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AdvertisementContinue reading the main storySupported byContinue reading the main storyAfter a 28-Year Ban, Alabama Could Allow Yoga in Public Schools“It’s just exercise,” said Jeremy Gray, a state lawmaker whose bill is making its way through the Legislature. But some people still say the practice has no place in the classroom.A yoga class in Birmingham, Ala. In 1993, parents in the state were raising concerns not only about yoga but also about hypnotism and “psychotherapeutic techniques.”Credit…Audra Melton for The New York TimesMarch 13, 2021, 9:57 a.m. ETFor nearly three decades, teaching yoga in Alabama’s public schools has been forbidden by the state’s school board.One lawmaker, Jeremy Gray, has been trying to change that since 2019. He made progress on Thursday, when the state’s House of Representatives passed a bill that would override the ban. The bill, which was approved by a vote of 73 to 25, will soon be taken up by the Senate.Mr. Gray, a Democrat representing Opelika, has taught and practiced yoga for years. He said that while some conservative legislators in the state might have opposed yoga because of its associations with Hinduism, officials on both sides of the aisle had been slowly warming to the idea.“Most of the senators that I’ve talked to are OK with it,” Mr. Gray said. “A lot of people in their districts have reached out to them, and a lot of their wives actually do yoga. So I think it has a good chance of passing.”His legislation would override a 1993 school board regulation that says that “school personnel shall be prohibited from using any techniques that involve the induction of hypnotic states, guided imagery, meditation or yoga.”The yoga bill is far from the only issue on the docket for Alabama lawmakers. Mr. Gray also has other legislative priorities, such as providing clean water for schools and improving the state’s policies on expunging criminal records.But because it hits at the intersection of some combustible issues — religion, culture and children’s education — the yoga bill has captured outsize news media attention. This year and last year, it was covered by multiple local, state and national news outlets, including The New York Times.Eric Johnston, a legal adviser for the Alabama Citizens Action Program, or ALCAP, a church-supported group that holds substantial influence in the Legislature, said the group intended to fight the bill when it reaches the Senate.Yoga is “a very important part of the Hindu religion,” he said. “As such, it does not need to be taught to small children in public schools.”Mr. Gray pointed out that his bill would allow schools and students to make their own decisions about whether to offer or participate in yoga classes. It also says that public schoolteachers cannot say “namaste,” a greeting often used in yoga, or any kind of chant.“You have to compromise in order to get that bipartisan support,” he said.Mr. Gray came across the issue largely by chance. In a speech at a public high school in Auburn, Ala., in 2019, he mentioned that yoga had helped him stay grounded while juggling responsibilities.After his remarks, teachers told him that they had been unable to arrange exercises for their students. “That’s how I learned it was banned,” Mr. Gray said.Around the time of the ban in 1993, parents in the state were raising concerns not only about yoga but also about hypnotism and “psychotherapeutic techniques.” According to an April 1993 article in The Anniston Star, one mother in Birmingham said her child had brought a relaxation tape home from school that made a boy “visibly high,” The Montgomery Advertiser reported.But for Mr. Gray, a former football player, yoga has long been a useful part of his exercise regimen. The gentle stretches helped him cool down after practices, he said, while the breathing exercises strengthened his lungs. (That, he added, may have helped him recover quickly from a bout of Covid-19 last year.)He introduced his first bill to challenge the yoga ban in 2019, but it quickly failed. His second attempt passed the House in 2020 but was put on the back burner because of the pandemic.This time, Mr. Gray is optimistic about the bill’s prospects. He said a Republican senator, Tom Whatley, had agreed to carry the legislation forward in the Senate, where, like the House, Republicans have a majority. (Mr. Whatley did not immediately respond to an email seeking comment on Friday.)Mr. Johnston, the adviser for ALCAP, which opposes the yoga bill, said he did not oppose the practice of yoga. “I think yoga is widely accepted, and even some Christian churches have yoga classes,” he added.But he framed the practice as inseparable from Hinduism, and therefore subject to the constitutional separation of religion and state. “You cannot have any kind of religious activities in elementary schools,” he said.Mr. Gray disagreed. “It’s just exercise,” he said. “We do it all the time in the gym. It’s not a big deal.”AdvertisementContinue reading the main story

SharecloseShare pageCopy linkAbout sharingimage copyrightReutersJordan’s health minister has resigned after six people died due to a lack of oxygen at a hospital ward treating Covid-19 patients, state media report. The deaths were reported early on Saturday at a new government facility in the town of Salt, about 14 miles (23km) west of the capital, Amman.Prime Minister Bisher al-Khasawneh had asked Health Minister Nathir Obeidat to step down over the incident. Police were sent to the hospital after dozens of relatives turned up.The oxygen shortage, which lasted for about an hour, reportedly also affected intensive care and maternity units at the facility, although there were no reports of fatalities on those wards. It is not yet clear why there was an oxygen shortage and an investigation is under way, Mr Obeidat said. The health minister had earlier said he felt a “moral responsibility” for what had happened. A forensic doctor at Jordan’s health ministry, Dr Adnan Abbas, told Petra news agency that all six patients who died on Saturday were being treated for coronavirus. image copyrightReutersDozens of relatives whose family members were receiving treatment at the Salt hospital turned up at the facility following the news, but were prevented from entering by police and security personnel. One relative, Fares Kharabsha, said he was inside the hospital when the incident occurred and saw staff carrying portable oxygen devices to patients, AP news agency reported.”They resuscitated a large number of people, including my father and mother,” he said, adding: “I saw people who died.”Jordan’s King Abdullah II has visited the hospital since the incident, Reuters news agency reported. The country has so far reported more than 460,000 cases of Covid-19 and 5,224 coronavirus-related deaths since the start of the pandemic.Jordan has stepped up measures to reduce the spread of the virus in recent weeks as cases have steadily increased since late January. Restrictions include overnight curfews at weekends, which prevent prayers inside mosques and masses in churches. The country, which has a population of about 10 million, began its vaccination programme in January. You might also be interested in:Covid-19: Tracking the global pandemic in maps and chartsHow will I know if I have coronavirus?

AdvertisementContinue reading the main storySupported byContinue reading the main storyEbola Survivor Infected Years Ago May Have Started New OutbreakGenetic sequencing of virus samples from patients in Guinea suggest that the new outbreak is a continuation of the 2014-16 epidemic.Researchers were shocked to discover that an Ebola outbreak in Guinea was most likely started by a man infected at least five years ago. Here a hospital worker in Guinea is given an Ebola vaccine.Credit…Carol Valade/Agence France-Presse — Getty ImagesMarch 12, 2021, 10:31 p.m. ETAn Ebola outbreak now occurring in Guinea was almost certainly started by someone who survived West Africa’s historic 2014-16 epidemic, harbored the virus for at least five years and then transmitted it via semen to a sex partner, researchers reported on Friday.The finding, based on genetic sequencing of virus samples taken from patients in the current outbreak, shocked researchers. Until now, the longest the virus had been known to persist in a survivor was 500 days.“It’s a stunner,” Dr. William Schaffner, an infectious-disease expert at Vanderbilt University who was not involved in the research, said in an interview. “This is an extraordinary phenomenon.”The current outbreak in Guinea was first recognized in January and has infected at least 18 people and killed nine.The discovery that a survivor most likely started the outbreak has profound implications. West Africa’s previous epidemic infected more than 28,000 people, killed more than 11,000 and left thousands of survivors, some of whom were already being shunned because of fears about the disease. The prospect that those who survived might be infectious for years is likely to worsen their plight.The new finding also raises the possibility that other outbreaks in the region, assumed to have begun with transmission from animals, may actually have been started by survivors with unrecognized, lingering infections.One possible solution, Dr. Schaffner said, would be “to vaccinate much of equatorial Africa” against Ebola even where there is no current outbreak. Effective vaccines are available, one made by Merck and another by Johnson & Johnson, but so far they have generally been used only in response to outbreaks.People recover from Ebola when their immune systems wipe out the virus. But certain parts of the body, including the eye, the central nervous system and the testes are so-called privileged sites, beyond the reach of the immune system. The virus can sometimes hide in those spots. But no one knew it could hide out for so long.“We have no idea how often this may be happening,” Dr. Schaffner said. “Some studies are underway. As you can imagine, it’s not easy to study hiding viruses in immunologically privileged sites, like the testicles, the eye and, rarely, the central nervous system. Those are not accessible places for easy study.”Genetic sequences of virus samples from the current patients were compared to those from the 2014-16 outbreak and were found to be so similar that they had to be closely related, researchers said. The report, posted online on Friday, involved researchers from the Guinea Ministry of Health, other labs in that country, Senegal’s Pasteur Institute, the University of Edinburgh, the University of Nebraska Medical Center and the company PraesensBio.The findings were reported earlier on Friday by Science and Stat.“There are very few genomic changes, and for those to occur, the virus has to multiply,” Dr. Schaffner said. “I think the virus is in hibernation for the most part.”“Among other things, it shows you what brilliant insights molecular whole-genome sequencing can provide,” he said. “Till this moment, all of us thought the current outbreak was a consequence of transmission from nature, from bats. But it likely came from a human reservoir.”Michael Wiley, a virologist at the University of Nebraska Medical Center and the chief executive of PraesensBio, which provided materials used to study the samples, described the current outbreak as a “continuation” of the previous one.He said persistent infections and sexual transmission had already been recognized during the West African outbreak and during one in the Democratic Republic of Congo. Each new milestone for viral persistence has come as a shock, he said: first 180 days, then 500 days, and now more than five years after the initial infection.The U.S. Centers for Disease Control and Prevention said in a statement provided by its spokesman, Thomas Skinner: “CDC has reviewed the sequencing data from samples taken during the current outbreak in Guinea. While we can’t be 100 percent certain, CDC agrees that data supports the conclusion that cases in the current outbreak are likely linked to cases in the area during the 2014-2016 West Africa Ebola outbreak.”He added: “This suggests the outbreak was likely started from a persistent infection, a survivor, and not a new introduction of the virus from the animal reservoir. While we have seen outbreaks in the Democratic Republic of Congo linked to survivors, the length of time between the end of the 2014-2016 outbreak and the emergence of this outbreak is surprising and highlights the need for further research to better understand the complex epidemiology and ecology of Ebola.”Dr. Ian Lipkin, a virologist at Columbia University, said that after male patients had several semen samples that tested negative for Ebola, they were generally assumed to have cleared the virus, but that that was not always a correct assumption.“Somebody who had Ebola should probably be monitored on a regular basis to make sure they’re negative and remain negative,” he said.AdvertisementContinue reading the main story

Cancer cells can dodge chemotherapy by entering a state that bears similarity to certain kinds of senescence, a type of “active hibernation” that enables them to weather the stress induced by aggressive treatments aimed at destroying them, according to a new study by scientists at Weill Cornell Medicine. These findings have implications for developing new drug combinations that could block senescence and make chemotherapy more effective.
In a study published Jan. 26 in Cancer Discovery, a journal of the American Association for Cancer Research, the investigators reported that this biologic process could help explain why cancers so often recur after treatment. The research was done in both organoids and mouse models made from patients’ samples of acute myeloid leukemia (AML) tumors. The findings were also verified by looking at samples from AML patients that were collected throughout the course of treatment and relapse.
“Acute myeloid leukemia can be put into remission with chemotherapy, but it almost always comes back, and when it does it’s incurable,” said senior author Dr. Ari M. Melnick, the Gebroe Family Professor of Hematology and Medical Oncology and a member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine. “A longstanding question in the field has been, ‘Why can’t you get rid of all the cancer cells?’ A similar question can be posed for many other types of aggressive cancer in addition to AML.”
For years, cancer researchers have studied how tumors are able to rebound after they appear to be completely wiped out by chemotherapy. One theory has been that because not all cells within a tumor are the same at the genetic level — a condition called tumor heterogeneity — a small subset of cells are able to resist treatment and begin growing again. Another theory involves the idea of tumor stem cells — that some of the cells within a tumor have special properties that allow them to re-form a tumor after chemotherapy has been given.
The idea that senescence is involved does not replace these other theories. In fact, it could provide new insight into explaining these other processes, Dr. Melnick said.
In the study, the researchers found that when AML cells were exposed to chemotherapy, a subset of the cells went into a state of hibernation, or senescence, while at the same time assuming a condition that looked very much like inflammation. They looked similar to cells that have undergone an injury and need to promote wound healing — shutting down the majority of their functions while recruiting immune cells to nurse them back to health.

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“These characteristics are also commonly seen in developing embryos that temporarily shut down their growth due to lack of nutrition, a state called embryonic diapause,” Dr. Melnick explained. “It’s not a special process, but normal biological activity that’s playing out in the context of tumors.”
Further research revealed that this inflammatory senescent state was induced by a protein called ATR, suggesting that blocking ATR could be a way to prevent cancer cells from adopting this condition. The investigators tested this hypothesis in the lab and confirmed that giving leukemia cells an ATR inhibitor before chemotherapy prevented them from entering senescence, thereby allowing chemotherapy to kill all of the cells.
Importantly, studies published at the same time from two other groups reported that the role of senescence is important not just for AML, but for recurrent cases of breast cancer, prostate cancer and gastrointestinal cancers as well. Dr. Melnick was a contributor to one of those other studies.
Dr. Melnick and his colleagues are now working with companies that make ATR inhibitors to find a way to translate these findings to the clinic. However, much more research is needed, because many questions remain about when and how ATR inhibitors would need to be given.
“Timing will be very critical,” he said. “We still have a lot to work out in the laboratory before we can study this in patients.”
Dr. Cihangir Duy, a former postdoctoral fellow in Dr. Melnick’s lab, was the study’s first author. Dr. Duy now leads his own lab at Fox Chase Cancer Center in Philadelphia.
Dr. Ari Melnick has been a paid consultant for KDAC Therapeutics, Epizyme, and Constellation Pharmaceuticals.

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How much did SARS-CoV-2 need to change in order to adapt to its new human host? In a research article published in the open access journal PLOS Biology Oscar MacLean, Spyros Lytras at the University of Glasgow, and colleagues, show that since December 2019 and for the first 11 months of the SARS-CoV-2 pandemic there has been very little ‘important’ genetic change observed in the hundreds of thousands of sequenced virus genomes.
The study is a collaboration between researchers in the UK, US and Belgium. The lead authors Prof David L Robertson (at the MRC-University of Glasgow Centre for Virus Research, Scotland) and Prof Sergei Pond (at the Institute for Genomics and Evolutionary Medicine, Temple University, Philadelphia) were able to turn their experience of analysing data from HIV and other viruses to SARS-CoV-2. Pond’s state-of-the-art analytical framework, HyPhy, was instrumental in teasing out the signatures of evolution embedded in the virus genomes and rests on decades of theoretical knowledge on molecular evolutionary processes.
First author Dr Oscar MacLean explains, “This does not mean no changes have occurred, mutations of no evolutionary significance accumulate and ‘surf’ along the millions of transmission events, like they do in all viruses.” Some changes can have an effect; for example, the Spike replacement D614G which has been found to enhance transmissibility and certain other tweaks of virus biology scattered over its genome. On the whole, though, ‘neutral’ evolutionary processes have dominated. MacLean adds, “This stasis can be attributed to the highly susceptible nature of the human population to this new pathogen, with limited pressure from population immunity, and lack of containment, leading to exponential growth making almost every virus a winner.”
Pond comments, “what’s been so surprising is just how transmissible SARS-CoV-2 has been from the outset. Usually viruses that jump to a new host species take some time to acquire adaptations to be as capable as SARS-CoV-2 at spreading, and most never make it past that stage, resulting in dead-end spillovers or localised outbreaks.”
Studying the mutational processes of SARS-CoV-2 and related sarbecoviruses (the group of viruses SARS-CoV-2 belongs to from bats and pangolins), the authors find evidence of fairly significant change, but all before the emergence of SARS-CoV-2 in humans. This means that the ‘generalist’ nature of many coronaviruses and their apparent facility to jump between hosts, imbued SARS-CoV-2 with ready-made ability to infect humans and other mammals, but those properties most have probably evolved in bats prior to spillover to humans.
Joint first author and PhD student Spyros Lytras adds, “Interestingly, one of the closer bat viruses, RmYN02, has an intriguing genome structure made up of both SARS-CoV-2-like and bat-virus-like segments. Its genetic material carries both distinct composition signatures (associated with the action of host anti-viral immunity), supporting this change of evolutionary pace occurred in bats without the need for an intermediate animal species.”
Robertson comments, “the reason for the ‘shifting of gears’ of SARS-CoV-2 in terms of its increased rate of evolution at the end of 2020, associated with more heavily mutated lineages, is because the immunological profile of the human population has changed.” The virus towards the end of 2020 was increasingly coming into contact with existing host immunity as numbers of previously infected people are now high. This will select for variants that can dodge some of the host response. Coupled with the evasion of immunity in longer-term infections in chronic cases (e.g., in immunocompromised patients), these new selective pressures are increasing the number of important virus mutants.
It’s important to appreciate SARS-CoV-2 still remains an acute virus, cleared by the immune response in the vast majority of infections. However, it’s now moving away faster from the January 2020 variant used in all of the current vaccines to raise protective immunity. The current vaccines will continue to work against most of the circulating variants but the more time that passes, and the bigger the differential between vaccinated and not-vaccinated numbers of people, the more opportunity there will be for vaccine escape. Robertson adds, “The first race was to develop a vaccine. The race now is to get the global population vaccinated as quickly as possible.”

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Sound sleep plays a critical role in healing traumatic brain injury, a new study of military veterans suggests.
The study, published in the Journal of Neurotrauma, used a new technique involving magnetic resonance imaging developed at Oregon Health & Science University. Researchers used MRI to evaluate the enlargement of perivascular spaces that surround blood vessels in the brain. Enlargement of these spaces occurs in aging and is associated with the development of dementia.
Among veterans in the study, those who slept poorly had more evidence of these enlarged spaces and more post-concussive symptoms.
“This has huge implications for the armed forces as well as civilians,” said lead author Juan Piantino, M.D., MCR, assistant professor of pediatrics (neurology) in the OHSU School of Medicine and Doernbecher Children’s Hospital. “This study suggests sleep may play an important role in clearing waste from the brain after traumatic brain injury — and if you don’t sleep very well, you might not clean your brain as efficiently.”
Piantino, a physician-scientist with OHSU’s Papé Family Pediatric Research Institute, studies the effects of poor sleep on recovery after traumatic brain injuries.
The new study benefited from a method of analyzing MRIs developed by study co-author Daniel Schwartz and Erin Boespflug, Ph.D., under the direction of Lisa Silbert, M.D., M.C.R., professor of neurology in the OHSU School of Medicine. The technique measures changes in the brain’s perivascular spaces, which are part of the brain’s waste clearance system known as the glymphatic system.

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“We were able to very precisely measure this structure and count the number, location and diameter of channels,” Piantino said.
Co-author Jeffrey Iliff, Ph.D., professor of psychiatry and behavioral sciences and of neurology at the University of Washington and a researcher at the VA Puget Sound Health Care System, has led scientific research into the glymphatic system and its role in neurodegenerative conditions such as Alzheimer’s disease. During sleep, this brain-wide network clears away metabolic proteins that would otherwise build up in the brain.
The study used data collected from a group of 56 veterans enrolled by co-authors Elaine Peskind, M.D., and Murray Raskind, M.D., at the Mental Illness Research, Education and Clinical Center at the VA Puget Sound between 2011 and 2019.
“Imagine your brain is generating all this waste and everything is working fine,” Piantino said. “Now you get a concussion. The brain generates much more waste that it has to remove, but the system becomes plugged.”
Piantino said the new study suggests the technique developed by Silbert could be useful for older adults.

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“Longer term, we can start thinking about using this method to predict who is going to be at higher risk for cognitive problems including dementia,” he said.
The study is the latest in a growing body of research highlighting the importance of sleep in brain health.
Improving sleep is a modifiable habit that can be improved through a variety of methods, Piantino said, including better sleep hygiene habits such as reducing screen time before bed. Improving sleep is a focus of research of other OHSU scientists, including Piantino’s mentor, Miranda Lim, M.D., Ph.D., associate professor of neurology, medicine and behavioral neuroscience in the OHSU School of Medicine.
“This study puts sleep at the epicenter of recovery in traumatic brain injury,” Piantino said.
The study was supported by the National heart, Lung and Blood Institute of the National Institutes of Health, award K23HL150217-01; the U.S. Department of Veterans Affairs Rehabilitation Research and Development Service Merit Review grant B77421; and NIH award P30AG008017-18.

SARS-CoV-2, the virus that causes COVID-19, has mutated throughout the pandemic. New variants of the virus have arisen throughout the world, including variants that might possess increased ability to spread or evade the immune system. Such variants have been identified in California, Denmark, the U.K., South Africa and Brazil/Japan. Understanding how well the COVID-19 vaccines work against these variants is vital in the efforts to stop the global pandemic, and is the subject of new research from the Ragon Institute of MGH, MIT and Harvard and Massachusetts General Hospital.
In a study recently published in Cell, Ragon Core Member Alejandro Balazs, PhD, found that the neutralizing antibodies induced by the Pfizer and Moderna COVID-19 vaccines were significantly less effective against the variants first described in Brazil/Japan and South Africa. Balazs’s team used their experience measuring HIV neutralizing antibodies to create similar assays for COVID-19, comparing how well the antibodies worked against the original strain versus the new variants.
“We were able to leverage the unique high-throughput capacity that was already in place and apply it to SARS-CoV-2,” says Balazs, who is also an assistant professor of Medicine at Harvard Medical School and assistant investigator in the Department of Medicine at MGH. “When we tested these new strains against vaccine-induced neutralizing antibodies, we found that the three new strains first described in South Africa were 20-40 times more resistant to neutralization, and the two strains first described in Brazil and Japan were five to seven times more resistant, compared to the original SARS-CoV-2 virus.”
Neutralizing antibodies, explains Balazs, work by binding tightly to the virus and blocking it from entering cells, thus preventing infection. Like a key in a lock, this binding only happens when the antibody’s shape and the virus’s shape are perfectly matched to each other. If the shape of the virus changes where the antibody attaches to it — in this case, in SARS-CoV-2’s spike protein — then the antibody may no longer be able to recognize and neutralize the virus as well. The virus would then be described as resistant to neutralization.
“In particular,” says Wilfredo Garcia-Beltran, MD, PhD, a resident physician in the Department of Pathology at MGH and first author of the study, “we found that mutations in a specific part of the spike protein called the receptor binding domain were more likely to help the virus resist the neutralizing antibodies.” The three South African variants, which were the most resistant, all shared three mutations in the receptor binding domain. This may contribute to their high resistance to neutralizing antibodies.
Currently, all approved COVID-19 vaccines work by teaching the body to produce an immune response, including antibodies, against the SARS-CoV-2 spike protein. While the ability of these variants to resist neutralizing antibodies is concerning, it doesn’t mean the vaccines won’t be effective.
“The body has other methods of immune protection besides antibodies,” says Balazs. “Our findings don’t necessarily mean that vaccines won’t prevent COVID, only that the antibody portion of the immune response may have trouble recognizing some of these new variants.”
Like all viruses, SARS-CoV-2 is expected to continue to mutate as it spreads. Understanding which mutations are most likely to allow the virus to evade vaccine-derived immunity can help researchers develop next-generation vaccines that can provide protection against new variants. It can also help researchers develop more effective preventative methods, such as broadly protective vaccines that work against a wide variety of variants, regardless of which mutations develop.

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There is a great need to generate various types of cells for use in new therapies to replace tissues that are lost due to disease or injuries, or for studies outside the human body to improve our understanding of how organs and tissues function in health and disease. Many of these efforts start with human induced pluripotent stem cells (iPSCs) that, in theory, have the capacity to differentiate into virtually any cell type in the right culture conditions. The 2012 Nobel Prize awarded to Shinya Yamanaka recognized his discovery of a strategy that can reprogram adult cells to become iPSCs by providing them with a defined set of gene-regulatory transcription factors (TFs). However, progressing from there to efficiently generating a wide range of cell types with tissue-specific differentiated functions for biomedical applications has remained a challenge.
While the expression of cell type-specific TFs in iPSCs is the most often used cellular conversion technology, the efficiencies of guiding iPSC through different “lineage stages” to the fully functional differentiated state of, for example, a specific heart, brain, or immune cell currently are low, mainly because the most effective TF combinations cannot be easily pinpointed. TFs that instruct cells to pass through a specific cell differentiation process bind to regulatory regions of genes to control their expression in the genome. However, multiple TFs must function in the context of larger gene regulatory networks (GRNs) to drive the progression of cells through their lineages until the final differentiated state is reached.
Now, a collaborative effort led by George Church, Ph.D. at Harvard’s Wyss Institute for Biologically Inspired Engineering and Harvard Medical School (HMS), and Antonio del Sol, Ph.D., who leads Computational Biology groups at CIC bioGUNE, a member of the Basque Research and Technology Alliance, in Spain, and at the Luxembourg Centre for Systems Biomedicine (LCSB, University of Luxembourg), has developed a computer-guided design tool called IRENE, which significantly helps increase the efficiency of cell conversions by predicting highly effective combinations of cell type-specific TFs. By combining IRENE with a genomic integration system that allows robust expression of selected TFs in iPSCs, the team demonstrated their approach to generate higher numbers of natural killer cells used in immune therapies, and melanocytes used in skin grafts, than other methods. In a scientific first, generated breast mammary epithelial cells, whose availability would be highly desirable for the repopulation of surgically removed mammary tissue. The study is published in Nature Communications.
“In our group, the study naturally built on the ‘TFome’ project, which assembled a comprehensive library containing 1,564 human TFs as a powerful resource for the identification of TF combinations with enhanced abilities to reprogram human iPSCs to different target cell types,” said Wyss Core Faculty member Church. “The efficacy of this computational algorithm will boost a number of our tissue engineering efforts at the Wyss Institute and HMS, and as an open resource can do the same for many researchers in this burgeoning field.” Church is the lead of the Wyss Institute’s Synthetic Biology platform, and Professor of Genetics at HMS and of Health Sciences and Technology at Harvard and MIT.
Tooling up
Several computational tools have been developed to predict combinations of TFs for specific cell conversions, but almost exclusively these are based on the analysis of gene expression patterns in many cell types. Missing in these approaches was a view of the epigenetic landscape, the organization of the genome itself around genes and on the scale of entire chromosome sections which goes far beyond the sequence of the naked genomic DNA.

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“The changing epigenetic landscape in differentiating cells predicts areas in the genome undergoing physical changes that are critical for key TFs to gain access to their target genes. Analyzing these changes can inform more accurately about GRNs and their participating TFs that drive specific cell conversions,” said co-first author Evan Appleton, Ph.D. Appleton is a Postdoctoral Fellow in Church’s group who joined forces with Sascha Jung, Ph.D., from del Sol’s group in the new study. “Our collaborators in Spain had developed a computational approach that integrated those epigenetic changes with changes in gene expression to produce critical TF combinations as an output, which we were in an ideal position to test.”
The team used their computational “Integrative gene Regulatory Network model” (IRENE) approach to reconstruct the GRN controlling iPSCs, and then focused on three target cell types with clinical relevance to experimentally validate TF combinations prioritized by IRENE. To deliver TF combinations into iPSCs, they deployed a transposon-based genomic integration system that can integrate multiple copies of a gene encoding a TF into the genome, which allows all factors of a combination to be stably expressed. Transposons are DNA elements that can jump from one position of the genome to another, or in this case from an exogenously provided piece of DNA into the genome.
“Our research team composed of scientists from the LCSB and CIC bioGUNE has a long-standing expertise in developing computational methods to facilitate cell conversion. IRENE is an additional resource in our toolbox and one for which experimental validation has demonstrated it substantially increased efficiency in most tested cases,” corresponding author Del Sol, who is Professor at LCSB and CIC bioGUNE. “Our fundamental research should ultimately benefit patients, and we are thrilled that IRENE could enhance the production of cell sources readily usable in therapeutic applications, such as cell transplantation and gene therapies.”
Validating the computer-guided design tool in cells
The researchers chose human mammary epithelial cells (HMECs) as a first cell type. Thus far HMECs are obtained from one tissue environment, dissociated, and transplanted to one where breast tissue has been resected. HMECs generated from patients’ cells, via an intermediate iPSC stage, could provide a means for less invasive and more effective breast tissue regeneration. One of the combinations that was generated by IRENE enabled the team to convert 14% of iPSCs into differentiated HMECs in iPSC-specific culture media, showing that the provided TFs were sufficient to drive the conversion without help from additional factors.
The team then turned their attention to melanocytes, which can provide a source of cells in cellular grafts to replace damaged skin. This time they performed the cell conversion in melanocyte destination medium to show that the selected TFs work under culture conditions optimized for the desired cell type. Two out of four combinations were able to increase the efficiency of melanocyte conversion by 900% compared to iPSCs grown in destination medium without the TFs. Finally, the researchers compared combinations of TFs prioritized by IRENE to generate natural killer (NK) cells with a state-of-the-art differentiation method based on cell culture conditions alone. Immune NK cells have been found to improve the treatment of leukemia. The researchers’ approach outperformed the standard with five out of eight combinations increasing the differentiation of NK cells with critical markers by up to 250%.
“This novel computational approach could greatly facilitate a range of cell and tissue engineering efforts at the Wyss Institute and many other sites around the world. This advance should greatly expand our toolbox as we strive to develop new approaches in regenerative medicine to improve patients’ lives,” said Wyss Founding Director Donald Ingber, M.D., Ph.D., who is also the Judah Folkman Professor of Vascular Biology at HMS and Boston Children’s Hospital, and Professor of Bioengineering at the Harvard John A. Paulson School of Engineering and Applied Sciences.

Since the pandemic hit, researchers have been uncovering ways COVID-19 impacts other parts of the body, besides the lungs.
Now, for the first time, a visual correlation has been found between the severity of the disease in the lungs using CT scans and the severity of effects on patient’s brains, using MRI scans. This research is published in the American Journal of Neuroradiology. It will be presented at the 59th annual meeting of the American Society of Neuroradiology (ASNR) and has also been selected as a semifinalist for that organization’s Cornelius Dyke Award.
The results show that by looking at lung CT scans of patients diagnosed with COVID-19, physicians may be able to predict just how badly they’ll experience other neurological problems that could show up on brain MRIs, helping improve patient outcomes and identify symptoms for earlier treatment.
CT imaging can detect illness in the lungs better than an MRI, another medical imaging technique. However, MRI can detect many problems in the brain, particularly in COVID-19 patients, that cannot be detected on CT images.
The study was led by Achala Vagal, MD, professor in the department of radiology, and Abdelkader Mahammedi, MD, assistant professor of radiology. Both are UC Health radiologists and members of the UC Gardner Neuroscience Institute.
“We’ve seen patients with COVID-19 experience stroke, brain bleeds and other disorders affecting the brain,” says Mahammedi. “So, we’re finding, through patient experiences, that neurological symptoms are correlating to those with more severe respiratory disease; however, little information has been available on identifying potential associations between imaging abnormalities in the brain and lungs in COVID-19 patients.
“Imaging serves as proof for physicians, confirming how an illness is forming and with what severity and helps in making final decisions about a patient’s care.”
In this study, which was conducted not only at UC, but also at large institutions in Spain, Italy and Brazil, researchers reviewed electronic medical records and images of hospitalized COVID-19 patients from March 3 to June 25, 2020. Patients who were diagnosed with COVID-19, experienced neurological issues and who had both lung and brain images available were included.
Of 135 COVID-19 patients with abnormal CT lung scans and neurological symptoms, 49, or 36%, were also found to develop abnormal brain scans and were more likely to experience stroke symptoms.
Mahammedi says this study will help physicians classify patients, based on the severity of disease found on their CT scans, into groups more likely to develop brain imaging abnormalities. He adds that this correlation could be important for implementing therapies, particularly in stroke prevention, to improve outcomes in patients with COVID-19.
“These results are important because they further show that severe lung disease from COVID-19 could mean serious brain complications, and we have the imaging to help prove it,” says Mahammedi. “Future larger studies are needed to help us understand the tie better, but for now, we hope these results can be used to help predict care and ensure that patients have the best outcomes.”
This research was supported by the National Institutes of Health (the National Institute of Neurological Disorders and Stroke and National Institute on Aging) (NS103824, NS117643, NS100417, 1U01NS100699, U01NS110772). Researchers cite no conflict of interest.

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Materials provided by University of Cincinnati. Original written by Katie Pence. Note: Content may be edited for style and length.

As the world continues to grapple with the COVID-19 pandemic, an international team of researchers have published a review of the best techniques to collect airborne aerosols containing viruses.
In the review, which was published by the Science of the Total Environment journal, a team led by the University of Surrey concluded that the most effective way to collect and detect airborne pathogens, particularly viruses, was to use cyclone sampling techniques.
For example, the sampler draws the air through the cyclone separator. It then uses centrifugal forces to collect the particles on a sterile cone containing the liquid collection vessel, such as DMEM (Dulbecco’s minimal essential medium). The collected sample can then be readily used for any analysis for virus detection.
The research team hope that this wide-ranging review can serve as an information hub packed with the best methods and samplers involved in airborne virus collection.
The study is part of the INHALE project — an EPSRC funded project that aims to assess air pollution’s impact on personal health in urban environments. The project involves Imperial College London, the University of Surrey and the University of Edinburgh.
The INHALE team also reviewed effective techniques for capturing fine (PM2.5) and ultrafine (PM0.1) particles to understand their toxicity and their role on reactive oxygen species in cells, their elemental composition and carbon content. The team also set out to find the best solution to prevent samples from being destroyed, a common problem found in toxicological experiments that makes large sample collection challenging. The study concluded that Harvard impactor samplers could be used for both indoor and outdoor environments to effectively collect these fine and ultrafine samples.
Professor Prashant Kumar, lead author of the study and Founding Director of the Global Centre for Clean Air Research at the University of Surrey, said: “The scientific community will have to become more efficient and resourceful if we are to overcome foes such as airborne viruses and air pollution. Knowing the right tools to use — as well as how and where to use them — is crucial in our ongoing fight to make the air we breathe cleaner and safer for all.”
Professor Fan Chung, co-lead of INHALE from Imperial College London, said: “I am pleased that this timely review found support for the techniques that have been adopted in the INHALE research program. The collection of ultrafine particles is of particular importance because of the commonly found difficulties of collecting enough for toxicity studies. Ultimately, the success of INHALE will depend on the ability to capture enough of these fine and ultrafine particles as far as possible in their natural state.”
Professor Chris Pain, co-lead of INHALE from Imperial College London, said: “Understanding the application of these sampling techniques is hugely important for environmental and health research in general and for the INHALE project itself, particularly concerning collecting ultra-fine particles.”
This work was supported by the EPSRC INHALE (Health assessment across biological length scales for personal pollution exposure and its mitigation) project (EP/T003189/1).

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Materials provided by University of Surrey. Note: Content may be edited for style and length.