Culture

A public health advisory issued by the US Food and Drug Administration (FDA) in 2003, followed by drug label warnings, indicated that children and adolescents taking antidepressants were at increased risk of developing suicidal thoughts and behaviors. Research has shown that these warnings reduced the diagnosis and treatment of depression among young people. Now, a new study suggests that the warnings may also have contributed to an increase in suicide deaths among youth.

The authors of the study, which is published in Psychiatric Research and Clinical Practice, estimate that there may have been 5,958 excess suicides nationally by 2010 among 43 million adolescents and 21 million young adults.

"Our findings suggest the boxed warnings may have contributed to the very thing the FDA was trying to prevent. More than two-thirds of depressed teens do not receive any depression care whatsoever, an issue now further exacerbated by COVID-19. We strongly recommend the FDA reexamine the use of these warnings," said principal investigator Stephen Soumerai, ScD, of Harvard Medical School and the Harvard Pilgrim Health Care Institute.

DNA and RNA have been compared to "instruction manuals" containing the information needed for living "machines" to operate. But while electronic machines like computers and robots are designed from the ground up to serve a specific purpose, biological organisms are governed by a much messier, more complex set of functions that lack the predictability of binary code. Inventing new solutions to biological problems requires teasing apart seemingly intractable variables - a task that is daunting to even the most intrepid human brains.

Two teams of scientists from the Wyss Institute at Harvard University and the Massachusetts Institute of Technology have devised pathways around this roadblock by going beyond human brains; they developed a set of machine learning algorithms that can analyze reams of RNA-based "toehold" sequences and predict which ones will be most effective at sensing and responding to a desired target sequence. As reported in two papers published concurrently today in Nature Communications, the algorithms could be generalizable to other problems in synthetic biology as well, and could accelerate the development of biotechnology tools to improve science and medicine and help save lives.

"These achievements are exciting because they mark the starting point of our ability to ask better questions about the fundamental principles of RNA folding, which we need to know in order to achieve meaningful discoveries and build useful biological technologies," said Luis Soenksen, Ph.D., a Postdoctoral Fellow at the Wyss Institute and Venture Builder at MIT's Jameel Clinic who is a co-first author of the first of the two papers.

Getting ahold of toehold switches

The collaboration between data scientists from the Wyss Institute's Predictive BioAnalytics Initiative and synthetic biologists in Wyss Core Faculty member Jim Collins' lab at MIT was created to apply the computational power of machine learning, neural networks, and other algorithmic architectures to complex problems in biology that have so far defied resolution. As a proving ground for their approach, the two teams focused on a specific class of engineered RNA molecules: toehold switches, which are folded into a hairpin-like shape in their "off" state. When a complementary RNA strand binds to a "trigger" sequence trailing from one end of the hairpin, the toehold switch unfolds into its "on" state and exposes sequences that were previously hidden within the hairpin, allowing ribosomes to bind to and translate a downstream gene into protein molecules. This precise control over the expression of genes in response to the presence of a given molecule makes toehold switches very powerful components for sensing substances in the environment, detecting disease, and other purposes.

However, many toehold switches do not work very well when tested experimentally, even though they have been engineered to produce a desired output in response to a given input based on known RNA folding rules. Recognizing this problem, the teams decided to use machine learning to analyze a large volume of toehold switch sequences and use insights from that analysis to more accurately predict which toeholds reliably perform their intended tasks, which would allow researchers to quickly identify high-quality toeholds for various experiments.

The first hurdle they faced was that there was no dataset of toehold switch sequences large enough for deep learning techniques to analyze effectively. The authors took it upon themselves to generate a dataset that would be useful to train such models. "We designed and synthesized a massive library of toehold switches, nearly 100,000 in total, by systematically sampling short trigger regions along the entire genomes of 23 viruses and 906 human transcription factors," 
said Alex Garruss, a Harvard graduate student working at the Wyss Institute who is a co-first author of the first paper. "The unprecedented scale of this dataset enables the use of advanced machine learning techniques for identifying and understanding useful switches for immediate downstream applications and future design."

Armed with enough data, the teams first employed tools traditionally used for analyzing synthetic RNA molecules to see if they could accurately predict the behavior of toehold switches now that there were manifold more examples available. However, none of the methods they tried - including mechanistic modeling based on thermodynamics and physical features - were able to predict with sufficient accuracy which toeholds functioned better.

A picture is worth a thousand base pairs

The researchers then explored various machine learning techniques to see if they could create models with better predictive abilities. The authors of the first paper decided to analyze toehold switches not as sequences of bases, but rather as two-dimensional "images" of base-pair possibilities. "We know the baseline rules for how an RNA molecule's base pairs bond with each other, but molecules are wiggly - they never have a single perfect shape, but rather a probability of different shapes they could be in," said Nicolaas Angenent-Mari, a MIT graduate student working at the Wyss Institute and co-first author of the first paper. "Computer vision algorithms have become very good at analyzing images, so we created a picture-like representation of all the possible folding states of each toehold switch, and trained a machine learning algorithm on those pictures so it could recognize the subtle patterns indicating whether a given picture would be a good or a bad toehold."

Another benefit of their visually-based approach is that the team was able to "see" which parts of a toehold switch sequence the algorithm "paid attention" to the most when determining whether a given sequence was "good" or "bad." They named this interpretation approach Visualizing Secondary Structure Saliency Maps, or VIS4Map, and applied it to their entire toehold switch dataset. VIS4Map successfully identified physical elements of the toehold switches that influenced their performance, and allowed the researchers to conclude that toeholds with more potentially competing internal structures were "leakier" and thus of lower quality than those with fewer such structures, providing insight into RNA folding mechanisms that had not been discovered using traditional analysis techniques.

"Being able to understand and explain why certain tools work or don't work has been a secondary goal within the artificial intelligence community for some time, but interpretability needs to be at the forefront of our concerns when studying biology because the underlying reasons for those systems' behaviors often cannot be intuited," said Jim Collins, Ph.D., the senior author of the first paper. "Meaningful discoveries and disruptions are the result of deep understanding of how nature works, and this project demonstrates that machine learning, when properly designed and applied, can greatly enhance our ability to gain important insights about biological systems." Collins is also the Termeer Professor of Medical Engineering and Science at MIT.

Now you're speaking my language

While the first team analyzed toehold switch sequences as 2D images to predict their quality, the second team created two different deep learning architectures that approached the challenge using orthogonal techniques. They then went beyond predicting toehold quality and used their models to optimize and redesign poorly performing toehold switches for different purposes, which they report in the second paper.

The first model, based on a convolutional neural network (CNN) and multi-layer perceptron (MLP), treats toehold sequences as 1D images, or lines of nucleotide bases, and identifies patterns of bases and potential interactions between those bases to predict good and bad toeholds. The team used this model to create an optimization method called STORM (Sequence-based Toehold Optimization and Redesign Model), which allows for complete redesign of a toehold sequence from the ground up. This "blank slate" tool is optimal for generating novel toehold switches to perform a specific function as part of a synthetic genetic circuit, enabling the creation of complex biological tools.

"The really cool part about STORM and the model underlying it is that after seeding it with input data from the first paper, we were able to fine-tune the model with only 168 samples and use the improved model to optimize toehold switches. That calls into question the prevailing assumption that you need to generate massive datasets every time you want to apply a machine learning algorithm to a new problem, and suggests that deep learning is potentially more applicable for synthetic biologists than we thought," said co-first author Jackie Valeri, a graduate student at MIT and the Wyss Institute.

The second model is based on natural language processing (NLP), and treats each toehold sequence as a "phrase" consisting of patterns of "words," eventually learning how certain words are put together to make a coherent phrase. "I like to think of each toehold switch as a haiku poem: like a haiku, it's a very specific arrangement of phrases within its parent language - in this case, RNA. We are essentially training this model to learn how to write a good haiku by feeding it lots and lots of examples," said co-first author Pradeep Ramesh, Ph.D., a Visiting Postdoctoral Fellow at the Wyss Institute and Machine Learning Scientist at Sherlock Biosciences.

Ramesh and his co-authors integrated this NLP-based model with the CNN-based model to create NuSpeak (Nucleic Acid Speech), an optimization approach that allowed them to redesign the last 9 nucleotides of a given toehold switch while keeping the remaining 21 nucleotides intact. This technique allows for the creation of toeholds that are designed to detect the presence of specific pathogenic RNA sequences, and could be used to develop new diagnostic tests.

The team experimentally validated both of these platforms by optimizing toehold switches designed to sense fragments from the SARS-CoV-2 viral genome. NuSpeak improved the sensors' performances by an average of 160%, while STORM created better versions of four "bad" SARS-CoV-2 viral RNA sensors whose performances improved by up to 28 times.

"A real benefit of the STORM and NuSpeak platforms is that they enable you to rapidly design and optimize synthetic biology components, as we showed with the development of toehold sensors for a COVID-19 diagnostic," said co-first author Katie Collins, an undergraduate MIT student at the Wyss Institute who worked with MIT Associate Professor Timothy Lu, M.D., Ph.D., a corresponding author of the second paper.

"The data-driven approaches enabled by machine learning open the door to really valuable synergies between computer science and synthetic biology, and we're just beginning to scratch the surface," said Diogo Camacho, Ph.D., a corresponding author of the second paper who is a Senior Bioinformatics Scientist and co-lead of the Predictive BioAnalytics Initiative at the Wyss Institute. "Perhaps the most important aspect of the tools we developed in these papers is that they are generalizable to other types of RNA-based sequences such as inducible promoters and naturally occurring riboswitches, and therefore can be applied to a wide range of problems and opportunities in biotechnology and medicine."

Additional authors of the papers include Wyss Core Faculty member and Professor of Genetics at HMS George Church, Ph.D.; and Wyss and MIT Graduate Students Miguel Alcantar and Bianca Lepe.

"Artificial intelligence is wave that is just beginning to impact science and industry, and has incredible potential for helping to solve intractable problems. The breakthroughs described in these studies demonstrate the power of melding computation with synthetic biology at the bench to develop new and more powerful bioinspired technologies, in addition to leading to new insights into fundamental mechanisms of biological control," said Don Ingber, M.D., Ph.D., the Wyss Institute's Founding Director. Ingber is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School and the Vascular Biology Program at Boston Children's Hospital, as well as Professor of Bioengineering at Harvard's John A. Paulson School of Engineering and Applied Sciences.

Engineers have invented a way to spray extremely thin wires made of a plant-based material that could be used in N95 mask filters, devices that harvest energy for electricity, and potentially the creation of human organs.

The method involves spraying methylcellulose, a renewable plastic material derived from plant cellulose, on 3D-printed and other objects ranging from electronics to plants, according to a Rutgers-led study in the journal Materials Horizons.

"This could be the first step towards 3D manufacturing of organs with the same kinds of amazing properties as those seen in nature," said senior author Jonathan P. Singer, an assistant professor in the Department of Mechanical and Aerospace Engineering in the School of Engineering at Rutgers University-New Brunswick. "In the nearer term, N95 masks are in demand as personal protective equipment during the COVID-19 pandemic, and our spray method could add another level of capture to make filters more effective. Electronics like LEDs and energy harvesters also could similarly benefit."

Thin wires (nanowires) made of soft matter have many applications, including the cilia that keep our lungs clean and the setae (bristly structures) that allow geckos to grip walls. Such wires have also been used in small triboelectric energy harvesters, with future examples possibly including strips laminated on shoes to charge a cell phone and a door handle sensor that turns on an alarm.

While people have known how to create nanowires since the advent of cotton candy melt spinners, controlling the process has always been limited. The barrier has been the inability to spray instead of spin such wires.

Singer's Hybrid Micro/Nanomanufacturing Laboratory, in collaboration with engineers at Binghamton University, revealed the fundamental physics to create such sprays. With methylcellulose, they have created "forests" and foams of nanowires that can be coated on 3D objects. They also demonstrated that gold nanoparticles could be embedded in wires for optical sensing and coloration.

Projections of potentially dramatic sea-level rise from ice-sheet melting in Antarctica have been wide-ranging, but a Rutgers-led team has created a model that enables improved projections and could help better address climate change threats.

A major source of sea-level rise could come from melting of large swaths of the vast Antarctic ice sheet. Fossil coral reefs jutting above the ocean's surface show evidence that sea levels were more than 20 feet higher about 125,000 years ago during the warm Last Interglacial (Eemian) period.

"Evidence of sea-level rise in warm climates long ago can tell us a lot about how sea levels could rise in the future," said lead author Daniel M. Gilford, a post-doctoral associate in the lab of co-author Robert E. Kopp, a professor in the Department of Earth and Planetary Sciences within the School of Arts and Sciences at Rutgers University-New Brunswick. "This evidence suggests that as climate change drives warming in the atmosphere and oceans, future global sea-level rise could reach considerable heights."

The study, published in the journal JGR: Earth Surface, delves into how paleoclimate evidence from about 125,000 years ago can be used to improve computer model projections of Antarctic ice-sheet collapse and sea-level rise. Such evidence is increasingly effective for improving projections, providing valuable insights into ice sheet vulnerability through at least 2150.

The study takes advantage of the similarities between past and potential future sea levels to train a statistical ice-sheet model, using artificial intelligence. The fast, simple, less expensive "emulator" - a form of machine learning software - is taught to mimic the behavior of a complex model that focuses on ice-sheet physics, enabling many more simulations than could be explored with the complex model alone. This avoids the costly run times of the complex ice-sheet model, which considers such phenomena as ice-sheet fractures due to surface melting and the collapse of tall seaside ice cliffs.

What may happen to the Antarctic ice sheet as the climate warms is the biggest uncertainty when it comes to global sea-level rise this century, the study notes. When combined with evidence of past sea levels, the new model can boost confidence in sea-level rise projections through at least 2150.

"If big swaths of the Antarctic ice sheet melted and collapsed about 125,000 years ago, when the polar regions were warmer than today, parts of the ice sheet may be similarly prone to collapse in the future as the climate warms, affecting our expectations of sea-level rise and coastline flooding over the next 130 years," Gilford said.

New estimates of sea levels about 125,000 years ago could be used to indicate whether, 75 years from now, Hurricane Sandy-like flooding (about 9 feet above ground level in New York City) is likely to occur once a century or annually along parts of the Northeast U.S. coastline. Improved projections could also be included in reports such as the Intergovernmental Panel on Climate Change's upcoming Sixth Assessment Report, likely helping officials and others decide how to address climate change threats.

Co-authors include Erica L. Ashe, a post-doctoral scientist in Kopp's lab, along with scientists at the University of Massachusetts Amherst, Pennsylvania State University and the University of Bremen.

Two-thirds of older adults rely on at least two prescription drugs, and more than half take two or more non-prescription drugs or supplements. And two in ten take five or more prescription drugs. Some of those pills, capsules and tablets may interact with one another in ways that could put them at risk.

But a new poll shows that most people over 50 haven't connected with a pharmacist to check for potential clashes among their prescription drugs, non-prescription drugs, and supplements, or the potential to save money by switching to lower-cost options.

Medicare Part D plans offer free in-depth medication reviews for enrollees who meet their eligibility criteria. However, participation has historically been low. The new poll shows 85% of Medicare Part D enrollees who had not had a medication review didn't know they could be eligible for one. Some non-Medicare plans also cover reviews, but 86% of all older adults without a medication review said they weren't aware that it could be covered.

The new findings come from the National Poll on Healthy Aging, based at the University of Michigan's Institute for Healthcare Policy and Innovation with support from AARP and Michigan Medicine, U-M's academic medical center. The new report draws on responses from a national sample of more than 2,000 adults aged 50 to 80.

The poll team worked with two faculty in the U-M College of Pharmacy who have studied the issue of multiple medication use, and the policies and practices aimed at improving use and reducing the risky side effects they can cause.

"These results show the importance of continuing efforts by physicians, pharmacists, other health care providers, insurers and policymakers to help older adults understand the importance of medication reviews," says Antoinette B. Coe, Pharm.D., Ph.D., an assistant professor of clinical pharmacy.

"Since older adults with multiple chronic illnesses and medications, high medication costs and Part D Medicare coverage may qualify for a covered medication review, and their health plans are graded publicly on how many qualified participants receive a review, our finding that so many are unaware of the option is surprising," says Karen B. Farris, Ph.D., M.P.A., a professor of clinical pharmacy.

Coe and Farris do note that the older adults at the highest risk of drug interactions - those taking five or more prescription medications - were more likely to have had a comprehensive medication review than those taking fewer medications, though there is still room for improvement.

The poll shows an opportunity for progress. When the poll team asked older adults who take multiple prescription medications if they'd be interested in going over them with a pharmacist, more than a third said yes.

The older a poll respondent was, the more likely she or he was to take multiple prescription and over-the-counter medications. In all, 30% of those over 65 took five or more prescription medications, compared with 19% of those aged 50 to 64. And 15% of those over 65 said they take five or more over-the-counter medications, vitamins and supplements, compared with 9% of those in their 50s and early 60s.

Preeti Malani, M.D., the poll director and a Michigan Medicine physician specializing in geriatrics and infectious diseases, notes that every older adult should keep a list of everything they take, whether they get it via a prescription or buy it directly. A providers or pharmacist can look at the list to try to spot any potential for interactions or opportunities to switch to lower-cost options that could provide the same benefits.

"It's also important to make sure you tell your doctors and other health care providers about everything you take, even over-the-counter vitamins or herbal remedies," she says. "Not only may they spot potential risks, but the computer systems that they use to track your care might identify potential interactions." She also notes that medication reviews can take place in person, by phone or via a video appointment.

"Managing multiple medications may be especially important for older adults," says Alison Bryant, Ph.D., senior vice president of research for AARP. "We know that people enrolled in Medicare Part D take an average of 4.5 medications each month. We encourage everyone taking medications or supplements to regularly discuss them with a health care provider."

The National Poll on Healthy Aging results are based on responses from a nationally representative sample of 2,048 adults aged 50 to 80 who answered a wide range of questions online. Questions were written, and data interpreted and compiled, by the IHPI team. Laptops and Internet access were provided to poll respondents who did not already have them.

A full report of the findings and methodology is available at http://www.healthyagingpoll.org, along with past National Poll on Healthy Aging reports.

COLUMBUS, Ohio - It's good to have friends and family to back you up when you need it - but it's even better if your supporters are close with each other too, a new set of studies suggests.

Researchers found that people perceived they had more support from a group of friends or family who all knew and liked each other than from an identical number of close relationships who were not linked.

The results suggest that having a network of people to lean on is only part of what makes social support so beneficial to us, said David Lee, who led the study as a postdoctoral fellow in psychology at The Ohio State University.

"The more cohesive, the more dense this network you have, the more you feel you can rely on them for support," said Lee, who is now an assistant professor of communication at the University at Buffalo.

"It matters if your friends can depend on each other, just like you depend on them."

Lee conducted the study with Joseph Bayer, assistant professor of communication, and Jonathan Stahl, graduate student in psychology, both at Ohio State. Their research was published online recently in the journal Social Psychology Quarterly.

The researchers conducted two online studies.

In one study, 339 people were asked to list eight people in their lives that they could go to for support in the last six months. Participants rated on a scale of 1 to 7 how much support they received from each person. (Most were listed as friends or family members, but some people also named co-workers, romantic partners, classmates or roommates).

Crucially for this study, participants were also asked to rate on a scale of 1 to 7 how close each possible pair of their eight supporters were to each other (from "they don't know each other" to "extremely close.")

Based on those answers, the researchers calculated the density of each participant's network - the closer and more interconnected their friends and family were to each other, the denser the network.

Results showed that the denser the networks, the more support that participants said they would be able to receive from them.

"We found that our support networks are more than the sum of their parts," said Bayer, who is a core faculty of Ohio State's Translational Data Analytics Institute.

"People who feel they have more social support in their lives may be focusing more on the collective support they feel from being part of a strong, cohesive group. It's having a real crew, as opposed to just having a set of friends."

A second study, involving 240 people, examined whether the density of a social network mattered in a specific situation where people needed help.

In this case, participants were asked to list two different groups of four people they could go to if they needed support. One group comprised four people who were not close to one another and the other group consisted of four people who were close with each other.

Participants were then asked to imagine a scenario in which their house had been broken into and they went to their network for support.

Half the people were told to think about going to the four people who were not close to one another, while the other half imagined reaching out to their four connected supporters.

Results showed that those who imagined going to their tight-knit group of friends or family perceived that they would receive more support than did participants who thought about going to their unconnected friends.

The results also offered preliminary evidence of two psychological mechanisms that could help explain why people feel better supported by a tight-knit group of friends.

In answers to survey questions, participants suggested that they thought of their group of close friends or family as one entity. They also were more likely to see a closer-knit group as part of their own identities. Both of these factors were related to perceiving more support, results showed.

The researchers said the results of both studies show it isn't just the number of friends and family you have in your network that is important.

"You can have two friends who are both very supportive of you, but if they are both friends with each other, that makes you feel even more supported," Stahl said.

On a practical level, that means it is important which friends we think about when we most need help or when we are feeling lonely in the midst of daily life.

"Focus on those friends who are connected to each other," Bayer said. "That's where we really perceive the most support."

A new study published in Arthritis Care & Research has examined patterns of 24-hour physical activity and sleep among patients with rheumatoid arthritis, lupus, and knee osteoarthritis.

In the 172-participant study, four profiles were apparent with differences characterized by variations in time spent sleeping (High and Low sleepers), non-ambulatory activities (High Sitters), and ambulatory activities (Balanced Activity).

Younger age, not having a job that involved a lot of sitting, and having outside walking as a habit were each associated with Balanced Activity relative to High Sitters.

Considering these profiles may be useful in efforts to help individuals with arthritis modify their activity or sleep behaviors.

"We all live our daily lives over 24 hours, and our study found that people with arthritis are likely to have one of four distinctly different patterns for how they allocate time in sleep and a variety of activities throughout their day," said lead author Lynne Feehan, PT, PhD, Department of Physical Therapy, University of British Columbia. "This suggests that a one-size-fits-all approach to supporting people with arthritis to modify their daily sleep or physical activity choices may not be appropriate."

Alison Hoens a patient partner on this study, noted, "As a patient living with rheumatoid arthritis and as a physical therapist, the findings of this study resonate strongly with me. The recognition that patients, even with similar diagnoses, are 'not all the same' speaks to the potential of tailoring support from healthcare providers to encourage healthy sleep, rest, and activity that align with a patient's habits and needs."

There are concerns that exposure to general anesthesia during surgery may contribute to an increased risk of Alzheimer's disease. To investigate, researchers compared exposure to general anesthesia versus regional anesthesia during elective surgery, looking for potential links to the development of dementia.

The Journal of the American Geriatrics Society study included 7,499 matched pairs of community-dwelling individuals aged 66 years or older who underwent surgery between 2007 and 2011 and were followed for up to 5 years.

The investigators found no difference in risk of being diagnosed with dementia for individuals who received general anesthesia when compared with those who received regional anesthesia.

"Many older adults experience changes in their cognition immediately following surgery and wonder what role the type of anesthetic might have played in these changes," said senior author Dallas P. Seitz, MD, PhD, FRCPC, of the University of Calgary, in Canada. "Our study provides evidence that anesthetic technique used during elective surgeries, general anesthesia or regional anesthesia is not associated with a long-term risk of developing dementia."

An analysis of relevant studies published to date has identified certain risk factors associated with suicidal behavior in adolescents. The analysis also revealed certain protective factors that may reduce the likelihood of suicidal behavior.

The analysis, which is published in the Journal of Child and Adolescent Psychiatric Nursing, included 66 studies. Internal risk factors included poor individual coping, smartphone abuse, nutritional imbalance, menstrual problems, poor lifestyle, and disturbed sleep patterns. External risk factors for adolescent suicide behavior included mental health history in parents, poor interactions in the family, and social problems.

Reframing to have a meaningful life, adequate nutrition, parent-child interactions, reading books and watching movies, and faith or religiosity are protective factors that may reduce the risk of suicidal behavior in adolescents.

"Loving others is imperative, loving yourself is courage. Don't be afraid to love yourself--you have to fight for yourself before fighting for others," said senior author Heni D. Windarwati, of the Universitas Brawijaya, in Indonesia.

Having a strong ethnic identity was linked with a lower risk of suicidal behaviors among Black college students in a recent study published in the Journal of Multicultural Counseling and Development.

The study examined the influence of cultural orientation (ethnic identity, Afrocentric worldview, and religiosity) and personal resources (resiliency and optimism) on suicidal behaviors among Black college students.

The investigators noted that for Black college students, especially as members of a racial/ethnic minority within the society, having a strong ethnic identity may be a stronger protective factor against suicidality as compared with religiosity and Afrocentric worldview.

Also, resilience and a sense of empowerment seemed to matter more than optimism in terms of decreasing suicidal behaviors. Black college students who endorsed a higher level of Afrocentric worldview, ethnic identity, or religiosity were more resilient, which in turn protected against suicidality.

"Most often, the uniqueness of Black persons' identity is viewed from a negative perspective. With increasing calls to respect and uphold Blacks' lives, our study sheds light to the positive role of Black ethnic identity in enhancing their psychological welfare," said co-author Pius N. Nyutu, PhD, of Fayetteville State University.

There's considerable risk that humans transmit SARS-CoV-2, the virus that causes COVID-19, to wildlife, according to a perspective article published in Mammal Review.

The authors noted that if SARS-CoV-2 were to infect and spread among wild mammals, it could potentially cause disease in some populations, in turn further endangering already threatened species.

Also, if SARS-CoV-2 could be sustainably transmitted among some mammalian populations or communities, this would create new animal reservoirs that could repeatedly source new outbreaks in humans and other animals.

The researchers urge people to take sanitary precautions when in direct or indirect contact with wild or feral mammal species to prevent human-to-wildlife SARS-CoV-2 transmission.

"We really should avoid turning our pandemic into a multi-species problem," said lead author Sophie Gryseels, PhD, of the University of Antwerp, KU Leuven, and the University of Arizona. "It's difficult enough to control the SARS-CoV-2 in human populations--imagine what it will be like if it spreads among wild mammals. They could also get sick and form a reservoir from which they can then again infect humans, but we can't ask animals to wear face masks and keep physical distance."

CLEVELAND, Ohio -- No one knows for sure how long they will live. A new study, however, suggests that leukocyte telomere length may offer some key insights into a woman's longevity and further demonstrates how maternal age at birth of last child affects telomere length and long-term health. Study results are published online today in Menopause, the journal of The North American Menopause Society (NAMS).

This is not the first time that the length of a woman's leukocyte telomeres has been linked with her projected lifespan. Telomeres are repeating DNA-protein complexes that protect the ends of chromosomes and have proven to be critical for maintaining genomic stability. Previous studies have suggested a link between telomere length and various chronic conditions such as cardiovascular disease, type 2 diabetes, some neurologic conditions, and various cancers.

A smaller study previously suggested that maternal age at the birth of a woman's last child affected telomere length. This new, larger-scale study included more than 1,200 perimenopausal and postmenopausal women of various ethnicities and backgrounds from the National Health and Nutrition Examination Survey. In addition, unlike previous studies, this study took into consideration sociodemographic factors related to childbearing patterns and health decisions.

The study confirmed that maternal age at last birth is positively associated with telomere length, meaning that women who delivered their last child later in life were likely to have longer telomeres, a biomarker of long-term health and longevity. This finding was restricted to women with one or two live births or who had used oral contraceptives.

Results are published in the article "Maternal age at last birth and leukocyte telomere length in a nationally representative population of perimenopausal and postmenopausal women."

"More research is needed to determine whether older maternal age at last birth causes telomeres to lengthen or whether telomere length serves as a proxy for general health and corresponds with a woman's ability to have a child at a later age," says Dr. Stephanie Faubion, NAMS medical director.

A team of scientists has discovered an ancient form of rubisco, the most abundant enzyme on Earth and critical to life as we know it.

Found in previously unknown environmental microbes, the newly identified rubisco provides insight into the evolution of the photosynthetic organisms that underlie the planet's food chains.

"Rubisco is the primary driver for producing food, so it can take CO2 from the atmosphere and fix that into sugar for plants and other photosynthetic organisms to use," said Doug Banda, a postdoctoral scholar in the lab of Patrick Shih, a UC Davis assistant professor and the director of Plant Biosystems Design at the Joint BioEnergy Institute (JBEI), which is managed by Lawrence Berkeley National Laboratory (Berkeley Lab). "It is also one of the oldest carbon-fixing enzymes on the planet."

Form I rubisco, which is found in plants, algae, and cyanobacteria, has a deep evolutionary history with the planet, going back nearly 2.4 billion years to the Great Oxygenation Event, when cyanobacteria literally transformed the Earth's atmosphere by introducing oxygen to it through photosynthesis. Rubisco's role in this foundational event makes it a key focus of scientists studying the evolution of life, as well as scientists seeking to develop bio-based fuels and renewable energy technologies.

In a study appearing in Nature Plants, Banda and researchers from UC Davis, UC Berkeley, and Berkeley Lab report the discovery and characterization of a previously undescribed lineage of form I rubisco - one that the researchers suspect diverged from form I rubisco prior to the evolution of cyanobacteria.

Found through metagenomic analysis of environmental samples and synthesized in a lab, the new lineage, called form I' rubisco, gives researchers new insights into the structural evolution of form I rubisco, potentially providing clues as to how this enzyme changed the planet.

"This could've been what a rubisco looked like before the rise of oxygen more than 2.4 billion years ago," said Shih, noting that the form I' rubisco provides scientists with a window into how ancient microbes might've fixed carbon before the rise of cyanobacteria and the form I rubisco.

An invisible world

Form I rubisco is a hexadecamer, meaning it's built from eight core, large molecular subunits with eight small subunits perched on top and bottom. Each piece of this protein's structure is integral to photosynthesis, and thus the carbon fixation process.

Other functional forms of rubisco exist in bacteria and microorganisms of the Archaea domain. These variants come in different shapes and sizes, and all perform the same step of photosynthesis. However, form I rubisco is responsible for the vast majority of carbon fixation on Earth.

Study co-author and collaborator Professor Jill Banfield, of UC Berkeley's Earth and Planetary Sciences Department, uncovered form I' rubisco after performing metagenomic analyses on groundwater samples. Metagenomic analyses allow researchers to examine genes and genetic sequences from uncultured microorganisms found in the environment.

Using the genes and genetic sequences provided by Banfield, Banda, and Shih successfully expressed form I' rubisco in the lab using E. coli. To learn how this newly identified form functions and how it compares to previously discovered rubisco enzymes, the scientists needed to build precise, 3D models of its structure. For this task, the lead authors turned to Berkeley Lab structural biologists Paul Adams, Henrique Pereira, and Michal Hammel.

First, Adams and Pereira performed X-ray crystallography - an approach that can generate images of molecules with atomic-level resolution - at Berkeley Lab's Advanced Light Source (ALS) (https://als.lbl.gov/). Then, to capture how the enzyme's structure changes during different states of activity, Hammel applied a technique called small-angle X-ray scattering (SAXS) using the SIBYLS beamline (https://sibyls.als.lbl.gov/) at the ALS.

SAXS is a lower-resolution technique, but unlike crystallography - which requires that sample molecules are frozen in crystal form - SAXS is performed in solution. When the data from the two approaches are combined, scientists can construct unprecedented models of complex molecules as they appear in nature.

"Like many enzymes key to life, rubisco has several protein domains connected together, and as it binds with other molecules during the photosynthesis reaction, it will cycle through different arrangements of those domains," said Hammel, a biophysicist in Berkeley Lab's Molecular Biophysics and Integrated Bioimaging (MBIB) Division. "Our techniques really worked hand-in-hand to reveal how this new, novel rubisco behaves in real-world, physiological conditions."

The ALS investigations showed that like form I rubisco, form I' rubisco is built from eight large subunits. However, it doesn't possess the small subunits that were previously thought to be essential to its carbon-fixing function.

The researchers now believe that form I' rubisco represents a missing link in the evolutionary history of form I rubisco's structure.

"The discovery of an octameric rubisco that forms without small subunits allows us to ask [evolutionary] questions about what life would've looked like without the functionality imparted by small subunits," said Banda.

Following the success of the structural investigation into form I' rubisco, Shih has enlisted Hammel, Adams, and Pereira to apply their complementary approach for studies of other crucial plant enzymes, including additional forms of rubisco.

"We've been working together at Berkeley Lab for over 10 years now, and it was really satisfying to be able to see what crystallography and SAXS combined can do to understand biology problems," said Pereira, an MBIB biophysicist. "Once, the scientists who use these different structural biology techniques would have seen themselves as in competition, racing each other to solve structures. But now it's pure collaboration."

The ALS is a Department of Energy (DOE) user facility and JBEI is a DOE Bioenergy Research Center. The crystallography beamline used in this research is operated by the Berkeley Center for Structural Biology and funded by the Howard Hughes Medical Institute. The SIBYLS beamline is supported by the National Cancer Institute grant Structural Biology of DNA Repair and the DOE Office of Science. This work was supported in part by the DOE Office of Science.

Since 2004, Claude Knauf (INSERM) and Patrice Cani (UCLouvain) have been collaborating on molecular and cellular mechanisms in order to understand the causes of the development of type 2 diabetes and above all to identify new therapeutic targets. In 2013, they created an international laboratory, 'NeuroMicrobiota Lab' (INSERM-UCLouvain), to identify links between the brain and intestinal bacteria.

Very quickly, they understood that the gut-brain axis plays a preponderant role in the regulation of sugar in the blood. When we eat, the gut (also called the 'second brain' owing to the neurons that compose it) contracts and digests food. Sugar and fat enter the body and their levels increase in the blood. Using this sugar and fat, the body then does its work or stores them. In a person with diabetes, this process malfunctions and the sugar level increases in abnormal proportions.

Taking a step further, the two researchers observed that the gut, when it digests, sends a signal to the brain, to find out what to do with the incoming fats and sugars. The brain then sends the message to various organs (liver, muscles, adipose tissue) to get ready to lower blood sugar and fat levels. In a diabetic individual, however, this mechanism doesn't work. Researchers have observed that the gut malfunctions and sends no signal to the brain. The cause is hypercontractility of the intestine, which interferes with communication with the brain. Suddenly, commands to get the sugar out of the blood no longer pass. The sugar remains, causing hyperglycaemia. The mechanism also impacts the action of insulin: no message means no insulin action, resulting in insulin resistance.

The researchers sought to understand this hypercontractility, by observing the differences in the constitution of the intestine as well as the action of prebiotics within the microbiota in 'normal' and 'diabetic' mice. They observed that a particular lipid was severely deficient in diabetic mice, but also in people with diabetes (although it's naturally present in the intestines of healthy patients). The team therefore tested the impact of the lipid on the use of sugars, on the contraction of the intestine and, ultimately, on diabetes. NeuroMicrobiota research team members Anne Abot and Eve Wemelle discovered the lipid is the key to restoring the use of sugar. It works by acting directly on the second brain.

Today, the team has discovered and understood how our gut bacteria (or gut microbiota) play an important role in altering the production of bioactive lipids, and from there to restore perfect communication between the gut and the brain. Hence some of these lipids are essential messengers which act on very precise targets in the second brain (enkephalins or opioid receptors). Treatment possibilities include modifying the body's production of such lipids, could or taking them orally. These avenues are under study.

Using the same approach, the INSERM-UCLouvain research team, contributed to the discovery of a new bioactive lipid that reduces intestinal inflammation. It is directly produced by certain gut bacteria, also identified in this study and therefore the two approaches, either the lipid or one or more bacteria, could serve as a therapeutic target.

One in three of the 150,000 humans who die every day is a victim of cardiovascular disease, according to WHO. Half the Belgian population is overweight and presents cardiovascular and type 2 diabetes risks. This UCLouvain and INSERM research could potentially have an impact on a large portion of the population.

Researchers at the University of Massachusetts Amherst have identified a single-measure biomarker in sperm mitochondrial DNA that may predict male reproductive health and pregnancy success.

The discovery applies not just to couples seeking care for infertility but also for the general population. This biomarker could become a more accurate predictor of male infertility than semen parameters, on which health care organizations and clinicians have long relied.

"Clinically, the diagnosis of male infertility really hasn't changed in decades," says UMass Amherst environmental epigeneticist Richard Pilsner, corresponding author of the study published today, Oct. 6, in the journal Human Reproduction. "In the last 10 to 20 years, there have been major advances in the understanding of the molecular and cellular functions of sperm, but the clinical diagnosis hasn't changed or caught up."

In addition to Pilsner, the team of UMass researchers included lead author Allyson Rosati, who wrote the paper as part of her undergraduate honors thesis and recently completed a master's in molecular and cellular biology; Brian Whitcomb, associate professor of epidemiology in the School of Public Health and Health Sciences. They collaborated with reproductive and perinatal epidemiologist Germaine Buck Louis, dean of the College of Health and Human Services at George Mason University, and Sunni Mumford and Enrique Schisterman at the National Institute of Child Health & Human Development.

"This project is a really nice example of interdisciplinary work and team science," Whitcomb says. "This research required measurement of biomarkers in the laboratory combined with statistical modeling. Answering scientific questions like this one benefits from a broad range of expertise."

Mitochondrial DNA is maternally inherited, and sperm mitochondrial DNA copy number (mtDNAcn) typically decreases eight-to-10 fold during spermatogenesis to ensure that it is low upon fertilization. In previous research by Pilsner, Whitcomb and others, increased mtDNAcn and mitochondrial DNA deletions (mtDNAdel) were associated with decreased semen quality and lower odds of fertilization in men seeking fertility treatment.

"The logical next step was to determine if the associations between sperm mitochondrial biomarkers and fertilization among couples seeking infertility treatment could be extended to couples from the general population," Pilsner says.

The researchers accessed sperm samples from the Longitudinal Investigation of Fertility and the Environment (LIFE) study, which recruited 501 couples from Michigan and Texas from 2005 to 2009 to examine the relationships between lifestyle, including environmental chemicals, and human fertility.

They assessed sperm mtDNAcn and mtDNAdel from 384 semen samples and analyzed their association with the probability of pregnancy within one year. They found that men with higher sperm mtDNAcn had as much as 50% lower odds of cycle-specific pregnancy and 18% lower probability of pregnancy within 12 months.

"Remarkably, we saw a strong inverse association between sperm mitochondrial biomarkers and couples' time-to-pregnancy," Pilsner says.

Adds Whitcomb, "Mitochondrial DNA in sperm seems to reflect some underlying physiological phenomenon that affects sperm function."

More research is needed to further examine the impact of changes in mtDNAcn and mtDNAdel, which may result from defective mitochondria or damaged mtDNA. "We need to take advantage of our understanding of the molecular toolkit that we have to develop a better predictor of male fertility, as well as fecundability," Pilsner says.

A next step is to examine the factors mediating the changes in sperm mitochondrial DNA. They could include environmental toxins or other causes of inflammation and oxidative stress, the scientists hypothesize.

"Understanding what is causing the retention of mitochondrial copy number during spermatogenesis will help us come up with better platforms to intervene and to promote better reproductive success," Pilsner says.