Culture

Aerosols are tiny solid or liquid particles suspended in the air. They influence the climate by absorbing or scattering sunlight and serving as cloud condensation nuclei. Moreover, they can impact human well-being through adverse health effects of fine particulate matter.

A large fraction of particulate matter consists of nitrate, sulfate, and ammonium ions. The formation of these major aerosol components is strongly influenced by aerosol acidity, which varies widely between different regions with aerosol pH values ranging from ~1 to ~6. The drivers of these large variations, however, are not clear.

Researchers have now discovered how important the water content and total mass concentration of aerosol particles are for their acidity. A team led by Yafang Cheng and Hang Su from the Max Planck Institute for Chemistry discovered that these factors can be even more important than the dry particle composition. For populated continental areas with high anthropogenic emissions of ammonia from agriculture, traffic, and industry, they found that aerosol pH can be efficiently buffered and stabilized at different levels by the conjugate acid-base pair of ammonium ions and ammonia (NH4+/NH3).

The investigations now published in the interdisciplinary research journal `Science´ started with the question if and how the pH of aerosols is buffered in different continental regions. To address this issue, the scientists from Mainz developed a new theory of multiphase buffering in aerosols, analyzed atmospheric measurement data and performed global model simulations of aerosol composition and acidity.

"It turned out that the acid-base pair NH4+/NH3 is buffering the aerosol pH over most populated continental areas, even though the acidity may vary by multiple pH units", says Yafang Cheng, Minerva Research Group leader at the Max Planck Institute for Chemistry. "Variations in water content are responsible for 70-80 percent of global variability in aerosol pH in ammonia-buffered regions, which was not previously known and can be explained by our new multiphase buffer theory", she adds.

In particular, the Max Planck researchers used their model to compare aerosol composition and acidity for two very different geographic regions and conditions. In the southeastern United States during summer, the air is clean, and the few atmospheric aerosol particles contain little water at pH values around ~1, whereas there are typically high aerosol concentrations with high water content at pH values around ~5 over the North China Plain in winter. "We find that these large differences in aerosol pH are primarily due to differences in aerosol loading and water content rather than differences in the nitrate content as assumed in earlier studies," explains Guangjie Zheng, a postdoc in Yafang Cheng's group.

"Globally, ~70% of urban areas are in the ammonia-buffered regime", summarizes Hang Su, scientific group leader in the Multiphase Chemistry Department of the institute. "Thus, the newly discovered multiphase buffer mechanism is important to understand haze formation and aerosol effects on human health and climate in the Anthropocene."

The results of the team around Cheng and Su not only imply that aerosol pH and atmospheric multiphase chemistry are strongly affected by the pervasive human influence on ammonia emissions and the nitrogen cycle in the Anthropocene. They also improve the understanding how air pollution develops and thus provide an important approach for possible control measures.

Ever since the first cases of a mysterious disease in the early 1980s exploded into the HIV/AIDS pandemic, researchers have been searching for ways to outsmart the deadly virus. Now thanks to anti-retroviral therapy, people living with HIV can live relatively normal lifespans--as long as they take their medications every day.

"If they ever stop, in short order the virus rebounds and resets at the high levels seen before starting-- and that seems to be the case even after decades of therapy," says Mark Painter, Ph.D., a graduate student in the University of Michigan Medical School's department of microbiology and immunology.

The reason is that HIV can hide inside the human genome, lying dormant and ready to emerge at any time. Because of this, a true cure for HIV relies on waking the latent virus and eliminating it before it has a chance to again take hold of the body's cells, an approach known as shock and kill.

Working with a team under the direction of Kathleen Collins, M.D., Ph.D., they set out to find a weapon to kill HIV by targeting a protein called Nef. In 1998, Collins, who is a professor of internal medicine and microbiology and immunology, discovered that HIV uses Nef to evade the body's immune system by overriding the functioning of a protein on a cell's surface that lets immune cells know that the cell is infected and in need of elimination. By disabling this protein, called MHC-I, infected cells are able to proliferate.

The research tried determine if there was an FDA-approved drug or molecule already on the market that could override Nef, restore the functioning of MHC-I and allow the body's own immune system, specifically cells known as cytotoxic T lymphocytes, to recognize the HIV-infected cells and destroy them.

"We started out screening a library of 200,000 small molecules and found none inhibited Nef," says Painter. Undeterred, they approached David Sherman, Ph.D. of the U-M Life Sciences Institute, whose lab studies the biosynthesis of natural products from microbes, such as cyanobacteria.

"Often synthetic molecules have quite a low molecular weight, meaning they are fairly small. And if you need to disrupt a large protein surface or interface, such as with Nef, a small molecule won't work well or at all," explains Sherman. "A natural products library like the one at the LSI, on the other hand, is going to have molecules with a large range of weights and sizes."

After screening approximately 30,000 molecules, they discovered that a class of antibiotic molecules called pleicomacrolides inhibited Nef.

"Pleicomacrolides are widely used in lab experiments when you want to shut down the lysosome. Because of this, they are considered toxic and risky to use as drugs," says Painter. The lysosome is an essential cell organelle used to break down worn out cell parts, viruses and bacteria.

However, the team determined that a pleicomacrolide called concanamycin A inhibits Nef at much lower concentrations than those needed to inhibit the lysosome. "As a lead compound for drug development, it's fairly exciting because we can use a very low dose, and inhibit Nef without short-term toxicity to the cells," said Painter.

In a proof of concept experiment, they treated HIV-infected, Nef expressing cells with concanamycin A and found that cytotoxic T cells were able to clear the infected T cells.

"It's been extremely gratifying for this project, which began in my lab over a decade ago to finally come to fruition. I had hoped we would find something that worked as well as this compound does but it was never a guarantee that we would actually be successful. This type of research is risky but extremely important because of the potential reward," says Collins. But, she adds, the molecule is not yet ready to be used as a drug for treatment of HIV infected people. "More research will be needed to optimize the compound. We will need to further separate the potent Nef inhibitory activity from the more toxic effect on lysosomal function to make it a viable therapy."

Collins, Painter and their colleagues are continuing work on refining the chemistry of concanamycin A to make it even more viable as a potential therapy. When combined with ART and future treatments that shock latent HIV awake, Painter notes the therapy could be used to clear any remaining virus, essentially curing HIV.

CHAPEL HILL, NC - September 10, 2020 - UNC-Chapel Hill researchers have, for the first time, determined the high-resolution structure of a key DNA-sensing protein in the innate immune system called cGAS while it is bound to the nucleosome - the all-important unit of DNA packaging inside a cell's nucleus.

This research, published in Science, reveals in detail how the nucleosomes inside our cells block cGAS from unintentionally triggering the body's innate immune response to our own DNA. The work was led by Qi Zhang, PhD, associate professor of biochemistry and biophysics at the UNC School of Medicine, and Robert McGinty, MD, PhD, assistant professor of chemical biology and medicinal chemistry at the UNC Eshelman School of Pharmacy.

"Detecting and responding to foreign DNA from bacterial and viral pathogens is one of the most fundamental mechanisms for host defense," said Zhang, co-senior author. "A deeper understanding of functions and regulations of this important DNA sensor will have profound impacts on both basic research and translational development of cGAS-targeted therapeutics crucial to the betterment of human health."

McGinty, co-senior author, said, "This work was enabled by recent advances in cryo-electron microscopy technology that allows scientists, like those on our team, to observe the protein machines inside our cells with unprecedented clarity. By seeing how these proteins function normally, we can gain insights into how to manipulate their functions to treat diseases."

In the mammalian innate immune system, the protein cyclic GMP-AMP synthase (cGAS) detects foreign or damaged "self" DNAs. Upon DNA detection, cGAS synthesizes cyclic GMP-AMP (cGAMP), the second messenger molecule that activates the cGAS-STING signaling pathway to fight infections, inflammatory diseases, and cancers.

Because cGAS is a "universal" DNA sensor, it must be regulated to differentiate pathogenic DNA from the body's own healthy DNA to avoid any unintended immune responses. Previous research has shown that cGAS is enriched inside the nucleus where our genomic DNA is stored, but it remains a mystery as how cGAS ignores our own healthy DNA.

Using the UNC School of Medicine state-of-the-art Cryo-Electron Microscopy Core Facility, which was established in 2019, the Zhang and McGinty labs determined a 3.3Å-resolution cryo-EM structure of cGAS in complex with the nucleosome. The structure shows that cGAS employs two conserved amino acids to anchor to a negatively charged patch on the nucleosome surface. These protein-protein interactions allow the nucleosome to occupy a critical DNA sensing surface on cGAS and prevent cGAS from entering its functionally active DNA-bound state. Together with mutagenesis and functional assays, this study provides a near-atomic resolution depiction of how cGAS maintains the resting, inhibited state in the nucleus.

"These findings reshape the current paradigm of cGAS regulation and exemplify the role of the nucleosome in regulating diverse protein functions," said McGinty, who holds a joint faculty appointment at the UNC School of Medicine.

Zhang added, "Biomedical scientists will be able to apply our research to fields such as immunology, cancer biology, and gene regulation, as well as to drug discovery for infections, inflammatory diseases, and cancers."

The UNC School of Medicine laboratory of Camille Ehre, PhD, Assistant Professor of Pediatrics, produced striking images in respiratory tract cultures of the infectious form of the SARS-CoV-2 virus produced by infected respiratory epithelial cells. The New England Journal of Medicine featured this work in its "Images in Medicine" section.

Ehre, a member of the UNC Marsico Lung Institute and the UNC Children's Research Institute, captured these images to illustrate how intense the SARS-CoV-2 infection of the airways can be in very graphic and easily understood images. Her lab conducted this research in collaboration with the labs of Ralph Baric, PhD, the William R. Kenan Distinguished Professor of Epidemiology at the UNC Gillings School of Public Health, who holds a joint faculty appointment at the UNC Department of Microbiology and Immunology, and Richard Boucher, MD, the James C. Moeser Eminent Distinguished Professor of Medicine and Director of the Marsico Lung Institute at the UNC School of Medicine.

In a laboratory setting, the researchers inoculated the SARS-Co-V-2 virus into human bronchial epithelial cells, which were then examined 96 hours later using scanning electron microscopy.

The images, re-colorized by UNC medical student Cameron Morrison, show infected ciliated cells with strands of mucus (yellow) attached to cilia tips (blue). Cilia are the hair-like structures on the surface of airway epithelial cells that transport mucus (and trapped viruses) from the lung. A higher power magnification image shows the structure and density of SARS-CoV-2 virions (red) produced by human airway epithelia. Virions are the complete, infectious form of the virus released onto respiratory surfaces by infected host cells.

This imaging research helps illustrate the incredibly high number of virions produced and released per cell inside the human respiratory system. The large viral burden is a source for spread of infection to multiple organs of an infected individual and likely mediates the high frequency of COVID-19 transmission to others. These images make a strong case for the use of masks by infected and uninfected individuals to limit SARS-CoV-2 transmission.

Volcanoes are born and die - and then grow again on their own remains. The decay of a volcano in particular is often accompanied by catastrophic consequences, as was the most recent case for Anak Krakatau in 2018. The flank of the volcano had collapsed sliding into the sea. The resulting tsunami killed several hundred people on Indonesia's coast.

Continued volcanic activity after a collapse has not been documented in detail so far. Now and for the first time, researchers from the German Research Center for Geosciences GFZ and Russian volcanologists are presenting the results of a photogrammetric data series spanning seven decades for the Bezymianny volcano, Kamchatka, in the journal Nature Communications Earth and Environment. First author Alina Shevchenko from GFZ says, "thanks to the German-Russian cooperation we were able to analyze and reinterpret a unique data set".

Bezymianny had a collapse of its eastern sector in 1956. Photographs of helicopter overflights from Soviet times in combination with more recent satellite drone data have now been analyzed at GFZ Potsdam using state-of-the-art methods. The images show the rebirth of the volcano after its collapse. The initial re-growth began at different vents about 400 meters apart. After about two decades, the activity increased and the vents slowly moved together. After about fifty years, the activity concentrated on a single vent, which allowed the growth of a new and steep cone.

The authors of the study determined an average growth rate of 26,400 cubic meters per day - equivalent to about a thousand large dump trucks. The results make it possible to predict when the volcanic building may once again reach a critical height, so that it may collapse again under its own weight. The numerical modeling also explains the changes in stress within the volcanic rock and thus the migration of the eruption vents. Thomas Walter, volcanologist at the GFZ and co-author of the study, summarizes: "Our results show that the decay and re-growth of a volcano has a major impact on the pathways of the magma in the depth. Thus, disintegrated and newly grown volcanoes show a kind of memory of their altered field of stress". For future prognosis, this means that the history of birth and collapse must be included to be able to give estimates about possible eruptions or imminent collapses.

AURORA, Colo. (Sept. 9, 2020) - Researchers at the University of Colorado College of Nursing at the Anschutz Medical Campus found that a unique set of factors of the emergency department (ED) makes standard Clinical Decision Support (CDS) systems not as effective in helping to reduce antibiotic overprescribing in that environment.

Antimicrobial resistance is a major public health concern, accounting for 2.8 million infections and 35,000 deaths annually. Hospitals have focused on antibiotic stewardship programs (ASP) to reduce over prescribing of antibiotics, which is a major contributor to antimicrobial resistance. While this has been effective in reducing unnecessary antibiotic use by as much as 36% in inpatient settings, EDs are an exception where approximately 10 million outpatient antibiotic prescriptions are written annually in the US. Data show that up to 50% of the prescriptions were inappropriate or unnecessary.

The study, published in Applied Clinical Informatics, looked at three pediatric EDs to determine how the unique setting of the ED influences this pattern, and how Clinical Decision Support (CDS) systems can complement professional judgment in the ED setting and potentially reduce unnecessary antibiotic use. "The ED is unique. Several factors are at play - clinical judgment, provider fatigue, the busyness of the ED, workflow, technology, bed availability, social determinants of health of the patient and their families. said lead author Associate Professor Mustafa Ozkyanak, PhD. "These all impact antibiotic prescribing decisions."

The study of 38 ED providers analyzed these and additional factors to determine how to design a CDS system to assist with antimicrobial stewardship in pediatric emergency departments. It discovered that systems are rarely tailored to the context of the ED environment and end-user needs.

"ED clinicians often need to make rapid decisions and are frequently interrupted during the decision-making process," said Ozkaynak. Current CDS systems do not take this unique set of circumstances into account. "Significant opportunities exist to improve the appropriateness of antibiotic prescribing in the ED setting. Including relevant contextual data, considering the limitations of current CDS systems, and tailoring the design and implementation could all help in reducing unnecessary antibiotic use."

Tsukuba, Japan - It may sound like something out of a science fiction B-movie, but with the help of a mutant tomato, researchers from Japan have discovered that the development process of fruit rewires their central metabolism pathway.

In a study published this month in Proceedings of the National Academy of Sciences of the United States of America (PNAS), researchers from the University of Tsukuba have revealed that "fruit set"--the fruit development process in plants--rewired the central metabolism pathway in tomatoes via an increased sensitivity to the plant hormone gibberellin.

Tomatoes, although commonly thought of as vegetables, are actually fruit. Fruit set is the process whereby plant ovaries develop into fruits after pollination and fertilization, and in tomatoes the process is triggered by gibberellin. But the role of this hormone in the metabolic processes of fruit-setting ovaries is still mostly unknown.

"Pollination is usually key to bringing on fruit set, because it stimulates the buildup of plant growth hormones, including gibberellin, inside fertilized ovaries," says lead author of the study Professor Tohru Ariizumi. "Gibberellins stimulate aspects of plant development, such as fruit set, and trigger rapid ovary growth."

To examine fruit set in tomatoes, the researchers used multi-omics--specifically, looking at all the RNA, proteins, and small-molecule metabolites produced during metabolism--and enzyme activity data. Additionally, they used kinetic modelling to look at the earliest processes that occur during fruit set. Ovary growth during fruit set was measured using wild-type and procera mutant tomatoes, which are hypersensitive to gibberellin.

"Applying hormones like gibberellin to ovaries or genetic mutations in the negative regulatory genes of hormone cascades can bring on parthenocarpy," explains Professor Ariizumi. "Parthenocarpy is fruit set that is independent of pollination."

Gibberellins are signaling molecules that trigger signal transduction cascades--i.e., they activate or repress downstream genes that are responsible for carrying out particular developmental and growth processes.

"Our study looked at the biochemical mechanisms of fruit set. Our analysis was able to define the genes, proteins, enzymes and metabolites that were consistently affected by both pollination and procera-induced parthenocarpy, and highlighted that the central metabolism was consistently rewired," says Professor Ariizumi.

The results of this study contribute to a better understanding of fruit set metabolism, which will lead to new strategies for production. In particular, it may be possible to breed for parthenocarpic fruits (which are seedless), and to increase control of fruit survival during the early stages of development.

The article, "Fruit setting rewires central metabolism via gibberellin cascades," was published in Proceedings of the National Academy of Sciences of the United States of America (PNAS) at DOI: 10.1073/pnas.2011859117

Hartford, CT - Links between obesity and complications of COVID-19 have received increasing attention throughout the ongoing pandemic. But a different aspect of body weight - the social stigma that people face because of their weight - may also have harmful implications for people's health during the pandemic.

New research from the UConn Rudd Center for Food Policy and Obesity and the University of Minnesota shows that young adults who experienced weight stigma before the pandemic have higher levels of depressive symptoms, stress, eating as a coping strategy, and are more likely to binge-eat during COVID-19 compared to those who haven't experienced weight stigma.

Over the last decade, considerable evidence has documented harmful health consequences for people who are teased, bullied, stigmatized, or treated unfairly because of their body weight. Based on this knowledge, researchers wanted to learn whether such weight mistreatment predicts health behaviors during COVID-19 that may worsen health, especially in this time period of increased anxiety and stress for many Americans.

"Understanding whether weight stigma elevates risk for health challenges during the pandemic represents a critical first step for the development of health messaging, responses, and support during outbreaks of COVID-19 and similar public health emergencies," says lead author of the study Rebecca Puhl, professor of Human Development & Family Sciences and Deputy Director at the University of Connecticut's Rudd Center.

The study, published in the Annals of Behavioral Medicine, reports findings from 584 young adults enrolled in the population-based longitudinal EAT (Eating and Activity over Time) 2010-2018 study, who were invited to complete a follow-up survey during the COVID-19 outbreak. Weight stigma reported previously by these participants in 2018 was examined as a predictor of binge eating, eating to cope, physical activity, depressive symptoms, and stress during COVID-19.

Key findings include:

Pre-pandemic experiences of weight stigma in 2018 predicted higher levels of stress, depressive symptoms, eating to cope with stress, and binge eating among young adults during the COVID-19 pandemic.

The likelihood of engaging in binge eating during the pandemic was almost 3 times higher for people who had experienced weight stigma prior to the pandemic compared to those who hadn't.

Weight stigma predicted these health consequences for both males and females, regardless of their body weight.

Weight stigma predicted these worse health outcomes during both time periods of initial stay-at-home restrictions and after such restrictions had been lifted during the COVID-19 outbreak.

"Our findings importantly identify weight stigma, independent of BMI, as a factor that may worsen eating behaviors and psychological distress for young adults during this pandemic. These increased health risks, particularly for binge eating, indicate a need for supportive and educational resources to help lessen the negative impact of stigma on eating behaviors," says Dianne Neumark-Sztainer, professor at the University of Minnesota and principal investigator of the EAT cohort study.

"This research highlights the relevance of weight stigma to the COVID-19 pandemic," adds Puhl. "With additional outbreaks and more cases of COVID-19 expected in the coming months, it is important to support individuals who may be prone to worse health and health behaviors exacerbating their risk during these times of pandemic. Weight stigma warrants attention in research and discourse related to COVID-19 and should be considered in public health messaging."

A recent study that examined the psychological health of pregnant women during the COVID-19 outbreak uncovered fear and depression in many participants. The findings are published in the Journal of Clinical Nursing.

In an online questionnaire completed in February 2020 by 331 pregnant women in China without COVID-19, participants were mostly worried about the following: "potential infected people were unprotected and non-isolated," "self-infection could affect the health of their baby," and "they themselves becoming infected and being isolated" (83.1%, 78.6% and 56.2%, respectively).

Women's psychological responses to the COVID-19 outbreak increased pregnancy stress, whereas their sense of security decreased pregnancy stress.

The authors urged clinicians to promptly evaluate pregnant women's psychological responses and provide them with guidance to enhance their sense of security and alleviate their fears related to COVID-19.

"If a pregnant woman is diagnosed or suspected of COVID-19 infection, it may induce different degrees of psychological stress such as fear and anxiety, which would not be conducive to the mother's or child's health," said co-author Xiu-Min Jiang, RN, of Fujian Maternity and Child Health Hospital, in China. "It is essential for the health staff to build trust with pregnant women and their families, and to communicate accurate information to them during COVID-19 outbreak."

URL Upon Publication: https://onlinelibrary.wiley.com/doi/10.1111/jocn.15460

Emerging evidence suggests that obstructive sleep apnea (OSA) may negatively affect bone health. Results from a new study published in the Journal of Bone and Mineral Research now indicate that women with history of OSA may face a higher risk of spine, or vertebral, fractures.

Using information from the Nurses' Health Study, investigators examined data pertaining to 55,264 women without a prior history of bone fractures. OSA was self-reported in 1.3% of participants in 2002 and increased to 3.3% by 2012. Between 2002 and 2014, 461 vertebral fractures and 921 hip fractures occurred.

Women with a history of OSA had a 2-fold higher risk of vertebral fracture relative to those with no OSA history, with the strongest association observed for OSA associated with daytime sleepiness. No association was observed between OSA history and risk of hip fracture.

"Our study provides important evidence at the population level that obstructive sleep apnea may have an adverse impact on bone health that is particularly relevant to the development of vertebral fracture," said lead author Tianyi Huang, ScD, of Brigham and Women's Hospital. "Given that we used self-reported clinical diagnoses of sleep apnea and fracture in our study, future studies could use more deeply characterized data to further the understanding of the mechanisms linking sleep apnea to bone health and fracture risk."

Results from a new study suggest that lifestyle changes may help to improve cognition in older adults experiencing cognitive decline that precedes dementia.

In the study published in the Journal of the American Geriatrics Society, 119 individuals older than 65 years of age who were experiencing cognitive decline were randomized to a control group or an intervention group for 8 weeks. The control group received online information related to dementia and lifestyle risk factors, Mediterranean diet, physical activity, and cognitive engagement.

Participants were instructed to implement this information into their own lifestyles. The intervention group received the same online information, plus active components to assist with implementing this information into their lifestyles: dietitian sessions, an exercise physiologist session, and online brain training.

Over 6 months of follow-up, investigators noted that participants in the intervention group were able to improve their lifestyle and had higher cognition scores than those in the control group. The results suggest that lifestyle-based changes may modify the course of cognitive decline.

"We've known for some time that lifestyle changes such as these can reduce dementia risk in the general population. What this study adds is that with the right intervention, people experiencing cognitive decline may retain sufficient neuroplasticity for their brain to 'bounce back' from decline," said lead author Mitchell McMaster, a PhD student at The Australian National University.

A recent analysis published in Campbell Systematic Reviews indicates that body cameras worn by police do not have clear or consistent effects on officers' use of force, arrests, or other activities. Nor do they have significant effects on citizens' calls to police or assaults or resistance against officers. Body-worn cameras can reduce the number of citizen complaints against police officers, but it is unclear whether this finding signals an improvement in the quality of police-citizen interactions or a change in reporting.

The analysis summarizes evidence from 30 studies on the effects of body-worn cameras on various officer and citizen behaviors.

"For the police agencies that have already purchased body-worn cameras, researchers should continue testing for ways in which both police and citizens might gain benefits from the cameras' continued use," said lead author Cynthia Lum, PhD, of George Mason University. "These could include limiting the discretion that officers have with body-worn camera use; using body-worn cameras for coaching, training, or evidentiary purposes; and finding ways that body-worn cameras can be used to strengthen police-citizen relationships, internal investigations, or accountability systems."

Children born to mothers who had diabetes during pregnancy may age faster biologically and be at an increased risk for obesity and high blood pressure, according to Rutgers researchers.

The study, published in the journal Epigenetics, explored how more than 1,000 children born to mothers in China aged on a cellular level. Researchers examined their exposure to gestational diabetes in utero and their DNA methylation, or epigenetic age, which indicates how experiences and exposures reflect true biological age even in early childhood.

Accelerated aging, which can be determined by evaluating if a person's estimated DNA methylation age is greater than their chronological age, has been shown to be associated with cardiovascular risks and poor health outcomes later in life.

The researchers measured the epigenetic age of 1,156 children who were ages 3 to 10 in Tianjin, China, to see how it differed from their chronological age. They found that children born to mothers who had diabetes while pregnant had a higher epigenetic age -- or were "older" than their actual age -- and that this epigenetic age is associated with higher weight, body mass index, body fat percentage, upper-arm circumference and blood pressure.

"These findings suggest that gestational diabetes may have long-term effects on epigenetic aging in offspring and lead to poorer cardiometabolic health outcomes," said lead author Stephanie Shiau, an instructor at the Rutgers School of Public Health.

The findings support the need for further studies using longitudinal samples to evaluate the association between epigenetic age and later onset of adult metabolic diseases.

In the United States, between 2 percent to 10 percent of pregnancies are affected by the condition annually, according to the National Institutes of Health.

Researchers at the University of Cambridge and the University of Zurich have discovered that a drug newly approved for cancer improves kidney dysfunction in a mouse model of Dent disease 2 and Lowe syndrome

The study is published today in Kidney International and offers hope for the first disease-modifying treatment. In addition to kidney dysfunction, characteristic of Dent disease 2, boys with Lowe syndrome also require eye cataract surgery as newborns, and suffer seizures and other disabilities. Only supportive treatments are available, such as nutrient supplements and help with learning.

These rare diseases are caused by the lack of an enzyme called OCRL that normally controls the lipid composition of cell membranes. The disruption activates a system of filaments inside the cells, called the actin cytoskeleton, in the wrong place. The actin blockage means that the cells in the kidneys that usually reabsorb filtered proteins and essential nutrients don't work properly, causing a loss of these in the urine.

Dr Jennifer Gallop's group at the Wellcome Trust/ Cancer Research UK Gurdon Institute in Cambridge worked out how the actin system was being activated by the disruption in cell membrane lipids. "By understanding the details of what is happening in cells during Lowe syndrome and Dent disease 2," said Dr Gallop, "we realised that alpelisib, a drug that is already approved for use in patients with cancer, could prevent the actin blockage". This is because alpelisib targets a different step in the pathway, and rebalances the lipid composition.

The Gallop group teamed up with Professor Oliver Devuyst from the Institute of Physiology, University of Zurich to test alpelisib in a humanized mouse model of Lowe syndrome and Dent disease 2. Devuyst said "amazingly, treatment with alpelisib improved the actin cytoskeleton of the kidney cells and rescued the reabsorption of the filtered proteins".

The researchers don't yet know whether the drug will work in patients and if their neurological symptoms will be helped as well. However, because alpelisib has been used before in another rare disease in children, as well as in adults, there is evidence that it is safe. These efforts of repurposing a drug could potentially lead to the cost-effective development of a treatment for these rare disorders.

With life expectancy increasing, age-related diseases are also on the rise, including sarcopenia, the loss of muscle mass due to aging. Researchers from the University of Basel's Biozentrum have demonstrated that a well-known drug can delay the progression of age-related muscle weakness.

Already in our best years, our muscles begin to shrink and their strength dwindles. Unfortunately, this is a natural part of aging. For some people, the decline in muscle mass and function is excessive. This condition, called sarcopenia, affects every second or third person over 80, reducing mobility, autonomy and quality of life.

The causes of sarcopenia are diverse, ranging from altered muscle metabolism to changes in the nerves supplying muscles. Researchers led by Professor Markus Rüegg have now discovered that mTORC1 also contributes to sarcopenia and its suppression with the well-known drug rapamycin slows age-related muscle wasting.

Rapamycin preserves muscle function

"Contrary to our expectations, the long-term mTORC1 suppression with rapamycin is overwhelmingly beneficial for skeletal muscle aging in mice, preserving muscle size and strength," says Daniel Ham, first author of the study. "Neuromuscular junctions, the sites where neurons contact muscle fibers to control their contraction, deteriorate during aging. Stable neuromuscular junctions are paramount to maintaining healthy muscles during aging and rapamycin effectively stabilizes them." The researchers also demonstrate that permanently activating mTORC1 in skeletal muscle accelerates muscle aging.

Molecular signature of sarcopenia

In collaboration with Professor Mihaela Zavolan's team, the scientists identified a molecular ?signature? of sarcopenia, with mTORC1 as the key player. To help the scientific community further investigate how gene expression in skeletal muscle changes during aging or in response to rapamycin treatment, they developed the user-friendly web application, SarcoAtlas, which is supported by sciCORE, the Center for Scientific Computing at the University of Basel.

There is currently no effective pharmacological therapy to treat sarcopenia. This study provides hope that it may be possible to slow down age-related muscle wasting with treatments that suppress mTORC1 and thereby extend the autonomy and life quality of elderly people.