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Tag: Karolinska Institute

  • Penis fibroblasts crucial for erection, underestimated.

    Penis fibroblasts crucial for erection, underestimated.

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    Regular erections could be important for maintaining erectile function, according to a new study on mice published in Science by researchers at Karolinska Institutet. “We discovered that an increased frequency of erections leads to more fibroblasts that enable erection and vice versa, that a decreased frequency results in fewer of these cells,” says principal investigator Christian Göritz.

    Newswise — In a new study on mice, researchers at Karolinska Institutet and Uppsala University in Sweden show that connective tissue cells called fibroblasts have a previously unknown and very important function in mediating erection.

    “Fibroblasts are the most abundant cells in the penis of both mice and humans, but they have been neglected in research,” says Eduardo Guimaraes, researcher at the Department of Cell and Molecular Biology at Karolinska Institutet and first author of the paper. “Now we can show, using a very precise method called optogenetics, that they have a very important role in regulating blood flow in the penis, which is what makes the penis erect.”

    The study shows that fibroblasts mediate erection by taking up the neurotransmitter noradrenaline, which leads to the widening of blood vessels in the penis. How effective this process is depends on the number of fibroblasts.

    The body adapts

    The researchers were also able to show that the number of fibroblasts in the penis is affected by the frequency of erections. The more frequent the more fibroblasts and vice versa; a lower frequency of erections reduced the number of fibroblasts.

    “It’s not so strange really. If you exert yourself a lot, your body adapts. If you run regularly, it will eventually become easier to breathe while running,” says Christian Göritz, senior researcher at the Department of Cell and Molecular Biology at Karolinska Institutet, who led the study.

    In terms of what conclusions can be drawn for humans from studies on mice, Christian Göritz says that in this case there are significant similarities.

    “The basic mechanisms of erection are very similar in all mammals regarding anatomy, cell structure and so on,” he says. “However, there is one difference between humans and most mammals – they have a bone in their penis. This means that effective blood flow regulation is probably even more important for human reproduction.”

    Fewer fibroblasts with age

    Older mice had fewer fibroblasts in the penis, which was also reflected in lower blood flow. The ability to get an erection decreases with age also in humans, which could be partly due to fewer fibroblasts in the penis. The researchers therefore believe that it could be possible to train the ability to get an erection to counteract impotence in the same way as you can train your strength or fitness at the gym.

    “This is not something we have shown in our study, so it is a bit speculative, but a reasonable interpretation is that it gets easier if you have regular erections,” says Christian Göritz.

    He hopes that the new knowledge of the role of fibroblasts in erection may also lead to new treatments for erectile dysfunction.

    The research was mainly funded by the Bertil Hållsten Foundation and the Knut and Alice Wallenberg Foundation. There are no reported conflicts of interest.


    Facts: Erectile dysfunction, or impotence, affects between 5 and 20 per cent of all men, with the incidence increasing with age. Erectile dysfunction often negatively affects the quality of life and physical and psychosocial health, both for the patient and their family. Common risk factors, apart from age, are similar to those for cardiovascular disease: inactivity, obesity, hypertension, smoking, high cholesterol levels and metabolic syndrome. Source: Region Stockholm knowledge support Viss.nu.


    Publication: “Corpora cavernosa fibroblasts mediate penile erection”, Eduardo Linck Guimaraes, David Oliveira Dias, Wing Fung Hau, Anais Julien, Daniel Holl, Maria Garcia-Collado, Soniya Savant, Evelina Vågesjö, Mia Phillipson, Lars Jakobsson, Christian Göritz. Science, online 8 February 2024, doi: 10.1126/science.ade8064.



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  • Adolescent fitness may not provide as much future cardiovascular health benefit as believed.

    Adolescent fitness may not provide as much future cardiovascular health benefit as believed.

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    Newswise — There is a well-known relationship between good physical fitness at a young age and a lower risk of cardiovascular disease later in life. However, when researchers adjusted for familial factors by means of sibling analysis, they found a weaker association, although the link between high body mass index (BMI) and cardiovascular disease remained strong. The study, which was conducted by researchers from Karolinska Institutet and other universities, is published in JAMA Network Open.

    “This does not mean that fitness is irrelevant,” says the study’s last author Viktor Ahlqvist, doctoral student at the Department of Global Public Health, Karolinska Institutet. “We could still see an association, although it was weaker after taking into account factors shared by full siblings. We also think that adolescence is an important time in life for establishing good habits such as exercising and having a healthy diet.”

    Challenging to prove causal associations

    Many observational studies have previously demonstrated links between various risk factors at a young age and cardiovascular disease in adulthood. However, whether the associations are causal is challenging to prove because of the potential influence of unaccounted genetic and environmental factors. A collaborative team including researchers from Karolinska Institutet in Sweden has therefore tried to examine if a large proportion of cardiovascular diseases in adulthood could indeed be prevented with a lower BMI, lower blood pressure, improved physical fitness or improved muscle strength in adolescence.

    Sourcing data from the Swedish Military Conscription Register and other Swedish registries, the researchers identified over a million 18-year-old males and followed them for 60 years. Almost half of them were full brothers.

    “The strength of our study, which makes it more reliable than many other conventional observational studies, is that we have used sibling analyses,” says the study’s first author Marcel Ballin, researcher at Uppsala University and analyst at Region Stockholm’s Centre for Epidemiology and Community Medicine. “By doing so we could examine how the relationship changes when controlling for all shared sibling factors. This includes environmental factors such as childhood environment and half of the genetics.”

    High BMI is a strong risk factor

    The results show that a high BMI in late adolescence was strongly associated with future cardiovascular disease, even after the researchers had controlled for shared familial factors. However, the association between physical fitness and cardiovascular disease was considerably weaker in the sibling analysis, suggesting that many previous observational studies might have overestimated the relevance of adolescent fitness to cardiovascular health later in life.

    “Our conclusion is that of the risk factors studied, high BMI is the strongest individual risk factor for cardiovascular disease, and that efforts to tackle the obesity epidemic should continue to be given high priority,” says co-author Daniel Berglind, docent at the Department of Global Public Health, Karolinska Institutet. “A good level of fitness and muscle strength in adolescence doesn’t seem as crucial, but physical activity still remains important for public health, as it can bring other health benefits.”

    Several limitations

    The study examined the association between risk factors at a young age and future cardiovascular disease; other disease outcomes were not investigated. The researchers had no data on whether the participants’ risk factors varied later in life, and they only studied men, which makes it difficult to extend their findings to women. The Military Conscription Register also lacks details on certain risk factors for future cardiovascular disease, such as diet, alcohol consumption, smoking, blood lipids and blood glucose.

    The researchers received no specific grant for this study. Co-author Martin Neovius is on the advisory panels for Ethicon, Johnson & Johnson and Itrim and has been a consultant for the Swedish armed forces outside the scope of this study. No other conflicts of interest have been reported.

    Publication: “Genetic and environmental factors and cardiovascular disease risk in adolescents”, Marcel Ballin, Martin Neovius, Francisco B. Ortega, Pontus Henriksson, Anna Nordström, Daniel Berglind, Peter Nordström, Viktor H. Ahlqvist, JAMA Network Open, online 17 November 2023, doi: 10.1001/jamanetworkopen.2023.43947.

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  • One More COVID Summer?

    One More COVID Summer?

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    Since the pandemic’s earliest days, epidemiologists have been waiting for the coronavirus to finally snap out of its pan-season spree. No more spring waves like the first to hit the United States in 2020, no more mid-year surges like the one that turned Hot Vax Summer on its head. Eventually, or so the hope went, SARS-CoV-2 would adhere to the same calendar that many other airway pathogens stick to, at least in temperate parts of the globe: a heavy winter peak, then a summer on sabbatical.

    But three and a half years into the outbreak, the coronavirus is still stubbornly refusing to take the warmest months off. Some public-health experts are now worried that, after a relatively quiet stretch, the virus is kick-starting yet another summer wave. In the southern and northeastern United States, concentrations of the coronavirus in wastewater have been slowly ticking up for several weeks, with the Midwest and West now following suit; test-positivity rates, emergency-department diagnoses of COVID-19, and COVID hospitalizations are also on the rise. The absolute numbers are still small, and they may stay that way. But these are the clear and early signs of a brewing mid-year wave, says Caitlin Rivers, an epidemiologist at Johns Hopkins University—which would make this the fourth summer in a row with a distinct coronavirus bump.

    Even this far into the pandemic, though, no one can say for certain whether summer waves are a permanent COVID fixture—or if the virus exhibits a predictable seasonal pattern at all. No law of nature dictates that winters must come with respiratory illness, or that summers will not. “We just don’t know very much about what drives the cyclical patterns of respiratory infections,” says Sam Scarpino, an infectious-disease modeler at Northeastern University. Which means there’s still no part of the year when this virus is guaranteed to cut us any slack.

    That many pathogens do wax and wane with the seasons is indisputable. In temperate parts of the world, airborne bugs get a boost in winter, only to be stifled in the heat; polio and other feces-borne pathogens, meanwhile, often rise in summer, along with gonorrhea and some other STIs. But noticing these trends is one thing; truly understanding the triggers is another.

    Some diseases lend themselves a bit more easily to explanation: Near the equator, waves of mosquito-borne illness, such as Zika and Chikungunya, tend to be tied to the weather-dependent life cycles of the insects that carry them; in temperate parts of the world, rates of Lyme disease track with the summertime activity of ticks. Flu, too, has pretty strong data to back its preference for wintry months. The virus—which is sheathed in a fragile, fatty layer called an envelope and travels airborne via moist drops—spreads best when it’s cool and dry, conditions that may help keep infectious particles intact and spittle aloft.

    The coronavirus has enough similarities to flu that most experts expect that it will continue to spread in winter too. Both viruses are housed in a sensitive skin; both prefer to move by aerosol. Both are also relatively speedy evolvers that don’t tend to generate long-lasting immunity against infection—factors conducive to repeat waves that hit populations at a fairly stable clip. For those reasons, Anice Lowen, a virologist at Emory University, anticipates that SARS-CoV-2 will continue to show “a clear wintertime seasonality in temperate regions of the world.” Winter is also a time when our bodies can be more susceptible to respiratory bugs: Cold, dry air can interfere with the movement of mucus that shuttles microbes out of the nose and throat; aridity can also make the cells that line those passageways shrivel and die; certain immune defenses might get a bit sleepier, with vitamin D in shorter supply.

    None of that precludes SARS-CoV-2 spread in the heat, even if experts aren’t sure why the virus so easily drives summer waves. Plenty of other microbes manage it: enteroviruses, polio, and more. Even rhinoviruses and adenoviruses, two of the most frequent causes of colds, tend to spread year-round, sometimes showing up in force during the year’s hottest months. (Many scientists presume that has something to do with these viruses’ relatively hardy outer layer, but the reason is undoubtedly more complex than that.) An oft-touted explanation for COVID’s summer waves is that people in certain parts of the country retreat indoors to beat the heat. But that argument alone “is weak,” Lowen told me. In industrialized nations, people spend more than 90 percent of their time indoors.

    That said, an accumulation of many small influences can together create a seasonal tipping point. Summer is a particularly popular time for travel, often to big gatherings. Many months out from winter and its numerous infections and vaccinations, population immunity might also be at a relative low at this time of year, Rivers said. Plus, for all its similarities to the flu, SARS-CoV-2 is its own beast: It has so far affected people more chronically and more severely, and has generated population-sweeping variants at a far faster pace. Those dynamics can all affect when waves manifest.

    And although certain bodily defenses do dip in the cold, data don’t support the idea that immunity is unilaterally stronger in the summer. Micaela Martinez, the director of environmental health at WE ACT for Environmental Justice, in New York, told me the situation is far more complicated than that. For years, she and other researchers have been gathering evidence that suggests that our bodies have distinctly seasonal immunological profiles—with some defensive molecules spiking in the summer and another set in winter. The consequences of those shifts aren’t yet apparent. But some of them could help explain when the coronavirus spreads. By the same token, winter is not a time of disease-ridden doom. Xaquin Castro Dopico, an immunologist at the Karolinska Institute, in Sweden, has found that immune systems in the Northern Hemisphere might be more inflammation-prone in the winter—which, yes, could make certain bouts of illness more severe but could also improve responses to certain vaccinations.

    All of those explanations could apply to COVID’s summer swings—or perhaps none does. “Everybody always wants to have a very simple seasonal answer,” Martinez told me. But one may simply not exist. Even the reasons for the seasonality of polio, a staunch summertime disease prior to its elimination in the U.S., have been “an open question” for many decades, Martinez told me.

    Rivers is hopeful that the coronavirus’s permanent patterns may already be starting to peek through: a wintry heyday, and a smaller maybe-summer hump. “We’re in year four, and we’re seeing the same thing year over year,” she told me. But some experts worry that discussions of COVID-19 seasonality are premature. SARS-CoV-2 is still so fresh to the human population that its patterns could be far from their final form. At an extreme, the patterns researchers observed during the first few years of the pandemic may not prelude the future much at all, because they encapsulate so much change: the initial lack and rapid acquisition of immunity, the virus’s evolution, the ebb and flow of masks, and more. Amid that mishmash of countervailing influences, says Brandon Ogbunu, an infectious-disease modeler at Yale, “you’re going to get some counterintuitive dynamics” that won’t necessarily last long term.

    With so much of the world now infected, vaccinated, or both, and COVID mitigations almost entirely gone, the global situation is less in flux now. The virus itself, although still clearly changing at a blistering pace, has not pulled off an Omicron-caliber jump in evolution for more than a year and a half. But no one can yet promise predictability. The cadence of vaccination isn’t yet settled; Scarpino, of Northeastern University, also isn’t ready to dismiss the idea of a viral evolution surprise. Maybe summer waves, to the extent that they’re happening, are a sign that SARS-CoV-2 will remain a microbe for all seasons. Or maybe they’re part of the pandemic’s death rattle—noise in a system that hasn’t yet quieted down.

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    Katherine J. Wu

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  • Major genetic study reveals unexpectedly high variation in T-cell receptor genes between persons

    Major genetic study reveals unexpectedly high variation in T-cell receptor genes between persons

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    Newswise — T-cells that are part of our immune system are central in the protection against infections and cancer. With the help of TCRs, the cells recognize foreign invaders and tumor cells.

    “It was previously unknown how variable human TCR genes are”, says Gunilla Karlsson Hedestam, professor at the department of microbiology, tumor and cell biology at Karolinska Institutet and the study’s lead author.

    Using deep sequencing of blood samples, the researchers examined TCR genes in 45 people originating from sub-Saharan Africa, East Asia, South Asia and Europe. The researchers showed that these genes vary greatly between different persons and population groups. The results were confirmed by analyses of several thousand additional cases from the 1000 Genomes project.

    “We found that every individual, other than identical twins, has a unique set of TCR gene variants. These differences reveal possible mechanisms underlying the wide range of responses to infections and vaccines that we observe at the population level”, says Martin Corcoran, the first author of the study.

    “We discovered 175 new gene variants, which doubles the number of known TCR gene variants. An unexpected and surprising finding is that certain gene variants originate from Neanderthals and one of these is present in up to 20% of modern humans in Europe and Asia.”

    Gunilla Karlsson Hedestam explains that the variation in these genes cannot be detected with the standard methods used in whole genome sequencing, but with the development of specialized deep sequencing methods and analysis software that allow highly precise definition of B- and T-cell receptor genes, this is now possible.

    “As these genes are among the most variable in our genome, the results also provide new information about how our immune system has developed over the course of history, says Martin Corcoran. We are particularly interested in uncovering the function of the TCR variants we have inherited from Neanderthal ancestors. The frequency of these variants in modern humans suggests an advantageous function in our biology and we are keen to understand this”, adds Martin Corcoran.

    The findings and the new TCR gene database the researchers now publish can be of great importance in the development of new therapeutic approaches in the future.

    “Understanding human genetics is fundamental for the development of targeted treatments. The methods described in the study provide new opportunities, not the least in the cancer field where T-cells are central to several promising forms of immunotherapy”, says Gunilla Karlsson Hedestam.

    The results can also shed light on other areas of research.

    “The findings can lead to the development of new diagnostics and therapies in a range of medical disciplines, including precision medicine”, says Gunilla Karlsson Hedestam.

    What is the next step in your research?

    “We are now investigating the functional significance of several of the newly discovered gene variants and how this variation impacts our T-cell responses. We are also planning extended studies involving large groups of individuals to examine the role of TCR gene variation in diseases we know involve T cells, such as infectious diseases, cancer, and autoimmune disorders”, says Gunilla Karlsson Hedestam.

    Main funding for the study comes from an ERC Advanced Grant and the Swedish Research Council.  

    Publication: “Archaic humans have contributed to large-scale variation in modern human T cell receptor genes”, Martin Corcoran, Mark Chernyshev, Marco Mandolesi, Sanjana Narang, Mateusz Kaduk, Kewei Ye, Christopher Sundling, Anna Färnert, Taras Kreslavsky, Carolina Bernhardsson, Maximilian Larena, Mattias Jakobsson, Gunilla B. Karlsson Hedestam, Immunity, online February 15, doi: 10.1016/j.immuni.2023.01.026

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  • Common immune cells can prevent intestinal healing

    Common immune cells can prevent intestinal healing

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    Newswise — B cells are critical to the proper functioning of the immune system. However, researchers at Karolinska Institutet have shown that they can sometimes do more harm than good, as their numbers greatly increase after bowel damage, preventing the tissue from healing. The results, which are presented in the journal Immunity, can be of significance to the treatment of inflammatory bowel disease.

    B cells are a type of white blood cell that have an important function in the immune system, in part by producing the antibodies that attack bacteria and viruses. Previous research has shown that people with chronic inflammatory bowel disease (IBD), such as Crohn’s disease or ulcerative colitis, have many more B cells in their intestines than healthy individuals. It has therefore been proposed that B cells might affect the severity of these diseases. Researchers at Karolinska Institutet in Sweden have now tried to discover if, and if so how, B cells contribute to IBD.

    Sharp increase during healing

    “We’ve been able to show that the B cell population increases sharply in the colon during the healing of colonic lesions, and that these cells mainly accumulate in areas where the damage is severe,” says principal investigator Eduardo Villablanca, associate professor at the Department of Medicine (Solna), Karolinska Institutet. “This prevents, in turn, the interaction between two other cell types – stromal and epithelial cells – which is needed for the tissue to heal.”

    The researchers studied an experimental model of colitis and tissue from patients with ulcerative colitis, using a range of methods to analyse cell populations. Focusing particularly on how B cells affect healing in the intestinal mucosa, they found that mice lacking B cells recovered much more quickly after bowel damage than regular mice. The finding that the B cells seem to do more harm than good in colonic inflammation can be of significance to the treatment of IBD.

    Drugs that affect B cells

    “There are already approved drugs that affect the B cell response and that are used for other diseases,” says Gustavo Monasterio, postdoc in Dr Villablanca’s research group at Karolinska Institutet and one of the leading authors. “We now want to test if depleting B cells at specific time windows could also work with IBD. We also need to find out if the accumulation of B cells can have a long-term beneficial effect, such as by changing the composition of bacteria in the gastrointestinal tract.”

    The study was supported by grants from the Swedish Research Council, the Swedish Cancer Society, the Knut and Alice Wallenberg Foundation (the Wallenberg Academy Fellow programme) and the German research foundation DFG. Eduardo Villablanca has received research grants from the pharmaceutical company F. Hoffmann-La Roche and co-author Camilla Engblom is scientific consultant for the biotech company 10X Genomics Inc. Julio Saez-Rodriguez receives funding from Glaxo Smith Kline and Sanofi and consultancy fees from Travere Therapeutics.

    Publication: “B cell expansion hinders the stroma-epithelium regenerative crosstalk during mucosal healing”. Annika Frede, Paulo Czarnewski, Gustavo Monasterio, Kumar P. Tripathi, David A Bejarano, Ricardo O. Ramirez Flores, Chiara Sorini, Ludvig Larsson, Xinxin Luo, Laura Geerlings, Claudio Novella-Rausell, Chiara Zagami, Raoul Kuiper, Rodrigo A Morales, Francisca Castillo, Matthew Hunt, Livia Lacerda Mariano, Yue O. O. Hu, Camilla Engblom, Ana-Maria Lennon-Dumenil, Romy Mittenzwei, Nadine Hövelmeyer, Joakim Lundeberg, Julio Saez-Rodriguez, Andreas Schlitzer, Srustidhar Das, Eduardo J. Villablanca. Immunity, online 2 December 2022, doi: 10.1016/j.immuni.2022.11.002.

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  • Positive media coverage of cannabis studies regardless of therapeutic effect

    Positive media coverage of cannabis studies regardless of therapeutic effect

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    Newswise — In cannabis trials against pain, people who take placebos report feeling largely the same level of pain relief as those who consume the active cannabinoid substance. Still, these studies receive significant media coverage regardless of the clinical outcome, report researchers from Karolinska Institutet in Sweden in a study published in JAMA Network Open.

    “We see that cannabis studies are often described in positive terms in the media regardless of their results,” says the study’s first author Filip Gedin, postdoc researcher at the Department of Clinical Neuroscience, Karolinska Institutet. “This is problematic and can influence expectations when it comes to the effects of cannabis therapy on pain. The greater the benefit a treatment is assumed to have, the more potential harms can be tolerated.”

    The study is based on an analysis of published clinical studies in which cannabis has been compared with placebo for the treatment of clinical pain. The change in pain intensity before and after treatment were the study’s primary outcome measurement.

    The analysis drew on 20 studies published up to September 2021 involving almost 1,500 individuals.

    The results of the study show that pain is rated as being significantly less intense after treatment with placebo, with a moderate to large effect. The researchers also observed no difference in pain reduction between cannabis and placebo, which corroborates results from another recently published meta-analysis. 

    “There is a distinct and clinically relevant placebo response in studies of cannabis for pain,” says Dr Gedin.

    The researchers also examined a possible connection between the magnitude of the therapeutic effect shown by the cannabis studies and the coverage they receive in the media and in academic journals. Media presence was measured through Altmetric, which is a method of evaluating mentions in the media, in blogs and on social media. Academic impact was measured in terms of citations by other researchers.

    The analysis of media presence included a total of 136 news items in traditional media and in blogs and was categorised as positive, negative or neutral, depending on how the results were presented concerning the effectiveness of cannabis as a treatment for pain.

    The researchers found that the cannabis studies received much greater media attention than other published studies. The coverage was substantial regardless of the magnitude of the placebo response and regardless of the therapeutic effect of cannabis. They also observed no link between the proportion of positively described news about a study and the effect it reported. 

    The researchers add the caveat that their study combined trials of varying designs and quality and therefore the results should be interpreted with caution.

    This research was financed by Riksbankens Jubileumsfond (Karin Jensen). The researchers report no potential conflicts of interest.

    Publication: “Placebo Response and media attention in randomized clinical trials assessing cannabis-based therapies for pain: A systematic review and meta-analysis”, Filip Gedin, Sebastian Blomé, Moa Ponten, Maria Lalouni, Jens Fust, Andreé Raquette, Viktor Vadenmark Lundquist, William H. Thompson and Karin Jensen, JAMA Network Open, online 28 November, 2022, doi: 10.1001/jamanetworkopen.2022.43848

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