the ischaemically stressed myocardium.

Results of the investigation are published in the Journal of Heart and Lung Transplantation.

"We were able to get a comprehensive view on how the heart's functional, structural and metabolic aspects of healing are influenced by AAMs patch transplantation following acute ischemia," says Docent Esko Kankuri from University of Helsinki.

Heart's pumping function preserved, also improved functional recovery

The research group ulitized complementary tools, including systematic postoperative functional echocardiographic follow-up, histomorphometric analyses and finally site-selective proteomics in tandem with functional bioinformatics.

"We demonstrated not only preservation of heart's pumping function following critical ischemic insult but also improved functional recovery following AAMs transplantation during follow-up," says Docent Maciej Lalowski from University of Helsinki.

"We identified 1 005 proteins from the myocardium, of which 216 were differentially expressed immediately below the AAMs patch in 'subtransplant' area and 43 in the interventricular septum remote to the AAMs transplantation site," Lalowski continues.

The therapy is currently undergoing clinical safety and feasibility evaluation as an adjuvant to the coronary artery bypass grafting operation.

Dublin, Tuesday, 30 June 2020: Researchers have identified a critical new step in how brain cells function in people with one of the most common forms of epilepsy. This could lead to new treatment approaches for people with drug-resistant epilepsy.

The study was led by researchers at FutureNeuro, the SFI Research Centre for Chronic and Rare Neurological Diseases, hosted by RCSI University of Medicine and Health Sciences with colleagues at Severo Ochoa-Centre for Molecular Biology (CBMSO) of Madrid and Institute for Research in Biomedicine (IRB) of Barcelona. The research is published in Brain.

Changes in gene activity are known to be important in the development of epilepsy. Normally, a molecule called messenger RNA is produced when a gene is active. This becomes the template for the production of the proteins that brain cells use to function. A critical step is the addition of a short sequence called a poly(A) tail. This has never been studied before in epilepsy. The team discovered that this tailing process (polyadenylation) is dramatically altered for about one third of the genes of someone with epilepsy, changing protein production in the brain.

"Our discovery adds another piece to the puzzle to help us understand why gene activity is different in someone with epilepsy," said Dr Tobias Engel, FutureNeuro Investigator and Senior Lecturer in the School of Physiology and Medical Physics at RCSI. "It is remarkable that so many active genes in the brain show a change in this polyadenylation process. We believe that this could ultimately lead us to new targeted treatments, allowing us to investigate if we could stop a person from developing epilepsy."

Epilepsy is one of the most common chronic brain diseases, affecting over 65 million people worldwide. While current drug treatments are usually effective in suppressing seizures, they do not work in one third of people with epilepsy and have no effect on the underlying causes of the disease.

"Regulated poly(A) tailing of messenger RNAs is a step in gene expression regulation barely explored in brain diseases, and our study should foster its investigation in other brain conditions in which gene expression alteration is suspected," said Dr José Lucas, Research Professor at Severo Ochoa-Centre for Molecular Biology of Madrid.

Prof. David Henshall, Director of FutureNeuro and Professor of Physiology in the School of Physiology and Medical Physics at RCSI, said, "Our aim in FutureNeuro is to provide faster diagnostics, precision therapeutics and eHealth enabled solutions for those with chronic and rare neurological diseases. This research is a great example of how understanding basic mechanisms of a disease can guide us to new targets for treatment."