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Researchers at Michigan Medicine have discovered yet another functional autoantibody in COVID-19 patients that contributes to the disease’s development and the “firestorm” of blood clots and inflammation it induces.
A growing body of studies suggests COVID-19 emulates many aspects of systemic autoimmune disorders, including the release of a flurry of overactive immune cells that produce toxic webs of proteins and DNA called neutrophil extracellular traps, or NETs.
For this study, the team analyzed serum from over 300 hospitalized COVID patients, searching for a novel autoantibody that shields the toxic NETs from being destroyed and produces a lasting noxious effect in a patient’s body.
The results, published in JCI Insight, reveal markedly elevated levels of the anti-NET antibodies in many of the participants. Those with higher levels of the autoantibodies were more likely to develop severe COVID-19 symptoms.
“We see a slew of different antibodies produced in COVID-19 patients, and now we discovered another clinically significant one that is likely contributing to severe COVID,” said Yu (Ray) Zuo, M.D., lead author and a rheumatologist at Michigan Medicine. “They feed into the inflammatory storm that we’re seeing in the most serious cases of viral infection.”
Researchers generated NETs in the lab and incubated them with COVID patient serum. They found the serum from patients with higher levels of anti-NET antibodies struggled to degrade the toxic traps.

Tens of millions of patients around the world suffer from persistent and potentially life-threatening wounds. These chronic wounds, which are also a leading cause of amputation, have treatments, but the cost of existing wound dressings can prevent them from reaching people in need.
Now, a Michigan State University researcher is leading an international team of scientists to develop a low-cost, practical biopolymer dressing that helps heal these wounds.
“The existing efficient technologies are far too expensive for most health care systems, greatly limiting their use in a timely manner,” said Morteza Mahmoudi, an assistant professor in the Michigan State University College of Human Medicine and the Precision Health Program. “An economically accessible, practical and effective technology is needed.”
To develop that new technology, Mahmoudi tapped into years of experience and expertise, having studied advanced materials to heal heart tissue, fight infections and support immune systems. But the team also kept an eye on cost, working to develop a product that could be made available to as many patients as possible, even in resource constrained markets.
“My goal is always to make something that works and is practical,” Mahmoudi said. “I want to see my research become clinical products that help patients.”
With his latest work, published July 19 in the journal Molecular Pharmaceutics, Mahmoudi is getting closer to that goal. He’s working with partners in the United Kingdom who have started a company to oversee the development and approval of the new technology.

Errors in the metabolic processes of mitochondria are responsible for a variety of diseases such as Parkinson’s and Alzheimer’s. Scientists needed to find out just how the necessary building blocks are imported into the complex biochemical apparatus of these cell areas. The TOM complex (translocase of the outer mitochondrial membrane) is considered the gateway to the mitochondrion, the proverbial powerhouse of the cell. The working group headed by Professor Chris Meisinger at the Institute of Biochemistry and Molecular Biology at the University of Freiburg has now demonstrated — in human cells — how signaling molecules control this gate. A signaling protein called DYRK1A modifies the molecular machinery of TOM and makes it more permeable for enzymes that are important for the cell metabolism. The group has thus discovered the first signaling protein that directly influences this import process in humans. Their work has been published in the journal Nature Communications.
Developmental disorders in a new light
In neurodevelopmental disorders such as autism, microcephaly and Down’s syndrome, DYRK1A is defective. “The connection with mitochondria is new. These results allow us to better understand these disorders and develop treatment strategies,” says Dr. Adinarayana Marada, a member of Meisinger’s team.
“For a long time, researchers thought that the TOM complex was a rigid structure in the mitochondrial membrane whose doors were always open,” Meisinger explains. His team recently demonstrated signaling mechanisms in baker’s yeast that alter the subunits of the TOM complex depending on the metabolic state of the cell, or in response to sudden stress. In this way, the cell can specifically control the influx of precursor proteins for building elements of the metabolism, and it can adapt the function of the mitochondria to an altered cellular state. Whether such mechanisms also exist in humans was previously unknown.
DYRK1A acts upon the TOM complex
The first authors of the study, Dr. Corvin Walter and Dr. Adinarayana Marada of Meisinger’s research group, developed a systematic approach to track down signaling mechanisms such as those triggered by protein kinases, in humans. Over several years, they tested candidates using cell biological and bioinformatic methods and found what they were looking for — DYRK1A, one such protein kinase, acts on the TOM complex. “With this, we actually found the needle in the haystack,” says Walter.
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Materials provided by University of Freiburg. Note: Content may be edited for style and length.

The variant can dodge some of the immune system’s defenses, but is still vulnerable to vaccines.England lifted nearly all of its pandemic restrictions on Monday, which some Britons have hailed as “freedom day.” The British government, however, made a notable exception: People traveling to England from France must continue to quarantine upon their arrival, even if they are fully vaccinated.The rule, announced on Friday, was spurred by concerns about the presence of the Beta variant of the coronavirus in France and is intended as a precautionary measure, officials said.“While vaccines are helping us turn the tables against this virus, we need to continue to proceed cautiously,” Dr. Jenny Harries, the chief executive of the U.K. Health Security Agency, said in a statement on Friday. “That means maintaining our defenses against new variants and protecting our hard-won progress through the exceptional vaccination rollout.”Here are answers to some common questions about the Beta variant.What is the Beta variant?The Beta variant, formerly known as B.1.351, was first detected in South Africa last year. It contains several mutations, in a protein called spike, that help the virus bind more tightly to human cells.It also contains the E484K mutation, sometimes known as the “Eek” mutation, which appears to help the virus partially evade antibodies. This mutation has emerged independently in multiple variants, including Gamma, which surfaced in Brazil, and in some samples of Alpha, which was first identified in Britain.The World Health Organization and the Centers for Disease Control and Prevention have both designated Beta as a “variant of concern.”Why are people worried about it?Signs encouraged vaccinations outside the Pfizer South Africa headquarters in Johannesburg in March.João Silva/The New York TimesScientists and health officials became concerned about Beta because it spread quickly through South Africa and research indicated that some vaccines were less powerful against it.In February, for instance, South Africa stopped using the AstraZeneca-Oxford vaccine after clinical trials suggested that the vaccine did not provide good protection against mild or moderate illness caused by Beta. (Subsequent research has suggested that several authorized vaccines do provide strong protection against severe disease caused by the variant, however.)Some monoclonal antibody treatments are also less effective against the variant, although there are other authorized antibody treatments that appear to work well against it.Beta’s ability to bind tightly to human cells may also make it more transmissible; the C.D.C. notes that it appears to be roughly 50 percent more infectious than the original strain of the virus. It does not appear to be as contagious as Delta, however.Where is it common?Beta has now been reported in 123 countries, but it remains far less prevalent than Delta.Initially, Beta spread widely through South Africa, where it once made up more than 95 percent of virus samples sequenced in the country.It is no longer so dominant. In the last four weeks, Beta has accounted for just 5.6 percent of virus samples sequenced in South Africa, according to GISAID, a repository of viral genomes. (This decline is most likely because of the arrival of the highly contagious Delta variant, which now accounts for 77.6 percent of sequences.)Over the last four weeks, the variant has also represented 3.7 percent of virus samples sequenced in France, according to GISAID. It is especially common on Réunion, a French island in the Indian Ocean where Beta accounts for 31.2 percent of sequences.Beta is not common in the United States, where it represents just 0.1 percent of infections, according to C.D.C. estimates. It has been detected in Britain, but accounts for a negligible share of infections there.A Covid-19 patient in the I.C.U. of the Centre Cardiologique du Nord private hospital in Saint-Denis, near Paris, this year.Benoit Tessier/ReutersDo the vaccines work against Beta?The vaccines seem to be less powerful against Beta than against other versions of the virus. But studies suggest that two doses of several widely used vaccines should still offer strong protection.Studies in Qatar, where the Beta variant once accounted for half of all infections, have found that two doses of the Pfizer vaccine are 72 to 75 percent effective at preventing infection with Beta, a lower degree of protection than the shots provide against other variants. But both the Pfizer and Moderna vaccines provided strong protection against the worst outcomes; a full course of either vaccine was more than 95 percent effective at preventing severe disease and death.“Although Pfizer effectiveness was only 75 percent against Beta, and thus breakthrough infections with Beta are not uncommon, these breakthrough infections are mild, and it is very rare for someone fully vaccinated to require serious hospitalization or to die after a Beta breakthrough infection,” Laith Abu-Raddad, an infectious disease epidemiologist at Weill Cornell Medicine-Qatar who led both studies, said in an email.In an additional bit of good news, he added, there is also “no sign” that the protection these vaccines provide against Beta has waned in the first several months after the shots.In a clinical trial in South Africa, conducted when Beta was dominant, the Johnson & Johnson vaccine had an efficacy rate of 64 percent overall, but 82 percent efficacy at preventing severe disease.

A new robotic neck brace from researchers at Columbia Engineering and their colleagues at Columbia’s Department of Otolaryngology may help doctors analyze the impact of cancer treatments on the neck mobility of patients and guide their recovery.
Head and neck cancer was the seventh most common cancer worldwide in 2018, with 890,000 new cases and 450,000 deaths, accounting for 3% of all cancers and more than 1.5% of all cancer deaths in the United States. Such cancer can spread to lymph nodes in the neck, as well as other organs in the body. Surgically removing lymph nodes in the neck can help doctors investigate the risk of spread, but may result in pain and stiffness in the shoulders and neck for years afterward.
Identifying which patients may have issues with neck movement “can be difficult, as the findings are often subtle and challenging to quantify,” said Scott Troob, assistant professor of otolaryngology — head and neck surgery and division chief of facial plastic and reconstructive surgery at Columbia University Irving Medical Center. However, successfully targeting what difficulties they might have with mobility can help patients benefit from targeted physical therapy interventions, he explained.
The current techniques and tools that doctors have to judge the range of motion a patient may have lost in their neck and shoulders are somewhat crude, explained Sunil K. Agrawal, a professor of mechanical engineering and rehabilitative and regenerative medicine and director of the ROAR (Robotics and Rehabilitation) Laboratory at Columbia Engineering. They usually either provide unreliable measurements or require too much time and space to set up for use in routine clinical visits.
To develop a more reliable and portable tool to analyze neck mobility, Agrawal and his colleagues drew inspiration from a robotic neck brace they previously developed to analyze head and neck motions in patients with amyotrophic lateral sclerosis (ALS). In partnership with Troob’s group, they have now designed a new wearable robotic neck brace. Their study appears July 12 in the journal Wearable Technologies.
The new brace was made using 3D-printed materials and inexpensive sensors. The easy-to-wear device was based on the head and neck movements of 10 healthy individuals.
“This is the first study of this kind where a wearable robotic neck brace has been designed to characterize the full head and neck range of motion,” Agrawal said.
In the new study, the researchers used the prototype brace, along with electrical measurements of muscle activity, to compare the neck mobility of five cancer patients before and one month after surgical removal of neck lymph nodes. They found their device could precisely detect changes in patient neck movements during routine clinical visits.
“Use of the sensing neck brace allows a surgeon to screen patients postoperatively for movement difficulty, quantify their degree of impairment, and select patients for physical therapy and rehabilitation,” Troob said.
“Patients consistently identify need for rehabilitation and guided exercises after surgery as an unmet need in their medical care,” Troob said. “This work will lay the foundation for the appropriate identification of patients for intervention. We additionally hope that through using the neck brace, we will be able to objectively quantify their improvement and develop evidence-based rehabilitative programs.”
In the future, the researchers hope to investigate larger groups of patients and use the neck brace to follow patients through physical therapy to develop evidence-based protocols for rehabilitation, Troob said. They also would like to develop similar braces for other surgical sites, such as the forearm, ankle, or knee, he added.

Did you know multiple sclerosis (MS) means multiple scars? New research shows that the brain and spinal cord scars in people with MS may offer clues to why they developprogressive disability but those with related diseases where the immune system attacks the central nervous system do not.
In a study published in Neurology, Mayo Clinic researchers and colleagues assessed if inflammation leads to permanent scarring in these three diseases: MS. Aquaporin-4 antibody positive neuromyelitis optica spectrum disorder (AQP4-NMOSD). Myelin oligodendrocyte glycoprotein antibody associated disorder (MOGAD).They also studied whether scarring may be a reason for the absence of slow progressive disability in AQP4-NMOSD and MOGAD, compared with MS.
“The differences in scarring that we found will help physicians distinguish these three diseases more easily to aid in diagnosis,” says Eoin Flanagan, M.B., B.Ch., a Mayo Clinic neurologist and senior author of the study. “More importantly, our findings improve our understanding of the mechanisms of nerve damage in these three diseases and may suggest an important role of such scars in the development of long-term disability in MS.”
In all three of these diseases, the body’s immune system targets the myelin, the insulation around nerves. This causes inflammation and leads to removal of myelin, called demyelination, within the brain and spinal cord. Visual problems, numbness, weakness, or bowel or bladder dysfunction are common symptoms. Areas of demyelination, known as lesions, appear as white spots on an MRI. The repair mechanisms within the body try to reinsulate the nerves and repair the lesions, but this may be incomplete, leading to a scar that remains visible on future MRIs. Just like an electrical cable without its insulation, this scar may leave nerve fibers vulnerable to further damage and to degenerate over time.
The study included 156 patients, consisting of 67 patients with MS; AQP4-NMOSD, 51; and MOGAD, 38. These patients had172 attacks, or relapses, combined.

A chemical modification that occurs in some RNA molecules as they carry genetic instructions from DNA to cells’ protein-making machinery may offer protection against non-alcoholic fatty liver, a condition that results from a build-up of fat in the liver and can lead to advanced liver disease, according to a new study by UCLA researchers.
The study, conducted in mice, also suggests that this modification — known as m6A, in which a methyl group attaches to an RNA chain — may occur at a different rate in females than it does in males, potentially explaining why females tend to have higher fat content in the liver. The researchers found that without the m6A modification, differences in liver fat content between the sexes were reduced dramatically.
In addition, in a preclinical model, the investigators demonstrated that gene therapy can be used to enhance or add modifications to key RNAs to slow down or reduce the severity of liver disease.
Fatty liver can develop when liver fat content increases due to dietary or genetic factors, potentially leading to advanced liver scarring and disease, as seen in cirrhosis and other conditions. High liver fat content is also associated with increased risk of cardiovascular disease.
In recent years, scientists have identified hundreds of chemical modifications like m6A that can occur in RNA molecules, altering the RNA’s instructions for making proteins without affecting the core DNA. Some modifications can be beneficial, as in the case of liver disease; others can have a detrimental effect.
Using a unique mouse model missing m6A RNA modifications in the liver and a control model that included the modifications, the authors compared the effects of diets with differing fat contents to assess the effects of the modifications on fatty liver disease. In addition, they used measurements from human patients who had undergone liver biopsies during bariatric surgery to correlate markers of m6A RNA modifications with liver fat content and inflammation.
A key question moving forward is how genetic and environmental factors affect the body’s natural ability to create RNA modifications. Because m6A appears to act as a protective checkpoint that slows the accumulation of fat in the liver, the investigators hope their findings will spur future research on the development of therapies to enhance chemical modifications as a way to protect against liver disease and similar disorders.
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Materials provided by University of California – Los Angeles Health Sciences. Original written by Alana Prisco. Note: Content may be edited for style and length.

Holly, Chris and Delyth have all spent much of the past year shielding at home, because they are considered to be “clinically extremely vulnerable”.Although the advice to shield ended in April, they have all continued to be extremely cautious and are concerned about surging coronavirus cases as nearly all legal restrictions in England are lifted.All of them have had both vaccinations. But no vaccine is 100% effective and some people with weak or suppressed immune systems may not get as much benefit from the vaccine. Guidance for people in England identified as being clinically extremely vulnerable has been updated from 19 July. The government says they should, as a minimum, follow the same guidance as everyone else but may also wish to take extra precautions such as shopping at quiet times, meeting people outside, and continuing social distancing.

Most legal restrictions on social contact have been lifted in England. There are no longer limits on how many people can meet indoors and nightclubs have reopened.The lifting of restrictions comes as cases and hospitalisations due to Covid are rising. Patients at a hospital in Nottingham have urged the public to “be careful” as the changes come into place.

Children aged 12-17 with underlying health conditions will be offered the Pfizer-BioNTech vaccine, the government has said. Speaking in the House of Commons, Vaccines Minister Nadhim Zahawi said children in the age range will also be offered a vaccine “if they live with someone who is immunosuppressed”.Read more: Covid: Hundreds of thousands of under-18s to get vaccine