Publisher Health

Alzheimer’s disease is predominant in elderly people, but the way age-related changes to lipid composition affect the regulation of biological processes is still not well understood. Links between lipid imbalance and disease have been established, in which lipid changes increase the formation of amyloid plaques, a hallmark of Alzheimer’s disease.
This imbalance inspired researchers from Aarhus University in Denmark to explore the role of lipids comprising the cellular membranes of brain cells.
In Biointerphases, by AIP Publishing, the researchers report on the significant role lipids may play in regulating C99, a protein within the amyloid pathway, and disease progression. Lipids have been mostly overlooked from a therapeutic standpoint, likely because their influence in biological function is not yet fully understood.
Toxic amyloid plaques are formed within the brain when a series of enzymes cleave the protein APP, which sits within the neuronal cell membrane, to form C99, which in turn is cleaved to release the amyloid-beta peptide that can form plaques.
Both C99 and APP are able to protect themselves from cleavage by forming homodimers, a protein composed of two polypeptide chains that are identical. The interaction between C99 molecules is regulated by lipids that make up the membrane in which the protein sits.
“We showed that a change in the cholesterol content of the neuronal cell membrane can change how the C99 dimerizes,” said Amanda Dyrholm Stange, one of the authors. “Our work suggests age-related changes to cholesterol content in the membrane weakens the C99-C99 interaction, which consequently decreases the ‘protective’ effect of the dimerization process, leading to the hypothesis of why more toxic amyloid-beta peptides are released in the elderly.”
Therapeutics for Alzheimer’s disease currently “have a very high failure rate, with no therapeutics developed for a very long period of time, so a novel strategy is desperately needed,” said co-author Nils Anton Berlund. “Attempting to modulate the composition of the lipid membrane would be an entirely new class of Alzheimer’s disease therapeutics but also immensely challenging without side effects.”
The researchers postulate shifting the strategy away from targeting proteins to instead targeting the lipid concentration of membranes may be worthwhile.
“We hope our work will lead the pharmaceutical/biotechnology sector to choose lipid modulation as a means for targeting in drug development, because these changes in lipid composition are linked not just to Alzheimer’s but a large host of diseases — from diabetes to cardiovascular disease,” said co-author Birgit Schiøtt. “We also hope it will lead to more research and funding toward understanding the fundamental science behind the possible regulatory roles of lipids.”
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Materials provided by American Institute of Physics. Note: Content may be edited for style and length.

With preseason football training on the horizon, a new study shows that head impacts experienced during practice are associated with changes in brain imaging of young players over multiple seasons.
The research, conducted by scientists at Wake Forest School of Medicine and the University of Texas Southwestern, is published in the June 15 issue of the Journal of Neurosurgery: Pediatrics.
“Although we need more studies to fully understand what the measured changes mean, from a public health perspective, it is motivation to further reduce head impact drills used during practice in youth football,” said the study’s corresponding author Jill Urban, Ph.D., assistant professor of biomedical engineering at Wake Forest School of Medicine.
The purpose of the study was to examine changes in head impact exposure (HIE) pre- and post-season in a group of 47 athletes who participated in youth football for two or more consecutive years between 2012 and 2017. None of the 47 youth athletes sustained a clinically diagnosed concussion during the study period.
A group of 16 youth athletes who participated in non-contact sports, such as swimming, tennis and track, served as the control group.
Pre- and post-season MRIs were completed for both groups of study participants using diffusion tensor imaging (DTI), a type of neuroimaging that can be used to assess the integrity of the brain’s white matter, indicating possible sites of injury.
In addition, the research team gathered biomechanical data of linear and rotational head accelerations of head impacts from the football group during all practice and games via the Riddell Head Impact Telemetry System in the helmets. That information was transmitted in real time to a sideline data collection field unit for later analysis.
In 19 of the 47 youth football athletes, brain images were obtained pre- and post-season for two consecutive football seasons. Using data from the DTIs and the head impact telemetry system, the researchers found variations in head impact exposures (i.e., the number and severity of head impacts measured) from year-to-year and between athletes. For example, in an examination of data from three consecutive seasons, some youths experienced more impacts in their second year of play than in their first, while other youths experienced fewer impacts in later years of play.
“We observed variability in the amount and direction of imaging changes in the brain related to the amount of exposure that the players experienced on the field,” Urban said. “If we can take efforts to reduce that exposure on-field, we can potentially mitigate changes in brain imaging.
“Our findings further support ongoing efforts to reduce the number of head impacts in football practices. In an upcoming study, we plan to engage stakeholders in the youth football community to develop and test practical solutions informed by the data we collect on the field to reduce head impacts in practice.”
The study was supported by three grants from the National Institutes of Health, namely National Institute of Neurological Disorders and Stroke grants R01NS094410 and R01NS082453, and National Center for Advancing Translational Sciences grant KL2TR001421.
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Materials provided by Wake Forest Baptist Medical Center. Note: Content may be edited for style and length.

Artificial intelligence (AI) may offer a way to accurately determine that a person is not infected with COVID-19. An international retrospective study finds that infection with SARS-CoV-2, the virus that causes COVID-19, creates subtle electrical changes in the heart. An AI-enhanced EKG can detect these changes and potentially be used as a rapid, reliable COVID-19 screening test to rule out COVID-19 infection.
The AI-enhanced EKG was able to detect COVID-19 infection in the test with a positive predictive value — people infected — of 37% and a negative predictive value — people not infected — of 91%. When additional normal control subjects were added to reflect a 5% prevalence of COVID-19 — similar to a real-world population — the negative predictive value jumped to 99.2%. The findings are published in Mayo Clinic Proceedings.
COVID-19 has a 10- to 14-day incubation period, which is long compared to other common viruses. Many people do not show symptoms of infection, and they could unknowingly put others at risk. Also, the turnaround time and clinical resources needed for current testing methods are substantial, and access can be a problem.
“If validated prospectively using smartphone electrodes, this will make it even simpler to diagnose COVID infection, highlighting what might be done with international collaborations,” says Paul Friedman, M.D., chair of Mayo Clinic’s Department of Cardiovascular Medicine in Rochester. Dr. Friedman is senior author of the study.
The realization of a global health crisis brought together stakeholders around the world to develop a tool that could address the need to rapidly, noninvasively and cost-effectively rule out the presence of acute COVID-19 infection. The study, which included data from racially diverse populations, was conducted through a global volunteer consortium spanning four continents and 14 countries.
“The lessons from this global working group showed what is feasible, and the need pushed members in industry and academia to partner in solving the complex questions of how to gather and transfer data from multiple centers with their own EKG systems, electronic health records and variable access to their own data,” says Suraj Kapa, M.D., a cardiac electrophysiologist at Mayo Clinic. “The relationships and data processing frameworks refined through this collaboration can support the development and validation of new algorithms in the future.”
The researchers selected patients with EKG data from around the time their COVID-19 diagnosis was confirmed by a genetic test for the SARS-Co-V-2 virus. These data were control-matched with similar EKG data from patients who were not infected with COVID-19.

Exposure to the rhinovirus, the most frequent cause of the common cold, can protect against infection by the virus which causes COVID-19, Yale researchers have found.
In a new study, the researchers found that the common respiratory virus jump-starts the activity of interferon-stimulated genes, early-response molecules in the immune system which can halt replication of the SARS-CoV-2 virus within airway tissues infected with the cold.
Triggering these defenses early in the course of COVID-19 infection holds promise to prevent or treat the infection, said Ellen Foxman, assistant professor of laboratory medicine and immunobiology at the Yale School of Medicine and senior author of the study. One way to do this is by treating patients with interferons, an immune system protein which is also available as a drug.
“But it all depends upon the timing,” Foxman said.
The results were published June 15th in the Journal of Experimental Medicine.
Previous work showed that at the later stages of COVID-19, high interferon levels correlate with worse disease and may fuel overactive immune responses. But recent genetic studies show that interferon-stimulated genes can also be protective in cases of COVID-19 infection.

Adults who skip breakfast are likely to miss out on key nutrients that are most abundant in the foods that make up morning meals, a new study suggests.
An analysis of data on more than 30,000 American adults showed that skipping breakfast — and missing out on the calcium in milk, vitamin C in fruit, and the fiber, vitamins and minerals found in fortified cereals — likely left adults low on those nutrients for the entire day.
“What we’re seeing is that if you don’t eat the foods that are commonly consumed at breakfast, you have a tendency not to eat them the rest of the day. So those common breakfast nutrients become a nutritional gap,” said Christopher Taylor, professor of medical dietetics in the College of Medicine at The Ohio State University and senior author of the study.
According to the U.S. Department of Agriculture’s latest dietary guidelines, calcium, potassium, fiber and vitamin D are considered “dietary components of public health concern” for the general U.S. population — with iron added for pregnant women — because shortages of those nutrients are associated with health problems.
Most research related to breakfast has focused on the effects of the missed morning meal on children in school, which includes difficulty focusing and behavioral problems.
“With adults, it’s more like, ‘You know how important breakfast is.’ But now we see what the implications really are if they miss breakfast,” Taylor said.

A tickle in the nose can help trigger a sneeze, expelling irritants and disease-causing pathogens. But the cellular pathways that control the sneeze reflex go far beyond the sinuses and have been poorly understood. Now, a team led by researchers at Washington University School of Medicine in St. Louis has identified, in mice, specific cells and proteins that control the sneeze reflex.
“Better understanding what causes us to sneeze — specifically how neurons behave in response to allergens and viruses — may point to treatments capable of slowing the spread of infectious respiratory diseases via sneezes,” said Qin Liu, PhD, an associate professor of anesthesiology and the study’s senior investigator.
The findings are published June 15 in the journal Cell.
“We study the neural mechanism behind sneezing because so many people, including members of my own family, sneeze because of problems such as seasonal allergies and viral infections,” said Liu, a researcher in the university’s Center for the Study of Itch and Sensory Disorders. “Our goal is to understand how neurons behave in response to allergies and viral infections, including how they contribute to itchy eyes, sneezing and other symptoms. Our recent studies have uncovered links between nerve cells and other systems that could help in the development of treatments for sneezing and for fighting infectious respiratory diseases.”
Sneezing is the most forceful and common way to spread infectious droplets from respiratory infections. Scientists first identified a sneeze-evoking region in the central nervous system more than 20 years ago, but little has been understood regarding how the sneeze reflex works at the cellular and molecular level.
In the new study, Liu and her team established a mouse model in an attempt to identify which nerve cells send signals that make mice sneeze. The researchers exposed the mice to aerosolized droplets containing either histamine or capsaicin, a pungent compound made from chili peppers. Both elicited sneezes from the mice, as they do in people.
By examining nerve cells that already were known to react to capsaicin, Liu’s team was able to identify a class of small neurons linked to sneezing that was caused by that substance. The researchers then looked for molecules — called neuropeptides — that could transmit sneeze signals to those nerve cells, and found that a molecule called neuromedin B (NMB) was required for sneezing.
Conversely, when they eliminated the NMD-sensitive neurons in the part of the nervous system that evoked sneezes in the mice, they blocked the sneeze reflex. Those neurons all make a protein called the neuromedin B receptor. In mice without that receptor, sneezing again was greatly reduced.
“Interestingly, none of these sneeze-evoking neurons were housed in any of the known regions of the brainstem linked to breathing and respiration,” Liu said. “Although we found that sneeze-evoking cells are in a different region of the brain than the region that controls breathing, we also found that the cells in those two regions were directly connected via their axons, the wiring of nerve cells.”
The researchers also found they could stimulate the sneeze reflex by exposing part of the mouse brain to the NMB peptide. Further, the animals began to sneeze even though they had not been exposed to any capsaicin, histamine or other allergens.
Because many viruses and other pathogens — including the majority of human rhinoviruses and coronaviruses such as Middle East respiratory syndrome coronavirus (MERS-CoV) and SARS-CoV-2, the coronavirus that causes COVID-19 — are spread in part by aerosolized droplets, Liu said it may be possible to limit the spread of those pathogens by targeting NMB or its receptor to limit sneezing in those known to be infected.
“A sneeze can create 20,000 virus-containing droplets that can stay in the air for up to 10 minutes,” Liu explained. “By contrast, a cough produces closer to 3,000 droplets, or about the same number produced by talking for a few minutes. To prevent future viral outbreaks and help treat pathological sneezing caused by allergens, it will be important to understand the pathways that cause sneezing in order to block them. By identifying neurons that mediate the sneeze reflex, as well as neuropeptides that activate these neurons, we have discovered targets that could lead to treatments for pathological sneezing or strategies for limiting the spread of infections.”

Women exposed to higher levels of air pollution during pregnancy have babies who grow unusually fast in the first months after birth, putting on excess fat that puts them at risk of obesity and related diseases later in life, new CU Boulder research shows.
The study of Hispanic mother-child pairs, published this week in the journal Environmental Health, is the latest to suggest that poor air quality may contribute at least in part to the nation’s obesity epidemic, particularly among minority populations who tend to live in places with more exposure to toxic pollutants.
About one in four Hispanic youth in the United States are obese, compared to about 14% of white youth and 11% of Asian youth.
“Higher rates of obesity among certain groups in our society are not simply a byproduct of personal choices like exercise and calories in, calories out. It’s more complicated than that,” said senior author Tanya Alderete, an assistant professor in the Department of Integrative Physiology. “This study and others suggest it can also relate to how much of an environmental burden one carries.”
Previous research has shown pregnant women who smoke or are chronically exposed to air pollution tend to have smaller birthweight babies. In the first year of life, those babies tend to race to catch up, gaining weight unusually fast. Accelerated weight gain in early life has been linked to diabetes, heart disease and weight problems in childhood and adolescence.
“This period, either during pregnancy or shortly after birth, is a critical window of development and adverse exposures can program the infant to have a host of problems later in life,” said lead author William Patterson, a doctoral student.

Researchers at the University of Helsinki and the Beatson Institute for Cancer Research in Glasgow have discovered how mutated cells promote their chances to form cancer. Typically, the accumulation of harmful cells is prevented by active competition between multiple stem cells in intestinal glands, called crypts.
“The functioning of intestinal stem cells relies on growth factors, named Wnts, produced by the surrounding environment. Intestinal cancers typically originate from stem cells where mutations allow growth independent of these factors. When we removed a gene called Notum, which renders Wnts inactive, from mutated stem cells, the number of precancerous adenomas in the intestine was greatly reduced. We found that mutated cells use this gene to block environmental factors critical to normal stem cells gaining advantage in competition,” says Postdoctoral Researcher Nalle Pentinmikko.
The research group of Assistant Professor Pekka Katajisto at the Institute of Biotechnology of the University of Helsinki had already previously discovered that the same gene, also called an ‘ageing gene’, is expressed in normal tissue when we age, reducing the ability of stem cells to repair damage. The current study shows that mutated cells use the same gene in order to establish a permanent footing in the tissue.
“Mutated cells kind of hijack the ageing gene and use it against the healthy stem cells,” Katajisto says.
The results from this study may lead to the development of new therapies, because the function of the enzyme encoded by the ageing gene can be blocked pharmacologically. The research group led by Katajisto has previously used a compound for this purpose in aged research animals to enhance the function of aged stem cells. In the current study, researchers used the same method to reduce the chance of mutated cells winning in competition. A three-week treatment reduced the number of adenomas in animal models.
“The results are promising and create a foundation for developing new therapies for patients predisposed to intestinal cancers. This research demonstrates that by enhancing the natural mechanisms of how tissues remove damaged cells, we could also reduce cancer risk in other tissues,” Pekka Katajisto concludes.
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Materials provided by University of Helsinki. Note: Content may be edited for style and length.

Hypertension is a widespread comorbidity of patients with obesity that greatly increases the risk of mortality and disability. In recent years, researchers have found that a high-calorie diet increases the density of blood vessels (hypervascularization) in the hypothalamus — an important “eating control” area in our brain. Researchers hypothesized that elevated hormone levels of leptin are associated with a higher risk of developing hypertension. However, the exact mechanisms that contribute to the condensed growth of blood vessels in the hypothalamus were unknown.
New research conducted by Cristina García-Cáceres’ research group at Helmholtz Zentrum München has now revealed that obese mice do not increase the amount of blood vessels in the hypothalamus when they lack the hormone leptin. Leptin is produced by adipose tissue, is involved in the control of hunger and satiety, and plays an important role in the regulation of fat metabolism in humans and mammals.
Once the researchers increased the hormone leptin in these mice, certain brain cells, the astrocytes, boosted the production of a specific growth factor. This growth factor, in turn, promoted vessel growth. The result was an increased number of vessels in the hypothalamus (and no other brain region). The scientists thus demonstrated that leptin is mainly responsible for the increased concentration of vessels in the hypothalamus and that this process is mediated via astrocytes.
“We provide a paradigm shift in our understanding of how the hypothalamus controls blood pressure in obesity,” explains first author Tim Gruber. “While previous research has focused primarily on neurons, our research highlights the new role of astrocytes, historically assumed less relevant than neurons, in controlling blood pressure.”
Looking into the future, according to study leader Cristina García-Cáceres, one important question remains: How exactly do astrocytes communicate with neurons? “We have started to answer this question using in vivo real-time imaging of astrocyte-neuron circuit function in the hypothalamus,” the researcher says.
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Materials provided by Helmholtz Zentrum München – German Research Center for Environmental Health. Note: Content may be edited for style and length.

Researchers have identified two subgroups of adolescents who self-harm and have shown that it is possible to predict those individuals at greatest risk almost a decade before they begin self-harming.
The team, based at the MRC Cognition and Brain Sciences Unit, University of Cambridge, found that while sleep problems and low self-esteem were common risk factors, there were two distinct profiles of young people who self-harm — one with emotional and behavioural difficulties and a second group without those difficulties, but with different risk factors.
Between one in five and one in seven adolescents in England self-harms, for example by deliberately cutting themselves. While self-harm is a significant risk factor for subsequent suicide attempts, many do not intend suicide but face other harmful outcomes, including repeatedly self-harming, poor mental health, and risky behaviours like substance abuse. Despite its prevalence and lifelong consequences, there has been little progress in the accurate prediction of self-harm.
The Cambridge team identified adolescents who reported self-harm at age 14, from a nationally representative UK birth cohort of approximately 11,000 individuals. They then used a machine learning analysis to identify whether there were distinct profiles of young people who self-harm, with different emotional and behavioural characteristics. They used this information to identify risk factors from early and middle childhood. The results are published in the Journal of the American Academy of Child and Adolescent Psychiatry.
Because the data tracked the participants over time, the researchers were able to distinguish factors that appear alongside reported self-harm behaviour, such as low self-esteem, from those that precede it, such as bullying.
The team identified two distinct subgroups among young people who self-harm, with significant risk factors present as early as age five, nearly a decade before they reported self-harming. While both groups were likely to experience sleep difficulties and low self-esteem reported at age 14, other risk factors differed between the two groups.