Publisher Health

New findings from Cleveland Clinic researchers show for the first time that the gut microbiome impacts stroke severity and functional impairment following stroke. The results, published in Cell Host & Microbe, lay the groundwork for potential new interventions to help treat or prevent stroke.
The research was led by Weifei Zhu, Ph.D., and Stanley Hazen, M.D., Ph.D., of Cleveland Clinic’s Lerner Research Institute. The study builds on more than a decade of research spearheaded by Dr. Hazen and his team related to the gut microbiome’s role in cardiovascular health and disease, including the adverse effects of TMAO (trimethylamine N-oxide) — a byproduct produced when gut bacteria digest certain nutrients abundant in red meat and other animal products.
“In this study we found that dietary choline and TMAO produced greater stroke size and severity, and poorer outcomes in animal models,” said Dr. Hazen, chair of the Department of Cardiovascular & Metabolic Sciences and director of Cleveland Clinic’s Center for Microbiome & Human Health. “Remarkably, simply transplanting gut microbes capable of making TMAO was enough to cause a profound change in stroke severity.”
Previously, Dr. Hazen and his team discovered that elevated TMAO levels can lead to the development of cardiovascular disease. In clinical studies involving thousands of patients, they have shown that blood levels of TMAO predict future risk of heart attack, stroke and death -findings that have been replicated around the world. Earlier studies, also led by Drs. Zhu and Hazen, were the first to show a link between TMAO and enhanced risk for blood clotting.
“This new study expands on these findings, and for the first time provides proof that gut microbes in general — and through TMAO specifically — can directly impact stroke severity or post-stroke functional impairment,” said Dr. Hazen.
The researchers compared brain damage in preclinical stroke models between those with elevated or reduced TMAO levels. Over time, those with higher levels of TMAO had more extensive brain damage and a greater degree of motor and cognitive functional deficits following stroke. The researchers also found that dietary changes that alter TMAO levels, such as eating less red meat and eggs, impacted stroke severity.
“Functionality after a stroke — which occurs when blood flow to the brain is blocked — is a major concern for patients,” said Dr. Hazen, who is also co-section head of Preventive Cardiology & Cardiac Rehabilitation in Cleveland Clinic’s Miller Heart, Vascular & Thoracic Institute. “To understand if choline and TMAO affect post-stroke functionality, in addition to stroke severity, we compared performance on various tasks pre-stroke, and then both in the short- and long-term following stroke.”
The team found that a gut microbe enzyme critical to TMAO production called CutC drove heightened stroke severity and worsened outcomes.
According to Dr. Zhu, targeting this gut microbe enzyme may be a promising approach to prevent stroke. “When we genetically silenced the gut microbe gene that encodes CutC, stroke severity significantly diminished,” she said. “Ongoing research is exploring this treatment approach, as well as the potential for dietary interventions to help reduce TMAO levels and stroke risk, since both a Western diet and a diet rich in red meat are known to elevate TMAO levels. Switching to plant-based protein sources helps to lower TMAO.”
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Postdoctoral Researcher Outi Keinänen from the University of Helsinki developed a method to radiolabel plastic particles in order to observe their biodistribution on the basis of radioactivity with the help of positron emission tomography (PET). As a radiochemist, Keinänen has in her previous radiopharmaceutical studies utilised PET imaging combined with computed tomography (CT), which produces a very accurate image of the anatomical location of the radioactivity signal.
In the recently completed study, radiolabelled plastic particles were fed to mice, and their elimination from the body was followed with PET-CT scans. This was the first time that the movement and location of plastic particles in a living mammalian system were observed in real time.
The study utilised polystyrene particles of four different sizes: 20 nm, 220 nm, 1 µm and 6 µm. The journey of the radiolabelled plastic particles through the gastrointestinal tract was followed for two days (48 hours) through PET-CT scans.
The study, which was recently published in Scientific Reports journal, demonstrated that most of the particles had been eliminated from the mice naturally, through faeces within two days. Not much translocation of plastic particles from the gastrointestinal tract to elsewhere in the body was seen, and the smallest particles were eliminated from the body at a faster rate than the larger ones.
In addition to PET imaging, the findings were verified by thoroughly measuring the radioactivity of the tissues and organs of the mice. The persistence of the radiolabel on the surface of the plastic particles was verified by collecting murine gastrointestinal tracts at several different time points after administering the particles. The gastrointestinal tracts of mice that were put down at different timepoints were cut open, ground and separated into several fractions based on size. The share of the non-attached radiolabel was very small compared to the radiolabel still attached to the plastic particles. This was proof that the monitored radiation signal described the passage of the plastic particles well.
First and foremost, the study surveyed the usefulness of PET imaging in the study of micro- and nanoplastics, demonstrating that PET imaging enables accurate and non-invasive observation of plastic particles in living animals. Consequently, PET imaging may well become an important element of investigations into the health effects of plastics on mammals.
“While only a single small dose of polystyrene particles was fed to the mice, people are exposed daily to a range of micro- and nanoplastics. Therefore, we cannot draw direct conclusions on the accumulation of plastics in mammals and their effects on the basis of this study alone,” Keinänen notes.
“In addition to ingesting plastics, the air we breathe contains small particles of plastic. Further studies are in fact in the pipeline,” Keinänen promises.
Next up, the researchers wish to investigate the long-term consequences of daily exposure to micro- and nanoplastics, as well as the accumulation of inhaled plastic particles in mice. In future projects, the aim is to use different plastic materials in addition to polystyrene, the type of plastic used in this study.
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Alternative splicing can lead to the formation of numerous protein variants. For the first time, alternative splicing has now been systematically analysed for the family of glutamate receptors.
Proteins are encoded by genes — however, this information is divided into small coding sections, which are only assembled during a process called splicing. Various combinations are possible, some of which are still unknown. Dr. Robin Herbrechter and Professor Andreas Reiner from the junior research group Cellular Neurobiology at Ruhr-Universität Bochum (RUB) now systematically analysed alternative splicing in the family of ionotropic glutamate receptors (iGluRs), which is essential for signal processing in the brain. These findings were published in the journal Cellular and Molecular Life Sciences on 8 June 2021.
Huge splicing diversity in the brain
The human genome was sequenced around 20 years ago. Since then, the sequence information encoding our proteins is known — at least in principle. However, this information is not continuously stored in the individual genes, but is divided into smaller coding sections. These coding sections, also known as exons, are assembled in a process called splicing. Depending on the gene, different exon combinations are possible, which is why they are referred to as different or alternative splicing combinations.
Almost all 20,000 human genes can be alternatively spliced. A particularly huge variety of different splice variants is found in the brain, which allows for creating a huge diversity and allows to adapt the proteins to specific requirements. “However, it is not easy to determine, which protein variants are actually present,” says Andreas Reiner. “Sequencing of already-spliced messenger RNAs (mRNAs), so-called RNA-Seq data, which are now increasingly being obtained with high-throughput approaches, offers a way out.” Robin Herbrechter and Andreas Reiner now used such data to obtain an overview of all ionotropic glutamate receptor splice variants.
New glutamate receptor variants detected
Using bioinformatic methods, the researchers aligned billions of mRNA sequence snippets to the genome to reconstruct the frequency of individual splice events. This method also enabled them to detect new, previously unknown splice variants. There were quite a few surprises: the systematic analysis showed that some variants found in the previously studied model organisms mouse and rat do not occur in humans at all, or are much less abundant than previously assumed.
“Among the newly identified isoforms, some are particularly exciting, as they are quite different from the previously known variants and could thus have new functions,” says Robin Herbrechter. This includes a protein domain formed by the gene of the GluA4 AMPA receptor, as well as the first description of a delta receptor 1 (GluD1) isoform. While the focus will now be on analysing these variants, also further bioinformatic analyses are planned, for example to determine which cell types produce the different splice variants.
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Research published today in the Journal of General Virology has identified missed cases of SARS-CoV-2 by retrospective testing of throat swabs.
Researchers at the University of Nottingham screened 1,660 routine diagnostic specimens which had been collected at a Nottingham hospital between 2 January and 11 March 2020 and tested for SARS-CoV-2 by PCR. At this stage of the pandemic, there was very little COVID-19 testing available in hospitals, and to qualify patients had to meet a strict criterion, including recent travel to certain countries in Asia or contact with a known positive case.
Three previously unidentified cases of SARS-CoV-2 infection were identified by the retrospective screening, including one from a 75-year-old female whose positive swab was collected on 21 February 2020. This patient, referred to as Patient 1, died on 3 March; two days before the first official death from COVID-19 was recorded in the UK. Patient 1 had not recently travelled abroad or been in contact with anyone known to have COVID-19 and so did not qualify for a PCR test at the time. In addition to being the first death, the researchers believe that Patient 1 is also the earliest described case of community transmission in the UK.
The further newly-identified cases occurred in a 64-year-old male and a 66-year-old male, both of whom showed signs of chest infections, and both of whom recovered. The samples were collected on 2 March and 8 March 2020 respectively. International travel was only removed as an essential criterion for a SARS-CoV-2 test on 12 March 2020.
The research group collaborated with the COVID-19 Genomics UK Consortium (COG-UK) to sequence the SARS-CoV-2 isolates collected from the swabs used in the study, and found evidence of community transmission in Nottingham as early as February 2020. Through this genome sequence data, the group identified multiple introductions of the virus into Nottingham during late February and the month of March, many of which were a distinct lineage of the virus which dominated early phases of the outbreak within the region.
Based on the findings, the researchers suggest that testing should have been made available to hospital patients with compatible symptoms but no travel history earlier in the pandemic response.
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Research published in the journal ACS Materials and Interfaces has provided new understanding of how false-negative results in Lateral Flow Tests occur and provides opportunity for simple improvements to be made.
Lateral Flow Devices were introduced late in 2020 on a global scale to help detect novel coronavirus infection in individuals, with test results produced rapidly in half an hour or less. However, their potential has been somewhat hindered by inadequate sensitivity, with a high number of false-negative results.
Using X-ray fluorescence imaging from Diamond Light Source, researchers from King’s College London set out to identify what could be causing these false-negative results, and what potential modifications could enable increased accuracy.
They identified that the underlying technology of many Lateral Flow Devices is highly accurate and able to theoretically detect trace amounts of the COVID-19 virus, but the limitations fall to the read-out of the device — the technology used to communicate the result of the test.
In the study, they have suggested several potentially simple modifications to the Lateral Flow Devices that could lead to improved performance.
Professor Owen Addison from King’s College London said: “Methods to detect infectious individuals who do not show or are yet to show symptoms remain essential for the management of the current pandemic. Lateral Flow Devices are the simplest and most accessible tests available, and our findings show great scope for improving the deficiencies that these tests have been recently criticized for.”
The collaboration saw researchers from King’s College London, Guy’s and St Thomas’ Hospital Trust work with Diamond Light Source, a national science facility, where they used light in the form of X-rays that can be up to 100 billion times brighter than the sun to image how the virus interacts with the tests. The project was supported by a rapid award of experimental time at the science facility.
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Researchers from the University of Kent’s School of Psychology have found that when people are presented with the idea of a Covid-19 “immunity passport,” they show less willingness to follow social distancing and face covering guidelines. However, this willingness seems to return when people read more cautious information about Covid-19 immunity.
PhD students Ricky Green and Mikey Biddlestone and Professor Karen Douglas asked participants from the UK and USA to imagine they had either recovered from Covid-19 or were currently infected. Participants asked to imagine that they had recovered were also presented with information regarding “immunity passports” and cautious versus incautious Covid-19 immunity information. Cautious information emphasised that past infection does not equal immunity whereas incautious information argued that past infection does equal immunity.
The research published by the Journal of Applied Social Psychology showed that for people asked to imagine past Covid-19 infection, reading about “immunity passports” was associated with lower social distancing and face covering intentions. Participants who then read incautious immunity information reported even lower intentions. However, when participants were presented with cautious immunity information these negative effects vanished. People asked to imagine that they were infected reported higher social distancing and hygiene intentions.
Lead researcher Ricky Green said: “People who suspect they have previously had Covid-19 show less willingness to follow pandemic guidelines, presumably because they assume they have become immune to the virus since they were infected. This is concerning because social distancing guidelines are in place to protect others as well as oneself, and the exact nature of infection-acquired immunity is still not clear.
“This research suggests that early public announcements surrounding immunity passports, without prefacing them with cautious information about the unclear evidence on Covid-19 immunity, may have undermined efforts to promote virus-mitigating behaviours. Focusing on ‘acting like you have it’ appears to be helpful in encouraging better public behaviour.”
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Materials provided by University of Kent. Original written by Olivia Miller. Note: Content may be edited for style and length.

Several different causes of ageing have been discovered, but the question remains whether there are common underlying mechanisms that determine ageing and lifespan. Researchers from the Max Planck Institute for Biology of Ageing and the CECAD Cluster of Excellence in Ageing research at the University Cologne have now come across folate metabolism in their search for such basic mechanisms. Its regulation underlies many known ageing signalling pathways and leads to longevity. This may provide a new possibility to broadly improve human health during ageing.
In recent decades, several cellular signalling pathways have been discovered that regulate the lifespan of an organism and are thus of enormous importance for ageing research. When researchers altered these signalling pathways, this extended the lifespan of diverse organisms. However, the question arises whether these different signalling pathways converge on common metabolic pathways that are causal for longevity.
The search begins in the roundworm
The scientists started their search in the roundworm Caenorhabditis elegans, a well-known model organism for ageing research. “We studied the metabolic products of several, long-lived worm lines. Our analyses revealed that, among other things, we observed clear changes in the metabolites and enzymes of the folate cycle in all worm lines. Since folate metabolism plays a major role in human health, we wanted to further pursue its role in longevity,” explains Andrea Annibal, lead author of the study.
A common mechanism for longevity
Folates are essential vitamins important for the synthesis of amino acids and nucleotides — the building blocks of our proteins and DNA. “We tuned down the activity of specific enzymes of folate metabolism in the worms. Excitingly, the result was an increase in lifespan of up to 30 percent,” says Annibal. “We also saw that in long-lived strains of mice, folate metabolism is similarly tuned down. Thus, the regulation of folate metabolism may underlie not only the various longevity signalling pathways in worms, but also in mammals.”
“We are very excited by these findings because they reveal the regulation of folate metabolism as a common shared mechanism that affects several different pathways of longevity and is conserved in evolution,” adds Adam Antebi, director at the Max Planck Institute for Biology of Ageing. “Thus, the precise manipulation of folate metabolism may provide a new possibility to broadly improve human health during ageing.” In future experiments, the group aims to find out the mechanism by which the folate metabolism affects longevity.
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A study led by Fernando Colchero, University of Southern Denmark and Susan Alberts, Duke University, North Carolina, that included researchers from 42 institutions across 14 countries, provides new insights into the aging theory “the invariant rate of ageing hypothesis,” which states that every species has a relatively fixed rate of aging.
“Human death is inevitable. No matter how many vitamins we take, how healthy our environment is or how much we exercise, we will eventually age and die,” said Fernando Colchero.
He is an expert in applying statistics and mathematics to population biology and an associate professor at Department of Mathematics and Computer Science, University of Southern Denmark.
“We were able to shed light on the invariant rate of ageing hypothesis by combining an unpresented wealth of data and comparing births and deaths patterns on nine human populations with information from 30 non-human primate populations, including gorillas, chimpanzees and baboons living in the wild and in zoos” said Fernando Colchero.
In order to explore this hypothesis, the researchers analyzed the relationship between life expectancy, this is the average age at which individuals die in a population, and lifespan equality, which measures how concentrated deaths are around older ages.
Their results show that, as life expectancy increases, so does lifespan equality. So, lifespan equality is very high when most of the individuals in a population tend to die at around the same age such as observed in modern Japan or Sweden — which is around their 70s or 80s. However, in the 1800s lifespan equality was very low in those same countries, since deaths were less concentrated at old ages, resulting also in lower life expectancy.
“Life expectancy has increased dramatically and still does in many parts of the world. But this is not because we have slowed our rate of aging; the reason is that more and more infants, children and young people survive and this brings up the average life expectancy,” said Fernando Colchero.
Previous research from some of the authors of the study has unraveled the striking regularity between life expectancy and lifespan equality among human populations, from pre-industrial European countries, hunter gatherers, to modern industrialize countries.
However, by exploring these patterns among our closest relatives, this study shows that this pattern might be universal among primates, while it provides unique insights into the mechanisms that produce it.
“We observe that not only humans, but also other primate species exposed to different environments, succeed in living longer by reducing infant and juvenile mortality. However, this relationship only holds if we reduce early mortality, and not by reducing the rate of ageing” said Fernando Colchero.
Using statistics and mathematics the authors show that even small changes in the rate of ageing would make a population of, say, baboons, to demographically behave as a population of chimpanzees or even humans.
‘Not all is lost’, says Fernando Colchero, ‘medical science has advanced at an unprecedented pace, so maybe science might succeed in achieving what evolution could not: to reduce the rate of ageing’.
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Research by Oregon State University suggests a pair of compounds originating from hops can help thwart a dangerous buildup of fat in the liver known as hepatic steatosis.
The findings, published today in eLife, are important because the condition affects roughly one-fourth of people in the United States and Europe. While heavy drinking is often associated with liver problems, people with little or no history of alcohol use comprise that 25%, which is why their illness is known as non-alcoholic fatty liver disease, or NAFLD.
Resistance to insulin, the hormone that helps control blood sugar levels, is a risk factor for NAFLD, as are obesity, a high-fat diet and elevated levels of fat in the blood. The liver helps the body process nutrients and also acts as a filter for the circulatory system, and too much fat in the liver can lead to inflammation and liver failure.
In a mouse-model study, Oregon State researchers led by Adrian Gombart showed that the compounds xanthohumol and tetrahydroxanthohumol, abbreviated to XN and TXN, can mitigate diet-induced accumulation of fat in the liver.
XN is a prenylated flavonoid produced by hops, the plant that gives beer its flavor and color, and TXN is a hydrogenated derivative of XN.
In the study, 60 mice were randomly assigned to one of five groups — low-fat diet, high-fat diet, high-fat diet supplemented by XN, high-fat diet supplemented by more XN, and high-fat diet supplemented by TXN.

A group of scientists led by researchers at the University of North Carolina at Chapel Hill, Weill Cornell Medicine and NewYork-Presbyterian reported that the Moderna mRNA vaccine and a protein-based vaccine candidate elicited durable neutralizing antibody responses to SARS-CoV-2 in pre-clinical research. There were no adverse effects.
The research, published June 15 in Science Immunology, suggests that vaccines for young children are likely important, safe tools to curtail the pandemic.
The co-senior authors of the paper are Kristina De Paris, PhD, professor of microbiology and immunology at the UNC School of Medicine, and Sallie Permar, MD, PhD, chair of the Department of Pediatrics at Weill Cornell Medicine. Co-first authors are Carolina Garrido, PhD, at Duke University, and Alan Curtis, PhD, at UNC-Chapel Hill.
“Safe and effective vaccines for young children will help limit the spread of COVID-19 because we know children can transmit the virus to others, whether they get sick from SARS-CoV-2 infection or remain asymptomatic,” said Permar, who is pediatrician-in-chief at NewYork-Presbyterian Komansky Children’s Hospital. “Moreover, many children have become sick and even died from the infection, with many more negatively impacted by the measures put in place to curb the spread. Thus, young children deserve protection from COVID.”
The strong neutralizing antibody responses elicited by the vaccines in 16 baby rhesus macaques persisted for 22 weeks, and the researchers are conducting challenge studies this year to better understand potential long-lasting protection of the vaccines.
“The level of potent antibodies we observed were comparable to what has been seen in adult macaques, even though the doses were 30 micrograms instead of the 100 microgram adult doses,” said De Paris, who is a member of the UNC Children’s Research Institute and the UNC Institute of Global Health and Infectious Diseases. “With the Moderna vaccine, we observed specific strong T cell responses, as well, which we know are important to limiting disease severity.”
To evaluate SARS-CoV-2 infant vaccination, the researchers immunized two groups of 8 infant rhesus macaques at 2.2 months of age and 4 weeks later at the California National Primate Research Center. Each animal received one of two vaccine types: a preclinical version of the Moderna mRNA vaccine or a protein-based vaccine developed by the Vaccine Research Center of the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, with an adjuvant from 3M that stimulates cells through toll-like receptor 7 and 8. The adjuvant was formulated in an emulsion by the Infectious Disease Research Institute (IDRI).