Texas Tech University’s Biological Threat Research Laboratory (BTRL) played a key role in detecting the first case of highly pathogenic avian influenza (HPAI) A (H5N1) transmitted from a mammal (dairy cow) to a human.
The case was made public in an article published in the New England Journal of Medicine. Steve Presley, the director of The Institute of Environmental and Human Health (TIEHH) and the BTRL, and Cynthia Reinoso Webb, the biological threat coordinator at TIEHH, were co-authors on the journal publication.
The journal article explains that in March a farm worker who reported no contact with sick or dead birds, but who was in contact with dairy cattle, began showing symptoms in the eye and samples were collected by the regional health department to test for potential influenza A.
Initial testing of the samples was performed at the BTRL, which is a component of the Centers for Disease Control and Prevention (CDC) Laboratory Response Network-Biological (LRN-B) located at TIEHH.
“It’s a huge thing that the virus has jumped from birds to mammals, dairy cows in this case, and then to humans,” Presley said. “That’s why this paper in the New England Journal of Medicine is very significant. It’s going to lay the foundation, I believe, for a lot of research in the future of how the virus is evolving.”
The involvement of Texas Tech’s BTRL is a continuation of the partnership between regional, state and federal public health partners.
“Being part of the CDC LRN-B, we have the standing capability to test for a lot of biological threats and some that are considered emergent,” Reinoso Webb explained.

The lab’s standby status allowed Reinoso Webb and the Texas Tech BTRL team to respond quickly to the needs of the regional public health authority. Knowing the potential dangers of the virus, Reinoso Webb pushed the testing into the safest laboratory available, and the team went to work.
Having received the samples in the early evening, results were being reported to regional, state and federal levels within hours. By the next day the samples were on their way to the CDC for further testing and confirmation.
“We were on the phone with the CDC until around midnight discussing different scenarios and follow up requirements,” Reinoso Webb said. “There is a lot of federal reporting. It was a very complicated case, even though it was two samples and one patient.
“But we had this wonderful communication with the CDC and made sure we did everything by the book. This is how it’s been structured, and this is how the communication was supposed to happen.”

Published7 minutes agoShareclose panelShare pageCopy linkAbout sharingBy Fergus WalshMedical editorThe right for terminally ill people on the Isle of Man to be helped to die could be a step closer after crucial votes in its parliament on Tuesday.Members will debate whether lethal drugs should be self-administered or given to those eligible by doctors.The island could become the first part of the British Isles to pass assisted-dying legislation.If royal assent is received next year, its first assisted death could come as soon as 2027.Another crown dependency, Jersey, is set to vote on proposals next week, although it has yet to introduce a bill. Both islands set their own laws.Dr Alex Allinson, a politician and doctor, introduced the private members’ bill at Tynwald, the Isle of Man parliament.He told the BBC that “fewer than a dozen” people a year would be expected to opt for an assisted death, which was now “a step closer” to becoming reality.How will the legislation work?Last week, members of the House of Keys (MHKs), roughly equivalent to the House of Commons at Westminster, began debating the clauses of the Assisted Dying Bill, which passed its second reading in October.Proposed Isle of Man assisted dying laws progressThis is a pivotal stage of the legislation as politicians vote on the details of who would be eligible. The bill allows for the provision of assisted dying for terminally ill adults with capacity and a “clear and settled intention” to end their lives.Two key changes to the original bill have been approved so far. Firstly, MHKs voted to increase the required residency period on the Isle of Man from one year to five, after concerns that it could encourage so-called “death tourism”.Secondly, politicians backed a change to allow those with less than a year to live the right to die, rather than six months as originally proposed.Dr Allinson said the legislation would help “a very small number of people” to have “autonomy and control over how and when they die”.But Julie Edge, another member of the House of Keys, described it as a “kill bill” saying there were not enough safeguards in place, adding that it could put “additional cost and pressures on the health service”, and deter doctors from coming to the island.The clauses yet to be voted on concern the involvement of the medical profession in assisted dying. The bill currently states that two doctors must verify that people meet the eligibility criteria.One of the most controversial areas to be voted on is whether patients could ask a doctor to give them a lethal injection, a form of voluntary euthanasia. The other option is to restrict it to patients self-administering the drugs.Once the clauses stage is completed at the House of Keys, the bill will then go for Third Reading – usually a formality – before being sent to the Legislative Council, the equivalent of the House of Lords. After that it would require the Privy Council in London to grant Royal Assent.There would then follow a period of at least a year while the health service on the island sets up the system and decides how it should operate. However, the island’s chief minister, Alfred Cannan, has said the bill should be put to a public vote before it becomes law. His proposal for a referendum may not be voted on until next month. Medical concernsA third of doctors who responded to an Isle of Man Medical Society survey last year said they would consider leaving if the legislation was introduced.Manx doctors reject assisted dying bill in surveyDr Duncan Gerry, a geriatrician, fears that the legislation will be a “slippery slope”. He told the BBC: “When you allow people to be killed by their doctor, it begins a journey that doesn’t stop. “Vulnerable people will start out with an offer, which becomes a suggestion, which becomes an obligation to die.”However, Sue Biggerstaff says the current law forces people like her husband Simon to die in excruciating pain.Simon was diagnosed with motor neurone disease, or MND, in July 2021 and within a month was paralysed from the neck down. She says his final months were “hateful” because he was in constant pain despite “wonderful” support from district nurses, doctors and a hospice team. “Simon had intravenous morphine in both legs, and both arms and patches. And he was still in pain. It was unbearable to watch.”She says Simon had open wounds which would not heal: “They told me that Simon’s body was decomposing while he was still alive. Nobody should be made to go through that.”Sue says he asked a doctor how long it would take to die if he refused food, and was told about 30 days.Simon, 65, died 11 months after his diagnosis. She concluded: “I hate having to relive this but I will do it over and over again if it just stops other people having to go through it.”Clare Barber, a former nurse, is another member of the House of Keys who is backing the legislation. She says she has seen “first-hand” some people unable to have a pain-free death.”I have worked in intensive care, hospice, nursing homes, and I’ve come across people who have openly expressed a will for assisted dying, because they’re suffering. “They have absolute capacity and the ability to make those decisions, but they’re not allowed to,” she says.”We empower people to make decisions about their healthcare all the way through their life, but when it comes to making those decisions around a good death, we take the ultimate decision away from them.”Religious objectionsBill Leishman, a Baptist minister, is part of Churches Alive in Mann, a Christian faith group which is united in its opposition to assisted dying.”My big concern for this bill is for vulnerable people, who don’t have much agency for themselves and the effect that it could have: the dangers of coercion, the dangers of unintended consequences and the dangers for people who feel suicidal.”He said with annual nursing home costs “north of £50,000” a year, where a child’s inheritance is “quickly dwindling away” he could see pressure being brought to bear on an elderly parent to opt for an assisted death.He told the BBC he would feel he was living in a place that was “less compassionate” than other parts of the British Isles if the Isle of Man was to set a precedent by introducing assisted dying.Jersey also looks likely to change the law after its politicians approved the principle of legalising assisted dying in 2021. Jersey’s States Assembly will vote next week on specific proposals including an option to allow an assisted death for those who are not terminally ill but who have an “incurable physical medical condition that is causing unbearable suffering”. If proposals are approved, and legislation is drawn up, the Jersey parliament says the earliest date the law would come into effect would be the summer of 2027.In Scotland, a private member’s bill to allow assisted dying was introduced in March – the third attempt since 2010. It is expected to be debated at Holyrood later this year.France looks set to change its law after President Macron gave his support for assisted dying. The National Assembly will be debating a bill introduced by the French health minister later this month.At Westminster, a fresh attempt to introduce assisted dying is likely after the general election. In 2015, MPs overwhelmingly rejected plans for a right to die in England and Wales.Since then, several countries, including New Zealand, Australia and Canada, have introduced assisted dying.ContentiousAssisted suicide, as many opponents would prefer to call it, is one of the most contentious issues facing society. It involves a complex balance between ethics and law, morality and medicine. The question is whether there should be a right for people to control how and when they die, and whether the health service should be allowed to provide the means to hasten their end.The Commons Health and Social Care Committee recently published a report analysing the spread of assisted dying globally.It concluded that palliative and end-of-life care had not got worse in countries following the introduction of a right to die, and that “in several jurisdictions” there had been an improvement.More on this storyProposed Isle of Man assisted dying laws progressPublished31 October 2023Manx doctors reject assisted dying bill in surveyPublished18 October 2023

A deadly strain of cholera bacteria that emerged in Indonesia back in 1961 continues to spread widely to this day, claiming thousands of lives around the world every year, sickening millions — and, with its persistence, baffling scientists. Finally, in a study published today in Nature, researchers from The University of Texas at Austin have discovered how this dangerous strain has held out over decades.
A longstanding mystery about the strain of Vibrio cholerae (V. cholerae) responsible for the seventh global cholera pandemic is how this lineage has managed to out-compete other pathogenic variants. The UT team identified a unique quirk of the immune system that protects the bacteria from a key driver of bacterial evolution.
“This component of the immune system is unique to this strain, and it has likely given it an extraordinary advantage over other V. Cholerae lineages,” said Jack Bravo, a UT postdoctoral researcher in molecular biosciences and corresponding author on the paper. “It has also allowed it to defend against parasitic mobile genetic elements, which has likely played a key part in the ecology and evolution of this strain and ultimately contributed to the longevity of this pandemic lineage.”
Cholera and other bacteria, like all living things, evolve through a series of mutations and adaptations over time, allowing for new developments in a changing environment, such as antibiotic resistance. Some of the drivers of evolution in microbes are even smaller DNA structures called plasmids that infect, exist and replicate inside a bacterium in ways that can change bacterial DNA. Plasmids also can use up energy and cause mutations that are less advantageous for the bacteria.
Through a combination of laboratory analysis and cryo-electron-microscope imaging, the research team identified a unique two-part defense system that these bacteria have that essentially destroys plasmids, thus protecting and preserving the bacterial strain.
The World Health Organization estimates that cholera infects 1.3 million to 4 million people a year and that between 21,000 and 143,000 die annually. The bacterium is usually spread through contaminated water and food or contact with an infected person’s fluids. Severe cases are marked by diarrhea, vomiting and muscle cramps that can lead to dehydration, sometimes fatally. Outbreaks occur mostly in areas with poor sanitation and drinking water infrastructure. Although there is currently a vaccine to fight cholera, protection against severe symptoms drops after only three months. With new interventions needed, researchers say their study offers a potential new avenue for drugmakers to explore.
“This unique defense system could be a target for treatment or prevention,” said David Taylor, associate professor of molecular biosciences at UT and an author on the paper. “If we can remove this defense, it could leave it vulnerable, or if we can turn its own immune system back on the bacteria, it would be an effective way to destroy it.”
The defense system outlined in the paper consists of two parts that work together. One protein targets the DNA of plasmids with remarkable accuracy, and a complementary enzyme shreds the DNA of the plasmid, unwinding the helix of the DNA moving in opposite directions.
Researchers noted that this system is also similar to some of the CRISPR-Cascade complexes, which are also based on bacterial immune systems. The CRISPR discovery eventually revolutionized gene-editing technologies that have brought about massive biomedical breakthroughs.
Delisa A. Ramos, Rodrigo Fregoso Ocampo and Caiden Ingram of UT were also authors on the paper. The research was funded by the National Institute of General Medical Sciences (NIGMS) of the National Institutes of Health and a Welch Foundation research grant.

Rice University’s Peter Wolynes and his research team have unveiled a breakthrough in understanding how specific genetic sequences, known as pseudogenes, evolve. Their paper was published May 13 by the Proceedings of the National Academy of Sciences.
Led by Wolynes, the D.R. Bullard-Welch Foundation Professor of Science, professor of chemistry, biosciences and physics and astronomy and co-director of the Center for Theoretical Biological Physics (CTBP), the team focused on deciphering the complex energy landscapes of de-evolved, putative protein sequences corresponding to pseudogenes.
Pseudogenes are segments of DNA that once encoded proteins but have since lost their ability to do so due to sequence degradation — a phenomenon referred to as devolution. Here, devolution represents an unconstrained evolutionary process that occurs without the usual evolutionary pressures that regulate functional protein-coding sequences.
Despite their inactive state, pseudogenes offer a window into the evolutionary journey of proteins.
“Our paper explains that proteins can de-evolve,” Wolynes said. “A DNA sequence can, by mutations or other means, lose the signal that tells it to code for a protein. The DNA continues to mutate but does not have to lead to a sequence that can fold.”
The researchers studied junk DNA in a genome that has de-evolved. Their research revealed that a mutation accumulation in pseudogene sequences typically disrupts the native network of stabilizing interactions, making it challenging for these sequences, if they were to be translated, to fold into functional proteins.
However, the researchers observed instances where certain mutations unexpectedly stabilized the folding of pseudogenes at the cost of altering their previous biological functions.

They identified specific pseudogenes, such as cyclophilin A, profilin-1 and small ubiquitin-like modifier 2 protein, where stabilizing mutations occurred in regions crucial for binding to other molecules and other functions, suggesting a complex balance between protein stability and biological activity.
Moreover, the study highlights the dynamic nature of protein evolution as some previously pseudogenized genes may regain their protein-coding function over time despite undergoing multiple mutations.
Using sophisticated computational models, the researchers interpreted the interplay between physical folding landscapes and the evolutionary landscapes of pseudogenes. Their findings provide evidence that the funnellike character of folding landscapes comes from evolution.
“Proteins can de-evolve and have their ability to fold compromised over time due to mutations or other means,” Wolynes said. “Our study offers the first direct evidence that evolution is shaping the folding of proteins.”
Along with Wolynes, the research team includes lead author and applied physics graduate student Hana Jaafari ; CTBP postdoctoral associate Carlos Bueno ; University of Texas at Dallas graduate student Jonathan Martin; Faruck Morcos, associate professor in the Department of Biological Sciences at UT-Dallas; and CTBP biophysics researcher Nicholas P. Schafer.
The implications of this research extend beyond theoretical biology with potential applications in protein engineering, Jaafari said.
“It would be interesting to see if someone at a lab could confirm our results to see what happens to the pseudogenes that were more physically stable,” Jaafari said. “We have an idea based on our analysis, but it’d be compelling to get some experimental validation.”

Most alcohol enters the bloodstream via the mucous membrane layer of the stomach and the intestines. These days, the consequences of this are undisputed: even small amounts of alcohol impair people’s ability to concentrate and to react, increasing the risk of accidents. Drinking large quantities on a regular basis is detrimental to one’s health: common consequences include liver disease, inflammation of the gastrointestinal tract and cancer. According to the World Health Organization, around 3 million people die every year from excessive alcohol consumption.
Researchers at ETH Zurich have now developed a protein gel that breaks down alcohol in the gastrointestinal tract. In a study recently published in the journal Nature Nanotechnology, they show that in mice, the gel converts alcohol quickly, efficiently and directly into harmless acetic acid before it enters the bloodstream, where it would normally develop its intoxicating and harmful effects.
Reducing health damage caused by alcohol
“The gel shifts the breakdown of alcohol from the liver to the digestive tract. In contrast to when alcohol is metabolised in the liver, no harmful acetaldehyde is produced as an intermediate product,” explains Professor Raffaele Mezzenga from the Laboratory of Food & Soft Materials at ETH Zurich. Acetaldehyde is toxic and is responsible for many health problems caused by excessive alcohol consumption.
In the future, the gel could be taken orally before or during alcohol consumption to prevent blood alcohol levels from rising and acetaldehyde from damaging the body. In contrast to many products available on the market, the gel combats not only the symptoms of harmful alcohol consumption but also its causes. Yet, the gel is only effective as long as there is still alcohol in the gastrointestinal tract. This means it can do very little to help with alcohol poisoning, once the alcohol has crossed into the bloodstream. Nor does it help to reduce alcohol consumption in general. “It’s healthier not to drink alcohol at all. However, the gel could be of particular interest to people who don’t want to give up alcohol completely, but don’t want to put a strain on their bodies and aren’t actively seeking the effects of alcohol,” Mezzenga says.
Main ingredients: Whey, iron and gold
The researchers used ordinary whey proteins to produce the gel. They boiled them for several hours to form long, thin fibrils. Adding salt and water as a solvent then causes the fibrils to cross-link and form a gel. The advantage of a gel over other delivery systems is that it is digested very slowly. But to break down the alcohol, the gel needs several catalysts.

The researchers used individual iron atoms as the main catalyst, which they distributed evenly over the surface of the long protein fibrils. “We immersed the fibrils in an iron bath, so to speak, so that they can react effectively with the alcohol and convert it into acetic acid,” says ETH researcher Jiaqi Su, the first author of the study. Tiny amounts of hydrogen peroxide are needed to trigger this reaction in the intestine. These are generated by an upstream reaction between glucose and gold nanoparticles. Gold was chosen as a catalyst for hydrogen peroxide because the precious metal is not digested and therefore stays effective for longer in the digestive tract. The researchers packed all these substances — iron, glucose and gold — into the gel. This resulted in a multi-stage cascade of enzymatic reactions that ultimately converts alcohol into acetic acid.
Gel works in mice
The researchers tested the effectiveness of the new gel on mice that were given alcohol just once as well as on mice that were given alcohol regularly for ten days. Thirty minutes after the single dose of alcohol, the prophylactic application of the gel reduced the alcohol level in the mice by 40 percent. Five hours after alcohol intake, their blood alcohol level had dropped by as much as 56 percent compared to the control group. Harmful acetaldehyde accumulated less in these mice, and they exhibited greatly reduced stress reactions in their livers, which was reflected in better blood values.
In the mice that were given alcohol for ten days, the researchers were able to demonstrate not only a lower alcohol level but also a lasting therapeutic effect of the gel: the mice that were given the gel daily in addition to alcohol showed significantly less weight loss, less liver damage and hence better fat metabolism in the liver as well as better blood values. Other organs in the mice, such as the spleen or the intestine, as well as their tissues also showed much less damage caused by alcohol.
Patent pending
In an earlier study of administering iron through whey protein fibrils, the researchers had discovered that iron reacts with alcohol to form acetic acid. As this process was too slow and too ineffective at the time, they changed the form in which they attached the iron to the protein fibrils. “Instead of using larger nanoparticles, we opted for individual iron atoms, which can be distributed more evenly on the surface of the fibrils and therefore react more effectively and quickly with the alcohol,” Mezzenga says.
The researchers have already applied for a patent for the gel. While several clinical tests are still required before it can be authorised for human use, the researchers are confident that this step will also be successful, as they already showed that the whey protein fibrils that make up the gel are edible.

In emergency rooms and intensive care units across the country, clinicians make split-second decisions about which antibiotics to give a patient when a life-threatening infection is suspected. A new U-M study reveals that these decisions may have unintended consequences for patient outcomes.
Beginning in 2015, a 15-month national shortage of a commonly prescribed antibiotic, piperacillin/tazobactam, known by the brand name Zosyn, provided a unique opportunity to compare rates of death in hospitalized patients with sepsis who were administered two different types of antibiotics — one that spares the gut microbiome and one that profoundly alters it.
Piperacillin/tazobactam is a broad-spectrum antibiotic that is commonly administered for sepsis, a life-threatening complication from infection. In its absence, clinicians commonly instead use another antibiotic, cefepime, which has similar activity against common sepsis pathogens but, unlike piperacillin/tazobactam, has minimal effects on anaerobic gut bacteria.
“We saw this Zosyn shortage as a one-of-a-kind opportunity to ask whether this antibiotic, which we know depletes the gut of anaerobic bacteria, makes a difference in terms of patient outcomes,” said Robert Dickson, M.D. of the Department of Medicine’s Division of Pulmonary & Critical Care Medicine and Deputy Director of the Weil Institute for Critical Care Research & Innovation.
In health, the gut microbiome is largely populated by anaerobic bacteria that rarely cause disease. Prior work by the study team has revealed that even a single dose of piperacillin/tazobactam kills most of these anaerobic gut bacteria, which play important roles in the body’s metabolism, immunity, and prevention of infections.
Dickson, Rishi Chanderraj, M.D. of the Division of Infectious Disease, Michael Sjoding, M.D. of the Division of Pulmonary & Critical Care Medicine and their multidisciplinary team at U-M and the VA Ann Arbor used patient record data to look at outcomes in 7,569 patients. The team compared 4,523 patients who were treated were piperacillin/tazobactam with 3,046 patients who received cefepime.
They found marked differences: treatment with piperacillin-tazobactam was associated with a 5 percent increase in 90-day mortality, more days on a ventilator, and more time with organ failure.

“These are powerful antibiotics that are administered to patients every day in every hospital nationwide,” said Chanderraj. “Clinicians use them because they are trying to treat every possible pathogen that might be causing their patients’ illness. But our results suggest that their effects on the microbiome might also have important effects on patient outcomes.”
The study builds on previous work by the study team that suggested critically ill patients may do worse when given antibiotics that deplete the gut of anaerobes. They have also seen similar effects when studying animal models.
“Our prior work suggested that there might be harm with piperacillin/tazobactam, but it was an observational study that had some limitations,” said Sjoding, the study’s senior author. “That’s why the drug shortage was such an amazing opportunity. It created an almost perfect natural experiment that let us test the difference between these two drugs on patient outcomes in a very rigorous manner.”
A recent clinical trial pitted these two antibiotics against each other and compared side effects and mortality after two weeks. That trial did not find any differences in the short term — a finding that the U-M team also observed in their analysis.
“When we looked at two-week outcomes in our study, we didn’t find differences either,” said Chanderraj. “But the differences at three months were dramatic.”
Overall, the new findings suggest that treatment with piperacillin/tazobactam instead of cefepime may contribute to one additional death per every 20 septic patients treated.
“A 5% mortality difference has enormous implications because sepsis is so common,” said Dickson. “Every day, thousands of clinicians are deciding which of these drugs to use in septic patients.”
Physicians should give more thought about whether anti-anerobic antibiotics are warranted before prescribing them, added Chanderraj. “We need to think about antibiotics like chemotherapy. In the right context, treatment can be lifesaving, but in the wrong context, it can be quite harmful.”

Suddenly they appear and — like the SARS-CoV-2 coronavirus — can trigger major epidemics: Viruses that nobody had on their radar. They are not really new, but they have changed genetically. In particular, the exchange of genetic material between different virus species can lead to the sudden emergence of threatening pathogens with significantly altered characteristics. This is suggested by current genetic analyses carried out by an international team of researchers. Virologists from the German Cancer Research Center (DKFZ) were in charge of the large-scale study.
“Using a new computer-assisted analysis method, we discovered 40 previously unknown nidoviruses in various vertebrates from fish to rodents, including 13 coronaviruses,” reports DKFZ group leader Stefan Seitz. With the help of high-performance computers, the research team, which also includes Chris Lauber’s working group from the Helmholtz Center for Infection Research in Hanover, has sifted through almost 300,000 data sets. According to virologist Seitz, the fact that we can now analyze such huge amounts of data in one go opens up completely new perspectives.
Virus research is still in its relative infancy. Only a fraction of all viruses occurring in nature are known, especially those that cause diseases in humans, domestic animals and crops. The new method therefore promises a quantum leap in knowledge with regard to the natural virus reservoir. Stefan Seitz and his colleagues sent genetic data from vertebrates stored in scientific databases through their high-performance computers with new questions. They searched for virus-infected animals in order to obtain and study viral genetic material on a large scale. The main focus was on so-called nidoviruses, which include the coronavirus family.
Nidoviruses, whose genetic material consists of RNA (ribonucleic acid), are widespread in vertebrates. This species-rich group of viruses has some common characteristics that distinguish them from all other RNA viruses and document their relationship. Otherwise, however, nidoviruses are very different from each other, i.e. in terms of the size of their genome.
One discovery is particularly interesting with regard to the emergence of new viruses: In host animals that are simultaneously infected with different viruses, a recombination of viral genes can occur during virus replication. “Apparently, the nidoviruses we discovered in fish frequently exchange genetic material between different virus species, even across family boundaries,” says Stefan Seitz. And when distant relatives “crossbreed,” this can lead to the emergence of viruses with completely new properties. According to Seitz, such evolutionary leaps can affect the aggressiveness and dangerousness of the viruses, but also their attachment to certain host animals.
“A genetic exchange, as we have found in fish viruses, will probably also occur in mammalian viruses,” explains Stefan Seitz. Bats, which — like shrews — are often infected with a large number of different viruses, are considered a true melting pot. The SARS-CoV-2 coronavirus probably also developed in bats and jumped from there to humans.
After gene exchange between nidoviruses, the spike protein with which the viruses dock onto their host cells often changes. Chris Lauber, first author of the study, was able to show this by means of family tree analyses. Modifying this anchor molecule can significantly change the properties of the viruses to their advantage — by increasing their infectiousness or enabling them to switch hosts. A change of host, especially from animals to humans, can greatly facilitate the spread of the virus, as the corona pandemic has emphatically demonstrated. Viral “game changers” can suddenly appear at any time, becoming a massive threat and — if push comes to shove — triggering a pandemic. The starting point can be a single double-infected host animal.
The new high-performance computer process could help to prevent the spread of new viruses. It enables a systematic search for virus variants that are potentially dangerous for humans, explains Stefan Seitz. And the DKFZ researcher sees another important possible application with regard to his special field of research, virus-associated carcinogenesis: “I could imagine that we could use the new High Performance Computing (HPC) to systematically examine cancer patients or immunocompromised people for viruses. We know that cancer can be triggered by viruses, the best-known example being human papillomaviruses. But we are probably only seeing the tip of the iceberg so far. The HPC method offers the opportunity to track down viruses that, previously undetected, nestle in the human organism and increase the risk of malignant tumors.”
Chris Lauber, Xiaoyu Zhang, Josef Vaas, Franziska Klingler, Pascal Mutz, Arseny Dubin, Thomas Pietschmann, Olivia Roth, Benjamin W. Neuman, Alexander E. Gorbalenya, Ralf Bartenschlager, Stefan Seitz: Deep mining of the Sequence Read Archive reveals major genetic innovations in coronaviruses and other nidoviruses of aquatic vertebrates.

People with a common heart condition were able to use significantly more oxygen while exercising after taking an investigational drug in an international clinical trial, according to a study published today in the New England Journal of Medicine. The finding wasalso presented today at the European Society of Cardiology’s Heart Failure 2024 meeting in Lisbon, Portugal.
Oregon Health & Science University is part of the randomized, double-blind Phase 3 trial that is evaluating the experimental drug aficamten, which was developed by Cytokinetics to treat the obstructive form of hypertrophic cardiomyopathy, or HCM. Of the 282 adults participating in the trial, 19 enrolled through OHSU — the most of any trial center.
“By having more oxygen available during exercise, patients with obstructive hypertrophic cardiomyopathy can more easily walk, perform household chores, and do other everyday tasks,” said cardiologist Ahmad Masri, M.D., M.S., who co-wrote today’s paper and directs the OHSU Knight Cardiovascular Institute’s Hypertrophic Cardiomyopathy Center. “Our latest clinical trial results suggest aficamten is a promising treatment for HCM.”
HCM affects about 1 in 500 people and is one of the most common causes of sudden death for youth and otherwise healthy athletes. Often caused by inherited gene mutations, it thickens heart muscles and makes it difficult for the heart to work as it should. It causes shortness of breath and reduces people’s ability to exercise. The obstructive form of HCM reduces blood flow out of the heart.
About half of the trial’s participants were given the experimental drug, and the other half took a placebo and served as the study’s control group. Scientists measured the participants’ oxygen levels while they used treadmills or bicycles. Those who took aficamten had a significant increase in their maximum oxygen use — 1.7 milliliters per kilogram per minute more than those in the control group.
Having an increased peak oxygen uptake can improve a patient’s ability to be physically active, whereas reduced oxygen uptake can increase the risk of experiencing heart failure, needing a heart transplant, and dying.
Non-drug treatment options for obstructive HCM include surgery to remove excess heart muscle. In 2022, the Food and Drug Administration also approved mavacamten as the first drug designed to target the underlying cause of obstructive HCM. However, mavacamten may increase the risk of heart failure and it interacts with several commonly used medications. As a result, patients who use mavacamten must also undergo intense monitoring.
During the past decade, OHSU has been involved in many research studies exploring new HCM treatment options. It has been a center for several mavacamten studies and is participating in gene therapy research. The university is also currently involved in four other aficamten trials that are evaluating it as a potential treatment for various forms of HCM and in different types of patients, including children.
“This is an exciting time for treating HCM,” Masri said. “While we continue to offer traditional surgical and procedural therapies for HCM, we are now also able to offer patients other treatment options: therapies that were recently approved by the FDA and investigational therapies that are available by participating in clinical trials.”

Nature gave ticks, mosquitoes and leaches a quick-acting way to keep blood from clotting while they extract their meal from a host.
Now the key to that method has been harnessed by a team of Duke researchers as a potential anti-clotting agent that could be used as an alternative to heparin during angioplasty, dialysis care, surgeries and other procedures.
Publishing in the journal Nature Communications, the researchers describe a synthetic molecule that mimics the effects of compounds in the saliva of blood-sucking critters. Importantly, the new molecule can also be swiftly reversed, enabling clotting to resume when needed after treatment.
“Biology and evolution figured out anti-coagulation multiple times with a highly potent strategy,” said senior author Bruce Sullenger, Ph.D., professor in the departments of Surgery, Cell Biology, Neurosurgery and Pharmacology & Cancer Biology at Duke University School of Medicine. “It’s the perfect model.”
Sullenger and colleagues at Duke and the University of Pennsylvania — including lead author Haixiang Yu, Ph.D., a member of Sullenger’s lab — started from the observation that all blood-sucking organisms evolved a similar system to inhibit blood clotting. The anti-clotting agent in their saliva uses a two-pronged process, binding to the surface of certain clotting proteins in the host’s blood, and entering into the protein’s core to temporarily inactivate clotting during a blood meal.
Blood-sucking organisms target different proteins among the sequence of more than two dozen molecules involved in clotting, but the research team concentrated on engineering molecules to home in on thrombin and factor Xa in human blood, achieving the dual-action anti-clotting function against these proteins.
The next challenge was devising a way to reverse the process — essential for clinical applications to ensure that people don’t hemorrhage. With the activation mechanism fully elucidated, the researchers were able to reverse engineer an antidote that quickly restores clotting.

“We believe this approach could be safer for patients and generate less inflammation, as well,” Yu said.
Another plus is that it is a synthetic molecule, unlike the current clinical standard for the past 100 years, heparin. Heparin is isolated from pig intestines, requiring a massive farming infrastructure that generates pollution and greenhouse gases.
“This is part of a new passion of mine — improving agents that control blood clotting to help patients, while also being responsible from a climate perspective,” Sullenger said. “The medical field is starting to recognize that there’s a big problem here, and we need to find alternatives to using animals for making medicines.”
In addition to Sullenger and Yu, study authors include Shekhar Kumar, James W. Frederiksen, Vladimir N. Kolyadko, George Pitoc, Juliana Layzer, Amy Yan, Rachel Rempel, Samuel Francis, and Sriram Krishnaswamy.
The study received funding support from the National Institutes of Health (P01-HL139420, 23POST1018721). Duke has submitted a patent application on the thrombin and factor Xa EXACT inhibitors; Sullenger and Yu are listed as inventors.

Researchers from the Kops group in collaboration with researchers from the University of Edinburgh, made a surprising new discovery in the structure of the centromere, a structure that is involved in ensuring that chromosomes are segregated properly when a cell divides. Mistakes in chromosome segregation can lead to cell death and cancer development. The researchers discovered that the centromere consists of two subdomains. This fundamental finding has important implications for the process of chromosome segregation and provides new mechanisms underlying erroneous divisions in cancer cells. The research was published in Cell on May 13th 2024.
Our bodies consist of trillions of cells, most of which have a limited life span and therefore need to reproduce to replace the old ones. This reproduction process is referred to as cell division or mitosis. During mitosis, the parent cell will duplicate its chromosomes in order to pass down the genetic material to the daughter cells. The resulting identical pairs of chromosomes, the sister chromatids, are held together by a structure called the centromere. The sister chromatids then need to be evenly split over the two daughter cells to ensure that each daughter cell is an exact copy of the parent cell. If errors happen during the segregation, one daughter cell will have too many chromosomes, while the other has too few. This can lead to cell death or cancer development.
The role of the centromere
The centromere is a part of the chromosome that plays a vital role in chromosome segregation during mitosis. The process of dividing the sister chromatids over the cells is guided by the interaction between the centromeres and structures known as spindle microtubules. These spindle microtubules are responsible for pulling the chromatids apart and thus separating the two sister chromatids. Carlos Sacristan Lopez, the first author of this study, explains: ‘If the attachment of the centromere to the spindle microtubules does not occur properly it leads to chromosome segregation mistakes which are frequently observed in cancer.’ Understanding the structure of the centromere can contribute to more insights into the function of the centromere and its role in erroneous chromosomal segregation.
A surprising discovery
To investigate the centromere structure, the researchers used a combination of imaging and sequencing techniques. The super-resolution microscopy imaging took place at the Hubrecht Institute, while the group of Bill Earnshaw performed the sequencing. This collaboration led to a surprising new discovery in the centromere structure. Previously believed to consist of a compact structure attaching to multiple spindle microtubules, it was instead revealed that the centromere consists of two subdomains. Carlos explains: ‘This discovery was very surprising, as subdomains bind microtubules independently of each other. Yet, to form correct attachments, they must remain closely connected. In cancer cells, however, we often observe that subdomains uncouple, resulting in erroneous attachments and chromosome segregation errors.’
This very exciting and fundamental discovery contributes to our understanding of the origin of chromosome segregation errors which are frequently seen in cancer.