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An international consortium of leading migraine scientists identified more than 120 regions of the genome that are connected to risk of migraine. The groundbreaking study helps researchers better understand the biological basis of migraine and its subtypes and could speed up the search for new treatment of the condition, which affects over a billion individuals worldwide.
In the largest genome study of migraine yet, researchers have more than tripled the number of known genetic risk factors for migraine. Among the identified 123 genetic regions are two that contain target genes of recently developed migraine-specific drugs.
The study involved leading migraine research groups in Europe, Australia and the United States working together to pool genetic data from more than 873,000 study participants, 102,000 of whom had migraine.
The new findings, published on February 3, 2022 in the journal Nature Genetics, also uncovered more of the genetic architecture of migraine subtypes than was previously known.
Neurovascular mechanisms underlie migraine pathophysiology
Migraine is a very common brain disorder with over a billion patients worldwide. The exact cause of migraine is unknown, but it is believed to be a neurovascular disorder with disease mechanisms both within the brain and the blood vessels of the head.

Teams at the Institut Pasteur, CNRS, Vaccine Research Institute (VRI) and Université de Paris have discovered a new function of anti-HIV-1[1] antibodies by applying cutting-edge microscopy techniques to in vitro viral cultures. The scientists found that certain antibodies already known for effectively targeting HIV-1 envelope (Env) protein can prevent infected cells from releasing viral particles, thus halting viral spread. The antibodies are Y-shaped, enabling them to attach themselves between the infected cell and viral particles or directly between viral particles. This chain composed of antibodies and viral particles prevents viral spread. These findings demonstrate that these powerful antibodies exhibit different antiviral activities in addition to neutralization. The study is published in the February 2, 2022 issue of Nature Communications.
Broadly neutralizing antibodies (bNAbs) targeting virus envelope (Env) protein have significant potential for treating HIV-1. They were initially identified in rare cases of patients whose serum was capable of inhibiting numerous HIV strains. These antibodies exhibit multiple antiviral activities. As well as neutralizing the virus, i.e. preventing it from infecting new cells, they also kill infected cells. Consequently, they are referred to as polyfunctional molecules. It is necessary to fully understand the scope of these antiviral activities in order to use existing antibodies more effectively or refine the selection criteria for new antibodies. It is moreover useful to further investigate the polyfunctionality of anti-HIV-1 antibodies in order to improve our understanding of the role played by antibodies and thus tackle other viral infections.
Initially, teams at the Institut Pasteur, CNRS, VRI and Université de Paris sought to determine whether antibodies were capable of preventing infected cells from producing viral particles. To that end, they cultured CD4 T cells (HIV’s natural target) in vitro with various antibodies for 24 hours. They subsequently measured the quantity of viral particles produced by the cells in the culture medium and the quantity of viral particles remaining in the cells. As a result of these experiments, the scientists were able to demonstrate that certain antibodies increased virus quantity in cells but reduced it in the culture medium. This intriguing finding led them to believe that certain antibodies impeded the release of viral particles without preventing their production.
To test this theory, the scientists used various microscopy techniques to observe cells’ production of viral particles. They initially examined the cells by fluorescence microscopy, a technique used to differentiate virus proteins. This enabled them to demonstrate that infected cells accumulate large quantities of mature viral protein. This finding suggests that full viral particles accumulate in cells. To determine the precise location of these viral particles, the scientists subsequently used scanning electron microscopy to observe the surface of infected cells. “Using this method, we observed that these antibodies (bNAbs) prompt an accumulation of viral particles at the surface of cells, forming clusters and highly atypical structures (see illustration),” comments Timothée Bruel, co-last author of the study and scientist in the Virus and Immunity Unit[2] at the Institut Pasteur.
Next, the scientists combined a transmission electron microscopy technique with immunogold labeling. This enabled them to demonstrate that antibodies interpose themselves between viral particles and the infected cell, forming a chain cluster. Experiments with mutant antibodies subsequently demonstrated that the antibodies’ Y shape creates this clustered structure. Their arms are capable of linking two viruses, or one virus to the infected cell membrane, and their attachment points are sufficiently strong to prompt this phenomenon.
“We have demonstrated that only the most powerful antibodies tether viral particles at the surface of infected cells. Trapped viral particles can no longer infect new cells,” concludes Olivier Schwartz, co-last author of the study and Head of the Virus and Immunity Unit at the Institut Pasteur.
This work has revealed a new antiviral activity for broadly neutralizing anti-HIV-1 antibodies. It deepens our understanding of these antibodies’ mechanism of action and explains their efficacy in clinical trials. The scientists are now examining antibodies targeting other viruses, including SARS-CoV-2, to determine whether they also inhibit viral spread through this mechanism.
[1] HIV-1 is the pandemic form of the human immunodeficiency virus. The other less common type is HIV-2.
[2] This is named the “Virology Unit” at the CNRS (CNRS/Institut Pasteur).
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Managing blood sugar levels requires round-the-clock attention for people diagnosed with diabetes. A more healthful diet and increased physical activity can help, but many with the condition also need to take regular shots of insulin — the primary hormone that regulates sugar. To deliver this drug in a less invasive way, researchers in ACS Applied Bio Materials now report a prototype insulin-loaded patch that comfortably sticks to the inside of a person’s cheek.
According to the American Diabetes Association, approximately 6 million Americans use insulin to help control their diabetes, either because their bodies don’t make the hormone (Type 1) or don’t respond well to what they do make (Type 2). People primarily take insulin by injecting themselves with pens or syringes, or they have semi-permanent pumps implanted. These methods are invasive and uncomfortable, and they require safe needle or biohazard disposal and sterile conditions. Researchers have explored other ways to deliver insulin through the skin, such as gel-like lotions. But the skin is too good of a barrier, and drugs move into the body slowly. In contrast, the membrane lining the inside of the mouth is very thin, about one quarter the thickness of skin, making it a potential place for drugs to easily enter the bloodstream. So, Sabine Szunerits and colleagues wanted to see if a material they had previously developed — a polymer fiber mat that is activated by heat to release drugs — could attach to the cheek’s lining and deliver insulin.
The researchers first soaked small squares of a nanofiber mat, made from electrospun fibers of poly(acrylic acid), β-cyclodextrin and reduced graphene oxide, in a solution with insulin for three hours. Then the team applied the insulin-loaded patches onto cheek linings and corneas from pigs. Heating the material with a near-infrared laser for 10 minutes to 122F activated the material and released insulin into the two types of membranes several times faster than through skin. In addition, the researchers placed the patches in vivo inside the cheeks of three insulin-dependent pigs. The cheek linings showed no irritation or visual changes from the laser’s heat. As soon as the material was activated, the pigs’ blood sugar levels declined. Simultaneously, the animals’ plasma insulin levels increased, which the researchers say is proof-of-concept that this preliminary platform is efficient at getting insulin into the bloodstream. Finally, six human volunteers placed a placebo version of the patch inside their cheeks, saying that it felt comfortable over a two-hour period. The researchers say their next step is to conduct further preclinical studies of the prototype on animal models.
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Bacteria are extremely resourceful when it comes to adapting to a given environment. A team of researchers has now discovered a new trick bacteria use: a kind of sponge that absorbs certain messengers.
Each year, at least 1.27 million people die from an infection with bacteria that are resistant to standard antibiotics, a study recently published in the journal The Lancet reveals. The authors fear that this number could rise to as many as ten million people by 2050.
This makes the hunt for new substances that are effective against resistant bacterial strains more urgent than ever. A potential approach focuses on programmable RNA-based antibiotics. However, this requires an in-depth understanding of the key RNA-based signalling pathways and mechanisms during an infection.
New signalling pathways identified
This is the subject of research at the Institute for Molecular Infection Biology (IMIB) of the University of Würzburg and at the Helmholtz Institute for RNA-based Infection Research. Researchers in the laboratory of Professor Jörg Vogel, who holds the Chair of Molecular Infection Biology I at JMU and Managing Director of the HIRI, have figured out new details of these signalling pathways and mechanisms. They present the results of their study in the latest issue of the journal Molecular Cell.
Gianluca Matera, a Ph.D. student at the IMIB, provides more information on the background of the paper he co-authored with Jörg Vogel, saying: “A lot of bacteria, such as Escherichia coli and Salmonella enterica, have a cell envelope consisting of an outer and an inner membrane. The main function of this envelope is to shield the bacteria from their environment but it also has to be permeable for nutrients which the bacteria need to thrive.”
A previously unknown player

Wastewater-based epidemiological tracking of COVID-19 in the Tokyo 2020 Olympic and Paralympic village showed that SARS-CoV-2 was present in areas without diagnosed individuals.
The Tokyo 2020 Olympics and Paralympics, delayed by a year due to the COVID-19 pandemic, were held between July 21 and September 21, 2021. The games were held without spectators, and athletes and support staff in the Olympic village were tested daily for SARS-CoV-2, to ensure that the pandemic was kept under control.
A team of researchers from Japan, led by Hokkaido University’s Masaaki Kitajima, Associate Professor at the Faculty of Engineering, has used wastewater-based epidemiology (WBE) to show that SARS-CoV-2, the novel coronavirus, was present in more areas of the village than indicated by the antigen test. Their findings were published as a Rapid Communication in the Journal of Travel Medicine. The team included Specially Appointed Professor Michio Murakami at the Center for Infectious Disease Education and Research, Osaka University; Ryo Iwamoto from Shionogi & Co., Ltd.; Professor Hiroyuki Katayama at the Graduate School of Engineering, The University of Tokyo; and Professor Seiya Imoto at The Institute of Medical Science, The University of Tokyo (IMSUT).
The use of WBE to monitor the spread of the pandemic is well established, and is currently implemented in a number of cities across the world. Recent research has focused on using WBE to track the pandemic at smaller scales, from mass events all the way down to individual airplane flights.
The authors set out to assess the incidence of COVID-19 in the Olympic and Paralympic village. To do so, they collected a total of 690 wastewater samples between July 14 and September 8, 2021, from manholes in seven distinct areas in the village. The samples were collected daily, tested for the presence of SARS-CoV-2 by a qPCR-based method, and the results were reported to the Tokyo Organizing Committee. Results were also correlated with the clinical data that was gathered separately.
SARS-CoV-2 was detected in 233 of the 690 samples, including in areas where no positive cases were detected by clinical testing. The authors posit that this is due to two factors: WBE detects the virus in asymptomatic and post-quarantine patients, and the daily screenings in the village used an antigen test — which does not detect low viral loads. In addition, sequencing identified the presence of SARS-CoV-2 variants in the samples.
“This study demonstrates that WBE is an effective tool in tracking and controlling the spread of COVID-19 during mass gatherings,” said Kitajima. “It can also be used to determine the presence and prevalence of variants in asymptomatic patients.”
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Scientists have successfully tested in the lab a tiny biosensor they developed that can detect biomarkers tied to traumatic brain injuries.
In a study published recently in the journal Small, the Ohio State University researchers say their waterproof biosensor includes an “unprecedented combination of features” that may allow it to detect changes in the concentrations of various chemicals in the body and send the results to researchers in real time.
The chip is flexible and thinner than a human hair, making it minimally invasive for use in the brain.
“We have a long way to go from our tests in the lab, but these findings were very encouraging,” said study co-author Jinghua Li, assistant professor of materials science and engineering at Ohio State.
Although a biosensor such as the one the team developed could have many potential uses, Li and her co-authors were particularly focused in this study on how the sensor could be used to monitor patients with traumatic brain injuries (TBI).
After such an injury, secondary damage can occur that can be detected by changes in sodium and potassium ion concentrations in the brain’s cerebrospinal fluid, said Li, who is a member of Ohio State’s Chronic Brain Injury (CBI) Program.

Add a little spicy seasoning to a low sodium meal, and adults over the age of 60 may have a harder time noticing a lack of salt, according to a new study in the journal Food Quality and Preference.
Led by Carolyn Ross, a professor of Food Sciences at Washington State University, the study tested saltiness perception in older adults using white sauce formulations with varying amounts of salt and different spices and seasonings added.
The results of the analysis showed the addition of chipotle seasoning to the white sauce made it difficult for the study participants to differentiate between the samples with low and high levels of salt. Conversely, the addition of herbs, such as basil leaves, garlic powder and coarse ground pepper, was not as effective at masking the samples with less salt. The research points to the significant role that spice could play in reducing salt intake for people over 60.
“We were working specifically with a population of older adults to see if we could reduce the amount of salt in a product and then tailor it to their tastes,” Ross said. “This is important because the ability to taste and smell is known to weaken with age, and weaker perception of salty flavors may induce people to season their food with excessive salt, which may increase their risk of cardiovascular disease.”
For their study, Ross and María Laura Montero, a postdoctoral researcher in the WSU School of Food Sciences, recruited 39 healthy people over the age of 60 to participate in an in-person taste testing experiment that took place over several days slightly prior to the onset of the COVID-19 pandemic.
Previous research examining saltiness perception in older adults has tended to use water as a matrix for tasting experiments rather than actual food products. To generate more realistic data in terms of what people actually enjoy eating, Ross and Montero used a white sauce formulation that is commonly found in ready-to-eat Cajun chicken pasta meals.
The study participants were asked to compare three different formulations of the sauce at five different salt concentrations. One of the formulations had no added herbs, the second had just herbs, and the third had both herbs and chipotle seasoning. Their results showed the formulation with both herbs and chipotle seasoning made it difficult for the seniors to determine the amount of salt being used while the formulation with exclusively herbs did not.
In addition to administering the taste test, the researchers surveyed their participants about their oral and olfactory health, the number and type of medications they were taking and any other pre-existing conditions that might affect their saltiness perception.
Their analysis showed there was a positive correlation between poor oral health and the number of medications each participant was taking, which could be a result of less saliva production; however, their data on whether or not this was the main cause of lowered saltiness perception wasn’t conclusive.
Moving forward, when it is once again feasible to recruit participants for in-person studies, the researchers plan to follow-up with a larger study evaluating lower salt concentrations as well as different herb and spice concentrations.
“To date, a clear relationship between taste loss, and thus higher taste thresholds, and eating behavior remains to be established,” Ross said. “So, we are investigating a bunch of different possible factors.”
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Materials provided by Washington State University. Original written by Will Ferguson. Note: Content may be edited for style and length.

A team led by researchers from the University of Waterloo discovered that a significant increase in tear secretion and tear film stability after participating in aerobic exercise can be another remedy for relieving dry, itchy eyes.
Every time we blink, our eyes are covered in tear film — an essential protective coating necessary for maintaining healthy ocular function. Healthy tear film comprises three layers-oil, water, and mucin-that work together to hydrate the ocular surface and protect against infection-causing irritants like dust or dirt.
When any part of the tear film becomes unstable, the ocular surface can develop dry spots, causing eye symptoms like itchiness or stinging and burning sensations.
“With so much of our activity tied to screen usage, dry eye symptoms are becoming increasingly common,” said Heinz Otchere, a PhD candidate in vision science at Waterloo. “Instead of having to use eye drops or other alternative treatments, our study aimed to determine if remaining physically active can be an effective preventative measure against dryness.”
Fifty-two participants were divided into two groups — athlete and non-athlete — to participate in an exercise session. Participants in the athlete group exercised at least five times per week, while non-athlete participants exercised no more than once per week. Researchers, which included experts from the University of Cape Coast in Ghana, performed visual examinations before and five minutes after each exercise session, where tear secretion and tear break-up time were assessed.
While participants in the athlete group showed the largest increase, Otchere says all participants experienced a meaningful boost in tear quantity and tear film stability after the exercise session.
“It can be challenging for people to regularly exercise when the demand is there to work increasingly longer hours in front of screens,” Otchere said. “However, our findings show physical activity can be really important for not just our overall well-being, but for our ocular health too.”
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Investigators from UCLA Jonsson Comprehensive Cancer Center have identified a germline biomarker signature that successfully predicts which patients will suffer serious side effects that occur in up to 3 in ten patients on anti-PD1/PDL1 therapy, a promising new approach to treating cancer.
Checkpoint inhibitors that enhance the immune system against PD-1 and PD-L1 show great promise, having substantially improved the prognosis for patients with several advanced cancers, including melanoma, renal cell carcinoma, non-small cell lung cancer, Hodgkin lymphoma, and head and neck cancer.
As promising as they are, these therapies are also associated with a unique set of side effects, called immune-related adverse events (irAEs), believed to be the result of an immune system overstimulated by the therapy. While these side effects are generally treatable, they can in rare cases be very serious, even fatal. In addition, there’s currently no way to predict which patients will develop irAEs before starting treatment, requiring clinicians to watch and wait after treatment begins. Notably, the toxicity from checkpoint therapy does not appear to be associated with a patient’s cancer or their response to the treatment, supporting the idea that it is a patient-specific reaction.
With a growing need to identify which patients are at risk for irAEs, investigators led by Joanne B. Weidhaas, MD, PhD, MSM, of UCLA Jonsson Comprehensive Cancer Center, vice chair Department of Radiation Oncology, and director Division of Molecular and Cellular Oncology at UCLA Health, examined DNA signatures in 99 patients, looking for patterns that would indicate if inherited DNA biomarkers would predict toxicity. In findings published in Journal for Immunotherapy of Cancer, they report that they were able to identify a biomarker panel that predicts toxicity with 80% accuracy.
“These findings represent an important step toward personalizing checkpoint therapy, the use of which is growing rapidly,” said Dr. Weidhaas. “While we are still at the early stages of understanding the mechanisms by which these germline mutations regulate immunity and the systemic stress response, our repeated findings that these variant panels can predict systemic toxic responses to cancer therapy are potentially paradigm-shifting.”
The authors of the study say applying these findings may improve clinicians’ ability to offer truly personalized cancer therapy by enabling consideration of toxicity along with other data that can predict patients’ response to treatment. “As the efficacy of cancer therapy improves, resulting in higher and higher rates of long-term cancer control,” they write, “cure without harm will only become an increasingly important endpoint.”
Funding: JW was supported by NCI Grant CA238998.
Competing interests: JW has created intellectual property that was patented at Yale University and licensed to MiraDx, a company that she cofounded. MiraDx has developed miRSNP panels that were applied to blinded samples in this analysis.

An international team of researchers has discovered that Schwann cells — which are abundant in the peripheral nervous system and create a protective sheath around nerve fibers — play an essential role in migraine pain. Their study, conducted in mice and human Schwann cells and published in Nature Communications, illustrates how pain is signaled from within Schwann cells and finds several ways to block this signaling, providing potential targets for new migraine treatments.
Migraines affect more than 15 percent of adults, with women twice as likely as men to experience these intense headaches. Calcitonin gene-related peptide (CGRP), a small protein in the nervous system, is known to play an important role in migraine pain; in fact, a new class of drugs to prevent migraines use injections of monoclonal antibodies to target CGRP or its receptor.
“While CGRP has been implicated in migraine pain, how it causes pain has been an area of controversy in the scientific community,” said Nigel Bunnett, PhD, professor and chair of the Department of Molecular Pathobiology at NYU College of Dentistry. Bunnett led the study with Pierangelo Geppetti, MD, professor of clinical pharmacology at the University of Florence and director of the Headache Center of Careggi University Hospital.
“The success of CGRP monoclonal antibodies for migraine and the poor ability of antibodies to penetrate the blood brain barrier suggest that CGRP causes pain in the periphery rather than within the brain,” added Bunnett, a researcher in the NYU Pain Research Center.
To explore the cellular mechanism of CGRP-evoked pain, Bunnett and his colleagues focused on Schwann cells, which are found outside the brain in the peripheral nervous system. The researchers studied mice in which the CGRP receptor, called CLR/RAMP1, was disabled in Schwann cells. They modified the CGRP receptor by deleting RAMP1, one of two important components of the receptor, from Schwann cells in the facial area of mice.
In normal mice, administering CGRP made the facial region very sensitive, a proxy for migraine pain. However, in mice lacking the CGRP receptor in Schwann cells, CGRP did not cause pain. In a second experiment, the researchers administered capsaicin — a chemical found in spicy chili peppers. Capsaicin activates an ion channel called TRPV1, which releases CGRP and usually causes pain. Again, capsaicin did not cause migraine-like pain in mice lacking the CGRP receptor in Schwann cells, providing further support for the idea that the CGRP receptor in Schwann cells plays a critical role in migraine pain.