Publisher Health

New insights into how genetic factors affect the body’s immune response in type 1 diabetes have been published in eLife.
The findings provide evidence of a direct link between genetic factors associated with susceptibility to type 1 diabetes and immune functionality, particularly involving immune T cells. They also highlight 11 genes which could be explored as potential candidates for new treatments.
Type 1 diabetes develops when the body’s immune system mistakenly attacks groups (or islets) of insulin-producing beta cells in the pancreas. There are currently over nine million people diagnosed with type 1 diabetes, but there is no cure and patients need to have regular insulin injections to manage the condition. People with certain genetic variations are more susceptible to type 1 diabetes. But while previous studies have identified around 60 associated variations, it is still unknown how they influence the condition.
“To characterise the body’s immune response in type 1 diabetes, we need to look at both the proportion of immune cells and their production of proteins — cytokines — that stimulate the immune system,” explains Xiaojing Chu, a Doctorate Student at the University Medical Center Groningen, the Netherlands. Chu is a co-first author of the study alongside Anna Janssen, a Medical Doctor and PhD Candidate, and Hans Koenen, Assistant Professor, at Radboud University Medical Center, the Netherlands. “In our study, we explored how genetic factors affect immune cells and their cytokine production in people with type 1 diabetes, as well as the differences between the immune response in patients and a healthy response.”
To do this, the researchers collected blood samples from 243 volunteers of Dutch descent with type 1 diabetes, aged 20-84 years old. They then applied a technique called genetic association analysis on more than 200 immune cell traits and more than 100 cytokine production profiles to identify genetic determinants of immune functionality. They compared the results to those obtained in a group of 500 healthy individuals from previous studies that characterised the impact of genetic factors on immune responses in these individuals.*
Their analyses showed that genetic variants determining susceptibility to type 1 diabetes significantly affect T-cell composition. Specifically, a group of these cells, called CCR5+ regulatory T cells, was actively involved in type 1 diabetes through an area of the genome called the constrained coding region.
The team then used a technique called genome-wide quantitative trait loci (QTL) mapping to analyse immune traits. This revealed 15 genetic ‘commands’ that influence the behaviour of immune cells in type 1 diabetes. Of these, 12 have not previously been reported in healthy people, implying a disease-specific genetic regulation. Additionally, the team identified 11 genes as potential candidates for drug development.
“Our findings provide a deeper understanding of the immune mechanisms involved in the development of type 1 diabetes and that affect the general inflammatory response in patients. We hope this work will open up new avenues for the development of much-needed treatments,” concludes Yang Li, Professor of Computational Biology and Director of the Centre for Individualised Infection Medicine (CiiM), Helmholtz Centre for Infection Research, Hannover, Germany. Li is a co-senior author of the study alongside Cees Tack, Professor in Internal Medicine at Radboud University Medical Center, Nijmegen, the Netherlands.
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Scientists have demonstrated how some fast-growing bacteria can retreatment with antibiotics, according to a study published today in eLife.
The results show that fast-growing individuals within bacterial colonies display a significantly higher expression of active ribosomes — particles within the cell that synthesise proteins. This helps the bacteria avoid the accumulation of an important class of antibiotics called macrolides and therefore resist therapies. These findings could be used to inform the development of improved antibiotic compounds that target this survival strategy.
Bacterial infections can cause food poisoning, pneumonia, sepsis and other serious diseases. While they can be treated with antibiotics, the overuse of these drugs in recent years means that bacteria are becoming increasingly resistant to them, posing a significant threat to global health.
For an antibiotic to be effective against infection, it needs to reach its cellular target at a sufficient concentration to inhibit bacterial growth.
“Antibiotic resistance continues to threaten the viability of current treatments. We need to understand how individual bacteria within a colony can prevent antibiotics from entering their cells, so that we can target this mechanism with new therapies,” says Urszula Łapińska, PDRA at the University of Exeter, UK. “Most existing data around drug permeability in bacteria has been attained through measurements that either take an average result from a large population or are derived from a small number of bacteria. This means that little is known about the variability in individual drug accumulation across many single cells in a bacterial colony.”
To address this gap, Łapińska and the team began with the hypothesis that variations in how bacteria respond to drugs could be driven by the varying drug transport rates between individual cells. To test this, the team used a multi-analytical approach, combining microfluidics-microscopy, bacteria that pose a health threat — namely Escherichia coli, Pseudomonas aeruginosa, Burkholderia cenocepacia and Staphylococcus aureus and fluorescent probes derived from antibiotics by Dr Mark Blaskovich at the University of Queensland. This approach allowed the team to examine the interactions between commonplace antibiotics and many live, individual bacteria in real-time, during drug dosage. By combining this approach with mathematical modelling techniques developed by Prof Krasimira Tsaneva-Atanasova at the University of Exeter, the team obtained data that they could use to quickly and efficiently identify individual bacteria that are antibiotic resistant.
Their analyses demonstrated that fast-growing individuals within a colony avoid the accumulation of macrolides within their cells — a discovery that contrasts with current thinking that slow cell growth is the major contributor to survival to antibiotics without genetic variation. This avoidance is enabled by a significantly higher amount of ribosomes before drug treatment, compared to the individuals’ slow-growing counterparts. Ribosomes enable essential cellular processes, including efflux — a system that pumps toxic substances, such as antimicrobial compounds, out of the cell.
Using this new knowledge, the researchers then showed that chemically manipulating the outer membrane of the bacterial cells allows to eradicate fast-growing variants that exhibit low macrolide accumulation, therefore aiding our fight against antibiotic resistance.
“This work reveals a hitherto unrecognised survival strategy in some members of bacterial colonies ,” concludes Dr Stefano Pagliara, Senior Lecturer in Microfluidics at the University of Exeter, UK. “These insights will directly benefit microbiologists and clinicians who are working on the development of more effective antibiotic therapies. In the longer term, we hope that using our novel approach in clinical settings will help inform the design of improved drugs and help us in the fight against antibiotic resistance.”
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A new study published in today’s issue of Biochemistry is the first to explore the effects of multiple mutations in the evolution of SARS-CoV-2 variants. The findings can help scientists better understand the properties of current and new variants.
The results can also be used to better inform the development of vaccines and therapeutics to counter the threats posed by variants.
“Earlier studies, including ours, have focused on explaining the effect of single mutations and not the mechanism underlying the co-evolution of mutations,” said the paper’s corresponding author Krishna Mallela, PhD, professor in the department of pharmaceutical sciences at the University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences located on the University of Colorado Anschutz Medical Campus.
“Our study helps explain the concept of convergent evolution by balancing positive and negative selection pressures,” he adds.
The new paper, co-authored by Vaibhav Upadhyay, Casey Patrick and Alexandra Lucas from Mallela’s lab, was featured on the journal’s cover. The paper provides the physical basis for why approved antibody therapeutics are not working in neutralizing the recent variants of concern, such as Omicron and its subvariants.
“Understanding the mechanisms underlying the antibody escape and the location of mutations in the spike protein will help in developing new antibody therapeutics that will work against new variants by targeting epitopes with minimal mutations or developing broad neutralizing antibodies that target multiple epitopes,” said Mallela.
The study found that certain mutations appear repeatedly in emerging variants showing convergent evolution. One such evolution occurs at three amino acid positions K417, E484 and N501 in the spike protein’s receptor binding domain (RBD). Nearly half of 4.3 million variant sequences in GISAID database that contain any of these three mutations have all three occurring together. Although individual mutations have both beneficial and deleterious/adverse effects, when they come together, deleterious/adverse effects get canceled out, leading to improved selection of the mutations together.
The researchers examined the physical mechanisms underlying the convergent evolution of the three mutations by delineating the individual and collective effects of mutations on binding to angiotensin converting enzyme 2 receptor, immune escape from neutralizing antibodies, protein stability and expression.
They found the three RBD mutations perform very distinct and specific roles that contribute toward improving the virus fitness and build the case for their positive selection, even though individual mutations have deleterious effects that make them prone to negative selection. Compared to the wild-type, K417T escapes Class 1 antibodies and has increased stability and expression; however, it has decreased ACE2 receptor binding. E484K escapes Class 2 antibodies; however, it has decreased receptor binding, stability and expression. N501Y increases receptor binding; however, it has decreased stability and expression. When these mutations come together, the deleterious effects are mitigated due to the presence of compensatory effects. Triple mutant K417T/E484K/N501Y has increased ACE2 receptor binding, escapes both Class 1 and Class 2 antibodies and has similar stability and expression as that of the wild-type.
The authors conclude the collective effect of these mutations is far more advantageous for virus fitness than the individual mutations and the presence of multiple mutations improves the selection of individual mutations.
Mallela concludes, “As SARS-CoV-2 has evolved from Alpha to Omicron, more and more mutations are accumulating. We hope that by providing research that understands the role of these mutations, we can help further propel research and the development of new therapies to better combat new variants.”
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Materials provided by University of Colorado Anschutz Medical Campus. Original written by Julia Milzer. Note: Content may be edited for style and length.

Poultry is responsible for more than one out of every five cases of salmonella infection in the U.S. But traditional methods of testing the chicken you grab off the grocery shelf may not be enough to detect all strains of the bacteria, according to new research from the University of Georgia.
Published in Applied and Environmental Microbiology, the study analyzed national salmonella data from the U.S. Department of Agriculture Food Safety Inspection Service from 2016 to 2020.
The researchers found that overall cases of salmonella contamination in chicken decreased from 9% in 2016 to 6.57% in 2020. But nationally, the cases of salmonella infection in people have remained stable during this same period.
“When I first started at the Poultry Diagnostic and Research Center four years ago and met with several different poultry companies, one of the things they said to me was that the salmonella they find on the farms is not the same type of salmonella they find in the processing plant,” said Nikki Shariat, corresponding author of the study and an assistant professor in the College of Veterinary Medicine.
That disconnect makes it challenging for the poultry industry to know which types of salmonella to target with new vaccines and other interventions that can reduce the amount of high-risk types of salmonella in the birds.
The researchers partnered with the Georgia Poultry Lab Network in Gainesville, Georgia, to examine what strains of salmonella, known as serotypes, were present in breeder chickens versus the strains present in chicken products.

Dietary guidelines form the basis for nutrition advice and regulations around the world. While there is strong scientific consensus around most existing guidelines, one question has recently stirred debate: Should consumers be warned to avoid ultra-processed foods?
Two papers published today in The American Journal of Clinical Nutrition (AJCN) outline the case for and against using the concept of ultra-processed foods to help inform dietary guidelines beyond conventional food classification systems. The authors, Carlos A. Monteiro, MD, PhD, of the University of São Paulo in São Paulo, Brazil, and Arne Astrup, MD, PhD, of Novo Nordisk Foundation in Hellerup, Denmark, will discuss the issue in a live virtual debate June 14 during NUTRITION 2022 LIVE ONLINE.
The debate centers around NOVA, a system developed by Monteiro and colleagues that classifies foods by their degree of industrial processing, ranging from unprocessed or minimally processed to ultra-processed. NOVA defines ultra-processed foods as those made using sequences of processes that extract substances from foods and alter them with chemicals or additives in order to formulate the final product. Ultra-processed foods are characteristically designed to be cheap, palatable and convenient; examples include soft drinks and candy, packaged snacks and pastries, ready-to-heat products, and reconstituted meat products or plant-based alternatives.
Studies have linked consumption of ultra-processed foods — which are often high in salt, sugar and fat — with weight gain and an increased risk of chronic diseases, even after adjusting for the amount of salt, sugar and fat in the diet. While the mechanisms behind these associations are not fully understood, Monteiro argues that the existing evidence is sufficient to justify discouraging consumption of ultra-processed foods in dietary recommendations and government policies.
“The negative dietary effects of ultra-processed foods have now been made clear by many nationally-representative studies,” Monteiro wrote in his position paper. “[Guidelines] should emphasize the preference for unprocessed or minimally processed foods and freshly made meals and make explicit the need to avoid ultra-processed foods.”
In a counterargument, Astrup argues that classifying foods according to their processing methods does not meaningfully improve upon existing systems and could lead to unintended consequences. For example, there are both nutritional and environmental benefits to increasing the emphasis on plant-based foods, yet many healthful plant-based meat and dairy alternatives are considered ultra-processed. Astrup also contends that unhealthful foods like fries, burgers and pizza would be considered ultra-processed if purchased from a fast-food restaurant but minimally processed if made at home with similar ingredients.
“Clearly, many aspects of food processing can affect health outcomes, but conflating them into the notion of ultra-processing is unnecessary, because the main determinants of chronic disease risk are already captured by existing nutrient profiling systems,” wrote Astrup. “The NOVA classification adds little to existing nutrient profiling systems; characterizes several healthy, nutrient-dense foods as unhealthy; and is counterproductive to solve the major global food production challenges.”
The papers are part of Great Debates in Nutrition (https://academic.oup.com/ajcn/pages/great_debates), a series created and edited by David S. Ludwig, MD, PhD, to advance the mission of the American Society for Nutrition (ASN) to facilitate productive discourse on controversies in nutrition science.
“Scholarly debate is a hallmark of the scientific process,” said AJCN Editor-in-Chief Christopher P. Duggan, MD. “We established Great Debates in Nutrition as a forum for timely and collegial discourse on hot topics in nutrition that have direct relevance for clinical care and public health. By facilitating a rational examination of the evidence, this venue can help to reduce polarization and politicization while moving the field forward.”
Monteiro and Astrup will debate the topic from 2-3:30 p.m. Tuesday, June 14, as part of NUTRITION 2022 LIVE ONLINE. Susan B. Roberts, PhD, of Tufts University will serve as Discussant for the session. After the debate, the authors will produce consensus statements on the topic, to be published in AJCN.
About NUTRITION 2022 LIVE ONLINE
NUTRITION 2022 LIVE ONLINE is part of a new year-around experience featuring ASN’s flagship annual meeting held virtually June 14-16, 2022, plus learning and networking opportunities that will be offered throughout the year. The online annual meeting is a dynamic virtual event showcasing new research findings and timely discussions on food and nutrition. Scientific symposia explore hot topics including clinical and translational nutrition, food science and systems, global and public health, population science and cellular and physiological nutrition and metabolism. https://nutrition.org/nutrition-2022/ #NutritionLiveOnline

A new study from researchers at the Johns Hopkins Bloomberg School of Public Health found that people who smoked tobacco cigarettes developed heart failure at twice the rate of those who never smoked. This higher rate occurred in two major heart failure subtypes and confirms that cigarette smoking presents a significant risk factor for both.
The study is thought to be one of the first to assess smoking’s association with both heart failure subtypes: reduced ejection fraction and preserved ejection fraction.
For their study, the researchers analyzed records from a long-running study of nearly 9,500 individuals in four U.S communities. The study found that participants who had stopped smoking retained a significantly increased risk of either type of heart failure for decades after they’d stopped smoking.
The study was published online June 6in the Journal of the American College of Cardiology.
“These findings underline the importance of preventing smoking in the first place, especially among children and young adults.” says study senior author Kunihiro Matsushita, MD, PhD, associate professor in the Bloomberg School’s Department of Epidemiology. “We hope our results will encourage current smokers to quit sooner rather than later, since the harm of smoking can last for as many as three decades.”
Heart failure is a progressive condition in which the heart loses its ability to pump enough blood to meet the body’s needs. It’s one of the most common causes of disability and death in developed countries, with more than 6 million adults living with heart failure in the U.S. alone, according to the Centers for Disease Control and Prevention most recent data. Besides cigarette smoking, risk factors for heart failure include obesity, hypertension, diabetes, coronary artery disease, and advanced age.

Most parents know it even if they can’t prove it: When a baby becomes distressed, its mother has a unique power to soothe and calm the infant with little more than a loving embrace and some tender words.
To the lay person, it’s one of life’s mysteries — operating almost as if by magic — and not even in the research fields of pediatrics and behavioural neuroscience is the process well understood.
The story is also different for new mothers who experience post-partum depression (PPD), which affects up to 20% of people who give birth.
“Myriad studies have shown that mothers with postpartum depression struggle calming their distressed babies,” says John Krzeczkowski, postdoctoral fellow in the Department of Psychology and with the LaMarsh Centre for Child and Youth Research. “However, it is not known how mothers’ soothing signals are transmitted to their baby, how postpartum depression disrupts this process, or if treating depressed mothers can alter these signals.
“To investigate this, my team and I examined links between mother and infant physiology when babies were distressed.”
Krzeczkowski is the lead author of “Follow the leader: Maternal transmission of physiological regulatory support to distressed infants in real-time,” published today in the Journal of Psychopathology and Clinical Science.

A new study provides a better understanding of how the pandemic virus causes depression, anxiety, and the loss of concentration known as “brain fog” in patients that develop long COVID.
In most individuals, the virus, SARS-CoV-2, is successfully cleared by the immune system, but some struggle with prolonged complications, the cause of which is unknown.
Led by researchers from NYU Grossman School of Medicine, the study, which examined hamsters and human tissue samples, found that, well after the initial viral infection was over, the most profound biological changes occur in the olfactory system, made up of the nasal cavity, the specialized cells lining it, and the adjacent brain region that receives input on odors, the olfactory bulb. While a recent study from the same lab showed how SARS-COV-2 infection hinders the sense of smell by changing the activity of certain olfactory proteins (receptors), the new study reveals how the sustained immune reaction in olfactory tissue affects brain centers that govern emotion and cognition.
Published online June 7in Science Translational Medicine, the study is the first to show that hamsters previously infected with SARS-CoV-2 develop a unique inflammatory response in olfactory tissue, say the study authors. Unlike much of the COVID-19 research published to date, this study benchmarked how the response to SARS-CoV-2 in hamsters compared to influenza A, the virus responsible for the ‘swine flu’ pandemic in 2009. Specifically, the study found that while the two viruses generated a similar response in the lungs, only SARS-CoV-2 triggered a chronic immune response in the olfactory system that was still evident one month post-viral clearance.
This chronic inflammatory state seen with SARS-CoV-2 corresponded with an inrushing of immune cells such as microglia and macrophages, which clean up debris left in the wake of the dead and dying olfactory cell lining. They recycle that material but also trigger additional production of cytokines, pro-inflammatory signaling proteins. This biology was also evident in olfactory tissue taken from autopsies in patients that had recovered from initial COVID-19 infections, but had died of other causes.
“Given the systemic scope of its findings, this study suggests that the molecular mechanism behind many long COVID-19 symptoms stems from this persistent inflammation while describing an animal model close enough to human biology to be useful in the design of future treatments,” says senior study author Benjamin tenOever, PhD, professor in the Departments of Medicine and Microbiology at NYU Langone Health.

The most effective intervention to prevent preterm birth is the administration of a natural hormone, progesterone, in patients at risk for premature delivery. Two categories of patients have been eligible for this treatment: those with a short cervix and those with a previous preterm birth.
But research published this week in the American Journal of Obstetrics and Gynecology by researchers of the Perinatology Research Branch at the Wayne State University School of Medicine indicates that progesterone is not effective in reducing the rate of preterm birth in women with a history of such birth.
In the article, “Does vaginal progesterone prevent recurrent preterm birth in women with a singleton gestation and a history of spontaneous preterm birth? Evidence from a systematic review and meta-analysis,” the researchers call for revision of American College of Obstetricians and Gynecologists, and Society for Maternal-Fetal Medicine guidelines that recommend the use of progesterone in women with a history of spontaneous pre-term birth.
“We have advocated that vaginal progesterone reduces the rate of preterm birth in women with a short cervix. This evidence is solid and derived from multiple studies including randomized clinical trials, meta-analyses and implementation research,” said Roberto Romero, M.D., DMedSci, chief of the Eunice Kennedy Shriver National Institute of Child Health and Human Development’s Perinatology Research Branch and Professor of Molecular Obstetrics and Genetics at the Wayne State University School of Medicine. “Some people believe that vaginal progesterone is effective not only in women with a short cervix but also in patients with a prior history of preterm birth. We have completed a systematic review and meta-analysis that shows that this is not the case.”
The effective use of vaginal progesterone in women identified with a short cervix via sonograph to prevent pre-term birth was identified and developed by the PRB in 2010. But extrapolating these findings to patients with a prior history of preterm birth is not correct, the latest findings show.
Women with a history of spontaneous preterm birth have a 2.5- to four-fold increased risk of subsequent such issues compared to women with no history of pre-term birth. The American College of Obstetricians and Gynecologists, and the Society for Maternal-Fetal Medicine recommend the use of vaginal progesterone or 17α-hydroxyprogesterone caproate for all pregnant women with a history of pre-term birth.
“We believe it is important to understand the limitations of a successful strategy to avoid overtreatment. We advocate for universal screening of cervical length and the identification of patients who may benefit from a specific intervention. In other words, individualized medicine and not one size fits all,” said Dr. Romero, who published the findings with Agustin Conde-Agudelo, M.D., M.P.H., Ph.D., adjunct professor of Obstetrics and Gynecology, and head of the Unit of Perinatal Epidemiology, Systematic Reviews and Meta-analyses.
The team reviewed findings from 10 randomized controlled trials that compared vaginal progesterone to placebo or no treatment in asymptomatic women with a singleton gestation and a history of spontaneous preterm birth. They found no convincing evidence that the use of progesterone prevented pre-term birth in these women.
Preterm labor, Dr. Romero explained, is a syndrome associated with multiple mechanisms of disease, including infection and/or inflammation, decidual hemorrhage and vascular disease, uterine overdistention, cervical disease, disruption of maternal-fetal tolerance, maternal stress and decline in progesterone action. The syndromic nature of preterm labor explains why a single method of intervention does not prevent all or even predict most cases of preterm birth, he said.
For more information, please see this video: https://youtu.be/b2IeXYSvtf8

People with HIV have a higher rate of breakthrough COVID-19 infections after vaccination, compared to people without HIV, according to findings from a study led by researchers at the Johns Hopkins Bloomberg School of Public Health.
In the study, the researchers analyzed anonymized health records among nearly 114,000 people fully vaccinated with either two doses of mRNA vaccines or one dose of the J&J viral vector vaccine as of June 30, 2021 through December 31, 2021. Comparing vaccine recipients with and without HIV, the researchers found that the chance of a positive SARS-CoV-2 test result or a COVID-19 diagnosis within nine months after full vaccination, though low, was 28 percent higher among people with HIV. The risk of breakthrough infection during the period examined was 3.8 percent for the non-HIV group and 4.4 percent for the HIV group.
The results are published June 7 in JAMA Network Open.
“These findings should alert all people with HIV to their greater risk of COVID-19 breakthrough, and can inform official recommendations about COVID-19 vaccination for people with HIV,” says study senior author Keri Althoff, PhD, associate professor in the Bloomberg School’s Department of Epidemiology.
Public health officials have had concerns about potentially elevated COVID-19 risk among people with weakened immune systems, including those with HIV, since the start of the pandemic. The Centers for Disease Control and Prevention currently recommends that people who are “moderately or severely immunocompromised” — a category that includes people with HIV who are untreated or have low CD4 T-cell counts (