Publisher Health

New research combining computer modeling and experiments with macaques shows the body’s immune system helps control human immunodeficiency virus (HIV) infections largely by suppressing viral production in already infected cells while also killing viral infected cells, but only within a narrow time window at the start of a cell’s infection.
“To eliminate HIV, we have to understand how the immune system attempts to control the infection,” said Ruy M. Ribeiro, a theoretical biologist at Los Alamos National Laboratory who led the development of the model underpinning the research. Ribeiro is the corresponding author of the paper about the findings, published in Nature Communications.
The research team included Los Alamos Senior Fellow Alan S. Perelson and a former Los Alamos postdoctoral researcher now at the Fred Hutchinson Cancer Research Center. Their collaborators at the University of Pittsburg managed the experiments with macaques infected with simian immunodeficiency virus (SIV) to validate the model. SIV infections in monkeys behaves the same way as HIV in humans.
Helping the immune system attack HIV
“The immune system can’t eliminate an HIV infection,” Ribeiro notes, “but pinpointing the existing mechanism by which it is to some extent controlling HIV is very important for designing treatments to enhance that mechanism. If we can modulate the immune system to help control HIV better, we may be able to cure the disease at some point.”
Under the overall leadership of Perelson, Los Alamos has been a global leader in modeling viral infections, including HIV, since the mid-1990s. For the Nature Communications paper, the research team extended a mathematical model published in 2017 by Ribeiro and others at Los Alamos that simulates the interactions and lifecycle of cells that will be infected, already infected cells and the virus.
The new model also simulates the potential effects of the immune response, which include killing the cells, generating proteins that suppress the production of virus or helping mount a defense that prevents the virus entering cells.

An early phase in the process of developing Alzheimer’s disease is a metabolic increase in a part of the brain called the hippocampus, report researchers from Karolinska Institutet in a study published in Molecular Psychiatry. The discovery opens up for new potential methods of early intervention.
Alzheimer’s disease is the most common form of dementia and strikes about 20,000 people in Sweden every year. Researchers now show that a metabolic increase in the mitochondria, the cellular power plants, is an early indicator of the disease.
The teams behind the study used mice that developed Alzheimer’s disease pathology in a similar way to humans. The increase in metabolism in young mice was followed by synaptic changes caused by disruption to the cellular recycling system (a process known as autophagy), a finding that was awarded the Nobel Prize in Physiology or Medicine in 2016.
After a time, metabolism in the Alzheimer brain usually declines, which contributes to the degradation of synapses. This the researchers could also see in the older mice, which had had the disease for longer time.
“The disease starts to develop 20 years before the onset of symptoms, so it’s important to detect it early — especially given the retardant medicines that are starting to arrive,” says Per Nilsson, associate professor at the Department of Neurobiology, Care Sciences and Society, Karolinska Institutet. “Metabolic changes can be a diagnostic factor in this.”
Maria Ankarcrona, professor at the same department continues:
“Interestingly, changes in metabolism can be seen before any of the characteristic insoluble plaques have accumulated in the brain. The different energy balance tallies with what we’ve seen in images of the Alzheimer brain, but we’ve now detected these changes at an earlier stage.”
The study was conducted in close partnership between both researchers’ groups, who analysed the part of the mouse brain called the hippocampus, a structure that plays an important part in short-term memory and that is affected early in the pathological process.

Does electromagnetic radiation emitted by mobile phones affect semen quality? While various environmental and lifestyle factors have been proposed to explain the decline in semen quality observed over the last fifty years, the role of mobile phones has yet to be demonstrated. A team from the University of Geneva (UNIGE), in collaboration with the Swiss Tropical and Public Health Institute (Swiss TPH), has published a major cross-sectional study on the subject. It shows that frequent use of mobile phones is associated with a lower sperm concentration and total sperm count. However, researchers did not find any association between mobile phone use and low sperm motility and morphology. Read the results in Fertility & Sterility.
Semen quality is determined by the assessment of parameters such as sperm concentration, total sperm count, sperm motility and sperm morphology. According to the values established by the World Health Organization (WHO), a man will most probably take more than one year to conceive a child if his sperm concentration is below 15 million per milliliter. In addition, the percentage chance of pregnancy will decrease if the sperm concentration is below 40 million per milliliter.
Many studies have shown that semen quality has decreased over the last fifty years. Sperm count is reported to have dropped from an average of 99 million sperm per millilitre to 47 million per millilitre. This phenomenon is thought to be the result of a combination of environmental factors (endocrine disruptors, pesticides, radiation) and lifestyle habits (diet, alcohol, stress, smoking).
Assessing the impact of mobile phones
Is the mobile phone also to blame? After conducting the first national study (2019) on the semen quality of young men in Switzerland, a team from the University of Geneva (UNIGE) has published the largest cross-sectional study on this topic. It is based on data from 2886 Swiss men aged 18 to 22, recruited between 2005 and 2018 at six military conscription centres.
In collaboration with the Swiss Tropical and Public Health Institute (Swiss TPH), scientists studied the association between semen parameters of 2886 men and their use of mobile phones. ”Men completed a detailed questionnaire related to their lifestyle habits, their general health status and more specifically the frequency at which they used their phones, as well as where they placed it when not in use,” explains Serge Nef, full professor in the Department of Genetic Medicine and Development at the UNIGE Faculty of Medicine and at the SCAHT — Swiss Centre for Applied Human Toxicology, who co-directed the study.
These data revealed an association between frequent use and lower sperm concentration. The median sperm concentration was significantly higher in the group of men who did not use their phone more than once a week (56.5 million/mL) compared with men who used their phone more than 20 times a day (44.5 million/mL). This difference corresponds to a 21% decrease in sperm concentration for frequent users ( >20 times/day) compared to rare users (
Is 4G less harmful than 2G?

In a Finnish study, significant differences in the gene activity of the fetal intestine, brain and placenta were identified, depending on the microbes in the mother’s body and the compounds produced by them. The findings indicate that maternal microbes are important to her offspring’s development and health.
The microbiota of the mother or dam is thought to be important for the development and health of her offspring. However, so far little is known about how interactions with the microbiota begin and what the mechanisms of action are.
A collaborative study carried out at the Universities of Helsinki, Eastern Finland and Turku investigated how the maternal microbiota affects fetal development by comparing the foetuses of normal and germ-free mouse dams living in a sterile environment. The researchers measured gene expression and the concentrations of small-molecular compounds, or metabolites, in the fetal intestine, brain and placenta.
“The effects of the dam microbiota and the metabolites it produces on fetal development have not been previously investigated in such a comprehensive manner. Our study sheds light on the significance of the microbiota and the mechanisms by which the microbiota affects individual development and pregnancy. We identified previously unknown compounds in the fetus, which are likely to be microbial and which can be important for individual development,” says Mikael Niku, the principal investigator of the study from the Faculty of Veterinary Medicine, University of Helsinki.
The researchers demonstrated that there were considerable differences in gene expression in the intestine, brain and placenta of the foetuses of germ-free and normal mouse dams. In the gut, genes associated with the immune system and host-microbe interactions were less active in the foetuses of germ-free dams. There were significant differences in the expression of genes in the brain associated with the development and functioning of the nervous system. In the placenta, there were differences in the expression of several important genes that regulate pregnancy. The differences were more extensive in male foetuses, indicating that they may be more sensitive to the effects of the maternal microbiota, at least in mice.
The researchers discovered that the expression of many important genes was associated with the concentration of metabolites likely to be modulated by the maternal microbiota. These metabolites were absent in the foetuses of germ-free dams, or occurred at least at significantly lower concentrations.
“It would appear that such microbial products are likely to affect the development of the intestine and brain as well as the functioning of the placenta. Many of these metabolites are previously unknown,” Niku notes.
The group is now investigating the occurrence of microbial metabolites in other mammals: piglets and calves, as well as in the meconium and amniotic fluid samples of babies.
Today, deficiencies in the host-microbe interactions of the early stages of life caused by, for example, an unbalanced environment or antibiotics, may predispose the offspring to dysfunction in the immune system, such as inflammatory bowel diseases and allergies.
“Our research helps us understand the origin of such disorders, making it potentially possible in the future to enhance their prevention and treatment,” Niku muses.

IBD is an umbrella term for chronic inflammatory bowel diseases, with a population prevalence of around 0.5%. The main types of IBD are ulcerative colitis and Crohn’s disease. Unlike irritable bowel syndrome (IBS), IBD results in visible damage to the intestinal mucous membrane.
IBD is characterized by intermittent symptoms. Periods of high disease activity are sometimes followed by longer periods of low or no activity. However, the extent to which IBD patients with low disease activity are also at increased risk of serious infections, including sepsis, has been unclear.
The current study, published in the journal Clinical Gastroenterology and Hepatology, included data on 55,626 individuals diagnosed with IBD. ‘Serious infections’ referred to infections requiring hospitalization.
The difference between healed and unhealed
The results show that during periods of low disease activity but active gastrointestinal inflammation, known as microscopic inflammation, there was an increased risk of being affected by serious infections compared to periods of microscopically healed intestinal mucosa.
In the case of microscopic inflammation, the number of serious infections was 4.62 per 100 people per year. The corresponding figure for microscopically healed mucosa was 2.53. This corresponded to a 59% relative risk increase for residual microscopic gastrointestinal inflammation, on adjusting the results for various confounders.
Interestingly, the results held true even after adjusting for the prescribed IBD medications, and were otherwise similar regardless of age group, sex, and level of education.

A susceptibility to gain weight may be written into molecular processes of human cells, a Washington State University study indicates.
The proof-of-concept study with a set of 22 twins found an epigenetic signature in buccal or cheek cells appearing only for the twins who were obese compared to their thinner siblings. With more research, the findings could lead to a simple cheek swab test for an obesity biomarker and enable earlier prevention methods for a condition that effects 50% of U.S. adults, the researchers said.
“Obesity appears to be more complex than simple consumption of food. Our work indicates there’s a susceptibility for this disease and molecular markers that are changing for it,” said Michael Skinner, a WSU professor of biology and corresponding author of the study published in the journal Epigenetics.
The study focused on twins to help eliminate the role of genetics and instead focus on epigenetics, molecular processes which are separate from DNA but influence how genes are expressed. The fact that the epigenetic signature was found in cheek cells rather than fat cells also suggests that the obesity signature is likely found throughout the human system.
The signature’s systemic nature also suggests that something may have occurred early in one twin’s life that triggered obesity susceptibility, Skinner added. It’s also possible that it was inherited by one twin and not the other.
For this study, Skinner worked with lead author Glen Duncan, director of the Washington State Twin Registry based at WSU, to identify 22 twin pairs, both identical and fraternal, who were discordant for obesity: one sibling had a body mass index of 30 or higher, the standard for obesity defined by the Centers of Disease Control and Prevention, while the other sibling was in the normal range of 25 and below.
The research team analyzed cells from cheek swabs provided by the twins. In the cells from the twin siblings who were obese, they found similar epigenetic changes to DNA methylation regions, areas where molecular groups made of methane attach to DNA, regulating gene expression or turning genes on or off.

A new study has shown that women who are taking the oral contraceptive pill are less likely to report depression.
The research, which analysed data from 6,239 women in the United States aged 18-55 years old, found that the prevalence of major depression amongst users of the oral contraceptive pill (OCP) was significantly lower, at 4.6%, compared to former OCP users (11.4%).
The study was led by researchers at Anglia Ruskin University (ARU), alongside experts from the Dana-Farber Cancer Institute in Boston and University of California, Davis.
The researchers suggest two possible explanations for their findings, which are contrary to a commonly held belief that OCP can cause depression.
One is that taking the pill can remove concerns about unwanted pregnancy, therefore helping to improve the mental health of OCP users. It is also possible the results could be influenced by “survivor bias,” where women who experience signs of depression while using OCP stop taking it, moving them into the category of former users.
The cross-sectional study, which used data collected by the Center for Disease Control and Prevention in the United States, controlled for demographic characteristics, chronic conditions, and the use of antidepressants.
In both users and former users, widowed, divorced or separated women, obese women or those with a history of cancer were more likely to report depression. In addition, in former users, depression was more commonly reported in women who were Black or Hispanic, were smokers, had lower levels of education, or were experiencing poverty.

Many hidden genetic variations can be detected with Chameleolyser, a new method developed in Nijmegen. The information is already yielding new patient diagnoses and may also lead to the discovery of as yet unknown disease genes, write Wouter Steyaert and Christian Gilissen of Radboudumc in Nature Communications.
Medical science has been using exome sequencing to map the genes of individual patients with rare diseases for about 15 years. With this technique, the DNA of a person’s approximately 20,000 human genes are cut into small pieces so the DNA letters can be read off. This creates a huge amount of tiny DNA fragments, which are then reassembled into whole genes like a jigsaw puzzle. The result is an overview of that single person’s 20,000 genes.
Evolutionary engine
‘Unfortunately, such an overview is never quite complete,’ says Christian Gilissen, professor of Genome Bioinformatics. ‘That’s because of the evolution of our genome, our hereditary material. When copying DNA, things sometimes go wrong. Small pieces of DNA disappear or are added. Some pieces are copied more than once. It also happens that a copied gene is placed somewhere else in the genome, giving you a pseudogene in addition to the original gene. These genetic “sloppinesses” are very important because they are the engine of evolution. This is how genetic changes arise. Changes that can be without effect or beneficial, but sometimes also cause new diseases.’
Confusing pseudogenes
Zooming in on the gene and pseudogenes for a moment. The gene has a function, the pseudogen usually does not. Over time, small changes, mutations, can occur in both the gene and pseudogen. But gene and pseudogen are so similar that when sequencing it is not clear which piece belongs to the gene and which to the pseudogen. Gilissen: ‘For this reason, these DNA regions are not included in the analysis. A mutation found may originate from the pseudogen and have no meaning. If you add that mutation to the normal gene, you would make a wrong diagnosis. We don’t want that.’
Making the invisible visible
With Wouter Steyaert, Gilissen developed a method — Chameleolyser — that detects gene and pseudogen combinations in existing exome sequencing data and can also visualize the genetic variations between them. Steyaert: ‘We are now picking up a lot of genetic variation that was previously invisible. Per exome, we find about sixty additional genetic variants. For a number of people, this data allowed us to definitively determine the cause of their disease. With a new sequencing technique from PacBio, which analyzes longer stretches of DNA, we have established the reliability of our method.’
New disease genes, new diagnoses
The new method is interesting because it can be applied to already existing exome sequencing data. Thus, no new studies in patients are necessary. Any sequencing center in the world can apply the method. ‘Such a large-scale analysis can also provide new biological insights,’ Gilissen says. ‘In many disorders, the genetic cause can only be determined in half of the patients. We think we will also find new disease genes in those gene-pseudogen combinations. For some of those patients, that may be where the genetic cause for their condition lies.’

Those at risk for Type 2 diabetes may already know to avoid sugar, but new research suggests they may want to skip the salt as well.
A new study from Tulane University published in Mayo Clinic Proceedings found that frequently adding salt to foods was associated with an increased risk of developing Type 2 diabetes.
The study surveyed more than 400,000 adults registered in the UK Biobank about their salt intake. Over a median of 11.8 years of follow-up, more than 13,000 cases of Type 2 diabetes developed among participants. Compared to those who “never” or “rarely” used salt, participants who “sometimes,” “usually,” or “always” added salt had a respective 13%, 20%, and 39% higher risk of developing Type 2 diabetes.
“We already know that limiting salt can reduce the risk of cardiovascular diseases and hypertension, but this study shows for the first time that taking the saltshaker off the table can help prevent Type 2 diabetes as well,” said lead author Dr. Lu Qi, HCA Regents Distinguished Chair and professor at the Tulane University School of Public Health and Tropical Medicine.
Further research is needed to determine why high salt intake could be linked to a higher risk of Type 2 diabetes. However, Qi believes salt encourages people to eat larger portions, increasing the chances of developing risk factors such as obesity and inflammation. The study found an association between frequent consumption of salt and higher BMI and waist-to-hip ratio.
Qi said the next step is to conduct a clinical trial controlling the amount of salt participants consume and observing the effects.
Still, Qi said it’s never too early to start searching for low-sodium ways to season your favorite foods.
“It’s not a difficult change to make, but it could have a tremendous impact on your health,” Qi said.

Sperm can modulate their energetics by regulating their flagellar waveform — how the sperm oscillate their tails — in order to adapt to varying fluid environments, potentially optimizing their motility and navigation within the reproductive tract. This research is reported in a study publishing November 1 in the journal Cell Reports Physical Science.
“Our approach allowed us to investigate how variations in viscosity and shear rates affect sperm behavior at the single-cell level, which was not possible using traditional methods,” says senior study author Reza Nosrati of Monash University.
Biochemical and biophysical cues within the reproductive tract serve as filters against low-quality sperm and guidance mechanisms for high-quality sperm to navigate toward the egg. For example, during sexual intercourse, intensified mucus secretions within the oviduct stimulate fluid movement in the fallopian tube toward the uterus. This flow helps prevent pathogens from invading the reproductive tract by flushing them down and simultaneously selects sperm capable of swimming against the flow toward the egg via a phenomenon known as rheotaxis.
But due in part to the limitations of conventional microscopy methods and population-level studies, it has remained unclear how factors like fluid flow and viscosity interact to influence sperm flagellar beating behavior at the single-cell level. Moreover, current clinical practices largely utilize low-viscosity media and stagnant flow conditions, even though the practical advantages of considering physiologically relevant environments might be significant.
In this study, Nosrati and his team designed a “testing arena” for the sperm to observe their behavior under physiologically relevant conditions. This device leveraged microfluidics to examine sperm flagellar waveform and energetics in response to changes in flow and viscosity. By tethering bull sperm in a microchannel, the researchers exposed the same individual sperm to a range of viscosities and shear rates, which refer to the rates of change in velocity at which one layer of fluid passes over an adjacent layer. Using high-speed, high-resolution microscopy, the researchers quantified flagellar dynamics at 200 frames per second.
The findings showed that sperm flagellar waveforms are primarily influenced by viscosity rather than the shear rate, and their synergistic effect promotes energy-efficient beating behavior. The motility and energetics of sperm were less influenced by fluid flow in environments with lower viscosities. But in high-viscosity media, an increase in shear rate from 0 to 6 per second at 75 millipascal seconds reduced the flagellar curvature by 20%, and the flagellar beating frequency was highest at a shear rate of 3 per second, which is favorable for sperm rheotaxis.
According to the authors, this phenomenon suggests a potential increase in energy production and changes in flagellar beating behavior under these specific conditions to possibly enable rheotaxis and facilitate a transition from circular motion to rolling motion. This increased energetic output observed at a shear rate of 3 per second suggests that the sperm adjusts its power generation to adapt and respond to the fluid dynamics, thereby enabling efficient swimming against the flow.
Currently, the researchers are refining their imaging techniques and experimental platform for a follow-up study to examine free-swimming sperm under similar conditions. “It’s also crucial to better understand the importance of these media considerations with respect to sperm selection and fertilization,” Nosrati says. “We plan to run an animal study to evaluate how such properties can influence fertilization and embryo development in assisted reproduction to inform future treatment strategies for better outcomes.”
This work was supported by the Australian Research Council (ARC) Discovery Project, the Australian National Health and Medical Research Council, and Monash University.