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Tag: Genetics

  • Some mosquitoes like it hot

    Some mosquitoes like it hot

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    Newswise — Certain populations of mosquitoes are more heat tolerant and better equipped to survive heat waves than others, according to new research from Washington University in St. Louis.

    This is bad news in a world where vector-borne diseases are an increasingly global health concern. Most models that scientists use to estimate vector-borne disease risk currently assume that mosquito heat tolerances do not vary. As a result, these models may underestimate mosquitoes’ ability to spread diseases in a warming world.

    Researchers led by Katie M. Westby, a senior scientist at Tyson Research Center, Washington University’s environmental field station, conducted a new study that measured the critical thermal maximum (CTmax), an organism’s upper thermal tolerance limit, of eight populations of the globally invasive tiger mosquito, Aedes albopictus. The tiger mosquito is a known vector for many viruses including West Nile, chikungunya and dengue.

    “We found significant differences across populations for both adults and larvae, and these differences were more pronounced for adults,” Westby said. The new study is published Jan. 8 in Frontiers in Ecology and Evolution.

    Westby’s team sampled mosquitoes from eight different populations spanning four climate zones across the eastern United States, including mosquitoes from locations in New Orleans; St. Augustine, Fla.; Huntsville, Ala.; Stillwater, Okla.; St. Louis; Urbana, Ill.; College Park, Md.; and Allegheny County, Pa.

    The scientists collected eggs in the wild and raised larvae from the different geographic locations to adult stages in the lab, tending the mosquito populations separately as they continued to breed and grow. The scientists then used adults and larvae from subsequent generations of these captive-raised mosquitoes in trials to determine CTmax values, ramping up air and water temperatures at a rate of 1 degree Celsius per minute using established research protocols.

    The team then tested the relationship between climatic variables measured near each population source and the CTmax of adults and larvae. The scientists found significant differences among the mosquito populations.

    The differences did not appear to follow a simple latitudinal or temperature-dependent pattern, but there were some important trends. Mosquito populations from locations with higher precipitation had higher CTmax values. Overall, the results reveal that mean and maximum seasonal temperatures, relative humidity and annual precipitation may all be important climatic factors in determining CTmax.

    “Larvae had significantly higher thermal limits than adults, and this likely results from different selection pressures for terrestrial adults and aquatic larvae,” said Benjamin Orlinick, first author of the paper and a former undergraduate research fellow at Tyson Research Center. “It appears that adult Ae. albopictus are experiencing temperatures closer to their CTmax than larvae, possibly explaining why there are more differences among adult populations.”

    “The overall trend is for increased heat tolerance with increasing precipitation,” Westby said. “It could be that wetter climates allow mosquitoes to endure hotter temperatures due to decreases in desiccation, as humidity and temperature are known to interact and influence mosquito survival.”

    Little is known about how different vector populations, like those of this kind of mosquito, are adapted to their local climate, nor the potential for vectors to adapt to a rapidly changing climate. This study is one of the few to consider the upper limits of survivability in high temperatures — akin to heat waves — as opposed to the limits imposed by cold winters.

    “Standing genetic variation in heat tolerance is necessary for organisms to adapt to higher temperatures,” Westby said. “That’s why it was important for us to experimentally determine if this mosquito exhibits variation before we can begin to test how, or if, it will adapt to a warmer world.”

    Future research in the lab aims to determine the upper limits that mosquitoes will seek out hosts for blood meals in the field, where they spend the hottest parts of the day when temperatures get above those thresholds, and if they are already adapting to higher temperatures. “Determining this is key to understanding how climate change will impact disease transmission in the real world,” Westby said. “Mosquitoes in the wild experience fluctuating daily temperatures and humidity that we cannot fully replicate in the lab.”

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    Washington University in St. Louis

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  • I used DNA analysis to find my birth family, and it sent me across 3 continents | CNN

    I used DNA analysis to find my birth family, and it sent me across 3 continents | CNN

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    CNN
     — 

    When I sent DNA samples to genetic testing services searching for my birth family, I had no idea it would launch me on an adventure across three continents.

    In 1961, I was adopted at birth in California. Over the years, I’ve searched for my birth family on and off but have always been stymied by sealed records and tight-lipped officials. In the past decade, however, home DNA testing and easy online access to official records have changed the game.

    I spit into plastic tubes (one for each of the two big players in this industry in the United States: 23andMe and Ancestry.com), dropped them in the mail, and waited, anxiously, for the results. When the email arrived in early 2022, I was stunned.

    After a lifetime believing I was a basic White American, I learned that was only half true. My birth mother was born in Iowa. But it turned out my father was North African.

    I reached out to anonymous DNA matches through 23andMe and Ancestry’s messaging systems, but no one replied. Then came weeks of research using Ancestry.com and various public records databases until I was able to identify both my parents and find contact information for a handful of their close relatives.

    I discovered my birth father had been born in the mid-1930s in Casablanca. Romantic visions of Humphrey Bogart and Ingrid Bergman (fictionally) escaping the Nazis swam in my head.

    Records showed he had emigrated to the United States in 1959 and ended up in San Francisco. My mother had been raised in San Diego and also moved to San Francisco right after high school. But why had he left Morocco? What brought her to San Francisco? I had to know more.

    After days of imagining the best and worst, I drafted scripts for what to say to genetically close family members who most likely had no idea I even existed. Then I apprehensively reached out.

    To my great relief, my mother’s and father’s families both welcomed me with open arms – despite their shock at discovering I existed.

    I learned quickly that both my biological parents had died and was deeply disappointed I had forever missed my chance to meet them. Would things have been different if I’d searched harder earlier?

    But I was thrilled that all their siblings were still alive.

    From my new family, I pieced together a rough sketch of my parents’ stories: On opposite sides of the world, they had both butted heads with difficult parents and left home at the first opportunity. They both wound up in one of the most free-thinking places on Earth: San Francisco.

    He worked as floor installer in the city’s North Beach neighborhood, where she was a cocktail waitress and dancer. I pictured them meeting while he installed floors in a nightclub where she was working.

    By all accounts, it must have been a very brief affair. My father was living with a girlfriend, and my mother’s sister says she never once heard my mother discuss my father in any way. Other than the sister and her mother, no one else in her family was told she was pregnant. My father’s family says they are 100% certain he was never told, either.

    There were other big surprises: I was told my mother never had another child – or even a serious boyfriend – for the rest of her life. On my father’s side, I was shocked to learn I had a half-brother and half-sister and dozens of cousins in France and Morocco.

    They invited me to visit. I booked a trip to meet my father’s huge, welcoming family.

    The author's extended family owns property on a rocky promontory in Dar Bouazza, a coastal community just west of Casablanca.

    In Paris, a cousin threw me an exuberant party at her sunny suburban home, where I was warmly embraced by the entire French branch of the family. They gave me insiders’ hints tailored to my interests about where to go and what to see off the beaten track.

    At their recommendation, I spent an afternoon in a huge, beautiful city park in eastern Paris called Buttes-Chaumont. I ate dinner at the French equivalent of a working-class diner (a bouillon, named for the broth) called Julien. It was my third time in Paris, but now I saw it through new eyes, imagining myself as something of an honorary son of the city.

    Morocco was another world entirely. I had never traveled to a Muslim country or anywhere outside Europe or the Americas. The experience was a strange and magical combination of foreign adventure and comfort travel, buffered by family looking out for me.

    I spent the first six days in the seaside resort town of Dar Bouazza, about 45 minutes from Casablanca, where my large Moroccan family owns a set of neighboring summer homes just yards from the beach. The houses are built on property my grandfather bought nearly a century ago (when the land was thought to be worthless) as a place to escape the summer heat of Casablanca.

    A photo of Fez at sunset, taken from the roof of a riad in the Moroccan city.

    French is the family’s primary language, and my aunts and uncles don’t speak English. Some younger cousin was usually available to translate, but group conversations at the table or on the back deck were always in French, leaving me no way to join in. I resolved to learn conversational French by my next visit.

    Despite the language gap, I got to know them all – the stern uncle, the motherly aunts, the prankster cousin. And I recognized many of their personality traits and quirks – how boisterous, curious and sly they are – in myself.

    I spent nearly a week wolfing down delicious, authentic Moroccan meals such as lamb tajine (steam roasted with vegetables inside a ceramic dish of the same name) and pastilla (spiced, shredded chicken or game bird wrapped in filo pastry) cooked and served on seaside terraces by the small household staffs common in middle-class Moroccan homes.

    Exploring a new homeland

    Yet I wanted to see more of my father’s homeland, so I left on a tour of Fez and Marrakech arranged by a cousin and her husband, who happen to own a luxury travel company.

    Those two cities were beautiful and awe-inspiring, alien yet weirdly familiar. I experienced them in a unique and very personal way thanks to my DNA journey: as a son just one generation removed from his father’s homeland.

    Professional guides created tours personalized to my interests and my newly discovered family’s culture and history – right down to a side trip to my family’s ancestral mausoleum in Fez.

    I saw the things my father might have seen touring the cities’ colorful medinas (marketplaces) where the guides introduced me to shopkeepers by my new family name. I saw gorgeous mosques and unexpected sidelights such as Marrakech’s largest Jewish temple, Synagogue Lazama. I watched craftsmen at work, making pottery, leather goods and fabric just as it has been done for centuries.

    The Roman ruins at Volubilis are remarkably pristine because of their isolation and the fact that they were unoccupied for nearly a thousand years.

    The highlight of the tour was a side trip to the ancient Roman ruins at Volubilis, between Fez and the Moroccan capital of Rabat. The city was abandoned by Rome around the third century and was not excavated until the early 20th. Seeing well-preserved walls, foundations, and floor mosaics on site – something that simply cannot be seen in the Americas – was a superb experience for a history buff like me.

    The tour was capped by a hike in the High Atlas Mountains to spend an afternoon with a local family who gave me a Berber-style cooking lesson, teaching me how to stew lamb and vegetables in a traditional Moroccan tagine.

    The patriarch even loaned me a djellaba, a traditional Moroccan outer robe, to wear for a photo, which felt both strange and strangely comforting – a perfect encapsulation of the whole trip.

    The author and his host sample the results of his Berber cooking lesson.

    Getting a home DNA test can launch you on your own great adventure – intended or not.

    Former CNN correspondent Samuel Burke created an entire podcast series in partnership with CNN Philippines, “Suddenly Family,” around the surprises – pleasant and otherwise – that can spring from DNA analysis.

    “DNA testing can open up this Pandora’s Box that nobody in the DNA industry talks about,” he said.

    Burke said some people just want to know about genetic health conditions they may carry. Many more are just looking to learn more about their ethnicity, “how Irish, how Jewish, how Native American they are.” But he said few realize the testing services will connect them to other people, sometimes in unexpected ways.

    In Fez, Curran visited several workshops where fabrics, leather goods and ceramics are hand-crafted using ancient techniques and tools.

    Whether you know nothing about your family background or think you know everything, there are likely to be surprises. Among them, Burke lists finding out a parent was unfaithful or that you’re the product of artificial insemination. Or you could discover you’re not biologically related to one of your parents.

    Burke said being prepared is key to avoiding some of the pitfalls.

    “Expect that you will find out something unexpected.” And he says that if you suspect something bad, you can opt out of sharing your results. Burke added the single best piece of advice he’s heard while reporting on DNA is “slow down.” Don’t become “hell-bent on solving the mysteries” and sharing your results as quickly as possible.

    Whether or not your DNA testing has unexpected results, it can inspire some fascinating travel across the country or, as in my case, around the world.

    What I learned on my adventure, however, is that the best part – even more than the places you visit – is the people you bond with, your new-found family who are like you, but also very different.

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  • Decoding Diabetes: Can Epigenetics Hold the Key?

    Decoding Diabetes: Can Epigenetics Hold the Key?

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    Newswise — Do epigenetic changes cause type 2 diabetes, or do the changes occur only after a person has become ill? A new study by researchers at Lund University provides increased support for the idea that epigenetic changes can cause type 2 diabetes. The researchers behind the new findings published in Nature Communications now aim to develop methods for disease prevention.

    We inherit our genes from our parents, and they seldom change. However, epigenetic changes that arise due to environmental and lifestyle factors can affect the function of genes.

    “Our new extensive study confirms our previous findings from smaller studies, showing that epigenetic changes can contribute to the development of type 2 diabetes. In this study, we have also identified new genes that impact the development of the disease. Our hope is that with the help of these results, we can develop methods that can be used to prevent type 2 diabetes,” says Charlotte Ling, professor of diabetes and epigenetics at Lund University’s Diabetes Centre (LUDC), who led the study.

    The same epigenetic changes

    The researchers studied epigenetics in insulin-producing cells from donors and found 5584 sites in the genome with changes that differed between 25 individuals with type 2 diabetes and 75 individuals without the disease. The same epigenetic changes found in people with type 2 diabetes were also found in individuals with elevated blood sugar levels, which increase the risk of developing the disease.

    “Those of us who study epigenetics, have long tried to understand whether epigenetic changes cause type 2 diabetes or if the changes occur after the disease has already developed. Because we saw the same epigenetic changes in people with type 2 diabetes and individuals at risk for the disease, we conclude that these changes may contribute to the development of type 2 diabetes,” says Tina Rönn, lead author and researcher at LUDC.

    The study identified 203 genes with different expression in individuals with type 2 diabetes compared to the control group. The researchers found that the gene RHOT1 showed epigenetic changes in people with type 2 diabetes and that it also played a key role in insulin secretion in insulin-producing cells. When they knocked out the gene expression of RHOT1 in cells from donors without type 2 diabetes, insulin secretion decreased.

    “When we examined the same type of cells in rats with diabetes, we found a lack of RHOT1, confirming the gene’s importance for insulin secretion,” says Tina Rönn.

    Methods that can prevent the disease

    One goal of the research is to develop a blood-based biomarker that can predict who is at risk of developing type 2 diabetes. Therefore, the researchers investigated whether their results from insulin-producing cells in the pancreas were reflected in the blood of living people. They found epigenetic changes in the blood of a group of 540 people without the disease and they linked this to the future development of type 2 diabetes in half of the individuals.

    Factors such as unhealthy diet, sedentary lifestyle, and ageing increase the risk of type 2 diabetes, and they also affect our epigenetics. With the new study, researchers have identified new mechanisms that may make it possible to develop methods to help prevent type 2 diabetes.

    “If we succeed in developing an epigenetic biomarker, we can identify individuals with epigenetic changes before they become ill. These individuals can, for example, receive personalised lifestyle advice that can reduce their risk of disease, or we can develop methods that aim to correct the activity of certain genes using epigenetic editing,” says Charlotte Ling.

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    Newswise

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  • FDA Approves First CRISPR Treatment in U.S.

    FDA Approves First CRISPR Treatment in U.S.

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    It was only 11 years ago that scientists Jennifer Doudna and Emmanuelle Charpentier first described a new way to edit genes, called CRISPR, in a scientific paper. The discovery is so game-changing that the pair earned the Nobel Prize in Chemistry in 2020 for how it could transform the way genetic diseases are treated. Now, on Dec. 8, the U.S. Food and Drug Administration (FDA) approved the very first treatment in the country based on the technology.

    In the medical world, that’s lightning speed. “It’s incredible,” says Doudna, professor of chemistry and molecular and cell biology at the University of California, Berkeley. “It’s so exciting to see how fast, and frankly how safely and effectively, this therapy is being rolled out in humans.”

    The U.K. had already approved the CRISPR treatment, called exa-cel (brand name: Casgevy), from Vertex Pharmaceuticals and CRISPR Therapeutics (which was co-founded by Charpentier), to treat people with sickle cell disease and beta thalassemia. People with these conditions are born with genetically abnormal blood cells. In the case of sickle cell, the mutations in the gene coding for hemoglobin can cause blood cells to form a sickle shape, rather than a spherical one, and clog up small blood vessels, leading to potentially life-threatening episodes of pain and a higher risk of stroke. Patients with beta thalassemia develop anemia so severe that it can damage organs. Both conditions require lifelong and repeated blood transfusions. CRISPR can increase the population of healthy blood cells in both groups of patients. The FDA approved exa-cel for sickle cell disease, and will make a decision about treating beta thalassemia by March 2024.

    The agency also approved another more traditional gene therapy for the disease as well: lova-cel (brand name: Lygenia) from bluebird bio, giving sickle cell patients two powerful new ways of controlling the debilitating and painful attacks that are the hallmark of their disease.

    “Gene therapy holds the promise of delivering more targeted and effective treatments, especially for individuals with rare diseases where the current treatment options are limited,” said Dr. Nicole Verdun, director of the office of therapeutic products in the FDA’s Center for Biologics Evaluation and Research, in a statement announcing the approvals.

    How exa-cel and lova-cel work

    CRISPR is an ideal therapy for these conditions since it involves editing mutated genes in a one-time treatment that could lead to a functional cure. Doctors extract blood stem cells, which produce the body’s entire population of blood and immune cells, from a person’s bone marrow, then grow those cells in the lab. Then, they edit the genes in those cells to boost the production of fetal hemoglobin, which is able to carry more oxygen than adult hemoglobin but normally disappears after birth.

    Researchers looked for ways to increase fetal hemoglobin concentration after they learned that about 10% of all people naturally continue to make fetal hemoglobin throughout their adult lives and remain healthy. Among them, people who also had sickle cell disease seemed to have milder forms. Their theory was that increasing the amount of fetal hemoglobin in the blood could help healthy blood cells outcompete the sickled versions and significantly cut down on the chances that the sickled cells would link together and block small vessels. That became the basis of exa-cel.

    Exa-cel does this by using CRISPR to target the gene that shuts off fetal hemoglobin. “It’s like removing the stop sign and allowing traffic—in this case, fetal hemoglobin—to go forward down the road,” says Dr. Sharl Azar, medical director of the comprehensive sickle cell disease treatment center at Massachusetts General Hospital.

    Lova-cel uses a modified virus that can’t cause disease to introduce a new gene for hemoglobin that mimics the healthy version, with an added anti-sickling feature. Sickled cells tend to form long, stiff chains that can clog vessels and trigger pain, but lova-cel’s hemoglobin “breaks down the chain so they don’t form the long rods anymore,” says Rich Colvin, chief medical officer at bluebird. The end result is that patients have more healthy, unsickled blood cells so they cause fewer painful blockages.

    The FDA’s decision

    In making its decision on exa-cel, the FDA reviewed a study of 31 patients with sickle cell disease who had experienced repeated blockages in their blood vessels. After getting exa-cel, 29 had no such attacks for a year. While it’s not clear yet how long the effects will last, experts hope that these early results mean longer, and potentially life-long, freedom from hospital visits and painful episodes. For lova-cel, the agency looked at a study involving 32 patients; 28 did not experience any attacks during the two-year study period.

    The agency also considered possible side effects. In the case of CRISPR, the most dangerous is off-target editing, in which CRISPR alters the wrong genes or alters genes that can prompt cells to start dividing out of control into a tumor. So far, patients who have received the therapy have not experienced these or other serious side effects. With lova-cel, one of the biggest concerns is where the gene for the healthy hemoglobin is inserted; Colvin says that studies so far show that the gene is inserted up to three times in a single cell, which does not appear to prompt the cell to start dividing abnormally. But “only time will tell whether we have actually done more harm than good by doing these genetic modifications,” says Dr. Markus Mapara, director of the adult bone-marrow transplant and cell-therapy program at NewYork-Presbyterian/Columbia, who has conducted several gene-therapy trials and has consulted for CRISPR Therapeutics. Verdun at the FDA said during a briefing that the agency asked both companies to follow patients for 15 years to document any potential long-term effects of the therapies, including cancers.

    A one-time treatment, but an arduous road

    As life-changing as both therapies can be, treatment is a grueling, months-long process. Both procedures involve nearly a year of tests and procedures, including an invasive bone marrow transplant. “It’s not for the faint of heart,” says Dr. Monica Bhatia, director of the pediatric stem-cell-transplant program at NewYork-Presbyterian/Columbia. To be eligible for either therapy, people need to be over 12 years old and have had repeated episodes of blockages due to sickle cell.

    The first step is a series of exchange blood transfusions, in which some sickled cells are replaced with healthy cells. The outpatient procedure, which takes place over three to four months, temporarily reduces inflammation and the risk of blockages and attacks leading up to the treatment.

    Once the level of sickled cells has dropped low enough, patients are hospitalized so doctors can collect enough stem cells from their bone marrow to be either edited with CRISPR or modified to make healthy hemoglobin, and reinfused back in the patients. Because the bone marrow in sickle cell patients isn’t as robust as that in healthy people, this could take several extraction cycles, and some patients may not even be able to produce enough to qualify for treatment, says Mapara.

    If the doctors can recover enough stem cells, they are shipped to Vertex’s and bluebird’s labs, where scientists perform the CRISPR editing, which can take eight to 12 weeks, or the gene therapy so the cells can start producing healthy hemoglobin.

    Once the CRISPR or gene therapy cells are ready, patients receive high-dose chemotherapy in order to remove their existing bone marrow and make room for the newly edited cells, which will then seed a population of healthy blood and immune cells. This chemo is likely the most challenging part of the entire procedure—even more difficult, and potentially toxic, than the exa-cel or lova-cel itself. It can also be painful. “I tell my patients that on a scale of zero to 10, this high-dose chemo is close to a nine or 10,” says Bhatia.

    Three to four days after chemo, patients finally receive the infusion of CRISPR or gene therapy cells. Then, it’s another four to six weeks in the hospital as doctors monitor them for infections and evaluate how quickly healthy blood cells emerge.

    New hope

    As involved as the procedures are, they may end up being worth it for most patients, since they could free them from excruciating attacks and even effectively cure their disease. In Bhatia’s patients who have participated in the CRISPR trial, she says that about half of their hemoglobin cells turn healthy and half remain sickled—but that’s enough to keep them out of the hospital and able to attend school and work.

    The treatments represent new options for patients who have had very few, says Azar. Hydroxyurea, a drug that is used to treat certain cancers, is the only effective medicine to treat sickle cell; it works by keeping cells rounder rather than sickled, but patients need to continue taking the pills daily to control their pain episodes. Bone marrow transplants to replace sickled cells with healthy ones are also possible, but they’re most effective when the patient and donor are well-matched, making it unavailable for most patients. The best matches come from related donors—but there is only a 25% chance that a sibling would be a match, and because sickle cell is hereditary, patients with the disease have an even smaller chance of having a healthy sibling donor. Transplants from unrelated donors are possible through registries, but their effectiveness is much lower.

    “I think this therapy is remarkably transformative,” says Azar of exa-cel. “It gives us options. And it shines a light on a disease that has never had light shone on it before.”

    Most sickle cell doctors believe for most patients, both treatments would work equally well in the short term. Having a treatment that could functionally cure sickle cell could also spare patients the long-term organ damage that becomes a legacy of their disease.

    The sooner patients are treated, the better chance they have of continuing to live relatively healthy lives with healthy organs, says Mapara. Sickle cell attacks can damage bone, for example, and “once tissue is dead, it’s not reversible,” he says. That’s why he is glad to see that the therapy is approved for anyone 12 years or older, so that even younger patients can take advantage of the opportunity to treat their disease before they develop severe organ damage.

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    Alice Park

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  • Science Weighs In On Marijuana And Being Psychotic

    Science Weighs In On Marijuana And Being Psychotic

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    There are a number of myths about marijuana. For the canna-curious, you have to look at what data says to the real answer

    But one of the biggest fears from those with little experience—will I have an adverse reaction to smoking pot? For the canna-newbie and the canna-curious, it might be a wee bit worrying.   Science weighs in on marijuana and being psychotic.  Ignore the myths and look at the data so you consume without a concern.

    Canadian scientists tried to answer that question by determining if an individual’s genetic makeup could determine how they’d respond to THC, the cannabinoid responsible for inducing psychoactive sensations. What genetic technology expert John Lem of Lobos Genetics discovered was that genes could predict several key factors: your body’s metabolization of the drug, whether cannabis was more likely to induce paranoia into your systems, as well as the possibilities of memory loss and developing schizophrenia.

    RELATED: Can I Get High From Second-Hand Marijuana Smoke?

    All scientists would have to do, Lem attests, is a simple cheek swab that would test three different genes that could answer all those questions.

    “Looking into the science, we came to the conclusion that there is actually a genetic basis for someone’s reaction to THC,” Lem told CBC. “”If people understand how their body reacts to cannabis, that’s a good thing,” he added.

    However, another expert cautioned that such a genetic test could provide all the answers with 100% accuracy. Dr. Bernard Le Foll, a team member with the Centre of Addiction and Mental Health that created recommendations around cannabis usage, was quick to remind everyone that “there has been limited research done on cannabis.” He urged the need for tests with a larger number of participants before drawing any substantive conclusions.

    In addition, Le Foll said more factors are at play when understanding the body’s reactions to a type of drug like cannabis. Maybe in the future we’ll be better at accurately predicting someone’s response to marijuana, though “we’re not there just yet.”

    RELATED: The Ultimate Newbie’s Guide To Marijuana

    “The type of environment, the type of previous drug exposure, the dose — that is all very important, possibly more important than genetics,” added Le Foll.

    While we can’t fully know how cannabis will affect each individual, Lem added his test is only to help consumers make better decisions. As edible products hit stores this fall in Canada, it’s important people know not to take more than they need. But I’m not sure we needed a genetics test to help consumers understand not to be gluttons when using marijuana.

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    Brendan Bures

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  • Study Finds Link Between DNA And Cannabis Addiction

    Study Finds Link Between DNA And Cannabis Addiction

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    A study published in Nature Genetics that analyzed the genomes of more than 1 million people found sequences of DNA that could be linked to a disposition to cannabis addiction. What do you think?

    “So you’re saying being cool is genetic?”

    Judy Robison, Sous Chef

    Chiefs Fans Try To Name A Single Taylor Swift Song

    “That’s it, I’m flushing all my DNA down the toilet.”

    Wes Konner, Ringtone Composer

    “Damn, DNA runs in my family.”

    Seth Mendez, Process Auditor

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  • Recent study unveils genetics behind human head shape.

    Recent study unveils genetics behind human head shape.

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    Newswise — Researchers at the University of Pittsburgh and KU Leuven have discovered a suite of genes that influence head shape in humans. These findings, published this week in Nature Communications, help explain the diversity of human head shapes and may also offer important clues about the genetic basis of conditions that affect the skull, such as craniosynostosis.

    By analyzing measurements of the cranial vault — the part of the skull that forms the rounded top of the head and protects the brain — the team identified 30 regions of the genome associated with different aspects of head shape, 29 of which have not been reported previously.

    “Anthropologists have speculated and debated the genetics of cranial vault shape since the early 20th century,” said co-senior author Seth Weinberg, Ph.D., professor of oral and craniofacial sciences in the Pitt School of Dental Medicine and co-director of the Center for Craniofacial and Dental Genetics. “We knew from certain rare human conditions and animal experiments that genes play an important role in vault size and shape, but very little was known about the genetic basis for typical features we see in the general population, such as what makes someone’s head long and narrow versus short and wide. This study reveals some of the key genes driving variation in this part of the human body.”

    According to the researchers, one application of better understanding the factors that drive natural variation in human head shape is informing paleoanthropology studies, potentially shedding light on the early development of modern humans.

    Weinberg and colleagues used magnetic resonance (MR) scans from more than 6,000 adolescents to extract 3D surfaces corresponding to the cranial vault. After dividing the 3D vault surfaces into incrementally smaller anatomical subparts and quantifying the shape of these subparts, they tested more than 10 million genetic variants for evidence of statistical association with measures of vault shape.

    “Previous genetic studies of the cranial vault involved a small number of relatively simple measures,” added Weinberg.  “While such measures are often easy to obtain, they may fail to capture features that are biologically relevant. Our analysis used an innovative approach capable of describing 3D vault shape in much more comprehensive and nuanced ways. This approach increased our ability to find genetic associations.”

    An important discovery was that many of the strong associations are near genes that play key roles in the early formation of the head and face and regulation of bone development. For example, variants in and near the gene RUNX2, a major player in coordinating development of the skull, were associated with multiple aspects of vault shape.

    While some genes, including RUNX2, had global effects involving the entire vault, others showed more localized effects that only impacted a specific portion of the vault, such as the central forehead.

    When the researchers compared the 30 genomic regions associated with head shape across participants with European, African and Indigenous American ancestry, they found that the majority of genetic associations were shared across these different ancestral groups.

    Although the study focused on healthy participants, the findings may reveal important clues about the biological basis of diseases involving the cranial vault, according to Weinberg.

    One of these conditions is craniosynostosis, which occurs when the bones of the skull fuse too early while the brain is still growing rapidly. Without neurosurgery, craniosynostosis can cause permanent disfigurement, brain damage, blindness and even death. The team showed that variants near three genes associated with vault shape, BMP2, BBS9 and ZIC2, were also associated with craniosynostosis, suggesting that these genes could play a role in the development of the disease.

    “This kind of study is possible due to the availability of publicly funded resources,” said Weinberg. “The original study that generated these MR scans is focused on understanding brain development and behavior. By creatively leveraging these resources, we have managed to advance discovery beyond that original scope.”

    Other authors on the study were Seppe Goovaerts, Hanne Hoskens, Ph.D., Meng Yuan, Dirk Vandermeulen, Ph.D., all of KU Leuven; Ryan J. Eller, Ph.D., Noah Herrick, Ph.D., and Susan Walsh, Ph.D., all of Indiana University–Purdue University Indianapolis; Anthony M. Musolf, Ph.D., and Cristina M. Justice, Ph.D., both of the National Human Genome Research Institute; Sahin Naqvi, Ph.D., and Joanna Wysocka, Ph.D., both of Stanford University; Myoung Keun Lee, Heather L. Szabo-Rogers, Ph.D., Mary L. Marazita, Ph.D., and John R. Shaffer, Ph.D., all of Pitt; Paul A. Romitti, Ph.D., of the University of Iowa; Simeon A. Boyadjiev, M.D., of the University of California, Davis; Mark D. Shriver, Ph.D., of Penn State University; and Peter Claes, Ph.D., of KU Leuven and Murdoch Children’s Research Institute.

    This research was supported by the National Institute of Dental and Craniofacial Research (R01DE027023, R01DE016886, R03DE031061 and X01HL14053) and the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health.

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  • Twin study finds epigenetic signature for obesity

    Twin study finds epigenetic signature for obesity

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    Newswise — PULLMAN, Wash. – A susceptibility to gain weight may be written into molecular processes of human cells, a Washington State University study indicates.

    The proof-of-concept study with a set of 22 twins found an epigenetic signature in buccal or cheek cells appearing only for the twins who were obese compared to their thinner siblings. With more research, the findings could lead to a simple cheek swab test for an obesity biomarker and enable earlier prevention methods for a condition that effects 50% of U.S. adults, the researchers said.

    “Obesity appears to be more complex than simple consumption of food. Our work indicates there’s a susceptibility for this disease and molecular markers that are changing for it,” said Michael Skinner, a WSU professor of biology and corresponding author of the study published in the journal Epigenetics.

    The study focused on twins to help eliminate the role of genetics and instead focus on epigenetics, molecular processes which are separate from DNA but influence how genes are expressed. The fact that the epigenetic signature was found in cheek cells rather than fat cells also suggests that the obesity signature is likely found throughout the human system.

    The signature’s systemic nature also suggests that something may have occurred early in one twin’s life that triggered obesity susceptibility, Skinner added. It’s also possible that it was inherited by one twin and not the other.

    For this study, Skinner worked with lead author Glen Duncan, director of the Washington State Twin Registry based at WSU, to identify 22 twin pairs, both identical and fraternal, who were discordant for obesity: one sibling had a body mass index of 30 or higher, the standard for obesity defined by the Centers of Disease Control and Prevention, while the other sibling was in the normal range of 25 and below.

    The research team analyzed cells from cheek swabs provided by the twins. In the cells from the twin siblings who were obese, they found similar epigenetic changes to DNA methylation regions, areas where molecular groups made of methane attach to DNA, regulating gene expression or turning genes on or off.

    The study would need to be replicated with larger groups of people to develop a biomarker test for obesity, the authors said.

    The goal would be able to identify people earlier in life before they become obese so health care providers might help create interventions such as lifestyle changes, medication or both, said Duncan. 

    “Ultimately we would like to have some kind of preventative measure instead of our usual approach which is treatment,” he said. “It’s a simple fact that it’s better to prevent a disease, then try to treat it after you have it.”

    This research was funded by the John Templeton Foundation and the National Institutes of Health.

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  • Maternal microbiome linked to fetal development

    Maternal microbiome linked to fetal development

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    Newswise — The microbiota of the mother or dam is thought to be important for the development and health of her offspring. However, so far little is known about how interactions with the microbiota begin and what the mechanisms of action are.

    A collaborative study carried out at the Universities of Helsinki, Eastern Finland and Turku investigated how the maternal microbiota affects foetal development by comparing the foetuses of normal and germ-free mouse dams living in a sterile environment. The researchers measured gene expression and the concentrations of small-molecular compounds, or metabolites, in the foetal intestine, brain and placenta.

    “The effects of the dam microbiota and the metabolites it produces on foetal development have not been previously investigated in such a comprehensive manner. Our study sheds light on the significance of the microbiota and the mechanisms by which the microbiota affects individual development and pregnancy. We identified previously unknown compounds in the foetus, which are likely to be microbial and which can be important for individual development,” says Mikael Niku, the principal investigator of the study from the Faculty of Veterinary Medicine, University of Helsinki.

    The researchers demonstrated that there were considerable differences in gene expression in the intestine, brain and placenta of the foetuses of germ-free and normal mouse dams. In the gut, genes associated with the immune system and host–microbe interactions were less active in the foetuses of germ-free dams. There were significant differences in the expression of genes in the brain associated with the development and functioning of the nervous system. In the placenta, there were differences in the expression of several important genes that regulate pregnancy. The differences were more extensive in male foetuses, indicating that they may be more sensitive to the effects of the maternal microbiota, at least in mice.

    The researchers discovered that the expression of many important genes was associated with the concentration of metabolites likely to be modulated by the maternal microbiota. These metabolites were absent in the foetuses of germ-free dams, or occurred at least at significantly lower concentrations.

    “It would appear that such microbial products are likely to affect the development of the intestine and brain as well as the functioning of the placenta. Many of these metabolites are previously unknown,” Niku notes.

    The group is now investigating the occurrence of microbial metabolites in other mammals: piglets and calves, as well as in the meconium and amniotic fluid samples of babies.

    Today, deficiencies in the host–microbe interactions of the early stages of life caused by, for example, an unbalanced environment or antibiotics, may predispose the offspring to dysfunction in the immune system, such as inflammatory bowel diseases and allergies.

    “Our research helps us understand the origin of such disorders, making it potentially possible in the future to enhance their prevention and treatment,” Niku muses.

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  • Find-and-Replace Genome Editing with CRISPR: A Promising Therapeutic Strategy

    Find-and-Replace Genome Editing with CRISPR: A Promising Therapeutic Strategy

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    Newswise — Severe Combined Immunodeficiencies (SCIDs) are a group of debilitating primary immunodeficiency disorders, primarily caused by genetic mutations that disrupt T-cell development. SCID can also affect B-cell and natural killer cell function and counts. Left untreated, SCID proves fatal within the first year of life. The conventional treatment for SCID patients involves allogeneic hematopoietic stem cell transplantation (HSCT), but the challenges of finding compatible donors and potential complications like graft-versus-host disease (GVHD) pose significant hurdles in this approach.

    A groundbreaking solution has emerged with the advent of genome editing (GE), particularly using CRISPR-Cas9 technology. This cutting-edge gene therapy research offers hope for many genetic disorders such as SCID. The CRISPR-Cas9 system creates site-specific double-strand breaks in the DNA, allowing for precise gene editing. The repair process can either disrupt a specific gene or correct it, potentially targeting nearly any gene in the genome. This development opens the door to therapeutic interventions for a wide range of genomic diseases.

    One promising genome-editing approach, CRISPR-Cas9 Homology-directed repair (HDR)-mediated GE, offers the potential for precise gene insertion. In certain subtypes of SCID, an alternative to HSCT can involve conventional CRISPR-Cas9 HDR-mediated gene insertion, but it carries inherent risks, especially in cases like RAG2-SCID. RAG2 is nuclease involved in DNA cleavage during lymphocyte development, and CRISPR-Cas9 HDR-mediated gene insertion may lead to uncontrolled RAG2 nuclease activity and harmful structural variations.

    In response, researchers from Bar-Ilan University in Israel propose a novel replacement strategy, termed GE x HDR 2.0: Find and Replace. This approach, outlined in a paper published today in Nature Communications, combines CRISPR-Cas9-mediated genome editing with recombinant adeno-associated serotype 6 (rAAV6) DNA donor vectors to precisely replace the RAG2 coding sequence while preserving regulatory elements. This strategy can be applied also to other genes with hot spot regions for disease-causing mutations.

    Dr. Ayal Hendel, of Bar-Ilan University’s Goodman Faculty of Life Sciences, emphasized, “Our innovation hinges on a crucial insight: to efficiently trigger CRISPR-Cas9 HDR-mediated GE for precise coding sequence replacement, it’s essential to separate the distal homology arm from the cleavage site and align it with the sequence immediately downstream of the segment needing replacement. In this process, elongating the distal homology arm length in the donor is of paramount importance. By preserving endogenous regulatory elements and intronic sequences, our approach faithfully reproduces natural gene expression levels, thus reducing the associated risks of unregulated gene expression. This groundbreaking technique, which involves replacing entire coding sequences or exons while retaining critical regulatory elements, brings hope to patients with RAG2-SCID and holds promise for the treatment of various other genetic disorders.”

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  • Whaling decimated more fin whales than previously estimated

    Whaling decimated more fin whales than previously estimated

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    Key takeaways

    • Whaling in the 20th century destroyed 99% of the Eastern North Pacific fin whale breeding  population.
    • Because there is enough genetic diversity, current conservation measures should help the population rebound without becoming inbred.
    • The future of fin whales in the Gulf of California depends on the recovery of the Eastern North Pacific population.

    Newswise — A new genomic study by UCLA biologists shows that whaling in the 20th century destroyed 99% of the Eastern North Pacific fin whale breeding, or “effective,” population — 29% more than previously thought.

    But there is also some good news: Genes among members of this endangered species are still diverse enough that current conservation measures should be be enough to help the population rebound without becoming inbred. The study also found that the health of this group is essential for the survival of highly isolated, genetically distinct fin whales in the Gulf of California.

    The study, published in Nature Communications, is among the first to use whole genome information to get a picture of the size and genetic diversity of today’s population. Previous studies had to rely on whaling records or mitochondrial DNA, which is inherited only from the mother, providing limited genetic information.

    In the 19th century, whaling decimated most whale species around the world but left the largest ones — blue and fin whales — largely untouched. That changed with the advent of industrial whaling in the 20th century. By midcentury, close to a million fin whales worldwide had been slaughtered, at least 75,000 of these in the Eastern North Pacific.

    “When you look at whaling records, you can only tell how many were killed. You can’t tell how many there were to begin with,” said corresponding author Meixi Lin, who worked on the project as a UCLA doctoral student and is now a Carnegie Institution for Science postdoctoral fellow at Stanford University. “We know 20th century whaling was severe, but we didn’t know how severe it was for fin whales.”

    To find out, then-postdoctoral researcher and corresponding author Sergio Nigenda-Morales extracted DNA from tissue samples taken from wild fin whales in the Eastern North Pacific and the Gulf of California. He rounded this out with DNA provided by colleagues at the National Oceanic and Atmospheric Administration. In all, 50 whales were studied. Fin whales from the Gulf of California were included because the population there had been undisturbed by whaling, enabling researchers to assess their genetic diversity and learn how they were related to the Eastern North Pacific population.

    “Getting samples from live whales is hard, because you don’t know where they’re going to be —and when they come up, you only have a moment to take the sample before they go back underwater,” said Nigenda-Morales, now an assistant professor at Cal State San Marcos. “It is a humbling experience to conduct field research and interact with the second-largest animal on the planet.”

    The genome analyses revealed that the Gulf of California population diverged around 16,000 years ago, with a population that hovered around 114 adults of reproductive age. The population of breeding adults is a key indicator of a species’ ability to sustain itself. The Eastern North Pacific effective population remained at around 24,000 individuals for thousands of years, until a severe decline happened between 26 and 52 years ago — a period that coincides with 20th century whaling — to only about 305 individuals.

    Past ecological studies had suggested a 70% reduction in fin whale populations, while earlier genetic studies estimated a much larger pre-whaling population.

    “It’s usually hard to detect such strong recent reductions in the genome. But in this case, fin whales were really abundant before, which made the sudden reduction very obvious in our data. If the reduction hadn’t been so strong, we wouldn’t have been able to detect it,” Nigenda-Morales said.

    When a population suffers such a drastic decline, harmful genes left in the remaining organisms can become amplified over time as the small population size inevitably forces individuals carrying those genes to breed together. These harmful genes can reduce the health of the overall population and cause it to die out. Genetic diversity is still high among Eastern North Pacific whales, meaning that multiple versions of many genes are still plentiful and harmful genes have not yet become common.

    “Most of this variation originated long, long ago, so genetic diversity in the small number of surviving individuals comes from their ancient history,” said co-author Kirk Lohmueller, a UCLA professor of ecology and evolutionary biology.

    Luckily, thanks to the slow pace of fin whale reproduction, the population reduction caused by whaling at its strongest point lasted for only two fin whale generations — a 50-year span — and ended with the implementation of the international whaling moratorium in 1985. Since then, the population has slowly recovered, and harmful genes have not had time to pile up.

    However, computer simulations show that if the population remains at its current size, the diversity will begin to vanish. The study’s authors write that the most important thing governments can do to aid fin whale recovery is to continue to enforce the whaling ban so that fin whales have time to increase their numbers.

    The future of fin whales in the Gulf of California also depends on the recovery of the Eastern North Pacific population. The genomic analysis showed that many harmful genes have become common in the former group, and that the only source of new genetic variants is the occasional Eastern North Pacific whale who wanders into their territory about once in every three generations. This infusion of new genetic material, however, has been enough to keep the population going.

    For now, current protections for both populations appear sufficient, though they will need to remain in place for a long time. But climate change, ship strikes and other human-caused disturbances could jeopardize the species’ recovery. The authors expect that ongoing research will help identify additional conservation measures.

    “With improvement in computational models, we can incorporate factors like climate change and relate the risk of extinction from human-mediated processes with what’s happening at the genomic level,” said Lohmueller. “Continuing to develop such models is as important as collecting more data.”

    Nigenda-Morales and Lin undertook the research as doctoral students of UCLA professor and senior author Robert Wayne, who continued working on the project until he passed away late last year. The authors have dedicated the paper to him.

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  • Research Reveals Deep Neural Networks’ Unique Perception of the World.

    Research Reveals Deep Neural Networks’ Unique Perception of the World.

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    Newswise — CAMBRIDGE, MA — Human sensory systems are very good at recognizing objects that we see or words that we hear, even if the object is upside down or the word is spoken by a voice we’ve never heard.

    Computational models known as deep neural networks can be trained to do the same thing, correctly identifying an image of a dog regardless of what color its fur is, or a word regardless of the pitch of the speaker’s voice. However, a new study from MIT neuroscientists has found that these models often also respond the same way to images or words that have no resemblance to the target.

    When these neural networks were used to generate an image or a word that they responded to in the same way as a specific natural input, such as a picture of a bear, most of them generated images or sounds that were unrecognizable to human observers. This suggests that these models build up their own idiosyncratic “invariances” — meaning that they respond the same way to stimuli with very different features.

    The findings offer a new way for researchers to evaluate how well these models mimic the organization of human sensory perception, says Josh McDermott, an associate professor of brain and cognitive sciences at MIT and a member of MIT’s McGovern Institute for Brain Research and Center for Brains, Minds, and Machines.

    “This paper shows that you can use these models to derive unnatural signals that end up being very diagnostic of the representations in the model,” says McDermott, who is the senior author of the study. “This test should become part of a battery of tests that we as a field are using to evaluate models.”

    Jenelle Feather PhD ’22, who is now a research fellow at the Flatiron Institute Center for Computational Neuroscience, is the lead author of the open-access paper, which appears today in Nature Neuroscience. Guillaume Leclerc, an MIT graduate student, and Aleksander Mądry, the Cadence Design Systems Professor of Computing at MIT, are also authors of the paper.

    Different perceptions

    In recent years, researchers have trained deep neural networks that can analyze millions of inputs (sounds or images) and learn common features that allow them to classify a target word or object roughly as accurately as humans do. These models are currently regarded as the leading models of biological sensory systems.

    It is believed that when the human sensory system performs this kind of classification, it learns to disregard features that aren’t relevant to an object’s core identity, such as how much light is shining on it or what angle it’s being viewed from. This is known as invariance, meaning that objects are perceived to be the same even if they show differences in those less important features.

    “Classically, the way that we have thought about sensory systems is that they build up invariances to all those sources of variation that different examples of the same thing can have,” Feather says. “An organism has to recognize that they’re the same thing even though they show up as very different sensory signals.”

    The researchers wondered if deep neural networks that are trained to perform classification tasks might develop similar invariances. To try to answer that question, they used these models to generate stimuli that produce the same kind of response within the model as an example stimulus given to the model by the researchers.

    They term these stimuli “model metamers,” reviving an idea from classical perception research whereby stimuli that are indistinguishable to a system can be used to diagnose its invariances. The concept of metamers was originally developed in the study of human perception to describe colors that look identical even though they are made up of different wavelengths of light.

    To their surprise, the researchers found that most of the images and sounds produced in this way looked and sounded nothing like the examples that the models were originally given. Most of the images were a jumble of random-looking pixels, and the sounds resembled unintelligible noise. When researchers showed the images to human observers, in most cases the humans did not classify the images synthesized by the models in the same category as the original target example.

    “They’re really not recognizable at all by humans. They don’t look or sound natural and they don’t have interpretable features that a person could use to classify an object or word,” Feather says.

    The findings suggest that the models have somehow developed their own invariances that are different from those found in human perceptual systems. This causes the models to perceive pairs of stimuli as being the same despite their being wildly different to a human.

    Idiosyncratic invariances

    The researchers found the same effect across many different vision and auditory models. However, each of these models appeared to develop their own unique invariances. When metamers from one model were shown to another model, the metamers were just as unrecognizable to the second model as they were to human observers.

    “The key inference from that is that these models seem to have what we call idiosyncratic invariances,” McDermott says. “They have learned to be invariant to these particular dimensions in the stimulus space, and it’s model-specific, so other models don’t have those same invariances.”

    The researchers also found that they could induce a model’s metamers to be more recognizable to humans by using an approach called adversarial training. This approach was originally developed to combat another limitation of object recognition models, which is that introducing tiny, almost imperceptible changes to an image can cause the model to misrecognize it.

    The researchers found that adversarial training, which involves including some of these slightly altered images in the training data, yielded models whose metamers were more recognizable to humans, though they were still not as recognizable as the original stimuli. This improvement appears to be independent of the training’s effect on the models’ ability to resist adversarial attacks, the researchers say.

    “This particular form of training has a big effect, but we don’t really know why it has that effect,” Feather says. “That’s an area for future research.”

    Analyzing the metamers produced by computational models could be a useful tool to help evaluate how closely a computational model mimics the underlying organization of human sensory perception systems, the researchers say.

    “This is a behavioral test that you can run on a given model to see whether the invariances are shared between the model and human observers,” Feather says. “It could also be used to evaluate how idiosyncratic the invariances are within a given model, which could help uncover potential ways to improve our models in the future.”

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    Massachusetts Institute of Technology (MIT)

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  • Newsmakers: Basic Research Findings by Johns Hopkins Scientists Focus on Gene Sequencing, Hearing Loss and a Brain Disorder

    Newsmakers: Basic Research Findings by Johns Hopkins Scientists Focus on Gene Sequencing, Hearing Loss and a Brain Disorder

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    Newswise — Yes, Scientists Have Sequenced the Entire Human Genome, But They’re Not Done Yet

    The human genome, from end to end, has been sequenced, meaning scientists worldwide have identified most of the nearly 20,000 protein-coding genes. However, an international group of scientists notes there’s more work to be done. The scientists point out that even though we have nearly converged on the identities of the 20,000 genes, the genes can be cut and spliced to create approximately 100,000 proteins, and gene experts are far from agreement on what those 100,000 proteins are.

    The group, which convened last fall at Cold Spring Harbor Laboratory in New York, has now published a guide for prioritizing the next steps in the effort to complete the human gene “catalog.”

    “Many scientists have been working on efforts to fully understand the human genome, and it’s much more difficult and complex than we thought,” says Steven Salzberg, Ph.D., Bloomberg Distinguished Professor of Biomedical Engineering, Computer Science, and Biostatistics at The Johns Hopkins University. “We have provided a state of the human gene catalog and a guide on what’s needed to complete it.”

    Salzberg, along with Johns Hopkins biomedical engineer and associate professor Mihaela Pertea, Ph.D., M.S., M.S.E., postdoctoral researcher Ales Varabyou and 19 other scientists, offered perspectives on the human gene catalog Oct. 4 in the journal Nature.

    The scientists say that while the final list of protein coding genes is nearly complete, scientists have not yet fully cataloged the variety of ways that a gene can be cut, or spliced, resulting in “isoforms” of proteins that are slightly different. Some protein isoforms will not affect the protein’s function but some may be different enough to result in increased risk for a particular trait, condition or illness.

    To complete the catalog, the scientists propose a comprehensive look at how each gene is expressed into functional and nonfunctional proteins and the three-dimensional shape of those proteins.

    The scientists also propose a focus on cataloging non-coding RNA genes. RNA is the genetic material that is transcribed by DNA and follows a molecular path to making proteins. Instead of proteins, non-coding RNA genes encode other types of molecular material that performs a cellular function.

    Finally, the international group emphasizes the importance of enhancing commonly used databases of gene variations that cause illness and disease, improving clinical laboratory standards for annotating DNA sequencing results and developing new technology to enable more effective and precise methods to match the wide array of proteins with their gene products.

    When It Comes to Hearing, the Left and Right Sides of the Brain Work Together, Mouse Research Shows

    Johns Hopkins-led research has revealed an extensive network of connections between the right and left sides of the brain when mice are exposed to different sounds. The researchers also found that some areas of the brain are specialized to recognize certain sounds, such as “calls” from the animals. Further, the researchers also found that deaf mice had far fewer right and left brain connections, suggesting that the brain needs to “hear” and process sound during early ages to spur development of left-right brain connections.

    The findings, say the researchers, may eventually help scientists pinpoint the time period when such brain connections and specialization form, and offer potential insights into how to restore hearing loss.

    “The auditory system is a collection of parts, which need to be connected properly,” says Johns Hopkins neuroengineer Patrick Kanold, Ph.D., a professor of biomedical engineering. “Using a novel microscope that enabled us to see both brain hemispheres at the same time, we found that some of those connections are between the right and left brain hemispheres, allowing functional specialization. When the brain does not get the right inputs, for example in hearing loss, these brain connections are missing. This obviously is an issue if we hope to restore hearing at a later age.”

    In efforts to find new ways to restore hearing, Kanold’s team will continue its work to identify the specific time period when brain connections form in response to sound and how to restore abnormal connections. The team is also continuing research to understand how the brain adapts to and modulates sound processing to filter out distracting signals, such as its recent work indicating that the brain’s frontal cortex provides specific signals to the auditory system during behaviors that might help in this filtering process.

    New Mouse Models May Help Scientists Find Therapies for Brain Development Disorder

    For more than 25 years, Richard Huganir, Ph.D., Bloomberg Distinguished Professor of Neuroscience and Psychological and Brain Sciences and director of the Solomon H. Snyder Department of Neuroscience, at the Johns Hopkins University School of Medicine, has studied the protein SYNGAP1 that is now known to be linked to a group of neurodevelopmental disorders that are usually diagnosed during early childhood. Working with biotechnology companies to find new therapies for the conditions, his team at Johns Hopkins Medicine reports it has developed new mouse models that more accurately represent genetic mutations in people who have SYNGAP1-related disorders.

    The new collection of mouse models, now available to scientists developing treatments, have several variations in the SYNGAP1 gene, which were discovered to cause conditions marked by seizures, cognitive impairment, social deficits and sleep disturbances.

    The SYNGAP1 gene, found also in humans, makes proteins that regulate synapses, the space between two neurons where they trade chemical and molecular messages. When SYNGAP1 is mutated, as in the case of SYNGAP1-related disorders in people, neurons make less of the protein in the synapse, and learning and memory are impaired.

    In other mouse models, called “knock-out” models, the SYNGAP1 gene is removed entirely. Huganir says both the knock-out models and the new versions — “knock-in” models, which carry a variety of SYNGAP1 mutations linked to the disorders — will be helpful in finding therapies that boost SYNGAP1 protein production.

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  • Florida Keys’ new “margarita snails” are bright yellow

    Florida Keys’ new “margarita snails” are bright yellow

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    Newswise — The “Margaritaville” in Jimmy Buffett’s famous song isn’t a real place, but it’s long been associated with the Florida Keys. This string of tropical islands is home to the only living coral barrier reef in the continental US, along with many animals found nowhere else in the world. One of them is a newly-discovered, bright yellow snail, named in honor of Margaritaville. The lemon- (or, key-lime-) colored snail, along with its lime-green cousin from Belize, is the subject of a study published in the journal PeerJ.

    These marine snails are distant relatives of the land-dwelling gastropods you might find leaving slimy trails in your garden. Nicknamed “worm snails,” they spend most of their lives in one place. “I find them particularly cool because they are related to regular free-living snails, but when the juveniles find a suitable spot to live, they hunker down, cement their shell to the substrate, and never move again,” says Rüdiger Bieler, curator of invertebrates at the Field Museum in Chicago and the study’s lead author. “Their shell continues to grow as an irregular tube around the snail’s body, and the animal hunts by laying out a mucus web to trap plankton and bits of detritus.”

    Bieler has spent the past four decades studying invertebrate animals living in the Western Atlantic, but these particular snails “are so small and so well-hidden that we’ve not encountered them before during our scuba diving surveys. We had to look very closely,” he says. The new species belong to the same family of marine snails as the invasive “Spider-Man” snail that the same team described from the Vandenberg shipwreck off the Florida Keys in 2017.  

    He and his colleagues, including fellow Field Museum curator Petra Sierwald, came across the lemon-yellow snails in the Florida Keys National Marine Sanctuary, and they found a similar, lime-colored snail in Belize. “Many snails are polychromatic– within the same species, you get different colors,” says Bieler. “In a single population, even a single little cluster, one might be orange, one might be gray. I think they do it to confuse fish and not give them a clear target, and some have warning coloration.”

    “Initially, when I saw the lime-green one and the lemon-yellow one, I figured they were the same species,” says Bieler. “But when we sequenced their DNA, they were very different.”

    Based on these molecular data, Bieler, Sierwald, and their co-authors Timothy Collins, Rosemary Golding, Camila Granados-Cifuentes, John Healy and Timothy Rawlings, placed the snails in a new genus, Cayo, after the Spanish word for a small, low island. The yellow snail was named Cayo margarita after the citrusy drinks in Jimmy Buffet’s “Margaritaville.” The lime snail’s name, Cayo galbinus, means “greenish-yellow.” 

    The Cayo snails have a key trait in common with another worm snail genus, Thylacodes, for which the team described a new species from Bermuda and named Thylacodes bermudensis. While only distantly related, these snails all have brightly colored heads poking out of their tubular shells. “Our thought is this is a warning color,” says Bieler. “They have some nasty metabolites in their mucus. That also might help explain why they’re able to have exposed heads– on the reef, everybody is out to eat you, and if you don’t have any defensive mechanism, you will be overgrown by the corals and sea anemones and all the stuff around you. It seems like the mucus might help deter the neighbors from getting too close.”

    Bieler says that the study is important because it helps illuminate the biodiversity of coral reefs, which are under severe threat due to climate change. “There have been increases in global water temperatures, and some species can handle them much better than others,” says Bieler. The Cayo snails have a tendency to live on pieces of dead coral, and as more coral is killed off, the snails might spread. 

    Moreover, says Bieler, “it’s another indication that right under our noses, we have undescribed species. This is in snorkeling depth in a heavily touristed area, and we’re still finding new things  all around us.”

    This study was contributed to by scientists at the Field Museum, Florida International University, Queensland Museum, and Cape Breton University. 

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  • MSU finds genetic rescue is underused for endangered species recovery

    MSU finds genetic rescue is underused for endangered species recovery

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    Newswise — EAST LANSING, Mich. – During a recent review of the U.S. Fish and Wildlife Service’s recovery plans for more than 200 endangered and threatened vertebrate species in the United States, Michigan State University researchers made an interesting discovery. They found that two-thirds of these species could benefit from a gene-boosting diversity strategy known as genetic rescue. Surprisingly, just three of these plans to support species recovery currently use this approach.

    Genetic rescue is an increase in population size caused by the movement of new genetic material from one population to another. This can happen through either human-assisted intervention or natural migration. As a conservation tool, this strategy can increase the genetic diversity of small, isolated populations and help them recover from inbreeding.

    “These small, isolated populations are becoming more frequent, fragmented and in trouble,” said Sarah Fitzpatrick, an associate professor in the Department of Integrative Biology in the College of Natural Science and a W.K. Kellogg Biological Station faculty member. “They might benefit from some human-assisted migration to help infuse deteriorating populations with more genetic variation, which can help them respond to changes in the environment as well.”

    Translocating, or the act of moving individuals from one place to another, is a common practice that has most often been used outside the context of genetic rescue. 

    “This is pretty common in fish management,” said Cinnamon Mittan-Moreau, an MSU Ecology, Evolution and Behavior Presidential Postdoctoral Fellow based at KBS. “Managers have been moving animals and plants around for more than a century, just not with the intention of increasing genetic variation.”

    The good news is that, in many cases, the logistics of carrying out these translocations have already been overcome, and so the time is ripe for more attempts at genetic rescue. Despite this, however, this strategy continues to be left out of species recovery plans.

    “We found that over two-thirds of the 222 species we evaluated would be good candidates for consideration of genetic rescue,” said Fitzpatrick. “And yet, we found only three examples of implementation of genetic rescue. As genomic resources become available for more species, we hope to see increased incorporation of genetic information in recovery planning, including informed translocation actions for the purpose of genetic rescue.”

    Along with Fitzpatrick and Mittan-Moreau, co-authors on this study include post-doctoral researcher Jessica Judson and former laboratory manager Madison Miller.

    “There’s a lot of opportunity for this to help, but we don’t see it very often,” said Mittan-Moreau. “No one had done this full review to see if this could be considered more often for endangered species plans.”

    The paper was published in the Journal of Heredity.

    Read on MSUToday.  

    ###

    Michigan State University has been advancing the common good with uncommon will for more than 165 years. One of the world’s leading research universities, MSU pushes the boundaries of discovery to make a better, safer, healthier world for all while providing life-changing opportunities to a diverse and inclusive academic community through more than 400 programs of study in 17 degree-granting colleges. 

    For MSU news on the Web, go to MSUToday. Follow MSU News on Twitter at twitter.com/MSUnews.

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    Michigan State University

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  • Largest-Ever Genetic Study of Suicide Finds New Risk Factors

    Largest-Ever Genetic Study of Suicide Finds New Risk Factors

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    BYLINE: Caroline Seydel

    Newswise — The reasons why people attempt suicide are complex and include external triggers like trauma and stress, as well as inherited genetic factors. A new study has identified 12 DNA variants, or variations in the human genetic code, that are associated with risk of attempting suicide. The research highlights strong genetic links between suicide attempt and factors that influence physical and behavioral health—including impulsivity, smoking, chronic pain, ADHD, pulmonary conditions, and heart disease. These findings suggest that some of the genetic underpinnings of suicide are shared with these conditions.

    One day, this information could lead to a better understanding of biological causes of suicide and improvements in prevention strategies. Eventually, such advances could help health care providers identify people who may need mental health support.

    “Many people who die from suicide have significant health conditions associated with that risk,” says Anna Docherty, Ph.D., the study’s corresponding author and associate professor of psychiatry at Huntsman Mental Health Institute at the University of Utah. “If we can use genetic information to characterize the health risks of those who attempt suicide, we can better identify those patients who need contact with the mental health care system.” The research published online on October 1 in the American Journal of Psychiatry.

    Scientists at HMHI, Icahn School of Medicine at Mount Sinai, Duke University School of Medicine, Durham Veterans Affairs Health Care System, and Vanderbilt University Medical Center led the collaboration with multiple institutions worldwide. They analyzed data from 22 different populations across the globe, including people of diverse ancestral and ethnic backgrounds.

    Understanding genetic risk of suicide

    No single gene causes suicide. Rather, the cumulative effect of many different genes influences a person’s risk. “In psychiatry, we have many tiny genetic effects, but when we account for all of them together, we start to see a real genetic risk signal,” Docherty explains.

    To tease out such a diffuse signal, researchers applied statistical methods to data collected from a large number of people and identified genetic variations that are more common among individuals who have attempted suicide. The new analysis combines data from the Million Veteran Program (MVP) and the International Suicide Genetics Consortium (ISGC). Together, these include 43,871 documented suicide attempts and 915,025 ancestry-matched controls, making this the largest genetic study of suicide to date.

    A meta-analysis of the studies identified new genetic variants that correlated with suicide attempt. The researchers then compared all variant signals with previously published genetic data on more than 1,000 other traits and disorders, including psychiatric conditions (e.g., ADHD), physical conditions (e.g., heart disease), and behaviors (e.g., smoking), and determined that genetic variants linked to suicide attempt are also linked to other health conditions.

    “That allowed us to look at how genetic risk for suicide overlaps with genetic risk for depression, heart disease, and many other risk factors,” Docherty says. “It showed significant overlap with mental health conditions, but also a lot of physical health conditions, particularly for smoking and lung-related illnesses. This is something we can’t necessarily see in medical records of people who die from suicide.”

    The results do not mean that people with any one of these health factors are at high risk for attempting suicide, notes Hillary Coon, Ph.D., study co-author and professor of psychiatry at HMHI. Rather, combining the genetic predisposition with other stressors—which could include other genetic risk factors, health conditions, life circumstances, or traumatic events—could increase that risk, she explains.

    Initial analyses support the idea that many of the DNA variants that the scientists identified are located in genes with known biological functions, bolstering the case that changes in these genes could affect a person’s physiology or behavior. Several of the genes control processes in cells such as managing cellular stress, repairing damaged DNA, and communicating with the immune system. Most are also highly expressed in the brain and are known targets of antipsychotic and antidepressant drugs.

    Scientists will need to carry out additional studies to determine whether the variants directly or indirectly impact suicide risk, and how. The research so far has shown an association and not cause and effect.

    Understanding how suicide is linked to other health conditions could open doors to new ways of assessing—and treating—suicide risk, Docherty adds. “We want to start to explore the biological underpinnings that are common across suicide and these health factors, because that will lead to the most convincing drug targets,” she says.

    # # #

    The research published as “Genome-wide association study meta-analysis of suicide attempt identifies twelve genome-wide significant loci and implicates genetic risks for specific health factors” with support from the National Institutes of Health, Huntsman Mental Health Institute, the American Foundation for Suicide Prevention, Janssen Research and Development, LLC, Clark Tanner Research Foundation, Clinical Science Research and Development Sevice of the Veterans Health Administraton Officde of Research and Development, and the Brain and Behavior Research Foundation.

    About Huntsman Mental Health Institute  

    Huntsman Mental Health Institute (HMHI) was established in 2021 following the Huntsman Foundation’s historic gift of $150 million to the University of Utah. HMHI is a university-wide Institute with a reputation throughout the Mountain West as a leader in advanced psychiatric treatment and care, serving a diverse population from young children to geriatric patients. Researchers at HMHI develop and apply the most advanced methods in genetics, imaging, epidemiology, and big data analysis. HMHI is also the regional training center for psychiatry and other mental health disciplines. HMHI’s main 170-bed full-service hospital is adjacent to the University of Utah campus, and HMHI’s 1,644 faculty, staff, and students provide clinical, research, and training programs in more than 20 locations across Utah and Idaho.   

    For more information, visit HMHI.utah.edu and join the conversation on TikTok, Instagram, Twitter, LinkedIn, YouTube, and Facebook. 

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    University of Utah Health

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  • Scientists who paved way for COVID-19 mRNA vaccines win Nobel prize

    Scientists who paved way for COVID-19 mRNA vaccines win Nobel prize

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    Katalin Karikó and Drew Weissman have been awarded the Nobel prize in medicine for their work on messenger RNA technology, which enabled the development of the first vaccines against COVID-19.

    The Nobel Assembly at Sweden’s Karolinska Institute, which is responsible for selecting the winner of one of science’s most prestigious prizes, said on Monday that the discoveries “were critical for developing effective mRNA vaccines against COVID-19.”

    mRNA vaccines work by delivering into the body genetic instructions for building proteins that are present in the virus being immunized against. That spurs cells to create those proteins, which the body then recognizes as foreign and attacks; training the immune system and creating protection against the actual virus.

    In the early 1990s, Karikó, from Hungary, was working at the University of Pennsylvania looking at how mRNA could be used in medicine. She was joined in her research by U.S. colleague Weissman, an immunologist specializing in dendritic cells, which are responsible for the body’s immune response during vaccination.

    Together, the scientists discovered how to alter mRNA so that it wasn’t immediately detected by the body’s immune system and could deliver its payload to the target cells. Further work by the pair improved the efficiency of mRNA, so that it stimulated more protein production.

    “Through their discoveries that base modifications both reduced inflammatory responses and increased protein production, Karikó and Weissman had eliminated critical obstacles on the way to clinical applications of mRNA,” said the Nobel Assembly.

    As well as laying the groundwork for mRNA vaccines, Karikó was employed from 2013 to 2022 at vaccine developer BioNTech, which, together with Pfizer, produced the first COVID-19 vaccine approved in the EU.

    Pharma companies are now developing mRNA vaccines and therapies for a swathe of different diseases including flu, tuberculosis, HIV, malaria, Lyme disease, Zika and various types of cancer.

    The award comes with a cash prize of 11 million Swedish krona (€950,000). In 1951, Max Theiler won the prize for his work helping discover the vaccine against yellow fever.

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    Carlo Martuscelli

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  • Protein p53 regulates learning, memory, sociability in mice

    Protein p53 regulates learning, memory, sociability in mice

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    BYLINE: Jenna Kurtzweil

    Newswise — Researchers have established the protein p53 as critical for regulating sociability, repetitive behavior, and hippocampus-related learning and memory in mice, illuminating the relationship between the protein-coding gene TP53 and neurodevelopmental and psychiatric disorders like autism spectrum disorder.

    “This study shows for the first time that p53 is linked directly to autism-like behavior,” said Nien-Pei Tsai, an associate professor of molecular and integrative biology at the University of Illinois Urbana-Champaign and a researcher at the Beckman Institute for Advanced Science and Technology.

    In living systems, genes act as a biological version of binary code, using the letters A, C, G, and T instead of ones and zeroes to spell out cellular marching orders. Some genes — called coding genes — instruct cells to create proteins with specific functions. For example, the gene TP53 instructs cells to create the protein p53; its job is to regulate how other genes are expressed.

    In this study, Tsai and his colleagues lowered hippocampal p53 levels in mice, looking for changes in gene expressions related to behavior. They observed that the decreased p53 levels:

    • Promoted repetitive behavior in mice.
    • Reduced sociability in mice.
    • Impaired hippocampus-dependent learning and memory, especially in male mice.

    The researchers also observed that p53 levels were elevated after a period of active communication between hippocampal neurons called long-term potentiation. Flexible neuron firing — known as plasticity — is related to positive learning and memory outcomes.

    In a 2018 study, Tsai and his colleagues identified p53 as a key protein involved in the irregular brain cell activity seen in ASD and epilepsy. In future studies, they aim to explore how p53 coordinates the expression of those autism-linked genes to guide behavior.

    Editor’s notes:

    The paper associated with this study is titled “Tumor suppressor p53 modulates activity-dependent synapse strengthening, autism-like behavior and hippocampus-dependent learning” and appears in the journal Molecular Psychiatry.

    Research reported in this press release was supported by the National Institutes of Health under award numbers R01NS105615, R01MH124827, and R21MH122840. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

    Access the free paper online: https://www.nature.com/articles/s41380-023-02268-9

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    Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign

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  • Latest Insights: Men’s Hair Loss

    Latest Insights: Men’s Hair Loss

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    Newswise — A receding hairline, a total loss of hair from the crown, and ultimately, the classical horseshoe-shaped pattern of baldness: Previous research into male pattern hair loss, also termed androgenetic alopecia, has implicated multiple common genetic variants. Human geneticists from the University Hospital of Bonn (UKB) and by the Transdisciplinary Research Unit “Life & Health” of the University of Bonn have now performed a systematic investigation of the extent to which rare genetic variants may also contribute to this disorder. For this purpose, they analyzed the genetic sequences of 72,469 male participants from the UK Biobank project. The analyses identified five significantly associated genes, and further corroborated genes implicated in previous research. The results have now been published in the prestigious scientific journal Nature Communications.

    Male-pattern hair loss is the most common form of hair loss in men, and is largely attributable to hereditary factors. Current treatment options and risk prediction are suboptimal, thus necessitating research into the genetic underpinnings of the condition. To date, studies worldwide have focused primarily on common genetic variants, and have implicated more than 350 genetic loci, in particular the androgen receptor gene, which is located on the maternally inherited X chromosome. In contrast, the contribution to this common condition of rare genetic variants has traditionally been assumed to be low. However, systematic analyses of rare variants have been lacking. “Such analyses are more challenging as they require large cohorts, and the genetic sequences must be captured base by base, e.g., through genome or exome sequencing of affected individuals,” explained first author Sabrina Henne, who is a doctoral student at the Institute of Human Genetics at the UKB and the University of Bonn. The statistical challenge lies in the fact that these rare genetic variants may be carried by very few, or even single, individuals. “That is why we apply gene-based analyses that first collapse variants on the basis of the genes in which they are located,” explained corresponding author PD Dr. Stefanie Heilmann-Heimbach, who is a research group leader at the Institute of Human Genetics at the UKB at the University of Bonn. Among other methods, the Bonn researchers used a type of sequence kernel association test (SKAT), which is a popular method for detecting associations with rare variants, as well as GenRisk, which is a method developed at the Institute of Genomic Statistics and Bioinformatics (IGSB) at the UKB and the University of Bonn.

    Possible relevance of rare variants in male-pattern hair loss

    The research involved the analysis of genetic sequences from 72,469 male UK Biobank participants. Within this extensive data set, Bonn geneticists, together with researchers from the IGSB and the Center for Human Genetics at the University Hospital Marburg, examined rare gene variants that occur in less than one percent of the population. Using modern bioinformatic and statistical methods, they found associations between male-pattern hair loss and rare genetic variants in the following five genes: EDA2R, WNT10A, HEPH, CEPT1, and EIF3F.

    Prior to the analyses, EDA2R and WNT10A were already considered candidate genes, as based on previous analyses of common variants. “Our study provides further evidence that these two genes play a role, and that this occurs through both common and rare variants,” explained Dr. Stefanie Heilmann-Heimbach. Similarly, HEPH is located in a genetic region that has already been implicated by common variants, namely the EDA2R/Androgen receptor, which is a region that has consistently shown the strongest association with male-pattern hair loss in past association studies. “However, HEPH itself has never been considered as a candidate gene. Our study suggests that it may also play a role,” explained Sabrina Henne. “The genes CEPT1 and EIF3F are located in genetic regions that have not yet been associated with male-pattern hair loss. They are thus entirely new candidate genes, and we hypothesize that rare variants within these genes contribute to the genetic predisposition. HEPH, CEPT1, and EIF3F represent highly plausible new candidate genes, given their previously described role in hair development and growth.” Furthermore, the results of the study suggest that genes that are known to cause rare inherited diseases affecting both skin and hair (such as the ectodermal dysplasias) may also play a role in the development of male-pattern hair loss. The researchers hope that the puzzle pieces they have discovered will improve understanding of the causes of hair loss, and thus facilitate reliable risk prediction and improved treatment strategies.

    The research was supported by funding from the Medical Faculty of the University of Bonn. Prof. Dr. Markus Nöthen, Director of the Institute of Human Genetics at UKB and co-author of the study, is a member of the Transdisciplinary Research Area (TRA) “Life and Health” at the University of Bonn. The publication costs in open access format were funded by the DEAL project of the University of Bonn.

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    Universitatsklinikum Bonn

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  • New method to study microRNA activity in single cells

    New method to study microRNA activity in single cells

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    Newswise — MicroRNAs are small molecules that regulate gene activity by binding to and destroying RNAs produced by the genes. More than 60% of all human genes are estimated to be regulated by microRNAs, therefore it is not surprising that these small molecules are involved in many biological processes including diseases such as cancer. To discover the function of a microRNA, it is necessary to find out exactly which RNAs are targeted by it. While such methods exist, they require a lot of material typically in order of millions of cells, to work.

    Now researchers at Stockholm University and SciLifeLab have developed a new method to detect microRNA targets at the level of single cells. Such cells are each around one-hundredth millimeter in diameter and weigh less than a billionth gram, and comprise the basic building blocks of living organisms. With their new sensitive method, the researchers can follow microRNA targeting of thousands of RNAs during biological processes such as the cell cycle or differentiation into red blood cells. In these processes, the researchers find that microRNAs – surprisingly – perform quite different tasks in each cell. In the future, it will be possible to also apply this method to study microRNA targeting in whole tissues, to find out exactly what is happening in each of the many cell types that comprise complex organs such as brains.

    Marc Friedländer, associate professor at Stockholm University, says: “In our research team, we want to understand and ultimately make mathematical models of gene regulation at the level of the single cell. Our new method is a huge leap towards making this possible”.

    The work was spearheaded by Dr. Inna Biryukova, who took a leading role in developing the laboratory method, and by PhD student Vaishnovi Sekar, who performed the bulk of the advanced computational analyses. Vaishnovi Sekar highlights the challenges of the project: “In terms of complexity of the computational work, this is uncharted territory, and we lacked reference points and thresholds. We had to explore a myriad of approaches to devise a methodology that not only works but also yields biologically meaningful observations.”

    The study was supported by ERC and Vetenskapsrådet and has been published in the journal Nature Biotechnology.

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    Stockholm University

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