Publisher Health

A multidisciplinary team of researchers from Duke-NUS Medical School and the Agency for Science, Technology and Research (A*STAR) in Singapore discovered a new mitochondrial peptide called MOCCI that plays an important role in regulating inflammation of blood vessel and immunity. The study, published in the journal Nature Communications, revealed how one gene encoded two molecules that provide two-pronged protection following viral infection.
Chronic and excessive inflammation of the blood vessels, known as vascular inflammation, can lead to tissue damage and cardiovascular diseases such as atherosclerosis and fibrosis. Although some therapies have shown promising results in clinical trials, they have considerable side effects, such as immunosuppression leading to increased risk of infection, and limited efficacy. Therefore, more effective treatments are urgently needed.
“In this study, we aimed to identify new targets to combat inflammation in the lining of blood vessels. Specifically, we wanted to target small naturally-produced peptides that have not been studied before,” explained Assistant Professor Lena Ho, from the Cardiovascular and Metabolic Diseases Programme at Duke-NUS, who led the team that included Associate Professor Ashley St John, Assistant Professor Owen Rackham and Senior Research Fellow Dr Cheryl Lee.
The Duke-NUS team, in collaboration with colleagues from the Institute of Molecular and Cell Biology at A*STAR Singapore, investigated a group of peptides called Mito-SEPs that localise in mitochondria, the cellular organelles well-known for their role in cellular energy production. After observing that Mito-SEPs appear to be involved in regulating inflammation, they screened cells from the lining of human aortic blood vessels to uncover peptides involved in this process.
They found a new peptide, which they named MOCCI — short for Modulator of Cytochrome C oxidase during Inflammation — that is made only when cells undergo inflammation and infection.
To their surprise, they discovered that MOCCI is a hitherto unknown component of Complex IV, a part of a series of enzymes in the mitochondria responsible for energy production, called the electron transport chain. During inflammation, MOCCI incorporates into Complex IV to dampen its activity. Collaborating with Assoc Prof St John at Duke-NUS, the researchers found that this dampening is required to reduce inflammation following viral infection.
“Our finding that the composition of the electron transport chain changes in response to inflammation is novel. MOCCI in essence repurposes part of the energy production centre in the cell to regulate inflammation,” said Dr Lee, the lead author of this study.
The researchers also discovered that MOCCI is made together with a micro-RNA molecule called miR-147b. The two molecules are made from different sections of the same gene. MOCCI originates from the sequence of the gene that codes for proteins, while miR-147b is made from the non-coding section.
While the miR-147b molecule also exerts anti-inflammatory effects, it actively prevents viruses from replicating at the same time. This implies that MOCCI and miR-147b function in tandem to help to control viral infection and suppress inflammation.
“This dual-pronged strategy is an elegant mechanism that the body has put in place to prevent excessive and potentially tissue-damaging inflammation during infection, such as the cytokine storm seen in COVID-19 infection, and colitis” said Asst Prof Ho. “The gene encoding MOCCI is one of the first genes described to have both coding and non-coding functions. The fact these dual functions are coordinated to achieve a concerted biological outcome is a significant finding in cell biology.”
Professor Patrick Casey, Senior Vice-Dean for Research at Duke-NUS, commented, “Medicine and healthcare advance with the aid of new discoveries in fundamental research. This study by Asst Prof Ho and her collaborators provides valuable insight on inflammation and immunity — a topic that has become even more important in the context of COVID-19.”
The researchers say the next step is to explore how to develop targeted pharmacological treatments that can mimic the anti-inflammatory effects of MOCCI and miR147b. They also plan to investigate the role of MOCCI in common chronic inflammatory diseases such as colitis and psoriasis.
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Researchers at Albert Einstein College of Medicine have designed an experimental drug that reversed key symptoms of Alzheimer’s disease in mice. The drug works by reinvigorating a cellular cleaning mechanism that gets rid of unwanted proteins by digesting and recycling them. The study was published online today in the journal Cell.
“Discoveries in mice don’t always translate to humans, especially in Alzheimer’s disease,” said co-study leader Ana Maria Cuervo, M.D., Ph.D., the Robert and Renée Belfer Chair for the Study of Neurodegenerative Diseases, professor of developmental and molecular biology, and co-director of the Institute for Aging Research at Einstein. “But we were encouraged to find in our study that the drop-off in cellular cleaning that contributes to Alzheimer’s in mice also occurs in people with the disease, suggesting that our drug may also work in humans.” In the 1990s, Dr. Cuervo discovered the existence of this cell-cleaning process, known as chaperone-mediated autophagy (CMA) and has published 200 papers on its role in health and disease.
CMA becomes less efficient as people age, increasing the risk that unwanted proteins will accumulate into insoluble clumps that damage cells. In fact, Alzheimer’s and all other neurodegenerative diseases are characterized by the presence of toxic protein aggregates in patients’ brains. The Cell paper reveals a dynamic interplay between CMA and Alzheimer’s disease, with loss of CMA in neurons contributing to Alzheimer’s and vice versa. The findings suggest that drugs for revving up CMA may offer hope for treating neurodegenerative diseases.
Establishing CMA’s Link to Alzheimer’s
Dr. Cuervo’s team first looked at whether impaired CMA contributes to Alzheimer’s. To do so, they genetically engineered a mouse to have excitatory brain neurons that lacked CMA. The absence of CMA in one type of brain cell was enough to cause short-term memory loss, impaired walking, and other problems often found in rodent models of Alzheimer’s disease. In addition, the absence of CMA profoundly disrupted proteostasis — the cells’ ability to regulate the proteins they contain. Normally soluble proteins had shifted to being insoluble and at risk for clumping into toxic aggregates.
Dr. Cuervo suspected the converse was also true: that early Alzheimer’s impairs CMA. So she and her colleagues studied a mouse model of early Alzheimer’s in which brain neurons were made to produce defective copies of the protein tau. Evidence indicates that abnormal copies of tau clump together to form neurofibrillary tangles that contribute to Alzheimer’s. The research team focused on CMA activity within neurons of the hippocampus — the brain region crucial for memory and learning. They found that CMA activity in those neurons was significantly reduced compared to control animals.

A natural compound previously demonstrated to counteract aspects of aging and improve metabolic health in mice has clinically relevant effects in people, according to new research at Washington University School of Medicine in St. Louis.
A small clinical trial of postmenopausal women with prediabetes shows that the compound NMN (nicotinamide mononucleotide) improved the ability of insulin to increase glucose uptake in skeletal muscle, which often is abnormal in people with obesity, prediabetes or Type 2 diabetes. NMN also improved expression of genes that are involved in muscle structure and remodeling. However, the treatment did not lower blood glucose or blood pressure, improve blood lipid profile, increase insulin sensitivity in the liver, reduce fat in the liver or decrease circulating markers of inflammation as seen in mice.
The study, published online April 22 in the journal Science, is the first randomized clinical trial to look at the metabolic effects of NMN administration in people.
Among the women in the study, 13 received 250 mg of NMN orally every day for 10 weeks, and 12 were given an inactive placebo every day over the same period.
“Although our study shows a beneficial effect of NMN in skeletal muscle, it is premature to make any clinical recommendations based on the results from our study,” said senior investigator Samuel Klein, MD, the William H. Danforth Professor of Medicine and Nutritional Science and director of the Center for Human Nutrition. “Normally, when a treatment improves insulin sensitivity in skeletal muscle, as is observed with weight loss or some diabetes medications, there also are related improvements in other markers of metabolic health, which we did not detect in our study participants.”
The remarkable beneficial effects of NMN in rodents have led several companies in Japan, China and in the U.S. to market the compound as a dietary supplement or a neutraceutical. The U.S. Food and Drug Administration is not authorized to review dietary supplement products for safety and effectiveness before they are marketed, and many people in the U.S. and around the world now take NMN despite the lack of evidence to show clinical benefits in people.
The researchers studied 25 postmenopausal women who had prediabetes, meaning they had higher than normal blood sugar levels, but the levels were not high enough to be diagnosed as having diabetes. Women were enrolled in this trial because mouse studies showed NMN had the greatest effects in female mice.
NMN is involved in producing an important compound in all cells, called nicotinamide adenine dinucleotide (NAD). NAD plays a vital role in keeping animals healthy. Levels of NAD decline with age in a broad range of animals, including humans, and the compound has been shown to contribute to a variety of aging-associated problems, including insulin resistance in studies conducted in mice. Supplementing animals with NMN slows and ameliorates age-related decline in the function of many tissues in the body.
Co-investigator Shin-ichiro Imai, MD, PhD, a professor of developmental biology and of medicine who has been studying NMN for almost two decades and first reported on its benefits in mice said, “This is one step toward the development of an anti-aging intervention, though more research is needed to fully understand the cellular mechanisms responsible for the effects observed in skeletal muscle in people.”
Insulin enhances glucose uptake and storage in muscle, so people who are resistant to insulin are at increased risk for developing Type 2 diabetes. But the researchers caution that more studies are needed to determine whether NMN has beneficial effects in the prevention or management of prediabetes or diabetes in people. Klein and Imai are continuing to evaluate NMN in another trial involving men as well as women.
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Materials provided by Washington University School of Medicine. Original written by Jim Dryden. Note: Content may be edited for style and length.

Spinal cord nerve cells branching through the body resemble trees with limbs fanning out in every direction. But this image can also be used to tell the story of how these neurons, their jobs becoming more specialized over time, arose through developmental and evolutionary history. Salk researchers have, for the first time, traced the development of spinal cord neurons using genetic signatures and revealed how different subtypes of the cells may have evolved and ultimately function to regulate our body movements.
The findings, published in the journal Science on April 23, 2021, offer researchers new ways of classifying and tagging subsets of spinal cord cells for further study, using genetic markers that differentiate branches of the cells’ family tree.
“A study like this provides the first molecular handles for scientists to go in and study the function of spinal cord neurons in a much more precise way than they ever have before,” says senior author of the study Samuel Pfaff, Salk Professor and the Benjamin H. Lewis Chair. “This also has implications for treating spinal cord injuries.”
Spinal neurons are responsible for transmitting messages between the spinal cord and the rest of the body. Researchers studying spinal neurons have typically classified the cells into “cardinal classes,” which describe where in the spinal cord each type of neuron first appears during fetal development. But, in an adult, neurons within any one cardinal class have varied functions and molecular characteristics. Studying small subsets of these cells to tease apart their diversity has been difficult. However, understanding these subset distinctions is crucial to helping researchers understand how the spinal cord neurons control movements and what goes awry in neurogenerative diseases or spinal cord injury.
“It’s been known for a long time that the cardinal classes, as useful as they are, are incomplete in describing the diversity of neurons in the spinal cord,” says Peter Osseward, a graduate student in the Pfaff lab and co-first author of the new paper, along with former graduate student Marito Hayashi, now a postdoctoral fellow at Harvard University.
Pfaff, Osseward and Hayashi turned to single-cell RNA sequencing technologies to analyze differences in what genes were being activated in almost 7,000 different spinal neurons from mice. They used this data to group cells into closely related clusters in the same way that scientists might group related organisms into a family tree.

The foods people buy at a workplace cafeteria may not always be chosen to satisfy an individual craving or taste for a particular food. When co-workers are eating together, individuals are more likely to select foods that are as healthy — or unhealthy — as the food selections on their fellow employees’ trays. “We found that individuals tend to mirror the food choices of others in their social circles, which may explain one way obesity spreads through social networks,” says Douglas Levy, PhD, an investigator at the Mongan Institute Health Policy Research Center at Massachusetts General Hospital (MGH) and first author of new research published in Nature Human Behaviour. Levy and his co-investigators discovered that individuals’ eating patterns can be shaped even by casual acquaintances, evidence that corroborates several multi-decade observational studies showing the influence of people’s social ties on weight gain, alcohol consumption and eating behavior.
Previous research on social influence upon food choice had been primarily limited to highly controlled settings like studies of college students eating a single meal together, making it difficult to generalize findings to other age groups and to real-world environments. The study by Levy and his co-authors examined the cumulative social influence of food choices among approximately 6,000 MGH employees of diverse ages and socioeconomic status as they ate at the hospital system’s seven cafeterias over two years. The healthfulness of employees’ food purchases was determined using the hospital cafeterias’ “traffic light” labeling system designating all food and beverages as green (healthy), yellow (less healthy) or red (unhealthy).
MGH employees may use their ID cards to pay at the hospitals’ cafeterias, which allowed the researchers to collect data on individuals’ specific food purchases, and when and where they purchased the food. The researchers inferred the participants’ social networks by examining how many minutes apart two people made food purchases, how often those two people ate at the same time over many weeks, and whether two people visited a different cafeteria at the same time. “Two people who make purchases within two minutes of each other, for example, are more likely to know each other than those who make purchases 30 minutes apart,” says Levy. And to validate the social network model, the researchers surveyed more than 1,000 employees, asking them to confirm the names of the people the investigators had identified as their dining partners.
“A novel aspect of our study was to combine complementary types of data and to borrow tools from social network analysis to examine how the eating behaviors of a large group of employees were socially connected over a long period of time,” says co-author Mark Pachucki, PhD, associate professor of Sociology at the University of Massachusetts, Amherst.
Based on cross-sectional and longitudinal assessments of three million encounters between pairs of employees making cafeteria purchases together, the researchers found that food purchases by people who were connected to each other were consistently more alike than they were different. “The effect size was a bit stronger for healthy foods than for unhealthy foods,” says Levy.
A key component of the research was to determine whether social networks truly influence eating behavior, or whether people with similar lifestyles and food preferences are more likely to become friends and eat together, a phenomenon known as homophily. “We controlled for characteristics that people had in common and analyzed the data from numerous perspectives, consistently finding results that supported social influence rather than homophily explanations,” says Levy.
Why do people who are socially connected choose similar foods? Peer pressure is one explanation. “People may change their behavior to cement the relationship with someone in their social circle,” says Levy. Co-workers may also implicitly or explicitly give each other license to choose unhealthy foods or exert pressure to make a healthier choice.
The study’s findings have several broader implications for public health interventions to prevent obesity. One option may be to target pairs of people making food choices and offer two-for-one sales on salads and other healthful foods but no discounts on cheeseburgers. Another approach might be to have an influential person in a particular social circle model more healthful food choices, which will affect others in the network. The research also demonstrates to policymakers that an intervention that improves healthy eating in a particular group will also be of value to individuals socially connected to that group.
“As we emerge from the pandemic and transition back to in-person work, we have an opportunity to eat together in a more healthful way than we did before,” says Pachucki. “If your eating habits shape how your co-workers eat — even just a little — then changing your food choices for the better might benefit your co-workers as well.”
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Holly Elgison and Len Schillaci are a mixed vaxxed couple, and they are far from alone.“I was always going to get the vaccine, 100 percent,” said Ms. Elgison, a medical claims auditor in Valrico, Fla.Her husband, a disaster insurance adjuster, said he will pass. “To be honest with you, I think that the worst of Covid is behind us,” Mr. Schillaci said. “I’m good.”As the Biden administration seeks to get 80 percent of adult Americans immunized by summer, the continuing reluctance of men to get a shot could impede that goal.Women are getting vaccinated at a far higher rate — about 10 percentage points — than men, even though the male-female divide is roughly even in the nation’s overall population. The trend is worrisome to many, especially as vaccination rates have dipped a bit recently.The reasons for the U.S. gender gap are many, reflecting the role of women in specific occupations that received early vaccine priority, political and cultural differences and long standing patterns of women embracing preventive care more often generally than men.The gap exists even as Covid-19 deaths worldwide have been about 2.4 times higher for men than among women. And the division elucidates the reality of women’s disproportionate role in caring for others in American society.“It could matter to localized herd immunity,” said Alison Buttenheim, an associate professor of nursing at the University of Pennsylvania and expert on vaccine hesitancy. “While most experts are fretting about larger gaps by race, political party, religion and occupational group,” she said, many of which overlap with the gender disparities, “I haven’t heard of any specific initiatives to target men.”In Los Angeles County, where 44 percent of women over 16 have gotten their first shot — compared with 30 percent of men — officials are scrambling to figure out how to do just that.“We are very concerned about it and are planning to embark on some targeted outreach among men,” said Dr. Paul Simon, the chief science officer at the Los Angeles County Department of Public Health, who said that the disparities are of particular concern for Black and Latino men. Only 19 percent of Black males in Los Angeles County and 17 percent of Latino males have received at least one dose of the vaccine, compared with 35 percent of Asian men and 32 percent of white men, according to the most recent data available from early this month.“We don’t fully understand it,” Dr. Simon said. “One of our messaging strategies will be that the vaccine is not only important for you but, in addition, is a means of protecting others in your family.”In Los Angeles County, 44 percent of women over 16 had gotten their first shot — compared with about 30 percent of men.Frederic J. Brown/Agence France-Presse — Getty ImagesThe early divisions in vaccine rates by gender could largely be explained by demographics. Americans over 70 got the first sets of doses, and women make up a larger proportion of that age group. In many states, health care workers and schoolteachers were also given vaccine priority: Women account for three-quarters of full-time health care workers and over 75 percent of public schoolteachers in the United States are female.The disparities show both where women do the paid and unpaid labor of life. For instance, women lost the majority of the earliest jobs in food services, retail businesses, health care and government jobs. The mothers among them have done most of the work in the shift to remote schooling and caring for parents and sick relatives.The combination may have increased their vaccine motivation in two ways: They are seeking to protect the rest of their family and they are desperate to get back in the work force. Indeed, just as women drove the job losses last year, they are leading the economic recovery now; roughly half a million women joined the labor force in March, in part because in-person schooling has resumed across much of the country.“In addition to women being disproportionately represented in several essential jobs,” said Pilar Gonalons-Pons, an assistant professor of sociology at the University of Pennsylvania who specializes in gender issues, “they are also disproportionately represented as unpaid caregivers for older adults in their families and communities, and this can also be an additional motivation for getting the vaccine.”In many ways, the pattern with vaccines reflects longstanding gender differences when it comes to preventive health care. Women are on average more likely to get annual physicals than men, even when adjusted for pre-existing health conditions and other factors, and are more likely than men to get preventive care.Men are more likely than women to engage in behaviors that hurt their health — like heavy drinking, smoking and illicit drug use — and are more overweight compared to women. Men are less likely to visit doctors regularly and go to the emergency room in a crisis and to get basic dental care, according to federal data. Vaccines are no exception: Historically, influenza vaccination is much higher among females — about 63 percent compared to 53 percent — though the gap narrows in Americans over 75 years old.The coronavirus vaccine “is the latest expression of the tried-and-true gender gap we’ve long witnessed in preventive health care seeking patterns,” said Lindsey Leininger, a health policy researcher and clinical professor at Tuck School of Business at Dartmouth College.But experts say that even in the context of general male health care recalcitrance, there may be some factors that are specific to this vaccine that are preventing more male shots in arms. Because the sign up has been cumbersome and confusing, men may have had less patience in navigating the system, which has largely taken place online, a process that women might find easier since they tend to get more of their health care information online.“We have to figure out if disparities are about access, if men are having more difficulty navigating the appointment systems,” Mr. Simon of Los Angeles said.Further, when it comes to the coronavirus — which has been the subject of rampant misinformation, evolving medical advice and politicization — other dynamics may be at work.“Some men have a sense that they are not necessarily susceptible,” Mr. Simon said health care workers have told officials. “They have weathered this for more than a year and have a sense of omnipotence.”Public health and academic experts have been long concerned with the “macho” effect that prevents men from getting all sorts of health care, and fear that it might be exacerbated with this vaccine. (Notably, in the most male service branch of the military, the Marines, about 40 percent of those who were offered the vaccine by the Defense Department have turned it down.)A selfie after receiving a Covid shot at the First Baptist Church of Glenarden in Upper Marlboro, Md., last month.Erin Schaff/The New York Times“This avoidance has been linked to masculinity ideals of men being strong, invincible and not asking for help,” said Kristen W. Springer, an associate professor in the Department of Sociology at Rutgers University in New Jersey who has done research on this trait.“In other words, these cultural ideals lead men to avoid important health care in order to act masculine,” she said. “Now that the vaccine is available to everyone, it will be interesting to watch male-female differences in vaccine uptake, because these will more likely reflect social and cultural ideas about gender and health, such as the cultural idea that ‘real men’ don’t need preventive health care.”At this stage, U.S. health authorities have not released data on nonbinary adults and vaccination.There may also be political connections. Women are far more likely than men to register as Democrats, and polls demonstrate that Republicans across the country have been far less likely than Democrats to embrace the vaccine.So who will men listen to? Not their wives and female friends or doctors, it seems. For their recent preprint study, Leah Witus and Erik Larson, professors at Macalester College in Saint Paul, Minn., watched videos with men and women that featured identical information about the vaccine. Among the 1,184 Americans who watched them, most were positively influenced by the male narrator while the female narrator got a far more mixed response.“The male-narrated version of the video increased vaccination intention in viewers,” said Ms. Witus, “but the female-narrated had mixed associations with vaccine propensity, and in some viewers, those that identified as conservative, actually decreased vaccination intention.”This may spell victory for Mr. Schillaci as he and his wife subtly joust for influence over their 20-year-old son’s vaccination decision. Mr. Schillaci has been sharing his views with his son, whom his wife is prodding to take a shot.“I would rather he got the shot, and I hope that he’ll consider it,” said Ms. Elgison.But Ms. Elgison’s own decision may benefit her son, even if he decides against the vaccine.As often happens in life, men may find their gaps covered by women. “To the extent most people live and socialize in a mixed-gender setting, the men will benefit from the higher coverage among women,” Ms. Buttenheim said.Ms. Elgison, however, still has a trump card she hopes might work. “I would like my son to get it so we can all travel together,” she said. “I explained to him that it’s possible that we could protect his dad.”

Note: Figures reflect weekly totals of positive flu tests, from public and clinical laboratories.·Source: Centers for Disease Control and Prevention […]

A synthetic DNA vaccine candidate for Middle East respiratory syndrome coronavirus (MERS-CoV) developed at The Wistar Institute induced potent immune responses and afforded protective efficacy in non-human primate (NHP) models when given intradermally in abbreviated, low-dose immunization regimen. A similar vaccine candidate was previously shown to be safe and tolerable with a three-dose intramuscular injection regimen in a recently completed human phase 1 study and is currently in expanded studies of phase 1/2a trial.
New results were published today in JCI Insight.
“While several vaccine products are being advanced against MERS and other coronaviruses, low-dose delivery and shortened regimes are crucial to rapidly induce protective immunity, particularly during emerging outbreaks, as the current SARS-CoV-2 pandemic has emphasized,” said David B. Weiner, Ph.D., Wistar executive vice president, director of the Vaccine & Immunotherapy Center (VIC) and W.W. Smith Charitable Trust Professor in Cancer Research, who led the study.
Researchers evaluated the immunogenicity and protective efficacy of their MERS synthetic vaccine when delivered intradermally using a shortened two-dose immunization schedule compared with intramuscular delivery of higher doses in NHP.
“Given that human efficacy trials for MERS vaccines may be challenging due to the low number of yearly cases, animal models such as our NHP model are valuable as a bridge with human data coming from early-phase clinical trials,” said Weiner.
In this study, Weiner and team report robust antibody neutralizing antibodies and cellular immune responses in all conditions tested. A rigorous virus challenge experiment showed that all vaccination groups were protected against MERS-CoV compared to unvaccinated control animals. However, the low-dose regimen with intradermal delivery was more impactful in controlling disease and symptoms than the higher dose delivered intramuscularly in NHP models.
“To our knowledge, this is the first demonstration of protection with an intradermally delivered coronavirus vaccine,” said Ami Patel, Ph.D., Caspar Wistar Fellow at the Vaccine & Immunotherapy Center and one of the lead authors of the paper. “Intradermal delivery of synthetic DNA vaccines has significant advantages for rapid clinical development. It can be dose sparing and has higher tolerability in people compared with intramuscular injection. The positive results of this study are important not only for the advancement of this MERS vaccine but also for development of other vaccines.”
“Our team is also advancing a COVID-19 vaccine through clinical trials, and we were able to do so in a very short time thanks to our previous experience developing the MERS vaccine,” added Weiner.
Importantly, no evidence of adverse effects on the lungs was observed in any of the dosing groups compared to unimmunized control animals. Through the assessment of a large panel of blood cytokines, researchers showed significant decrease in all mediators of inflammation, which further suggests the vaccine prevents the destructive inflammation induced by coronaviruses.
“In the past twenty years, three new coronaviruses have emerged and caused human outbreaks. The current SARS-CoV-2 pandemic has further emphasized the importance of rapid infection control for coronaviruses and other emerging infectious diseases,” said Emma L. Reuschel, Ph.D., a staff scientist in the Weiner lab and co-first author on the study. “Vaccine candidates that are simple to deliver, well tolerated, and can be readily deployed in resource-limited settings will be important to achieve control of infection.”
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Research has identified critical factors that enable dangerous bacteria to spread disease by surviving on surfaces in hospitals and kitchens.
The study into the mechanisms which enable the opportunistic human pathogen Pseudomonas aeruginosa to survive on surfaces, could lead to new ways of targeting harmful bacteria.
To survive outside their host, pathogenic bacteria must withstand various environmental stresses. One mechanism is the sugar molecule, trehalose, which is associated with a range of external stresses, particularly osmotic shock — sudden changes to the salt concentration surrounding cells.
Researchers at the John Innes Centre analysed how trehalose is metabolised by P. aeruginosa to define its role in protection against external stresses.
Combining analytical biochemistry and reverse genetics — using mutated bacteria lacking key functions — they show that trehalose metabolism in P. aeruginosa is connected to biosynthesis of the carbon storage molecule glycogen.
Experiments showed that disruption of either trehalose or glycogen pathways significantly reduced the ability of P. aeruginosa to survive on human-made surfaces such as kitchen or hospital counters.
The study found that while both trehalose and glycogen are important for stress tolerance in P. aeruginosa they counter distinct stresses: trehalose helps the bacteria to survive in conditions of elevated salt; glycogen contributes to survival in dry (desiccated) environments.
The findings raise the possibility of targeting the trehalose and glycogen pathways to limit pathogen survival on human-made surfaces.
“We have shown how a dangerous human pathogen Pseudomonas aeruginosa responds to environmental challenges, such as salt stress or drying out. Disrupting the production of certain stress-tolerance sugars in this bug significantly reduces its ability to survive on kitchen and hospital worksurfaces,” said corresponding author of the study Dr Jacob Malone.
An unexpected finding was how the bacteria operates different pathways for different stresses, said Dr Malone: “Conventional wisdom says that trehalose was responsible for both phenotypes, but we have shown that trehalose only protects against osmo-stress and glycogen is needed to protect against desiccation. We were also surprised to see such a marked drop in surface survival when we disrupted the pathways in the bugs.”
The next step for the research is to understand how trehalose and glycogen metabolic pathways are regulated in P. aeruginosa and closely related species. The group also wants to understand how glycogen accumulation allows the bacteria to survive in dry environments and provide more explanation of how and when different parts of the pathways are turned on and off.
P. aeruginosa is a significant pathogen in animals as well as humans. In humans it primarily affects immunocompromised individuals, where it is a major cause of pneumonia and hospital-acquired infections. Chronic P. aeruginosa infections occur in 80% of adult cystic fibrosis patients, where it is the primary cause of morbidity and mortality.
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Engineers have developed a new material that mimics human cartilage — the body’s shock absorbing and lubrication system, and it could herald the development of a new generation of lightweight bearings.
Cartilage is a soft fibrous tissue found around joints which provides protection from the compressive loading generated by walking, running or lifting. It also provides a protective, lubricating layer allowing bones to pass over one another in a frictionless way. For years, scientists have been trying to create a synthetic material with the properties of cartilage.
To date, they have had mixed results.
But in a paper published in the journal Applied Polymer Materials, researchers at the University of Leeds and Imperial College London have announced that they have created a material that functions like cartilage.
The research team believes a cartilage-like material would have a wide-range of uses in engineering.
Cartilage is a bi-phasic porous material, meaning it exists in solid and fluid phases. It switches to its fluid phase by absorbing a viscous substance produced in the joints called synovial fluid. This fluid not only lubricates the joints but when held in the porous matrix of the cartilage, it provides a hydroelastic cushion against compressive forces.