SharecloseShare pageCopy linkAbout sharingimage copyrightReutersIndia has said a new variant of the coronavirus first discovered there in March may be linked to a deadly second wave.Samples containing the “double mutant”- or B.1.617 variant – have been found in several states with high case numbers.An official with the National Centre for Disease Control said, however, that they had still been unable to fully establish a correlation.A double mutant is when two mutations come together in the same virus.What is the India Covid variant?India is a Covid disaster – it didn’t have to beMeanwhile, India reported a record 412,000 cases in the space of 24 hours on Wednesday, and 3,980 deaths. The government’s top scientific adviser also warned a third wave is inevitable.Speaking at a health ministry news briefing, K VijayRaghavan admitted that experts had not anticipated the “ferocity” of the surge in cases. “Phase three is inevitable, given the high levels of circulating virus,” he added during a news briefing. “But it is not clear on what timescale this phase three will occur… We should prepare for new waves.”The current surge of the virus has already overwhelmed the healthcare system with hospital beds, oxygen and even crematorium space in short supply.Several states are under localised lockdowns and curfews, but the government is reluctant to impose a national lockdown, for fear of the impact on the economy. Where has the ‘double mutant’ variant been found?Out of roughly 13,000 samples sequenced, more than 3,500 were found to be variants of concern – including B.1.617 – across eight states. The B.1.617 variant was reported in several states reporting surges including Maharashtra, Karnataka, West Bengal, Gujarat and Chhattisgarh.For more than a month, Delhi insisted that the variant had no link to the current surge. Virologist Dr Shahid Jameel told the BBC’s Vikas Pandey earlier that India started seriously looking at mutations fairly late, with sequencing efforts only “properly started” in mid-February 2021.India is sequencing just over 1% of all samples at the moment. “In comparison, the UK was sequencing at 5-6% at the peak of the pandemic. But you can’t build such capacity overnight,” he said.Indians’ desperate wait for Covid jab to get longerUS backs waiver on vaccine patents to boost supplyAnd although the central government now says there is a correlation, it added the link is not “fully established”.”Its epidemiological and clinical correlation is not fully established… without the correlation, we cannot establish direct linkage to any surge. However, we have advised states to strengthen public health response – increase testing, quick isolation, prevent crowds, vaccination,” Sujeet Singh, National Centre for Disease Control said.image copyrightGetty ImagesWhere are we with case numbers?A number of states reported their highest fatalities in a single day on Wednesday – including the northern states of Uttar Pradesh, Haryana and Punjab and Tamil Nadu and Karnataka in the south.The western state of Maharashtra, which has had the highest caseload throughout the pandemic, reported 920 deaths.However, experts say the tally could be far higher due to reduced testing, and under-reporting of deaths. In a weekly report, the World Heath Organization said that India accounted for nearly half the coronavirus cases reported worldwide last week, and a quarter of deaths. Indian delegates in UK for G7 talks self-isolateCovid cases at Everest raise fears of outbreakAn Indian delegation that travelled to the G7 Foreign Ministers’ meeting in London this week, is self-isolating after two of its members tested positive for Covid-19. India’s foreign minister Subrahmanyam Jaishankar travelled with the delegation to London, and says he will attend the rest of the summit virtually. What about vaccines?India has been unable to meet an ambitious vaccination programme – it initially wanted to vaccinate 300 million people by July – and there’s been a dramatic drop in jabs because of a shortage of doses.Just 269 million people out of a population of 1.4 billion have received both shots, and about 128 million have only received a single dose. Vaccine stocks in the country have nearly dried up, with the latest age bracket to become eligible – adults under the age of 45 – struggling to register and secure appointments.Experts say lockdowns and vaccinations are the only way out, but that the government would need to act now in order to break the chain.

SharecloseShare pageCopy linkAbout sharingimage copyrightReutersThe US has thrown its support behind an initiative at the World Trade Organization (WTO) to waive intellectual property protections for coronavirus vaccines.India and South Africa proposed the move, which they said would increase vaccine production around the world. But drugs manufacturers argue it may not have the desired effect.US Trade Representative Katherine Tai said that “extraordinary times call for extraordinary measures”. And she warned that it would take time for WTO members to reach a consensus decision on the matter.India and South Africa were the leading voices in a group of about 60 countries which for the last six months has been trying to get the patents on vaccines set aside. However, they met with strong opposition from the previous US administration of Donald Trump, the UK and the EU. But Mr Trump’s successor as US President, Joe Biden, has taken a different tack. He backed a waiver during the 2020 presidential campaign and reiterated his support on Wednesday. The head of the World Health Organization (WHO) called the move a “monumental moment” in the fight against Covid-19. How will we know Covid vaccines are safe?Vaccine makers ‘should work with poorer countries’Covid map: Where are cases the highest?image copyrightReutersWhat would the waiver mean?If approved, supporters say, the waiver would allow production of vaccines to be ramped up and provide more affordable doses for less wealthy countries.Many developing countries have argued that rules requiring countries to protect patents and other forms of intellectual property are an obstacle to ramping up the production of vaccines and other products needed to tackle the pandemic.The US had previously helped block WTO negotiations about the waiver proposal led by India and South Africa aimed at helping developing countries to produce vaccines using the intellectual property of pharmaceutical companies.Ms Tai said the US would now embark on negotiations at the WTO to try and secure the waiver. This could take time as WTO decisions require a consensus of all 164 members.An extraordinary momentIt is a truly extraordinary moment. President Biden’s trade representative released a statement saying the White House would support a waiver on the intellectual property rights owned by the makers of Covid-19 vaccines during the pandemic. The campaign for this has been going on amongst NGOs, some US Congressional Democrats and some developing countries such as India and South Africa. And as recently as March the US, the UK and the EU were resisting the moves in negotiations at the WTO in Geneva. Katherine Tai has been seeing top pharmaceutical companies and also raised the issue with UK International Trade Secretary Liz Truss at a virtual meeting last month. In an interview with the BBC last month, WTO chief Ngozi Okonjo-Iweala told the BBC that if vaccine manufacturers failed to supply the world, they would have to transfer the know-how. Drugs companies are adamant that the patents are not the bottleneck here, it is manufacturing capacity. But the Indians and South Africans have disagreed, with South African President Cyril Ramaphosa decrying what he called “vaccine apartheid”, saying his country and some in South America could ramp up production.The US move does tilt the balance of power in the WTO towards a waiver. But the position of both the UK and the European Union will now also come under careful scrutiny. What has the reaction been?Tedros Adhanom Ghebreyesus, head of the WHO, called the US decision “historic” and marked “a monumental moment in the fight against Covid-19”.But pharmaceutical companies have voiced their opposition, insisting that patents are not the primary obstacle, and cautioned that the move could stifle innovation.The International Federation of Pharmaceutical Manufacturers and Associations called the move “disappointing”.”A waiver is the simple but the wrong answer to what is a complex problem,” the Geneva-based lobby group said.Dr Amesh Adalja, senior scholar at the Johns Hopkins Center for Health Security, told the Reuters news agency that the waiver “amounts to the expropriation of the property of the pharmaceutical companies whose innovation and financial investments made the development of Covid-19 vaccines possible in the first place”.

After being postponed by coronavirus, the Tokyo Olympics are now only months away. But what has it been like for the athletes during the pandemic – and how have they coped with the delay?BBC Minute’s Kash Jones has been talking to two athletes about what their last year has been like.

It is estimated that a doctor dies every three to four weeks in the UK from suicide.Dr Dan Gearon’s cousin Liz took her own life in 2016. She had been an anaesthetist at King’s College London. Following Liz’s death, Dan created the charity, You Okay, Doc? to provide doctors with a safe space to talk about their mental health.Now as the pandemic starts to ease, Dan and many other doctors across the country are voicing the need to have better mental health services for medics.If you’ve been affected by any issues in this story, you can find support at BBC Action Line.Video by Gem O’Reilly

Two studies showed the vaccine to be more than 95 percent effective at protecting against severe disease or death from the variants first identified in South Africa and the U.K.The Pfizer-BioNTech coronavirus vaccine is extraordinarily effective at protecting against severe disease caused by two dangerous variants, according to two studies published Wednesday.The studies, which are based on the real-world use of the vaccine in Qatar and Israel, suggest that the vaccine can prevent the worst outcomes — including severe pneumonia and death — caused by B.1.1.7, the variant first identified in the U.K., and B.1.351, the variant first identified in South Africa.“This is really good news,” said Dr. Annelies Wilder-Smith, an infectious disease researcher at the London School of Hygiene and Tropical Medicine. “At this point in time we can confidently say that we can use this vaccine, even in the presence of circulating variants of concern.”Previous research suggested that B.1.1.7 is more infectious and more deadly than other variants, but that vaccines still worked well against it. But vaccines appeared to be less effective against B.1.351, according to earlier studies.One of the new studies, which appeared in the New England Journal of Medicine, is based on information about more than 200,000 people that was pulled from Qatar’s national Covid-19 databases between Feb. 1 and March 31.During that time, the variants were widespread there: Sequencing conducted between Feb. 23 and March 18 suggested that roughly half of the coronavirus infections in that period were caused by B.1.351 and 44.5 percent were caused by B.1.1.7.In multiple analyses, the researchers found that the vaccine was 87 to 89.5 percent effective at preventing infection with B.1.1.7 among people who were at least two weeks past their second shot. It was 72.1 to 75 percent effective at preventing infection with B.1.351 among those who had reached the two-week point.Even that slightly reduced effectiveness against infection with B.1.351 is still largely good news, one of the study’s authors, Laith Abu-Raddad, an infectious disease epidemiologist at Weill Cornell Medicine-Qatar, said. “We’re talking about a variant which is probably the nastiest of all the variants of concern,” he said. “It’s not the 95 percent we were hoping, but the 75 percent is really great.”The vaccine was highly effective at protecting against the worst outcomes. Over all, it was 97.4 percent effective at preventing severe, critical or fatal disease from any form of the coronavirus, and 100 percent effective at preventing severe, critical or fatal disease caused by B.1.1.7 or B.1.351. (This slight difference in effectiveness is likely a result of the fact that the sample sizes were smaller for the subgroups of patients with a documented variant, Dr. Abu-Raddad said.)The second new study, which was published in The Lancet, was conducted by researchers at the Israel Ministry of Health and Pfizer. It is based on more than 230,000 coronavirus infections that occurred in Israel between Jan. 24 and April 3. During that period, B.1.1.7 accounted for nearly 95 percent of all coronavirus cases in the country, which has vaccinated more than half of its population.The researchers found that the vaccine was more than 95 percent effective at protecting against coronavirus infection, hospitalization and death among fully vaccinated people 16 and older. It also worked well in older adults. Among those 85 or older, the vaccine was more than 94 percent effective at protecting against infection, hospitalization and death.As the percentage of fully vaccinated people in each age group grew, the incidence of coronavirus infections in that cohort fell, the researchers found. The declines in infection rates matched the timing of increasing vaccine coverage in each age group better than the start of a nationwide lockdown. The results suggest that Israel’s rapid pace of vaccination has been responsible for the decline in infections in the country.“I’m just really happy to see this data that in the real world these vaccines are having such an amazing impact on curtailing infection and disease,” said Akiko Iwasaki, an immunologist at Yale University.Both studies also reported that two doses of the vaccine provided significantly more protection than one dose did. In the Israel study, for example, one dose of the vaccine was 77 percent effective against death, while two doses were 96.7 percent effective.“It absolutely emphasizes the need for the second dose,” said Dr. Kathleen Neuzil, who directs the Center for Vaccine Development and Global Health at the University of Maryland School of Medicine.Together, the studies suggest that even with the new variants, vaccination remains a plausible path out of the pandemic, experts said. “If we can get vaccines to the world and get coverage up,” Dr. Neuzil said, “I believe we can get on top of this and we can get on top of the emergence of new variants.”

By discovering a potential new cellular mechanism for migraines, researchers may have also found a new way to treat chronic migraine.
Amynah Pradhan, associate professor of psychiatry at the University of Illinois Chicago, is the senior author of the study, whose goal was to identify a new mechanism of chronic migraine, and propose a cellular pathway for migraine therapies. The study, “Neuronal complexity is attenuated in preclinical models of migraine and restored by HDAC6 inhibition, is published in eLife.
Pradhan, whose research focus is on the neurobiology of pain and headache, explained that the dynamic process of routing and rerouting connections among nerve cells, called neural plasticity, is critical to both the causes and cures for disorders of the central nervous system such as depression, chronic pain, and addiction.
The structure of the cell is maintained by its cytoskeleton which is made up of the protein, tubulin. Tubulin is in a constant state of flux, waxing and waning to change the size and shape of the cell. This dynamic property of the cell allows the nervous system to change in response to its environment.
Tubulin is modified in the body through a chemical process called acetylation. When tubulin is acetylated it encourages flexible, stable cytoskeleton; while tubulin deacetylation — induced by histone deacetylase 6, or HDAC6, promotes cytoskeletal instability.
Studies in mice models show that decreased neuronal complexity may be a feature, or mechanism, of chronic migraine, Pradhan said. When HDAC6 is inhibited, tubulin acetylation and cytoskeletal flexibility is restored. Additionally, HDAC6 reversed the cellular correlates of migraine and relieved migraine-associated pain, according to the study.
“This work suggests that the chronic migraine state may be characterized by decreased neuronal complexity, and that restoration of this complexity could be a hallmark of anti-migraine treatments. This work also forms the basis for development of HDAC6 inhibitors as a novel therapeutic strategy for migraine,” the researchers report.
Pradhan said this research reveals a way to possibly reset the brain toward its pre-chronic migraine state.
“Blocking HDAC6 would allow neurons to restore its flexibility so the brain would be more receptive to other types of treatment. In this model we are saying, maybe chronic migraine sufferers have decreased neuronal flexibility. If we can restore that complexity maybe we could get them out of that cycle,” she said.
Once out of the cycle of decreased neuronal complexity, the brain may become more responsive to pain management therapies, Pradhan said. HDAC6 inhibitors are currently in development for cancer, and HDCA6 as a target has been identified for other types of pain.
“It opens up the possibility of something we should be looking at on a broader scale,” she said. “Are these changes maybe a hallmark of all sorts of chronic pain states?”
Migraine is a common brain disorder that is estimated to affect 14% of the world population. Current U.S. cost estimates for migraine are as high as $40 billion annually. One particularly debilitating subset of migraine patients are those with chronic migraine, defined as having more than 15 headache days a month. Migraine therapies are often only partially effective or poorly tolerated, creating a need for more diverse drug therapies.

Researchers have created a probe that glows when it detects an enzyme associated with issues that can lead to blood clots and strokes.
The team of researchers, from the Department of Chemistry and the National Lung and Heart Institute at Imperial College London, demonstrated that their probe quickly and accurately detects the enzyme in modified E. Coli cells.
They are now expanding this proof-of-concept study, published in the Journal of the American Chemical Society and funded by the British Heart Foundation (BHF), with the hope of creating rapid tests for cardiovascular problems and a new way to track long-term conditions.
The build-up of plaque in the arteries — known as atherosclerosis — can lead to coronary artery disease and stroke, and is one of the leading causes of death in the Western world.
As atherosclerosis progresses, intraplaque haemorrhages (IPHs) can occur when portions of the plaque break away from the artery walls. These events can lead to the formation of more vulnerable plaques and blood clots, restricting blood flow to the heart and the brain and potentially leading to chronic diseases or catastrophic events like strokes.
Detecting IPHs and their impacts would therefore provide a warning system and allow early diagnosis of vascular conditions. The research team designed a chemical probe that can detect rises in levels of an enzyme that accompanies IPHs and even plaque instabilities that precede IPHs.

Last year, Charles O. Elson, M.D., demonstrated a potential preventive treatment for Crohn’s disease, a form of inflammatory bowel disease. He used a mouse model that included immune-reactive T cells from patients with Crohn’s disease in a flagellin peptide-specific immunotherapy. This study provided proof-of-principle that a flagellin-directed immunotherapy might provide similar benefits in patients.
Now University of Alabama at Birmingham researchers have moved a step closer to possible clinical testing of this treatment, say Elson and co-first authors Katie Alexander, Ph.D., and Qing Zhao, M.D., Ph.D. Their study, published in the journal Gastroenterology, is the first to describe IgG antibodies in Crohn’s disease specific for human-derived flagellins of bacteria belonging to the Lachnospiraceae family. Knowledge of the specific flagellin epitopes that drive the pathogenic adaptive immune response in Crohn’s disease is necessary information for Elson’s potential triple-punch Crohn’s disease treatment. Goals of the treatment are removing or exhausting pathogenic T memory cells and increasing the number of immunomodulatory T regulatory cells.
Elson is a professor, Alexander an assistant professor and Zhao a postdoctoral fellow in the UAB Department of Medicine Division of Gastroenterology and Hepatology.
Crohn’s disease and ulcerative colitis — another type of inflammatory bowel disease — are characterized by dysregulated adaptive immune responses to the microbiota in genetically susceptible individuals, but the human specificity of these responses had so far been largely undefined. Mouse microbiota flagellins have previously been defined as immunodominant antigens in Crohn’s disease.
Flagellins are building blocks of the hairlike motility flagella that extend from the bacterial cell wall. Flagellin is a potent immune activator and antigen, and it is the only known microbial protein that has three receptors for innate immunity encoded in the host genome, in addition to immunoglobulin and T cell receptors.
The UAB researchers individually probed blood sera from 87 healthy volunteers, 152 patients with Crohn’s disease and 170 patients with ulcerative colitis. They used protein arrays of microbiota bacterial flagellins of both mouse and human origin, and they analyzed sera for IgG and IgA antibody responses.
They found selective patterns of antibody reactivity to microbiota flagellins among the inflammatory bowel disease patients.
The Crohn’s disease patients — but not the ulcerative colitis patients — had augmented serum IgG antibodies to Lachnospiraceae flagellins from various species of Roseburia and one species of Eubacterium. These bacteria are normal residents in the human ileum, the third segment of the small intestine. A subset of the Crohn’s disease patients had very high responses, with antibodies against more than 10 different flagellins.
For that subset of Crohn’s disease patients, the multiflagellin hyper-reactivity was associated with indications of severe dysregulated immune response. Patients in the subset had: 1) elevated flagellin-specific T memory cells; 2) a reduced ratio of flagellin-reactive T regulatory to T effector cells; and 3) a high frequency of disease complications.
“Thus,” Elson said, “Crohn’s disease patients displayed a strong adaptive immune response to human-derived Lachnospiraceae flagellins, which may be targeted for prognosis and future personalized therapies.”
Story Source:
Materials provided by University of Alabama at Birmingham. Original written by Jeff Hansen. Note: Content may be edited for style and length.

The most complete picture yet is coming into focus of how antibodies produced in people who effectively fight off SARS-CoV-2 work to neutralize the part of the virus responsible for causing infection. In the journal Science, researchers at The University of Texas at Austin describe the finding, which represents good news for designing the next generation of vaccines to protect against variants of the virus or future emerging coronaviruses.
Previous research focused on one group of antibodies that target the most obvious part of the coronavirus’s spike protein, called the receptor-binding domain (RBD). Because the RBD is the part of the spike that attaches directly to human cells and enables the virus to infect them, it was rightly assumed to be a primary target of the immune system. But, testing blood plasma samples from four people who recovered from SARS-CoV-2 infections, the researchers found that most of the antibodies circulating in the blood — on average, about 84% — target areas of the viral spike protein outside the RBD — and, apparently, for good reason.
“We found these antibodies are painting the entire spike, both the arc and the stalk of the spike protein, which looks a bit like an umbrella,” said co-corresponding author Greg Ippolito, who is a research associate professor in UT Austin’s Department of Molecular Biosciences and an assistant professor of oncology at the university’s Dell Medical School. “The immune system sees the entire spike and tries to neutralize it.”
Many of these non-RBD-directed antibodies the team identified act as a potent weapon against the virus by targeting a region in a part of the spike protein located in what would be the umbrella’s canopy called the N-terminal domain (NTD). These antibodies neutralize the virus in cell cultures and were shown to prevent a lethal mouse-adapted version of the virus from infecting mice.
The NTD is also a part of the viral spike protein that mutates frequently, especially in several variants of concern. This suggests that one reason these variants are so effective at evading our immune systems is that they can mutate around one of the most common and potent types of antibody in our arsenals.
“There’s an evolutionary arms race going on between the virus and our immune systems,” said Jason Lavinder, research associate in the McKetta Department of Chemical Engineering and co-corresponding author of the new study. “We’re all developing a standard immune response to this virus that includes targeting this one spot and that’s exerting selective pressure on the virus. But then the virus is also exerting its evolutionary strength by trying to change around our selective immune pressures.”
Despite these maneuvers by SARS-CoV-2, the researchers said about 40% of the circulating antibodies target the stalk of the spike protein, called the S2 subunit, which is also a part that the virus does not seem able to change easily.

You might call Candida albicans a shape-shifter: As this fungus grows, it can multiply as single, oval-shaped cells called yeast or propagate in an elongated form called hypha, consisting of thread-like filaments.
This dual nature can help the pathogen survive in the body, where it can cause disease, including dangerous hospital-acquired infections.
But how does this switching ability occur?
New research identifies one factor that may contribute. In a study that will be published on May 5 in the journal mSphere, University at Buffalo biologists Guolei Zhao and Laura Rusche report that a protein called Sir2 may facilitate C. albicans’ transition from ovoid yeast to thread-like hypha. C. albicans cells that were missing the Sir2 gene were less likely to form true hyphae in lab experiments than cells of the same species that had that gene.
“When we got rid of the Sir2 gene, we saw less of the true hyphae form,” says Zhao, first author and a PhD candidate in biological sciences in the UB College of Arts and Sciences. This is interesting, she says, because both the “tiny round yeast form” and the “elongated hyphae form” are “essential to infection,” helping C. albicans invade different niches of the human body.
The influence of Sir2 on morphology differed depending on the cells’ surroundings: In a nutrient-poor environment, C. albicans cells that were missing the Sir2 gene were less likely to form both true hyphae and pseudohyphae, a sort of in-between stage where the cells are elongated and grow in chains. But in a nutrient-rich situation, C. albicans lacking the Sir2 gene formed more pseudohyphae even as the formation of true hyphae declined.