Publisher Health

Scientists have waited months for access to highly accurate protein structure prediction since DeepMind presented remarkable progress in this area at the 2020 Critical Assessment of Structure Prediction, or CASP14, conference. The wait is now over.
Researchers at the Institute for Protein Design at the University of Washington School of Medicine in Seattle have largely recreated the performance achieved by DeepMind on this important task. These results will be published online by the journal Science on Thursday, July 15.
Unlike DeepMind, the UW Medicine team’s method, which they dubbed RoseTTAFold, is freely available. Scientists from around the world are now using it to build protein models to accelerate their own research. Since July, the program has been downloaded from GitHub by over 140 independent research teams.
Proteins consist of strings of amino acids that fold up into intricate microscopic shapes. These unique shapes in turn give rise to nearly every chemical process inside living organisms. By better understanding protein shapes, scientists can speed up the development of new treatments for cancer, COVID-19, and thousands of other health disorders.
“It has been a busy year at the Institute for Protein Design, designing COVID-19 therapeutics and vaccines and launching these into clinical trials, along with developing RoseTTAFold for high accuracy protein structure prediction. I am delighted that the scientific community is already using the RoseTTAFold server to solve outstanding biological problems,” said senior author David Baker, professor of biochemistry at the University of Washington School of Medicine, a Howard Hughes Medical Institute investigator, and director of the Institute for Protein Design.
In the new study, a team of computational biologists led by Baker developed the RoseTTAFold software tool. It uses deep learning to quickly and accurately predict protein structures based on limited information. Without the aid of such software, it can take years of laboratory work to determine the structure of just one protein.
RoseTTAFold, on the other hand, can reliably compute a protein structure in as little as ten minutes on a single gaming computer.
The team used RoseTTAFold to compute hundreds of new protein structures, including many poorly understood proteins from the human genome. They also generated structures directly relevant to human health, including those for proteins associated with problematic lipid metabolism, inflammation disorders, and cancer cell growth. And they show that RoseTTAFold can be used to build models of complex biological assemblies in a fraction of the time previously required.
RoseTTAFold is a “three-track” neural network, meaning it simultaneously considers patterns in protein sequences, how a protein’s amino acids interact with one another, and a protein’s possible three-dimensional structure. In this architecture, one-, two-, and three-dimensional information flows back and forth, thereby allowing the network to collectively reason about the relationship between a protein’s chemical parts and its folded structure.
“We hope this new tool will continue to benefit the entire research community,” said Minkyung Baek, a postdoctoral scholar who led the project in the Baker laboratory at UW Medicine.

Adenovirus vaccine vectors, such as the ChAdOx1 nCov-19 construct which has risen to prominence as a major vaccine for COVID-19, may generate robust long-term immune system responses, according to scientists from the Universities of Oxford and the Cantonal Hospital St.Gallen, Switzerland.
Writing in the journal Nature Immunology, they detail an investigation into one of the key features of adenovirus vaccines — their ability to generate strong and sustained populations of the ‘killer’ T-cell element of the immune system.
In an animal model, they observed that adenoviruses are able to get into long-lived tissue cells, known as fibroblastic reticular cells, which in turned formed small, well organised clusters, acting as ‘training grounds’ for these T-cells, appearing to explain how these vaccines sustain robust immune system responses.
Paul Klenerman, Sidney Truelove Professor of Gastroenterology at the University of Oxford’s Nuffield Department of Medicine, and one of the lead authors of the paper, said:
“Millions of people will have received adenovirus vaccines around the world, not only the Oxford-AstraZeneca vaccine, but the J&J vaccine, and also the Chinese and Russian versions. The ultimate goal with these vaccines is the induction of long-term immune system protection using both antibodies and T-cells. This research helps us to understand more on the process of vaccination, and why the effects on killer T-cells are so prolonged.”
The researchers show that adenovirus vectors can target specific cells — known as stromal cells in tissues such as the lung — generating antigen ‘depots’ in these long-lived cells. These stromal cells were originally thought just to provide an inert scaffold for the tissues, but it appears that they are very dynamic cells with a major role in immune control. The long lived nature of the cells means that the antigen can be ‘shown’ to the immune system many times, effectively boosting the response, a critical element of generation of protective T-cells.
They were also able to investigate other mechanisms which may explain the particular efficacy of adenovirus vectors, including the key chemical messenger involved in signalling to T cells. This is a factor called IL-33 — a so-called “alarmin” released when the stromal cells receive signals of distress. IL-33 acts to strongly boost to the metabolism of the T cells, resulting in effectively more energetic cells and a highly protective immune response.
Burkhard Ludewig, Professor at the University of Zurich, and Head of the Medical Research Center, Cantonal Hospital St. Gallen, Switzerland, also a lead author of the paper, said:
“Adenoviruses have co-evolved with humans over a very long time, and learned a lot about the human immune system in the process. Viruses are always the best teachers, and here they have taught us an important lesson about how best to boost killer T cell responses. The T cells that come from these cellular training camps appear to have a very high level of “fitness.” Hopefully we can put this to good use in designing new vaccines — vaccines that we still desperately need for diseases such as TB, HIV, hepatitis C and cancers.”
The researchers will now continue to investigate these particular pathways for immunization against emerging pathogens, both in pre-clinical models, and clinical studies, with the goal of helping to accelerate further development of crucial vaccines.
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Materials provided by University of Oxford. Note: Content may be edited for style and length.

BBC Newcastle presenter Lisa Shaw died after a bleed on the brain, a week after receiving her first dose of AstraZeneca vaccine. She had been taken to hospital after developing severe headaches.Her husband, Gareth Eve, says he is aware of the risk of rare side effects that come with vaccines. He says a choice of Covid vaccines should be offered to people – something that the UK does not routinely do currently.The vaccine was listed as a possible factor on Lisa’s interim death certificate, and a coroner’s inquest will now look into the 44-year-old’s cause of death.The MHRA has said: “Over 81 million doses of vaccines against Covid-19 have now been administered in the UK, saving thousands of lives… No effective medicine or vaccine is without risk and our advice remains that the benefits of the AstraZeneca vaccine outweigh the risks in the majority of people and it’s still vitally important that people come forward for their vaccination and their second dose when they are invited to do so.”A statement from the Department of Health and Social Care says: “All vaccines being used in the UK have undergone robust clinical trials and have met the Medicines and Healthcare products Regulatory Agency (MHRA) strict standards of safety effectiveness and quality.”If you are feeling emotionally distressed by this report, support is available in the UK at www.bbc.co.uk/actionline

The latest investigations into a promising new genetic test for glaucoma — the leading cause of blindness worldwide — has found it has the ability to identify 15 times more people at high risk of glaucoma than an existing genetic test.
The study, just published in JAMA Ophthalmology, builds on a long-running international collaboration between Flinders University and the QIMR Berghofer Medical Research Institute and other research partners around the world to identify genetic risk factors for glaucoma. “Early diagnosis of glaucoma can lead to vision-saving treatment, and genetic information can potentially give us an edge in making early diagnoses, and better treatment decisions,” says lead researcher Associate Professor Owen Siggs, from Flinders University in South Australia and the Garvan Institute of Medical Research in Sydney, NSW.
Senior author, Flinders University Professor Jamie Craig, says the latest research highlights the potential of the test in glaucoma screening and management.
“Genetic testing is not currently a routine part of glaucoma diagnosis and care, but this test has the potential to change that. We’re now in a strong position to start testing this in clinical trials,” says Professor Craig, a consulting ophthalmologist who also runs a in world-leading glaucoma research program at Flinders University, funded by Australia’s NHMRC.
The latest results benchmarked the performance of genetic testing on 2507 Australian individuals with glaucoma, and 411,337 individuals with or without glaucoma in the UK.
One in 30 Australians will ultimately develop glaucoma, many of whom are diagnosed late due to lack of symptoms.
Once diagnosed, several treatment options can slow or halt the progression of glaucoma vision loss.
The new test, performed on a blood or saliva sample, has the potential to identify high-risk individuals before irreversible vision loss occurs.
Members of the research team are also launching a spin-out company to develop an accredited test for use in clinical trials, with recruitment expected to begin in 2022.
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Materials provided by Flinders University. Note: Content may be edited for style and length.

Contamination of urban lakes, rivers and surface water by human waste is creating pools of ‘superbugs’ in Low- and Middle-Income Countries (LMIC) — but improving access to clean water, sanitation and sewerage infrastructure could help to protect people’s health, a new study reveals.
Researchers studied bodies of water in urban and rural sites in three areas of Bangladesh — Mymensingh, Shariatpur and Dhaka. They found more antibiotic resistant faecal coliforms in urban surface water compared to rural settings, consistent with reports of such bacteria in rivers across Asia.
Publishing their findings in mSystems today, researchers from the University of Birmingham and the International Centre for Diarrhoeal Disease Research, Bangladesh call for further research to quantify the drivers of antibiotic resistance in surface waters in Bangladesh.
Lead author Willem van Schaik, Professor of Microbiology and Infection at the University of Birmingham, commented: “The rivers and lakes of Dhaka are surrounded by highly-populated slums in which human waste is directly released into the water. The presence of human gut bacteria links to high levels of antibiotic resistance genes, suggesting that such contamination is driving the presence of these ‘superbugs’ in surface water.
“Interventions aimed at improving access to clean water, sanitation and sewerage infrastructure may thus be important to reduce the risk of antimicrobial resistance spreading in Bangladesh and other LMICs. While levels of antibiotic resistance genes are considerably lower in rural than in urban settings, we found that antibiotics are commonly used in fish farming and further policies need to be developed to reduce their use.”
The prevalence of antibiotic-resistant bacteria causing infections is increasing globally, but the clinical issues, including significant morbidity and mortality, posed by these bacteria are particularly alarming in LMICs. The prevalence multidrug-resistant E. coli among healthy humans is relatively high in Bangladesh, as it is in other LMICs.
Dhaka, has a population of around 16 million people, with a population density that ranks among the highest of any megacity, but less than 20% of households are directly connected to sewerage infrastructure.
The research team found that urban surface waters in Bangladesh are particularly rich in antibiotic resistance genes, with a higher number of them associated with plasmids indicating that they are more likely to spread through the population.
Antibiotic-resistant bacteria that colonize the human gut can be passed into rivers, lakes and coastal areas through the release of untreated wastewater, the overflow of pit latrines during monsoon season or by practices such as open defecation.
These contaminated environments are often used for bathing, for the washing of clothes and food preparation equipment, thus increasing the risk of human gut colonisation by antibiotic-resistant bacteria.
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Materials provided by University of Birmingham. Note: Content may be edited for style and length.

Indiana Jones hates snakes. And he’s certainly not alone. The fear of snakes is so common it even has its own name: ophidiophobia.
Kibret Mequanint doesn’t particularly like the slithery reptiles either (he actually hates them too) but the Western University bioengineer and his international collaborators have found a novel use for snake venom: a body tissue ‘super glue’ that can stop life-threatening bleeding in seconds.
Over the past 20 years, Mequanint has developed a number of biomaterials-based medical devices and therapeutic technologies — some of which are either licensed to medical companies or are in the advanced stage of preclinical testing.
His latest collaborative research discovery is based on a blood clotting enzyme called reptilase or batroxobin found in the venom of lancehead snakes (Bothrops atrox), which are amongst the most poisonous snakes in South America.
Taking advantage of this clotting property, Mequanint and the international research team designed a body tissue adhesive that incorporates the special enzyme into a modified gelatin that can be packaged into a small tube for easy, and potentially life-saving, application.
“During trauma, injury and emergency bleeding, this ‘super glue’ can be applied by simply squeezing the tube and shining a visible light, such as a laser pointer, over it for few seconds. Even a smartphone flashlight will do the job,” said Mequanint, a Western engineering professor.
Compared to clinical fibrin glue, considered the industry gold standard for clinical and field surgeons, the new tissue sealant has 10 times the adhesive strength to resist detachment or washout due to bleeding. The blood clotting time is also much shorter, cutting it in half from 90 seconds for fibrin glue to 45 seconds for the new snake venom ‘super glue.’
This new biotechnology translates to less blood loss and more life-saving. The super-sealant was tested in models for deep skin cuts, ruptured aortae, and severely injured livers — all considered as major bleeding situations.
“We envision that this tissue ‘super glue’ will be used in saving lives on the battlefield, or other accidental traumas like car crashes,” said Mequanint. “The applicator easily fits in first aid kits too.”
In addition, the new snake venom ‘super glue’ can be used for suture-free, surgical wound closures.
Snake extract-laden hemostatic bioadhesive gel cross-linked by visible light was published today in the journal Science Advances. For the discovery, Mequanint collaborated with bioengineers, scientists and medical practitioners at the University of Manitoba and Army Medical University in Chongqing, China.
“The next phase of study which is underway is to translate the tissue ‘super glue’ discovery to the clinic,” said Mequanint.
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Materials provided by University of Western Ontario. Original written by Jeff Renaud. Note: Content may be edited for style and length.

Penn State College of Engineering researchers set out to develop technology capable of localizing and imaging blood clots in deep veins. Turns out their work may not only identify blood clots, but it may also be able to treat them.
The team, led by Scott Medina, assistant professor of biomedical engineering, published its results in Advance Healthcare Materials.
“Deep vein thrombosis is the formation of blood clots in deep veins, typically in a person’s legs,” said Medina. “It’s a life-threatening blood clotting condition that, if left unaddressed, can cause deadly pulmonary embolisms — when the clot travels to the lungs and blocks an artery. To manage DVT, and prevent these life-threating complications, it’s critical to be able to rapidly detect, monitor and treat it.”
The challenge, according to Medina, is that current diagnostic imaging methods lack the resolution required to precisely pinpoint potential breeding grounds for clots and monitor the clots in real time. DVT can sometimes present as swelling and aching in a person’s leg, which can then be examined via ultrasound.
“Ultrasound isn’t great for diagnosing DVT,” Medina said. “It can tell you that a region of fluid flow may look odd, which might be related to a clot — but maybe not. You follow up with blood tests to look for specific factors, and, together, you might be able to diagnose a clot.”
Once a clot is diagnosed, a clinician may order either pharmaceuticals to help break it apart or a procedure that involves snaking a probe to the clot to grab it and physically remove it from the body. The pharmaceuticals may not be enough to break the clot apart, though, or they could trigger bleeding issues elsewhere in the body, while the procedure option is invasive and carries risks, including potential infection.

A therapy made from a Covid patient’s own blood is being trialled to treat lung scarring that’s left after hospitalisation.Doctors at Guy’s and St Thomas’ NHS Foundation Trust in London have begun a small trial using patients’ white blood cells. Filmed by Julius Peacock, edited by Rachael Buchanan

Juli Mazi, who identifies as a naturopathic doctor, also sold “immunization pellets” to patients, federal prosecutors said.A homeopathic doctor in California is the first person to face federal charges for selling fake Covid-19 vaccination cards, the authorities said.The doctor, Juli A. Mazi of Napa, Calif., also sold Covid-19 “immunization pellets” to patients, federal prosecutors said. She was arrested on Wednesday and charged with one count of wire fraud and one count of false statements related to health care matters, according to a criminal complaint. Ms. Mazi faces up to 20 years in prison and hundreds of thousands of dollars in fines, the authorities said.Ms. Mazi sold pellets for $243 that she said contained a “very minute amount” of the coronavirus that would trigger an immune response and provide “lifelong immunity to Covid-19,” the complaint said. To encourage customers to purchase the pellets, prosecutors said, Ms. Mazi falsely told them that the three Covid-19 vaccines authorized for use in the United States contained “toxic ingredients.”She also offered homeopathic immunizations for childhood illnesses that she falsely claimed would satisfy immunization requirements for California schools, according to the complaint.Ms. Mazi could not immediately be reached for comment. It was not immediately clear if she had a lawyer.She describes herself on her website as a naturopathic doctor who received her doctorate from the National University of Natural Medicine in Portland, Ore. She is trained in “traditional medical sciences” and “ancient and modern modalities” that use nature to heal, the site says.She also offers “classical homeopathy,” a medical system developed more than 200 years ago in Germany. It uses the theory that a disease can be cured by a substance that produces similar symptoms, and the notion that medications are more effective at minimum dosages, according to the National Center for Complementary and Integrative Health. There is little evidence to support homeopathy as an effective treatment for illnesses, the center said, citing a 2015 assessment by Australia’s National Health and Medical Research Council. A number of concepts in homeopathy are not consistent with fundamental scientific concepts, the center said.The authorities began investigating Ms. Mazi after someone filed a complaint in April saying that relatives had purchased the Covid-19 immunization pellets from her and that they had not received any of the approved Covid-19 vaccinations. In addition to the pellets, prosecutors said, Ms. Mazi also sent the family Covid-19 vaccination cards that listed Moderna. She instructed them to mark the cards to falsely state that they received the vaccine on the date they ingested the pellets.Ms. Mazi distributed Covid-19 vaccination cards to patients falsely indicating that they had been given the Moderna vaccine, prosecutors said.Jeff Chiu/Associated PressIt’s unclear how many people purchased Covid-19 immunization pellets from Ms. Mazi, but she received more than $200,000 through Square, a digital payment processing company, from January 2020 to May 2021, the complaint said. A majority of the transactions did not indicate the purpose of the payments, but 25 transactions amounting to more than $7,500 were noted to indicate that they were for Covid-19 treatments, according to the complaint.“This defendant allegedly defrauded and endangered the public by preying on fears and spreading misinformation about F.D.A.-authorized vaccinations, while also peddling fake treatments that put people’s lives at risk,” Lisa O. Monaco, deputy attorney general, said in a statement. She added that the use of false vaccination cards allowed people to “circumvent efforts to contain the spread of the disease.”Steven J. Ryan, special agent in charge of the Department of Health and Human Services Office of Inspector General, said the department would continue to investigate “fraudsters” who mislead the public.“This doctor violated the all-important trust the public extends to health care professionals — at a time when integrity is needed the most,” he said in a statement.In May, the authorities in California arrested the owner of a bar on charges that he had sold fake Covid-19 vaccination cards at his business. There are also concerns that people sharing photographs of their vaccination card, complete with their name and birth date, could make themselves vulnerable to identity theft or scams.

To date, there are no effective antidotes against most virus infections. An interdisciplinary research team at the Technical University of Munich (TUM) has now developed a new approach: they engulf and neutralize viruses with nano-capsules tailored from genetic material using the DNA origami method. The strategy has already been tested against hepatitis and adeno-associated viruses in cell cultures. It may also prove successful against corona viruses.
There are antibiotics against dangerous bacteria, but few antidotes to treat acute viral infections. Some infections can be prevented by vaccination but developing new vaccines is a long and laborious process.
Now an interdisciplinary research team from the Technical University of Munich, the Helmholtz Zentrum München and the Brandeis University (USA) is proposing a novel strategy for the treatment of acute viral infections: The team has developed nanostructures made of DNA, the substance that makes up our genetic material, that can trap viruses and render them harmless.
DNA nanostructures
Even before the new variant of the corona virus put the world on hold, Hendrik Dietz, Professor of Biomolecular Nanotechnology at the Physics Department of the Technical University of Munich, and his team were working on the construction of virus-sized objects that assemble themselves.
In 1962, the biologist Donald Caspar and the biophysicist Aaron Klug discovered the geometrical principles according to which the protein envelopes of viruses are built. Based on these geometric specifications, the team around Hendrik Dietz at the Technical University of Munich, supported by Seth Fraden and Michael Hagan from Brandeis University in the USA, developed a concept that made it possible to produce artificial hollow bodies the size of a virus.