Culture

CINCINNATI - As the world scrambles to control the growing COVID-19 coronavirus pandemic, new research in Nature Structural & Molecular Biology shows viruses also play a key evolutionary role in mammals' ability to reproduce and survive.

Scientists in the Cincinnati Children's Perinatal Institute and at Azabu University in Japan obtained their data by studying laboratory mice and human germline cells.

In two separate papers appearing in the same edition of the journal, they reveal two distinct and fundamental processes underlying germline transcriptomes. They also show that species-specific transcriptomes are fine-tuned by endogenous retroviruses in the mammalian germline

Germline transcriptomes include all the messenger RNA in germline cells, which contain either the male or female half of chromosomes passed on as inherited genetic material to offspring when species mate. This means that germline transcriptomes define the unique character of sperm and egg to prepare for the next generation of life.

Although the studies are separate they complement one another, according to Satoshi Namekawa, PhD, principal investigator on both papers and a scientist in the Division of Reproductive Science at Cincinnati Children's.

"One paper, Maezawa and Sakashita et al., explores super-enhancers, which are robust and evolutionally conserved gene regulatory elements in the genome. They fuel a tightly regulated burst of essential germline genes as sperm start to form," Namekawa said.

"The second study, Sakashita et al., involves endogenous retroviruses that act as another type of enhancer - gene regulatory elements in the genome - to drive expression of newly evolved genes. This helps fine tune species-specific transcriptomes in mammals like humans, mice, and so on.

Clinical Relevance

Together the studies have significant potential ramifications for clinical practice, according to study authors, who include a multi-disciplinary mix of developmental biologists, bioinformaticians and immuno-biologists. Dysregulation of gene expression in the formation of male sperm is closely associated with male infertility and birth defects.

Viruses, especially endogenous retroviruses (ERVs) that are an inherent part of mammalian biology, can dramatically influence gene expression, investigators report. ERVs are molecular remnants of retroviruses that infect the body and over time incorporate into the genome.

"What we learn from our study is that, in general, viruses have major roles in driving evolution," Namekawa explained. "In the long-term, viruses have positive impacts to our genome and shape evolution."

Super-Enhancer Switch

The study, Maezawa and Sakashita et al., combined biological testing of mouse models and human germline cells with computational biology, including genome-wide profiling of gene regulatory elements in germline cells.

Those tests revealed that the the genome-wide reorganization of super-enhancers drives bursts of germline gene expression after germ cells enter meiosis, a specialized form of cell division that produces the haploid genome of germ cells.

The study further demonstrates the molecular process through whichsuper-enhancer switching takes place in germ cells. Super-enhancers are regulated by two molecules that act as gene-burst control switches - the transcription factor A-MYB and SCML2, a critical silencing protein in sperm formation.

TEs and Jumping Genes

Endogenous retroviruses are a group of transposable elements (TEs), mobile genetic elements that account for approximately 40-50 percent of a given mammalian genome. Also referred to as "jumping genes," TEs have long been considered genetic threats because transposition can be harmful if, for example, the process disrupts protein-coding genes.

Building on findings from the 1950s that TEs can function as genetic regulatory elements, Namekawa and his collaborators (Sakashita et al.) produced data showing that ERV-driven mechanisms help fine tune species-specific transcriptomes.

In rodents with type 2 diabetes, a single surgical injection of a protein called fibroblast growth factor 1 can restore blood sugar levels to normal for weeks or months. Yet how this growth factor acts in the brain to generate this lasting benefit has been poorly understood.

Clarifying how this occurs might lead to more effective diabetes treatments that tap into the brain's inherent potential to ameliorate the condition.

"Until recently, the brain's ability to normalize elevated blood sugar levels in diabetic animals was unrecognized," said Dr. Michael Schwartz, professor of medicine at the University of Washington School of Medicine and co-director of the UW Medicine Diabetes Institute. "By interrogating cellular and molecular responses induced in the hypothalamus by a brain peptide called fibroblast growth factor 1, our international teams' latest findings chart a path towards a more complete understanding how this effect is achieved.

"These insights," he said, "may one day inform therapeutic strategies for inducing sustained diabetes remission, rather than simply lowering blood sugar levels on a day-to-day basis as current treatments do."

Type 2 diabetes affects 10% of the U.S. population. It is closely tied to obesity and causes serious health problems including heart disease, vision loss, kidney failure, dementia, difficult-to-cure infections, and nerve damage. It also increases the risk of needing amputations. Control of blood sugar levels can prevent these problems, but is often hard to achieve and becomes an ongoing struggle for many patients.

In two companion papers in the Sept. 7 editions of Nature Communications and Nature Metabolism, international teams of researchers describe the intricate biology of the brain's response to fibroblast growth factor 1. The first team describes robust cellular responses that appear to safeguard brain-signaling pathways critical to keeping blood sugar in check.

A second team, containing some of the same researchers, made discoveries about extracellular matrix assemblies called "perineuronal nets" that enmesh groups of neurons involved in blood sugar control. The investigators learned that fibroblast growth factor 1 repairs perineuronal nets that have been damaged by diabetes. This response is required for diabetes remission to be sustained.

Dr. Tunes Pers, of the Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen in Denmark, and diabetes and obesity researcher Dr. Michael Schwartz at UW Medicine in Seattle were senior authors of the Nature Communications report. The lead authors from their labs were Dr. Marie Bentsen and Dr. Dylan Rausch.

The international team of scientists that they assembled began by detailing changes of gene expression induced by fibroblast growth factor 1 treatment across diverse brain cell types located in the hypothalamus. This small region of the brain regulates many body functions, including levels of blood sugar, hunger, food intake, and energy use and storage.

The scientists found that glial cells, which not only provide structural support but also help to organize and regulate neurocircuit activity, responded more intensely than did neurons, brain cells known for electrical transmission of information.

The researchers also observed enhanced interactions between astrocytes and a subset of neurons that make agouti-related protein (called Agrp neurons). Astrocytes are abundant, star-shaped glial cells that nourish neurons and support their electrical transmissions. Agrp neurons are essential components of the melanocortin signaling system, a brain circuit crucial to control of feeding, body weight and blood sugar.

Excessive activation of Agrp neurons is known to dampen melanocortin signaling. This effect has been linked to diabetes development in people and rodents. The researchers noted that prohibiting melancortin signaling after fibroblast growth factor 1 injection into the brain prevents sustained diabetes remission.

Among other cell types that responded robustly to fibroblast growth factor 1 are tanycytes, elongated, nutrient-sensing glial cells found only in the hypothalamus. Their contributions to normalizing of glucose levels require additional study.

The paper published in Nature Metabolism looked at structures that the scientists called "the previously unrecognized participants" in the mechanism behind fibroblast growth factor 1's ability to induce diabetes remission.

These are the perineuronal nets that enmesh blood sugar-regulating neurons in the hypothalamus, including Agrp neurons. The lead author of this paper is Kim Alonge, acting instructor in medicine at the UW School of Medicine. The senior author is Michael Schwartz.

Perineuronal nets promote neurocircuit stability by enmeshing neurons and girding the connections between them. The researchers wanted to know if obesity-related diabetes is associated with structural changes in these perineuronal nets, and whether those could be treated.

The research team noted that in the Zucker Diabetes Fatty rat model of type 2 diabetes, these nets are scarce in the hypothalamus compared to rats with normal blood sugar levels, Yet in other parts of the brain the nets are normal.

This loss of perineuronal nets was rapidly reversed following a single injection of fibroblast growth factor 1 into the brain. The ability of fibroblast growth factor 1 to ameliorate diabetes was hampered by removing the nets through enzymatic digestion. In contrast, intact perineuronal nets are not required for fibroblast growth factor 1 to affect food intake.

These finding identify perineuronal nets as key targets for sustained diabetes remission induced by the action of fibroblast growth factor 1. The researchers speculate that perhaps these nets help to constrain the activity of Agrp neurons and thereby pump up melanocortin signaling.

The researchers plan to continue to try to bridge the gap between the cellular (and extracellular) responses to fibroblast growth factor 1 and the normalization of blood sugar levels. This, they hope, may ultimately uncover novel strategies for achieving sustained diabetes remission in patients.

Patients with autoimmune inflammation of their thyroid may be at greater risk of developing anxiety, according to a study being presented at e-ECE 2020. The study found that people with anxiety may also have inflammation in their thyroid gland that can be reduced by taking the non-steroidal anti-inflammatory, ibuprofen. These findings suggest that thyroid function may play an important role in the development of anxiety disorders and that thyroid inflammation should be investigated as an underlying factor in psychiatric disorders, such as anxiety.

At present, up to 35% of the young population (25-60 years) in developed countries have an anxiety disorder. Anxiety can have a severe impact of people's quality of life and ability to work and socialise, and anti-anxiety medication does not always have a lasting effect. Current examinations for anxiety disorders usually focus on dysfunction of the nervous system and do not take into account the role of the endocrine system.

The thyroid gland produces the hormones thyroxine (T4) and triiodothyronine (T3) that are essential for regulating heart, muscle and digestive function, brain development and bone maintenance. Autoimmune inflammation in the thyroid occurs when our bodies wrongly produce antibodies that attack the gland and causes damage. Recent studies indicate that anxiety disorders can be associated with the dysfunction of the thyroid gland. Therefore, it is important to understand how this may contribute to anxiety, so that patients can be treated more effectively.

Dr Juliya Onofriichuk from Kyiv City Clinical Hospital investigated thyroid function in 29 men (average age 33.9) and 27 women (average age 31.7) with diagnosed anxiety, who were experiencing panic attacks. Ultrasounds of their thyroid glands assessed thyroid function and levels of thyroid hormones were measured. The patients with anxiety showed signs of inflammation of their thyroid glands but their function was not affected, with thyroid hormone levels all within the normal range, although slightly elevated. They also tested positive for antibodies directed against the thyroid. Treatment for 14 days with ibuprofen and thyroxine reduced thyroid inflammation, normalised thyroid hormone levels and reduced their anxiety scores.

"These findings indicate that the endocrine system may play an important role in anxiety. Doctors should also consider the thyroid gland and the rest of the endocrine system, as well as the nervous system, when examining patients with anxiety," Dr Onofriichuk explains.

This knowledge could help patients with anxiety receive more effective treatment that improves thyroid function and could have a long-term positive effect on their mental health. However, sex and adrenal gland hormones were not taken in to account in this study, and these can also have a serious effect on anxiety.

Dr Onofriichuk now plans to conduct further research that examines the levels of thyroid, sex and adrenal hormones (cortisol, progesterone, prolactin, oestrogen and testosterone) in patients with dysfunctional thyroid glands and anxiety disorders. This research aims to help understand more clearly the role of the endocrine system in the development of anxiety and could lead to better management of anxiety disorders.

COVID-19 patients can suffer long-term lung and heart damage but, for many, this tends to improve over time, according to the first, prospective follow-up of patients infected with the coronavirus, presented at the European Respiratory Society International Congress. [1]

Researchers in the COVID-19 'hot spot' in the Tyrolean region of Austria recruited consecutive coronavirus patients to their study, who were hospitalised at the University Clinic of Internal Medicine in Innsbruck, the St Vinzenz Hospital in Zams or the cardio-pulmonary rehabilitation centre in Münster, Austria. In their presentation to the virtual congress today (Monday), they reported on the first 86 patients enrolled between 29 April and 9 June, although now they have over 150 patients participating.

The patients were scheduled to return for evaluation six, 12 and 24 weeks after their discharge from hospital. During these visits, clinical examinations, laboratory tests, analysis of the amounts of oxygen and carbon dioxide in arterial blood, lung function tests, computed tomography (CT) scans and echocardiograms were carried out.

At the time of their first visit, more than half of the patients had at least one persistent symptom, predominantly breathlessness and coughing, and CT scans still showed lung damage in 88% of patients. However, by the time of their next visit 12 weeks after discharge, the symptoms had improved and lung damage was reduced to 56%. At this stage, it is too early to have results from the evaluations at 24 weeks.

"The bad news is that people show lung impairment from COVID-19 weeks after discharge; the good news is that the impairment tends to ameliorate over time, which suggests the lungs have a mechanism for repairing themselves," said Dr Sabina Sahanic, who is a clinical PhD student at the University Clinic in Innsbruck and part of the team that carried out the study, which includes Associate Professor Ivan Tancevski, Professor Judith Löffler-Ragg and Dr Thomas Sonnweber in Innsbruck.

The average age of the 86 patients included in this presentation was 61 and 65% of them were male. Nearly half of them were current or former smokers and 65% of hospitalised COVID-19 patients were overweight or obese. Eighteen (21%) had been in an intensive care unit (ICU), 16 (19%) had had invasive mechanical ventilation, and the average length of stay in hospital was 13 days.

A total of 56 patients (65%) showed persistent symptoms at the time of their six-week visit; breathlessness (dyspnoea) was the most common symptom (40 patients, 47%), followed by coughing (13 patients, 15%). By the 12-week visit, breathlessness had improved and was present in 31 patients (39%); however, 13 patients (15%) were still coughing

Tests of lung function included FEV1 (the amount of air that can be expelled forcibly in one second), FVC (the total volume of air expelled forcibly), and DLCO (a test to measure how well oxygen passes from the lungs into the blood). These measurements also improved between the visits at six and 12 weeks. At six weeks, 20 patients (23%) showed FEV1 as less than 80% of normal, improving to 18 patients (21%) at 12 weeks, 24 patients (28%) showed FVC as less than 80% of normal, improving to 16 patients (19%) at 12 weeks, and 28 patients (33%) showed DLCO as less than 80% of normal, improving to 19 patients (22%) at 12 weeks.

The CT scans showed that the score that defines the severity of overall lung damage decreased from eight points at six weeks to four points at twelve weeks. Damage from inflammation and fluid in the lungs caused by the coronavirus, which shows up on CT scans as white patches known as 'ground glass', also improved; it was present in 74 patients (88%) at six weeks and 48 patients (56%) at 12 weeks.

At the six-week visit, the echocardiograms showed that 48 patients (58.5%) had dysfunction of the left ventricle of the heart at the point when it is relaxing and dilating (diastole). Biological indicators of heart damage, blood clots and inflammation were all significantly elevated.

Dr Sahanic said: "We do not believe left ventricular diastolic dysfunction is specific to COVID-19, but more a sign of severity of the disease in general. Fortunately, in the Innsbruck cohort, we did not observe any severe coronavirus-associated heart dysfunction in the post-acute phase. The diastolic dysfunction that we observed also tended to improve with time."

She concluded: "The findings from this study show the importance of implementing structured follow-up care for patients with severe COVID-19 infection. Importantly, CT unveiled lung damage in this patient group that was not identified by lung function tests. Knowing how patients have been affected long-term by the coronavirus might enable symptoms and lung damage to be treated much earlier and might have a significant impact on further medical recommendations and advice."

In a second poster presentation to the Congress [3], Ms Yara Al Chikhanie, a PhD student at the Dieulefit Santé clinic for pulmonary rehabilitation and the Hp2 Lab at the Grenoble Alps University, France, said that the sooner COVID-19 patients started a pulmonary rehabilitation programme after coming off ventilators, the better and faster their recovery.

Patients with severe COVID-19 can spend weeks in intensive care on ventilators. The lack of physical movement, on top of the severe infection and inflammation, leads to severe muscle loss. The muscles for breathing are also affected, which weakens the breathing capacity. Pulmonary rehabilitation, which involves physical exercises and advice on managing symptoms, including shortness of breath and post-traumatic stress disorder, is crucial for helping patients to recover fully.

Ms Al Chikhanie used a walking test to evaluate the weekly progress of 19 patients [4] who had spent an average of three weeks in intensive care and two weeks in a pulmonary ward before being transferred to the Dieulefit Santé clinic for pulmonary rehabilitation. Most were still unable to walk when they arrived, and they spent an average of three weeks in rehabilitation. The walking test measured how far the patients could walk in six minutes. At the beginning, they were able to walk an average of 16% of the distance that, in theory, they should be able to walk normally if healthy. After three weeks of pulmonary rehabilitation, this increased to an average of 43%, which was a significant gain but still a serious impairment.

Ms Al Chikhanie said: "The most important finding was that patients who were admitted to pulmonary rehabilitation shortly after leaving intensive care, progressed faster than those who spent a longer period in the pulmonary ward where they remained inactive. The sooner rehabilitation started and the longer it lasted, the faster and better was the improvement in patients' walking and breathing capacities and muscle gain. Patients who started rehabilitation in the week after coming off their ventilators progressed faster than those who were admitted after two weeks. But how soon they can start rehabilitation depends on the patients being judged medically stable by their doctors. Despite the significant improvement, the average period of three weeks in rehabilitation wasn't enough for them to recover completely.

"These findings suggest that doctors should start rehabilitation as soon as possible, that patients should try to spend as little time as possible being inactive and that they should enrol with motivation in the pulmonary rehabilitation programme. If their doctors judge it to be safe, patients should start physical therapy exercises while still in the hospital's pulmonary ward."

Thierry Troosters, who was not involved in the study, is President of the European Respiratory Society and Professor in Rehabilitation Sciences at KU Leuven, Belgium. He said: "Anecdotal evidence has been emerging since the start of the COVID-19 pandemic that many patients suffer debilitating long-term after-effects from the coronavirus. Dr Sahanic's presentation is important because it is one of the first, comprehensive prospective follow-ups of these patients and shows the serious, long-term impact of COVID-19 on the lungs and heart. It is sobering to hear that more than half of the patients in this study showed damage to their lungs and hearts 12 weeks after hospital discharge, and that nearly 40% were still suffering from symptoms such as breathlessness. The good news, however, is that patients do improve and this surely will help the rehabilitation process, as discussed in the second presentation.

"Ms Al Chikhanie's research complements this information and shows how essential it is for patients to start pulmonary rehabilitation as soon as they are physically able to do so. This is why rehabilitation can also be started in the ward, if programmes are adapted to the capabilities of the patient. This is perfectly in line with a recent statement of our Society where we also advocate for tailored rehabilitation. It is clear from both these studies that rehabilitation, including physical and psychologic components, should be available for patients as soon as possible and it should continue for weeks if not months after they have been discharged from hospital in order to give patients the best chances of a good recovery. Governments, national health services and employers should be made aware of these findings and plan accordingly." [5]

A research group led by Prof. XUE Tian from the University of Science and Technology of China (USTC) of the Chinese Academy of Sciences (CAS), collaborating with Prof. WU Qian form Beijing Normal University and Prof. WANG Xiaoqun from Institute of Biophysics of CAS, provided a comprehensive transcriptomic atlas based on 119520 single cells of retina of human and macaque at different ages.

This work, which provides valuable basic for the molecular regulation of aging progression and related diseases, was published in National Science Review on August 25th 2020.
Vision is the most important perception for humans and animals. The human retina is a specialized light-sensitive tissue of neurons, glia, and nourishing blood vessels. Different cell in the retina convert the incoming light into electrochemical signals and then relay to the brain for visual formation. However, as people age, the function of the retina deteriorates and the risk of various aging related diseases increases. Thus, it is necessary to understand the aging process and underlying complexities of the retina to help rescuing age-related retinal diseases.

Researchers collected 119520 cell transcriptomes of human and macaque retina from young to old. Firstly, by comparing the human and macaque retinal cell composition and regional molecular differences, researchers found that though rods of humans and macaques can be both divided into two subtypes by MYO9A expression, the proportion of MYO9A- cells varied between the two species.

Later, researchers then compared the macular area with the peripheral area of the retina. The results showed that there were significant differences in gene expression in macular area and peripheral area between Muller Glia (MG) and Cone.

Researchers used the aging database to fit the macular and peripheral regions of the retina and calculate the aging curves of the two regions. The results showed that the degree of senescence in macular area was higher than that in peripheral area, which was consistent with the high expression of MGs in peripheral area.

In addition, studies have found that rods are significantly damaged in the aging process, especially MYO9A- rod cells are more likely to reduce in the aging process.

Finally, they generated a dataset showing the cell-type and region-specific gene expression associated with 55 types of human retinal disease.

This study is the first international report on the single-cell transcriptome atlas of retinal in human and non-human primates, which not only systematically analyzes the molecular characteristics of various cell types in the human retina during the aging process, but also reveals the regional and cell subtype specific evolution of retinal aging.

As the flu season approaches, a strained public health system may have a surprising ally -- the common cold virus.

Rhinovirus, the most frequent cause of common colds, can prevent the flu virus from infecting airways by jumpstarting the body's antiviral defenses, Yale researchers report Sept. 4 in the journal The Lancet Microbe.

The findings help answer a mystery surrounding the 2009 H1N1 swine flu pandemic: An expected surge in swine flu cases never materialized in Europe during the fall, a period when the common cold becomes widespread.

A Yale team led by Dr. Ellen Foxman studied three years of clinical data from more than 13,000 patients seen at Yale New Haven Hospital with symptoms of respiratory infection. The researchers found that even during months when both viruses were active, if the common cold virus was present, the flu virus was not.

"When we looked at the data, it became clear that very few people had both viruses at the same time," said Foxman, assistant professor of laboratory medicine and immunobiology and senior author of the study.

Foxman stressed that scientists do not know whether the annual seasonal spread of the common cold virus will have a similar impact on infection rates of those exposed to the coronavirus that causes COVID-19.

"It is impossible to predict how two viruses will interact without doing the research," she said.

To test how the rhinovirus and the influenza virus interact, Foxman's lab created human airway tissue from stem cells that give rise to epithelial cells, which line the airways of the lung and are a chief target of respiratory viruses. They found that after the tissue had been exposed to rhinovirus, the influenza virus was unable to infect the tissue.

"The antiviral defenses were already turned on before the flu virus arrived," she said.

The presence of rhinovirus triggered production of the antiviral agent interferon, which is part of the early immune system response to invasion of pathogens, Foxman said.

"The effect lasted for at least five days," she said.

Foxman said her lab has begun to study whether introduction of the cold virus before infection by the COVID-19 virus offers a similar type of protection.

What The Article Says: A hospitalist charts his emotional journey in this narrative essay from when once brightly colored signs declared hospital workers as heroes to now when the signs have faded and the steady and intense work of helping patients with COVID-19 has seemingly become mundane.

Authors: Bernard E. Trappey, M.D., of the University of Minnesota in Minneapolis, is the author.

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

(doi:10.1001/jama.2020.17249)

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

A trial of a simple yet effective surgery has led Australian experts to promote it as an option to specialists around the world for managing difficult obstructive sleep apnoea (OSA) cases.

After rigorous evaluation of the surgery, excellent outcomes were shown in sleep apnea patients who had been unable to use continuous positive pressure airway (CPAP) treatment, with patients achieved relief from snoring and disrupted sleep and experienced improved general health. according to a new report in the Journal of the American Medical Association (JAMA).

Almost 1 billion people are estimated to have OSA globally, with the main treatment CPAP tolerated by only half of those who try it. Almost 30% of people with OSA wake up very easily with light sleep and other problems caused by minor airway narrowing.

The multi-level surgical technique combining a new version of palate surgery with a low risk tongue procedure to create an improved airway resulted in a substantial reduction in the number of night-time apnoea events and improvements in daytime sleepiness and quality of life. After removing any tonsils, the palate is repositioned and the tongue treated to open up the airway and reduce obstruction.

Flinders University's Emeritus Professor Doug McEvoy says the surgery offers promise to millions of people around the world who suffer from obstructive sleep apnoea but cannot adapt to using a CPAP mask or similar device each night.

"This trial is the result of extensive prior research into the surgical treatment of sleep apnoea and gives new hope to people who, without treatment, would each day continue to feel sleepy and depressed and may have their lives cut short by the detrimental effects of long-term interrupted sleep," says Professor McEvoy.
Lead author University of Wollongong Professor Stuart MacKay, who will give further details of the surgical clinical trial at the global online European Respiratory Society congress on 7 September and in a JAMA podcast, says about half of

patients prescribed CPAP treatment are not using it consistently long term.

"It's very exciting to see so many patients getting a better night's sleep with reduced snoring and less health risk after this surgery, " says Professor MacKay.

The paper, 'Effect of Multilevel Upper Airway Surgery vs Medical Management on the Apnea-Hypopnea Index and Patient-Reported Daytime Sleepiness Among Patients with Moderate or Severe Obstructive Sleep Apnea: The SAMS Randomized Clinical Trial' (2020) is due to be published by JAMA on September 4.

Unequal compensation reduces people's motivation to work, even among those who stand to benefit from unfair advantages, finds a new UCL-led study.

The researchers found that large disparities in rewards offered for the same task reduce people's happiness, which in turn reduce their willingness to work, in the study published in PLOS One.

Lead author, Dr Filip Gesiarz (UCL Psychology & Language Sciences) said: "Here we have shown the psychological impacts of inequality of opportunity, and how it can hurt the productivity and well-being of everyone involved.

"Our findings may shed light on how psychological mechanisms, apart from structural barriers, can contribute to higher unemployment and lower university application rates of people from disadvantaged backgrounds. It's more difficult to motivate yourself to work hard if you know that other people will be more generously rewarded for the same effort."

For the study, 810 participants were asked to complete a simple task in exchange for some money. In different scenarios across three experiments, participants were told that other people were being paid more or less than they were for the same task, to varying degrees of inequality. They were given the option of refusing to work on a given task, and in some of the trials, they were also asked how they were feeling.

The researchers found that when people were told there were wide disparities in pay between them and their peers, they were less willing to work, including participants who were told that other people were being paid much less than they were.

The findings show how people are less motivated to work if they are being paid less than others, but also if they perceive the whole system to be unjust.

Dr Gesiarz said: "People who are economically disadvantaged might face a two-fold reduction in motivation and well-being - first due to their lower relative position, and second due to their reaction to the unfair distribution of opportunities."

The findings showed that a large disparity in rewards brought about greater unhappiness, which was in turn associated with lower willingness to work. People were more likely to refuse to work in an unfair scenario, even if they would benefit, and despite their refusal being a private decision that had no impact on other people's rewards.

The researchers speculate that the negative feelings caused by arbitrary disparities may in part explain why disadvantaged people are more likely to experience anxiety and depression.

Co-author Dr Jan-Emmanuel De Neve (University of Oxford) said: "This study documents yet another example of a 'poverty trap': a situation in which being put at a disadvantage by random circumstances decreases a person's motivation to work, further worsening their situation."

Senior author Professor Tali Sharot (UCL Psychology & Language Sciences) said: "Whether inequality will negatively affect those at the top in 'the real world', outside the lab, remains to be studied. One thing to consider is that in our experiment, people were made aware that their position was randomly assigned. In the 'real world' people many times assume that their good fortune is justified by their talent and effort and therefore inequality might not have a negative influence on the motivation and well-being of privileged individuals in those situations. This is an important question that we hope to answer in the future."

Although immune responses are generated by a complex, hierarchical arrangement of immune system organs, tissues, and components, the unit of the cell has a particularly large effect on disease progression and host survival. These cell-level defense mechanisms, known as cell-autonomous immunity, are among the most important determinants of human survival, and are millions to billions of years old, inherited from our prokaryotic and single-celled ancestors.

The authors of a new paper published in the September 2020 issue of The Quarterly Review of Biology argue that understanding how cell-autonomous immunity has evolved in primates is crucial to understanding the human evolution, not only because infectious agents thought to have affected human genomic evolution are excellent manipulators of cell-autonomous immunity, but because these defenses are found in every cell in every body system.

In "Cell-Autonomous Immunity and the Pathogen-Mediated Evolution of Humans: Or How Our Prokaryotic and Single-Celled Origins Affect the Human Evolutionary Story," Jessica F. Brinkworth and Alexander S. Alvarado discuss how the ubiquity of cell-autonomous immunity highlights a biological reality not commonly addressed in human evolutionary studies - pathogens can mediate the evolution of all body cells, and therefore, all human body systems.

The article examines these ancient tactics in light of evolutionarily important human pathogens and illustrates inter-primate differences in their function. The authors posit that, often considered an independent physiological system in human evolutionary biology, the immune system is ubiquitous, integrated into every other aspect of human physiology. "We argue, therefore, that immunity and pathogen-mediated natural selection is a consideration in the examination of the evolution and function of any human physiological system or trait."

The authors show how human pathogens considered important in the evolution of the human genome manipulate cell-autonomous immunity and have shaped primate evolution, including phagosomes like Yersinia pestis (the causative bacteria of plague) and antimicrobial peptides like Toxoplasma gondii, the 1-2 million-year-old obligate intracellular feline-borne parasite.

"The ancient nature of these defenses is an important consideration in human evolutionary studies because their antiquity is both why cell-autonomous immunity exists in every cell, and the pathogens commonly considered the most pernicious and to have exerted the most stringent selective pressure on the human lineage tend to be organisms that bear microbiological innovations that manipulate these tactics," the authors write.

The paper also illustrates that these defenses are diverging in primate immune cells, and present evidence that they are also changing in "nonimmune" tissues. "For decades, it has been understood that microorganisms and cell-autonomous immune responses to them alter human behavior and vice versa. Incorporation of the same biological relationships between pathogens, cell-autonomous defenses, and body system X extended to other physiological systems or traits at the center of the classic questions of human evolutionary biology (e.g., why does skin color vary in humans, why do primate placentae vary in shape and size, how did human bipedal locomotion evolve, how does primate bone and dental microstructure vary) can enrich and improve our understanding of why such features evolved."

For this kind of information to contribute to a better understanding of the gross features of human evolution, however, the authors say researchers in this area must increase integration of molecular and morphological methods or findings in human evolutionary studies. "Any examination of human evolutionary biology, regardless of physiological system and when possible, should consider autonomous immunity of the cells in that system and how microorganisms have shaped them."

A team of scientists, led by researchers at University of California San Diego School of Medicine, report that a class of drugs used for a broad array of conditions, from allergies and colds to hypertension and urinary incontinence, may be associated with an increased risk of cognitive decline, particularly in older adults at greater risk for Alzheimer's disease (AD).

The findings were published in the September 2, 2020 online issue of Neurology, the medical journal of the American Academy of Neurology.

Anticholinergic drugs are widely used for dozens of conditions, minor and major. Some of these medications require a prescription, while others can be purchased over the counter. They work by blocking acetylcholine -- a type of neurotransmitter or chemical messenger known to be critical for memory function -- from binding to receptors on certain nerve cells. The effect is to inhibit parasympathetic nerve impulses, which are involved in a variety of involuntary muscle movements, such as those in the gastrointestinal tract and lungs, and bodily functions like salivation, digestion and urination.

Researchers reported that cognitively normal study participants who were taking at least one anticholinergic drug at baseline were 47 percent more likely to develop mild cognitive impairment (MCI), often a precursor to dementia such as AD, while being tracked over a period of up to a decade compared to participants who did not take such drugs.

"This study, led by Alexandra Weigand, suggests that reducing anticholinergic drug use before cognitive problems appear may be important for preventing future negative effects on memory and thinking skills, especially for people at greater risk for Alzheimer's disease," said senior author Lisa Delano-Wood, PhD, associate professor in the Department of Psychiatry at UC San Diego School of Medicine. Weigand is a graduate student in the San Diego State University/University of California San Diego Joint Doctoral Program in Clinical Psychology.

Six hundred and eighty-eight adults were involved in the study, evenly divided by sex with an average age of 74. None of the participants displayed cognitive or memory problems at the beginning of the study. Each reported whether they were taking anticholinergic drugs. One-third were taking such medications, with an average of 4.7 anticholinergic drugs per person. Participants were given annual comprehensive cognitive tests for up to 10 years.

The scientists also looked at whether participants had biomarkers for AD in their cerebrospinal fluid, such as certain types of proteins, or a well-known genetic risk factor for AD. They found that participants with AD biomarkers who were taking anticholinergic drugs were four times more likely to develop MCI than persons lacking biomarkers and not taking the drugs.

Similarly, persons at genetic risk for AD who took anticholinergic drugs were approximately 2.5 times more likely to develop MCI than those without genetic risk factors and who were not taking the drugs.

"We believe this interaction between anticholinergic drugs and Alzheimer's risk biomarkers acts in a 'double hit' manner," said Weigand, the study's first author. "In the first hit, Alzheimer's biomarkers indicate that pathology has started to accumulate in and degenerate a small region called the basal forebrain that produces the chemical acetylcholine, which promotes thinking and memory. In the second hit, anticholinergic drugs further deplete the brain's store of acetylcholine. This combined effect most significantly impacts a person's thinking and memory."

Study authors noted that, although older persons metabolize anticholinergic drugs differently than younger people, anticholinergic medications were being taken at levels much higher than the lowest effective dose recommended for older adults, with 57 percent taken at twice the recommended dosage and 18 percent at least four times the recommended dosage.

"This points to a potential area for improvement since reducing anticholinergic drug dosages may possibly delay cognitive decline," said Weigand. "It's important for older adults who take anticholinergic medications to regularly consult with their doctors and discuss medication use and dosages."

Delano-Wood noted that more work is needed to examine brain and cognitive effects of anticholinergic medications and whether these medications accelerate age-related cognitive changes or directly lead to neurodegenerative disorders, such as AD. "Clinical 'deprescribing' studies are currently underway at certain research sites across the nation in an effort to investigate whether reducing or stopping use of these drugs does, in fact, lead to reductions in progressive cognitive impairment," Delano-Wood said.

The hemoglobin in the red blood cells ensures that our body cells receive sufficient oxygen. When the blood pigment is broken down, "heme" is produced, which in turn can influence the protein cocktail in the blood. Researchers at the University of Bonn have now discovered in complex detective work that the "activated protein C" (APC) can be commandeered by heme. At the same time, APC can also reduce the toxic effect of heme. Perspectively, the findings may provide the basis for better diagnostic and therapeutic approaches to blood diseases. The study has been published online in advance in the journal "Antioxidants & Redox Signaling". The print version will be published soon.

"Blood is a juice of very special kind," is what Johann Wolfgang von Goethe had his Mephistopheles say. The hemoglobin gives blood its red color and ensures that the erythrocytes (red blood cells) can bind oxygen for breathing. This is managed by the hemoglobin-bound molecule "heme", which is a complex composing of a central iron ion and a porphyrin molecule. "The breakdown of erythrocytes results in a pool of so-called labile, regulatory heme," explains Prof. Dr. Diana Imhof from the Pharmaceutical Institute of the University of Bonn. As it can exert toxic effects in high concentrations, the body tries to keep the amount of heme in check.

It has been known for quite some time that this "labile, regulatory heme" affects the function of biomolecules. The team around Diana Imhof has now discovered in meticulous detective work which of the many proteins in the blood is particularly under the control of heme. "Over the last few years, our research group has established a large database of model peptides," reports Imhof. The peptides are individual protein "snippets" from which the sometimes huge and complex structures are built. Instead of studying the giant molecules, the proteins, in their entirety, the researchers first took a shortcut with the snippets.

Researchers searched like profilers for "suspects"

The pharmacists at the University of Bonn proceeded in a similar way to profilers in thrillers, who draw conclusions about the perpetrator's behavior from crime scene traces, circumstantial evidence and the type of crime. The researchers used an algorithm to systematically search the database for protein fragments that might potentially interact with heme. Using these data, they were able to conclude that the "activated protein C" (APC) is a particular candidate for heme binding. This enzyme is known for its anticoagulant and clot-dissolving effect, but can also take over cell-protective and anti-inflammatory tasks.

"So far, the impact of heme on the function of APC has been unknown," says Imhof's colleague and lead author of the study, Marie-Thérèse Hopp. The researchers investigated the association with pure compounds in the test tube and by using blood plasma samples provided by the Institute of Experimental Hematology and Transfusion Medicine at the University Hospital Bonn. There, Prof. Dr. Bernd Pötzsch and Dr. Nasim Shahidi Hamedani also supported the pharmacists with know-how, APC samples, test systems and access to specific devices. "We demonstrated that the enzymatic and anticoagulant activity of APC is reduced in the presence of heme," reports Hopp. For example, if there is too little APC or its activity is restricted, the risk of a clot forming in the bloodstream increases, thereby causing thrombosis, heart attack or stroke. Indeed, diseases with an increased incidence of labile heme (hemolytic diseases), such as sickle cell disease, are often associated with thrombotic complications.

Greater scope than previously assumed

"For this reason, the influence of heme on the enzyme APC is more significant than has probably been suspected so far," says Imhof. Furthermore, the team discovered that APC might protect the cells of the inner blood vessel wall like a bodyguard against the cytotoxic effect of heme. The researchers cultivated human endothelial cells and exposed them to heme. If APC was present at the same time, the toxic effect of heme on the cells was suppressed.

"We are convinced that this interaction between APC and heme is significant, because many other blood proteins we were looking for did not bind heme," says Imhof. It might be worthwhile to further investigate the impact of labile, regulatory heme on APC in order to also gain new diagnostic and therapeutically relevant insights regarding blood coagulation disorders that occur in hemolytic diseases. Imhof: "The terrain should be explored much more thoroughly than has been the case to date."

The future economy based on renewable and sustainable energy sources might utilize battery-powered cars, large-scale solar and wind farms, and energy reserves stored in batteries and chemical fuels. Although there are examples of sustainable energy sources in use already, scientific and engineering breakthroughs will determine the timeline for widespread adoption.

One proposed paradigm for shifting away from fossil fuels is the hydrogen economy, in which hydrogen gas powers society’s electrical needs. To mass produce hydrogen gas, some scientists are studying the process of splitting water — two hydrogen atoms and one oxygen atom — which would result in hydrogen fuel and breathable oxygen gas.

Feng Lin, an assistant professor of chemistry in the Virginia Tech College of Science, is focusing on energy storage and conversion research. This work is part of a new study published in the journal Nature Catalysis that solves a key, fundamental barrier in the electrochemical water splitting process where the Lin Lab demonstrates a new technique to reassemble, revivify, and reuse a catalyst that allows for energy-efficient water splitting. Chunguang Kuai, a former graduate student of Lin’s, is first author of the study with Lin and co-authors chemistry graduate students Zhengrui Xu, Anyang Hu, and Zhijie Yang.

The core idea of this study goes back to a subject in general chemistry classes: catalysts. These substances increase the rate of a reaction without being consumed in the chemical process. One way a catalyst increases the reaction rate is by decreasing the amount of energy needed for the reaction to commence.

Water may seem basic as a molecule made up of just three atoms, but the process of splitting it is quite difficult. But Lin’s lab has done so. Even moving one electron from a stable atom can be energy-intensive, but this reaction requires the transfer of four to oxidize oxygen to produce oxygen gas.

“In an electrochemical cell, the four-electron transfer process will make the reaction quite sluggish, and we need to have a higher electrochemical level to make it happen,” Lin said. “With a higher energy needed to split water, the long-term efficiency and catalyst stability become key challenges.”

In order to meet that high energy requirement, the Lin Lab introduces a common catalyst called mixed nickel iron hydroxide (MNF) to lower the threshold. Water splitting reactions with MNF work well, but due to the high reactivity of MNF, it has a short lifespan and the catalytic performance decreases quickly.

Lin and his team discovered a new technique that would allow for periodic reassembling to MNF’s original state, thus allowing the process of splitting water to continue. (The team used fresh water in their experiments, but Lin suggests salt water – the most abundant form of water on Earth – could work as well.)

MNF has a long history with energy studies. When Thomas Edison tinkered with batteries more than a century ago, he also used the same nickel and iron elements in nickel hydroxide-based batteries. Edison observed the formation of oxygen gas in his nickel hydroxide experiments, which is bad for a battery, but in the case of splitting water, production of oxygen gas is the goal.

“Scientists have realized for a long time that the addition of iron into the nickel hydroxide lattice is the key for the reactivity enhancement of water splitting.” Kuai said. “But under the catalytic conditions, the structure of the pre-designed MNF is highly dynamic due to the highly corrosive environment of the electrolytic solution.”

During Lin’s experiments, MNF degrades from a solid form into metal ions in the electrolytic solution — a key limitation to this process. But Lin’s team observed that when the electrochemical cell flips from the high, electrocatalytic potential to a low, reducing potential, just for a period of two minutes, the dissolved metal ions reassemble into the ideal MNF catalyst. This occurs due to a reversal of the pH gradient within the interface between the catalyst and the electrolytic solution.

“During the low potential for two minutes, we demonstrated we not only get nickel and iron ions deposited back into the electrode, but mixing them very well together and creating highly active catalytic sites,” Lin said. “This is truly exciting, because we rebuild the catalytic materials at the atomic length scale within a few nano-meter electrochemical interface.”

Another reason that the reformation works so well is that the Lin Lab synthesized novel MNF as thin sheets that are easier to reassemble than a bulk material.

Validating findings through X-rays

To corroborate these findings, Lin’s team conducted synchrotron X-ray measurements at the Advanced Photon Source of Argonne National Laboratory and at Stanford Synchrotron Radiation Lightsource of SLAC National Accelerator Laboratory. These measurements use the same basic premise as the common hospital X-ray but on a much larger scale.

“We wanted to observe what had happened during this entire process,” Kuai said. “We can use X-ray imaging to literally see the dissolution and redeposition of these metal irons to provide a fundamental picture of the chemical reactions.”

Synchrotron facilities require a massive loop, similar to the size of the Drillfield at Virginia Tech, that can perform X-ray spectroscopy and imaging at high speeds. This provides Lin high levels of data under the catalytic operating conditions. The study also provides insights into a range of other important electrochemical energy sciences, such as nitrogen reduction, carbon dioxide reduction, and zinc-air batteries.

“Beyond imaging, numerous X-ray spectroscopic measurements have allowed us to study how individual metal ions come together and form clusters with different chemical compositions,” Lin said. “This has really opened the door for probing electrochemical reactions in real chemical reaction environments.”

The work was supported by the Department of Chemistry startup funds and the Institute for Critical Technology and Applied Science.

Journal

Nature Catalysis

DOI

10.1038/s41929-020-0496-z

CAMBRIDGE, MA - September 2, 2020—Rapid Reviews: COVID-19 (RR:C19), is an open-access overlay journal published by the MIT Press that accelerates peer review of COVID-19-related research preprints to advance new and important findings and prevent the dissemination of false or misleading scientific news.

For the month of August, the preprints selected for review covered a wide range of subjects with peer reviewers finding recommendations for new prognostic scores to guide clinical decision making and hospital admissions and a study of estrogen levels and COVID-19 symptoms in women particularly noteworthy and useful.

Peer reviewers also flag as potentially misleading new research on whether beta-coronavirus MHV, a pathogen of mice, uses deacidification of lysosomes to exit cells while avoiding degradation. They caution decision-makers to not act on this research.

New August peer reviews from RR:C19, in order of the evidence scale rating (strong, reliable, potentially informative, not informative, or misleading) as provided by each of the two reviewers:

The utility of established prognostic scores in COVID-19 hospital admissions: a multicentre prospective evaluation of CURB-65, NEWS2, and qSOFA by Freddy Frost, et al. Preprint | Reviews

Evidence Scale Rating: Strong/Strong

Summary: This robust analysis is novel and of high interest for the medical community. This study informs how new prognostic scores should be created to more accurately guide clinical decision-making in patients with COVID-19. Reviewers: Michael Meisner and Kapil Gururangan

Progenitor identification and SARS-CoV-2 infection in long-term human distal lung organoid cultures by Ameen A. Salahudeen, et al. Preprint | ReviewsEvidence Scale Rating: Reliable/Strong

Summary: This study offers a chemically-defined human lung organoid culture system and employs this model to identify club cells as a novel target in SARS-CoV-2 infection. The findings reported are reliable for informing future COVID-19 research. Reviewers: Jaymin Kathiriya and Jeffrey A. Whitsett

Estrogen and COVID-19 symptoms: associations in women from the COVID Symptom Study by Ricardo Costeira, et al. Preprint | Reviews

Evidence Scale Rating: Reliable/Reliable

Summary: This is a reliable study that shows the protective role of estrogens against COVID-19 severe complications among 1.6 million UK women. Novel findings show potential increased risk amongst postmenopausal women and a potentially protective role of COCP in premenopausal women. Reviewers: Giovanni Grandi and Azure Grant

Anti-SARS-CoV-2 IgG from severely ill COVID-19 patients promotes macrophage hyper-inflammatory responses. Preprint | ReviewEvidence Scale Rating: Reliable/Reliable

Summary: This study introduces a novel therapeutic approach to treating COVID-19. Study motivates further investigation of whether selectively inhibiting FcR receptor-driven inflammation could result in more targeted and effective COVID-19 interventions. Reviewers: Sarah Stanley, Scott Biering, and Saumendra N. Sarkar

Intestinal receptor of SARS-CoV-2 in inflamed IBD tissue is downregulated by HNF4A in ileum and upregulated by interferon regulating factors in colon by Bram Verstockt, et al. Preprint | Review

Evidence Scale Rating: Reliable/Potentially Informative

Summary: Study claims increased susceptibility of IBD patients to SARS-CoV-2 infection. Study lacks sufficient evidence to support the authors’ claims concerning the importance of IBD medication in COVID-19 risk management. Claims are not actionable except to prompt further research. Reviewers: Girija Goyal, Cicely Fadel, Donald Ingber, and Magdalena Kasendra

Medical Costs of Keeping the US Economy Open During COVID-19 by Jiangzhuo Chen, et al. Preprint | Reviews

Evidence Scale Rating: Reliable/Potentially Informative

Summary: A major benefit of this analysis is that it presents a credible,flexible model for estimating the costs of COVID-19, although models will require updating with valid evidence. Sufficient compliance with lockdown guidelines could substantially reduce the medical costs of COVID-19. Reviewers: Christine Eibner, Raffaele Vardavas, and Mehdi Shiva

The infection fatality rate of COVID-19 inferred from seroprevalence data by John Ioannidis. Preprint | Reviews

Evidence Scale Rating: Potentially informative/Potentially informative

Summary: This study finds substantial heterogeneity in the infection fatality rate (IFR)across different locations. Data are useful and add to the emerging picture on IFR, however, substantial conclusions cannot be drawn. Reviewers: Timothy Hallett, Kenji Mizumoto, and Gerardo Chowell

Predicted success of prophylactic antiviral therapy to block or delay SARS-CoV-2 infection depends on the drug’s mechanism of action by Peter Czuppon, et al. Preprint | Review

Evidence Scale Rating: Reliable/Not informative

Summary: Authors claim that stochastic modeling can be used to predict the efficacy of repurposed drugs to prevent or treat SARS-CoV-2 infections. Readers and decision makers should assess results with some caution. Reviewers: Anna Bershteyn and Praveen P Nekkar Rao

Clinical validation of innovative, low cost, kit-free, RNA processing protocol for RT-PCR based COVID-19 testing by Nikhil Shri Sahajpal, et al. Preprint | Reviews

Evidence Scale Rating: Potentially informative/Not Informative

Summary: While informative, there are many flaws in the protocol testing if SARS-CoV2 RNA can be amplified from nasopharyngeal swab samples. The protocol does not appear to support claims that authors have made that this approach will decrease assay time, reduce cost, and instrumentation. Reviewers: Aditi Bhargava Bhargava and Mohamed Sharafeldin

β-Coronaviruses use lysosomal organelles for cellular egress by S Ghost, et al. Preprint | Reviews

Evidence Scale Rating: Misleading/Potentially informative

Summary: This study claims β-coronaviruses utilize a lysosome-mediated egress mechanism. In its current form, this pre-print includes numerous unsubstantiated, misleading, or poorly supported claims and is unreliable for informing future COVID-19 research. Reviewers: David Avram Sanders and Cristina Risco Ortiz

Researchers from Florida State University are shedding light on nutrient levels in the Gulf of Mexico with new findings published this month in the Journal of Geophysical Research - Oceans.

The Gulf of Mexico receives considerable levels of nutrients from the rivers that empty into it, especially the Mississippi River, which causes the Gulf's northern shelf waters to become overly enriched and more susceptible to algae growth. But scientists have remained unsure whether a significant portion of those nutrients ever leave the Gulf to potentially impact the chemistry of the North Atlantic Ocean.

"The Gulf of Mexico is an economically important body of water, as the surrounding areas rely on it for tourism, fisheries and oil production, and it also has significant ecological diversity," said Samantha Howe, a graduate student in the College of Arts and Sciences' Department of Earth, Ocean and Atmospheric Science, who led the research. "It is important to track the nutrient input from the Mississippi and Atchafalaya River System to the Gulf as those nutrients contribute to harmful algal blooms on the Northern Gulf Shelf."

Researchers found no evidence that nitrate from the Mississippi-Atchafalaya River System is mixing across the Northern Gulf shelf into the open waters of the Gulf of Mexico. The findings are consistent with recent modeling work by fellow scientists that indicates 90 percent of Mississippi River nutrients are retained in the near-shore ecosystem, which implies that nutrients from the Mississippi River do not leave the Gulf.

"In order to assess and manage ecological challenges in the Gulf, it is critical to understand whether the nutrients are processed and retained nearshore or whether they are transported to the North Atlantic," Howe said. "This finding is valuable to know, as these ecosystems must harbor the nutrient burden."

To conduct the study, the team collected and analyzed water samples taken during four different research cruises to the Gulf and the Florida Straits from 2011 to 2018.

The research is the first ever to provide isotopic composition measurements of nitrate in the Gulf of Mexico, as well as a new isotopic profile from the Florida Straits. These new water column profiles were then compared with prior measurements from the North and South Atlantic and with the magnitude of nitrogen inputs to the Gulf.

Howe, who earned her bachelor's degree in environmental science from FSU in Spring 2019, is now pursuing her master's in aquatic environmental science. She began the nutrient research as part of her honors undergraduate thesis while working in the research lab of study co-author, Associate Professor of Oceanography Angela Knapp.

"Samantha's thesis looked for distinct geochemical signatures of nitrate from the Mississippi River and whether this nitrate made it off the Northern Gulf of Mexico shelf into the deep waters of the Gulf that mix with the Loop Current and leave via the Florida Straits to enter the North Atlantic," Knapp said.

Howe's collaborators on the study include co-authors Knapp and Carlos Miranda, a 2017 graduate of the FSU Department of Chemistry and Biochemistry and the FSU Department of Biological Science, and colleagues from the University of Southern Mississippi and the University of New Hampshire.

"This work has important implications for understanding the fate of nutrients from the Mississippi Atchafalaya River System and how to manage human inputs to coastal ecosystems," Knapp said.