Publisher Health

The DNA molecule is not naked in the nucleus. Instead, it is folded in a very organized way by the help of different proteins to establish a unique spatial organization of the genetic information. This 3D spatial genome organization is fundamental for the regulation of our genes and has to be established de novo by each individual during early embryogenesis. Researchers at the MPI of Immunobiology and Epigenetics in Freiburg in collaboration with colleagues from the Friedrich Mischer Institute in Basel now reveal a yet unknown and critical role of the protein HP1a in the 3D genome re-organization after fertilisation. The study published in the scientific journal Nature identifies HP1a as an epigenetic regulator that is involved in establishing the global structure of the genome in the early Drosophila embryo.
The information of the human genome is encoded by approximately 3 billion DNA base pairs and packaged into 23 pairs of chromosomes. If all chromosomes could be disentangled and linearly aligned, they would be a thin thread of about 2 meters. The DNA molecule must be extensively packaged to fit inside the nucleus, the size of which is in the micrometer range. “The DNA thread is not simply stuffed into the cell nucleus. Instead, it is folded in a very organized way to ensure that different parts of the genome, sometimes several thousand base pairs away from each other, can intercommunicate for appropriate gene functions,” says Nicola Iovino, group leader at the MPI of Immunobiology and Epigenetics in Freiburg.
Part of this packaging are histone proteins acting as spools around which DNA is winded and thereby compacted. This complex of DNA and proteins is called chromatin. As such, chromatin is the fundament for further packaging of the genetic material into chromosomes whose structure is mostly known for its characteristic cross shape. The chromosomes themself occupy distinct positions within the nucleus, known as chromosome territories, that also enable efficient packaging and organization of the genome.
The full machinery contributing to this 3D chromatin organization remains unexplored. Now the lab of Nicola Iovino at the MPI in Freiburg, in collaboration with Luca Giorgetti from the Friedrich Miescher Institute in Basel (Switzerland), was able to show the fundamental role of the heterochromatin protein 1a (HP1a) in the reorganization of the 3D chromatin structure after fertilization. By combining powerful Drosophila genetics with 3D genome modeling, they discovered that HP1a is required to establish a proper chromatin 3D structure at multiple hierarchical levels during early embryonic development.
Early embryos as a model to study chromatin reprogramming
The degree of packaging as well as the corresponding gene activity is influenced by epigenetic modifications. These are small chemical groups that are installed on the histones. “Proteins that carry out these epigenetic modifications can be thought of as being either writers, erasers or reader of the given epigenetic modification. We discovered that the reader protein HP1a is required to establish chromatin structure during early embryonic development in Drosophila,” says Fides Zenk, first-author of the study.

Using a new single-cell technique, WEHI researchers have uncovered a way to understand the programming behind how stem cells make particular cell types.
The research uncovered 30 new genes that program stem cells to make the dendritic cells that kick-start the immune response.
By uncovering this process, the researchers hope they will be able to find new immunotherapy treatments for cancer, and plan to expand this technique in other areas such as discovering new drug targets in tumour initiation.
At a glance WEHI researchers have developed a new single cell method to understand the programming behind what causes stem cells to make particular cell types. By testing daughters of a single stem cell in different parallel tests, researchers found 500 genes that predicted dendritic cell fate. Using a CRISPR screen, they discovered 30 key genes amongst the 500 that program dendritic cell production. Researchers intend to expand use of this technique to find the ‘big bang’ moment in cancer development to identify new drug targets to fight cancer.Studying ‘sister’ cells
Led by Dr Shalin Naik, Dr Luyi Tian, Ms Sara Tomei and Mr Jaring Schreuder and published in Immunity, the research outlined the processes involved in kick-starting the generation of dendritic cells driven by the hormone Flt3 ligand, which is used in immunotherapy.

Is it the difficulty of a task that determines whether or not students are stressed when working on it? Biologists working in biology didactics set out to find out the answers; to this end, the team used questionnaires and measured the heart rate in 209 test participants.
“This enables us to contrast the subjective perception of stress with an objective measurement method and compare the two,” explains Nina Minkley. Contrary to expectations, it turned out that the effort invested in the task does not increase with its difficulty, nor does the stress level. The study was featured in the journal Frontiers in Education.
Simple questionnaire surveys criticised
To date, the stress experience of students has mostly been surveyed with questionnaires. But this approach has been criticised, because many factors have an effect on one’s own perception that have nothing to do with the task. “For example, women often report higher stress levels than men,” points out Nina Minkley. The researchers can only speculate why this is the case. In the current study, they used an objective method of measuring stress levels.
They equipped 209 secondary school students who were working on biology tasks with chest straps that monitor the heart rate. They also had the participants fill out several questionnaires on their self-concept, their interest in biology and their perception of the tasks. “When we are relaxed, the individual heartbeats differ slightly, whereas when we are stressed, they are less variable,” explains Nina Minkley. Thus, the change in heart rate variability is an objective measurement of the stress level.
Mental effort causes stress
Comparing the questionnaire answers with the measured heart rates revealed that it was mainly mental engagement, i.e. the effort the students invested in solving the tasks, that correlated with the objective stress level. Contrary to expectations, however, more difficult tasks did not increase stress. “Perhaps some tasks can be so difficult that students don’t even try to work on them,” concludes Nina Minkley. “Such objective measures could be used in future studies primarily to survey subjective cognitive stress dimension.”
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High intensity interval training has become increasingly popular as it’s a quick and effective way to improve health. This is all the more important as countries around the world emerge from lockdowns due to coronavirus and are looking for quick and easy way to exercise again.
Recently, researchers have been studying whether shorter variations of HIIT, involving as little as 4-min of high intensity exercise per session (excluding a warm up and cool down), also improve health.
A new review paper published in the Journal of Physiology collates a decade’s worth of research on the topic of this so-called low-volume high HIIT for health.
The current World Health Organisation (WHO) physical activity guidelines (150-300 min of moderate activity/week or 75-100min of vigorous activity/week) may be unattainable for a large portion of the population who are time poor due to family or work commitments.
This hypothesis is supported by the increasing rates of physical inactivity amongst adults in high income countries.
The findings of this study show that low-volume HIIT (typically involving less than ~20 mins total exercise time — inclusive of warm up and cool down) yields comparable improvements to interventions meeting the current guidelines despite requiring significantly less time.

A number of SARS-CoV-2 variants have emerged from immunocompromised hosts, research has identified. It is thought that variants of concern — including B.1.1.7, a variant first identified in Kent — were a result of long-term infection in people with a weakened immune system.
Persistent infections in immunocompromised people could cause the virus to mutate more frequently because the person’s immune system cannot clear the virus as quickly as the immune system of a healthy person.
Authors Professor Wendy Barclay, Dr Thomas Peacock, Professor Julian Hiscox and Rebekah Penrice-Randal explain the importance of monitoring genetic changes in SARS-CoV-2 for future control of the virus: “As more and more variants appear, we are getting a better picture of their shared similarities and differences and can better predict what other new variants will look like. Putting all this information together will also help us design booster vaccines that protect against as many variants as possible or design targeted diagnostics” they said.
Their review discusses where mutations have occurred, what part of the virus they affect and how the resulting variants could impact vaccination efforts. According to the authors, mutations in SARS-CoV-2 are expected, as the virus is adapting to humans. “Sequencing of human seasonal coronaviruses has not been done on a scale like SARS-CoV-2, particularly when they would have initially spread into humans. SARS-CoV-2 is at the start of its journey in humans whereas other human coronaviruses have been around, in some cases, for many decades” they said.
Variants with the same or similar mutations have emerged independently in different countries: “SARS-CoV-2 is probably still finding its way in humans in terms of optimal infection and transmission. The scale of the outbreak and the massive sequencing efforts will identify concurrent mutations; basically, the virus is undergoing the same types of selection pressures wherever you are in the world, and the outbreak was all seeded by the same original virus,” explained the authors.
Mutations of particular interest include those in the spike protein. This protein allows the virus to enter host cells and is the main target of the immune system, including immunity generated by all current SARS-CoV-2 vaccines.

The proposal to spend $400 billion over eight years faces political challenges and a funding system not designed for the burden it has come to bear.President Biden’s $400 billion proposal to improve long-term care for older adults and those with disabilities was received as either a long overdue expansion of the social safety net or an example of misguided government overreach.Republicans ridiculed including elder care in a program dedicated to infrastructure. Others derided it as a gift to the Service Employees International Union, which wants to organize care workers. It was also faulted for omitting child care.For Ai-jen Poo, co-director of Caring Across Generations, a coalition of advocacy groups working to strengthen the long-term care system, it was an answer to years of hard work.“Even though I have been fighting for this for years,” she said, “if you would have told me 10 years ago that the president of the United States would make a speech committing $400 billion to increase access to these services and strengthen this work force, I wouldn’t have believed it would happen.”What the debate over the president’s proposal has missed is that despite the big number, its ambitions remain singularly narrow when compared with the vast and growing demands imposed by an aging population.Mr. Biden’s proposal, part of his $2 trillion American Jobs Plan, is aimed only at bolstering Medicaid, which pays for somewhat over half the bill for long-term care in the country. And it is targeted only at home care and at community-based care in places like adult day care centers — not at nursing homes, which take just over 40 percent of Medicaid’s care budget.Still, the money would be consumed very fast.Consider a key goal: increasing the wages of care workers. In 2019, the typical wage of the 3.5 million home health aides and personal care aides was $12.15 an hour. They make less than janitors and telemarketers, less than workers in food processing plants or on farms. Many — typically women of color, often immigrants — live in poverty.The aides are employed by care agencies, which bill Medicaid for their hours at work in beneficiaries’ homes. The agencies consistently report labor shortages, which is perhaps unsurprising given the low pay.Raising wages may be essential to meet the booming demand. The Labor Department estimates that these occupations will require 1.6 million additional workers over 10 years.It won’t be cheap, though. Bringing aides’ hourly pay to $20 — still short of the country’s median wage — would more than consume the eight-year outlay of $400 billion. That would leave little money for other priorities, like addressing the demand for care — 820,000 people were on states’ waiting lists in 2018, with an average wait of more than three years — or providing more comprehensive services.The battle over resources is likely to strain the coalition of unions and groups that promote the interests of older and disabled Americans, which have been pushing together for Mr. Biden’s plan. And that’s even before nursing homes complain about being left out.The president “must figure out the right balance between reducing the waiting list and increasing wages,” said Paul Osterman, a professor at the Massachusetts Institute of Technology’s Sloan School of Management who has written about the nation’s care structures. “There’s tension there.”Elder care has long been at the center of political battles over social insurance. President Lyndon B. Johnson considered providing the benefit as part of the creation of Medicare in the 1960s, said Howard Gleckman, an expert on long-term care at the Urban Institute. But the chairman of the House Ways and Means Committee, Wilbur Mills, warned how expensive that approach would become when baby boomers started retiring. Better, he argued, to make it part of Medicaid and let the states bear a large chunk of the burden.This compromise produced a patchwork of services that has left millions of seniors and their families in the lurch while still consuming roughly a third of Medicaid spending — about $197 billion in 2018, according to the Kaiser Family Foundation. By Kaiser’s calculations, Medicaid pays for roughly half of long-term care services; out-of-pocket payments and private insurance together pay a little over a quarter of the tab. (Other sources, like programs for veterans, cover the rest.)Unlike institutional care, which state Medicaid programs are required to cover, home and community-based care services are optional. That explains the waiting lists. It also means there is a wide divergence in the quality of services and the rules governing who gets them.Although the federal government pays at least half of states’ Medicaid budgets, states have great leeway in how to run the program. In Pennsylvania, Medicaid pays $50,300 a year per recipient of home or community-based care, on average. In New York, it pays $65,600. In contrast, Medicaid pays $15,500 per recipient in Mississippi, and $21,300 in Iowa.A home health aide accompanies a patient to a vaccine appointment. Elder care has long been at the center of political battles over social insurance.James Estrin/The New York TimesThis arrangement has also left the middle class in the lurch. The private insurance market is shrinking, unable to cope with the high cost of care toward the end of life: It is too expensive for most Americans, and it is too risky for most insurers.As a result, middle-class Americans who need long-term care either fall back on relatives — typically daughters, knocking millions of women out of the labor force — or deplete their resources until they qualify for Medicaid.Whatever the limits of the Biden proposal, advocates for its main constituencies — those needing care, and those providing it — are solidly behind it. This would be, after all, the biggest expansion of long-term care support since the 1960s.“The two big issues, waiting lists and work force, are interrelated,” said Nicole Jorwic, senior director of public policy at the Arc, which promotes the interests of people with disabilities. “We are confident we can turn this in a way that we get over the conflicts that have stopped progress in past.”And yet the tussle over resources could reopen past conflicts. For instance, when President Barack Obama proposed extending the Fair Labor Standards Act of 1938 to home care workers, which would cover them with minimum-wage and overtime rules, advocates for beneficiaries and their families objected because they feared that states with budget pressures would cut off services at 40 hours a week.“We have a long road ahead of passing this into law and to implementation,” Haeyoung Yoon, senior policy director of the National Domestic Workers Alliance, said of the Biden proposal. Along the way, she said, supporters must stick together.Given the magnitude of the need, some wonder whether there might be a better approach to shoring up long-term care than giving more money to Medicaid. The program is perennially challenged for funds, forced to compete with education and other priorities in state budgets. And Republicans have repeatedly tried to curtail its scope.“It’s hard to imagine Medicaid is the right funding vehicle,” said Robert Espinoza, vice president for policy at PHI, a nonprofit research group tracking the home care sector.Some experts have suggested, instead, the creation of a new line of social insurance, perhaps funded through payroll taxes as Social Security is, to provide a minimum level of service available to everyone.A couple of years ago, the Long-Term Care Financing Collaborative, a group formed to think through how to pay for long-term elder care, reported that half of adults would need “a high level of personal assistance” at some point, typically for two years, at an average cost of $140,000. Today, some six million people need these sorts of services, a number the group expects to swell to 16 million in less than 50 years.In 2019, the National Academy of Social Insurance published a report suggesting statewide insurance programs, paid for by a dedicated tax, to cover a bundle of services, from early child care to family leave and long-term care and support for older adults and the disabled.This could be structured in a variety of ways. One option for seniors, a catastrophic insurance plan that would cover expenses up to $110 a day (in 2014 dollars) after a waiting period determined by the beneficiary’s income, could be funded by raising the Medicare tax one percentage point.Mr. Biden’s plan doesn’t include much detail. Mr. Gleckman of the Urban Institute notes that it has grown vaguer since Mr. Biden proposed it on the campaign trail — perhaps because he realized the tensions it would raise. In any event, a deeper overhaul of the system may eventually be needed.“This is a significant, historic investment,” Mr. Espinoza said. “But when you take into account the magnitude of the crisis in front of us, it’s clear that this is only a first step.”

Despite surgery and subsequent treatment with chemotherapy and radiation, the majority of patients experience recurrence of malignant brain tumours. Researchers at Linköping University, Sweden, and the Medical University of Graz, Austria, have shown in cells in culture that an ion pump can deliver drugs more accurately, which gives less severe adverse effects in chemotherapy. The results have been published in Advanced Materials Technologies.
“This is the first time an ion pump has been tested as a possible method to treat malignant brain tumours. We used cancer cells in the lab, and the results are extremely promising. However, it will probably take five to ten years before we see this new technology used in treatments for brain tumours,” says Daniel Simon, associate professor at the Laboratory of Organic Electronics at the Department of Science and Technology at Linköping University .
The scientists have used cells from glioblastoma, which is the most common and most aggressive type of cancer that can arise in the brain. When a brain tumour is surgically removed, small parts of the tumour are often left behind, embedded between the brain cells. Even high-precision surgery cannot remove these cells without damaging the surrounding healthy brain tissue. This means that radiation treatment and chemotherapy are used to stop the recurrence of the tumour.
In Sweden, around 30 cytostatics are available to treat different types of cancer. These chemotherapy agents are most often given either intravenously or as a tablet. But in order to reach the brain, they must first spread through the circulatory system and then pass through the blood-brain barrier. The walls of the small blood vessels in the brain are much less permeable than blood vessels in the rest of the body, and can prevent many substances in the blood entering the brain. Thus, only a few drugs that work against cancer can pass through.
Scientists at Linköping University and at the Medical University of Graz have now developed a method in which an implanted ion pump can be used to get around the blood-brain barrier and supply gemcitabine — an extremely effective chemotherapy agent that cannot normally pass the blood-brain barrier — directly into the brain with high precision. Gemcitabine is currently used to treat cancers in the pancreas, bladder and breast, where it acts by disrupting the cell division process in rapidly growing tumours. This means that gemcitabine does not affect brain cells, since these do not, in general, undergo cell division.
“The traditional glioblastoma treatment currently used in the clinics harms both cancer and neuronal cells to the same extent. However, with the gemcitabine ion pump, we tackle only the cancerous cells, while neurons stay healthy. In addition, our experiments on cultured glioblastoma cells show that more cancer cells are killed when we use the ion pump than when we use manual treatment,” says Linda Waldherr, postdoctoral fellow at the Medical University of Graz. She has conducted the study together with researchers at Linköping University.
When the ion pump is to transport gemcitabine from an electrolyte reservoir into cells or a tumour, a low current is used to “pump” the positively charged drug through an ion transport channel. The method is known as electrophoresis. The ion pump needs only a low current to pump the gemcitabine, which is an advantage since it avoids the risk that brain cells are activated and transmit unintended nerve signals. The low current and voltage also mean that eventual therapeutic technology will not require large power supplies or batteries to operate.
Rainer Schindl, associate professor at the Medical University of Graz, describes other advantages.
“The pressure inside the brain is extremely sensitive, and using an ion pump to transport the drug instead of a fluid-driven device means that the pressure is not affected. Also, the dosage is controlled by electrical charging, which makes the supply of the chemotherapy agent extremely precise. The next step will be to use the ion pump to evaluate different chemotherapy agents that have previously given adverse effects that are too serious or that are unable to pass the blood-brain barrier,” he says.
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Materials provided by Linköping University. Original written by Anders Ryttarson Törneholm. Note: Content may be edited for style and length.

Clusters of a virus known to cause stomach flu are resistant to detergent and ultraviolet disinfection, according to new research co-led by Danmeng Shuai, Ph.D., an associate professor of civil and environmental engineering at the George Washington University and Nihal Altan-Bonnet, Ph.D., a senior investigator and the head of the Laboratory of Host-Pathogen Dynamics at the National Heart, Lung, and Blood Institute, part of the National Institutes of Health. The findings suggest the need to revisit current disinfection, sanitation and hygiene practices aimed at protecting people from noroviruses.
Noroviruses are the leading cause of gastroenteritis around the world, with over 21 million cases each year in the United States alone.
In 2018, Altan-Bonnet’s team found that noroviruses can be transmitted to humans via membrane-enclosed packets that contain more than one virus. In the past, scientists thought that viruses spread through exposure to individual virus particles, but the 2018 study — and others — showed how membrane-enclosed clusters arrive at a human cell and release an army of viruses all at once.
For the new study, Shuai, Altan-Bonnet and the study’s first author Mengyang Zhang, a doctoral student co-advised through a GW/NIH Graduate Partnerships Program, looked at the behavior of these protected virus clusters in the environment. They found that the virus clusters could survive attempts to disinfect with detergent solutions or even UV light. Water treatment plants use UV light to kill noroviruses and other pathogens.
“These membrane-cloaked viruses are tricky,” Shuai said. “Past research shows they can evade the body’s immune system and that they are highly infectious. Our study shows these membrane enclosed viruses are also able to dodge efforts to kill them with standard disinfectants.”
According to the researchers, future studies must be done to find out if certain kinds of cleaning solutions or higher dosages of UV light would degrade the protective membrane and/or kill the viruses inside. Ultimately, the research could be used to devise more effective disinfection methods that could be used to clean surfaces at home, in restaurants and in places where norovirus can spread and cause outbreaks, like cruise ships.
“Our study’s findings represent a step towards providing rigorous guidelines for pathogen control, particularly in our built environment, and public health protection,” Altan-Bonnet said.
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Maintenance of good oral health is more important than use of antibiotics in dental procedures for some heart patients to prevent a heart infection caused by bacteria around the teeth, according to a new American Heart Association (AHA) scientific statement published today in the association’s flagship journal, Circulation.
Infective endocarditis (IE), also called bacterial endocarditis, is a heart infection caused by bacteria that enter the bloodstream and settle in the heart lining, a heart valve or a blood vessel. It is uncommon, but people with heart valve disease or previous valve surgery, congenital heart disease or recurrent infective endocarditis have a greater risk of complications if they develop IE. Intravenous drug use also increases risk for IE. Viridans group streptococcal infective endocarditis (VGS IE) is caused by bacteria that collect in plaque on the tooth surface and cause inflammation and swelling of the gums. There’s been concern that certain dental procedures may increase the risk of developing VGS IE in vulnerable patients.
The new guidance affirms previous recommendations that only four categories of heart patients should be prescribed antibiotics prior to certain dental procedures to prevent VGS IE due to their higher risk for complications from the infection:those with prosthetic heart valves or prosthetic material used for valve repair; those who have had a previous case of infective endocarditis; adults and children with congenital heart disease; or people who have undergone a heart transplant.