Publisher Health

Specific nuclear proteins act as a glue to pack genetic material in an absurdly small space in the human body. Proteins “gluing” DNA are called linker histones, and hold their secret in their electric charge. They are strongly positively charged, fusing to the strongly negatively charged DNA.
A simple attraction of opposites is thus key to tight packing of genes, with interactions so strong, they suggest the idea of glue keeping everything together.
In new research published in Nature Chemistry, Dr Davide Mercadante from the University of Auckland and a team of scientists from Switzerland, Iceland and the US, investigated how these genes are accessed if so tightly packed away? How can these molecules be broken apart to promote gene expression?
“We challenged existing notions, hypothesising that unstructured proteins would explain the plastic and dynamic world of genes,” Dr Mercadante says.
“By being fast moving, it is impossible to obtain a detailed picture of how disordered proteins take shape and from their structure we had to move our target to understand their dynamics.”
The researchers first labelled histones and DNA with fluorescent dyes responding to molecular dynamics and looked at the molecules through microscopy. This didn’t provide “molecular pictures” but only an idea of how molecules behaved from the indirect reading of dyes.
Molecular simulations, which can provide the finest details, were then tightly coupled to experiments and instructed to give reliable “snapshots” of the investigated molecules, providing clues of how tight interactions can also be functionally dynamic to potentially unpack genes.
A strongly negatively charged and unstructured protein known to interact with the linker histone is prothymosin-α. Could prothymosin-α compete with the DNA for the binding, evicting the histone to promote gene availability?
In experiments, prothymosin-α invaded the histone-DNA complex, forming a three-way complex before dislodging the histone.
“This has enormous implications, with strong but fuzzy molecular associations finely regulating gene access, this has deep repercussions on the world of biology and how we conceive protein activity,” Dr Mercadante says.
“Our work reinforces the notion that cellular processes can be mediated by unstructured proteins, challenging the historical view that function must be conveyed by specific protein structures. Here the lack of shape conveys the plasticity necessary to make the genetic material available in appreciable timescales, against the long-standing structure-to-function paradigm of biology.”
Co-authors on the research include Professor Benjamin Schuler, University of Zürich, Zürich, Switzerland; Dr Robert Best — National Institute of Health, Washington DC, USA; Associate Professor Pétur Heiðarsson, University of Iceland, Reykjavík, Iceland; Dr Alessandro Borgia, St Jude children’s hospital, Memphis, USA; Dr Madeleine Borgia, St Jude children’s hospital, Memphis, USA; Dr Daniel Nettels, University of Zürich, Zürich, Switzerland; Associate Professor Beat Fierz, École polytechnique fédérale de Lausanne, Lausanne, Switzerland.

Researchers in Scotland reported on Thursday that pregnant women with Covid were not only at greater risk of developing severe disease, but also more likely to lose their fetuses and babies in the womb or shortly after birth, compared with other women who gave birth during the pandemic.The risk of losing a baby through stillbirth or the first month of life was highest among women who delivered their babies within four weeks of the onset of a Covid infection: 22.6 deaths for every 1,000 births, four times the rate in Scotland of 5.6 deaths per 1,000 births.All of those deaths occurred in pregnancies among unvaccinated women, the researchers found. “Quite strikingly, no baby deaths occurred in women who had SARS-CoV-2 and were vaccinated,” said Dr. Sarah J. Stock, the paper’s first author, a maternal-fetal medicine specialist at the University of Edinburgh Usher Institute in Exeter. The study also found a higher rate of preterm birth among women diagnosed with Covid, a rate that spiked if the baby was born within a month of the mother falling ill. More than 16 percent of these women gave birth before 37 weeks of pregnancy, compared with 8 percent among other women. In Scotland, as in the United States, vaccination rates of pregnant women are low. Only one-third of pregnant women are vaccinated against the coronavirus, despite the protections afforded by immunization. Early research has found no evidence that the Pfizer-BioNTech or Moderna vaccines pose serious risks during pregnancy. Indeed, the Scottish study found that the vast majority of infections among pregnant women were in those who were completely unvaccinated or were only partially vaccinated. Only 11 percent of the total infections were reported among fully vaccinated pregnant women. Pregnant women who were unvaccinated were also four times as likely to be hospitalized, compared with vaccinated pregnant women.Dr. Stock and her colleagues analyzed data collected by the Covid-19 in Pregnancy in Scotland study, a national cohort of all women who were pregnant or became pregnant after March 1, 2020, through the end of October 2021. The team tracked 144,546 pregnancies in 130,875 women during this period.One weakness of the study is that the authors did not adjust for confounding factors, like maternal age or pre-existing medical conditions, which could lead to poor pregnancy outcomes regardless of coronavirus infection or Covid diagnosis (they also did not know whether women who were hospitalized were admitted because of Covid disease, or were just incidentally found to test positive at admission).Vaccination rates are low among pregnant women across the board, but are particularly low among younger women and those from lower socioeconomic backgrounds, the study noted. Future analyses will take these demographic factors and other confounding factors into account, the authors said.The Coronavirus Pandemic: Key Things to KnowCard 1 of 5The latest Covid data in the U.S.

As the world enters a third year of pandemic-related uncertainties, one thing does seem certain: The SARS-CoV-2 virus mutates and keeps us on our toes.
New research from the lab of Gary Whittaker, professor of virology in the Department of Microbiology and Immunology in the College of Veterinary Medicine, outlines key information about omicron’s older variant sibling, alpha, which emerged late in 2020. It turns out that the mutation that birthed alpha in the first place is very similar to the one that created omicron, but with very different results for the severity of each one.
Whittaker is corresponding author of “Functional Evaluation of the P681H Mutation on the Proteolytic Activation of the SARS-CoV-2 Variant B.1.1.7 (Alpha) Spike,” which published Dec. 10 in iScience. Other contributors included Susan Daniel, associate professor of chemistry and chemical biology in the College of Arts and Sciences; Diego Diel, associate professor of population medicine and diagnostic sciences (CVM); and postdoctoral researcher Javier Jaimes, Ph.D. ’18.
Scientists noticed a major mutation in a key region of alpha’s spike protein called the furin cleavage site. This site is thought to be where much of the virus’s nastiness comes from. However, “it actually turned out to be relatively inconsequential,” Whittaker said. While alpha had a notable mutation in the furin cleavage site, it had little effect on alpha’s ability to infect cells and cause disease.
However, alpha and omicron share the same furin cleavage mutation, and on a different genetic background this may explain why omicron spreads like wildfire but seems to cause less severe sickness. “Omicron has a lot of the same features as alpha,” Whittaker said. “So what we learned about alpha helps us understand omicron and possible future variants.”
Alpha may not be as familiar in the U.S. as it was elsewhere, Whittaker said, due to the timing of its debut on the world stage.

Threads or earphone cables placed in tight spaces get easily tangled. On the contrary, our body’s long and loose DNA packs into rod-shaped chromosomes one-millionth its size when the cell divides. If cell division occurs with DNA that is almost two meters in length, there is the risk of damage or loss in genetic information. Therefore, the condensation of chromosomes is essential to accurately transmitting genetic information.
A research team led by Professor Changyong Song and Dr. Daeho Sung, and Professor Jae-Hyung Jeon and Ph.D. candidate Chan Im in the Department of Physics at POSTECH, along with Professor Do Young Noh (Gwangju Institute of Science and Technology, GIST) used the X-ray from the third-generation synchrotron facility to analyze human chromosomes in their clustered state. These findings observed at the nanometer-scale resolution were published in the Proceedings of the National Academy of Sciences (PNAS).
The packing mechanism that condenses the chromosomes into one-millionth its size without any tangling and the 3D structure that enables this have puzzled researchers for over a half a century. However, it has been difficult to observe the chromosomes in their native condition. The researchers had to resort to detecting only some components of the chromosomes or infer their condensed state from looking at their uncoiled state.
This study verified the 3D structure of chromosomes by using coherent X-rays generated from the 3rd generation synchrotron facility after rapidly freezing the hydrated chromosomes and maintaining them in a cryogenic state. This is the research that uncovered the structure of the chromosomes in native states, unlike conventional techniques that thinly cut or dyed them.
Through the study, the research team confirmed that the chromosomes were formed in a fractal structure rather than the hierarchical structure stated in previous studies. In addition, a physical model showing the packing process of chromosomes was presented.
“Using coherent X-rays from the synchrotron, we have identified the 3D structure of chromosomes through high-resolution images at the nanometer-scale,” explained Professor Changyong Song. “The technique developed in the study not only provides the key to understanding genetics — the essence of all living things — but also to uncover the 3D structures of other materials, such as viruses, whose detailed structure is of significant importance.”
This research was conducted with the support from the Mid-Career Researcher Program, the Science Research Center (SRC) program, and the international joint research program of the National Research Foundation.
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Materials provided by Pohang University of Science & Technology (POSTECH). Note: Content may be edited for style and length.

People who use electronic cigarettes and test positive for COVID-19 have a higher frequency of experiencing COVID-19 symptoms, compared to people who don’t vape, according to new research from Mayo Clinic.
The study, which is published in the Journal of Primary Care & Community Health, finds that people who vape and test positive for COVID-19 symptoms have a higher frequency of experiencing symptoms such as headaches, muscle aches and pain, chest pain, nausea and vomiting, diarrhea, and loss of the sense of smell or taste. Also, the study finds that people who vape and also smoke tobacco, and who test positive for COVID-19, complained of labored breathing and had more frequent emergency department visits than those who did not vape.
“The study was designed to compare the frequency of common COVID-19 symptoms, such as loss of taste or smell, headache, muscle aches and chest tightness in COVID patients who vaped, compared with those who were not vapers,” says David McFadden, M.D., a Mayo Clinic internist and the study’s first author. “We interviewed more than 280 COVID-positive vapers and compared them with 1,445 COVID-positive people of the same age and gender, and who don’t vape. All of these common COVID symptoms were reported more frequently among people who vape.”
Study participants were at least 18 and tested positive for COVID-19 at testing sites in Minnesota and Wisconsin between March 1, 2020, and Feb. 28. Data were then gathered on age; gender; ethnicity; race; COVID-19 symptoms; emergency department visits and hospitalizations; and lifestyle history, such as vaping and smoking.
Use of e-cigarettes has grown significantly over the past decade, especially among high school students and young adults, though the short- and long-term health effects of e-cigarettes are unknown. While studies have not found a connection between using e-cigarettes and testing positive for COVID-19, the Mayo Clinic study finds an association between vaping and experiencing COVID-19 symptoms for those who test positive for COVID-19.
“There are a lot of studies that have shown that e-cigarette use may be associated with inflammation in the lungs and also may cause severe lung injury in certain users, causing a condition called e-cigarette or vaping use-associated lung injury,” says Robert Vassallo, M.D., a Mayo Clinic pulmonologist and critical care specialist, and co-author of the study. “Our research was not designed to test whether e-cigarette use increases the risk of acquiring COVID infection, but it clearly indicates that symptom burden in patients with COVID-19 who vape is greater than in those who do not vape.”
The uncertainties of the health effects of e-cigarette use are due in part to the variety of devices, ingredients in the vaping liquid, and use. Nonetheless, the study documented a significant difference in symptom frequency between those who vape and were COVID-19 positive and those who did not vape.
The increased inflammation of lung tissue promoted by COVID-19 infection and the inflammation induced by vaping may worsen the likelihood of systemic inflammation, with an associated increase in symptoms such as fever, myalgias, fatigue and headache, the study finds.
“During a pandemic with a highly transmissible respiratory pathogen like SARS-CoV-2 (the virus that causes COVID-19), it is highly advisable to reduce or stop vaping and e-cigarette use, and minimize the potential for increased symptoms and lung injury,” says Dr. Vassallo.
The study was supported in part by Mayo Clinic’s Department of Medicine, Division of General Internal Medicine, and by a Center for Clinical and Translational Science award from the National Center for Advancing Translational Sciences.
Dr. Vassallo reports receiving grant funding support from Pfizer Inc., Bristol-Myers Squibb Co. and Sun Pharmaceutical Industries Ltd. for research activities unrelated to this study. The authors report no other competing interests.
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Materials provided by Mayo Clinic. Original written by Jay Furst. Note: Content may be edited for style and length.

Despite unprecedented efforts to develop COVID-19 vaccines in record time amid the global pandemic, SARS-CoV-2 continues to spread rapidly with the emergence of new variants, such as delta and omicron, making the development of new therapeutic strategies critically important.
Preliminary studies early in the pandemic found evidence that countries with Bacillus Calmette-Guérin (BCG) vaccination programs, which fights tuberculosis, could be associated with a reduced number and/or severity of COVID-19 cases. While clinical trials are ongoing to further investigate, a University of Houston computational biology researcher is reporting cross reaction between the two illnesses that might help explain what could be driving immunity brought on by the BCG vaccination.
“The protection against SARS-CoV-2 induced by BCG vaccination may be mediated by cross-reactive T cell lymphocytes, which recognize peptides displayed by class I Human Leukocyte Antigens (HLA-I) on the surface of infected cells,” reports Dinler Amaral Antunes, assistant professor of computational biology and a corresponding author of the work published in the journal Frontiers in Immunology.
The researchers from UH, Pontifical Catholic University of Rio Grande do Sul and Rice University, implemented a large-scale computational screening to identify potential targets with biochemical similarities between the two illnesses.
T cell lymphocytes develop from stem cells and help protect the body from infection. T cell responses to SARS-CoV-2 are vital for helping resolve viral infections and protecting against reinfection by providing long-lasting immunity. Peptides are chains of amino acids connected to one another which can be derived from proteins of the virus, as well as from proteins of the host. HLAs are receptors that display these peptides to the immune system.
The research team screened over 13.5 million possible cross-reactive peptide pairs from BCG and SARS-CoV-2. The analysis produced a large dataset of cross-reactive clusters, which ultimately led to the identification of 40 peptide pairs with potential cross-reactivity with BCG peptides.
The top 40 list includes SARS-CoV-2-derived peptides GEAANFCAL, GEVITFDNL and FIAGLIAIV which have been independently shown to induce T cell response, Interferon Gamma (INF-γ) production and lymphocyte proliferation in COVID-19 patients. INF-γ is a critical component of immunity against viral and some bacterial infections.
“In addition, multiple peptides from our top 40 list have been reported to induce T cell activation in recent studies analyzing aspects of cellular immunity in COVID-19 patients,” said Antunes. “The development of peptide-based vaccines targeting coronaviruses and presenting cross-reactivity with existing pools of memory T cells, could be an interesting strategy to complement and extend the protection conferred by existing COVID-19 vaccines.”
The research team includes co-author André Fonseca, a postdoctoral researcher working in the Antunes lab; Ana Paula D. De Souza, Tiago C. Ferreto, Renata F. Tarabini, Rafael Bele and Felipe Rubin of Pontifical Catholic University of Rio Grande do Sul, Brazil; and Lydia E. Kavraki, Mauricio Menegatti Rigo of Rice University.
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Materials provided by University of Houston. Original written by Laurie Fickman. Note: Content may be edited for style and length.

Regularly eating a small serving of dried goji berries may help prevent or delay the development of age-related macular degeneration, or AMD, in healthy middle-aged people, according to a small, randomized trial conducted at the University of California, Davis.
AMD is the leading cause of vision loss in older people, and is estimated to affect more than 11 million in the United States and 170 million globally.
“AMD affects your central field of vision and can affect your ability to read or recognize faces,” said Glenn Yiu, a co-author of the study and an associate professor in the Department of Ophthalmology and Vision Sciences.
The researchers found that 13 healthy participants aged 45 to 65 who consumed 28 grams (about one ounce, or a handful) of goji berries five times a week for 90 days increased the density of protective pigments in their eyes. In contrast, 14 study participants who consumed a commercial supplement for eye health over the same period did not show an increase.
The pigments that increased in the group that ate goji berries, lutein and zeaxanthin, filter out harmful blue light and provide antioxidant protection. Both help to protect the eyes during aging.
“Lutein and zeaxanthin are like sunscreen for your eyes,” said lead author Xiang Li, a doctoral candidate in the Nutritional Biology Program.

Multiple sclerosis (MS), a progressive disease that affects 2.8 million people worldwide and for which there is no definitive cure, is likely caused by infection with the Epstein-Barr virus (EBV), according to a study led by Harvard T.H. Chan School of Public Health researchers.
Their findings will be published online in Science on January 13, 2022.
“The hypothesis that EBV causes MS has been investigated by our group and others for several years, but this is the first study providing compelling evidence of causality,” said Alberto Ascherio, professor of epidemiology and nutrition at Harvard Chan School and senior author of the study. “This is a big step because it suggests that most MS cases could be prevented by stopping EBV infection, and that targeting EBV could lead to the discovery of a cure for MS.”
MS is a chronic inflammatory disease of the central nervous system that attacks the myelin sheaths protecting neurons in the brain and spinal cord. Its cause is not known, yet one of the top suspects is EBV, a herpes virus that can cause infectious mononucleosis and establishes a latent, lifelong infection of the host. Establishing a causal relationship between the virus and the disease has been difficult because EBV infects approximately 95% of adults, MS is a relatively rare disease, and the onset of MS symptoms begins about ten years after EBV infection. To determine the connection between EBV and MS, the researchers conducted a study among more than 10 million young adults on active duty in the U.S. military and identified 955 who were diagnosed with MS during their period of service.
The team analyzed serum samples taken biennially by the military and determined the soldiers’ EBV status at time of first sample and the relationship between EBV infection and MS onset during the period of active duty. In this cohort, the risk of MS increased 32-fold after infection with EBV but was unchanged after infection with other viruses. Serum levels of neurofilament light chain, a biomarker of the nerve degeneration typical in MS, increased only after EBV infection. The findings cannot be explained by any known risk factor for MS and suggest EBV as the leading cause of MS.
Ascherio says that the delay between EBV infection and the onset of MS may be partially due the disease’s symptoms being undetected during the earliest stages and partially due to the evolving relationship between EBV and the host’s immune system, which is repeatedly stimulated whenever latent virus reactivates.
“Currently there is no way to effectively prevent or treat EBV infection, but an EBV vaccine or targeting the virus with EBV-specific antiviral drugs could ultimately prevent or cure MS,” said Ascherio.
Other Harvard Chan School researchers who contributed to this study include Kjetil Bjornevik, Marianna Cortese, Michael Mina, and Kassandra Munger.
Funding for this study came the National Institute of Neurological Disorders and Stroke, National Institutes of Health (NS046635, NS042194, and NS103891), the National Multiple Sclerosis Society (PP-1912-35234), the German Research Foundation (CO 2129/ 1-1), the National Institutes of Health (DP5- OD028145), and the Howard Hughes Medical Institute.
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Materials provided by Harvard T.H. Chan School of Public Health. Note: Content may be edited for style and length.

The human immune system, that marvel of complexity, subtlety, and sophistication, includes a billion-year-old family of proteins used by bacteria to defend themselves against viruses, scientists at Dana-Farber Cancer Institute and in Israel have discovered.
The findings, published online today by the journal Science, are the latest in a growing body of evidence that components of our immune system — as advanced a shield against disease as exists on the planet — evolved early in ancient forms of life. The study shows that the immune system absorbed already existing elements and, over eons of evolution, put them to use in novel ways to meet the requirements of creatures as biologically complicated as human beings.
“There has been a tremendous amount of work by researchers around the world to understand how the human immune system functions,” says the study’s senior author, Philip Kranzusch, PhD, of Dana-Farber. “The discovery that key parts of human immunity are shared in bacteria provides a new blueprint for research in this area.”
The proteins at the center of the study are known as gasdermins. When a cell becomes infected or turns cancerous, gasdermins form pores that punch holes in its membrane, causing it to die. Substances known as inflammatory cytokines leak from the holes, signaling the presence of infection or cancer and prompting the immune system to rally to the body’s defense.
This process, called pyroptosis, is one facet of the immune system’s repertoire for killing diseased or infected cells. It complements the better-known process of apoptosis, in which crippled or infected cells self-destruct after being damaged. “Pyroptosis represents one of the fastest ways that the innate immune system [the body’s first line of defense against pathogens] responds to potential threats,” says the new study’s co-first author, Alex Johnson, PhD, of Dana-Farber.
The human genome holds the code for six gasdermin proteins, which are expressed at varying levels in different cell types. For the current study, Johnson and his colleagues explored whether the ancestors of any of these proteins existed in bacteria.

A new study finds that while young and healthy mice show clear differences between daytime and nighttime body temperature rhythms, in older and diseased animals the difference essentially disappeared.
In humans and other mammals, body temperature oscillates in a 24-hour rhythm. This daily rhythm in body temperature is a critical factor in regulating many physiological processes. The loss of this rhythm is an important marker of, and contributor to, disease.
In a study published in the journal Chronobiology International, UCLA Health researchers looked at body temperature rhythms in young and middle-aged mice, and in a mouse model of Huntington’s Disease. They found that in young healthy mice, there is a distinct difference between the nighttime rhythm and daytime mode. At night, the young and healthy mice had strong higher frequency oscillations, while in the daytime, these body temperature oscillations were absent. But in the older and diseased animals, the night/day difference disappeared.
“In these older and diseased mice, as the song says, ‘it’s hard to tell the nighttime from the day,'” said Alan Garfinkel, Research Professor of Medicine and Integrative Biology and Physiology. “This loss of the ability to segregate daytime from nighttime rhythms may be a general phenomenon in health vs. disease, since virtually all hormones in the body have a similar pattern of nighttime vs daytime rhythms.”
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Materials provided by University of California – Los Angeles Health Sciences. Note: Content may be edited for style and length.