Publisher Health

It has long been understood that a parent’s DNA is the principal determinant of health and disease in offspring. Yet inheritance via DNA is only part of the story; a father’s lifestyle such as diet, being overweight and stress levels have been linked to health consequences for his offspring. This occurs through the epigenome — heritable biochemical marks associated with the DNA and proteins that bind it. But how the information is transmitted at fertilization along with the exact mechanisms and molecules in sperm that are involved in this process has been unclear until now.
A new study from McGill, published recently in Developmental Cell, has made a significant advance in the field by identifying how environmental information is transmitted by non-DNA molecules in the sperm. It is a discovery that advances scientific understanding of the heredity of paternal life experiences and potentially opens new avenues for studying disease transmission and prevention.
A paradigm shift in understanding of heredity
“The big breakthrough with this study is that it has identified a non-DNA based means by which sperm remember a father’s environment (diet) and transmit that information to the embryo,” says Sarah Kimmins, PhD, the senior author on the study and the Canada Research Chair in Epigenetics, Reproduction and Development. The paper builds on 15 years of research from her group. “It is remarkable, as it presents a major shift from what is known about heritability and disease from being solely DNA-based, to one that now includes sperm proteins. This study opens the door to the possibility that the key to understanding and preventing certain diseases could involve proteins in sperm.”
“When we first started seeing the results, it was exciting, because no one has been able to track how those heritable environmental signatures are transmitted from the sperm to the embryo before,” adds PhD candidate Ariane Lismer, the first author on the paper. “It was especially rewarding because it was very challenging to work at the molecular level of the embryo, just because you have so few cells available for epigenomic analysis. It is only thanks to new technology and epigenetic tools that we were able to arrive at these results.”
Changes in sperm proteins affect offspring
To determine how information that affects development gets passed on to embryos, the researchers manipulated the sperm epigenome by feeding male mice a folate deficient diet and then tracing the effects on particular groups of molecules in proteins associated with DNA.
They found that diet-induced changes to a certain group of molecules (methyl groups), associated with histone proteins, (which are critical in packing DNA into cells), led to alterations in gene expression in embryos and birth defects of the spine and skull. What was remarkable was that the changes to the methyl groups on the histones in sperm were transmitted at fertilization and remained in the developing embryo.
“Our next steps will be to determine if these harmful changes induced in the sperm proteins (histones) can be repaired. We have exciting new work that suggest that this is indeed the case,” adds Kimmins. “The hope offered by this work is that by expanding our understanding of what is inherited beyond just the DNA, there are now potentially new avenues for disease prevention which will lead to healthier children and adults.”
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Millions of people are administered general anesthesia each year in the United States alone, but it’s not always easy to tell whether they are actually unconscious.
A small proportion of those patients regain some awareness during medical procedures, but a new study of the brain activity that represents consciousness could prevent that potential trauma. It may also help both people in comas and scientists struggling to define which parts of the brain can claim to be key to the conscious mind.
“What has been shown for 100 years in an unconscious state like sleep are these slow waves of electrical activity in the brain,” says Yuri Saalmann, a University of Wisconsin-Madison psychology and neuroscience professor. “But those may not be the right signals to tap into. Under a number of conditions — with different anesthetic drugs, in people that are suffering from a coma or with brain damage or other clinical situations — there can be high-frequency activity as well.”
UW-Madison researchers recorded electrical activity in about 1,000 neurons surrounding each of 100 sites throughout the brains of a pair of monkeys at the Wisconsin National Primate Research Center during several states of consciousness: under drug-induced anesthesia, light sleep, resting wakefulness, and roused from anesthesia into a waking state through electrical stimulation of a spot deep in the brain (a procedure the researchers described in 2020).
“With data across multiple brain regions and different states of consciousness, we could put together all these signs traditionally associated with consciousness — including how fast or slow the rhythms of the brain are in different brain areas — with more computational metrics that describe how complex the signals are and how the signals in different areas interact,” says Michelle Redinbaugh, a graduate student in Saalman’s lab and co-lead author of the study, published today in the journal Cell Systems.
To sift out the characteristics that best indicate whether the monkeys were conscious or unconscious, the researchers used machine learning. They handed their large pool of data over to a computer, told the computer which state of consciousness had produced each pattern of brain activity, and asked the computer which areas of the brain and patterns of electrical activity corresponded most strongly with consciousness.

Could birth control pills help young female athletes recover faster from concussions and reduce their symptoms?
A new Northwestern Medicine pilot study has shown when a female athlete has a concussion injury during the phase of her menstrual cycle when progesterone is highest, she feels less stress. Feeling stressed is one symptom of a concussion. Feeling less stressed is a marker of recovery.
The study also revealed for the first time the physiological reason for the neural protection is increased blood flow to the brain as a result of higher levels of progesterone.
“Our findings suggest being in the luteal phase (right after ovulation) of the menstrual cycle when progesterone is highest — or being on contraceptives, which artificially increase progesterone — may mean athletes won’t have as severe symptoms when they have a concussion injury,” said co-author Amy Herrold, research assistant professor of psychiatry and behavioral sciences at Northwestern University Feinberg School of Medicine.
“Resolving those symptoms is especially problematic for our athletes who are trying to return to school, their sports and everyday life after a concussion,” said lead author Jennie Chen, research assistant professor of radiology at Feinberg.
The study was published in the Journal of Neurotrauma.

The findings of a recent analysis conducted by the Translational Genomics Research Institute (TGen), an affiliate of City of Hope, suggest that ecosystems suitable for harboring ticks that carry debilitating Lyme disease could be more widespread than previously thought in California, Oregon and Washington.
Bolstering the research were the efforts of an army of “citizen scientists” who collected and submitted 18,881 ticks over nearly three years through the Free Tick Testing Program created by the Bay Area Lyme Foundation, which funded the research, producing a wealth of data for scientists to analyze.
This new study builds on initial research led by the late Nate Nieto, Ph.D., at Northern Arizona University, and Daniel Salkeld, Ph.D., of Colorado State University.
This immense sample collection represented a multi-fold increase in the number of ticks that could be gathered by professional biologists conducting field surveys in far less time and at a fraction of the cost. This kind of citizen participation — which in the future could include smart-phone apps and photography — could become “a powerful tool” for tracking other animal- and insect-borne infectious diseases important for monitoring human and environmental health, according to study results published in the scientific journal PLOS ONE.
This study expands on previous work in California and is the first study to produce high resolution distributions of both actual and potential tick habitat in Oregon and Washington.
“This study is a great example of how citizen scientists can help — whether tracking climate change, fires, habitat changes or species distribution shifts — at a much finer scale than ever before,” said Tanner Porter, Ph.D., a TGen Research Associate and lead author of the study.

The vast majority of people infected with SARS-CoV-2 clear the virus, but those with compromised immunity — such as individuals receiving immune-suppressive drugs for autoimmune diseases — can become chronically infected. As a result, their weakened immune defenses continue to attack the virus without being able to eradicate it fully.
This physiological tug-of-war between human host and pathogen offers a valuable opportunity to understand how SARS-CoV-2 can survive under immune pressure and adapt to it.
Now, a new study led by Harvard Medical School scientists offers a look into this interplay, shedding light on the ways in which compromised immunity may render SARS-CoV-2 fitter and capable of evading the immune system.
The research, published March 16 in Cell, shows that a mutated SARS-CoV-2 from a chronically infected immunocompromised patient is capable of evading both naturally occurring antibodies from COVID-19 survivors as well as lab-made antibodies now in clinical use for treatment of COVID-19.
The patient case was originally described Dec. 3, 2020, as a New England Journal of Medicine report by scientists at Brigham and Women’s Hospital a few weeks before the U.K. and South African variants were first reported to the World Health Organization. Interestingly, the patient-derived virus contained a cluster of changes on its spike protein — the current target for vaccines and antibody-based treatments — and some of these changes were later detected in viral samples in the U.K. and South Africa, where they appear to have arisen independently, the researchers said.
The newly published study, which builds on the initial case report, shows something more alarming still. Some of the changes found in the patient-derived virus have not been identified yet in dominant viral variants circulating in the population at large. However, these changes have been already detected in databases of publicly available viral sequences. These mutations remain isolated, the authors of the report said, but they could be harbingers of viral mutants that may spread across the population.

Females who are fit and healthy tend to burn more fat when they exercise than men, according to new research from a team of sports nutritionists.
The research, comprising two new studies from academics led by the University of Bath’s Centre for Nutrition, Exercise & Metabolism, analysed the factors that most influenced individuals’ capacity to burn body fat when undertaking endurance sports.
How the body burns fat is important to all of us for good metabolic health, insulin sensitivity and in reducing the risk of developing Type II diabetes. But, for endurance sport competitions, such as running or cycling, how the body burns fat can make the difference between success and failure.
Previous research from the same team has shown how, for endurance athletes competing in distance events, the body’s carbohydrate stores deplenish quickly when exercising. This means that that an athletes’ ability to tap into their fat reserves to fuel them on becomes essential to their performance.
The first study, published in the International Journal of Sport Nutrition & Exercise Medicine, involved 73 healthy adults aged 19-63 (41 men; 32 women). It tested the lifestyle and biological factors for optimal fat burning by asking participants to take part in a cycling fitness test and measuring key indicators.
Their results found that females and those who were physically fitter, right across the age ranges, burnt fat more efficiently when exercising.
The second related paper, published in the journal Experimental Physiology, took this a stage further to explore what molecular factors in our muscles and fat tissue determine how fat is burnt. This experiment involved the researchers taking fat and muscle biopsies from participants to analyse how differences in the proteins in fat and muscle tissue might affect their ability to burn fat.
It found that the proteins in muscle that are involved in breaking down stored fat into the smaller fatty acids, and proteins involved in transporting those fatty acids into the mitochondria in muscle (the powerhouse of the cells) consistently correlated with a greater ability to burn fat. The molecular factors explored did not explain why females burned more fat than males, however.
Lead author on both papers, Ollie Chrzanowski-Smith from the University of Bath explains: “Our study found that females typically have a greater reliance upon fat as a fuel source during exercise than males. Understanding the mechanisms behind these sex differences in fuel use may help explain why being female seems to confer a metabolic advantage for insulin sensitivity, an important marker of metabolic health.”
The researchers note that the ability to burn fat as a fuel appears to protect against future weight gain, ensuring good weight management. However, they caution that the body’s ability to burn fat should not be equated with an ability to lose weight. Losing weight is primarily produced by an energy deficit (ie. consuming fewer calories than we expend). For weight loss, in particular where individuals might be overweight, they stress the importance of diet and exercise.
Dr Javier Gonzalez, also from the University of Bath’s Department for Health, added: “Weight management is mainly about energy balance, so to lose weight we need to eat fewer calories than we expend through our resting metabolism and physical activity. However, people with a higher ability to burn fat as a fuel seem to be somewhat protected against future weight gain, which might be related to how fat burning affects food intake and energy expenditure.
“Ultimately, a greater capacity to burn fat as a fuel has potential benefits for endurance athletes, by delaying the timepoint when they run out of precious carbohydrate stores.”
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Imposter syndrome is a considerable mental health challenge to many throughout higher education. It is often associated with depression, anxiety, low self-esteem and self-sabotage and other traits. Researchers at the Sidney Kimmel Medical College at Thomas Jefferson University wanted to learn to what extent incoming medical students displayed characteristics of imposter syndrome, and found that up to 87% of an incoming class reported a high or very high degree of imposter syndrome.
“Distress and mental health needs are critical issues among medical students,” says Susan Rosenthal, MD, lead author of the study published in the journal Family Medicine. “This paper identifies how common imposter syndrome is, and the personality traits most associated with it, which gives us an avenue to address it.”
Medical students nationwide report alarming rates of depression, anxiety and burnout. Identifying and intervening to support psychological well-being in these learners is a continuing challenge, especially among first year medical students.
Dr. Rosenthal and her colleagues examined imposter syndrome, which is defined as inappropriate feelings of inadequacy among high achievers, using a validated survey tool called the Clance Imposter Phenomenon (IP) Scale. Of the 257 students who completed the survey, 87% of students who reported high levels of imposter syndrome, were more likely to show an even higher degree of imposter syndrome at the end of their first year. They also found that students’ higher IP scores were associated with lower scores for self-compassion, sociability, self-esteem and higher scores on neuroticism/anxiety. Therefore, a high CIP score among entering students may be an indicator of future risk for experiencing psychological distress during medical school.
“Imposter syndrome is a malleable personality construct, and is therefore responsive to intervention,” says Dr. Rosenthal, who is also the medical college’s associate dean for Student Affairs. “Supportive feedback and collaborative learning, mentoring by faculty, academic support, individual counseling and group discussions with peers are all helpful. For many students, the most powerful first step in addressing and ameliorating imposter syndrome is normalizing this distorted and maladaptive self-perception through individual sessions with faculty and mentored small-group discussions with peers.”
It is of interest to note that the students in this study the medical college’s Class of 2020 were exposed to the traditional medical school curriculum. The following year, Jefferson introduced an innovative new curriculum, called JeffMD. Dr. Rosenthal and colleagues plan to compare the rates of imposter syndrome in students exposed to the novel curriculum. The new JeffMD curriculum emphasizes collaborative learning with a faculty mentor and a small group of students. The researchers hope, and will test whether this change in the learning environment can ameliorate feelings of imposterism.
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The link between psychological stress and physical health problems generally relates to a stress-induced immune response gone wild, with inflammation then causing damage to other systems in the body. It’s a predictable cascade — except in pregnancy, research suggests.
Scientists exploring the negative effects of prenatal stress on offspring mental health set out to find the immune cells and microbes in stressed pregnant mice most likely to trigger inflammation in the fetal brain — the source for anxiety and other psychological problems identified in previous research.
Instead, the researchers found two simultaneous conditions in response to stress that made them realize just how complex the cross-talk between mom and baby is during gestation: Immune cells in the placenta and uterus were not activated, but significant inflammation was detected in the fetal brain.
They also found that prenatal stress in the mice led to reductions in gut microbial strains and functions, especially those linked to inflammation.
“I thought it was going to be a fairly straightforward tale of maternal inflammation, changes in microbes and fetal inflammation. And while the changes in microbes are there, the inflammation part is more complex than I had anticipated,” said Tamar Gur, senior author of the study and assistant professor of psychiatry and behavioral health, neuroscience, and obstetrics and gynecology at The Ohio State University.
“The complex interplay between the stress response and the immune system is dysregulated by stress, which is problematic for the developing fetus. There are key changes during this critical window that can help shape the developing brain, so we want to figure out how we could potentially intervene to help regulate these systems.”
The study was published recently in Scientific Reports.

Wealthier northeastern US states and Western European countries tended to have significantly lower mortality rates during second-wave COVID-19 infections, new research from the University of Sydney and Tsinghua University has shown. However, the pattern was not as general as expected, with notable exceptions to this trend in Sweden and Germany.
Researchers say mortality change could have several explanations: European first-wave case counts were underestimated; First-wave deaths disproportionately affected the elderly; Second-wave infections tended to affect younger people; With some exceptions, lower mortality rates occurred in countries with more socialised and equitable health systems.The researchers, Nick James, Max Menzies and Peter Radchenko, believe their new methodology could assist epidemiologists to analyse data consistently to assess the impact of COVID-19 mortality across populations.
“We have been able to look at the mortality rates in a more dynamic way,” said Mr James from the University of Sydney.
They have published their results today in the mathematical journal Chaos.
“We take a time series of infection rates by country, apply an algorithmic approach to chop it up into first and later waves and then do some relatively simple optimisation and calculations to determine two different mortality numbers,” said Nick James, a PhD student in the School of Mathematics & Statistics at the University of Sydney.

Men and women are impacted differently by brain diseases, like Alzheimer’s disease and Parkinson’s disease. Researchers are urging their colleagues to remember those differences when researching treatments and cures.
In APL Bioengineering, by AIP Publishing, University of Maryland scientists highlight a growing body of research suggesting sex differences play roles in how patients respond to brain diseases, as well as multiple sclerosis, motor neuron disease, and other brain ailments.
That is progress from just a few years ago, said Alisa Morss Clyne, director of the university’s Vascular Kinetics Laboratory.
“I have worked with vascular cells for 20 years and, up until maybe about five years ago, if you asked if the sex of my cells mattered at all, I would have said no,” Clyne said. Then, she worked on a difficult study in which data appeared “all over the place.”
“We separated the cell data by sex, and it all made sense,” Clyne said. “It was an awakening for me that we should be studying this.”
As of 2020, an estimated 5.8 million Americans were diagnosed with Alzheimer’s disease, another 1 million with Parkinson’s disease, 914,000 with multiple sclerosis, and 63,000 with motor neuron disease. These diseases happen when nerve cells in the brain and nervous system quit working and, ultimately, die.
The changes are associated with the breakdown of what is called the blood-brain barrier — a border of cells that keeps the wrong kind of molecules in the bloodstream from entering the brain and damaging it.
Published research has shown differences in the blood-brain barriers of men and women. Some of the research suggests the barrier can be stronger in women than men, and the barriers in men and women are built and behave differently.
That could factor into known differences in the sexes, such as Alzheimer’s disease being more prevalent in older women than men, while Parkinson’s impacts men more frequently and tends to do so more severely.
The authors said they hope their article will serve as a reminder to researchers not just in their own field, but across the sciences, that accounting for sex differences leads to better results.
“I think there is an awakening in the past 10 years or so that you cannot ignore sex differences,” Clyne said. “My goal is to inspire people to include sex differences in their research, no matter what research they are doing.”
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Materials provided by American Institute of Physics. Note: Content may be edited for style and length.