Culture

A nasal therapy, built upon on the application of a new engineered IgM antibody therapy for COVID-19, was more effective than commonly used IgG antibodies at neutralizing the COVID-19 virus in animal models, according to research recently published by The University of Texas Health Science Center at Houston (UTHealth), The University of Texas Medical Branch at Galveston (UTMB Health), the University of Houston, and IGM Biosciences, Inc.

The study was published today in Nature.

Researchers engineered IgM antibodies and found that in all cases, these antibodies were significantly more potent than standard IgG antibodies in neutralizing the COVID-19 virus. One of the engineered IgM antibodies, IGM-6268, demonstrated a significantly increased potency against the original SARS-CoV-2 and emerging variants such as the current U.K., South African, and Brazilian variants of concern (VOC) and variants of interest (VOI), as well as the antibody escape mutants for the current Emergency Use Authorization antibodies. Additionally, IGM-6268 was shown to be highly effective for prophylaxis and treatment in mouse models when administered intranasally.

"High viral load in the respiratory tract correlates with severe illness and mortality in patients with COVID-19," said Zhiqiang An, PhD, director of UTHealth Texas Therapeutics Institute, professor and Robert A. Welch Distinguished University Chair in Chemistry at McGovern Medical School at UTHealth, and faculty member at MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences and one of the corresponding authors on the study. "Respiratory mucosal antibodies are key to clearing SARS-CoV-2 infection and reducing viral transmission and IgM antibodies are nature's first line of defense against pathogens such as viruses."

The current government-approved antibodies, which are all IgG antibodies, are administered intravenously at high doses and don't directly target the main sites of viral infection.

"SARS-CoV-2 has evolved mutations that severely compromise the neutralizing activities of multiple IgG monoclonal antibodies, including those under clinical trials and authorized for emergency use. Therefore, developing new antibody therapies that can overcome these challenges is an urgent unmet need, and we are pleased with the data published today," An said.

"Synergizing the strengths of multiple institutions from academia and industry is the key to the rapid translation from ideas to therapeutic candidates. This is another example of such success. The cross-institutional and academic-industry collaborations should be expanded to other disease indications," said Pei-Yong Shi, PhD, professor and co-senior author of the study from the Department of Biochemistry and Molecular Biology at UTMB Health.

This antibody has been licensed to biotech partner IGM Biosciences for drug development.

"The ability to use potently neutralizing IgM antibodies against SARS-CoV-2 with broad coverage of VOCs, VOIs, and viral escape mutants, is a very exciting application of the IGM platform," said Fred Schwarzer, CEO of IGM Biosciences. "We are grateful to our collaborators at UTHealth, UTMB Health, and our scientists at IGM for the exceptional work described in Nature today."

CHAPEL HILL, NC - Airway mucus consists of various proteins such as long mucins MUC5AC and MUC5B, both of which contribute greatly to the proper gel-like consistency of this most essential bodily fluid. UNC School of Medicine researchers led by mucin expert Mehmet Kesimer, PhD, had previously discovered that the total mucin concentrations in the lungs are associated with COPD disease progression and could be used as diagnostic markers of chronic bronchitis, a hallmark condition for patients with COPD. Kesimer and colleagues now report that one of these mucins, MUC5AC, is more closely and reliably associated with the development of COPD than is its brother, MUC5B.

The research, published in The Lancet Respiratory Medicine, shows that MUC5AC is found at elevated levels in smokers who had not yet developed COPD but whose lung function wound up decreasing over the course of the three-year study. Former smokers at-risk for COPD, on the other hand, had normal levels of MUC5AC at the start of the study and maintained proper lung function over three years. MUC5AC hyperconcentration in the lungs may be a key factor in predicting the risks and rates of progression to more severe disease, according to the study.

Recent nationwide efforts have focused on early- or pre-COPD to predict the risks of progression to COPD amongst smokers.

"Currently, we cannot forecast which individuals in the at-risk smokers group will progress to COPD because we don't have an objective biological marker to underpin the disease-causing pathways. Our research shows that MUC5AC could be a predictor of who will develop COPD from the large group of aging "at-risk" smokers," said Kesimer, senior author of the study, professor in the UNC Department of Pathology and Laboratory Medicine, and member of the UNC Marsico Lung Institute. "We think MUC5AC could be a new biomarker for COPD prognosis and it could be a biomarker for testing the effectiveness of therapeutic strategies."

MUC5AC could also become a target for pharmaceutical developers whose goal it is to halt COPD disease progression and help patients live more normal, active lives.

Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disease that causes obstructed airflow from the lungs and affects about 16 million people in the United States. Symptoms include breathing difficulty, coughing, mucus production, and wheezing. It's typically caused by long-term exposure to irritants, such as particulate matter like cigarette smoke. The two main conditions that contribute to COPD are chronic bronchitis, an inflammation of the lining of the bronchial tubes due to chronic mucin/mucus accumulation; and emphysema, when the tiny air sacs at the end of the smallest air passages of the lungs are destroyed.

There are some treatment options for COPD to attempt to slow disease progression and reduce symptoms, but treatments often don't work well, especially during late stages of the condition, and there is no cure.

The Kesimer Lab in the UNC Marsico Lung Institute uses various techniques, including mass spectrometry, to identify and measure the different biological mechanisms involved in lung conditions. For this study, the UNC team of scientists were able to measure the concentrations of MUC5AC and MUC5B in different groups of people, including people who had never smoked cigarettes, who had quit smoking, and who continue to smoke with or without COPD.

Smoking cigarettes has long been known to be a major risk factor for COPD, but Kesimer's work suggests that quiting smoking decreases the odds of developing COPD as we age.

"Our data indicate that increased MUC5AC concentrations in the airways may contribute to the initiation of COPD, as well as disease progression, symptom exacerbation, and how the disease progesses over time, in general,"Kesimer said. "We did not observe the same association with MUC5B."

The best thing an aging person can do to avoid the inevitable decline associated COPD is quit smoking immediately before airway obstruction sets in due to mucin/mucus accumulation. Through Kesimer's work, though, it might be possible to pinpoint which individuals are at the highest immediate risk for developing COPD soon.

Alexandria, Va., USA -- Dental care professionals are thought to be at enhanced risk of occupational exposure to SARS-CoV-2, but robust data to support this is lacking. The study "COVID-19: Seroprevalence and Vaccine Responses in UK Dental Care Professionals," published in the Journal of Dental Research (JDR), provides a longitudinal analysis of antibodies to SARS-CoV-2 spike glycoprotein, including early analysis of the impact of vaccination on the immune response.

In June 2020, I,507 West Midlands dental care professionals were recruited to test for baseline seroprevalence, or the proportion of the population that have circulating antibodies to SARS-CoV-2, indicating prior COVID-19 infection. The cohort was followed longitudinally for six months until January/February 2021 through the second wave of the COVID-19 pandemic in the United Kingdom and vaccination commencement.

Before enhanced personal protective equipment, natural infection with SARS-CoV-2 was significantly higher in dental care professionals. The baseline seroprevalence for dental care professionals was 16.3%, compared to estimates in the regional population of 6-7%. Following the introduction of increased infection control procedures, the rate of new infections in dental care practitioners was similar to the background population.

Seropositivity was retained in over 70% of participants at 3- and 6-month follow-up and conferred a 75% reduced risk of infection. Critically, only 5.3% of individuals infected in the first wave of COVID-19 produced a strong antibody response that provided robust protection from reinfection over 6 months. Even if antibodies waned, previous infection with SARS-CoV-2 led to a faster and stronger immune response following a single dose of the Pfizer-BioNTech 162b vaccine, indicating immunological memory.

"The data show that enhanced personal protective equipment used by dental care professionals is making a significant difference. The data also suggest that natural infection alone is unlikely to generate meaningful, durable herd immunity. This emphasizes the importance of vaccinations for controlling COVID-19" said JDR Editor-in-Chief Nicholas Jakubovics, Newcastle University, England. "This is an important and timely study with broad relevance that extends beyond the dental community."

Japanese researchers have developed and tested a prototype device -- wearable on the fingertips -- that incorporates the concept of 'light touch' to enhance the sense of balance. If widely implemented, the device should significantly reduce incidence of falls amongst seniors.

The findings are published in the journal Scientific Reports on April 1.

As we age, our sense of balance can become impaired. The resulting increase in postural sway in turn increases the risk of falls and consequent injuries. Meanwhile, older people make up a large and increasing proportion of the population in highly developed countries. This makes efforts to reduce the effects of postural sway ever more imperative.

Aids such as canes and walking frames help a great deal, but research suggests their use or misuse in certain circumstances such as on stairs or stepping into or out of vehicles can actually exacerbate the problem with sense of balance and increase the risk of injury.

In order to address the challenge of human balance in the elderly, in recent years a great deal of research has focussed on the phenomenon known as 'light touch.' Even with eyes closed, a subject that lightly touches a curtain or piece of paper draped in front of them with just their fingertips is given enough of a stimulus cue to reduce their swaying. This happens even though a curtain or piece of paper cannot deliver any postural support in the way that a cane or walking frame can.

Researchers with Yokohama National University (YNU) and the Prefectural University of Hiroshima wanted to test a way to create a 'virtual light touch' (VLT) system to achieve the same result--in effect creating a virtual curtain.

The first step was a basic VLT system that incorporated a small device that fits over a fingertip of a subject--much like wearing a thimble--and delivers a vibrotactile 'nudge' when they begin to sway. Assessment of swaying in this first attempt at a VLT was performed by a 3D motion capture system akin to what is used by special effects professionals in the movie industry.

Initial tests on subjects with this proof-of-concept system showed results equivalent to the use of a physical curtain.

"The use of such a large and complex motion capture system is no more practical in daily life than a curtain," said Keisuke Shima, Associate Professor at faculty of engineering of YNU and lead author of the study.

"But the tests on live subjects showed that the concept worked," added YNU researcher Mami Sakata, a co-author of the paper. "The next step was to transform the VLT into a system that could be used in everyday life."

The researchers swapped out the motion capture system for an accelerometer--an electromechanical device that measures acceleration forces--similar to what is found in most smartphones. The vibrotactile nudges were still delivered by the vibrotactile thimble device.

The accelerometer-and-vibrotactile-thimble VLT system was then tested on 150 volunteers ranging in age from their sixties to their nineties and again found that postural sway was reduced as significantly as a physical curtain.

The acceleration-based VLT set-up is immediately practical as a balance aid in everyday life as it involves a simple, lightweight and compact sensor and motor. It should enjoy widespread adoption amongst elderly people.

However, the researchers want to improve their system further by making the device even more lightweight and compact, and to enhance its reduction of postural sway. For this latter enhancement, they will need to explore precisely how the still poorly understood light-touch effect works to support human balance.

A new study looking at the benefits of good farmer seed production suggests women need more support to participate in contract farming - to the same extent as their male counterparts - and have more equality along the whole food value chain.

The CABI-led research - which sought to assess the benefits of good farmer seed production through a case study of the Good Seed Initiative in Tanzania - reveals that while around 70% of the labour to grow African Indigenous Vegetables (AIVs) is provided by women only 10 to 30% are contract farmers who own the fields, make decisions on sales and control revenues.

The paper, led by Dr Monica Kansiime and published in the journal Agriculture and Food Security, argues that the adoption of gender-inclusive approaches in contract farming arrangements is 'paramount' and can have multiple benefits including shared decision-making amongst men and women.

Quality seed is key to increasing crop production, nutrition and wellbeing but smallholder farmers in Tanzania have limited access to affordable quality seeds - over 90% of seed sown is saved by farmers from previous harvests, though its quality is often poor.

The Good Seed Initiative, which ran between 2013 and 2016, sought to enhance access to quality AIV seed through the promotion of farmer seed production using two models - contract farming and Quality Declared Seed (QDS).

The programme reached over a million consumers and growers through radio programmes, seed rallies, nutritional outreaches, cook shows, and agricultural shows and events. A policy brief was also developed and circulated to stakeholders in Tanzania on the production and sales of quality assured AIV seed.

Dr Kansiime's latest study - conducted in Arusha and Dodoma - assessed post-GSI project sustainability factors and explored the prospects of replicating the approach elsewhere and also discovered significant differences in the roles men and women play in the production of the AIVs.

Dr Kansiime said, "While farmer seed production under both models continued to thrive - creating avenues for income diversification and contributing over 50% to household incomes - we found a disparity between the roles men and women play in the production of AIVs.

"QDS seed production is challenged by a lack of access to foundation seed, inspections, and seed testing services - which are key to quality seed production - but another challenge is the apparent 'crowding out' of women in seed production. And it's not just in Tanzania, in Kenya, for example, less than 10% of women participate in contract farming arrangements for fruits and vegetables."

"QDS seed production is challenged by a lack of access to foundation seed, inspections, and seed testing services - which are key to quality seed production - but another challenge is the apparent 'crowding out' of women along the AIV value chain. And it's not just in Tanzania, in Kenya, for example, less than 10% of women participate in contract farming arrangements for fruits and vegetables."

The study revealed that the new farmers entering into seed production were mainly men especially in the north, with the fear that women would be excluded along the AIV value chain as the AIV enterprises become profitable.

Dr Dannie Romney, co-author of the paper, said, "The adoption of gender-inclusive approaches in contract farming arrangements is paramount and can have multiple benefits, including decision-making and benefit of both men and women from such arrangements."

MUSC Hollings Cancer Center researchers are finding solutions to the aging-related changes that reduce anti-cancer immunity. Besim Ogretmen, Ph.D., and colleagues found a novel link between aging, metabolism and anti-cancer T-cell function. Their work, published in Cell Reports, sheds light on an important pathway that cannot be ignored during cancer treatment.

Two broad questions in cancer research are: How can cancer treatments be improved, and what is the link between cancer and aging?

"We know that the protective T-cell response deteriorates with age. Mitochondrial function is now thought to be one of the central regulators of the aging process. Our experiments connected the dots with what was previously shown and highlighted some surprising and important pathways," said Ogretmen, who is the SmartState Endowed Chair in Lipidomics and Drug Discovery.

All cells in the human body, except red blood cells, contain structures called mitochondria. Mitochondria are a cell's central powerhouse -- they produce the chemical energy necessary for survival. Ogretmen's prior studies showed that a particular type of fatty molecule, called ceramide, causes mitochondrial dysfunction in cancer cells. In terms of cancer, mitochondrial dysfunction is thought to be a good thing since it weakens the cancer cells.

However, mitochondrial dysfunction might not be completely beneficial for cancer treatment. "We know that increased ceramide signaling is linked with aging, but it is important that we understand if this is also occurring in immune cells. Immunotherapy is becoming an increasingly important part of cancer treatment, so we must better understand the immune system in older people," he said.

Aging stress produces the bioactive sphingolipid called ceramide. This lipid promotes mitochondrial dysfunction by a biological mechanism called mitophagy, where the broken mitochondria are selectively destroyed to kill cancer cells. However, scientists do not know if T-cells use this same pathway or if their immune functions are changed by ceramide signaling.

The results, which were surprising, showed ceramide signaling weakens anti-tumor T-cells. The data showed that:

Aging decreases T-cell survival and function.

Aging stress induces mitophagy in T-cells.

Blocking certain ceramide molecules improves the anti-tumor function of aging T-cells.

"What this tells us is that ceramides need to be carefully controlled in a cancer setting," said Ogretmen. This is particularly important because there are several FDA-approved drugs, such as FTY720 for multiple sclerosis, that increase ceramide signaling. Systemic increase of ceramide signaling in cancer patients may be harmful because it weakens the anti-cancer function of the patient's immune system, he said.

Using multiple molecular methods, the team observed that T-cells from old mice, which were equivalent to approximately 50- to 60-year-old humans, had more ceramide accumulation in their mitochondria, which led to dysfunction. These cells had lower anti-tumor functions in cell culture and in cancer animal models. This biological pathway was confirmed by blocking ceramide signaling. Inhibiting ceramide metabolism by genetic or pharmacological means prevented mitophagy and restored the anti-cancer function of the aging T-cells, making them perform like younger counterparts.

"Our work was aided by a really strong team of collaborators and funding support from Hollings Cancer Center. The Team Science Award allowed us to generate this data, which has developed into something larger. We just resubmitted an NIH program project grant that focuses on the role of sphingolipids in T-cells and cancer," he said.

The team will continue to piece together the biological pathways and processes to ensure that these findings are applicable to humans. The next step is to understand how aging induces ceramide stress. In general, stress can invoke dormant cancers, and this may be related to ceramide signaling.

"Understanding the mechanism of ceramides and lipid metabolism in T-cells has broad implications in aging and immune cells in general. Our work is important because it allows us to understand autoimmune diseases and infections more fully, not just cancer." There is also a potential link to lifestyle choices and stress, which may accelerate the aging process of T-cells, he said.

DURHAM, N.H.-- Bears are known for being devoted and protective of their baby cubs, but research from the University of New Hampshire shows that they may also play a significant role in shielding gray fox from predators like coyotes, who compete with the fox for food and space. The research is one of the first studies to show how black bears provide a buffer to allow other, smaller carnivores to safely co-exist.

"Even though black bears and coyotes are the two most common carnivores in North America, we're still learning how they affect the ecosystems around them," said Rem Moll, assistant professor of wildlife ecology and lead author of the study. "What's unique about bears is that they hibernate, so they literally disappear for half a year, which we now know can shift animal habits in the ecosystem."

In the study, published in the journal Oecologia, researchers took a closer look at the hierarchy of carnivores to see if a major life trait, like hibernation, had a significant effect. In the western part of Nevada, near Lake Tahoe, the researchers tracked and monitored the top species of carnivores which included black bears, which are the largest and most dominant species, followed by coyotes, bobcats, and finally gray fox, which are the smallest (a bit larger than a cat) and most subordinate species. They found that in summer the gray fox stayed close to areas populated by black bears which appeared to provide a top-down buffering effect helping to protect the gray fox from the coyotes. But in the winter, when bears were hibernating, this pattern reversed and coyotes were three times more likely to move into the now vacant bear territories and the gray fox, no longer secure by the presence of the black bear, moved out. This pattern suggests that the top carnivore - black bears - provided a shield for the gray fox from competition with coyotes. But this "bear shield" was only seasonal, disappearing when the bears hibernated.

"In our field of research, there is something called the "landscape of fear" - the idea that there is a pecking order and that both predators and prey will change their behavior to avoid getting killed," said Moll. "For decades this was overlooked, so there aren't a lot of studies showing the connection between black bears and coyotes - two of the most common carnivores in the U.S. - but this work suggests that fear is important in defining the species roles in the ecosystem."

The researchers say even though this study was done near Lake Tahoe, where black bears were nearly extinct a few decades ago, they believe these instinctual actions could be a very common dynamic in any area where black bears, gray fox and coyotes co-exist.

Neurodegenerative disorders that cause dementia increase the risk of contracting severe COVID-19 and dying from the disease. For people with Alzheimer’s the risk is three times greater. It can be six times greater if they are over 80, according to a study conducted in Brazil by researchers at the University of São Paulo (USP) and Butantan Institute in partnership with colleagues at the Federal University of Rio de Janeiro (UFRJ).

An article on the study, which was supported by FAPESP, is published in Alzheimer’s & Dementia: The Journal of the Alzheimer's Association.

“We found that all causes of dementia are risk factors for severity and death in COVID-19 and that these risks are more pronounced for Alzheimer’s patients,” Sérgio Verjovski-Almeida, principal investigator for the project and a professor at USP’s Chemistry Institute, told Agência FAPESP.

Dementia had already been identified as a risk factor for COVID-19, alongside other comorbidities, such as cardiovascular and respiratory diseases, high blood pressure, diabetes, obesity, and cancer. One of the reasons is age: patients with dementia tend to be older, and many live in care homes where the risks of infection and viral transmission are greater.

However, no studies had previously been conducted to find out whether people with neurodegenerative disorders that cause dementia, such as Alzheimer’s and Parkinson’s, are more infected by the novel coronavirus and run a greater risk of progressing to the severe form of COVID-19 or dying from the disease, and none so far had set out to see whether old age heightens this risk.

To answer these questions, the researchers investigated data on positive diagnoses, hospitalizations and deaths from COVID-19 for a cohort of 12,863 patients over 65, who tested positive or negative for SARS-CoV-2. The data was included between March and August 2020 in UK Biobank, a biomedical database containing genetic and health information collected from half a million patients since 2006 by a team led by Rory Collins, Professor of Medicine and Epidemiology at the University of Oxford. 

Of the nearly 13,000 subjects, 1,167 tested positive for COVID-19 by RT-PCR. To control for a possible bias associated with younger asymptomatic individuals who were not tested, the researchers excluded subjects aged 49-65 and included only those aged 66 and older, stratifying them into three age groups: 66-74 (6,182), 75-79 (4,867), and 80-86 (1,814). 

“The advantages of using clinical data from UK Biobank include the amount of detail, as the records refer to all pre-existing diseases and whether the patient tested positive, was hospitalized and died from COVID-19,” Verjovski-Almeida explained. “This enabled us to assess the risk factors associated with infection, severity and death from the disease, including all causes of dementia, especially Alzheimer’s and Parkinson’s.”

Statistical analysis showed that all causes of dementia, especially Alzheimer’s, were risk factors for severity of the disease and death in the case of hospitalized patients, regardless of age.

Alzheimer’s specifically did not increase the risk of hospitalization compared with chronic comorbidities. After admission to hospital, however, Alzheimer’s patients ran a threefold risk of developing severe COVID-19 or dying from the disease compared with patients who did not have Alzheimer’s. For Alzheimer’s patients over 80 the risk was six times greater compared with patients in younger age groups.

“Some factor that hasn’t yet been identified increases the predisposition of Alzheimer’s patients to progress to severe COVID-19 and die from the viral disease,” Verjovski said. “The results of our study point to a need for special attention to these patients when hospitalized.”

Diagnostic hypotheses 

A possible explanation for the observed outcomes is that chronic inflammatory conditions or defective immune responses due to aging of the immune system (immunosenescence) may increase the vulnerability of these patients and reduce their capacity to mount an effective response to infection by the virus.

Another hypothesis is that Alzheimer’s alters the permeability of the blood-brain barrier, making infection of the central nervous system more likely.

Recent research has shown that SARS-CoV-2 is able to invade the central nervous system via the olfactory mucosa and that the presence of the virus in this region results in a local inflammatory immune response. The same study detected the virus in the brainstem, which comprises the primary cardiovascular and respiratory control center, raising the possibility that infection of the central nervous system may mediate or aggravate respiratory and cardiovascular problems in COVID-19 patients.

“We will now analyze these patients’ genomes, also available from UK Biobank, to find out which genes are mutated and may be implicated in the augmented risk of severe COVID-19 and death for Alzheimer’s patients,” Verjovski-Almeida said.

ITHACA, N.Y. - Water regulation in leaves is vital to a plant's health, affecting its growth and yield, disease susceptibility and drought resistance.

A breakthrough technology developed by Cornell University researchers uses nanoscale sensors and fiber optics to measure water status just inside a leaf's surface, where water in plants is most actively managed.

The engineering feat provides a minimally invasive research tool that will greatly advance the understanding of basic plant biology, and opens the door for breeding more drought-resistant crops. The technology could eventually be adapted for use as an agronomic tool for measuring water status in crops in real time.

The study in maize plants, "A Minimally Disruptive Method for Measuring Water Potential In-Planta Using Hydrogel Nanoreporters," published June 1 in the Proceedings of the National Academy of Sciences.

"One of the goals is to have tools that allow internal biology to be expressed out into the world in a way that can be captured and digitized," said senior author Abraham Stroock, professor in the Smith School of Chemical and Biomolecular Engineering in the College of Engineering.

"Current techniques for measurements of water potential require destructive sampling of leaves or disrupting leaf function," said co-first author Piyush Jain, a doctoral student in mechanical engineering. The new method, he said, "provides minimally disruptive and spatially and temporally resolved measurements of water potential in leaves of intact plants."

Outside of leaves' transport tissues, called xylem (the veins), lies an interior zone called the mesophyll, where most of the plant's photosynthesis and water stress occurs. Biologists suspect that signals are sent from here to the rest of the plant for managing water. Also, at the surfaces of leaves and stems, pores called stomata open and close to control the rate of exchange of gasses, mostly water vapor and carbon dioxide.

The new technology works in this microscopic zone.

"We are now sensing water right at that terminal place," Stroock said. "We've shown that by getting such a localized measurement, we can dissect the dynamics of water in the tissues" in minimally invasive ways, he said.

The technique involves injecting a nanoparticles formed of a soft synthetic hydrogel, called AquaDust, for measuring a leaf's water potential. The hydrogel, which occupies the interstitial spaces between cells in the mesophyll, is water-absorbent, swelling and shrinking based on water availability in the leaf.

The AquaDust contains dyes whose interactions allow it to fluoresce at different wavelengths depending on how close the dye molecules are to each other. By using fiber optics, the researchers can shine a light and get a spectrum back, which provides a measurement of water potential inside the leaf.

In the study, the researchers injected the AquaDust in multiple places along meters-long maize leaves and then measured the water gradients both along the length of the leaves and through the mesophyll. These measurements allowed them to develop a model of the tissue response to water stress and accurately predict the dynamics observed in the field.

This technology may have commercial applications for crop research, production agriculture, and manufacturing industries, but for now the researchers' focus is on the invaluable measurements of very local physiology of water management in plants. As a research tool, it allows plant biologists to better understand extremes of water stress, which could lead to breeding more water-efficient crops.

Sickle Cell Disease (SCD) is a genetically inherited group of red blood cell disorders. According to the CDC, an estimated 90,000 to 100,000 people in the United States live with this disease, and it disproportionately affects Black or African Americans; it occurs in roughly 1 in every 500 individuals in this demographic.

Researchers from the University of Pittsburgh Swanson School of Engineering used a unique and powerful MRI device to study the disease's impact on the brain and published their results in Neuroimage: Clinical. They discovered that SCD can have a severe effect on specific subfields of the hippocampus - a highly complex part of the human brain that controls learning and memory and is very susceptible to injury or disorders.

"This is a first-of-its-kind project that uses our lab's whole-body 7-Tesla magnetic resonance imager (7T MRI) alongside our optimized Tic Tac Toe RF head coil system to get clear and quality neural images of patients affected by SCD," said Tamer Ibrahim, professor of bioengineering and director of the Radiofrequency (RF) Research Facility and the 7-Tesla Bioengineering Research Program (7TBRP).

Individuals with SCD have red blood cells that contain an abnormal hemoglobin. This can cause the red blood cells to become hard, sticky and mutate into a unique crescent shape which inhibits the cell's passage through small blood vessels. These blockages affect blood and oxygen flow and consequently cause tissue damage -- the source of many SCD complications.

7-Tesla imaging has revealed abnormalities in the hippocampus for other neurodegenerative and neuroinflammatory diseases, so Ibrahim and his collaborators investigated SCD to see if it has a similar effect.

"Our findings support and extend previous reports of reduced hippocampal volume in SCD patients but provide more insights on the specific hippocampal subfields that are impacted," Ibrahim explained. "The subfields are tiny structures within the hippocampus which can only be seen in ultrahigh resolution acquisitions -- a feature of 7-Tesla imaging -- and enhanced with the 'Tic-Tac-Toe' antenna technology."

The next steps of this research are to investigate the mechanisms that lead to these structural changes in addition to electrical changes in the brain and how they relate to cognitive performance in SCD patients.

Advancing "Tic-Tac-Toe"-Themed MRI Technology

Ibrahim continues to improve the lab's 7-Tesla imaging technology, which is leveraged in 28 active collaborative projects funded by the National Institutes of Health. It is the most widely-used RF coil system in a given 7-Tesla site.

This advanced technology can provide higher resolution and enhanced contrast human MRI images, but its operational frequency (~?297 MHz) remains an obstacle in realizing the device's full potential. Ibrahim's group published recent findings related to their technology in Scientific Reports.

"The major challenge of the 7-Tesla imaging is the inhomogeneities, or lack of uniformity, of the RF fields inside the human head, resulting in brain images with voids in certain anatomical regions," said Tales Santini, a postdoctoral associate in the RF Research Facility. "In the past 12 years, our lab has developed innovative RF antenna designs which greatly increase the homogeneity of the fields, thus, enabling high resolution whole-brain images with minimal or no voids."

You would not be surprised to see an elephant in the savanna or a plate in your kitchen. Based on your prior experiences and knowledge, you know that is where elephants and plates are often to be found. If you saw a mysterious object in your kitchen, how would you figure out what it was? You would rely on your expectations or prior knowledge. Should a computer approach the problem in the same way? The answer may surprise you. Cold Spring Harbor Laboratory Professor Partha Mitra described how he views problems like these in a "Perspective" in Nature Machine Intelligence. He hopes his insights will help researchers teach computers how to analyze complex systems more effectively.

Mitra thinks it helps to understand the nature of knowledge. Mathematically speaking, many data scientists try to create a model that can "fit an elephant," or a set of complex data points. Mitra asks researchers to consider what philosophical framework would work best for a particular machine learning task:

"In philosophical terms, the idea is that there are these two extremes. One, you could say "rationalist," and the other "empiricist" points of view. And really, it's about the role of prior knowledge or prior assumptions."

Rationalists versus empiricists

A rationalist views the world through the lens of prior knowledge. They expect a plate to be in a kitchen and an elephant in a savanna.

An empiricist analyzes the data exactly as it is presented. When they visit the savanna, they no more expect to see an elephant than they do a plate.

If a rationalist came across this set of data points in the kitchen, they might at first be inclined to view it as a plate. Their prior knowledge states that a plate is likely to be found in a kitchen; it is highly unlikely to find an elephant. They have never seen this situation before, nor have they ever learned that such a situation could occur. Although their result takes in a certain amount of the data, it leaves out other parts. In this case, their methods have produced an incorrect result: a plate.

When an empiricist sees the same data, they will analyze it without regard to whether they are in the savanna or their kitchen. They will piece together an image from as many data points as possible. In this case, their result is a jagged image. It doesn't tell the empiricist if they are looking at an elephant, a plate, or anything else.

Neither the empiricist nor the rationalist is wrong. Both approaches work for various kinds of problems. However, in this case, if there is an elephant in the kitchen, it would pay to figure it out as quickly as possible. A middle ground between purely empirical and purely rationalist approaches may be best. With some prior knowledge of what an elephant looks like, you may notice the trunk and legs. And although the chances of an elephant being in your kitchen are low, it is certainly not impossible. Therefore, you would come to the conclusion that there is indeed an elephant in your kitchen, and you probably should leave--fast.

Predictable but wrong

Data scientists face this sort of problem all the time. They train computers to recognize new objects or patterns. Some machine learning programs may be able to process a lot of information and make many rules to fit the presented data, like the jagged image above. The jagged image might be reproducible when the same rules are applied to another similar data set. But just because the pattern is reproducible, that doesn't mean it accurately represents what is happening (the elephant).

There are historical examples of this dilemma. Two thousand years ago, Ptolemy developed a model of the universe that yielded excellent predictions for the movements of the moon and planets. His model was used successfully for centuries. However, Ptolemy used the wrong prior information: he placed the Earth at the center of the solar system and prioritized the circular motions of celestial objects. Johannes Kepler questioned this view in the 17th century and ultimately rejected Ptolemy's approach, which eventually led to Newton's law of universal gravitation. Although Ptolemy's complex model fit his own observations exceptionally well, it did not accurately represent what was happening. Mitra warns that "if you want to be an extreme empiricist, you really do need a lot of data. We now understand why under certain circumstances, such an approach can, in fact, succeed in a mathematically rigorous setting. Biological brains, on the other hand, are halfway in between. You do learn from experience, but you're not entirely data-driven."

Mitra hopes that data scientists will look to brain circuitry for inspiration when developing next-generation machine learning approaches. Vertebrate brains have circuits of different sizes, including medium-sized (mesoscale) ones. Those circuits are encoded with priors (known information, such as what animals look like, where they are found, or how to escape quickly from a charging elephant). At the same time, your brain is highly flexible, classifying new information and weighing the importance of different priors based on experience--elephants may not belong in a kitchen, but somehow, you have one anyway. Mitra concludes in his article:

"This points to the possibility of a new generation of intelligent machinery based on distributed circuit architectures which incorporate stronger priors, possibly drawing upon the mesoscale circuit architecture of vertebrate brains."

HOUSTON - (June 3, 2021) - Postpartum women in bad romantic relationships are not only more likely to suffer symptoms of depression, they are also at greater long-term risk of illness or death, according to new research from Rice University, Ohio State University and the University of California, Irvine.

"Longitudinal changes in HRV across pregnancy and postpartum: Effect of negative partner relationship qualities" will appear in the July 2021 edition of Psychoneuroendocrinology. The researchers examined how relationships and partner behavior are linked to depression and heart rate variability (HRV) in women between the third trimester of pregnancy and one year postpartum.

"The quality of relationship with one's spouse considerably affects one's mental health as well as biological health and physiology," said Lisa Christian, an associate professor of psychiatry and behavioral health at Ohio State University and a co-author of the study. "We were interested in learning more about the effects of relationship quality on health during the postpartum period, due to substantial changes occurring physically, mentally and in social and interpersonal lives at this time."

The researchers used the Positive and Negative Quality in Marriage Scale to measure negative relationship qualities and the Center for Epidemiologic Studies Depression Scale to evaluate mental health. The researchers also monitored HRV during regular check-ins with the study participants throughout the first year postpartum.

During pregnancy, HRV naturally drops. The researchers found that postpartum women who had poor relationships with their spouses or partners were more likely to report symptoms of depression. These were linked to HRV that was more likely to remain low following pregnancy.

This matters because HRV has a significant link to long-term health and wellness, said Ryan Linn Brown, a Rice psychology graduate student and Biobehavioral Mechanisms Explaining Disparities (BMED) lab researcher. She is the study's lead author.

"High HRV is good. It means your body is well-equipped to deal with and recover from stressors," she said. "Low HRV means your body isn't as capable of managing stress, and previous research has demonstrated that poorly managed stress can put you at greater risk of a host of health problems."

Brown said the research demonstrates a clear link between the quality of spousal relationships during pregnancy and postpartum depression and HRV, which ultimately can impact long-term wellness and mortality of new mothers.

The researchers hope the study findings will aid the development of mental health interventions that will help postpartum women live healthier lives.

RESEARCHERS at the University of Huddersfield have warned there is an urgent need for the country's mental health interventions to create strategies optimising the use of antidepressants after conducting a study which has highlighted an alarming rise in relation to usage and costs.

The open-access study, published by the international DARU Journal of Pharmaceutical Sciences, is entitled 'Surging trends in prescriptions and costs of antidepressants in England amid COVID-19' and has investigated the trends in prescriptions and costs of various antidepressants in England during the COVID-19 pandemic.

The researchers discovered that the total number of antidepressant prescriptions drugs dispensed during 2020 had increased by four million items since 2019 costing NHS England £139 million more than in the previous year.

This is attributed to the active pharmaceutical ingredient shortages witnessed during COVID19 coupled with a significantly higher cost of generic drugs during the pandemic, with just one product alone sertraline, an SSRI antidepressant drug, accounting for a majority of the additional costs.

While an increase in the number of prescriptions had been predicted because of the pandemic, said the University's Dr Syed Shahzad Hasan, one of the co-authors of the study, it was the sharp rise in antidepressant prescription costs which was a potential cause for concern and highlighted the urgent need for mental health interventions in the country and strategies to optimise the use of antidepressants.

The study also observes a meta-analysis of 100,000 patients using antidepressants which concluded that the risk of suicide doubled in children and adolescents.

"These findings are particularly important in the context of the COVID-19 pandemic," said Dr Hamid Merchant from the University. "Observational data suggest that young adults, up to 25 years of age, were impacted by the mental health issues during the pandemic, and hence, were more likely to use antidepressants."

Recommendations

The research recommends that further studies are needed to assess the age distribution of antidepressant prescriptions particularly focusing on adolescents and young adults who are at a higher risk of experiencing life-threatening adverse effects.

"It is, therefore, important to optimise the safe use of antidepressants, particularly in young adults," added Dr Merchant. "Not only to help with mental health but also in preventing the associated side-effects that may further increase the morbidity and mortality associated with depression in younger adults."

A new study by ecologist André de Roos* shows that differences between juveniles and adults of the same species are crucial for the stability of complex ecological communities. The research, published in Proceedings of the National Academy of Sciences, represents a major advance in ecological modeling at a time when biodiversity is declining and species around the world are rapidly going extinct.

Up to now, ecological models have focused exclusively on the interactions between species, ignoring the variations within them. The dragonflies, frogs, trout, and phytoplankton in a freshwater pond, for example, would be represented as nodes in a network, connected by edges that represent how each species feeds on the others. 

Using computer simulations, de Roos was able to model both the number of total species in a community and key variations within the same species, accounting for differences between juveniles and adults. He says these differences arise not only because adults reproduce, while juveniles grow and mature, but also because juveniles, being of smaller body size, are generally more limited by food availability than adults and run a much greater risk of being captured by predators. These differences lead to variations over time in the ratio of juveniles to adults, which tip the entire community from instability to stability.

"On the basis of the network of species interactions alone the simulated communities are predicted to be wildly unstable," he writes, "but these destabilizing forces are swamped and fully attenuated by the stabilizing effects of the dynamics of juvenile and adult densities."

The study advances a long-running debate in ecology over the relationship between species diversity and ecosystem stability. (A debate which, de Roos notes, was fueled by a 1972 paper by the late ecologist Robert May).  

"Ecologists have long intuited that diversity can stabilize ecosystems, and even protect them against collapse," de Roos says. "Theoretically, however, we struggled with a good explanation for that idea. What we're now discovering through computation and quantitative analysis is that our existing theories fall short, because diversity is more than just a number of species connected by a network of interactions. The interplay between different types of complexity is what determines the function of the system."

HAMILTON, ON (June 3, 2021) - A novel longitudinal study on heavy drinking in young adults and the psychological impacts of COVID-19 has revealed some unexpected findings that challenge preconceived notions regarding pandemic-related alcohol use.

In a sample of nearly 500 young adults ranging in age from 18 to 25, researchers saw a reduction in problematic drinking and alcohol consequences during the initial phase of the pandemic for both men and women. This is in contrast to many anecdotal reports of increased drinking and increased household spending on alcohol during that time period.

More startling, however, were the additional findings that showed increased rates of depression and anxiety symptoms among young women - increases that were not observed to a significant degree among male participants.

"These results reveal the complexity of the pandemic impacts," said senior author James MacKillop. MacKillop is the director of the Peter Boris Centre for Addictions Research of McMaster University and St. Joseph's Healthcare Hamilton, as well as a professor of psychiatry and behavioural neurosciences at McMaster.

Researchers suspect that restrictions on socializing contributed to the reduction of risky alcohol use observed in this age group. With a decreasing proportion of individuals living with roommates or in group living arrangements, peer influence - usually a strong predictor of alcohol misuse - has decreased.

"The study participants were young people, who typically drink in social settings," said Meenu Minhas, lead author of the study and a postdoctoral fellow at the Peter Boris Centre for Addictions Research. "If you take away bars, restaurants, and group events, like parties, it's not surprising that binge drinking in this group goes down too."

Conversely, the reported increase of mental health symptoms in the study illustrates some of the negative consequences associated with the pandemic. Among study participants, women showed a substantial increase in the odds of meeting the threshold for clinical depression from pre- to intra-pandemic. A similar effect was not found in male participants.

"We saw high levels of pandemic-related stress, irritability, sadness, which unfortunately were felt more strongly by females," said Minhas.

"Although certain public health measures were important in controlling the spread of the virus, the benefits of social support and interaction, which often act as buffers against the effects of stress, have also been reduced due to the pandemic," explained MacKillop.

Pandemic-related income loss was also found to be attributed to increased depression scores, with those reporting greater than 50 percent income loss experiencing significant increases in depressive symptoms. Researchers see this as a direct link between economic impacts and adverse mental health outcomes. They argue that government strategies that provide economic assistance may effectively act like an antidepressant when it comes to pandemic impacts on mental health.

Other studies on substance use during the pandemic have tended to use cross-sectional designs, meaning they do not account for changes over time. In contrast, the present study used a longitudinal design that tracked the same cohort before and during the pandemic.

"Collectively, these results indicate the importance of critical thinking and considering population subgroups when it comes to COVID-19's psychological impacts," said MacKillop. "Rather than uniform increases or decreases, it's increasingly clear that subgroups will show very different patterns, including both negative and, in some cases, positive changes."