Podcasts about la jolla institute

In this episode of On AIRR, Dr. Bjoern Peters, Professor at the La Jolla Institute for Immunology (LJI), explores how high-quality data serves as the foundation for advancing AI-based immunological predictions and diagnostics. Originally from Germany, Dr. Peters began his academic journey in theoretical physics at Hamburg, focusing on quantum optics, before pivoting to biophysics during his PhD at Humboldt University. This shift was inspired by the challenge of understanding epitope presentation pathways and the limitations of epitope-prediction algorithms, which led him to work with Dr. Alessandro Sette at LJI to develop the Immune Epitope Database (IEDB) — the world's largest resource for immune epitope data. Throughout the conversation, Dr. Peters traces the evolution of epitope research, starting with his work on MHC-peptide binding predictions and expanding into broader immunological data collection. He emphasizes that high-quality datasets often outcompete algorithmic improvements and shares the story of how the IEDB was established to consolidate immune epitope data. The conversation explores the status of data standardization and use of ontologies in structuring biomedical data, particularly in immunology. Dr. Peters highlights how work done by the IEDB and the Adaptive Immune Receptor Repertoire Community (AIRR-C) in these areas is critical for advancing immunology and enabling prediction and diagnostics. Finally, the discussion covers challenges of predicting epitopes from immune repertoires, the growing interest in using AIRR sequencing for diagnostics, and the importance of rigorous, unbiased validation of prediction models for clinical applications.  Comments are welcome to the inbox of onairr@airr-community.org or on social media under the tag #onAIRR. Further information can be found here: https://www.antibodysociety.org/the-airr-community/airr-c-podcast. The episode is hosted by Dr. Ulrik Stervbo and Dr. Zhaoqing Ding.  Announcements and links Peters Lab https://www.lji.org/labs/peters-lab Tools mentioned: Immune Epitope Database (IEDB) https://www.iedb.org  Ontology for Biomedical Investigations (OBI) https://obi-ontology.org  Other: Adaptive Immune Receptor Repertoire Community (AIRR-C) https://www.airr-community.org The Antibody Society (TAbS) https://www.antibodysociety.org Antibody News Podcast, by TAbS https://www.antibodysociety.org/antibody-news-podcast Sette Lab https://www.lji.org/labs/sette-lab   

Dr. Erica Saphire is President and CEO of La Jolla Institute. Her research explains, at the molecular level, how and viruses are pathogenic and provides the roadmap for medical defense. She talks about the capabilities of cryo-electron microscopy and how it can help illuminate the mechanisms of measles viral fusion. She also discusses her role leading La Jolla Institute.

Send us a textMichael J. Burton is the CEO of the Diabetes Research Institute Foundation ( https://diabetesresearch.org/ ), a philanthropic organization which funds the Diabetes Research Institute, one of the largest and most comprehensive research centers dedicated to curing diabetes.A passionate nonprofit executive, Michael has more than 30 years of experience in leading high-impact philanthropic programs and cultivating strategic relationships to secure transformative funding. Prior to assuming the role of CEO at DRIF, Michael advanced the missions of some of the nation's most dynamic and trusted institutions including Princeton University, The Pew Charitable Trusts and the American Association for Cancer Research (AACR).Michael's accomplished nonprofit career includes significant contributions in the advancement of cancer research and care, most recently as President and CEO of Gateway for Cancer Research, a Chicago-based nonprofit engaged in funding early phase clinical research, where he began his tenure as Chief Development Officer. Prior to that, Michael served as Chief Development Officer and Executive Director of the Foundation at the AACR, the nation's oldest and largest organization dedicated to the prevention and cure of all cancers. Michael's 15 years of experience in the oncology sector also includes leading the development program at Fox Chase Cancer Center as Senior Vice President and Chief Development Officer.Before working in the field of oncology, Michael had a distinguished career in higher education, most notably at the University of Pennsylvania, where he served as Special Assistant to the President during the tenure of Judith Rodin, the first female president of an Ivy League institution; and at Temple University, where he held the title of Assistant Dean and lead the development program at the Fox School of Business. Before entering higher education, Michael served as Legislative and Press Assistant to the late Congressman Tom Lantos, the only survivor of the Holocaust ever elected to Congress. Michael is a graduate of the University of Pennsylvania, where he earned a Bachelor's degree in Communications and a Master's degree in Public Administration. Prof. Dr. Matthias von Herrath, MD is the Scientific Director of the Diabetes Research Institute (DRI) and Stacy Joy Goodman Chair at the University of Miami School of Medicine ( https://med.miami.edu/faculty/matthias-georg-von-herrath ) where he is leading the DRI mission to conduct and accelerate research to delay, prevent and ultimately find a cure for type 1 diabetes.  He is widely recognized for his groundbreaking work in understanding the molecular mechanisms of T1D, an autoimmune disease in which the body's immune system attacks and destroys insulin-producing beta cells in the pancreas, and developing novel therapies for this disease. Prof. Dr. von Herrath served as a Professor and Director for the Type 1 Diabetes Research Center at La Jolla Institute for Allergy and Immunology, and also currently serves as Vice President and Senior Medical Officer at Novo Nordisk, a global healthcare company, where he is responsible for overseeing the company's research and development efforts in diabetes care.Prof. Dr. von Herrath earned his medical degree in 1988 from Freiburg Medical School, where he also completed a Ph.D. equivalent thesis on biochemistry. His postdoctoral training included an intensive care residency at Diakonie Hospital, Freiburg.#DiabetesResearchInstituteFoundation #T1D #Insulin #IsletCellTransplant #Regeneration #Immunomodulation #Immunoregulation #Autoimmune #UniversityOfMiami #Philanthropy #NovoNordisk #Instacart  #ProgressPotentialAndPossibilities #IraPastor #PodcSupport the show

A video snippet of our conversation. Full videos of all Ground Truths podcasts can be seen on YouTube here. The audios are also available on Apple and Spotify.Shane Crotty: A Landmark Study on Upper Airway Mucosal ImmunityTranscriptThis is the first time a Ground Truths podcast is being posted simultaneous with a new publication, this one in Nature, by Professor Shane Crotty and his colleagues at La Jolla Institute for Immunology. Shane is one of the leading immunologists and virologists in the country; he and his group published in 2020 the first detailed analysis for how our immune system responds to SARS-CoV-2. Shane also, among many other notable contributions during COVID, illuminated the role of hybrid immunity vs COVID, the differences between and additivity of vaccination and infection.Today's paper in Nature is indeed a landmark contribution doing something that hasn't been done before—to understand the underpinnings of mucosal immunity of the upper airway. 100 participants had monthly nasal and nasopharyngeal swabs throughout the pandemic. With a median of >100,000 cells per swab recovered, they undertook single-cell sequencing and full characterization of the cells (tissue-resident memory B cells, CD4+ and CD8+ T cells, germinal center follicular helper T cells and B cells, etc.) to determine optimal immune protection of the upper airway, the effect of infections by different variants, breakthrough infections, vaccination, and age.Here is the transcript of our conversation about the new report with links to the audio:Eric Topol (00:06):Hello, it's Eric Topol with Ground Truths, and with me today is Professor Shane Crotty from the La Jolla Institute of Immunology (LJI), not too far away from where I work at Scripps. And Shane has been a go-to immunologist colleague here in the Mesa, and he and his colleagues were the ones that really first published the response to SARS-CoV-2 as far as the immunologic response. And today we're doing something very unique. We're going to go over for the first time in the two year plus history of Ground Truths, going to have a publication with at least simultaneous or near simultaneous podcast. Shane, welcome and congratulations on this really important paper in Nature.Shane Crotty (00:57):Thanks, Eric. Thanks for having me. Yeah, somebody asked if I was going to go over to Scripps for the podcast and I was like, yeah, we could.Eric Topol (01:06):You could. You could. But no, it's good. And it's nice having the logo of this great institute you work at right in the right corner. And you've done so many contributions with your colleagues at La Jolla Institute. It's really a privilege to have a chance to learn from you and particularly about what we're going to talk about today, which is mucosal immunity to upper airway infections, which is especially germane to COVID. And we're actually in the middle of a significant wave of COVID right now. And I guess it would maybe be fair to say, Shane, that we've never truly understood the underpinnings, the real details of upper airway mucosal immunity. Is that a fair statement?Shane Crotty (01:53):Yeah, it is a fair statement.Eric Topol (01:56):Okay. So today we're going to crack the case. This paper from you and your colleagues, of course, you're the senior author and first author, Sydney Ramirez did a remarkable study. I mean, just extraordinary. This is why we're doing a special podcast about it. Maybe you could just kind of give us the overview of the design because you were doing things that haven't been done before.Shane Crotty (02:24):Sure. And, I would say the genesis even of it goes back to what you were introducing. I mean, during the pandemic, we like a lot of scientists spent a lot of time and energy trying to help understanding immune responses to this virus, and immune memory to this virus, and what was involved in protective immunity. And we're certainly proud of the work that we did. And it was hard work. And after a while we were exhausted and we stopped.Shane Crotty (02:59):And then we came back to it after a while and said, well, the virus is still here. And so many people have contributed so much to better understanding the virus and creating vaccines. But there are clearly still things we don't understand. What are those biggest knowledge gaps and where might we be able to contribute? And really to me the biggest one was location, location, location. This is a virus that infects your nose, infects your upper airway—your nose, and throat, and oral cavity. And then obviously if you get severe disease, the severe disease and death are from the lungs. And it's just been a big knowledge gap in terms of understanding what actually occurs in those tissues immunologically and what is associated with protective immunity or what could be associated with protective immunity. And sort of looking forward what might be helpful for mucosal vaccine development from things that we could learn.Shane Crotty (04:12):So we started from what we would call the basics, and what does immune memory look like in the upper airways in normal people? And that hasn't been available really even in, and we started this two years ago, even in the biggest atlases published of the human body. There was no upper airway tissue representation at all. And that's because technically it's just tough to access and difficult to reproducibly get at. And so, we recruited people to a group of 20 to 30 people to come to LJI once a month, and just started testing out, published and unpublished sampling techniques to see were there ways where we could reproducibly sample immune cells in the upper airways from people. And once we got things, so the keys for us were you got to have enough cells that you can collect to learn something from. And luckily with modern techniques of flow cytometry and single cell sequencing, you don't need that many cells. And so, we could get a hundred thousand cells on a swab and that's enough to do a lot with. And second, how reproducible was it? So we showed, we had people come in every month for a year and we could reproducibly find the same things in their swab; same cell types in their swabs. And the third thing was that people would come back.Shane Crotty (06:05):We found that if you have good nurses doing the techniques, we could find ways that this would be a sampling approach that was tolerable and people would come back for repeat measures, which is really valuable to see what's happening in people over time. So that was what we started from in the study and built from.Eric Topol (06:27):And if I am correct, you sampled two places with the swabs, one in the nose and one of the throat. Or, I think one which you have in the paper as the MT for something about the median nasal turbinate and the other adenoid in the back of the throat. Is that right?Shane Crotty (06:50):So all the sampling is a swab into your nose. And when we were doing that, we were really excited to see the diversity of immune cells, particularly T cells and B cells, memory T cells and B cells that we isolated. They're like, wow, there's actually a lot of interesting immune memory up in there. And the lab said, oh, by the way, we're seeing T follicular helper cells (TFH). Now that happens to be my favorite cell type.Eric Topol (07:22):Why is that, Shane? Of all the cells, why do you say that's your favorite? I know you publish a lot on it.Shane Crotty (07:31):Because those are the T cells that are required for basically all neutralizing antibody responses. All high-quality antibody responses depend on—almost all high-quality antibody responses depend on—T cell help. That T cell help comes from T follicular helper cells. Antibody evolution is certainly one of the coolest processes of the immune system. And all of that depends on T follicular helper cells. So the fact that for example, you could get Omicron neutralizing antibodies even after only being vaccinated with ancestral vaccine, that's the immune system making guesses of what variants would look like. And those guesses come about through this antibody evolution that's driven by T follicular helper cells. So, it's really one of the most brilliant things the immune system does, and that's a cell type that's really key, but those processes happen in lymphoid tissue. That's what happens in lymph nodes and spleen. And here we were sampling epithelium, your nasal epithelium, so the cells didn't really belong there.Shane Crotty (08:37):And so, that's what turned the study in another direction. And we said, okay, let's figure out why is it that these cells are present in these swabs? And we had a couple of possibilities. One possibility was that the swab was going all the way back to the posterior wall of your nasopharynx, your top of your throat and sampling adenoid tissue. So adenoid tonsils and adenoids are a true lymphoid tissue and they're a mucosal lymphoid tissue. And so, we came up with multiple ways to validate that that's what we were testing. And in fact, it was the Sydney Ramirez, a clinician, and the ENTs involved who said, well, let's just look. And so, they actually did endoscopies with the swab to actually see where the swab went. We've got videos of the swabs going into the adenoid crypt in the back, and then we've got measurements of here are the cells that you find on those swabs.Shane Crotty (09:58):And what's cool about it is that, yes, so we did studies with two sets. We then shifted to doing studies with two sets of swabs. One where we essentially went “halfway back” where we were detecting that epithelium of your nasal passages and then one where it was all the way back and detecting the adenoid lymphoid tissue. So here we've got two different sites in your upper airways that are about an inch apart, and we're detecting essentially completely different cells of the immune system at those two places. And we tend to think of the cells present in that epithelial tissue as probably the sentinels, the cells that are sitting there that can potentially immediately react and try and protect you against a viral or bacterial infection. Whereas the lymphoid tissue, the adenoids, is really about generating the immune responses in the first place and priming immune responses. And that's where these germinal centers can occur, which are where the TFH are where you can get antibody evolution. And so, we found in the course of the study that with this non-invasive technique that we can.Eric Topol (11:14):By the way, I don't want to be signing up for the one way up there because I mean just a mid-nose enough for me. So wow, I got to give credit to your study participants for coming back every month for a year to have that. Some people call it a brain biopsy.Video of swab of nasopharyngeal tissueShane Crotty (11:33):Right. So I will tell you, it is a different experience than the COVID nasopharyngeal swab might've gotten through your car window. If you're actually sitting down in a comfortable space and there's a nurse doing it with these particular goals. We really found, we had a hundred people in the study and a total of 300 swabs, and the vast majority of people came back if we asked them to.Eric Topol (12:06):That's great.Shane Crotty (12:07):And we're certainly very thankful for the volunteers. Obviously they were volunteering in the first place to participate. So I'm a little hesitant about the video because I've told people to not show it to potential volunteers because it definitely doesn't encourage you to volunteer. You're like, wait, that's what's happening? But actually, I've had it done on me.Video of the swab to the nasopharynx for adenoid (lymphoid tissue) access.Eric Topol (12:37):Not that bad.Shane Crotty (12:39):It's really pretty compelling. And by doing these repeated samples, we actually now have the capacity to look at ongoing immune responses like after an infection or vaccination in people and see how that results in the immune system changing and what might be the source of the protective immunity that comes up. So we've actually got data in the paper looking at this antibody evolution in real time. So we've got affinity maturation of B cells occurring in just normal healthy adults of mucosal B cells against COVID. And so, that's really helping us learn what's possible, basically to figure out, okay, if you're going to try and make a vaccine, what types of immune cells are even possible to generate in this tissue? And where might you try and generate them? Or if you're trying to study some disease state, what are types of cells that might be problematic?Eric Topol (13:45):Yeah, I mean, I think the idea that so many of us have been pushing for a nasal vaccine to induce mucosal immunity because, as you know very well, the current shots are not very good at any durable or substantial protection from upper airway infections of COVID or SARS-CoV-2 and other infections. So I think one of the most important parts of this report is that it lends itself well to helping towards artificially, if you will, make a vaccine to get the protective features that you were able to identify. Maybe you could just [speculate], if you had the ideal nasal airway, what would the cellular profile look like?Shane Crotty (14:44):Ah, I see. Yeah, great question. So, first of all, antibodies are great. So most of my career has been dedicated to most licensed vaccines. The correlate of protection is antibodies. Antibodies clearly can be protective, and if you can get them that's excellent, so certainly I would want, in terms of the non-cellular component, I would want antibodies present, neutralizing antibodies present in it.Eric Topol (15:26):Are these IgA or IgG?Shane Crotty (15:31):Yeah, in an ideal situation, what would I want? I'd want a mix of both, basically. The IgAs look like they have a little more protective efficacy, but the IgGs, just at a molecular level have a longer half-life, stick around a little. So yeah, I'd want both. And then really the premise for most of what we do is saying, in situations where antibody isn't enough or the antibodies don't stay around long enough, or you've got a variant that now obviates the protective efficacy of that particular antibody, are there other types of protective immunity you can have? And the immune system has other stuff besides antibodies for a reason. Of the lymphocytes in your blood, most of them aren't antibody producing cells. Most of them are other things. And so, well sticking with adjacent to antibodies, those antibodies in the mucosa, I'd want them to be made by cells that were literally right there. So plasma cells living in that site so that you've got basically the highest concentration of antibodies you can get because they're not having to diffuse through the whole body. They're just already at their highest concentration right there. Now antibodies come from B cells, that's what encodes the antibodies.Shane Crotty (17:03):And so, the B cells can make neutralizing antibodies if it turns out that you haven't made enough neutralizing antibodies, or if there's a variant that escapes those, maybe there are other B cells that could make, once you get infected, more B cells that could make more antibody rapidly infection, or B cells that recognize this variant that is mismatched to the current antibodies you have. But memory B cells are basically a library of different antibody specificities representing different guesses about what viral variants or structures might look like. And so, I would want memory B cells in that upper airway tissue that could reactivate quickly. There are memory B cells in your blood and we don't know how long it takes. And that's one of the reasons we're hoping we and others build upon this study. But it might take, let's say five days for memory B cells to go from your blood into your upper airway.Eric Topol (18:06):Oh, right.Shane Crotty (18:08):That's right, you were already quite sick by that point. Instead, if memory B cells are right there, as soon as virus showed up, they got activated. Now maybe after (we're not sure yet), but maybe after 48 hours those cells are now activated and doing something useful. That would be optimal. So then we can pivot to the T cell side. So there's a fantastic recognition that T cells being physically present in tissues, tissue resident memory cells, as they're most often called, can really have fantastic protective capacities. From a lot of mouse model systems where you can see T cells are in the skin or the liver, or whatever [tissue] are already there, they're more protective than if the cells are in the blood. So if you could also have T cells essentially permanently parked in the epithelium of your nasal passages and in the adenoid, hopefully those could essentially be sentinels for protective immunity, and as soon as you get infected, those T cells would reactivate and start killing off infected cells. 'That's the mix that I would want to see. And I think there's at least some reasonable evidence in the context of COVID that people who have T cells in their upper airways maybe manage to control the virus so quickly that it's a subclinical infection; they never notice when they get infected. And so, building on those types of observations, that's what I would want.Eric Topol (19:56):That sounds good. I like that. I'd like to have that in my nasal airway. Now, just to make sure I've got this, what you found, of course, the memory B cells, the T cell memory, CD8+, that is the cell-killing T cells that you mentioned, the resident T cells. One clarification on that, they are not really going to do much until there's been some cells that have been infected with the virus, right? Then they come alive and kill those cells. So they're not immediate, but they can work pretty quickly still though, right? If they're resident T cells?Shane Crotty (20:45):Yeah, in theory it might take as little as 12 hours for a virus to infect a cell, and then you get some antigen presentation on that cell that could activate the T cell.Eric Topol (20:58):And that's all happening perhaps within the incubation phase of the virus, right?Shane Crotty (21:07):Correct. That's a tough thing to study, but conceptually that's the way people tend to sketch it out.Eric Topol (21:13):Right. Now the other part of the story is, and you alluded to it earlier, is the lymphoid tissue up there, higher up where there are these germinal centers; is there anything different you want in these germinal centers? Do they contribute to mucosal immunity that you haven't already mentioned?Shane Crotty (21:36):So they really contribute in this forward looking sense or really in the classroom kind of sense. The germinal centers are where you're basically teaching the B cells in advance of seeing the infection either with your vaccine or with your previous infection, evolving better B cells and better antibodies and hopefully instructing them where to go reside to then be ready for the next infection. If you get really great protection that next time, hopefully then you don't need to start.Eric Topol (22:14):Right. So it's like the training grounds for this coordinated response, I guess. Now you also noted this, I mean this is a rich paper, which is we're illuminating something that's never been done before in human beings. I mean it's pretty damn important and impressive. But you also found that you had an age relationship. Can you tell us about that?Shane Crotty (22:39):Sure. This is one of our favorite parts of the study. I'd say in particular for several of the clinicians who were involved, because the general conversations people have about upper airway lymphoid tissue, like your tonsils and including your adenoids, is that adults don't really have functional lymphoid tissue in the upper airway that your tonsils atrophy by the time maybe you're 20 or something. So, immunologically, functionally, what that means is if you have let's say an intranasal vaccine or you get infected with a new [virus] like SARS-CoV-2, if those would normally be the sites that start your immune response, where does it now happen? And instead what we saw was, we had such a diverse group of people in our studies—we realized we had people from age 18 to 68—and so we could directly ask, in normal healthy individuals across a large age span of adulthood is there functional mucosal lymphoid tissue? And the answer was yes, it was there. But it definitely declines over time, and it's declining on a log scale. Our simplest statement was that 75% of everybody we sampled still had functional tissue, but the younger the people were, the more functional it was, and the more germinal centers actually we saw; again these training grounds.Eric Topol (24:35):So this is really important because we know for COVID and obviously for influenza and other respiratory infections that people of advanced age are much more susceptible. And here you are finding something that supports that ,and it's almost like, the thymus, it involutes. After that, what age 20, and our lymphoid tissue [involutes]. We're just set up to fail. Old codgers, like me we're defenseless, I guess, right?Shane Crotty (25:12):So what I've liked about that in a positive sense is that it's not that all of these things go to zero. Like for example, naive T cells are definitely less abundant in people over the age of 60 than under, but they're not zero. And the mucosal lymphoid tissue is definitely less abundant in people over the age of 60, but in most people it still wasn't zero. And I always think about these things from a vaccine immunology perspective, and fundamentally the difference between getting vaccinated and infected frequently is that the whole point of the vaccine is you get to generate the immune response on your own time. And so, even if you're starting with five times fewer T cells or five times fewer germinal centers, if you're getting to do all that training ground in advance, you can end up with just as many bispecific T cells as a 20-year-old or just as many memory B cells as a 20-year-old because these things occur on an exponential scale because of the cell divisions. And so, it might take you three extra days, for example, to get to the same level, which again, if you're racing a virus, can be the difference between life and death. But if it's not a race and if you're doing it in the context of a vaccine, it's a much smaller factor. And that's some of what we've been trying to learn.Eric Topol (26:42):Now we only have started to scratch the surface of your findings. One of the things that drives me nutty in reading papers, especially from great immunologists like you, is that in each figure there's like 20 different panels. We get to one of the figures, figure three is all the way to panel W. I mean that starts with A. That gives you a little impression of the data. It's rich, another one goes to N or R. I mean we're talking about a lot of data. So I've only started to really deconvolute what you've done here, which is just an amazing study. But what are some other things that we should touch on before wrapping up?Shane Crotty (27:35):A lot of the goal in this study was to establish baselines of what is normal in humans in the upper airways. And that's one reason why in this case there actually are a lot of figure panels because we could work out a bunch of individual parts of the immune system that really hadn't been characterized in this way before. And something we really cared about was durability of immune memory. It's often talked about, well, mucosal responses are inherently short-lived. And we're like, well, what does that mean? Does that mean there's just no memory? Is it different kinds of memory? And so, this is the first measurement of memory B cells in this tissue in an antigen specific way. And we were doing it in people who had had recent COVID breakthrough infections. And we saw really the mucosal memory was stable for six months. And so, to me that's quite encouraging that it's not one month and it's gone, at least with an infection, it's at least six months and it looks like it'll project out for substantially longer.Shane Crotty (28:53):Amongst those cells, many of them are IgA. IgA is this antibody isotype that's particularly mucosal associated. And only 5% of the memory B cells circulating in blood were IgA. Whereas many of the memory B cells in the local tissue were IgA, which we think is also telling us that there's a lot of immune memory and the immune system in this tissue that we're probably not sampling in the blood. And so, sampling blood's great, right? It's accessible and we can learn a lot from it, but it does look like there is some tissue compartmentalization.Eric Topol (29:37):Oh, not a question. And the findings you had of the resident T cell is so indicative of that. And what's really striking, of course Shane, is that as we assess the immune system in people at large, we look at a lymphocyte neutrophil ratio [in the blood], we get almost nothing. And then in the course of the pandemic, you and your colleagues there provided such granular data on B and T cells, CD4 and CD8 T cells, and that you illuminated things that are not done ever clinically. These are research, high tier research labs like yours. The only question I have on before I just wrap up with the nasal vaccine story, interferon wasn't really part of this. As we know SARS-CoV-2 can shut down the interferon response, it's considered a frontline part of the defense. Where does that fit into the mucosal immunity of the upper airway?Shane Crotty (30:46):Yeah, it's really important. And that's in this basic divide we do in the immune system, the innate immune system and the adaptive immune system. So everything I was talking about is the B cells, the T cells, and antibodies. That's all the adaptive immune system. That's all virus specific. And then the innate immune system is the generalists, and really sort of the fire alarm, just sensing some danger. And definitely in COVID interferon is very important. I'm quite intrigued to see if using these techniques. I'm curious to see if some of these other aspects of the immune system can compensate somewhat for the fact that this virus. To me, if this virus has one superpower, it's its incredible ability to evade triggering interferon for as long as it does. And that has this massive cascading effect to almost everything about the pandemic essentially. And so, I'm intrigued by whether in people who have immunity are there ways that these other cells of the immune system or even antibodies can do things when a viral infection occurs, that helps trigger the overall immune system to recognize that something's there, even in the absence of type 1 interferons. That's where I think for now it fits in.Eric Topol (32:14):Well. I think you've so aptly described, not surprisingly, the superpower of SARS-CoV-2, which I think a lot of people haven't realized that it's so good at shutting down that defense system. Now on the basis of you having really gotten this understanding of the mucosal immunity in the upper airway, does this make you think that the nasal vaccine that we aspire to have is more of a reality? Do you kind of know what the ideal profile might look like to keep people healthy and resist infections? Do you think this is achievable in any durable sense at high level success with a nasal spray vaccine?Shane Crotty (33:04):I'm optimistic for several reasons. One is we really saw a lot of different immune memory cell types that were present, that was encouraging and seeing the B cell memory durability for at least six months—pretty flat line for that six months—was encouraging. It looks like the immune system knows how to keep these cells around if it wants to for a significant period of time. We'll have to do more in follow up. But again, it was encouraging. Third, we had some people who were vaccinated only and some people who had breakthrough infections. And really in the vaccinated only, we didn't see T cell memory in the upper airways. And I actually consider that encouraging because it suggests local exposure does give you the memory and exposure in your arm really doesn't. So I think there is something to improve upon. It can be improved upon. And lastly, I get asked all the time, I'm sure you get asked all the time: Why aren't there more intranasal vaccines or inhaled vaccines, more mucosal vaccines in some way?Shane Crotty (34:25):And I think there's more than one reason, but I tend to be very practical, and I think one practical reason is there's very little to measure, to guide you in your vaccine development. If you have six ideas or six constructs that you think might work in humans as a nasal vaccine, you basically just have to pick one, try something, and hoping there's not much you can measure it clinical trials for what might be the type of response even. So for example, the FluMist vaccine, it's the only licensed inhaled vaccine, intranasal vaccine. In adults it doesn't have a clear correlate of protection. If you get vaccinated with that, your circulating antibody responses don't increase, but also increases in nasal antibody didn't correlate with protection well. So, what does that mean? That probably means there's other things going on up there that could be indicative of protection but weren't being measured before. So I'm hopeful with these types of approaches. Now, if you're an intranasal vaccine developer, you maybe have 4, 5, 6, 7, 8 ideas or constructs. If you can try those in a few people and make these different measurements and you've got your favorite immune profile that you might, now you have something to, it's more of an engineering problem. It's not a throwing a dart problem. You're like, yeah, this has given me the type of response that I like and I'm going to try and push this into clinical trials. So those are the things that I'm optimistic about moving forward.Eric Topol (36:04):Well, I love it because we really need it. And if anybody's optimistic that means a lot; it's yours. What you've done here has been quite extraordinary because you defined for the first time really the underpinnings of the mucosal immune response, the upper airway, you did it by age, you did it by variant, you did it by vaccine and infection. And most importantly, perhaps for longer term is you established what are the desirable features to have, which didn't exist before. It seemed like whatever I read for nasal vaccines, they were measuring some IgA or IgG, and they didn't get down to the memory B cells and the tissue resident T cells, memory cells, and all these other things that you found. You did all this single cell sequencing and flow cytometry. The work is just really fantastic. So Shane, just in closing, I just want to congratulate you.Eric Topol (37:05):You made seminal findings along the pandemic. You were the one that really illuminated hybrid immunity, the advantage of if you don't want to have an infection of COVID, but if you did have that and a vaccine, you kind of had some extra synergy, if you will. But here you've done something, you and your team. Unique. Congratulations on that. No surprise that it's in Nature this week. I'm sure a lot of people will share your optimism that we will have something beyond just shots in the future because COVID isn't going away. There's other respiratory pathogens. And finally, somebody did the right study, who knows immunology inside and out. So Shane, thanks very much.Shane Crotty (37:52):Thanks Eric. Very much appreciated particularly coming from you.*****************************************Thanks for listening, reading or watching!The Ground Truths newsletters and podcasts are all free, open-access, without ads.Please share this post/podcast with your friends and network if you found it informativeVoluntary paid subscriptions all go to support Scripps Research. Many thanks for that—they greatly helped fund our summer internship programs for 2023 and 2024.Thanks to my producer Jessica Nguyen and Sinjun Balabanoff for audio and video support at Scripps Research.Note: you can select preferences to receive emails about newsletters, podcasts, or all I don't want to bother you with an email for content that you're not interested in. Get full access to Ground Truths at erictopol.substack.com/subscribe

Dr. Miguel Reina-Campos is an Assistant Professor at the La Jolla Institute for Immunology in La Jolla, California. The Reina lab seeks to understand the underlying principles governing tissue immune networks that enable robust and long-term protection against infection and tumors. In this conversation, Miguel and Kellen talk about cancer, metabolism, tissue resident memory T cells, spatial transcriptomics, advice for postdocs pursuing academia, and much more. Reina Lab: https://www.lji.org/labs/reina-lab/ Reina BioRxiv 2024: https://pubmed.ncbi.nlm.nih.gov/38585842/ Reina Nature 2023: https://pubmed.ncbi.nlm.nih.gov/37648857/ Reina Cancer Cell 2019: https://pubmed.ncbi.nlm.nih.gov/30827887/ Reina Nature Reviews Immunology 2021: https://pubmed.ncbi.nlm.nih.gov/33981085/ Twitter/X: @MReinaCampos To help us spread science, please consider writing a review, sharing this episode with your friends and colleagues, or donating to support our work. Please reach out to us via email (kcavagnero@gmail.com) or X (@KellenCavagnero) with any questions, comments, topic suggestions, etc.

Dr. Mitchell Kronenberg is a Professor and President Emeritus at La Jolla Institute for Immunology. His lab studies how innate-like T cells adapt to different tissue environments. He talks about his work on MAIT cells and mucosal immunology, as well as his time leading the Institute.

Toshiaki Kawakami, M.D., Ph.D. Professor, La Jolla Institute for Immunology Center for Autoimmunity and Inflammation We spoke with Professor Toshiaki Kawakami or Toshi as his colleagues and students call him. He is one of the leaders of La Jolla Institute for Immunology was established in 1988 by a coalition of leaders from academia and industry. These leaders envisioned a unique and dynamic partnership between basic science and applied research, one that would lead to breakthroughs in the understanding of the immune system and improve human health through the development of treatments and cures for immune system disorders. Dr. Toshia's lab studies inflammatory diseases such as allergic asthma, food allergies and Crohn's disease, which have been rising in prevalence for the last several decades. He is particularly interested in histamine-releasing factor (HRF) and its role in promoting inflammation in the lung and gut. La Jolla Institute for Immunology Center for Autoimmunity and Inflammation Website: https://www.lji.org/research/research-centers/center-for-autoimmunity-and-inflammation/  

Lisa's unending journey for healthy living recently led her to discover Fountain Life, a company dedicated to revolutionizing the healthcare system in order to help people live longer and improve disease detection. It's a lofty mission and one that our guest, Fountain Life's Chief Medical and Science Officer Dr. Helen Messier, says is fundamental to the future of medicine. According to the American Cancer Society about 70% of all cancer deaths come from cancers for which there are currently no proven screening tests. So imagine if we could consistently find cancer at stage zero when it's most easily cured? Fountain Life claims their data-driven approach enables them to find cancer, cardiac, metabolic, and neurodegenerative disease early, before they can cause harm. Dr. Messier received a Bachelor of Science and a PhD in Molecular Immunology from the University of Alberta. She completed post-doctoral studies at the La Jolla Institute for Allergy and Immunology in San Diego, CA and received her MD from the University of Calgary. She's board certified in family medicine. In addition to leading the company's clinical and scientific programs, Dr. Messier will establish Fountain Life University to train Fountain Life certified practitioners and lead the effort to gain insights and publish findings from Fountain Life's vast amount of data. In addition to being related to the Hall of Fame hockey player Mark Messier, she found out on this episode that she's about to be related to the McCaffreys. Listen on for an informative conversation about a critical topic, which ends with a fun reveal. To learn more about Fountain Life's mission, offerings, and locations, visit their website. A reminder that you can watch this episode on our YouTube channel. Thanks as always for listening!

Dr. Alessandro Sette is a Center Head, Division Head, and Professor at the La Jolla Institute of Allergy and Immunology. His lab focuses on understanding the immune response, measuring immune activity, and developing disease intervention strategies against cancer, autoimmunity, allergy, and infectious diseases. He talks about bringing a biotech mindset back to academia, cross-reactive T cell responses to SARS-CoV-2, and compiling an immune-epitope database.

Why do autoimmune diseases mostly affect women? How come eight of the last ten drugs recalled by the FDA posed greater health risks for women than men? Dr. Erica Ollmann Saphire, President/CEO of La Jolla Institute for Immunology, breaks down her cutting-edge research on sex-based differences in the immune system. She explains why it matters, what women can do about it, and how it's likely to shape the future of medicine Note to All Readers: The information contained here reflects the views of AllianceBernstein L.P. or its affiliates and sources it believes are reliable as of the date of this podcast. AllianceBernstein L.P. makes no representations or warranties concerning the accuracy of any data. There is no guarantee that any projection, forecast or opinion in this material will be realized. Past performance does not guarantee future results. The views expressed here may change at any time after the date of this podcast. This podcast is for informational purposes only and does not constitute investment advice. AllianceBernstein L.P. does not provide tax, legal or accounting advice. It does not take an investor's personal investment objectives or financial situation into account; investors should discuss their individual circumstances with appropriate professionals before making any decisions. This information should not be construed as sales or marketing material or an offer or solicitation for the purchase or sale of any financial instrument, product or service sponsored by AllianceBernstein or its affiliates. The [A/B] logo is a registered service mark of AllianceBernstein, and AllianceBernstein® is a registered service mark, used by permission of the owner, AllianceBernstein L.P. © 2023 AllianceBernstein L.P.

In this episode, Kellen speaks with Dr. Mitchell Kronenberg. Mitch is the chief scientific officer of the La Jolla Institute for Immunology, an adjunct professor at UC San Diego, and the co-director of a collaborative effort between the La Jolla Institute and UC San Diego called the Program in Immunology. Mitch and Kellen talk about unconventional T cells, autoimmunity, barrier immunity, chimeric antigen receptor (CAR) T cells, and the future of immunology. They also discuss Mitch's philosophies related to science, mentorship, and life. Recent Kronenberg lab paper with intravital microscopy: https://pubmed.ncbi.nlm.nih.gov/35905286/ Kronenberg lab website: https://www.lji.org/labs/kronenberg/ Mitch's Wikipedia page: https://en.wikipedia.org/wiki/Mitchell_Kronenberg Correction: When Kellen mentioned the published CAR T trial in human autoimmunity, he misspoke and said multiple sclerosis (MS) but the trial he was referring to was in patients with lupus. That said, published preclinical data suggests CAR T therapy may also work in MS patients. CAR T cell therapy in patients with lupus: https://pubmed.ncbi.nlm.nih.gov/36109639/ CAR T cell therapy in MS mouse model: https://pubmed.ncbi.nlm.nih.gov/36206355/ Thank you to our sponsors, NCI & CCMI! Please take a few minutes to write us a review wherever you listened to this podcast—it will help us communicate great science. Finally, we would love to hear from you. Please send any questions or comments to @KellenCavagnero on Twitter.

Dr. Doug Ethell, Ph.D. is Founder and CEO at Leucadia Therapeutics ( https://www.leucadiatx.com/ ), a pre-clinical-stage company focused on diagnosing, treating and curing Alzheimer's disease. Leucadia's proprietary Arethusta® medical device is designed to restore the flow of cerebrospinal fluid (CSF) through the cribriform plate to flush toxins away from the part of the brain where Alzheimer's disease first appears. The company also recently launched eight Apps that help exercise memory and cognition, including a personalized memory tracker called ProCogny ( www.procogny.com ). ProCogny allows users to play memory-intensive puzzles and games, daily Brain Boost collections of mini-puzzles, and a non-clinical version of the Leucadia Memory Test. Dr. Ethell received a Ph.D. in Neurobiology from The University of British Columbia in Vancouver, was a Human Frontiers of Science Long Term Fellow at The Max Planck Institute for Psychiatry in Munich, a Staff Scientist at The Scripps Research Institute and La Jolla Institute for Allergy & Immunology, and a faculty member at the University of California Riverside. In 2017, Dr. Ethell was Professor of Neuroscience, Chair of Graduate Faculty, and Head of Molecular Neurobiology at The Western Univ of Health Sciences before joining Leucadia Therapeutics full-time. He has published more than 85 peer-reviewed articles and presentation abstracts. In 2020 Dr. Ethell published a novel: "Remembering Apples: A race to cure Alzheimer's disease" ( https://www.amazon.com/Remembering-Apples-race-Alzheimers-disease/dp/1735106607 ). Support the show

Wade is a PhD student of Biological Engineering at The University of California, San Diego and a member of The Rao Lab at the La Jolla Institute of Immunology. In this episode Wade and I talk towards his thesis and lab program, video games, investing in crypto, cloning, dieting, eating out, Tim Ferriss's 4 hour work week, food delivery services, automating tasks, decision fatigue, ASOT 1000, elk hunting, EconTalk's Russ Roberts,  and Tai Lopez.Support the show

In this Buddisode, we sit down with Dr. Simon Bélanger from the La Jolla Institute of Immunology (currently at Vir Biotechnology) to discuss his work on a transcription factor that can define early T follicular helper cell fate.

In this episode, Joaquin Reyna joins us to discuss his team's journey to winning the D Challenge 2021. Specifically by exploring the Genetics of Type 1 Diabetes through GWAS, eQTLs, Chromatin Looping. Ask the Expert is a ~30 minute digital cafe experience where scientists and grad students can meet and exchange with thought leaders in the field of type 1 diabetes. Link below to sign up for a seat in the cafe! https://thesugarscience.org/ask-the-expert/

Episode 54 of the Long Covid Podcast is a chat with Elizabeth Dreicer, CEO of Consuli. We chat a load about what Consuli does, and the study into Long Covid & immunology with La Jolla Institute of Immunology. It's a fascinating discussion so really interesting to everyone!Consuli.netConsuli Long Covid Study InformationLa Jolla Institute for Immunology~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~The Long Covid Podcast is self-produced & self funded. If you enjoy what you hear and are able to, please Buy me a coffee or purchase a mug to help cover costs.Share the podcast, website & blog: www.LongCovidPodcast.comFacebook @LongCovidPodcastInstagram & Twitter @LongCovidPodFacebook Support GroupSubscribe to mailing listPlease get in touch with feedback and suggestions or just how you're doing - I'd love to hear from you! You can get in touch via the social media links or at LongCovidPodcast@gmail.comZBiotics Pre-Alcohol ProbioticBreaks down the byproduct of alcohol responsible for rough mornings after drinking.Brand Support the show

Broccoli Reduces Your Risk of Four Major Diseases University of Illinois, June 23, 2022   It's one of the most advantageous veggies you can eat, and love it or hate it, broccoli offers an array of health benefits. University of Illinois researchers have identified candidate genes controlling the accumulation of phenolic compounds in broccoli. Consumption of phenolic compounds, including certain flavonoids, is associated with a lower risk of coronary heart disease, type II diabetes, asthma, and cancer.   Sulforaphane in broccoli can also help to prevent or slow the progress of one of the most common forms of arthritis. Scientists have also discovered that broccoli protects the skin against the sun's harmful ultraviolet rays.  Many studies have shown that a diet rich in vegetables -- particularly brassica vegetables such as broccoli -- is linked to decreased risk of heart disease and stroke. The researchers crossed two broccoli lines and tested their progeny in terms of total phenolic content and their ability to neutralize oxygen radicals in cellular assays. They then used a genetic technique called quantitative trait locus analysis to search for the genes involved in generating phenolics in the most promising progeny.   By identifying the genes involved in accumulating these compounds, the researchers are one step closer to breeding broccoli and related Brassica vegetables like kale and cabbage with mega-doses of phenolic compounds.   The good news is that phenolic compounds are flavorless and stable, meaning the vegetables can be cooked without losing health-promoting qualities.   Once these vegetables are consumed, the phenolic compounds are absorbed and targeted to certain areas of the body or concentrated in the liver. Flavonoids spread through the bloodstream, reducing inflammation through their antioxidant activity.   "These are things we can't make ourselves, so we have to get them from our diets," Juvik says. "The compounds don't stick around forever, so we need to eat broccoli or some other Brassica vegetable every three or four days to lower the risk of cancers and other degenerative diseases."       Can Chronic Cellphone Use Hinder your Infant's Development? Environmental Health Trust, June 23, 2022   The two most important communicative mechanisms a newborn innately has to navigate his world are eye gaze and crying. From birth, newborns are constantly developing speech, language and communication skills with every response they command from their caregiver. As early as 5 days old, an infant can tailor his cries to reflect hunger, wetness, or discomfort as well as differentiate between mother and caregiver. Additionally, very early on newborns and infants develop prelinguistic skills: eye gaze (signaling a cue for communication) and joint attention – the ability of an infant to rest his or her gaze on a object at the same time the caregiver is looking at the same object. It is speculated that eye gaze between baby and mother is one of the most important prelinguistic skills to occur before verbal communication develops.   However, excessive cell phone usage can work to hinder the communicative rhythm and bonding experience that new mothers and infants work to establish, especially within the first six months. Communicative cues can be easily missed and trying to decode differences in newborn cries (hunger vs wet diaper) can become very difficult. As it is so important for new mothers to pay attention to different cries, constant distraction from a cell phone can alter the way the other perceives the cry, thus making it more difficult to decode.    Infants are so intuitive early on, that even the slightest delay in response to a coo or a cry can alter the way they perceive their world. Additionally, if a mother is perusing high-emotion content that is so pertinent in Facebook and social media, the overflow of emotion may inadequately color her response to the infant.   Breastfeeding can also be affected by a constant need to search the web or pursue Facebook, taking away from a significant bonding period for mother and baby, according to Erin Odom.    Physically, the mother may be present but mentally they are “somewhere else”. Many mothers use the cellphone to pass the time during the long nursing/feeding sessions of early infancy. However, infants are highly communicative during feeding, and texting and social media, when so engrossing, can distract a mother from the needs of the infant.   Chronic cell phone usage such as texting and social media usage could absolutely hinder infant development as a result of missed cues on the part of the mother.    The early months of a newborn who continuously has to wait for mother while looking at the cellphone before responding, to cry initiation for communication or other cues, the brain's connections will actually reorganize around this delay, later dampening the development of instinctual communication between mother and infant.         Yoga And Meditation Could Potentially Reverse The Genetic Effects Of Stress Coventry University (UK), Antwerp University (Belgium), Radboud University (Netherlands), June 21, 2022 A review of multiple studies focusing on the effects of mindfulness practices like yoga and meditation has found that these efforts may have the potential to reverse genetic expressions of stress. As the analysis, published in the journal Frontiers in Immunology, explains: While some MBIs, such as yoga, Tai Chi, and Qigong, have a strong physical component, others like meditation and mindfulness, breath regulation techniques, and the relaxation response (RR) are mainly sedentary. Despite the variability in these techniques, they all seem to produce various psychological benefits on healthy and clinical populations, such as the reduction of perceived stress , the alleviation of depression, decreases in anxiety, or to help in coping with a chronic medical disease. However, it is less clear what are the mechanisms underpinning the self-reported benefits of MBIs. Noting that there is some speculation that “MBIs increase gray matter in the brain regions related to emotion regulation, learning, memory, self-referential processes, and perspective taking,” they acknowledged the evidence is not conclusive and set out to delve deeper into the genetic expressions of stress and how MBIs may affect them. The review analyzed 18 studies “that used gene expression analysis in research on meditation and related MBIs [mind-body interventions].” Ultimately, they found that “meditation and related MBIs [were associated with] downregulation of NF-κB-targeted genes, which can be understood as the reversal of the molecular signature of the effects of chronic stress.”h useful information unless the relationship between gene expression and psychological variables is directly explored.”   Curcumin-piperine combo may support heart health for diabetics: Study  Baqiyatallah University of Medical Science (Iran), June 25, 2022 A combination supplement containing curcuminoids plus piperine from black pepper may support heart health for diabetics by improving the levels and functionality of cholesterol, says a new study. The combination reduced total cholesterol and non-HDL cholesterol levels, and improved levels of Lp(a) [Lipoprotein(a)], a structural component of LDL. “Although elevated Lp(a) has been considered as an important risk factor for premature atherosclerotic CVD for quite a long time independently of LDL-C and non-HDL-C levels, until very recently, the possibilities of influencing Lp(a) were extremely limited,” wrote scientists from Iran, Croatia and the USA in Complementary Therapies in Medicine . “Hence, this finding that curcuminoids as naturally occurring dietary supplements can decrease elevated Lp(a) in patients with [type 2 diabetes] is very important since such supplements are becoming more and more popular and attractive to the patients.” On the other hand, the curcumin-piperine combination significantly increased HDL levels by 1.56 mg/dL, compared to only 0.2 mg/dL in the placebo group.   Parkinson's is partly an autoimmune disease, study finds Columbia University, June 21, 2022 Researchers have found direct evidence that autoimmunity—in which the immune system attacks the body's own tissues—plays a role in Parkinson's disease, the neurodegenerative movement disorder. The findings raise the possibility that the death of neurons in Parkinson's could be prevented by therapies that dampen the immune response. The study, led by scientists at Columbia University Medical Center (CUMC) and the La Jolla Institute for Allergy and Immunology, was published in Nature. "The idea that a malfunctioning immune system contributes to Parkinson's dates back almost 100 years," said study co-leader David Sulzer, PhD, professor of neurobiology (in psychiatry, neurology and pharmacology) at CUMC. "But until now, no one has been able to connect the dots. Our findings show that two fragments of alpha-synuclein, a protein that accumulates in the brain cells of people with Parkinson's, can activate the T cells involved in autoimmune attacks. "These findings, however, could provide a much-needed diagnostic test for Parkinson's disease, and could help us to identify individuals at risk or in the early stages of the disease." Scientists once thought that neurons were protected from autoimmune attacks. However, in a 2014 study, Dr. Sulzer's lab demonstrated that dopamine neurons (those affected by Parkinson's disease) are vulnerable because they have proteins on the cell surface that help the immune system recognize foreign substances. As a result, they concluded, T cells had the potential to mistake neurons damaged by Parkinson's disease for foreign invaders. The new study found that T cells can be tricked into thinking dopamine neurons are foreign by the buildup of damaged alpha-synuclein proteins, a key feature of Parkinson's disease. "In most cases of Parkinson's, dopamine neurons become filled with structures called Lewy bodies, which are primarily composed of a misfolded form of alpha-synuclein," said Dr. Sulzer.   Vegetarian diets produce fewer greenhouse gases and increase longevity, say new studies  Loma Linda Health University, June 25, 2022 Consuming a plant-based diet results in a more sustainable environment and reduces greenhouse gas emissions, while improving longevity, according to new research from Loma Linda University Health. Based on findings that identified food systems as a significant contributor to global warming, the study focuses on the dietary patterns of vegetarians, semi-vegetarians and non-vegetarians to quantify and compare greenhouse gas emissions, as well as assess total mortality. The mortality rate for non-vegetarians was almost 20 percent higher than that for vegetarians and semi-vegetarians. On top of lower mortality rates, switching from non-vegetarian diets to vegetarian diets or even semi-vegetarian diets also helps reduce greenhouse gas emissions. The vegetarian diets resulted in almost a third less emissions compared to the non-vegetarian diets. Modifying the consumption of animal-based foods can therefore be a feasible and effective tool for climate change mitigation and public health improvements, the study concluded. "The takeaway message is that relatively small reductions in the consumption of animal products result in non-trivial environmental benefits and health benefits," said Sam Soret, Ph.D., MPH, associate dean at Loma Linda University School of Public Health and co-author of the studies. "The study analyzed more than 73,000 participants. The level of detail we have on food consumption and health outcomes at the individual level makes these findings unprecedented,” Soret said. 

Unseasonably high temperatures have been recorded in both polar regions. Glaciologist Ruth Mottram discusses why they might be occurring now and the potential impact on her own work measuring climate change in Greenland. Erica Ollmann Saphire from the La Jolla Institute for Immunology tells us about her work developing new treatments for Ebola, she is looking to develop drugs which work not just on Ebola but also a range of related Viruses. And Eugene Koonin from the United States National Institutes of Health shows us how his computer modelling of the mutations of Sars Cov -2 suggest some good news - that the virus might not be able to mutate into further dangerous forms – at least not with its current set of genetic tools. Eugene is originally from Russia and both he and President Obama's science advisor John Holdren are keen to keep up ties with scientists in Russia despite the international sanctions now being applied over the war in Ukraine. Both point out that many Russian scientists have opposed the war, and that curtailing scientific collaboration could have a detrimental effect not just on science in Russia but elsewhere as well. Image: Penguins on an ice float, Paradise Harbor, also known as Paradise Bay, behind Lemaire and Bryde Islands in Antarctica. Credit: Leamus via Getty Images) Presenter: Roland Pease Producer: Alex Mansfield

Torniamo a parlare in dettaglio della risposta immunitaria che si verifica nei soggetti colpiti da COVID-19. Quale è il ruolo dei linfociti T? Che differenza c'è nella reazione di un organismo che è stato infettato rispetto ad un soggetto che ha ricevuto il vaccino? E come reagiscono i linfociti T alla variante Omicron? Ne parliamo ancora con Alessandro Sette, professore del La Jolla Institute for Immunology della California. --- Send in a voice message: https://anchor.fm/paziente-zero/message

Using a global collaboration established to find antibodies to fight Ebola, scientists have joined together to discover treatments for COVID-19. Erica Ollmann Saphire, Phd, of the La Jolla Institute for Immunology, shares how this collaboration, known as CoVIC, furthers science and public health while creating a template for rapid discovery. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 37669]

Using a global collaboration established to find antibodies to fight Ebola, scientists have joined together to discover treatments for COVID-19. Erica Ollmann Saphire, Phd, of the La Jolla Institute for Immunology, shares how this collaboration, known as CoVIC, furthers science and public health while creating a template for rapid discovery. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 37669]

Using a global collaboration established to find antibodies to fight Ebola, scientists have joined together to discover treatments for COVID-19. Erica Ollmann Saphire, Phd, of the La Jolla Institute for Immunology, shares how this collaboration, known as CoVIC, furthers science and public health while creating a template for rapid discovery. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 37669]

Using a global collaboration established to find antibodies to fight Ebola, scientists have joined together to discover treatments for COVID-19. Erica Ollmann Saphire, Phd, of the La Jolla Institute for Immunology, shares how this collaboration, known as CoVIC, furthers science and public health while creating a template for rapid discovery. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 37669]

Using a global collaboration established to find antibodies to fight Ebola, scientists have joined together to discover treatments for COVID-19. Erica Ollmann Saphire, Phd, of the La Jolla Institute for Immunology, shares how this collaboration, known as CoVIC, furthers science and public health while creating a template for rapid discovery. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 37669]

Using a global collaboration established to find antibodies to fight Ebola, scientists have joined together to discover treatments for COVID-19. Erica Ollmann Saphire, Phd, of the La Jolla Institute for Immunology, shares how this collaboration, known as CoVIC, furthers science and public health while creating a template for rapid discovery. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 37669]

Using a global collaboration established to find antibodies to fight Ebola, scientists have joined together to discover treatments for COVID-19. Erica Ollmann Saphire, Phd, of the La Jolla Institute for Immunology, shares how this collaboration, known as CoVIC, furthers science and public health while creating a template for rapid discovery. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 37669]

Using a global collaboration established to find antibodies to fight Ebola, scientists have joined together to discover treatments for COVID-19. Erica Ollmann Saphire, Phd, of the La Jolla Institute for Immunology, shares how this collaboration, known as CoVIC, furthers science and public health while creating a template for rapid discovery. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 37669]

Using a global collaboration established to find antibodies to fight Ebola, scientists have joined together to discover treatments for COVID-19. Erica Ollmann Saphire, Phd, of the La Jolla Institute for Immunology, shares how this collaboration, known as CoVIC, furthers science and public health while creating a template for rapid discovery. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 37669]

Welcome to Protecting Your Nest with Dr. Tony Hampton. Dr Sybil Cooper is a Functional Nutritional Counselor with certifications from the AIP and Primal Health Coach Institute. She earned her PhD in Immunology from La Jolla Institute for Allergy and Immunology. In her private wellness coaching Dr. Cooper helps women bust through brain fog, fatigue, and weight gain with lifestyle changes. In their discussion, Drs. Tony and Sybil talk about the multifaceted nature of wellness, the benefits of the ketogeic diet for sleep quality, customizing cultural dishes for a low-carb diet, overactive immune systems in communities of color, intermittent fasting, and primal health coaching. Thank you for listening to Protecting Your Nest. For additional resources and information, please see the links below.    Links:   Dr. Sybil Cooper: Website Twitter Facebook Instagram AIPCertified BIPOC Scholarship   Dr. Tony Hampton: Book Website Instagram Account Facebook Page LinkedIn Account Youtube Account Advocate Aurora Healthcare Profile Dr. Hampton's Low Carb Corner (Diet Doctor) Dr. Tony Hampton's Diet Doctor Author Page   Dr. Hampton's patient handout

Shane Crotty, a lead researcher at the La Jolla Institute of Immunology, has helped us out here on the VOSD Podcast throughout the pandemic. He laid out the science of COVID vaccines when they were new. He explained the Delta variant as it swept the country. And this week, he's back in an interview with Scott Lewis to talk about Omicron — the latest variant that demonstrates, as Crotty put it, “this virus is more clever than most anyone expected.” The interview starts around minute 33 of the podcast.  Also: The hunt for San Diego Unified's next superintendent. And a court ruling puts the Midway area's future in jeopardy. Support VOSD — and this podcast — today! Give at vosd.org/podcast2021 See omnystudio.com/listener for privacy information.

Shane Crotty, a lead researcher at the La Jolla Institute of Immunology, has helped us out here on the VOSD Podcast throughout the pandemic. He laid out the science of COVID vaccines when they were new. He explained the Delta variant as it swept the country. And this week, he's back in an interview with Scott Lewis to talk about Omicron — the latest variant that demonstrates, as Crotty put it, “this virus is more clever than most anyone expected.” The interview starts around minute 33 of the podcast.  Also: The hunt for San Diego Unified's next superintendent. And a court ruling puts the Midway area's future in jeopardy. Support VOSD — and this podcast — today! Give at vosd.org/podcast2021 See omnystudio.com/listener for privacy information.

​​On this episode of Feudal Future,  hosts Joel Kotkin and Marshall Toplansky are joined by Jill Stewart, organizational and political strategist, and Steve Pontell, a leading voice on community development, housing affordability and neighborhood transformation, to discuss the truth behind affordable housing. Jill Stewart was the Managing Editor at LA Weekly and laweekly.com. At LA Weekly, she oversaw a team of print and digital journalists who pursue the newspaper's brand of digital hyper-localism and analytical, print journalism. She also oversaw the newspaper's video team and video productions.Steve PonTell is the Chief Executive Officer and President of National CORE. In 1996, Steve founded the La Jolla Institute, a California-based nonprofit think tank that advances a better understanding of the critical elements necessary for both communities and corporations to achieve sustainable economic competitiveness. He is a nationally recognized authority on community development and creating forward-thinking organizations to maximize evolving market environments. Steve has a Bachelor of Science from California Polytechnic State University San Luis Obispo in City and Regional Planning and an EMBA from Claremont Graduate University's Drucker School of Business.Join the 'Beyond Feudalism' Facebook group to share your story, ask questions and connect with other citizen leaders: https://www.facebook.com/groups/beyondfeudalismTweet thoughts: @joelkotkin, @mtoplansky, #FeudalFuture #BeyondFeudalismLearn more about Joel's book 'The Coming of Neo-Feudalism': https://amzn.to/3a1VV87Sign Up For News & Alerts: http://joelkotkin.com/#subscribeThis show is presented by the Chapman Center for Demographics and Policy, which focuses on research and analysis of global, national and regional demographic trends and explores policies that might produce favorable demographic results over time.

Shane Crotty and his team at the La Jolla Institute of Immunology have been studying viruses for a long time. We wanted to talk to him again. He first joined our podcast in March when vaccines were first becoming available and we knew a lot less. Now, after a few months and a few major variants of the virus, we have new questions. Like, why is Delta so much worse? Is it OK to go to concerts and ball games? What's the deal with booster shots? Crotty and host Scott Lewis get into it. The post from March: voiceofsandiego.org/topics/news/bonus-podcast-its-all-a-race-interview-with-an-immunologist Keep up with the region's most important news at vosd.org/newsletters See omnystudio.com/listener for privacy information.

Shane Crotty and his team at the La Jolla Institute of Immunology have been studying viruses for a long time. We wanted to talk to him again. He first joined our podcast in March when vaccines were first becoming available and we knew a lot less. Now, after a few months and a few major variants of the virus, we have new questions. Like, why is Delta so much worse? Is it OK to go to concerts and ball games? What's the deal with booster shots? Crotty and host Scott Lewis get into it. The post from March: voiceofsandiego.org/topics/news/bonus-podcast-its-all-a-race-interview-with-an-immunologist Keep up with the region's most important news at vosd.org/newsletters See omnystudio.com/listener for privacy information.

We talk to La Jolla Institute of Immunology's Dr. Shane Crotty about health officials recommending that vaccinated people get a COVID-19 booster shot. Plus, with the school year starting, we talk about the latest guidance on what to do when a student tests positive for COVID-19. And, the binational Friendship Park has its 50th anniversary today, but is stil not fully reopened. A group of activists on both sides of the border is working to change that.

Red and processed meat linked to increased risk of heart disease, study shows Oxford University, July 21, 2021 Globally, coronary heart diseases (caused by narrowed arteries that supply the heart with blood) claim nearly nine million lives each year1, the largest of any disease, and present a huge burden to health systems. Until now, it has been unclear whether eating meat increases the risk of heart disease, and if this varies for different kinds of meat. Researchers at the University of Oxford's Nuffield Department of Population Health have conducted the largest systematic review of the prospective evidence to date, including thirteen cohort studies involving over 1.4 million people. The study participants completed detailed dietary assessments, and their health was tracked for up to 30 years. The results are published today in Critical Reviews in Food Science and Nutrition. Overall, the evidence from the analysis indicated that: Each 50 g/day higher intake of processed meat (e.g. bacon, ham, and sausages) increased the risk of coronary heart disease by 18%. Each 50 g/day higher intake of unprocessed red meat (such as beef, lamb and pork) increased the risk of coronary heart disease by 9%. There was no clear link between eating poultry (such as chicken and turkey) and an increased risk of coronary heart disease. The findings may be because of the high content of saturated fat in red meat, and of sodium (salt) in processed meat. High intakes of saturated fat increase levels of harmful low-density lipoprotein (LDL) cholesterol, whilst excess salt consumption raises blood pressure. Both LDL cholesterol and high blood pressure are well-established risk factors for coronary heart disease. Previous work from the same research team has also indicated that even moderate intakes of red and processed meat are associated with increased risk of bowel cancer2. Dr. Keren Papier (Nuffield Department of Population Health), co-lead author of the study, said: "Red and processed meat have been consistently linked with bowel cancer and our findings suggest an additional role in heart disease. Therefore, current recommendations to limit red and processed meat consumption may also assist with the prevention of coronary heart disease." Dr. Anika Knüppel, from the Nuffield Department of Population Health and the other co-lead author of the study, added: "We know that meat production is a major contributor to greenhouse gas emissions and we need to reduce meat production and thereby consumption to benefit the environment. Our study shows that a reduction in red and processed meat intake would bring personal health benefits too." Currently in the UK, about 10 in 100 people would be expected to eventually die from coronary heart disease. Based on the findings from the present study and current red and processed meat intakes in the UK,4 if all these 100 people reduced their unprocessed red meat intake by three-quarters (for example from four times a week to one time a week), or if they stopped consuming processed meat altogether, deaths from coronary heart disease would decrease from 10 in 100 down to 9 in 100. The studies involved in this analysis were mostly based on white adults living in Europe or the U.S.. The research team say more data are needed to examine these associations in other populations, including East Asia and Africa.   C is for Vitamin C -- a key ingredient for immune cell function Harnessing the combined power of Vitamin C and TET proteins may give scientists a leg up in treating autoimmune diseases   La Jolla Institute for Immunology and Emory University, July 22, 2021 You can't make a banana split without bananas. And you can't generate stable regulatory T cells without Vitamin C or enzymes called TET proteins, it appears.  Regulatory T cells (Tregs) help control inflammation and autoimmunity in the body. Tregs are so important, in fact, that scientists are working to generate stable induced Tregs (iTregs) in vitro for use as treatments for autoimmune diseases as well as rejection to transplanted organs. Unfortunately, it has proven difficult to find the right molecular ingredients to induce stable iTregs. Now scientists at La Jolla Institute for Immunology and Emory University School of Medicine report that Vitamin C and TET proteins can work together to give Tregs their life-saving power.  "Vitamin C can be used to stabilize iTregs generated in vitro," says LJI Instructor Xiaojing Yue, Ph.D., who served as co-first author for the EMBO Reports study. "We hope that these kinds of induced Tregs can be used in the future for treatment of autoimmune diseases and organ transplantation." The recent study, led by LJI Professor Anjana Rao, Ph.D., and Emory Instructor Benjamin G Barwick, Ph.D., builds on the previous discovery that Vitamin C can enhance the enzymatic activity of TET proteins and prompt the generation of stable iTregs under lab conditions. This finding was encouraging, but the scientists did not want to work toward new autoimmune therapies without first analyzing the gene expression patterns and other key epigenetic features of the induced Tregs.  "We wanted to study the entire system at a whole genome level using next generation sequencing technology to better understand the molecular features of these cells," says Yue. Study co-first author Daniela Samaniego-Castruita, a graduate student at LJI, spearheaded the analysis of gene expression and epigenetic changes in the iTregs. A major type of epigenetic modification involves the DNA itself through the addition or removal of molecules called methyl groups from cytosines, one of the four DNA bases. The methyl groups can be further oxidized by TET enzymes. All of these interactions can eventually change how cells "read" the DNA code.  Another type of epigenetic change involves the alteration of DNA accessibility: whether DNA is loosely or tightly coiled. As the DNA coils unwind, regulatory regions become exposed which subsequently influence gene expression. In their analysis, the researchers found TET proteins are absolutely required for maintaining the gene expression and epigenetic features that make Tregs as what they are; and adding Vitamin C led to iTregs with similar similar gene expression and epigenetic features as normal "wild type" Tregs found in the body. The study also reveals an intriguing connection between TET enzymatic activity, Vitamin C and IL-2/STAT5 signaling. "In mice that are deficient for components of IL-2/STAT5 signaling, such as IL-2, IL-2 receptors or STAT5, the Tregs cannot develop properly or they can have impaired function," Yue says. The researchers demonstrate that on one hand, TET-deficiency in Treg cells leads to impaired IL-2/STAT5 signaling; on the other hand, Vitamin C confers iTregs enhanced IL-2/STAT5 signaling by increasing the expression level of IL-2 receptor and the functional form of STAT5, and STAT5 binding to essential regions in the genome, rendering these cells survive better in tough environments with low IL-2 supplementation. "We are looking for more small molecules to stabilize TET activity and generate induced Tregs that are even more stable," says Yue. "These induced Tregs could eventually be used to treat patients." "This research gives us a new way to think about treating autoimmune diseases," says Samaniego-Castruita.       Resveratrol ameliorates high-fat-diet-induced abnormalities in liver glucose metabolism in mice via the AMPK pathway Hebei Medical Institute (China), July 19, 2021 A new study on high fat diet is now available. According to news originating from the Department of Internal Medicine by NewsRx correspondents, research stated, “Diabetes mellitus is highly prevalent worldwide.” Our news reporters obtained a quote from the research from Department of Internal Medicine: “High-fat-diet (HFD) consumption can lead to liver fat accumulation, impair hepatic glycometabolism, and cause insulin resistance and the development of diabetes. Resveratrol has been shown to improve the blood glucose concentration of diabetic mice, but its effect on the abnormal hepatic glycometabolism induced by HFD-feeding and the mechanism involved are unknown. In this study, we determined the effects of resveratrol on the insulin resistance of high-fat-diet-fed mice and a hepatocyte model by measuring serum biochemical indexes, key indicators of glycometabolism, glucose uptake, and glycogen synthesis in hepatocytes. We found that resveratrol treatment significantly ameliorated the HFD-induced abnormalities in glucose metabolism in mice, increased glucose absorption and glycogen synthesis, downregulated protein phosphatase 2A (PP2A) and activated Ca2+/CaM-dependent protein kinase kinase b (CaMKKb), and increased the phosphorylation of AMP-activated protein kinase (AMPK). In insulin-resistant HepG2 cells, the administration of a PP2A activator or CaMKKb inhibitor attenuated the effects of resveratrol, but the administration of an AMPK inhibitor abolished the effects of resveratrol. Resveratrol significantly ameliorates abnormalities in glycometabolism induced by HFD-feeding and increases glucose uptake and glycogen synthesis in hepatocytes.” According to the news editors, the research concluded: “These effects are mediated through the activation of AMPK by PP2A and CaMKKb.”     Hundreds of chemicals, many in consumer products, could increase breast cancer risk List includes potential carcinogens that act by stimulating production of hormones that fuel breast tumors Silent Spring Institute, July 22, 2021 Every day, people are exposed to a variety of synthetic chemicals through the products they use or the food they eat. For many of these chemicals, the health effects are unknown. Now a new study shows that several hundred common chemicals, including pesticides, ingredients in consumer products, food additives, and drinking water contaminants, could increase the risk of breast cancer by causing cells in breast tissue to produce more of the hormones estrogen or progesterone. "The connection between estrogen and progesterone and breast cancer is well established," says co-author Ruthann Rudel, a toxicologist and research director at Silent Spring Institute. "So, we should be extremely cautious about chemicals in products that increase levels of these hormones in the body." For instance, in 2002, when the Women's Health Initiative study found combination hormone replacement therapy to be associated with an increased risk of breast cancer, women stopped taking the drugs and incidence rates went down. "Not surprisingly, one of the most common therapies for treating breast cancer is a class of drugs called aromatase inhibitors that lower levels of estrogen in the body, depriving breast cancer cells of the hormones they need to grow," adds Rudel. To identify these chemical risk factors, Rudel and Silent Spring scientist Bethsaida Cardona combed through data on more than 2000 chemicals generated by the U.S. Environmental Protection Agency (EPA)'s ToxCast program. The goal of ToxCast is to improve the ability of scientists to predict whether a chemical will be harmful or not. The program uses automated chemical screening technologies to expose living cells to chemicals and then examine the different biological changes they cause. Reporting in the journal Environmental Health Perspectives, Rudel and Cardona identified 296 chemicals that were found to increase estradiol (a form of estrogen) or progesterone in cells in the laboratory. Seventy-one chemicals were found to increase levels of both hormones. The chemicals included ingredients in personal care products such as hair dye, chemical flame retardants in building materials and furnishings, and a number of pesticides. The researchers don't yet know how these chemicals are causing cells to produce more hormones. It could be the chemicals are acting as aromatase activators, for instance, which would lead to higher levels of estrogen, says Cardona. "What we do know is that women are exposed to multiple chemicals from multiple sources on a daily basis, and that these exposures add up." The Silent Spring researchers hope this study will be a wakeup call for regulators and manufacturers in how they test chemicals for safety. For instance, current safety tests in animals fail to look at changes in hormone levels in the animal's mammary glands in response to a chemical exposure. And, although high throughput testing in cells has been used to identify chemicals that activate the estrogen receptor, mimicking estrogen, the testing has not been used to identify chemicals that increase estrogen or progesterone synthesis. "This study shows that a number of chemicals currently in use have the ability to manipulate hormones known to adversely affect breast cancer risk," says Dr. Sue Fenton, associate editor for the study and an expert in mammary gland development at the National Institute of Environmental Health Sciences. "Especially concerning is the number of chemicals that alter progesterone, the potential bad actor in hormone replacement therapy. Chemicals that elevate progesterone levels in the breast should be minimized." The researchers outlined a number of recommendations in their study for improving chemical safety testing to help identify potential breast carcinogens before they end up in products, and suggest finding ways to reduce people's exposures, particularly during critical periods of development, such as during puberty or pregnancy when the breast undergoes important changes. The project is part of Silent Spring Institute's Safer Chemicals Program which is developing new cost-effective ways of screening chemicals for their effects on the breast. Knowledge generated by this effort will help government agencies regulate chemicals more effectively and assist companies in developing safer products.     Antioxidant activity of limonene counteracts neurotoxicity triggered by amyloid beta 1-42 oligomers in cortical neurons University of Naples (Italy), July 19, 2021 According to news reporting from Naples, Italy, by NewsRx journalists, research stated, “Many natural-derived compounds, including the essential oils from plants, are investigated to find new potential protective agents in several neurodegenerative disorders such as Alzheimer's disease (AD).” The news editors obtained a quote from the research from School of Medicine: “In the present study, we tested the neuroprotective effect of limonene, one of the main components of the genus * * Citrus* * , against the neurotoxicity elicited by Ab [ [1-42] ] oligomers, currently considered a triggering factor in AD. To this aim, we assessed the acetylcholinesterase activity by Ellman's colorimetric method, the mitochondrial dehydrogenase activity by MTT assay, the nuclear morphology by Hoechst 33258, the generation of reactive oxygen species (ROS) by DCFH-DA fluorescent dye, and the electrophysiological activity of K [ [V] ] 3.4 potassium channel subunits by patch-clamp electrophysiology. Interestingly, the monoterpene limonene showed a specific activity against acetylcholinesterase with an IC [ [50] ] almost comparable to that of galantamine, used as positive control. Moreover, at the concentration of 10 g/mL, limonene counteracted the increase of ROS production triggered by Ab [ [1-42] ] oligomers, thus preventing the upregulation of K [ [V] ] 3.4 activity. This, in turn, prevented cell death in primary cortical neurons, showing an interesting neuroprotective profile against Ab [ [1-42] ] -induced toxicity.” According to the news editors, the research concluded: “Collectively, the present results showed that the antioxidant properties of the main component of the genus * * Citrus* * , limonene, may be useful to prevent neuronal suffering induced by Ab [ [1-42] ] oligomers preventing the hyperactivity of K [ [V] ] 3.4.”     Meditation And Yoga Change Your DNA To Reverse Effects Of Stress, Study Shows Coventry University (UK), July 22, 2021 Many people participate in practices such as meditation and yoga because they help us relax. At least those are the immediate effects we feel. But much more is happening on a molecular level, reveal researchers out of Coventry University in England. Published in the journal Frontiers in Immunology, this new research examined 18 studies on mind-body interventions (MBIs). These include practices such as mindfulness meditation and yoga. Comprehensively, these studies encompassed 846 participants over 11 years. The new analysis reveals that MBIs result in molecular changes in the human body. Furthermore, researchers claim that these changes are beneficial to our mental and physical health. Body's Response to Stress Causes Damage To elaborate, consider the effect that stress has on the body. When we are under stress, the body increases the production of proteins that cause cell inflammation. This is the natural effect of the body's fight-or-flight response. It is widely believed that inflammation in the body leads to numerous illnesses, including cancer. Moreover, scientists also deduct that a persistent inflammation is more likely to cause psychiatric problems. Unfortunately, many people suffer from persistent stress, therefore they suffer from pro-inflammatory gene expression. But there is good news! According to this new analysis out of Coventry, people that practice MBIs such as meditation and yoga can reverse pro-inflammatory gene expression. This results in a reduced risk of inflammation-related diseases and mental conditions. Lead investigator Ivana Buric from Coventry University's Centre for Psychology, Behaviour and Achievement stated: Millions of people around the world already enjoy the health benefits of mind-body interventions like yoga or meditation, but what they perhaps don't realise is that these benefits begin at a molecular level and can change the way our genetic code goes about its business. These activities are leaving what we call a molecular signature in our cells, which reverses the effect that stress or anxiety would have on the body by changing how our genes are expressed. Put simply, MBIs cause the brain to steer our DNA processes along a path which improves our wellbeing. More needs to be done to understand these effects in greater depth, for example how they compare with other healthy interventions like exercise or nutrition. But this is an important foundation to build on to help future researchers explore the benefits of increasingly popular mind-body activities.               Large-scale study finds greater sedentary hours increases risk of obstructive sleep apnea Study finds that maintaining an active lifestyle can reduce the risk of OSA, encourages physicians to recommend exercise-based interventions for those at risk Brigham and Women's Hospital, July 22, 2021 A new study by investigators from Brigham and Women's Hospital examined the relationship between active lifestyles and the risk of obstructive sleep apnea (OSA). The study followed around 130,000 men and women in the United States over a follow-up period of 10-to-18 years and found that higher levels of physical activity and lower levels of sedentary behavior were associated with a lower risk of OSA. Their results are published in the European Respiratory Journal.  "In our study, higher levels of physical activity and fewer hours of TV watching, and sitting either at work or away from home were associated with lower OSA incidence after accounting for potential confounders," said Tianyi Huang, MSc, ScD, an Associate Epidemiologist at the Brigham. "Our results suggest that promoting an active lifestyle may have substantial benefits for both prevention and treatment of OSA."  OSA is a type of sleep apnea in which some muscles relax during sleep, causing an airflow blockage. Severe OSA increases the risk of various heart issues, including abnormal heart rhythms and heart failure.  Using the Nurses' Health Study (NHS), Nurses' Health Study II (NHSII) and Health Professionals Follow-Up Study (HPFS), the research team used statistical modeling to compare physical activity and sedentary hours with diagnoses of OSA. Both moderate and vigorous physical activity were examined separately and both were strongly correlated with lower risk of OSA, showing no appreciable differences in the intensity of activity. Moreover, stronger associations were found for women, adults over the age of 65 and those with a BMI greater than or equal to 25 kg/m2.  "Most prior observational studies on the associations of physical activity and sedentary behavior with OSA were cross-sectional, with incomplete exposure assessment and inadequate control for confounding," said Huang. "This is the first prospective study that simultaneously evaluates physical activity and sedentary behavior in relation to OSA risk."  This study also differs from others because of its large sample size and detailed assessment pf physical activity and sedentary behaviors. The research team was able to take many associated factors into account, making the findings more credible.  The authors note that all collected data, both of OSA diagnosis and physical activity or sedentary behavior, were self-reported. While all study participants were health professionals, mild OSA is often difficult to detect and can remain clinically unrecognized. Furthermore, only recreational physical activity was taken into consideration, leaving out any physical activity in occupational settings. Sedentary behavior was only counted as sitting while watching TV and sitting away from home or at work.  According to Huang, the next research steps would be to collect data using actigraphy, home sleep apnea tests and polysomnography, rather than self-reports.  In light of the findings, investigators encourage physicians to highlight the benefits of physical activity to lower OSA risk.  "We found that physical activity and sedentary behavior are independently associated with OSA risk," said Huang. "That is, for people who spend long hours sitting every day, increasing physical activity in their leisure time can equally lower OSA risk. Similarly, for those who are not able to participate in a lot of physical activity due to physical restrictions, reducing sedentary hours by standing or doing some mild activities could also lower OSA risk. However, those who can lower sedentary time and increase physical activity would have the lowest risk."

The Chain looks back to earlier this year when researchers virtually convened on the one-year anniversary of the first documented case of COVID-19 in the United States. This episode brings you a panel discussion from PepTalk Protein Science and Production Week, moderated by Karla Satchell, PhD, Professor of Microbiology and Co-Director of the Center for Structural Genomics of Infectious Diseases at Northwestern University. The panel discusses the role of data integration for the rapid R&D of therapeutics and vaccines, the immediate challenges in the new year – as the Delta variant spreads this summer in the United States -- and how we can transform nearsighted lessons learned into a farsighted vision of pandemic preparedness. Moderator: Karla Satchell, PhD, Professor, Microbiology; Principal Investigator and Co-Director, Center for Structural Genomics of Infectious Diseases, Northwestern UniversityPanelists:William Gillette, PhD, Principal Scientist, Protein Expression Laboratory, Leidos Biomedical ResearchArvind Ramanathan, PhD, Computational Biologist, Argonne National LaboratoryErica Ollmann Saphire, PhD, Professor, La Jolla Institute for ImmunologyAnupam Singhal, PhD, Senior Product Manager, Antibody Discovery, Marketing, Berkeley Lights, Inc.

Den vollständigen Standpunkte-Text (inkl ggf. Quellenhinweisen und Links) findet ihr hier: https://kenfm.de/die-popel-epidemiologie-von-wolfgang-wodarg Ein Standpunkt von Wolfgang Wodarg. Früher betrachtete man sie als gesund und ließ sie in Ruhe: Kinder, die keine Symptome zeigten, deren Nase höchstens ein bisschen lief, gehörten zum Alltag an Schulen. Heute ist jeder ein potenzieller Überträger einer Tod bringenden Krankheit. Man heilt keine Krankheiten, sondern fahndet nach verborgenen Infektionen und treibt so die Fallzahlen nach oben, hält das Land dauerhaft in Angst. Das brüsk in ein kindliches Nasenloch gerammte Wattestäbchen ist zum Symbolgegenstand unserer Zeit geworden. Dr. Wolfgang Wodarg, dessen neues Buch „Falsche Pandemien. Argumente gegen die Herrschaft der Angst“ in diesen Tagen im Rubikon-Verlag erscheint, ist ein erfahrener und unerschrockener Wissenschaftsrebell der ersten Stunde. Viel angefeindet, blieb er seinen einmal für richtig erkannten Thesen treu und spezifiziert sie nun in den Tagen von Massen-Zwangstests und aufdringlichen Impfkampagnen. Er dekonstruiert die irreführenden Zahlenspiele der Angstmacher und zeigt, welche Gefahr von den — speziell für Kinder — völlig unnötigen Impfungen für die Gesundheit ausgehen. Der schwedische Gesundheitsdienst hat am 29. April 2021 nach erneuten ausführlichen Konsultationen mit den zuständigen Fachgesellschaften bestätigt: „Die PCR-Technologie, die in Tests zum Nachweis von Viren verwendet wird, kann nicht zwischen Viren, die in der Lage sind, Zellen zu infizieren, und Viren, die vom Immunsystem inaktiviert wurden, unterscheiden, und daher können diese Tests nicht verwendet werden, um festzustellen, ob jemand infektiös ist oder nicht.“ Die Schweden setzen zur Infektionskontrolle vor allem auf klinische Parameter und entscheiden danach über entsprechende Beratung für Infektiöse und deren Umgebung (1). Tests bei Gesunden oder Symptomlosen gelten in Schweden als unsinnig, so wie bis vor eineinhalb Jahren in Deutschland und anderen Teilen der Welt ja auch. Der deutschen Bevölkerung werden jetzt andere Regeln auferlegt. Sie werden den Menschen nicht von Fachgesellschaften, sondern von der Politik zugemutet. Dabei umgehen Bundesregierung und Länderchefs sogar die Möglichkeit, ihre eigenen hochqualifizierten wissenschaftlichen Nutzenbewerter einzuschalten (2). Erstaunlicherweise hat man bei uns heutzutage etwas eigentlich Selbstverständliches aus den Augen verloren: Wer zum Beispiel als Kind, Jugendlicher oder als Lehrkraft zum Unterricht geht, der ist normalerweise nicht krank. Deshalb werden mit den Testorgien in deutschen Ländern grundsätzlich normal leistungsfähige Lehrkräfte und vor allem Kinder untersucht, denen höchstens mal die Nase läuft. Diese Kinder gehören — besonders im Winter — auch in den Klassenräumen schon immer dazu. Sie durchleben schon immer ohne ernste Probleme die ersten Kontakte mit zahlreichen Atemwegsviren, tauschen diese untereinander aus und werden dadurch für viele Jahre gegen sie immun. Wenn sie nach Hause kommen, lassen sie regelmäßig auch ihre Familie an diesem Immuntraining teilnehmen. Obwohl es sich dabei um Influenza-, Parainfluenza-, Rhino-, Adeno-, RS-, Metapneumo- und eben auch Coronaviren handelt, führt das nur in sehr seltenen Fällen zu stärkeren Symptomen, sondern eher zu Husten, Schnupfen, Heiserkeit. Die allermeisten merken von ihren Viruskontakten jedoch gar nichts. Aus diesen unterschiedlich intensiven, aber regelmäßigen natürlichen Begegnungen resultiert eine zelluläre, langanhaltende Herdenimmunität gegen alles, was so ähnlich aussieht wie die kontaktierten Viren (Kreuzimmunität) (3). In einer Übersichtsarbeit aus dem berühmten La Jolla Institute (4) in San Diego werden 1.434 unterschiedliche Epitope (molekulare Merkmale) bei SARS-CoV-2-Viren aufgeführt, die gegebenenfalls von unseren T-Zellen erkannt werden und eine Abwehrreaktion auslösen. Also auch die immer wieder neuen Mutanten haben keine Chance. Es war und ist unstrittig, dass junge wie ältere Menschen beim Auftreten von Symptomen sich erst einmal auskurieren sollten, bevor sie wieder unter Leute gehen. In früheren Jahren wurde aber kaum einmal ein Kind nur wegen laufender Nase oder etwas Husten nach Hause geschickt. Es waren natürlich schon immer diese kleinen munteren „Superspreader“, welche die Viren allen anderen zugänglich gemacht haben und auch zu Hause bei Eltern und Großeltern für Viren-Updates sorgten. Die derzeitigen popeligen Präventionsmaßnahmen wären vor zwei Jahren wohl noch als Zumutung vom Schulhof gejagt worden. Und das wäre auch weiterhin berechtigt. Nun sind aber die Menschen in vielen Ländern durch Regierungen, Medien und andere Profiteure der Angst — anders als in Schweden — immer noch darauf konditioniert, nicht Kranke, sondern positive Testergebnisse als Zeichen einer Bedrohung wahrzunehmen. Wer die Freiheiten der Menschen durch Bangemachen einschränken möchte, der braucht also gar keine Kranken. Es reicht aus, genügend viele Tests dort zu machen, wo vermutlich viele positive Ergebnisse zu erwarten sind. Derzeit sind die Labore in Deutschland mit wöchentlich über 1 Million PCR-Tests bereits stark belastet. Hinzu kommen die Antigen-Selbsttests. Die Deutsche Gesellschaft für Kinder- und Jugendmedizin e.V. warnte in ihrer Stellungnahme vom 26. März 2021 (5) vor einer wöchentlich zu erwartenden halben Million falsch positiver Tests:…weiterlesen hier: https://kenfm.de/die-popel-epidemiologie-von-wolfgang-wodarg +++ KenFM jetzt auch als kostenlose App für Android- und iOS-Geräte verfügbar! 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This episode of The Chain features a live panel discussion moderated by Erica Ollmann Saphire, PhD of La Jolla Institute for Immunology. Expert panelists from academia and government assess the COVID-19 antibody and vaccine development thus far, including what did and did not go well during the pandemic. They also look towards the future and the role mRNA vaccines may play for diseases like influenza, what we learned about the United States’ ability to manufacture during surge production, and what infrastructure is still needed to fight both the current crisis and future outbreaks. Erica Ollmann Saphire, PhD, Professor, La Jolla Institute for ImmunologyPeter Hotez, MD, PhD, FASTMH, FAAP, Dean, National School of Tropical Medicine; Professor, Departments of Pediatrics, Molecular Virology & Microbiology; Co-Head, Section of Pediatric Tropical Medicine; Health Policy Scholar, Baylor College of MedicineLakshmi Krishnan, PhD, Vice-President, Life Sciences, National Research Council Canada, Government of CanadaPeter W. Marks, MD, PhD, Director, FDA CBER

In this episode, Dr. Matthias von Herrath joins us to discuss his work at the La Jolla Institute for Immunology and at pharmaceutical company Novo Nordisk. He discusses one of his recently published papers, "Anti-interleukin-21 antibody and liraglutide for the preservation of β-cell function in adults with recent-onset type 1 diabetes: a randomised, double-blind, placebo-controlled, phase 2 trial".  Full paper link: https://www.thelancet.com/journals/landia/article/PIIS2213-8587(21)00019-X/fulltext 

Renowned virologist Shane Crotty, PhD joins us to address the most important COVID-19 questions: Should people who've been vaccinated or had COVID-19 continue to wear masks and physically distance? How will each vaccine hold up to the SARS-CoV-2 variants? What does the research say about people who've already had COVID-19 who get a vaccine? How long will immunity last for the vaccines or COVID-19 infection?   Shane Crotty is a Professor at the La Jolla Institute for Immunology, Center for Infectious Disease and Vaccine Research, Crotty Lab. Prof. Crotty also has an academic appointment with the University of California San Diego.   See his full bio here: https://www.lji.org/labs/crotty/#overview Prof. Crotty on Twitter: https://twitter.com/profshanecrotty   Interviewer: Kyle Allred, Physician Assistant, Producer and Co-Founder of MedCram.com   (This interview was recorded on March 23, 2021)   Just to clarify at 8:40 in the video: Prof. Crotty is describing a theoretical person when he says "I myself am comfortable getting infected..." He hasn't had COVID, and doesn't have that opinion. He was explaining one end of the spectrum of level of concern for individuals.   FIND THIS AND OTHER PROF. CROTTY EPISODES IN VIDEO FORMAT: https://youtu.be/6aOMs1loXN0 (this interview) https://youtu.be/eK0C5tFHze8 (Dec 16, 2020) https://youtu.be/j7xsOsrDmPQ (January 5, 2021)   THE MEDCRAM WEBSITE: Visit us for videos on over 60 medical topics and CME / CEs for medical professionals: https://www.medcram.com   All coronavirus updates are at MedCram.com ad-free (including more on RNA vaccines, COVID variants, South African Variant, Johnson and Johnson vaccine for COVID 19, and more): https://www.medcram.com/courses/coronavirus-outbreak-symptoms-treatment   DISCLAIMER: MedCram medical videos are for medical education and exam preparation, and NOT intended to replace recommendations from your doctor.   #COVID19 #Coronavirus #COVID19UK

This week, Scott Lewis got to talk to Dr. Shane Crotty, an immunologist and vaccine expert who leads the Crotty Lab at the La Jolla Institute for Immunology at UC San Diego. They broke down some of the science of COVID-19 as it tries to thrive in the world — and the race between us and the virus. Plus, Crotty answers listener questions. Support explanatory journalism at vosd.org/parkermatch See omnystudio.com/listener for privacy information.

This week, Scott Lewis got to talk to Dr. Shane Crotty, an immunologist and vaccine expert who leads the Crotty Lab at the La Jolla Institute for Immunology at UC San Diego. They broke down some of the science of COVID-19 as it tries to thrive in the world — and the race between us and the virus. Plus, Crotty answers listener questions. Support explanatory journalism at vosd.org/parkermatch See omnystudio.com/listener for privacy information.

Although vaccines will go a long way to reducing the number of cases of Covid, there’s still a need for other approaches. One of these could be an engineered biomolecule, designed by virologists Anne Moscona and Matteo Porotto, that blocks SARS-CoV-2 precisely at the moment it tries to enter cells in the nose and upper airways. Roland Pease talks to Anne Moscona about this “molecular mask”. We’re already beginning to see really encouraging analyses showing that Covid vaccines are performing as well in the real world as was promised by last year’s trials. Shane Crotty of the La Jolla Institute for Immunology discusses progress so far and the question of one dose or two with Roland. Lives can be saved if there’s an early warning system for earthquakes and tsunamis. Seismologist Zhongwen Zhan at CalTech has been experimenting with a newly installed 10,000 km cable laid along the Pacific coasts of north and south America by Google, all the way from Los Angeles to Santiago. What he was looking for were subtle changes in a property of light that’s important to IT engineers, and can detect subsea earthquakes. We are still sending too much waste to landfill sites. At the Commonwealth Science Conference this week Veena Sahajwalla of the University of New South Wales explained how she is creating small scale factories that can use discarded objects such as ceramics and textiles to make new products. Listener Paula from Kenya is a computer scientist, she can’t help but notice the inequality in her workplace. With only 1 in 10 countries having female heads of state, there is no doubt that men are in charge. Paula wants to know if there is any scientific underpinning to this inequality? Perhaps it can be explained by our brains and bodies? Or does evolution weigh in? Or maybe it is all down to society and the way we raise our boys and girls. The toys and ideals we give our children must surely have an impact. And most importantly, if we want a world run by men and women equally, how can we get there? We hear how Iceland became the most gender equal country in the world. Presented by Marnie Chesterton. Produced by Caroline Steel for the BBC World Service (Image: Getty Images)

While people across the country are lining up for the vaccines, many folks still have questions about how the vaccines work, whether they’re safe and if they’ll be effective against emerging COVID variants. Here to talk to us about all of Daniela Weiskopf, PhD, a brilliant researcher at the La Jolla Institute for Immunology. Dr. Weiskopf has devoted her career to understanding the immune system’s response to viral pathogens and spent the last thirteen years studying infectious viruses relevant to human health and disease. Most recently she’s focused her efforts on COVID-19 to help understand how we can defeat this deadly disease.   Resources talked about in this episode: Guest website - www.lji.org  

Although vaccines will go a long way to reducing the number of cases of Covid, there’s still a need for other approaches. One of these could be an engineered biomolecule, designed by virologists Anne Moscona and Matteo Porotto, that blocks SARS-CoV-2 precisely at the moment it tries to enter cells in the nose and upper airways. Roland Pease talks to Anne Moscona about this “molecular mask”. We’re already beginning to see really encouraging analyses showing that Covid vaccines are performing as well in the real world as was promised by last year’s trials. Shane Crotty of the La Jolla Institute for Immunology discusses progress so far and the question of one dose or two with Roland. Lives can be saved if there’s an early warning system for earthquakes and tsunamis. Seismologist Zhongwen Zhan at CalTech has been experimenting with a newly installed 10,000 km cable laid along the Pacific coasts of north and south America by Google, all the way from Los Angeles to Santiago. What he was looking for were subtle changes in a property of light that’s important to IT engineers, and can detect subsea earthquakes. We are still sending too much waste to landfill sites. At the Commonwealth Science Conference this week Veena Sahajwalla of the University of New South Wales explained how she is creating small scale factories that can use discarded objects such as ceramics and textiles to make new products. (Image: Getty Images) Presenter: Roland Pease Producer: Deborah Cohen

T-cellsimmunitet blev en stor nyhet sommaren 2020. Vissa hävdade att t-celler, i frånvaro av antikroppar, skulle bidra till flockimmunitet mot Covid-19. Det var en felaktig slutsats, menar forskarna. Sommaren och hösten 2020 talades det om t-celler och covid-19 i nyhetsmedier världen över. Bland annat pekade forskare på att t-celler från gamla förkylningar, orsakade av äldre coronavirus, möjligen kan ge ett skydd vid covid-19. Korsimmunitet kallas det. Dessa t-celler kan göra så att sjukdomen inte blir så svår. Forskningen om covid-19 och t-cellerna blev dock övertolkad och vantolkad, menar professorn Alessandro Sette, vars forskning i ämnet publicerades i flera vetenskapliga tidskrifter under 2020. Det talades om att t-celler ensamma kanske skulle bidra till flockimmunitet, men det är en slutsats som inte har stöd i forskningen, säger han. I Vetenskapsradion På Djupet hör du om hur korsimmunitet kan fungera vid covid-19. Och om hur forskningen, enligt forskarna själva, feltolkades och utnyttjades i politiska syften. I programmet hörs Alessandro Sette, professor i immunologi vid La Jolla Institute for Immunology, Annika Karlsson, forskare i virologi vid Karolinska institutet i Huddinge, Marcus Buggert, forskare i immunologi vid Karolinska institutet i Huddinge, Kevin Ng, doktorand i immunologi vid The Francis Crick Institute i Storbritannien, Björn Olsen, läkare och professor i infektionssjukdomar vid Uppsala universitet och Akademiska sjukhuset. Reporter Lisen Forsberg Producent Peter Normark peter.normark@sverigesradio.se

Professor Shane Crotty, Ph.D. explains recent coronavirus mutations and how they might impact COVID 19 vaccines and transmission. COVID-19 research of Prof. Crotty and his team was published Jan. 6, 2021, in the prestigious Journal Science: https://science.sciencemag.org/content/early/2021/01/05/science.abf4063.full Prof. Shane Crotty is a Professor at the La Jolla Institute for Immunology, Center for Infectious Disease and Vaccine Research, Crotty Lab. Prof. Crotty also has an academic appointment with the University of California San Diego. See his full bio here: https://www.lji.org/labs/crotty/#overview Prof. Crotty on Twitter: https://twitter.com/profshanecrotty Interviewer: Kyle Allred, Physician Assistant, Producer and Co-Founder of MedCram.com THE MEDCRAM WEBSITE: Visit us for videos on over 60 medical topics and CME / CEs for medical professionals: https://www.medcram.com All coronavirus updates are at MedCram.com ad-free (including more on RNA vaccines, COVID variants, South African Variant, Johnson and Johnson vaccine for COVID 19, and more): https://www.medcram.com/courses/coronavirus-outbreak-symptoms-treatment DISCLAIMER: MedCram medical videos are for medical education and exam preparation, and NOT intended to replace recommendations from your doctor. #COVID19 #Coronavirus #COVID19UK

Professor Shane Crotty, PhD answers a series of COVID 19 vaccine questions including what are the chances of long-term side effects? How safe is RNA vaccine (i.e. Pfizer / BioNTech and Moderna Vaccines) technology? How long does mRNA from a vaccine stay in our cells? What else goes in vaccines? How long does immunity last? Why are T-Cells so important? Why does Pfizer's vaccine need to stay SO cold? Shane Crotty, PhD is a Professor at the La Jolla Institute for Immunology, Center for Infectious Disease and Vaccine Research, Crotty Lab. Professor Crotty also has an academic appointment with the University of California San Diego. See his full bio here: https://www.lji.org/labs/crotty/#overview Professor Crotty on Twitter: https://twitter.com/profshanecrotty Interviewer: Kyle Allred, Physician Assistant, Producer and Co-Founder of MedCram.com THE MEDCRAM WEBSITE: Visit us for videos on over 60 medical topics and CME / CEs for medical professionals: https://www.medcram.com All coronavirus updates are at MedCram.com ad-free (including more on RNA vaccines, COVID variants, South African Variant, Johnson and Johnson vaccine for COVID 19, and more): https://www.medcram.com/courses/coronavirus-outbreak-symptoms-treatment DISCLAIMER: MedCram medical videos are for medical education and exam preparation, and NOT intended to replace recommendations from your doctor.

Dr. Brian Sullivan, a researcher and instructor at La Jolla Institute for Immunology, and Sarah Gregory discuss endotheliopathy and platelet dysfunction in Lassa fever.

Cosa succede agli anticorpi sviluppati dai pazienti colpiti da COVID-19? Spariscono rapidamente con il tempo? E siamo sicuri che un vaccino ci possa proteggere a lungo? Ne parliamo con Alessandro Sette, professore del La Jolla Institute for Immunology. --- Send in a voice message: https://anchor.fm/paziente-zero/message

Can You Get COVID-19 More Than Once? SciFri producer Elah Feder’s friend tested positive for antibodies a few months ago—but last month, she developed COVID-19 symptoms again. So far, only a handful of cases of COVID reinfection have been confirmed, but we don’t yet know the true rates. Cases could be missed if the first or second infection is asymptomatic, and sometimes, what looks like a case of reinfection is something else entirely. Over the past few months, we’ve seen both concerns that antibodies to SARS-CoV-2 fade quickly and reassurances that immunity probably endures. Akiko Iwasaki, an immunobiologist at Yale, along with Alessandro Sette and Shane Crotty of the La Jolla Institute for Immunology, explain what we know about the immune system’s ability to remember this virus, and what cases of reinfection could mean for the efficacy of vaccines. What Is The Future of Meat? More and more people are trying meat alternatives, and for good reason: The meat industry is a major contributor to climate change. Almost 15 percent of greenhouse gas emissions come from livestock, with cattle making up about two-thirds of that. Others avoid meat because of ethical problems with slaughtering animals. Altogether, plant-based meats are having a major moment, making their way onto the shelves of major grocery stores, and the menus of fast food chains. It’s now possible to eat a burger that tastes, looks, and feels like beef—while being entirely made of plants. Some scientists are devoting their careers to creating a future where more meat comes from plants, or even cells grown in a lab. Joining Ira to mull over the future of meat is Pat Brown, CEO of Impossible Foods, and Isha Datar, executive director of New Harvest, a non-profit that promotes the research and development of cell-based animal products.  

Il prof. Alessandro Sette del La Jolla Institute for Immunology torna a Paziente Zero per spiegare il risultato di un suo recente studio in cui evidenzia la correlazione tra linfociti e severità del contagio da COVID-19. --- Send in a voice message: https://anchor.fm/paziente-zero/message

Podcast: The Science Hour (LS 53 · TOP 0.5% what is this?)Episode: Covid- 19 – Good news on immunityPub date: 2020-11-22Tests on patients for up to 8 months following their infection with SARS- CoV-2 suggests an immune response can persist. Alessandro Sette and Daniela Weiskopf at the La Jolla Institute in California are optimistic this could mean vaccines would also confer long lasting immunity. An analysis of samples from Kenya's blood banks by Sophie Uyoga at the KEMRI-Wellcome Research Programme reveals far more people in Kenya contracted the virus than was previously know. The figures mean Kenya has similar levels of infection to many European countries. And a study of mosquitoes by Louis Lambrechts of the Pasteur Institute in Paris reveals why Zika, a virus originating in Africa is much more prevalent in other parts of the world. We also look at the future of the Nile. Ethiopia is building a massive Dam which will have consequences for Sudan and Egypt who are reliant on the Nile's waters says hydrologist Hisham Eldardiry from the University of Washington, Seattle. Every year, Western Afghanistan is hit with a fierce 120-day wind, and listener Hamid wants to know what causes this phenomenon? He's from the city of Herat, where what starts as a gentle breeze in the morning can pick up to become a dangerous gale just a few hours later, devastating buildings and causing power outages. The BBC's Abdullah Elham in Kabul tells us the country has plenty of other ‘friendly' wind but this one is considered ‘fierce'. CrowdScience talks to Professor Amir Aghakouchak to discover more about the phenomenon, and learns about the pollution problems Herat's summer storm causes in neighbouring Iran. But it's not all bad news. Professor Lorraine Remer explains how NASA used satellites to map how wind transport Saharan sand almost half way round the world, fertilising the Amazon rainforest. [IMAGE CREDIT: Getty Images]The podcast and artwork embedded on this page are from BBC World Service, which is the property of its owner and not affiliated with or endorsed by Listen Notes, Inc.

Tests on patients for up to 8 months following their infection with SARS- CoV-2 suggests an immune response can persist. Alessandro Sette and Daniela Weiskopf at the La Jolla Institute in California are optimistic this could mean vaccines would also confer long lasting immunity. An analysis of samples from Kenya’s blood banks by Sophie Uyoga at the KEMRI-Wellcome Research Programme reveals far more people in Kenya contracted the virus than was previously know. The figures mean Kenya has similar levels of infection to many European countries. And a study of mosquitoes by Louis Lambrechts of the Pasteur Institute in Paris reveals why Zika, a virus originating in Africa is much more prevalent in other parts of the world. We also look at the future of the Nile. Ethiopia is building a massive Dam which will have consequences for Sudan and Egypt who are reliant on the Nile’s waters says hydrologist Hisham Eldardiry from the University of Washington, Seattle. Every year, Western Afghanistan is hit with a fierce 120-day wind, and listener Hamid wants to know what causes this phenomenon? He’s from the city of Herat, where what starts as a gentle breeze in the morning can pick up to become a dangerous gale just a few hours later, devastating buildings and causing power outages. The BBC’s Abdullah Elham in Kabul tells us the country has plenty of other ‘friendly’ wind but this one is considered ‘fierce’. CrowdScience talks to Professor Amir Aghakouchak to discover more about the phenomenon, and learns about the pollution problems Herat’s summer storm causes in neighbouring Iran. But it’s not all bad news. Professor Lorraine Remer explains how NASA used satellites to map how wind transport Saharan sand almost half way round the world, fertilising the Amazon rainforest. [IMAGE CREDIT: Getty Images]

On this episode, I go over why we might only need to get vaccinated once for COVID, according to a new study from the La Jolla Institute of Immunology. I also go over the COVID-related wrongful death lawsuit against Tyson Foods in Iowa, as well as the reason people like Monica Palmer and Bill Hartmann from Wayne County and Emily Murphy are so dangerous.Lastly, I cover President Obama's memoir release and the pitiful Charlie Brown-style Christmas tree in Rockefeller Plaza. ----more----Sources:https://www.foxnews.com/politics/michigan-gop-election-checkers-rescind-certify-vote-claim-dems-bullied-them https://apnews.com/article/donald-trump-targets-vote-certification-29da6aac9cc41e47f3095855e7af7031 https://abcnews.go.com/Politics/dominion-employees-latest-face-threats-harassment-wake-trump/story?id=74288442&cid=social_twitter_abcnp https://www.nytimes.com/2020/11/17/health/coronavirus-immunity.html https://www.theloop.ca/the-annual-christmas-tree-at-rockefeller-center-just-went-up-and-its-peak-2020/ https://iowacapitaldispatch.com/2020/11/18/lawsuit-tyson-managers-bet-money-on-how-many-workers-would-contract-covid-19/

Tests on patients for up to 8 months following their infection with SARS- CoV-2 suggests an immune response can persist. Alessandro Sette and Daniela Weiskopf at the La Jolla Institute in California are optimistic this could mean vaccines would also confer long lasting immunity. An analysis of samples from Kenya’s blood banks by Sophie Uyoga at the KEMRI-Wellcome Research Programme reveals far more people in Kenya contracted the virus than was previously know. The figures mean Kenya has similar levels of infection to many European countries. And a study of mosquitoes by Louis Lambrechts of the Pasteur Institute in Paris reveals why Zika, a virus originating in Africa is much more prevalent in other parts of the world. We also look at the future of the Nile. Ethiopia is building a massive Dam which will have consequences for Sudan and Egypt who are reliant on the Nile’s waters says hydrologist Hisham Eldardiry from the University of Washington, Seattle. (Image: Credit: Getty Images) Presenter: Roland Pease Producer: Julian Siddle

In this episode, Christine Bender joins Monica Westley to discuss her latest research at the La Jolla Institute for Immunology in the Von Herrath Laboratory. Her major project focuses on study antigen-specific CD8 T cells, in pancreas from donors with type 1 diabetes and healthy donors. Make sure to look out for her new publication coming out soon in Science Advances in October. Want to read more about her research? Checkout the following paper linked below.Islet-Expressed CXCL10 Promotes Autoimmune Destruction of Islet Isografts in Mice With Type 1 Diabetes

This week’s episode includes author Finnian Mc Causland and Associate Editor Justin Ezekowitz as they discuss angiotensin-neprilysin inhibition and renal outcomes in heart failure with preserved ejection fraction. TRANSCRIPT BELOW Dr Carolyn Lam: Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to The Journal and its editors. I'm Dr Carolyn Lam, Associate Editor from the National Heart Center and Duke National University of Singapore. Dr Greg Hundley: And I'm Greg Hundley Associate Editor, director of the Pauley Heart Center at VCU Health in Richmond, Virginia. Dr Carolyn Lam: Greg, we're going to be talking about RNEs and renal outcomes in HFpEF. Oh, you got to hold me back this is going to be such an interesting discussion. But maybe let's grab our coffees. Are you ready to talk about some of the papers in today's issue? Dr Greg Hundley: You bet. Dr Carolyn Lam: Well the first paper I have really represents a novel gene therapy approach to atrial fibrillation. So doctors led by Dr Arora from Northwestern University Feinberg School of Medicine and colleagues used a novel gene therapy approach in a canine rapid atrial pacing model of atrial fibrillation to demonstrate that NADPH oxidase-2 or NOX2 generated oxidative injury by causing upregulation of a constitutively active form of acetylcholine-dependent potassium current, or IKH is an important mechanism underlying electrical remodeling in the fibrillating atrium. Dr Greg Hundley: Wow, Carolyn, very interesting. Tell us a little bit more about this gene therapy approach. Dr Carolyn Lam: They performed targeted expression of anti-NOX2 short hairpin RNA in the intact atria of the dogs, and then subjected those animals to rapid atrial pacing for a period of several weeks to months. The novel atrial gene therapy approach prevented the development of electrical remodeling and sustained atrial fibrillation thus demonstrating for the first time a clearer causative role for NOX2 generated oxidative injury in the creation, as well as the maintenance of electrical remodeling in atrial fibrillation. Furthermore, they demonstrate that a likely cellular and molecular mechanism by which oxidative injury created a vulnerable substrate for atrial fibrillation, the results of this study yield therefore valuable mechanistic insights into the pathogenesis of atrial fibrillation and have important therapeutic implications for this clinical management. Dr Greg Hundley: Very nice, Carolyn. We need more therapies for AFib. Boy, that's so informative. Well, the next paper that I have sort of merges the world of electrophysiology with the world of imaging and it comes to us from Dr Michela Casella from Centro Cardiologico Monzino. Among 162 consecutive patients, this study evaluated the combined utility of electroanatomic voltage mapping coupled with cardiovascular magnetic resonance imaging to guide endomyocardial biopsies. Dr Carolyn Lam: Oh, so interesting. A combined noninvasive and invasive electrical guide to perform cardiac biopsies, wow. So what did they find Greg? Dr Greg Hundley: So they found that the sensitivity of pooled electroanatomic voltage mapping and cardiovascular magnetic resonance was as high as 95%. EVM and CMR together conferred an endomyocardial biopsy positive predictive value of 89%. Endomyocardial biopsy analysis allowed to reach a new diagnosis different from the suspected diagnosis in 39% of patients, complication rates were low, mostly vascular access related, with no patients requiring urgent management. Most impressive for this manuscript are the illustrative figures that are provided. It's really a great article for those performing biopsies, doing imaging, or the EP procedures that guide the biopsy process. Dr Carolyn Lam: Really nice, Greg, thanks. Now for the last paper, have you ever thought about atherosclerosis as an autoimmune disease? Dr Greg Hundley: Well, I wonder, we're learning so much about our immune systems these days, perhaps. Dr Carolyn Lam: Indeed, throughout the inflammatory response that accompanies atherosclerosis auto-reactive CD4 positive T helper cells do accumulate in the atherosclerotic plaque. Apolipoprotein B-100 or Apo B is the core protein of LDL really serves as the auto antigen that drives the generation of pathogenic T helper one cells with pro inflammatory cytokine secretion. Yet there may also exist Apo B specific CD4 positive T cells with an athero protective regulatory T cell phenotype in healthy individuals. And that relationship between the protective Apo B reactive T regulatory cells and the pathogenic T helper one cells really has remained unknown until today's paper. And this is from Dr Ley from the La Jolla Institute for Immunology and colleagues is really the first report to characterize CD4 positive T cells recognizing Apo B in the mouse with a combination of a novel MHC II tetramer and single cell transcriptomics immuno receptor sequencing and functional evaluation, and their results demonstrated an unexpected mixed phenotype of Apo B reactive auto-immune T cells in atherosclerosis and suggest an initially protective auto immune response against Apo B with a progressive derangement in clinical disease. These findings really identify Apo B auto-reactive T regulatory cells as a novel cellular target in atherosclerosis. Dr Greg Hundley: Very nice Carolyn, boy that was a beautiful summary. I've got in the mail bag just a couple of things to talk about before you get to the discussion of some research letters. There's an ECG challenge from Dr Gunaseelan involving a young patient with chest pain. And then Theresa Wang has a very nice case series involving pulmonary hypertension, entitled Pressures at an All Time High. Dr Carolyn Lam: There's also an On My Mind piece by Dr Perman on overcoming fears to save lives. So COVID-19 and the threat to bystanders CPR in out-of-hospital cardiac arrest. There's a research letter by Dr Myhre on cardiovascular hospitalizations, influenza activity, and COVID-19 measures, another by Dr Gurbel on the first inhuman experience with inhaled acetylsalicylic acid for immediate platelet inhibition, the comparison with chewed and swallowed acetylsalicylic acid. A final research letter by Dr Zurek rounds us up regarding neuregulin one inducing cardiac hypertrophy and impaired cardiac performance in post myocardial infarction rats, very surprising because we thought this was protected. So there you have it for this issue, Greg, shall we go on to our future discussion? Dr Greg Hundley: Absolutely. Dr Carolyn Lam: In patients with heart failure, chronic kidney disease is really common and associated with a higher risk of renal events than in patients without chronic kidney disease. In fact, these renal events are really increasing in prominence in the heart failure literature. And so I'm really welcoming the discussion of today's feature paper, which looks at the renal effects of angiotensin neprilysin inhibition in patients with heart failure with preserved ejection fraction in the PARAGON trial. I'm so pleased to have with us the first and corresponding author of this paper, Dr Finnian Mc Causland from Brigham and Women's hospital, as well as our associate editor Dr Justin Ezekowitz from University of Alberta. Finnian, congratulations on this beautiful paper. Could you please tell us a little bit about the overview? What motivated it, what you found? Dr Finnian Mc Causland: It's long been a passion of mine to look at this interaction or intersection between cardiology and renal events. And if the truth be told, I had a moment in my life where I thought about being a cardiologist but I was swayed in other directions during my training in Ireland. Well, I've always been very much interested in this intersection, like I said, and so I've had the opportunity to work very closely with Scott Solomon and others at the Brigham who lead many of the heart failure trials that you are all aware of much more than I have been. And this particular subset of patients with heart failure with preserved ejection fraction is a very unique population that were studied in the PARAGON-HF trial. And we thought it was a unique opportunity to look at some of the pre-specified secondary end points, which were the renal outcomes in terms of trying to figure out what the effect of this was compared to valsartan therapy in this patient population. So I think looking at this intersection between heart failure and preserved ejection fraction and the deterioration of kidney function was the primary driver to look at this in the PARAGON heart failure trial, and to really look at the comparison between sacubitril-valsartan with valsartan in this patient population. Dr Carolyn Lam: Indeed, thanks so much Finnian, and here's a confession too. I really liked nephrology during my training. (laughs) I thought it was really cool and with all the interventions, and so I really admire the many things you think about, especially in these patients, who've got multisystem disease, but okay. Moving on with PARAGON, I know that the secondary outcomes were reported and it was really a striking effect on the renal events. And so glad that you're shedding more light in it. Could you tell us what this paper added? Dr Finnian Mc Causland: Yeah, so here we really got into I suppose the depths of the renal composite outcome and just to remind everybody that was a composite of a 50% or greater decline in eGFR, the development of end stage renal disease, or death from renal causes, so this was the composite outcome that was examined. We really evaluated this in a lot more detailed breaking our composite down into its individual components, as well as looking at it in totality. And I think the big take away point was that we found there was an almost 50% reduction in this primary renal composite outcome for patients on sacubitril-valsartan compared with valsartan. Dr Carolyn Lam: And what about the components and the sort of further analyses? Dr Finnian Mc Causland: Yeah, so getting into the, I suppose the details in a little bit more granularity, the major driver of those events will be 50% or greater decline in eGFR. And that's where the majority of these events really came from over the follow-up of PARAGON. And so this was assessed that various study business throughout the course of the few years that the patients followed up with PARAGON. And I think if we look at this slope and this was clarified in terms of the overall slope analyses of the eGFR. And we thought this relatively early separation in favor of sacubitril-valsartan so that there was less decline in eGFR over time compared with valsartan. So I think this was a supportive finding from the slope analysis that really got to this 50% threshold and that many people have examined in greater detail than they had the cardiovascular literature. So it takes a fair degree of kidney function decline to really reach that threshold of 50%. And so I think this was a very repulsed finding supported by the slope analyses. Dr Carolyn Lam: Yeah, and to the audience that's listening, you have to grab hold of figure three of this paper, and that shows the eGFR slopes, which is something that's I think really important in current heart failure literature, the concept of the eGFR decline. So really nice work. Congratulations again, Finnian. Justin, could you put these findings in context for us? Dr Justin Ezekowitz: Finnian once again, congratulations on getting this analysis. Pretty complex area to try to analyze and analyze properly, given that there's an expansive renal literature out there about looking at eGFR and how you look at it. So I think there's a couple of questions that come to mind when we think about the PARAGON trial overall. When we think about the protection of the kidneys over three, four, five years, my sense was from your analysis and perhaps you could expand on it is there seems to be very few events in those people with pretty preserved eGFR, but a greater number of events in those less than 60 mils per minute, and I'm wondering if you think that there's more of a unique place for medications such as sacubitril-valsartan and that cohort and if so is it really, that's where all the action is, but there's no real difference? Or do you think there's an interaction there that we should explore? Dr Finnian Mc Causland: Thinking back to the entry criteria for PARAGON-HF, one had to have an eGFR more than 30 mils per minute at baseline. And you had to go through this kind of complex running period where you didn't have elevations of creatinine or potassium that went inside the pre-specified ranges. So after you took that element of what many people would consider hemodynamic changes, acute hemodynamic changes out of it, you were left with participants who entered the double blind randomized period. And there, I think that's where again, we started to kind of see most of the end points in terms of follow-up, which again were mostly the eGFR decline. If you go to table two of the paper, you'll see the composite, the components of the renal composite broken out into those with eGFRs of less than 60 or 60 or greater at baseline. And even in both groups, I think you'll find that again they were both driven by the 50% decline, but you only really saw the end stage renal disease events or very few deaths from renal causes in those with eGFR of less than 60 mils per minute of baseline. And I think really what that speaks to is that these are the patients with quote unquote, chronic kidney disease at baseline are the ones who have that detrimenting kidney function to begin with. And so we're more likely to progress as we know than those with more preserved kidney function. And so if you followed patients both for really good kidney function over time, it's going to take a long time before they get that really severe decline due to the compensating mechanisms that the kidney has to preserve eGFR in the face of decline. So I think once you get into the more advanced disease, you really start to see the deterioration where there's very little renal functional reserve to cope with any additional damage or hemodynamic changes. So to me, it wasn't particularly surprising that that's where the action was. To answer your second point of should we be focusing therapy here? If you look at the median eGFR in the PARAGON heart failure study was around 63 mils per minute. So about half of these patients I suppose could be classified as having impaired kidney function. If you look at it by CKD criteria it's eGFR of less than 60. And so I think there's a huge opportunity there to really think about this population in terms of trying to look for interventional studies and potentially protect patients as we've seen with this molecule, and but also with others such as SGLT-2 inhibitors, what I'm really intrigued about is if this was persistent at eGFRs below 30, because of course, one of the most devastating icons for patients with kidney disease that we deal with is the development of end stage renal disease and those who go on to hemodialysis. So if there was some mechanism to prevent those even higher risk patients from progressing, I think that would be a huge opportunity for further research in this area. Dr Justin Ezekowitz: Thanks for that very complete and thorough answer Finnian, and that actually maybe leads to putting this in context for the majority of people who will read Circulation and the audience will most likely be cardiovascular specialists and understand a lot of what you said, but could you put this in context with other studies that really are nearby to this trial, such as CREDENCE where the eGFR slope might be slightly different, or even the UK HARP-III trial where the same molecule was used, but in a different population, I wonder if you could give us some context for these findings. Dr Finnian Mc Causland: Sure, yeah. I mean, I think the UK HARP-III trial maybe is the first one to discuss since this was a comparison of sacubitril-valsartan versus irbesartan. This was a study performed in the United Kingdom and they recruited patients with chronic kidney disease, a small proportion of those patients had heart failure, but this was not any of the pre-specified entry criteria for this study. And their primary outcome was the change in measured glomerular filtration rate after 12 months. And really they found that there was no significant difference at the 12 month mark between sacubitril-valsartan versus irbesartan. And so we were asked a similar question when we presented this study in abstract form at the American Society of Nephrology meeting in Washington last year. And I think a lot of the differences potentially relate to the difference in entry criteria for the patients. But also one might argue that 12 months of follow-up may not have been enough to see these differences in eGFR slope, which tend to occur, I suppose, rather later in the course of progressive kidney disease and heart failure. And so that may be part of the reason that we didn't see the differences with UK HARP-III. In terms of CREDENCE, obviously it's a different molecule. And if you look at our main eGFR decline over time in PARAGON-HF, it was around 0.7 mils per minute, per 1.7, three meters squared per year. And so this compares with the about 1.5 mils per minute in CREDENCE, remember CREDENCE recruited patients with chronic kidney disease. PARAGON-HF recruited patients with heart failure and preserved ejection fraction. So differences in terms of the inclusion criteria right off the bat. I think other big differences where the CREDENCE compared, and it kind of flows in versus placebo, there was an active comparator in PARAGON-HF in terms of it was sacubitril-valsartan versus valsartan. So we saw differences in eGFR slope, despite an active comparator, I think was also quite telling and that there appears to be some additional renal benefit in the additional sacubitril versus blast inhibition alone. And so I think the mechanisms is a whole other area, right? For research, I don't think we're entirely clear of the underlying mechanisms of this potential renal benefit, but I think we're pretty excited in the kidney community. Where now we have several molecules that may have potential to slow kidney functional decline, SGLT-2 inhibitors being one class potentially sacubitril-valsartan in another, and the top line results from their number are just out as well. And so there's ongoing trials that are looking at kidney function outcomes there. So we're getting pretty excited and we're not quite as jealous of the cardiology community as we used to be. Dr Carolyn Lam: I couldn't think of a better way to summarize those findings and to put it into context of other very hopeful medications for the cardio renal outcomes. Thank you so much Finnian for joining us today and for publishing such a great paper with us at Circulation. And thank you, Justin, for your perspectives. Dr Justin Ezekowitz: Thanks Carolyn, and Finnian congrats to your team as well. This has been a terrific paper to be able to handle and read and look at figure three, and it tells a lot of the story of what you saw. Dr Finnian Mc Causland: Thank you very much again for the opportunity and a big shout out to everybody that worked in PARAGON-HF and especially to the support from Scott Solomon and John McMurray for getting me involved. It's a pleasure to be part of this. Dr Carolyn Lam: Thank you so much from Greg and I for joining us today, tune in again, next week. Dr Greg Hundley: This program is copyright of the American Heart Association 2020.

Edward Vizcarra is the second co-host for “Welcome to Grad School.” He is from Santa Ana, CA and is currently working on a PhD in Biomedical Science at UC, Riverside. Listen to him talk about how he became interested in science and the research he has done while at UCSD, La Jolla Institute, and UCR.

In alcuni soggetti è stato riscontrato un riconoscimento, da partei dei linfociti-T, del virus SARS-COV-2 anche in pazienti che non si erano mai malati prima. Come è possibile? Ne parliamo con Alessandro Sette, professore della divisione della scoperta dei Vaccini del La Jolla Institute for Immunology, in California. --- Send in a voice message: https://anchor.fm/paziente-zero/message

In episode 74 of Inside Covid-19, two of the scientific world's leading lights, Dr Peter Piot and Dr Thomas File, warn about thus-far overlooked long term impacts on the human body of the coronavirus; and as the world's focus swings from stemming infections to beating off the virus, we take a close look at how scientists are working on how to better identify our immune responses – and how these can be bolstered. In this episode we'll get more on antibodies and immunity from the head of Discovery's Clinical Policy unit; and in a separate analysis, the professor of Infectious Diseases and Vaccines at the La Jolla Institute of Immunology in San Diego, California. - Alec Hogg

In episode 74 of Inside Covid-19, two of the scientific world's leading lights, Dr Peter Piot and Dr Thomas File, warn about thus-far overlooked long term impacts on the human body of the coronavirus; and as the world's focus swings from stemming infections to beating off the virus, we take a close look at how scientists are working on how to better identify our immune responses – and how these can be bolstered. In this episode we'll get more on antibodies and immunity from the head of Discovery's Clinical Policy unit; and in a separate analysis, the professor of Infectious Diseases and Vaccines at the La Jolla Institute of Immunology in San Diego, California. - Alec Hogg

If the world does not curb its greenhouse gas emissions, by the end of this century, the number of people dying annually because of extreme heat will be greater than the current global death toll from infectious diseases - that’s all infectiousness diseases, from malaria to diarrhoeal diseases to HIV. This is the grim assessment of climate researchers and economists of the Climate Impact Lab in the largest global study to date of health and financial impacts of temperature-related deaths. Roland Pease talks to Solomon Hsiang of the University of California, Berkeley. UK ecologists have new insights about how diseases jump the species barrier from wildlife to humans. With a global survey of land use and biodiversity, they’ve discovered that when natural habitats are converted to farmland or urbanised, the animal species that survive the change in greatest number are those species which carry viruses and bacteria with the potential to spread to us. This is particularly the case, says Rory Gibb of the University College London, with disease-carrying rodent species, bats and birds. Do past infections by mild cold coronaviruses prepare the immune systems of some people for infection by SARS-CoV-2? Could immune memory T cells made in response to these cold viruses lessen the severity of Covid-19? Alessandro Sette and Daniela Weiskopf of the La Jolla Institute for Immunology lead the team which published the latest contributions to these questions. Anglerfish are perhaps the weirdest inhabitants of the deep sea. Their sex lives are particularly strange because finding partners in the dark expanse of the ocean abyss is hard. Females are much bigger than males. When a male finds a female, he latches on her body with his teeth and over a couple of weeks, their flesh fuses so he is permanently attached. Her blood supplies him with all the food and oxygen he needs and he becomes an ever present supply of sperm whenever she produces eggs. But this fusion should be impossible. The female’s immune system should be rejecting her partner like a mismatched organ transplant. German scientists have now discovered that these fish do this by giving up the production of antibodies and immune T cells – essential for fighting infections in all other animals including us. It was a shocking discovery for Prof Thomas Boehm at the Max Planck Institute in Freiburg. Anyone else had their flight cancelled? The COVID 19 pandemic has had a huge impact on air travel – air traffic in 2020 is expected to be down 50 per cent on last year. But beyond the obvious disruption to business and people’s lives, how might the quieter skies affect our weather and climate? One curious listener, Jeroen Wijnands, who lives next to Schiphol airport in the Netherlands, noticed how there were fewer clouds and barely any rainfall since the flights dropped off. Could airplanes affect our local weather? Also, did we learn anything from another occasion when airplanes were grounded, during the post-9/11 shutdown? How will the current period impact our future climate? Marnie Chesterton investigates this question and discovers some of the surprising effects that grounded aircraft are having: on cloud formation, forecasting and climate change. (Image: Relatives of heatstroke victims, their heads covered with wet towels, wait outside a hospital during a heatwave in Karachi. .Credit: Rizwan Tabassum/AFP via Getty Images)

If the world does not curb its greenhouse gas emissions, by the end of this century, the number of people dying annually because of extreme heat will be greater than the current global death toll from infectious diseases - that’s all infectiousness diseases, from malaria to diarrhoeal diseases to HIV. This is the grim assessment of climate researchers and economists of the Climate Impact Lab in the largest global study to date of health and financial impacts of temperature-related deaths. Roland Pease talks to Solomon Hsiang of the University of California, Berkeley. UK ecologists have new insights about how diseases jump the species barrier from wildlife to humans. With a global survey of land use and biodiversity, they’ve discovered that when natural habitats are converted to farmland or urbanised, the animal species that survive the change in greatest number are those species which carry viruses and bacteria with the potential to spread to us. This is particularly the case, says Rory Gibb of the University College London, with disease-carrying rodent species, bats and birds. Do past infections by mild cold coronaviruses prepare the immune systems of some people for infection by SARS-CoV-2? Could immune memory T cells made in response to these cold viruses lessen the severity of Covid-19? Alessandro Sette and Daniela Weiskopf of the La Jolla Institute for Immunology lead the team which published the latest contributions to these questions. Anglerfish are perhaps the weirdest inhabitants of the deep sea. Their sex lives are particularly strange because finding partners in the dark expanse of the ocean abyss is hard. Females are much bigger than males. When a male finds a female, he latches on her body with his teeth and over a couple of weeks, their flesh fuses so he is permanently attached. Her blood supplies him with all the food and oxygen he needs and he becomes an ever present supply of sperm whenever she produces eggs. But this fusion should be impossible. The female’s immune system should be rejecting her partner like a mismatched organ transplant. German scientists have now discovered that these fish do this by giving up the production of antibodies and immune T cells – essential for fighting infections in all other animals including us. It was a shocking discovery for Prof Thomas Boehm at the Max Planck Institute in Freiburg. (Image: Relatives of heatstroke victims, their heads covered with wet towels, wait outside a hospital during a heatwave in Karachi. .Credit: Rizwan Tabassum/AFP via Getty Images) Presenter: Roland Pease Producer: Andrew Luck-Baker

La inmunidad contra la Covid-19 es esencial para poder salir adelante. Sin tratamientos eficaces ni vacunas listas al día de hoy, otras pistas toman relieve en este combate: la inmunidad cruzada podría ser un arma invisible que ayuda a adquirir una protección contra el temible virus. Y los pacientes asintomáticos que han dado positivo en los tests PCR podrían estar protegidos sin saberlo, gracias a la generación de anticuerpos neutralizantes, según un estudio reciente hecho por el Hospital Universitario de Estrasburgo (CHU de Strasbourg) y el Instituto Pasteur de Francia. Inmunidad, inmunidad, inmunidad, ésa es la cuestión en esta pandemia de la Covid-19. A la fecha no se ha encontrado ningún tratamiento eficaz, y la opción de que el 60 o 70 %  de la población se contagie con el nuevo coronavirus ya no es una solución como algunos pensaban al principio, por el alto riesgo que esto conlleva. Quedan las vacunas en esta búsqueda de la inmunidad. Varias vacunas en efecto están en preparación pero faltan meses para que alguna de ellas esté lista para su uso masivo, y esto en caso de superar con éxito la fase III de los ensayos clínicos en humanos. Lea aquí: ¿Llegará algún día la vacuna para el coronavirus? También se habla de la inmunidad adquirida al contraer la Covid-19, aunque aún no se sabe cuánto tiempo dura dicha inmunidad. Ahora bien, ¿qué sucede con los pacientes asintomáticos o que tuvieron síntomas leves? ¿Adquirieron ellos también la inmunidad? Inmunidad cruzada ¿Y si la esperanza para esta pandemia fuera la llamada inmunidad cruzada, es decir, haber adquirido anticuerpos no por haberse infectado con el nuevo coronavirus, el temible SARS-Cov2,  pero con uno de los cuatro coronavirus comunes en los humanos y que provocan los resfriados comunes? Es lo que algunos expertos creen. Un estudio publicado recientemente en la revista CELL y hecho por La Jolla Institute for Imunology abre esta perspectiva. La clave, los linfocitos T, células capaces de combatir al virus agresor y en particular, los linfocitos helpers y los linfocitos citotóxicos. Este primer estudio podría comprobarse más hasta que comenzara la temporada de catarros producidos por los coronavirus comunes, en la época de invierno. Lea aquí sobre la inmunidad cruzada Y aquí también ¿Qué pasa con los pacientes asintomáticos? Otra cuestión en este vasto campo de la inmunología es la de las personas asintomáticas que resultaron positivas con el test PCR, el test que se introduce en la nariz o en la garganta en busca de material genético del virus y comprobar así la presencia del virus. Estas personas, ¿son inmunes? Al parecer, tienen anticuerpos protectores, según un estudio llevado a cabo por el hospital universitario de Estrasburgo (CHU de Strasbourg) y el Instituto Pasteur en Francia. La profesora Samira Fafi-Kremer, autora principal de este estudio, es directora del Instituto de Virología del CHU de Estrasburgo: “Es un estudio hecho con personal médico sanitario, que presentaron pocos síntomas de la Covid-19 o no muy graves. Seleccionamos a 160 personas, que habían hecho el test PCR y que habían dado positivo al SARS-CoV2. Se les hizo entonces muestras de sangre, por una parte, un test serológico para verificar la presencia de anticuerpos y por otra, un test funcional que se llama test de neutralización, que sólo se hace en laboratorios de investigación, para verificar la presencia de anticuerpos neutralizantes, es decir anticuerpos que impiden la entrada del virus en la célula.” Los resultados demostraron que no sólo las personas habían desarrollado anticuerpos, pero que conforme pasaba más tiempo, la gran mayoría (98%) generó también un tipo de protección muy eficaz, los anticuerpos llamados neutralizantes. Estos anticuerpos “neutralizan” al virus fusionándose con partes de éste. Aquí puede escuchar el programa en su versión más larga:     El estudio también reveló que por lo menos estos anticuerpos neutralizantes estaban presentes hasta los 40 días del inicio de la infección. La siguiente etapa de esta investigación será dar un seguimiento a estas personas para saber cuánto tiempo dura dicha protección. De ahí que la siguiente etapa del estudio es hacer un seguimiento a tres, seis y doce meses después de iniciada la infección para saber saber si la respuesta neutralizante persiste. Una buena noticia entonces saber que incluso las personas asintomáticas generan anticuerpos neutralizantes protectores. Entrevistadas: Africa González, presidenta de la sociedad española de inmunología y catedrática de inmunología de la Universidad de Vigo, España (entrevista preparada y hecha por Aída Palau y Lucile Gimberg), y la profesora Samira Fafi-Kremer, directora del Instituto de Virología del CHU de Estrasburgo.  

Infectious diseases have profound influences on the evolution of their host populations. In the case of humans, the host species has also shaped pathogen dynamics and virulence via a multitude of factors from changes in social organization, group size, and exploitation of varied habitats and their animals and plant resources to agriculture, technology, rapid long-distance travel, medicine and global economic integration - which all continue to shape epidemics and the human host populations. This symposium will explore how infectious agents and humans have shaped each other over the eons. Series: "CARTA - Center for Academic Research and Training in Anthropogeny" [Health and Medicine] [Science] [Show ID: 35849]

Infectious diseases have profound influences on the evolution of their host populations. In the case of humans, the host species has also shaped pathogen dynamics and virulence via a multitude of factors from changes in social organization, group size, and exploitation of varied habitats and their animals and plant resources to agriculture, technology, rapid long-distance travel, medicine and global economic integration - which all continue to shape epidemics and the human host populations. This symposium will explore how infectious agents and humans have shaped each other over the eons. Series: "CARTA - Center for Academic Research and Training in Anthropogeny" [Health and Medicine] [Science] [Show ID: 35849]

Infectious diseases have profound influences on the evolution of their host populations. In the case of humans, the host species has also shaped pathogen dynamics and virulence via a multitude of factors from changes in social organization, group size, and exploitation of varied habitats and their animals and plant resources to agriculture, technology, rapid long-distance travel, medicine and global economic integration - which all continue to shape epidemics and the human host populations. This symposium will explore how infectious agents and humans have shaped each other over the eons. Series: "CARTA - Center for Academic Research and Training in Anthropogeny" [Health and Medicine] [Science] [Show ID: 35849]

Infectious diseases have profound influences on the evolution of their host populations. In the case of humans, the host species has also shaped pathogen dynamics and virulence via a multitude of factors from changes in social organization, group size, and exploitation of varied habitats and their animals and plant resources to agriculture, technology, rapid long-distance travel, medicine and global economic integration - which all continue to shape epidemics and the human host populations. This symposium will explore how infectious agents and humans have shaped each other over the eons. Series: "CARTA - Center for Academic Research and Training in Anthropogeny" [Health and Medicine] [Science] [Show ID: 35849]

Infectious diseases have profound influences on the evolution of their host populations. In the case of humans, the host species has also shaped pathogen dynamics and virulence via a multitude of factors from changes in social organization, group size, and exploitation of varied habitats and their animals and plant resources to agriculture, technology, rapid long-distance travel, medicine and global economic integration - which all continue to shape epidemics and the human host populations. This symposium will explore how infectious agents and humans have shaped each other over the eons. Series: "CARTA - Center for Academic Research and Training in Anthropogeny" [Health and Medicine] [Science] [Show ID: 35849]

Infectious diseases have profound influences on the evolution of their host populations. In the case of humans, the host species has also shaped pathogen dynamics and virulence via a multitude of factors from changes in social organization, group size, and exploitation of varied habitats and their animals and plant resources to agriculture, technology, rapid long-distance travel, medicine and global economic integration - which all continue to shape epidemics and the human host populations. This symposium will explore how infectious agents and humans have shaped each other over the eons. Series: "CARTA - Center for Academic Research and Training in Anthropogeny" [Health and Medicine] [Science] [Show ID: 35849]

Infectious diseases have profound influences on the evolution of their host populations. In the case of humans, the host species has also shaped pathogen dynamics and virulence via a multitude of factors from changes in social organization, group size, and exploitation of varied habitats and their animals and plant resources to agriculture, technology, rapid long-distance travel, medicine and global economic integration - which all continue to shape epidemics and the human host populations. This symposium will explore how infectious agents and humans have shaped each other over the eons. Series: "CARTA - Center for Academic Research and Training in Anthropogeny" [Health and Medicine] [Science] [Show ID: 35849]

Infectious diseases have profound influences on the evolution of their host populations. In the case of humans, the host species has also shaped pathogen dynamics and virulence via a multitude of factors from changes in social organization, group size, and exploitation of varied habitats and their animals and plant resources to agriculture, technology, rapid long-distance travel, medicine and global economic integration - which all continue to shape epidemics and the human host populations. This symposium will explore how infectious agents and humans have shaped each other over the eons. Series: "CARTA - Center for Academic Research and Training in Anthropogeny" [Health and Medicine] [Science] [Show ID: 35849]

Infectious diseases have profound influences on the evolution of their host populations. In the case of humans, the host species has also shaped pathogen dynamics and virulence via a multitude of factors from changes in social organization, group size, and exploitation of varied habitats and their animals and plant resources to agriculture, technology, rapid long-distance travel, medicine and global economic integration - which all continue to shape epidemics and the human host populations. This symposium will explore how infectious agents and humans have shaped each other over the eons. Series: "CARTA - Center for Academic Research and Training in Anthropogeny" [Health and Medicine] [Science] [Show ID: 35849]

Infectious diseases have profound influences on the evolution of their host populations. In the case of humans, the host species has also shaped pathogen dynamics and virulence via a multitude of factors from changes in social organization, group size, and exploitation of varied habitats and their animals and plant resources to agriculture, technology, rapid long-distance travel, medicine and global economic integration - which all continue to shape epidemics and the human host populations. This symposium will explore how infectious agents and humans have shaped each other over the eons. Series: "CARTA - Center for Academic Research and Training in Anthropogeny" [Health and Medicine] [Science] [Show ID: 35849]

Infectious diseases have profound influences on the evolution of their host populations. In the case of humans, the host species has also shaped pathogen dynamics and virulence via a multitude of factors from changes in social organization, group size, and exploitation of varied habitats and their animals and plant resources to agriculture, technology, rapid long-distance travel, medicine and global economic integration - which all continue to shape epidemics and the human host populations. This symposium will explore how infectious agents and humans have shaped each other over the eons. Series: "CARTA - Center for Academic Research and Training in Anthropogeny" [Health and Medicine] [Science] [Show ID: 35849]

Infectious diseases have profound influences on the evolution of their host populations. In the case of humans, the host species has also shaped pathogen dynamics and virulence via a multitude of factors from changes in social organization, group size, and exploitation of varied habitats and their animals and plant resources to agriculture, technology, rapid long-distance travel, medicine and global economic integration - which all continue to shape epidemics and the human host populations. This symposium will explore how infectious agents and humans have shaped each other over the eons. Series: "CARTA - Center for Academic Research and Training in Anthropogeny" [Health and Medicine] [Science] [Show ID: 35849]

Infectious diseases have profound influences on the evolution of their host populations. In the case of humans, the host species has also shaped pathogen dynamics and virulence via a multitude of factors from changes in social organization, group size, and exploitation of varied habitats and their animals and plant resources to agriculture, technology, rapid long-distance travel, medicine and global economic integration - which all continue to shape epidemics and the human host populations. This symposium will explore how infectious agents and humans have shaped each other over the eons. Series: "CARTA - Center for Academic Research and Training in Anthropogeny" [Health and Medicine] [Science] [Show ID: 35849]

Infectious diseases have profound influences on the evolution of their host populations. In the case of humans, the host species has also shaped pathogen dynamics and virulence via a multitude of factors from changes in social organization, group size, and exploitation of varied habitats and their animals and plant resources to agriculture, technology, rapid long-distance travel, medicine and global economic integration - which all continue to shape epidemics and the human host populations. This symposium will explore how infectious agents and humans have shaped each other over the eons. Series: "CARTA - Center for Academic Research and Training in Anthropogeny" [Health and Medicine] [Science] [Show ID: 35849]

Infectious diseases have profound influences on the evolution of their host populations. In the case of humans, the host species has also shaped pathogen dynamics and virulence via a multitude of factors from changes in social organization, group size, and exploitation of varied habitats and their animals and plant resources to agriculture, technology, rapid long-distance travel, medicine and global economic integration - which all continue to shape epidemics and the human host populations. This symposium will explore how infectious agents and humans have shaped each other over the eons. Series: "CARTA - Center for Academic Research and Training in Anthropogeny" [Health and Medicine] [Science] [Show ID: 35849]

A new study by the La Jolla Institute for Immunology suggests that patients who recovered from coronavirus may have a “robust” immunity against the virus. Plus, a new Kawasaki-like illness in children linked to the coronavirus has San Diego doctors re-evaluating recent cases of Kawasaki disease. Also, we look back at the life of local arts legend Bob Matheny. He died this week at the age of 91. And, a preview of “A Knight’s Tour,” a Kickstarter-backed independent film by UCSD alum Marvin Choi.

A study from researchers at the La Jolla Institute for Immunology offers the first detailed look at the immune response of patients who contracted and recovered from SARS-CoV-2, which is causing the coronavirus pandemic.

https://www.drlizmd.com  doctorlyster@gmail.com Dr. Elizabeth Lyster earned her medical degree from the University of California at Irvine, after graduating from Cornell University with honors. She pursues ongoing advanced postgraduate training in Bioidentical Hormone and Nutraceutical Replacement therapy and lifestyle modulation for men and women Carole.Banka@gmail.com Dr. Carole Banka has held faculty positions at  Scripps Research Institute and The La Jolla Institute for Molecular Medicine. In 2008, Dr. Banka joined the Department of Medicine at UCSD where she is an Associate Project Scientist.  Dr. Banka has served on the Doris A. Howell Foundation for Women's Health Research Board of Directors since 2008-2018. dedicating her life to  helping women better understand and combat heart disease, how to reconigize the symptons and not ignore the signs. CNM Jacqui Henrich Certifed Nurse Midwife  San Diego, CA Former:  Sharp Mary Birch Hospital for Women & Newborns RN American College of Nurse-Midwives Sharp Healthcare Youtube version https://youtu.be/N2r5ZOesnk4    

Today we are pleased to welcome Mathew Meyer, one of the few researchers to study psilocybin's role in ecology. We discuss his research paper « Why did the Mushroom Become Magic? » as well as many other publications that shed light on this compelling topic..Matthew Meyer is a budding research mycologist and currently works as a Microscopy Specialist at the La Jolla Institute for Immunology. In his spare time, he conducts citizen-science fungal research and he serves as the Membership Director for the San Diego Mycological Society. Matthew obtained his Bachelor's degree at Whitman College in Walla Walla, WA in 2017 and is currently applying to mycology PhD programs around the world. He hopes to study fungal chemical ecology with an emphasis on fungal-invertebrate interactions.https://drive.google.com/drive/folders/1SxetRrvgFjJnUi6pN1K3cUjzY2j18Eun?usp=sharing

A teleconference on the global spread of the coronavirus. As the coronavirus outbreak spreads throughout Asia and the rest of the world, scientists have emphasized the need for greater cooperation and transparency. So far, 82 have been confirmed dead with more than 2,700 infections in China. Many countries, including the United States, have issued travel warnings and evacuation plans. The 110 possible cases in 26 U.S. states and the continued global spread of the disease is already impacting financial markets, tourism and travel business, and influencing investor sentiment. The U.S. Centers for Disease Control and Prevention recently expanded its travel warning to all of China and a top U.S. health official urged Beijing to admit disease experts into the country. What can be done by the international community to stop the spread of the coronavirus? How does the current state of U.S.-China relations impact cooperation between the two countries as they work to stop the disease? Featuring: Dr. Ben Oppenheim, Scientist, Metabiota Dr. Ben Oppenheim is an applied political economist with 14 years of experience in international development, security, and global health. He currently works as a senior Scientist at Metabiota working within the Product Development group; his first product, a novel index measuring sovereign preparedness for pandemic disease outbreaks, is used by a leading global re-insurance company to design and price risk transfer policies. Dr. Erica Ollmann Saphire, Professor, La Jolla Institute for Immunology Erica Ollmann Saphire, Ph.D. is a Professor of the La Jolla Institute for Immunology. Her research explains, at the molecular level, how and why viruses like Ebola and Lassa are pathogenic and provides the roadmap for medical defense. Her team has solved the structures of the Ebola, Sudan, Marburg, Bundibugyo and Lassa virus glycoproteins. Moderator: Lorraine Schneider, Program Manager in Training & Exercise Design, Global Crisis Management, The Walt Disney Company Lorraine Schneider is a Pacific Council member and an emergency manager with experience in preparedness, response and recovery. She currently works as a Program Manager in Training & Exercise Design for The Walt Disney Company's Global Crisis Management team.

This month on Episode 7 of the Discover CircRes podcast, host Cindy St. Hilaire highlights two featured articles from the December 6, 2019 issue of Circulation Research and talks with Roy Silverstein and Yiliang Chen about their article, Mitochondrial Metabolic Reprogramming by CD36 Signaling Drives Macrophage Inflammatory Responses. Article highlights: McArdle, et al, et al. Migratory and Dancing Atherosclerotic Macrophages Skaria, et al. Cardioprotection with Endogenous αCGRP Transcript Dr Cindy St. Hilaire: Hi, welcome to Discover CircRes the monthly podcast of the American Heart Association journal, Circulation Research. I'm your host, Dr Cindy St. Hilaire, and I'm an Assistant Professor at the University of Pittsburgh. In this episode I'm going to share with you highlights from recent articles published in the December 6 issue of Circulation Research. We're also going to have an in-depth conversation with Drs Roy Silverstein and Yiliang Chen about their recent article on how macrophage CD36 modulates immunometabolism. Also, the American Heart Association Scientific Sessions were recently held in Philadelphia, PA and in this edition of Discover CircRes, we're going to feature a conversation with the editors in chief of Circulation Research and Circulation, Drs Jane Friedman and Joe Hill. The first article I'd like to highlight is titled Migratory Dancing Atherosclerotic Macrophages. The first author is Sarah McCardell and the corresponding author is Klaus Ley and the work was conducted at the La Jolla Institute of Immunology in La Jolla, California. A major component of atherosclerosis is the inflammatory response and atherosclerotic plaques contain a mix of macrophages. Some macrophages arise from proliferation of resident cells, while other macrophages can infiltrate in from the blood. And a few studies have shown that smooth muscle cells can acquire some macrophage-like markers. Some macrophages are anti-inflammatory while others are more pro-inflammatory. These variations have largely been determined using techniques that examine the cell surface marker expression, the transcription profiles, or by mass spectrometry. But how all these different types of macrophagia cells look and function in vivo has not been clearly defined nor visualized. McCardell and colleagues have now observed fluorescently-labeled macrophages in the atherosclerotic plaques of live mice. First, using single cell RNA sequencing, they identified key markers of macrophage subsets. These markers are Cx3cr1 and CD11c. They then generated Apoe knockout mice that could then express green fluorescent protein under the direction of the Cx3cr1 promoter and yellow fluorescent protein under the direction of CD11c. These fluorescent proteins could be expressed individually, they could be expressed together, or they could be expressed not at all. And then in these mice they used intravital microscopy to look at the carotid artery plaques and they found while green cells and double positive cells, so that is, cells expressing Cx3cr1or both Cx3cr1 and CD11c--these cells tended to stay in one place, but they could extrude these protrusions akin to dancing, while the yellow cells or the cells that were expressing CD11c alone were more spherical and migratory. RNA analysis revealed that migratory genes were indeed upregulated in the yellow cells as compared to the green cells. The work provides preliminary insights into plaque macrophage dynamics and presents a technical resource for investigating how such behaviors may influence disease progression and I highly recommend you check this article out online. They have included several videos in the supplementary data and they're really beautiful. You can actually see the macrophages moving around and dancing and moving through the tissue and it's really neat to think about maybe how people are going to use this in the future to study the role of macrophages and maybe even other inflammatory cells in atherosclerotic disease progression. The next paper I want to highlight is titled Blood Pressure Normalization-Independent Cardioprotective Effects of Endogenous, Physical Activity-Induced Alpha Calcitonin Gene-Related Peptide (αCGRP) in Chronic Hypertensive Mice. The first author is Tom Skaria and the corresponding author is Johannes Vogel and they are from the University of Zurich in Zurich, Switzerland. So chronic hypertension affects a ton of people, over a billion worldwide, and it is a main driver of cardiovascular mortality and morbidity and it's a leading risk for heart failure. The way chronic hypertension can contribute to heart failure is by increasing the sarcomere gene expression in cardiomyocytes. And this gene expression helps to promote cellular hypertrophy or the swelling of cells, the enlarging of cells. High blood pressure can also promote interstitial fibrosis. And this fibrosis, which is happening in between the cardiomyocytes, impairs the contractile function of those cardiomyocytes. And while there are some medications available to help treat hypertension, many patients are unresponsive to these anti-hypertensive therapies. Interestingly, we all know exercise is good for us, and we all know exercise is good for specifically our heart, but exercise itself also induces cardiac hypertrophy, but it does so without impairing cardiac contractility. So how does this do this? How does exercise cause hypertrophy, but do it without impairing contractility? One of the proteins thought to be involved is called alpha calcitonin gene related peptide or alpha CGRP and mice that have been deleted of alpha CGRP, when they exercise, they exhibit hearts that look like hypertensive hearts. So this group hypothesized that exercise-induced endogenous alpha CGRP suppresses hypertension induced pathological cardiac remodeling and they tested this hypothesis in a murine model of chronic hypertension. What they found was interesting--they found that endogenous alpha CGRP suppresses pathological cardiac remodeling and it helps to preserve the heart function and it also mediates the cardioprotective effects of regular exercise in the setting of chronic hypertension. A really interesting thing that this article highlights is that alpha CGRP is currently approved for the treatment of migraines. So what might that mean? That might mean that someone who is taking this long-term for migraines may actually carry the risk of cardiac impairment if they have chronic hypertension. Mid-November is when the annual American Heart Association Scientific Sessions are held. This year's scientific sessions were in Philadelphia, PA and the Editors-In-Chief of Circulation and Circulation Research, Drs Joe Hill and Jane Friedman, had the chance to sit down for a chat and I'm going to share with you what they discussed, and I hope you enjoy it. Here they are. Amit Khera: I'm Amit Khera. I'm Digital Strategies Editor for Circulation and I'm standing in this week for Carolyn Lam and Greg Hunley. And I'm also doing the Circ on the Run Podcast as well as Discover CircRes podcast with our two Editors-In-Chief. This is Jane Friedman, who recently took over as editor-in-chief of Circulation Research and Joseph Hill, who is the editor-in-chief of Circulation. So welcome to you both. We’re excited to do this. Dr Joseph Hill:Thank you. Dr Jane Freedman: Thank you. Amit Khera: The idea behind this, there's a session here at Sessions where we're running a little bit about Circulation Research and Circulation, pulling back the cover, if you will, and seeing behind the cloak as to what happens in the journal. So Dr Freedman, I'll start with you. Tell me a little bit about as the incoming editor of Circulation Research, some of your vision for the journal, what you're excited about. Dr Jane Freedman: Well, I'm thrilled to be the new editor of Circulation Research and I've assembled a fabulous team of associate editors, deputy editors and other staff and support that are going to continue to grow what's already a wonderful journal, to be the preeminent and primary journal for basic and translational cardiovascular sciences and also support and interact with the other AHA family of journals. Amit Khera: So obviously that starts with a great team and it sounds like you've assembled that. Anything new that you're thinking about and the redesign of Circ Research in your term? Dr Jane Freedman: So we're hoping to expand the original scientific content, so we can have a larger number of articles in original science and we can have the pages to be able to handle other areas of basic cardiovascular science to include new areas, emerging areas, things like that. We're also increasing some of our early career initiatives, so that's very important to us as well. Amit Khera: Fantastic. And you talk about expanding for science and Joe, that that leads to you. In the session tomorrow, one of the goals is when people submit their science, it really goes into a black box and people don't know what happens on the Editorial level. Can you maybe enlighten us a little what happens? Dr Joseph Hill: Jane and I had been friends for 20 or more years and we now have established a bidirectional mutually synergistic collaboration where we send papers each way. We have distinct missions but yet with significant overlap, and I think it's an incredibly exciting time for the entire portfolio of AHA journals. So as you say, most people that you hit send and you wait four to six weeks and either get a happy note or an unhappy note. And what happens at both our journals is we have a strategy of multiple touches on every paper. The paper that first comes in is first touched by a senior editor, either myself or James de Lemos and two or three others. And we will reject without review about 50% of the papers at that point. We publish six papers a week, but we get 110 a week, so we don't need to review 50 of them to pick the top six. Out of respect to our authors to save them time, out of respect to our reviewers who devote tremendous effort to reviewing papers, we don't send them papers that we don't think have a shot. That said, if a paper makes it past that first stage, there's about a 50% chance it'll get published either in our journal or in one of the subspecialty journals. Probably a 50/50 chance it'll be published somewhere in an AHA family journal. So if it makes it past that stage, we send it to an Associate Editor, of which you are one, and we have about 50 of them. A third are in Dallas, another third is in the US outside of Dallas, and another third are in countries around the world, 17 different countries. And that person will probably reject without review another 5% or 10% maybe, but he or she will dig into that paper and, in parallel send it out to two or sometimes three reviewers, who are trusted and valued advisors. They help that associate editor make a strong recommendation. He or she makes a decision to bring to the larger group that is informed by those reviewers. So already that paper has been touched by five different investigators. Typically, that associate editor will reach out electronically within his or her affinity group. We have an affinity group in epidemiology, heart failure intervention, basic science… asking other AEs, "Could you take a look at this paper? One reviewer said this, one said that, I'm sort of thinking this…" And then we'll have a conversation on our weekly video conference and then a decision goes out to the authors. So every paper is touched by at least five and sometimes 10 different editors and reviewers, which we have found has been a powerful way to really dig into and identify things that one or two people might've missed. Amit Khera: You know, one thing I note here is how many people touch these articles, yet how efficient and how fast this process is. And that's a testament to the goals of the journal to be really responsive and rapid for our authors. One big part of that, and I'll come back to Dr Freedman, is peer review, right? So associate editors have a lot of work and we're affinity groups and so forth, but really critical is these peer reviewers, and in the modern era we're all so busy. Tell us a little bit about the value of peer review and how we enhance the value to the peer reviewers themselves. Dr Jane Freedman: Just as you said, the peer reviewers are absolutely central, valued, and vital parts of making the journal run correctly and we, like Circulation, our associate editors send them out to three different peer reviewers and they have a very fixed amount of time to review the articles and they provide these wonderful comments. We also very heavily rely on our Editorial Board. They know the drill that it needs to be back within a fixed amount of time and for the most part they do it. It's an interesting question. What's the value to them? I've been a reviewer too. It's part of your payback. It's part of educating yourself about what's new and interesting. There's a lot of reasons for doing it. People enjoy being on the Editorial Board and interacting with the journal. But fundamentally, as an editor, you're incredibly grateful to your reviewers. They are the unsung heroes of making a journal work. Amit Khera: And you mentioned sending out to three. When you have disparate reviews, it's amazing when some people love it and some people hate it. Dr Jane Freedman: Yeah. Amit Khera: How do you handle that? Dr Jane Freedman: Yeah. Well, sometimes it's apparent from the reviews why that happened. Someone may have focused on something that the editorial group thinks is less important or they focused on something that's addressable. The other thing we do similar to Joe, is we have a video conference call every single week on Wednesdays, and that's a period where people can vet any concerns or questions. And then my editors, my associate and deputy editors, know we have an open communication at all times. So I very frequently, when they have questions about reviews and how to reconcile disparate reviews, we'll have an ongoing conversation about that. Amit Khera: It sounds like of course you're actively engaged in how this is a dynamic process. I mentioned one thing as digital strategies editor, and I know both at Circ Research and Circulation, I was thinking how do we bring these articles to life? How do we have the most people read them or engage with them? And one is traditional social media, so Twitter and Facebook, which is incredibly important. Podcast, we have a monthly podcast, we have a weekly podcast, and really hope that people listen to them because they're really full of important information. And finally, I think what people don't appreciate is the media. So we work with AHA media. Some of our top stories get over a million media impressions, go all around the world and there's Professional Heart Daily. So there's so many ways that we're bringing articles to life. Joe, I'm going to finish with you. This is a Circ family. The value of having a family of journals and how we keep cohesion and for authors when they're submitting to serve a family of journals. What's the value and how does that add? Dr Joseph Hill: Well, there has been complete turnover of all the Editors-In-Chief in the entire family of journals, of which there are 12. And we are all quite similar in our personalities, in our perspectives on the importance, the ultimate importance of validity. The first question we ask is this true? If it's not, it's gone. It doesn't get referred. We reject it. Even if it's going to be on the front page of the New York Times and cited 10,000 times. And all of us hold ourselves to that same standard. So our vectors are all pointed in the same direction. We also care about impact, not impact factor, but does it change the way you think? Does it matter? Is it incremental or does it really move the needle? So we are now in a situation, I think, a wonderful situation where we all sink or swim together. We send papers all around, as you know very well. We send papers to the sub-specialty journals, we send 20 or 30 a week on an extraordinarily regular basis, and we send papers horizontally to Circ Research or Hypertension or Stroke and so forth. So it is a syncytium now I would say of a family of journals where we are all looking out for each other. Jane cares about our journal and we care about her journal and that's a really a wonderful situation to be in. Amit Khera: Well thanks. That family and how this fluidity of articles and thought and exchanges is really part of the value and ultimately the goal is for a great paper to find a great home and I think in the Circ family we do that. Dr Cindy St. Hilaire: Great. So I'm here with Drs Roy Silverstein and Yiliang Chen and today we're going to be discussing their paper titled Mitochondrial Metabolic Reprogramming by CD36 Signaling Drives Macrophage Inflammatory Responses. And this article is in the December 6th, 2019 edition of Circulation Research. So thank you both for joining me today. I'm really looking forward to learning more about the study, but before we really dig into it, could you please introduce yourselves and maybe give us a little bit about your background? Dr Roy Silverstein: Hi, I'm Roy Silverstein. I am a physician scientist, chair of the department of medicine at Medical College of Wisconsin in Milwaukee and also a senior investigator at the Blood Research Institute, which is part of what is now called Versiti Blood Center of Wisconsin. I'm a hematologist. Dr Yiliang Chen: Hi, my name is a Yiliang Chen. I graduate a PhD from University of Toledo, Ohio State. Then I chose to join Roy Silverstein's lab because I'm fascinated with this macrophage biology and immune functions in a disease called atherosclerosis, which is well-known inflammatory diseases. Dr Roy Silverstein: Can I make a little note that Dr Chen is currently supported by a scientist development grant from the American Heart Association, which is I think a nice tie-in? Dr Cindy St. Hilaire: Yeah. Dr Yiliang Chen: Yeah. I want to take this opportunity really saying American Heart Association to support our research. Dr Cindy St. Hilaire: Well that's wonderful. And now we get to publish this beautiful story. So it's come full circle. So you stated the objective of this paper was to investigate the mechanisms by which dyslipidemia, oxidative stress, and macrophage activation are linked in athero. And you focused on immunometabolism and you also focused on a protein called CD36. So before we get too deep in the weeds, can you give us a short little primer on what is immunometabolism in the context of athero, and also maybe a little bit about the molecule CD36? Dr Roy Silverstein: Well let me take the CD36 piece and then I'll let Dr Chen take the immunometabolism piece. So CD36 is a protein that's expressed on quite a few different cell types. We think that on muscle and fat its main purpose is to translocate free fatty acids from the external environment into the cell. In the case of fat, for storage, and in the case of muscle, for beta oxidation and energy, but in macrophages and immune cells and platelets, it has a different role. It serves as a scavenger receptor, part of the innate immune system, and it recognizes structures that we call DAMPs-danger associated molecular patterns. And the specific DAMPs that are recognized include oxidized low-density lipoprotein or what we call Ox-LDL. Dr Cindy St. Hilaire: Okay, so now could you give us a little bit about immunometabolism? Dr Yiliang Chen: Sure. So for metabolism, especially the process related to ATP or energy production, normally we call it bioenergetics and it is import. For so many years, people understand for the immune cell to get activated, they may produce proteins or somehow sometimes they need to proliferate. So there's a lot of energy is required during this whole process, right? But the old dogma is that the metabolism is only activated just to support the production of energy, especially the ATP. Right. But the emerging evidence has shown that, actually it's not that simple. For example, if you use LPS or bacterial product to activate to M1 status, the cells mainly use the glycolysis. They don't use the mitochondria Ox-LDL so TCA cycle to produce ADP. While the M2 activation is total different story. They switch it to the mitochondria ATP production and not using the glycolysis and it seems the metabolism is the underlying mechanism that driving these immune activations of the macrophages. So we want to ask, what kind of metabolism is going on in those ox-LDL-stimulated macrophages and is it related to atherosclerosis? So finally we figured out, okay, everything is focusing on a mitochondria function, which is interesting. But in our situation, very interesting, we find when the cells treat with oxidized LDL, actually they largely shut down the mitochondria OXPHOS. Then the Mito can switch ROS production of reactive oxygen species in shall we call it ROS. So that makes things quite interesting because it is well known oxidative stress is commonly observed during atherosclerosis. And also the mitochondria dysfunction actually, they are also commonly observed in the human patients with cardiovascular diseases. That kind of thing, everything together. Dr Cindy St. Hilaire: So you found that fatty acid metabolism, which is induced by this oxidized LDL, leads to the metabolic shift in the mitochondria, this switch you just described. And that shift leads to an accumulation of long chain fatty acids, but you also noticed independent of the metabolism in the mitochondria, you notice dysfunctions in what you call the mitochondrial network, and I'm wondering is it the accumulation of these long chain fatty acids that drives alterations in the mitochondrial network, or is it the other way around? I guess what I'm curious about is the interplay between that metabolic shift and just the baseline function of the mitochondria. Is one causing the other? Is it bi-directional? Dr Yiliang Chen: It sounds like a chicken and egg question. Dr Cindy St. Hilaire: Exactly. Dr Yiliang Chen: I think it's not that simple. For me, I was saying initially the cell try to adapt to this oxo LDL microenvironment. They try to stimulate the fatty acid trafficking into the mitochondria. But a side effect, what we think is, when you shut down a fatty acid oxidation while you're trafficking them there, that naturally will lead to accumulation of fatty acid. Those lipids may very well insert into the inner membrane of mitochondria then leads to the defects and that pretty much explained the EN images we show in our paper. Yeah. Exactly. Dr Cindy St. Hilaire: So the fact that the cell can't break down these long chain fatty acids, they're accumulating and potentially disrupting the mitochondrial membrane integrity. Dr Roy Silverstein: It's a form of lipodystrophy, not lipodystrophy, but lipotoxicity. Dr Yiliang Chen: Essentially, I think this is a defect in metabolism that leads to chronic inflammation. Dr Cindy St. Hilaire: Yeah. So your study focused on macrophages and atherosclerotic plaques and there's a huge body of evidence that shows inflammation and macrophage contribute to atherosclerotic disease progression pretty much throughout the whole plaque development. But there's also a body of evidence that shows smooth muscle cells can transdifferentiate and acquire macrophage-like phenotypes and they can also express CD36. It's one of the markers that people look for in that. And so I'm wondering, do you think this metabolic shift is operative in the smooth muscle or the macrophage-like smooth muscle cells? I guess that's the better thing to call them. Do you think that metabolic shift is operative and is contributing more so to the plaque or do you think this is innate to the macrophage from the immune system? Dr Roy Silverstein: I think that's a very provocative question. Thank you for it. Our in vitro experiments would not answer that question yet. We'd start with macrophages in those experiments, but it would be very interesting to look at smooth muscle cells that have been pushed towards that phenotype. We do, however, have some in vivo data that suggests that the cells that we call macrophages are behaving this way. And we can't say for certain that those are haematopoietically-derived cells versus smooth muscle derived cells. Dr Cindy St. Hilaire: So your study focused on the role of CD36 on macrophages, however, you mentioned in your introduction at the beginning that CD36 has also, it's in the GI track, it's on the muscle cells, it's on adipose tissue. It's also on the skin. And I'm wondering if you think these findings are specific only to the resident macrophages in the plaques or is this a broader function in macrophages? And I guess I'm thinking of this in the context of your study because it used the Apoe CD36 double knockout. So these are full body knockouts missing Apoe and functional CD36. And so I'm wondering, I guess, what would happen if CD36 was only removed from the macrophage cells itself? And I guess I'm thinking about this in context of something like metabolic syndrome. Could this be operative in adipose cells expressing CD36 or muscle cells or something like that? Kind of a more speculative question. Dr Roy Silverstein: That's great. You're helping us write our next grant. Dr Yiliang Chen: Yeah. Great question. Dr Cindy St. Hilaire: Give me 10%. Give me a little bit. Dr Roy Silverstein: I think one of the things that we've found over the years is that CD36 signaling in response to DAMPs, and even in response to fatty acid, involves a generalizable pattern that involves recruitment of what you might call a signalosome inside the cell. That signalosome typically would include members of the SARC family kinases, specific map kinases, a guanine nucleotide exchange factor called VAV, and other downstream signaling complexes. So we believe that that creates some opportunity for context specific signaling, but it does seem that a common theme is the generation of intracellular reactive oxygen species. Dr Cindy St. Hilaire: So I guess the bigger question after all of this, after your great findings, is what is the potential to leverage these findings in terms of developing therapies? Is there a novel pathway we can start to target or to think about targeting and how would you kind of go about that? Dr Yiliang Chen: Yeah. For that, that is our ongoing investigation. So based on the story in this paper, we are saying the mitochondria dysfunction and ROS production will activate and be pathway and drive this chronic inflammation, right? So if this is true, the particular question we are asking now is can we find a way to suppress mitochondrial ROS production or find a way to correct this fatty acid defect? Dr Cindy St. Hilaire: Do you think your findings on the metabolic shift of macrophage and how those contribute to atherosclerosis, how do you think those findings inform what the Cantos trial showed and the Cantos trial, which people may not be familiar with, used immunomodulation. Essentially, it was an antibody to block IO1 beta signaling and it had mediocre affects. The MI numbers were down, but the death rates were the same. Do you think that targeting the metabolism of the immune cells specifically as opposed to targeting the inflammation pathway outside of the cells is a more targeted and therefore maybe more precise approach? Dr Roy Silverstein: Yeah. I think that's a good observation. In my mind, what the Cantos study really showed us is that blocking inflammation in the broad sense, in a very upstream sense, can have an impact on human atherosclerotic heart disease. And I think that's really important observation and it validates the concept of inflammation as a target for atherosclerosis. Dr Cindy St. Hilaire: All of us breathed a sigh of relief once we're okay. It is an inflammation disease. Dr Roy Silverstein: Yeah. And it also decreased cancer, right? So it's double victory. Dr Cindy St. Hilaire: Yes. It did. Exactly. Yeah. Dr Roy Silverstein: But my thought is that we could maybe get a little bit upstream of that in a specific way. And perhaps the most translatable discovery here is the importance of mitochondrial reactive oxygen species as the source. Most people have looked at the NOX pathways, the NADP H oxidase pathways or broad spectrum. Dr Cindy St. Hilaire: I looked at that in my graduate studies. Dr Roy Silverstein: Yeah. So, you know that literature, and using broad heavy-handed approaches to create a “antioxidant effect” and most of those clinical trials have been extremely disappointing. But they haven't really targeted specific reactive oxygen species or specific sources. And we have this inhibitor that Dr Chen used in his experiment called mito-TEMPO which targets the mitochondria through a molecular mechanism and had a significant impact on the downstream production of pro-inflammatory product. So we think, or I think at least, that that is potentially an interesting target to basically prevent that reversal of mitochondrial function. Dr Cindy St. Hilaire: Thank you so much for taking the time to speak with me today. It's been wonderful, and I look forward to reading more of your papers in the future. Dr Roy Silverstein: Thanks. Dr Yiliang Chen: Thank you. Dr Cindy St. Hilaire: That's it for highlights from the December 6th issue of Circulation Research. Thank you so much for listening. This podcast is produced by Rebecca McTavish, edited by Melissa Stoner, and supported by the editorial team of Circulation Research. Some of the copy text for the highlighted articles is provided by Ruth Williams. Thank you to our guests, Dr Roy Silverstein and Dr Yiliang Chen and Drs Jane Friedman and Joe Hill for sharing their discussion with us. I'm your host, Dr Cindy St Hilaire, and this is Discover CircRes, your source for the most up-to-date and exciting discoveries in basic cardiovascular research.  

In this mini episode of the podcast recorded at HLTH in Las Vegas, Marc Iskowitz sits down with Seqster's Ardy Arianpour, founder and CEO, about his session, the health-data interoperability company's just-announced deal with La Jolla Institute for Immunology, its future plans, and what he's gleaned over the first two days of the conference.