Podcasts about Mucin

Matters Microbial #87: Dietary Protein and the Microbiome April 17, 2025 Today, Dr. Manuel Kleiner, Associate Professor of Microbiomes and Complex Microbial Communities at North Carolina State University,  joins the #QualityQuorum to discuss how diet can influence the microbiome in fascinating ways. Host: Mark O. Martin Guest: Manuel Kleiner Subscribe: Apple Podcasts, Spotify Become a patron of Matters Microbial! Links for this episode An overview of “pink pigmented facultative methylotrophs,” which can lead to wonderful “leaf prints.” Gnotobiotic versus “germ-free” animals. A solid review of the gut microbiome and the relationship to health. An article describing how proteins are digested by the microbiota. A description of glycan degrading enzymes and the gut microbiome. An overview of mucin. Description of metaproteomics by Dr. Kleiner. Description of metagenomics. Gut microbiota and dysbiosis. An overview of inflammatory bowel disease. An overview of Bacteroides thetaiotaomicron. An overview of Akkermansia muciniphila. The possibility of microbes “farming” us for mucus! The wide ranging and deeply fascinating website for Dr. Kleiner's research group. Dr. Kleiner's faculty website. Intro music is by Reber Clark Send your questions and comments to mattersmicrobial@gmail.com

Funding for the NIH and US biomedical research is imperiled at a momentous time of progress. Exemplifying this is the work of Dr. Anna Greka, a leading physician-scientist at the Broad Institute who is devoted to unlocking the mysteries of rare diseases— that cumulatively affect 30 million Americans— and finding cures, science supported by the NIH.A clip from our conversationThe audio is available on iTunes and Spotify. The full video is linked here, at the top, and also can be found on YouTube.Transcript with audio and external linksEric Topol (00:06):Well, hello. This is Eric Topol from Ground Truths, and I am really delighted to welcome today, Anna Greka. Anna is the president of the American Society for Clinical Investigation (ASCI) this year, a very prestigious organization, but she's also at Mass General Brigham, a nephrologist, a cell biologist, a physician-scientist, a Core Institute Member of the Broad Institute of MIT and Harvard, and serves as a member of the institute's Executive Leadership Team. So we got a lot to talk about of all these different things you do. You must be pretty darn unique, Anna, because I don't know any cell biologists, nephrologists, physician-scientist like you.Anna Greka (00:48):Oh, thank you. It's a great honor to be here and glad to chat with you, Eric.Eric Topol (00:54):Yeah. Well, I had the real pleasure to hear you speak at a November conference, the AI for Science Forum, which we'll link to your panel. Where I was in a different panel, but you spoke about your extraordinary work and it became clear that we need to get you on Ground Truths, so you can tell your story to everybody. So I thought rather than kind of going back from the past where you were in Greece and somehow migrated to Boston and all that. We're going to get to that, but you gave an amazing TED Talk and it really encapsulated one of the many phenomenal stories of your work as a molecular sleuth. So maybe if you could give us a synopsis, and of course we'll link to that so people could watch the whole talk. But I think that Mucin-1 or MUC1, as you call it, discovery is really important to kind of ground our discussion.A Mysterious Kidney Disease Unraveled Anna Greka (01:59):Oh, absolutely. Yeah, it's an interesting story. In some ways, in my TED Talk, I highlight one of the important families of this story, a family from Utah, but there's also other important families that are also part of the story. And this is also what I spoke about in London when we were together, and this is really sort of a medical mystery that initially started on the Mediterranean island of Cyprus, where it was found that there were many families in which in every generation, several members suffered and ultimately died from what at the time was a mysterious kidney disease. This was more than 30 years ago, and it was clear that there was something genetic going on, but it was impossible to identify the gene. And then even with the advent of Next-Gen sequencing, this is what's so interesting about this story, it was still hard to find the gene, which is a little surprising.Anna Greka (02:51):After we were able to sequence families and identify monogenic mutations pretty readily, this was still very resistant. And then it actually took the firepower of the Broad Institute, and it's actually from a scientific perspective, an interesting story because they had to dust off the old-fashioned Sanger sequencing in order to get this done. But they were ultimately able to identify this mutation in a VNTR region of the MUC1 gene. The Mucin-1 gene, which I call a dark corner of the human genome, it was really, it's highly repetitive, very GC-rich. So it becomes very difficult to sequence through there with Next-Gen sequencing. And so, ultimately the mutation of course was found and it's a single cytosine insertion in a stretch of cytosines that sort of causes this frameshift mutation and an early stop codon that essentially results in a neoprotein like a toxic, what I call a mangled protein that sort of accumulates inside the kidney cells.Anna Greka (03:55):And that's where my sort of adventure began. It was Eric Lander's group, who is the founding director of the Broad who discovered the mutation. And then through a conversation we had here in Boston, we sort of discovered that there was an opportunity to collaborate and so that's how I came to the Broad, and that's the beginnings of this story. I think what's fascinating about this story though, that starts in a remote Mediterranean island and then turns out to be a disease that you can find in every continent all over the world. There are probably millions of patients with kidney disease in whom we haven't recognized the existence of this mutation. What's really interesting about it though is that what we discovered is that the mangled protein that's a result of this misspelling of this mutation is ultimately captured by a family of cargo receptors, they're called the TMED cargo receptors and they end up sort of grabbing these misfolded proteins and holding onto them so tight that it's impossible for the cell to get rid of them.Anna Greka (04:55):And they become this growing heap of molecular trash, if you will, that becomes really hard to manage, and the cells ultimately die. So in the process of doing this molecular sleuthing, as I call it, we actually also identified a small molecule that actually disrupts these cargo receptors. And as I described in my TED Talk, it's a little bit like having these cargo trucks that ultimately need to go into the lysosome, the cells recycling facility. And this is exactly what this small molecule can do. And so, it was just like a remarkable story of discovery. And then I think the most exciting of all is that these cargo receptors turn out to be not only relevant to this one mangled misshapen protein, but they actually handle a completely different misshapen protein caused by a different genetic mutation in the eye, causing retinitis pigmentosa, a form of blindness, familial blindness. We're now studying familial Alzheimer's disease that's also involving these cargo receptors, and there are other mangled misshapen proteins in the liver, in the lung that we're now studying. So this becomes what I call a node, like a nodal mechanism that can be targeted for the benefit of many more patients than we had previously thought possible, which has been I think, the most satisfying part about this story of molecular sleuthing.Eric Topol (06:20):Yeah, and it's pretty extraordinary. We'll put the figure from your classic Cell paper in 2019, where you have a small molecule that targets the cargo receptor called TMED9.Anna Greka (06:34):Correct.Expanding the MissionEric Topol (06:34):And what's amazing about this, of course, is the potential to reverse this toxic protein disease. And as you say, it may have applicability well beyond this MUC1 kidney story, but rather eye disease with retinitis pigmentosa and the familial Alzheimer's and who knows what else. And what's also fascinating about this is how, as you said, there were these limited number of families with the kidney disease and then you found another one, uromodulin. So there's now, as you say, thousands of families, and that gets me to part of your sleuth work is not just hardcore science. You started an entity called the Ladders to Cures (L2C) Scientific Accelerator.Eric Topol (07:27):Maybe you can tell us about that because this is really pulling together all the forces, which includes the patient advocacy groups, and how are we going to move forward like this?Anna Greka (07:39):Absolutely. I think the goal of the Ladders to Cures Accelerator, which is a new initiative that we started at the Broad, but it really encompasses many colleagues across Boston. And now increasingly it's becoming sort of a national, we even have some international collaborations, and it's only two years that it's been in existence, so we're certainly in a growth mode. But the inspiration was really some of this molecular sleuthing work where I basically thought, well, for starters, it cannot be that there's only one molecular node, these TMED cargo receptors that we discovered there's got to be more, right? And so, there's a need to systematically go and find more nodes because obviously as anyone who works in rare genetic diseases will tell you, the problem for all of us is that we do what I call hand to hand combat. We start with the disease with one mutation, and we try to uncover the mechanism and then try to develop therapies, and that's wonderful.Anna Greka (08:33):But of course, it's slow, right? And if we consider the fact that there are 30 million patients in the United States in every state, everywhere in the country who suffer from a rare genetic disease, most of them, more than half of them are children, then we can appreciate the magnitude of the problem. Out of more than 8,000 genes that are involved in rare genetic diseases, we barely have something that looks like a therapy for maybe 500 of them. So there's a huge mismatch in the unmet need and magnitude of the problem. So the Ladders to Cures Accelerator is here to address this and to do this with the most modern tools available. And to your point, Eric, to bring patients along, not just as the recipients of whatever we discover, but also as partners in the research enterprise because it's really important to bring their perspectives and of course their partnerships in things like developing appropriate biomarkers, for example, for what we do down the road.Anna Greka (09:35):But from a fundamental scientific perspective, this is basically a project that aims to identify every opportunity for nodes, underlying all rare genetic diseases as quickly as possible. And this was one of the reasons I was there at the AI for Science Forum, because of course when one undertakes a project in which you're basically, this is what we're trying to do in the Ladders to Cures Accelerator, introduce dozens of thousands of missense and nonsense human mutations that cause genetic diseases, simultaneously introduce them into multiple human cells and then use modern scalable technology tools. Things like CRISPR screens, massively parallel CRISPR screens to try to interrogate all of these diseases in parallel, identify the nodes, and then develop of course therapeutic programs based on the discovery of these nodes. This is a massive data generation project that is much needed and in addition to the fact that it will help hopefully accelerate our approach to all rare diseases, genetic diseases. It is also a highly controlled cell perturbation dataset that will require the most modern tools in AI, not only to extract the data and understand the data of this dataset, but also because this, again, an extremely controlled, well controlled cell perturbation dataset can be used to train models, train AI models, so that in the future, and I hope this doesn't sound too futuristic, but I think that we're all aiming for that cell biologists for sure dream of this moment, I think when we can actually have in silico the opportunity to make predictions about what cell behaviors are going to look like based on a new perturbation that was not in the training set. So an experiment that hasn't yet been done on a cell, a perturbation that has not been made on a human cell, what if like a new drug, for example, or a new kind of perturbation, a new chemical perturbation, how would it affect the behavior of the cell? Can we make a predictive model for that? This doesn't exist today, but I think this is something, the cell prediction model is a big question for biology for the future. And so, I'm very energized by the opportunity to both address this problem of rare monogenic diseases that remains an unmet need and help as many patients as possible while at the same time advancing biology as much as we possibly can. So it's kind of like a win-win lifting all boats type of enterprise, hopefully.Eric Topol (12:11):Yeah. Well, there's many things to get to unpack what you've just been reviewing. So one thing for sure is that of these 8,000 monogenic diseases, they have relevance to the polygenic common diseases, of course. And then also the fact that the patient family advocates, they are great at scouring the world internet, finding more people, bringing together communities for each of these, as you point out aptly, these rare diseases cumulatively are high, very high proportion, 10% of Americans or more. So they're not so rare when you think about the overall.Anna Greka (12:52):Collectively.Help From the Virtual Cell?Eric Topol (12:53):Yeah. Now, and of course is this toxic proteinopathies, there's at least 50 of these and the point that people have been thinking until now that, oh, we found a mangled protein, but what you've zeroed in on is that, hey, you know what, it's not just a mangled protein, it's how it gets stuck in the cell and that it can't get to the lysosome to get rid of it, there's no waste system. And so, this is such fundamental work. Now that gets me to the virtual cell story, kind of what you're getting into. I just had a conversation with Charlotte Bunne and Steve Quake who published a paper in December on the virtual cell, and of course that's many years off, but of course it's a big, bold, ambitious project to be able to say, as you just summarized, if you had cells in silico and you could do perturbations in silico, and of course they were validated by actual experiments or bidirectionally the experiments, the real ones helped to validate the virtual cell, but then you could get a true acceleration of your understanding of cell biology, your field of course.Anna Greka (14:09):Exactly.Eric Topol (14:12):So what you described, is it the same as a virtual cell? Is it kind of a precursor to it? How do you conceive this because this is such a complex, I mean it's a fundamental unit of life, but it's also so much more complex than a protein or an RNA because not only all the things inside the cell, inside all these organelles and nucleus, but then there's all the outside interactions. So this is a bold challenge, right?Anna Greka (14:41):Oh my god, it's absolutely from a biologist perspective, it's the challenge of a generation for sure. We think taking humans to Mars, I mean that's an aspirational sort of big ambitious goal. I think this is the, if you will, the Mars shot for biology, being able to, whether the terminology, whether you call it a virtual cell. I like the idea of saying that to state it as a problem, the way that people who think about it from a mathematics perspective for example, would think about it. I think stating it as the cell prediction problem appeals to me because it actually forces us biologists to think about setting up the way that we would do these cell perturbation data sets, the way we would generate them to set them up to serve predictions. So for example, the way that I would think about this would be can I in the future have so much information about how cell perturbations work that I can train a model so that it can predict when I show it a picture of another cell under different conditions that it hasn't seen before, that it can still tell me, ah, this is a neuron in which you perturbed the mitochondria, for example, and now this is sort of the outcome that you would expect to see.Anna Greka (16:08):And so, to be able to have this ability to have a model that can have the ability to predict in silico what cells would look like after perturbation, I think that's sort of the way that I think about this problem. It is very far away from anything that exists today. But I think that the beginning starts, and this is one of the unique things about my institute, if I can say, we have a place where cell biologists, geneticists, mathematicians, machine learning experts, we all come together in the same place to really think and grapple with these problems. And of course we're very outward facing, interacting with scientists all across the world as well. But there's this sort of idea of bringing people into one institute where we can just think creatively about these big aspirational problems that we want to solve. I think this is one of the unique things about the ecosystem at the Broad Institute, which I'm proud to be a part of, and it is this kind of out of the box thinking that will hopefully get us to generate the kinds of data sets that will serve the needs of building these kinds of models with predictive capabilities down the road.Anna Greka (17:19):But as you astutely said, AlphaFold of course was based on the protein database existing, right? And that was a wealth of available information in which one could train models that would ultimately be predictive, as we have seen this miracle that Demi Hassabis and John Jumper have given to humanity, if you will.Anna Greka (17:42):But as Demis and John would also say, I believe is as I have discussed with them, in fact, the cell prediction problem is really a bigger problem because we do not have a protein data bank to go to right now, but we need to create it to generate these data. And so, my Ladders to Cures Accelerator is here to basically provide some part of the answer to that problem, create this kind of well-controlled database that we need for cell perturbations, while at the same time maximizing our learnings about these fully penetrant coding mutations and what their downstream sequelae would be in many different human cells. And so, in this way, I think we can both advance our knowledge about these monogenic diseases, build models, hopefully with predictive capabilities. And to your point, a lot of what we will learn about this biology, if we think that it involves 8,000 or more out of the 20,000 genes in our genome, it will of course serve our understanding of polygenic diseases ultimately as well as we go deeper into this biology and we look at the combinatorial aspects of what different mutations do to human cells. And so, it's a huge aspirational problem for a whole generation, but it's a good one to work on, I would say.Learning the Language of Life with A.I. Eric Topol (19:01):Oh, absolutely. Now I think you already mentioned something that's quite, well, two things from what you just touched on. One of course, how vital it is to have this inner or transdisciplinary capability because you do need expertise across these vital areas. But the convergence, I mean, I love your term nodal biology and the fact that there's all these diseases like you were talking about, they do converge and nodal is a good term to highlight that, but it's not. Of course, as you mentioned, we have genome editing which allows to look at lots of different genome perturbations, like the single letter change that you found in MUC1 pathogenic critical mutation. There's also the AI world which is blossoming like I've never seen. In fact, I had in Science this week about learning the language of life with AI and how there's been like 15 new foundation models, DNA, proteins, RNA, ligands, all their interactions and the beginning of the cell story too with the human cell.Eric Topol (20:14):So this is exploding. As you said, the expertise in computer science and then this whole idea that you could take these powerful tools and do as you said, which is the need to accelerate, we just can't sit around here when there's so much discovery work to be done with the scalability, even though it might take years to get to this artificial intelligence virtual cell, which I have to agree, everyone in biology would say that's the holy grail. And as you remember at our conference in London, Demi Hassabis said that's what we'd like to do now. So it has the attention of leaders in AI around the world, obviously in the science and the biomedical community like you and many others. So it is an extraordinary time where we just can't sit still with these tools that we have, right?Anna Greka (21:15):Absolutely. And I think this is going to be, you mentioned the ASCI presidency in the beginning of our call. This is going to be the president gets to give an address at the annual meeting in Chicago. This is going to be one of the points I make, no matter what field in biomedicine we're in, we live in, I believe, a golden era and we have so many tools available to us that we can really accelerate our ability to help more patients. And of course, this is our mandate, the most important stakeholders for everything that we do as physician-scientists are our patients ultimately. So I feel very hopeful for the future and our ability to use these tools and to really make good on the promise of research is a public good. And I really hope that we can advance our knowledge for the benefit of all. And this is really an exciting time, I think, to be in this field and hopefully for the younger colleagues a time to really get excited about getting in there and getting involved and asking the big questions.Career ReflectionsEric Topol (22:21):Well, you are the prototype for this and an inspiration to everyone really, I'm sure to your lab group, which you highlighted in the TED Talk and many other things that you do. Now I want to spend a little bit of time about your career. I think it's fascinating that you grew up in Greece and your father's a nephrologist and your mother's a pathologist. So you had two physicians to model, but I guess you decided to go after nephrology, which is an area in medicine that I kind of liken it to Rodney Dangerfield, he doesn't get any respect. You don't see many people that go into nephrology. But before we get to your decision to do that somehow or other you came from Greece to Harvard for your undergrad. How did you make that connect to start your college education? And then subsequently you of course you stayed in Boston, you've never left Boston, I think.Anna Greka (23:24):I never left. Yeah, this is coming into 31 years now in Boston.Anna Greka (23:29):Yeah, I started as a Harvard undergraduate and I'm now a full professor. It's kind of a long, but wonderful road. Well, actually I would credit my parents. You mentioned that my father, they're both physician-scientists. My father is now both retired, but my father is a nephrologist, and my mother is a pathologist, actually, they were both academics. And so, when we were very young, we lived in England when my parents were doing postdoctoral work. That was actually a wonderful gift that they gave me because I became bilingual. It was a very young age, and so that allowed me to have this advantage of being fluent in English. And then when we moved back to Greece where I grew up, I went to an American school. And from that time, this is actually an interesting story in itself. I'm very proud of this school.Anna Greka (24:22):It's called Anatolia, and it was founded by American missionaries from Williams College a long time ago, 150 and more years ago. But it is in Thessaloniki, Greece, which is my hometown, and it's a wonderful institution, which gave me a lot of gifts as well, preparing me for coming to college in the United States. And of course, I was a good student in high school, but what really was catalytic was that I was lucky enough to get a scholarship to go to Harvard. And that was really, you could say the catalyst that propelled me from a teenager who was dreaming about a career as a physician-scientist because I certainly was for as far back as I remember in fact. But then to make that a reality, I found myself on the Harvard campus initially for college, and then I was in the combined Harvard-MIT program for my MD PhD. And then I trained in Boston at Mass General in Brigham, and then sort of started my academic career. And that sort of brings us to today, but it is an unlikely story and one that I feel still very lucky and blessed to have had these opportunities. So for sure, it's been wonderful.Eric Topol (25:35):We're the ones lucky that you came here and set up shop and you did your productivity and discovery work and sleuthing has been incredible. But I do think it's interesting too, because when you did your PhD, it was in neuroscience.Anna Greka (25:52):Ah, yes. That's another.Eric Topol (25:54):And then you switch gears. So tell us about that?Anna Greka (25:57):This is interesting, and actually I encourage more colleagues to think about it this way. So I have always been driven by the science, and I think that it seems a little backward to some people, but I did my PhD in neuroscience because I was interested in understanding something about these ion channels that were newly discovered at the time, and they were most highly expressed in the brain. So here I was doing work in the brain in the neuroscience program at Harvard, but then once I completed my PhD and I was in the middle of my residency training actually at Mass General, I distinctly remember that there was a paper that came out that implicated the same family of ion channels that I had spent my time understanding in the brain. It turned out to be a channelopathy that causes kidney disease.Anna Greka (26:43):So that was the light bulb, and it made me realize that maybe what I really wanted to do is just follow this thread. And my scientific curiosity basically led me into studying the kidney and then it seemed practical therefore to get done with my clinical training as efficiently as possible. So I finished residency, I did nephrology training, and then there I was in the lab trying to understand the biology around this channelopathy. And that sort of led us into the early projects in my young lab. And in fact, it's interesting we didn't talk about that work, but that work in itself actually has made it all the way to phase II trials in patients. This was a paper we published in Science in 2017 and follow onto that work, there was an opportunity to build this into a real drug targeting one of these ion channels that has made it into phase II trials. And we'll see what happens next. But it's this idea of following your scientific curiosity, which I also talked about in my TED Talk, because you don't know to what wonderful places it will lead you. And quite interestingly now my lab is back into studying familial Alzheimer's and retinitis pigmentosa in the eye in brain. So I tell people, do not limit yourself to whatever someone says your field is or should be. Just follow your scientific curiosity and usually that takes you to a lot more interesting places. And so, that's certainly been a theme from my career, I would say.Eric Topol (28:14):No, I think that's perfect. Curiosity driven science is not the term. You often hear hypothesis driven or now with AI you hear more AI exploratory science. But no, that's great. Now I want to get a little back to the AI story because it's so fascinating. You use lots of different types of AI such as cellular imaging would be fusion models and drug discovery. I mean, you've had drug discovery for different pathways. You mentioned of course the ion channel and then also as we touched on with your Cell paper, the whole idea of targeting the cargo receptor with a small molecule and then things in between. You discussed this of course at the London panel, but maybe you just give us the skinny on the different ways that you incorporate AI in the state-of-the-art science that you're doing?Anna Greka (29:17):Sure, yeah, thank you. I think there are many ways in which even for quite a long time before AI became such a well-known kind of household term, if you will, the concept of machine learning in terms of image processing is something that has been around for some time. And so, this is actually a form of AI that we use in order to process millions of images. My lab has by produced probably more than 20 million images over the last few years, maybe five to six years. And so, if you can imagine it's impossible for any human to process this many images and make sense of them. So of course, we've been using machine learning that is becoming increasingly more and more sophisticated and advanced in terms of being able to do analysis of images, which is a lot of what we cell biologists do, of course.Anna Greka (30:06):And so, there's multiple different kinds of perturbations that we do to cells, whether we're using CRISPR or base editing to make, for example, genome wide or genome scale perturbations or small molecules as we have done as well in the past. These are all ways in which we are then using machine learning to read out the effects in images of cells that we're looking at. So that's one way in which machine learning is used in our daily work, of course, because we study misshape and mangled proteins and how they are recognized by these cargo receptors. We also use AlphaFold pretty much every day in my lab. And this has been catalytic for us as a tool because we really are able to accelerate our discoveries in ways that were even just three or four years ago, completely impossible. So it's been incredible to see how the young people in my lab are just so excited to use these tools and they're becoming extremely savvy in using these tools.Anna Greka (31:06):Of course, this is a new generation of scientists, and so we use AlphaFold all the time. And this also has a lot of implications of course for some of the interventions that we might think about. So where in this cargo receptor complex that we study for example, might we be able to fit a drug that would disrupt the complex and lead the cargo tracks into the lysosome for degradation, for example. So there's many ways in which AI can be used for all of these functions. So I would say that if we were to organize our thinking around it, one way to think about the use of machine learning AI is around what I would call understanding biology in cells and what in sort of more kind of drug discovery terms you would call target identification, trying to understand the things that we might want to intervene on in order to have a benefit for disease.Anna Greka (31:59):So target ID is one area in which I think machine learning and AI will have a catalytic effect as they already are. The other of course, is in the actual development of the appropriate drugs in a rational way. So rational drug design is incredibly enabled by AlphaFold and all these advances in terms of understanding protein structures and how to fit drugs into them of all different modalities and kinds. And I think an area that we are not yet harnessing in my group, but I think the Ladders to Cures Accelerator hopes to build on is really patient data. I think that there's a lot of opportunity for AI to be used to make sense of medical records for example and how we extract information that would tell us that this cohort of patients is a better cohort to enroll in your trial versus another. There are many ways in which we can make use of these tools. Not all of them are there yet, but I think it's an exciting time for being involved in this kind of work.Eric Topol (32:58):Oh, no question. Now it must be tough when you know the mechanism of these families disease and you even have a drug candidate, but that it takes so long to go from that to helping these families. And what are your thoughts about that, I mean, are you thinking also about genome editing for some of these diseases or are you thinking to go through the route of here's a small molecule, here's the tox data in animal models and here's phase I and on and on. Where do you think because when you know so much and then these people are suffering, how do you bridge that gap?Anna Greka (33:39):Yeah, I think that's an excellent question. Of course, having patients as our partners in our research is incredible as a way for us to understand the disease, to build biomarkers, but it is also exactly creating this kind of emotional conflict, if you will, because of course, to me, honesty is the best policy, if you will. And so, I'm always very honest with patients and their families. I welcome them to the lab so they can see just how long it takes to get some of these things done. Even today with all the tools that we have, of course there are certain things that are still quite slow to do. And even if you have a perfect drug that looks like it fits into the right pocket, there may still be some toxicity, there may be other setbacks. And so, I try to be very honest with patients about the road that we're on. The small molecule path for the toxic proteinopathies is on its way now.Anna Greka (34:34):It's partnered with a pharmaceutical company, so it's on its way hopefully to patients. Of course, again, this is an unpredictable road. Things can happen as you very well know, but I'm at least glad that it's sort of making its way there. But to your point, and I'm in an institute where CRISPR was discovered, and base editing and prime editing were discovered by my colleagues here. So we are in fact looking at every other modality that could help with these diseases. We have several hurdles to overcome because in contrast to the liver and the brain, the kidney for example, is not an organ in which you can easily deliver nucleic acid therapies, but we're making progress. I have a whole subgroup within the bigger group who's focusing on this. It's actually organized in a way where they're running kind of independently from the cell biology group that I run.Anna Greka (35:31):And it's headed by a person who came from industry so that she has the opportunity to really drive the project the way that it would be run milestone driven, if you will, in a way that it would be run as a therapeutics program. And we're really trying to go after all kinds of different nucleic acid therapies that would target the mutations themselves rather than the cargo receptors. And so, there's ASO and siRNA technologies and then also actual gene editing technologies that we are investigating. But I would say that some of them are closer than others. And again, to your question about patients, I tell them honestly when a project looks to be more promising, and I also tell them when a project looks to have hurdles and that it will take long and that sometimes I just don't know how long it will take before we can get there. The only thing that I can promise patients in any of our projects, whether it's Alzheimer's, blindness, kidney disease, all I can promise is that we're working the hardest we possibly can on the problem.Anna Greka (36:34):And I think that is often reassuring I have found to patients, and it's best to be honest about the fact that these things take a long time, but I do think that they find it reassuring that someone is on it essentially, and that there will be some progress as we move forward. And we've made progress in the very first discovery that came out of my lab. As I mentioned to you, we've made it all the way to phase II trials. So I have seen the trajectory be realized, and I'm eager to make it happen again and again as many times as I can within my career to help as many people as possible.The Paucity of Physician-ScientistsEric Topol (37:13):I have no doubts that you'll be doing this many times in your career. No, there's no question about it. It's extraordinary actually. There's a couple of things there I want to pick up on. Physician-scientists, as you know, are a rarefied species. And you have actually so nicely told the story about when you have a physician-scientist, you're caring for the patients that you're researching, which is, most of the time we have scientists. Nothing wrong with them of course, but you have this hinge point, which is really important because you're really hearing the stories and experiencing the patients and as you say, communicating about the likelihood of being able to come up with a treatment or the progress. What are we going to do to get more physician-scientists? Because this is a huge problem, it has been for decades, but the numbers just keep going lower and lower.Anna Greka (38:15):I think you're absolutely right. And this is again, something that in my leadership of the ASCI I have made sort of a cornerstone of our efforts. I think that it has been well-documented as a problem. I think that the pressures of modern clinical care are really antithetical to the needs of research, protected time to really be able to think and be creative and even have the funding available to be able to pursue one's program. I think those pressures are becoming so heavy for investigators that many of them kind of choose one or the other route most often the clinical route because that tends to be, of course where they can support their families better. And so, this has been kind of the conundrum in some ways that we take our best and brightest medical students who are interested in investigation, we train them and invest in them in becoming physician-scientists, but then we sort of drop them at the most vulnerable time, which is usually after one completes their clinical and scientific training.Anna Greka (39:24):And they're embarking on early phases of one's careers. It has been found to be a very vulnerable point when a lot of people are now in their mid-thirties or even late thirties perhaps with some family to take care of other burdens of adulthood, if you will. And I think what it becomes very difficult to sustain a career where one salary is very limited due to the research component. And so, I think we have to invest in our youngest people, and it is a real issue that there's no good mechanism to do that at the present time. So I was actually really hoping that there would be an opportunity with leadership at the NIH to really think about this. It's also been discussed at the level of the National Academy of Medicine where I had some role in discussing the recent report that they put out on the biomedical enterprise in the United States. And it's kind of interesting to see that there is a note made there about this issue and the fact that there needs to be, I think, more generous investment in the careers of a few select physician-scientists that we can support. So if you look at the numbers, currently out of the entire physician workforce, a physician-scientist comprised of less than 1%.Anna Greka (40:45):It's probably closer to 0.8% at this point.Eric Topol (40:46):No, it's incredible.Anna Greka (40:48):So that's really not enough, I think, to maintain the enterprise and if you will, this incredible innovation economy that the United States has had this miracle engine, if you will, in biomedicine that has been fueled in large part by physician investigators. Of course, our colleagues who are non-physician investigators are equally important partners in this journey. But we do need a few of the physician-scientists investigators I think as well, if you really think about the fact that I think 70% of people who run R&D programs in all the big pharmaceutical companies are physician-scientists. And so, we need people like us to be able to work on these big problems. And so, more investment, I think that the government, the NIH has a role to play there of course. And this is important from both an economic perspective, a competition perspective with other nations around the world who are actually heavily investing in the physician-scientist workforce.Anna Greka (41:51):And I think it's also important to do so through our smaller scale efforts at the ASCI. So one of the things that I have been involved in as a council member and now as president is the creation of an awards program for those early career investigators. So we call them the Emerging-Generation Awards, and we also have the Young Physician-Scientist Awards. And these are really to recognize people who are making that transition from being kind of a trainee and a postdoc and have finished their clinical training into becoming an independent assistant professor. And so, those are small awards, but they're kind of a symbolic tap on the shoulder, if you will, that the ASCI sees you, you're talented, stay the course. We want you to become a future member. Don't give up and please keep on fighting. I think that can take us only so far.Anna Greka (42:45):I mean, unless there's a real investment, of course still it will be hard to maintain people in the pipeline. But this is just one way in which we have tried to, these programs that the ASCI offers have been very successful over the last few years. We create a cohort of investigators who are clearly recognized by members of the ASCI is being promising young colleagues. And we give them longitudinal training as part of a cohort where they learn about how to write a grant, how to write a paper, leadership skills, how to run a lab. And they're sort of like a buddy system as well. So they know that they're in it together rather than feeling isolated and struggling to get their careers going. And so, we've seen a lot of success. One way that we measure that is conversion into an ASCI membership. And so, we're encouraged by that, and we hope that the program can continue. And of course, as president, I'm going to be fundraising for that as well, it's part of the role. But it is a really worthy cause because to your point, we have to somehow make sure that our younger colleagues stay the course that we can at least maintain, if not bolster our numbers within the scientific workforce.Eric Topol (43:57):Well, you outlined some really nice strategies and plans. It's a formidable challenge, of course. And we'd like to see billions of dollars to support this. And maybe someday we will because as you say, if we could relieve the financial concerns of people who have curiosity driven ideas.Anna Greka (44:18):Exactly.Eric Topol (44:19):We could do a lot to replenish and build a big physician-scientist workforce. Now, the last thing I want to get to, is you have great communication skills. Obviously, anybody who is listening or watching this.Eric Topol (44:36):Which is another really important part of being a scientist, no less a physician or the hybrid of the two. But I wanted to just go to the backstory because your TED Talk, which has been watched by hundreds of thousands of people, and I'm sure there's hundreds of thousands more that will watch it, but the TED organization is famous for making people come to the place a week ahead. This is Vancouver used to be in LA or Los Angeles area and making them rehearse the talk, rehearse, rehearse, rehearse, which seems crazy. You could train the people there, how to give a talk. Did you have to go through that?Anna Greka (45:21):Not really. I did rehearse once on stage before I actually delivered the talk live. And I was very encouraged by the fact that the TED folks who are of course very well calibrated, said just like that. It's great, just like that.Eric Topol (45:37):That says a lot because a lot of people that do these talks, they have to do it 10 times. So that kind of was another metric. But what I don't like about that is it just because these people almost have to memorize their talks from giving it so much and all this coaching, it comes across kind of stilted and unnatural, and you're just a natural great communicator added to all your other things.Anna Greka (46:03):I think it's interesting. Actually, I would say, if I may, that I credit, of course, I actually think that it's important, for us physician-scientists, again, science and research is a public good, and being able to communicate to the public what it is that we do, I think is kind of an obligation for the fact that we are funded by the public to do this kind of work. And so, I think that's important. And I always wanted to cultivate those communication skills for the benefit of communicating simply and clearly what it is that we do in our labs. But also, I would say as part of my story, I mentioned that I had the opportunity to attend a special school growing up in Greece, Anatolia, which was an American school. One of the interesting things about that is that there was an oratory competition.Anna Greka (46:50):I got very early exposure entering that competition. And if you won the first prize, it was in the kind of ancient Rome way, first among equals, right? And so, that was the prize. And I was lucky to have this early exposure. This is when I was 14, 15, 16 years old, that I was training to give these oratory speeches in front of an audience and sort of compete with other kids who were doing the same. I think these are just wonderful gifts that a school can give a student that have stayed with me for life. And I think that that's a wonderful, yeah, I credit that experience for a lot of my subsequent capabilities in this area.Eric Topol (47:40):Oh, that's fantastic. Well, this has been such an enjoyable conversation, Anna. Did I miss anything that we need to bring up, or do you think we have it covered?Anna Greka (47:50):Not at all. No, this was wonderful, and I thoroughly enjoyed it as well. I'm very honored seeing how many other incredible colleagues you've had on the show. It's just a great honor to be a part of this. So thank you for having me.Eric Topol (48:05):Well, you really are such a great inspiration to all of us in the biomedical community, and we'll be cheering for your continued success and thanks so much for joining today, and I look forward to the next time we get a chance to visit.Anna Greka (48:20):Absolutely. Thank you, Eric.**************************************Thanks for listening, watching or reading Ground Truths. Your subscription is greatly appreciated.If you found this podcast interesting please share it!That makes the work involved in putting these together especially worthwhile.All content on Ground Truths—newsletters, analyses, and podcasts—is free, open-access.Paid subscriptions are voluntary and all proceeds from them go to support Scripps Research. They do allow for posting comments and questions, which I do my best to respond to. Many thanks to those who have contributed—they have greatly helped fund our summer internship programs for the past two years. And such support is becoming more vital In light of current changes of funding and support for biomedical research at NIH and other US governmental agencies.Thanks to my producer Jessica Nguyen and to Sinjun Balabanoff for audio and video support at Scripps Research. Get full access to Ground Truths at erictopol.substack.com/subscribe

There's an ingredient that nobody's really talking much about that's being sneaked into our food and is eroding our first line of defense against all of the chronic diseases of aging.  The most likely things to take away our resilience or kill us early are metabolic dysfunction, cardiovascular disease, cancer, neurodegenerative disease and autoimmune diseases.  We have a built-in protective defense system, but it's getting literally dissolved away by this food ingredient.  Eliminating it will help you age at an elite level so you're capable of living more as you get older, rather than less.Come hang out with meSend me a message: healthcouragecollective@gmail.comTake My Udemy Course about The Basics of Female Bioidentical Hormone Replacement Therapy: 

When Celeste Guptill believed her stomach was swollen a bit more than usual following the birth of her tenth child, she thought it might be due to age or some sort of gastrointestinal issue.  However, a CT scan revealed a tumor leading to a diagnosis of pseudomyxoma peritonei (PMP), a rare type of appendix cancer.  The tumor was surgically removed, but Celeste was fortunate to find a specialist who performed a second procedure called HIPEC, which included heated chemotherapy.  Cancer-free for more than five years, Celeste says that physically, she can do everything she could do prior to her diagnosis.

I had a conversation with a friend about all of the changes that we're experiencing being in perimenopause. I shared that I'm dealing with some skin issues and it was frustrating me. This friend recommended I try snail mucin, and I eventually did. In this episode Im talking about how my experience with this product mirrors the journey of self-discovery. Resources Mentioned & Show Notes:I created the Inner Strength Journal to help you recognize that sneaky voice of fear, pretending and performing so you can choose authenticity and courage instead. Because you deserve to live a life that's truly YOU.Your favorite version of you is waiting to be discovered, buy your copy today -– https://www.innerstrengthjournal.comDid you enjoy this episode? There's more in our private community! Get 7 days free in Glow Circle and share space with women who, just like you, are discovering themselves and finding the support and resources to grow in confidence – https://www.glowcircle.us COSRx Snail Mucin 96% Power Repairing Essence -- https://amzn.to/3XUBWmBConnect Elsewhere:www.confidencecoachingforher.cominstagram.com/confidencecoachingforher

Snail mucin: Snail'd it! - Fish skin grafts - Dupi okay in patch testing - Tattoo complications - Mavorixafor and WHIM syndrome - Want to donate to the cause? Do so here! Donate to the podcast: uofuhealth.org/dermasphere Check out our video content on YouTube: www.youtube.com/@dermaspherepodcast and VuMedi!: www.vumedi.com/channel/dermasphere/ The University of Utah's Dermatology ECHO: ⁠physicians.utah.edu/echo/dermatology-primarycare - ⁠ Connect with us! - Web: ⁠dermaspherepodcast.com/⁠ - Twitter: @DermaspherePC - Instagram: dermaspherepodcast - Facebook: www.facebook.com/DermaspherePodcast/ - Check out Luke and Michelle's other podcast, SkinCast! ⁠healthcare.utah.edu/dermatology/skincast/⁠ Luke and Michelle report no significant conflicts of interest… BUT check out our friends at: - ⁠Kikoxp.com ⁠(a social platform for doctors to share knowledge) - ⁠www.levelex.com/games/top-derm⁠ (A free dermatology game to learn more dermatology!

It's been a while since we have had an experimental show on SCC, but when this product came up all over our social media, we couldn't resist. Some things sound too gross to be true and slathering your face with snail secretions for glowing, acne-free skin is one of them. So obviously we had to try it out.  Expect the usual antics from Lauren and Nicole. Tune in for more. To pre order our book “Have You Tried This?” click here  https://www.amazon.co.uk/Have-You-Tried-This-Only/dp/1801293139/ref=sr_1_2?crid=1O7EA4ZF1O5CS&keywords=have+you+tried+this&qid=1699449028&sprefix=have+you+tried+%2Caps%2C125&sr=8-2 For our exclusive merch - https://self-care-club.myspreadshop.co.uk/ Join our private facebook group https://www.facebook.com/groups/1115099072702743/?ref=share_group_link Instagram  https://www.instagram.com/selfcareclubpod/ YouTube https://youtube.com/c/SelfCareClub TikTok https://vm.tiktok.com/ZMLnXyS1S/ Email hello@theselfcareclub.co.uk  Website www.theselfcareclub.co.uk Studio production by @launchpodstudios Music by purpleplanet.com Learn more about your ad choices. Visit podcastchoices.com/adchoices

Snail mucin, also known as snail secretion filtrate, has become a popular ingredient in skincare due to its potential benefits for various skin concerns. Here's a summary: Benefits: Considerations: Overall: Snail mucin shows promise as a versatile skincare ingredient with potential benefits for hydration, repair, and anti-aging. However, thorough research on ethical sourcing, product quality, and individual suitability is crucial before incorporating it into your routine.

It's the end of the year and we're dragging ourselves to the finish line. Our faces feel the strain! We discuss some "best of 2023" skincare advice we've never heard before, the status of the Dr. Brenner investigation and snail mucin. Or should it be slug mucin?

Kieran Corley, Snail farmer and founder of Bragan Skincare joined Sean on the show today to discuss how he uses his snails to help make his products...

Kieran Corley, Snail farmer and founder of Bragan Skincare joined Sean on the show today to discuss how he uses his snails to help make his products...

Amy first learned of the "snail stuff" she puts on her face from her go-to face girl, Keri (@thenashvillebeautygirl) and ever since she's been obsessed. There are so many benefits and since Amy's not an expert....she brought one on Valerie Johnston who is a consultant to Biopelle for product, scientific and training resources. Valerie is highly knowledgeable and experienced and gives us all the details! Amy is simply a fan of this stuff, as are some of you, so she wanted an expert to break things down! "Snail Stuff" = Biopell's Tensage 40 The Radiance Eye Cream Amy loves! You can also hit up Biopelle.com to learn more. Make sure to check Amy's "snail" highlight button on her Instagram page (@RadioAmy) to grab a code that may work - it's not always active - but worth looking into + Amy will always share on IG when Amazon has it on sale!    HOST: Amy Brown // RadioAmy.com // @RadioAmySee omnystudio.com/listener for privacy information.

This was an 'all over the place' episode. Kim and Jen give updates on their lives and their new jobs. Jen talks about the useless double space after a period, being caught red-handed, and just biting the bullet. Kim had a fever and a lost scrapbooking dream. Jen has a colorful character sitting next to her on the plane, and they delve into the use of snail snot...mucin.https://www.everydayhealth.com/healthy-skin/snail-mucin-101-a-detailed-guide/https://www.google.com/search?q=escaped+convict+pennsylvania&rlz=1C1CHBF_enUS833US836&oq=escaped+con&gs_lcrp=EgZjaHJvbWUqDQgBEAAYgwEYsQMYgAQyDQgAEAAYgwEYsQMYgAQyDQgBEAAYgwEYsQMYgAQyDQgCEAAYgwEYsQMYgAQyBggDEEUYOTIGCAQQABgDMg0IBRAAGIMBGLEDGIAEMgcIBhAAGIAEMgcIBxAAGIAEMgcICBAAGIAEMgcICRAAGIAE0gEINjI0MGowajeoAgCwAgA&sourceid=chrome&ie=UTF-8Twisted Teachers Podcast wants to hear from you!Leave us a voice message! https://www.speakpipe.com/TwistedTeachersWebsite-Twistedteacherspodcast.comLINKTREE :https://linktr.ee/twistedteacherContact us via email: Twistedteachers2@gmail.comInstagram: @twisted__teacher; @inked_educator68; @escaping_educationTik Tok: @inkededucator @escape_educationFacebook: @TwistedTeacherLinkedIn: https://www.linkedin.com/in/jennifersquireroberts

Slimy, Moisturizing, and Healing - Join us on a fascinating journey into the world of skincare as we unveil one of the industry's most intriguing ingredients: snail mucin. Often described as nature's hidden gem, snail mucin has taken the beauty world by storm. But what exactly is snail mucin, and why is it making waves in skincare?

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.06.547951v1?rss=1 Authors: Cloots, E., Guilbert, P., Provost, M., Neidhardt, L., Van de Velde, E., Fayazpour, F., De Sutter, D., Savvides, S. N., Eyckerman, S., Janssens, S. Abstract: As secretory cells specialized in the production of mucins, intestinal goblet cells are challenged by the need for efficient protein folding. Goblet cells express Inositol-Requiring Enzyme 1{beta} (IRE1{beta}), a unique unfolded protein response (UPR) sensor that is part of an adaptive mechanism that regulates the demands of mucin production and secretion. However, how IRE1{beta} activity is tuned to mucus folding load remains unknown. We identified the disulfide isomerase and mucin chaperone AGR2 as a goblet cell specific protein that crucially regulates IRE1{beta}-, but not IRE1-mediated signaling. AGR2 binding to IRE1{beta} disrupts IRE1{beta} dimerization, thereby blocking its downstream endonuclease activity. Depletion of endogenous AGR2 from goblet cells induces spontaneous IRE1{beta} activation, suggesting that alterations in AGR2 availability in the endoplasmic reticulum sets the threshold for IRE1{beta} activation. We found that AGR2 mutants lacking their catalytic cysteine or displaying the disease-associated mutation H117Y were no longer able to dampen IRE1{beta} activity. Collectively, these results demonstrate that AGR2 is a central chaperone regulating the goblet cell UPR by acting as a rheostat of IRE1{beta} endonuclease activity. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.06.530313v1?rss=1 Authors: Jäverfelt, S., Hellsen, G., Kaji, I., Goldenring, J. R., Pelaseyed, T. Abstract: A dense glycocalyx, composed of the megaDalton-sized membrane mucin MUC17, coats the microvilli in the apical brush border of transporting intestinal epithelial cells, called enterocytes. The establishment of the MUC17-based glycocalyx in the mouse small intestine occurs at the critical suckling-weaning transition. The enterocytic glycocalyx extends 1 m into the intestinal lumen and prevents the gut bacteria from directly attaching to the enterocytes. To date, the mechanism behind apical targeting of MUC17 to the brush border remains unknown. Here, we show that the actin-based motor proteins MYO1B and MYO5B, and the sorting nexin SNX27 regulate the intracellular trafficking of MUC17 in enterocytes. We demonstrate that MUC17 turnover at the brush border is slow and controlled by MYO1B and SNX27. Furthermore, we report that MYO1B regulates MUC17 protein levels in enterocytes, whereas MYO5B specifically governs MUC17 levels at the brush border. Together, our results extend our understanding of the intracellular trafficking of membrane mucins and provide mechanistic insights into how defective trafficking pathways render enterocytes sensitive to bacterial invasion. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Everything you need to know about these ingredients. Will you be incorporating them into your skincare routine? IG: @pureskinoc  Facebook: @pureskinoc    TikTok: @pureskinoc Website/Online Store: www.PureSkinOC.com Skin Care Coaching: Sign Up! This is a Redd Rock Music Podcast IG: @reddrockmusic www.reddrockmusic.com Learn more about your ad choices. Visit megaphone.fm/adchoices

With the advent of the Human Microbiome Project and advancing technologies in whole-genome sequencing, the critical role of the gastrointestinal microbiome becomes clearer and clearer. We know the microbiome helps extract nutrients from the diet, creates important systemic metabolites, communicates with our skin and brain, and so much more. That being said, one such bacteria continues to stand out in the crowd– Akkermansia muciniphila. This bacterium, or lack thereof, may be a key player in obesity, metabolic disorders, inflammatory bowel disease, and ‘leaky gut'. In today's episode, we explain the vital role of Akkermansia muciniphila. We discuss dietary strategies to boost levels and the new Akkermansia probiotic supplement! Today on The Lab Report: 2:30 The mucus layer of the GI tract  6:00 Mucin vs. mucus and altering the mucus layer 7:35 Akkermansia muciniphila 11:55 Logical Speculation – High levels good or bad?   14:10 Clinical implications of low levels of Akkermansia 16:40 Strategies to boost Akkermansia 18:05 Finally! A new Akkermansia probiotic! 19:05 Berberine is kinda awesome 20:00 Question of the Day How does Genova evaluate Akkermansia and mucin? Additional Resources: GI Effects + Microbiomix Pendulum Life  (Use Promo Code GENOVA for 20% off your first month of a Pendulum membership!) Subscribe, Rate, & Review The Lab Report Thanks for tuning in to this week's episode of The Lab Report, presented by Genova Diagnostics, with your hosts Michael Chapman and Patti Devers. If you enjoyed this episode, please hit the subscribe button and give us a rating or leave a review. Don't forget to visit our website, like us on Facebook, follow us on Twitter, Instagram, and LinkedIn. Email Patti and Michael with your most interesting and pressing questions on functional medicine: podcast@gdx.net. And, be sure to share your favorite Lab Report episodes with your friends and colleagues on social media to help others learn more about Genova and all things related to functional medicine and specialty lab testing. To find a qualified healthcare provider to connect you with Genova testing, or to access select products directly, visit Genova Connect. Disclaimer: The content and information shared in The Lab Report is for educational purposes only and should not be taken as medical advice. The views and opinions expressed in The Lab Report represent the opinions and views of Michael Chapman and Patti Devers and their guests.  See omnystudio.com/listener for privacy information.

Erik Brynjolfsson speaks about the imminent future of artificial intelligence and how it will change the world. He discusses the potential impacts of machine learning, deep learning, and neural networks, and their impact on technology, the economy, and society.

A new research paper was published in Oncotarget on July 28, 2022, entitled, “Chemoradiation-induced alteration of programmed death-ligand 1, CD8+ tumor-infiltrating lymphocytes and mucin expression in rectal cancer.” DNA damage and resulting neoantigen formation is considered a mechanism for synergy between radiotherapy and PD-1/PD-L1 pathway inhibition to induce antitumor immune response. In a new research study, by Marina Baretti, Qingfeng Zhu, Wei Fu, Jeffrey Meyer, Hao Wang, Robert A. Anders, and Nilofer S. Azad from Johns Hopkins University School of Medicine, researchers investigated neoadjuvant chemoradiotherapy (nCRT)-induced changes in CD8+ tumor infiltrating lymphocyte, PD-L1 and mucin expression in rectal cancer patients. “The synergistic effects of CRT and PD-1/PD-L1 immunotherapy has been supported by several retrospective analyses in different cancer types, including esophageal cancer, bladder cancer, and lung cancer also support[ed] [14, 21, 22]. However, the role of nCRT to interact synergistically with immune checkpoint inhibitor treatment to improve tumor control in rectal cancer remains uncertain.” Full press release - https://www.oncotarget.com/news/pr/oncotarget-chemoradiation-induced-alteration-of-programmed-death-ligand-cd-tumor-infiltrating-lymphocytes-and-mucin-expression-in-rectal-cancer/ DOI: https://doi.org/10.18632/oncotarget.28255 Correspondence to: Marina Baretti – Email: mbarett1@jh.edu Keywords: programmed death ligand 1, tumor-infiltrating lymphocytes, immune checkpoints, colorectal cancer, neoadjuvant chemoradiotherapy About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media: Twitter – https://twitter.com/Oncotarget Facebook – https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Instagram – https://www.instagram.com/oncotargetjrnl/ LinkedIn – https://www.linkedin.com/company/oncotarget/ Pinterest – https://www.pinterest.com/oncotarget/ LabTube – https://www.labtube.tv/channel/MTY5OA SoundCloud – https://soundcloud.com/oncotarget For media inquiries, please contact: media@impactjournals.com

Dr. Inti Zlobec, professor of digital pathology at the Institute of Pathology in the University of Bern, discusses her team's recent publication in Modern Pathology on the role of image analysis in assessing area of extracellular mucin and predicting consensus molecular subtypes (CMS) in colorectal carcinoma. The utilized deep learning algorithm had an excellent agreement with pathologists' estimates of mucin areas. Coupled with MSI, mucinous area estimates may predict CMS classification using only histopathology. This highlights the great potential of Image based classifier of molecular subtypes of colon cancer. Study by Nguyen, HG., Lundström, O., Blank, A. et al. Image-based assessment of extracellular mucin-to-tumor area predicts consensus molecular subtypes (CMS) in colorectal cancer. Mod Pathol 35, 240–248 (2022) See acast.com/privacy for privacy and opt-out information.

On today's show, Valerie and Perry answers questions about...Is snail mucin a worthwhile ingredient?Do blackhead suction devices work?Will a humidifier help your skin?Beauty Science storiesGarnier teams up with Walmart to launch clean beauty hair care brandLawsuit oil free  Four Ways to Ask a question -1. Become a patron and ask through there. These get top attention.2. You can record your question on your smart phone and email to thebeautybrains@gmail.com3. Send it to us via social media (see links below)4. Submit it through the following form - Ask a questionSupport the Beauty BrainsThe Beauty Brains are now on Patreon! If you want to support the show Patreon is the best way to do it. This will help keep the show going and avoid any of those pesky advertisements that I find so maddening in other podcasts that I listen to. Thank you to all of our Patrons!Social media accountson Instagram we're at thebeautybrains2018on Twitter, we're thebeautybrainsAnd we have a Facebook pageBe Brainy about your Beauty!Support the show (https://www.patreon.com/thebeautybrains?fan_landing=true)

For the past 30 days, Lauren has been using a product by the K Beauty brand CosRX called Snail 96 Mucin Power Essence. It is a light watery consistent essence that has highest concentration of snail slime at 96%. Snail slime is a new up and coming ingredient in the cosmetic world, you're going to be seeing more and more of it. It is an ingredient that really cannot cause any harm to the skin, it boasts many beneficial claims but also needs more scientific research to back up it's claims. Lauren's updating us with her 30 days on snail slime and Kelsey is serving us the science behind this ingredient. We also talk: - White Lotus - Bob Ross - Val Kilmer - The Murdaugh Family Murders (give it a goog)

It's the worst!  Watching your hair slide down the shower drain or clumping up on your brush is a horrible feeling, especially for women!Our hair is connected to our identity, our youth, and our health.While it’s natural for some women to experience hair loss at certain times in their menstrual cycles or times of the year, hair loss is also caused by specific health conditions including a thyroid imbalance.So the question here is....Why does a thyroid imbalance cause thinning hair?Your hair normally grows in a healthy cyclical pattern with most of the hair follicles growing while only a small number are “resting.”With a thyroid imbalance, this cycle can be thrown off, resulting in more hair follicles “resting” than growing — and more hair falling out.Hair loss is a very common symptom of a thyroid imbalance.But thyroid imbalances often arise slowly and remain unnoticed by women and their doctors in the early phases.Even with a lab test, your doctor may say everything is fine with your thyroid, even though you strongly suspect that something is wrong.This is because standard labs have a very wide range for what is “normal” in terms of thyroid test results.So how do you know if your hair loss is connected to a thyroid disorder?So here are 5 signs and symptoms your hair loss is connected to a thyroid disorder1. Thinning eyebrowsHypothyroidism - which is an underactive thyroid  often causes general hair loss as well as thinning of the outer third of the eyebrows.We don’t know exactly why the eyebrow is targeted in thyroid disorders, but this is a good indicator that your thyroid hormones may be low.2. Hair that is brittle, dry, and breaking easily.Dry, brittle hair is also connected to low thyroid function. And research published in the Journal of Clinical Endocrinology & Metabolism finds that thyroid hormones increase growth and color in hair.Low thyroid hormone can lead to the early release of the hair shaft and root, as well as premature gray or white hair.3. Feeling exhausted all the time, even after 8 hours of sleep.The thyroid is the master of our metabolism, so it affects the way we use and store energy.With low thyroid hormone, metabolism slows down. This can often lead to persistent fatigue as well as weight gain4. Puffiness in the faceMany people with hypothyroidism have an excess of a compound called mucin.Mucin is part of our connective tissue and is present in blood vessels and cells all over the body. It absorbs water and may cause excess water retention in an individual with an underactive thyroid imbalance.5. Yellowing of the palms of your hands. Yellowing of the skin on your hands can happen with a thyroid imbalance due a build-up of carotene in your blood. Hypothyroidism can slow the conversion of carotene to vitamin A.If you think your hair loss might be connected to a thyroid imbalance, begin supporting your thyroid — and your hair — naturally.Adaptogens are the safest and best way to help the body cope with stress.  Other products like CBD can also help.Shop our Evoq Beauty Root Revival Hair Growth System (2x's more powerful than Minoxidil) and CBD @evoqbeauty  and www.evoqbeauty.coLove and light!Share the Love:If you like The Awakened Beauty Podcast….Subscribe, Rate & Review via iTunesVisit us at awakenedbeautyhq.com for updates.Businesses: www.evoqbeauty.com | www.beautyecology.comInstagram @awakenbeautyhqInstagram @evoqbeautyWatch on Youtube at my channel: Awaken Beauty PodcastShop natural health and beauty products with EVOQHere’s how!Go to awakenbeauty-hq on ITunes and write your biggest takeaway in the rate and review section. Just pretend it says “ah ha” here!! Don’t just review the episode, I would love your ah-ha moment from this episode that is more specific so you can confirm your takeaway as you write, but also help others capture your brilliance. It’ll take 3 minutes from your day. What you declare will be life to others. So remember, go to I tunes to rate and review.Comment or question you’d like to ask Kassandra.P.S! Your review is not only paramount in helping others discover the show, but we also read each and every submission personally…and they mean the world to us.Love and Light! - KassandraIn the Meantime, STAY IN THE CONVERSATION! @awakenbeautyhq | #awakenbeauty#hairlosts #hairgrowth #naturalhaircare #organicbeauty #organicsalon #thyroidimbalance #thyroid #hormones

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.29.227785v1?rss=1 Authors: Zhang, Y., Zhao, W., Mao, Y., Chen, Y., Hu, L., Zhu, J., Gong, M., Cheng, J., Yang, H. Abstract: The densely glycosylated spike (S) proteins that are highly exposed on the surface of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) facilitate viral attachment, entry, and membrane fusion. We have previously reported all the 22 N-glycosites and site-specific N-glycans in the S protein protomer. Herein, we report the comprehensive and precise site-specific O-glycosylation landscapes of SARS-CoV-2 S proteins, which were characterized using high-resolution mass spectrometry. Following digestion using trypsin and trypsin/Glu-C, and de-N-glycosylation using PNGase F, we determined the mucin-type (GalNAc-type) O-glycosylation pattern of S proteins, including unambiguous O-glycosites and the 6 most common O-glycans occupying them, via Byonic identification and manual validation. Finally, 43 O-glycosites were identified in the insect cell-expressed S protein. Most glycosites were modified by non-sialylated O-glycans such as HexNAc(1) and HexNAc(1)Hex(1). In contrast, 30 O-glycosites were identified in the human cell-expressed S protein S1 subunit. Most glycosites were modified by sialylated O-glycans such as HexNAc(1)Hex(1)NeuAc(1) and HexNAc(1)Hex(1)NeuAc(2). Our results are the first to reveal that the SARS-CoV-2 S protein is a mucin-type glycoprotein; clustered O-glycans often occur in the N- and the C-termini of the S protein, and the O-glycosite and O-glycan compositions vary with the host cell type. These site-specific O-glycosylation landscapes of the SARS-CoV-2 S protein are expected to provide novel insights into the viral binding mechanism and present a strategy for the development of vaccines and targeted drugs. Copy rights belong to original authors. Visit the link for more info

Talk to a Dr. Berg Keto Consultant today and get the help you need on your journey (free consultation). Call 1-540-299-1557 with your questions about Keto, Intermittent Fasting or the use of Dr. Berg products. Consultants are available Monday through Friday from 8:30 am to 9 pm EST. Saturday & Sunday 9 am to 5 pm EST. USA Only. Take Dr. Berg's Free Keto Mini-Course! In this podcast, I want to talk to you about vitamin A and your immune system. Now, I've done plenty of other videos on the role of zinc, vitamin D, and vitamin C in the immune system, but I haven't touched on vitamin A yet. Vitamin A is an essential part of the immune system. A vitamin A deficiency will leave your body susceptible to infections—especially in the respiratory system, including your lungs, sinuses, and throat. You need vitamin A for your mucous membranes. In particular, vitamin A is required for the creation of mucin. Mucin is an essential part of the mucus membrane. Vitamin A is also involved in the epithelial layer and lymphatic system layer. Each of these acts as a barrier for microbes. When pathogens enter the body, your body triggers macrophages. These are large phagocytic cells that consume pathogens and clean up other harmful debris. Macrophages are your body's first line of defense against infection. Your thymus gland, which is right above the heart, helps train your immune cells. The thymus can actually activate and synthesize vitamin A. Vitamin A is also required for dendritic cells and neutrophil traps. When you're low in vitamin A, your risk increases for: • Ulcerative colitis • MS • Psoriasis • Lupus How can you get more vitamin A? The best source of vitamin A are: • Beef • Liver • Cod liver oil • Mackerel • Salmon • Goat cheese • Butter • Cream cheese • Eggs • Vegetables (pre-vitamin A in carotenoid form) Dr. Eric Berg DC Bio: Dr. Berg, 51 years of age is a chiropractor who specializes in weight loss through nutritional & natural methods. His private practice is located in Alexandria, Virginia. His clients include senior officials in the U.S. government & the Justice Department, ambassadors, medical doctors, high-level executives of prominent corporations, scientists, engineers, professors, and other clients from all walks of life. He is the author of The 7 Principles of Fat Burning. FACEBOOK: fb.me/DrEricBerg?utm_source=Podcast&utm_medium=Anchor TWITTER: http://twitter.com/DrBergDC?utm_source=Podcast&utm_medium=Post&utm_campaign=Daily%20Post YOUTUBE: http://www.youtube.com/user/drericberg123?utm_source=Podcast&utm_medium=Anchor DR. BERG'S SHOP: https://shop.drberg.com/?utm_source=Podcast&utm_medium=Anchor MESSENGER: https://www.messenger.com/t/drericberg?utm_source=Podcast&utm_medium=Anchor DR. BERG'S VIDEO BLOG: https://www.drberg.com/blog?utm_source=Podcast&utm_medium=Anchor

In this episode, we will be diving extensively into a powerful muscle promoting mechanism known as phospholipase. Following that, we dive into a potential treatment for cancer using an unlikely ally. Finally, I discuss research out of McMaster University developing a new style of antibiotic. Phospholipase (1:18) https://www.youtube.com/watch?v=EtV3yWw0hz8&t=3s Cancer & Unlikely Ally (19:20) Xue Zhang, Tingting Zhang, John N. Davis, Andrea Marzi, Anthony M. Marchese, Michael D. Robek, Anthony N. van den Pol. Mucin-like domain of Ebola virus glycoprotein enhances selective oncolytic actions against brain tumors. Journal of Virology, 2020; DOI: 10.1128/JVI.01967-19 Antibiotic: (25:15) https://www.sciencedaily.com/releases/2020/02/200212131523.htm

The Journal of Rheumatology's Editor-in-Chief Earl Silverman talks about this month's selection of articles that are most relevant to the clinical rheumatologist. This month's selections include: Therapy with Biologic Agents After Diagnosis of Solid Malignancies: Results from the Corrona Registry Dimitrios A. Pappas, Sabrina Rebello, Mei Liu, Jennifer Schenfeld, YouFu Li, David H. Collier and Neil A. Accortt DOI: https://doi.org/10.3899/jrheum.171457 Opioid Use in Patients with Ankylosing Spondylitis Is Common in the United States: Outcomes of a Retrospective Cohort Study Victor S. Sloan, Anna Sheahan, Jeffrey L. Stark and Robert Y. Suruki DOI: https://doi.org/10.3899/jrheum.180972 Clinical Outcomes and Clinico-pathological Correlations in Lupus Nephritis with Kidney Biopsy Showing Thrombotic Microangiopathy Chao Li, Desmond Y.H. Yap, Gavin Chan, Yu-bing Wen, Hang Li, Colin Tang, Xue-mei Li, Xue-wang Li and Tak Mao Chan DOI: https://doi.org/10.3899/jrheum.180773 MicroRNA-mediated Regulation of Mucin-type O-glycosylation Pathway: A Putative Mechanism of Salivary Gland Dysfunction in Sjögren Syndrome Alessia Gallo, Serena Vella, Fabio Tuzzolino, Nicola Cuscino, Antonella Cecchettini, Francesco Ferro, Marta Mosca, Ilias Alevizos, Stefano Bombardieri, Pier Giulio Conaldi and Chiara Baldini DOI: https://doi.org/10.3899/jrheum.180549 Response to Early-onset Pamidronate Treatment in Chronic Nonbacterial Osteomyelitis: A Retrospective Single-center Study Caroline Marie Andreasen, Anne Grethe Jurik, Mia B. Glerup, Christian Høst, Birgitte T. Mahler, Ellen-Margrethe Hauge and Troels Herlin DOI: https://doi.org/10.3899/jrheum.181254 To read all the full articles visit www.jrheum.org Music by David Hilowitz

Vincent Racaniello, Michael Schmidt, Michele Swanson and Elio Schaechter How a bacterium helps dengue virus replicate in the mosquito gut, and minicells as a damage disposal mechanism in E. coli. Become a patron of TWiM. Links: Please take the TWiM listener survey Bacteria help dengue virus in mosquito gut (Cell Host Micr) Fungus helps dengue virus in mosquito gut (TWiV 479) Minicells for disposal of damaged goods (mSphere) TWiM Listener survey Subscribe to TWiM (free) on iTunes, Google Podcasts, Stitcher, Android, RSS, or by email. You can also listen on your mobile device with the Microbeworld app. Become a Patron of TWiM! Send your microbiology questions and comments to twim@microbe.tv

Snail slime skincare is having a moment. But where does the mucin come from, and what happens to the snails? Credits: Reported by Gaby Del Valle, staff writer at The Outline. The Outline World Dispatch is produced and hosted by James T. Green. Our theme is by John Lagomarsino. Learn more about your ad choices. Visit megaphone.fm/adchoices

26 April 2013: In this podcast, Dr. Robert Dellavalle speaks with Dr. Victoria Werth about increased mucin in patients with dermatomyositis and how this relates to increased accumulation of a sugar chondroitin sulfate, CD44 Variant 7 and Osteopontin. This clinical finding has been modeled in in vitro experiments of stretched fibroblasts and provides an example of how the immune system can trigger a chronic inflammatory response in the skin.

Niklas Lollo interviews Vickie Ly, of the NASA Ames Research Center, about her work with NASA Develop: an applied science capacity building initiative. Her work weaves remote sensing, watercolor videos and environmental problem-solving to improve the Navajo Nation's drought monitoring and water management efforts.TRANSCRIPTSpeaker 1:Method to the madness is next. You're listening to method to the badness, a biweekly public affairs show on k l x Berkeley Celebrating Bay area innovators. I'm your host, Nicholas Lolo. And today I'm going to be interviewing Vicki Lee and her science researcher and science communicator at NASA Ames Research Center in mountain view, California. Welcome to [00:00:30] the show, Vickie. So you work at the NASA Ames research center and in particular you work with the NASA developed program. Mine explaining what the NASA developed program is. Speaker 2:So NASA developed is a program within the applied sciences and what we do is be partner with other organizations, non-governmental governmental, um, different agencies and we partner with them to utilize NASA earth observation data, satellite data, and we apply that to different environmental concerns [00:01:00] and issues that they have. What are some sort of environmental concerns that you might apply it to? So for example, one of the main projects I've been working on is with the Navajo nation. And what we've been doing is figuring out how we can use NASA satellite data, precipitation data, and apply that to different drought monitoring efforts that they have. And it's, it's a really arid and dry place. It's located in the four corners of, um, Arizona, Utah, New Mexico [00:01:30] and Colorado. People may be familiar with monument valley. Yeah, that's right. Yeah. And so when you're driving out there, you're just seeing these big red rocks, blue skies, beautiful country out there. Speaker 2:Um, but it's also a lot, there's also a lot of challenges and um, in particularly it's looking at water, it's looking at water availability and it's looking at how you monitor water. And this has been a challenge [00:02:00] in the past and with climate change it's potentially going to be more variable and more difficult for monitoring water. Yeah, definitely. I think, um, I think the biggest challenges in the Navajo nation is how to, how to monitor water and how to monitor drought on a continuous scale and with spatial continuity and spatial coverage. [00:02:30] Why is NASA working with these communities? Speak about that, that tension. Um, was it difficult to approach them or did they approach you? Um, how did the connection start? Yeah. So how this partnership started between NASA and the Navajo nation was through Cindy Schmitt, who was a longtime researcher at of NASA Ames in mountain view, California. Speaker 2:And she's been working with different end judge Digitas groups for over 10 years. Um, she put us in touch [00:03:00] with this gentleman by the name of Ramsay, um, with a Navajo technical university. And then we started talking to the Department of Water Resources and then we started talking to them about different issues that they're having. And um, one of them was looking at how, looking at how they collect water and looking at how they collect precipitation, um, data in specific. And with that, how do they calculate, um, [00:03:30] something called the SPI or standard precipitation index, something that tells how wet or dry and area is and sort of how severely, um, or sort of it's a gauge at looking at, um, drought and whether an area is experiencing drought or not. So I want to take a step back here. Satellites can capture precipitation data. Yeah. So satellites can do all types of things. Speaker 2:Um, I think that what [00:04:00] most people are most familiar with in terms of satellites is looking at land cover, looking at land cover change, um, or just looking at maps of the places that they want to go and the places that they do go. And they do that by taking a bunch of high resolution images or low resolution depending on, yeah. So it kind of depends on um, sort of the frequency that you're looking at and sort of the range in the electromagnetic spectrum that you're [00:04:30] looking at. Maybe you're looking at red, green, blue, what we all look at in images and pictures that we see with our naked eye. Um, I e maps that we use on line like Google maps, but in other cases you can also look at near infrared or infrared, um, or other parts of the spectrum to get other types of information that you wouldn't be able to with your, with all near your eyes. Speaker 2:How have they been collecting data before this? They have rain gauge [00:05:00] stations and re-engage rain gauges all across the Navajo nation and that sort of just like a bucket collecting water. And then they're recording the observations on any given day essentially. Yeah. So they have, it's essentially like a, a bucket and then, um, it collects rain and then every single, every single monthly, they go out on a certain day of the month, then they go out and drive to all of the rain cans and then, um, [00:05:30] measure what is, what has been collected for that month. So they were collecting data in buckets and having to drive around once per month. Why was that not sufficient? They actually still do that. They go out and still collect all of the rain gauge data monthly. But you know, one of the things is the Navajo nation is the biggest native territory in the u s and both and size. Speaker 2:I mean, it's the size of [00:06:00] West Virginia to drive out and collect all of that data takes a lot of time and um, to maintain those places. And some of those places are so, um, rain stations, weather stations. And so, um, to maintain those also takes a lot of upkeep. So the utility of using satellite data is that it is continuous and regular and [00:06:30] it doesn't, you don't have to go out and get it. You just go onto your computer and download it. And it can be more precise too. Yeah, I mean it provides spatial, um, coverage versus having like one rain gauge and having just one point, you'll can look at entire areas and you can look at precipitation and how it covers all this area. And then you're able to take that precipitation [00:07:00] data, compare it to, um, a historical average and be able to say much more about a whole territory, a whole area than you are from a single point or sort of interpretating from different points. Speaker 2:And can you describe a bit how the tool actually works? Yeah, so there's three main steps, um, within d sat. The first is to calculate an SBI. So you choose the type of SBI you want [00:07:30] to look at, uh, one month, six month or 12 month. Um, all of those correspond to different types of drought that you're looking at, agricultural, immunological, and then you choose the starting day or starting month. And the starting year and ending year. So that sort of gives you a range of time that you want to look at and calculate your spis for. Um, then in the next step you, um, are able to take what you've calculated [00:08:00] those spis and um, be able to look at statistics of those. So you are able to look at, you're able to look at statistics for a certain boundary. So you choose, um, the data that you've processed. Speaker 2:And then you choose a certain boundary that you want to look at, for example, like agencies. And then within every single agency you're able to look at the statistics for that agency. So you can see, um, [00:08:30] the mean SPI for from April, 2014 to current. Um, and then the last step, which is really the, um, jazz hands snap, it's the, I don't know how to just the time lapse animations. Yeah. Yeah. So, um, the [00:09:00] last step is sort of the shiny step, sort of the, you're quoted as saying it's the bread and butter and the Cherry on top. Speaker 2:Yes, it is both the bread and butter and also the cherry on top. Um, and within the last step you're able to visualize the spis. So, um, sort of addressing that issue of having spatial continuity [00:09:30] and coverage. Um, you're able to visualize SBI rasters, um, on a map and you're able to overlay different boundaries on top of that. So you can look at the Navajo nation political territories, watersheds, eco regions, um, on top of that and, and over time as well over a seasons or years. That's the sort of get in, get a sense for the history of drought or [00:10:00] rain in the area. Yeah, that's right. So based on the time that you selected in the previous step of the calculate SBI, um, then you're able to look at the time range and um, you're able to sort of run through time and see the changes seasonally. Speaker 2:Um, and one other feature that is in there is plot analytics, um, which allows you to look at a certain area, um, within a boundary [00:10:30] and you identify that area and then it breaks it down of how much, what percent of that area is experiencing, what type of droughts it really wet, um, a really dry and everything in between. Okay. So you come in with a lot of this technical expertise and these sophisticated instruments. Is it difficult or was it a challenge for you to not appear like you're just imposing your ideas [00:11:00] on this community that has been working on monitoring its own water resources? Yeah, I think that, um, that's definitely a really big consideration. One. And when working with the Nova nation and with different indigenous communities, because you know, a lot of people are very interested in working with different indigenous communities. Speaker 2:Um, and there's great need, but a lot of groups also go in and, [00:11:30] um, create something and then sort of depart. And in that, in trying to create a project, it was also how to create a partnership. How do you create a longterm partnership and how to really think about how this project is a stepping stone for other projects to come. And so how did you eat better, create that partnership? How did sort of approach them? I know you made some videos. Were those helpful? Yeah. So to better build some of those at [00:12:00] partnership. Um, one we had lots and lots of telecoms, which is always a lot of fun because you get to talk to people without seeing their face. That's a teleconference. Yes. A seller conference. Speaker 2:So we had lots of telecoms, but in addition, um, we wanted to make some videos that sorta explained our project and something that we could use to explain our project, but also they could use to explain our partnership and [00:12:30] where we're going. And so one of the things that I wanted to do with the videos was to sort of take out our narration as much as possible and to use more of their narration. Um, because no one can really describe problem more than the person and people that are actually experiencing it. So, um, I hopped on the phone, I asked Theresa show one of the principal hydrologists if I could interview her. And at first she was like, um, [00:13:00] you want to what? And I was like, can I interview you for a video? And she's like, you're making a video. And I was like, just trust me. Speaker 2:It's all gonna work out. She's like, does my face have to be on it? And I was like, now your face doesn't have to be on it. Um, I think you should explain the videos a little more because they're very creative. I guess the idea came, I remember trying to think about how we could create a video and what it would look like. [00:13:30] And I was thinking about like how we could get imagery, um, what type of images we would use and video and all of that. And in thinking about that one, the thing with youth with remote sensing with using satellites is that, uh, remote sensing implies that it's remote. So you actually aren't there. Like we work in California while the nomination is mostly in Arizona. So I was trying to think how could we collect data, how could we collect film, how [00:14:00] could we collect sound, how could we get these sort of technical details of a video. Speaker 2:And I was kind of hitting a wall because I'm like, well, we aren't out there. We won't be able to make it out there just to shoot anything. Um, and that would take a lot of time to and resources that we don't have. And um, at the same time, um, one of my friends, Abby van Mucin was teaching a decal, um, here at [00:14:30] UC Berkeley and a decal is a student course. That's right. It's a student led course and she teaches this decal decal on how to take notes and how to illustrate your notes. So you ended up making these like beautiful watercolor videos. And this was inspired by Abby [inaudible]. Yeah. So Abby does these really great water color videos and it's sort of in, everything's in motion. So you're watching this hand move across the screen [00:15:00] painting all of these different images and transitioning from one scene to another. Speaker 2:I was really inspired by her work because I thought it was a really great way to one, explain something because you're watching this blank canvas turn into something and then at the same time you're also watching one idea transform into another idea, transform into another idea, transcend, formed another idea. So in a way it was like how do we connect all the dots [00:15:30] in a project? You know, how do we explain the issue? How do we explain what we're trying to address? How do we explain what we are trying to develop? Um, the tool that we're trying to develop, how do we explain the technical things without being too technical? One of the solutions is make it pretty right. Nobody can refuse it. Pretty pretty picture. And when the viewer watches the picture of pier, they get a better sense of how [00:16:00] everything is connected. And I think we have a bit of the audio to share here today. Of course the listeners won't get the full experience for that. They can go on youtube and check out the video at NASA, develop beyond a shadow of a drought. Speaker 3:If you leave on a half Pinko monitor water. If you leave 45 with a rock area, you have to drive all the way over to five hours. How many sites, and you know they do that every month. [00:16:30] We would like to cut back to where we could manage a few of the site and some are going to be managed by [inaudible]. If we could get some of our data remotely and religiously, it would help our program tremendously Speaker 3:from one of the things that we wanted to do is to show the Navajo leadership. That's when we get emergency drought dollars. Where do we concentrate the leaf or [00:17:00] the way it is right now? Every time we have a drought, drought mitigation dollars get equally stripped at 110 chapters. You want a big shirt that's dropped. Mitigation dollars goes into chapters that we did the most with our tool. Water managers like Robert and Teresa, and better understand which agencies are in a greater state of drought. They're using NASA earth observations, drought mitigation resources [00:17:30] can be focused in the places where they're needed the most Speaker 4:[inaudible]. Speaker 2:It really is a work. Did you find that useful for your project to have to integrate it with a storyboard and with the music? Yeah, definitely. Um, [00:18:00] it was really helpful because that storyboard served for our outline, for our papers. It served for an outline for our presentations. Um, so you took the video storyboard and then turned it into a academic paper. Yeah. And then we just filled in like technical details and all of the other stuff that we needed to put in there. Wow, that's a pretty good idea. Yeah, because you're drawing, you're literally drawing out all of the details and [00:18:30] if you can explain it to somebody that's walking down the street and that street being the Internet, then you can explain it definitely to any of your peers. And so this really helped me with the community, um, with the Navajo nation to help them understand your abilities at NASA. Speaker 2:Yeah, I think so because, I mean, one of the things is people are always asking, well, what's NASA doing here? Um, I've had the [00:19:00] fortune of traveling some with Cindy Schmitt to, um, another reservation, the patchy reservation. And I, I don't think I've ever been asked that in my whole life. Um, the number of times I've, Vanessa, like, uh, so what's NASA doing here? Um, and it was a way that, um, for the video to be used in a way the video could be used by our partners in the Navajo [00:19:30] nation to explain what they're trying to use the tool for. Um, two different people that are visiting the Department of Resource Water Resources. It's a really easy and shareable medium and it takes not a lot of time to watch. So now that you've sort of built the partnership, um, or at least establish some measure of, of partnership, what has been the give and take, like on the project of improving their [00:20:00] water monitoring, when you're creating something, you want that give and take because you want to improve it, you want it, you're creating something for an end user. Speaker 2:And so in these later stages of the project, um, in these later stages of the project, I've mostly been working with Carl McAllen who's a senior hydrologist. And, um, he's actually the main going to be the main person using m d PSAT, the tool that we're developing. [00:20:30] We'll show him like, this is what we've been trying out, this is what we've been testing, how does this look? Um, and then he'll say, that looks great. Or he'll, we'll be installing things on his computer or walking him through installations, um, or troubleshooting things on his computer with him and I'll screen share his screen and, um, we'll just sort of have this back and forth and we meet pretty much weekly to do so. [00:21:00] Well, so what have you been learning through the partnership? I think what we've been learning is how can this tool actually be used. Speaker 2:You know, we go through the ups and downs of like, is this going to be used at all? Is all of this effort even going to be worth anything? Um, and then we go through these highs of like, oh, this is gonna change everything. And you know, Carl Avon says that too. I'll be like, this is going to be like historic and so why [00:21:30] is it going to be so historic? In his words, it's going to change the way that they do things. The ideas that will change the way that they'll be able to calculate those SPI values and report does SPF values indicating how dry in areas or the degree of trout that an area is experiencing so that you can tell the difference between one area and another area and be able to send drought relief dollars to one area versus another [00:22:00] area. How have they been allocating Jabil leaf dollars before this project? Speaker 2:So that Navajo nation is split up to agencies which are equivalent to states and they divided equally amongst all of the states. So you can think of that in the u s that wouldn't really make sense because certain areas are inherently more dry and inherently more wet. But um, areas are going to experience way more drought than other areas. And so it's the same thing in the Navajo nation. We want to be [00:22:30] able to look at where areas are experiencing the most drought. So you'll be able to target the dollars exactly for those areas that need it most. Yeah, exactly. And that goes back to one of the main things that we wanted to address in this project is the ability to, um, say that one area is drought is experiencing more drought than another. Um, these, besides collecting rain gauge data, the Navajo nation currently uses, um, [00:23:00] SBI values calculated by the western regional climate center. Speaker 2:That's really long mouthful, but basically that only splits the Navajo nation up into three different values. So you're having three values to explain, um, an area that's as large as West Virginia and those values are explaining what degree of drought in each area is experiencing versus having any finer detail of splitting it up by agencies [00:23:30] or chapters or watersheds or any other boundary. So is the Department of water resources retaining any of its old methodology, um, or how is it integrating what it has previously been working on with the new DSM in taking the next steps? That's sort of what we're thinking about. How do, how does this tool fit into the current methodology? And, um, so does it make sense to keep on using the western regional climate center calculations? Does it [00:24:00] make sense to use duset in what context? It doesn't make sense to use it just for monthly. Speaker 2:It doesn't make sense to use it to calculate statistics. Does it make sense just to use it, the raster map. That's sort of something that we're trying to figure out right now in these later stages. And it's, it's really interesting because I feel like we're finally getting to a stage where it's becoming a little bit more real. You know, it's, it's being tested, it's being used [00:24:30] and the next step is really well how is it going to be used? How is it actually going to be implemented and how it will sort of the downstream effects change because of that. It's kind of interesting cause I think it's going to be kind of a lot of trial and error from here on out. Um, and it's going to take some experimentation and, but there is a lot of promise. One of the exciting things that this project will be a part of is a larger indigenous [00:25:00] people's initiative. Speaker 2:I'm working title acronym to be created. Um, that is a partnership between NASA and, um, different indigenous communities in that initiative. Um, the idea is really to, to create a space where NASA can be come a facilitator with different communities. How do we bring tools, how do we create projects together? How do we create these longterm partnerships, [00:25:30] um, where we're educating, um, the youth, we're educating, um, college students, we're engaging community members and creating projects that are meaningful, culturally significant, sort of environmentally important. So not just drought. You might be moving on to whatever is relevant for that particular community. Yeah, definitely. I think that there's a lot of opportunity to expand much more and the idea sort [00:26:00] of to get coverage across the u s so having the southwest pocket, um, with the Nava nation and the Paci and working in the southeast as well as in lake country as well as in um, the Pacific northwest. Speaker 2:All of these different areas are experiencing different types of environmental change. And so with that brings a lot of opportunity for us to be involved and um, [00:26:30] to create different projects and collaborations. So y'all at NASA develop, have tried to, you know, make this very accessible I guess and a, a, a great user interface which maybe scientists don't typically develop. Um, and having open source code put up on get hub. Um, can you tell me a little bit more about those projects and what was the motivation behind creating open source code? Yeah, I [00:27:00] guess, I mean the idea behind NASA capacity building and a lot of the initiatives that we have in applied sciences is working with the public and serving the public. And um, in that, I mean the idea when we're creating this is how do we, how do we get this in other people's hands? Speaker 2:How do we, how can, how can we, can we use this in other areas? I mean, so many different parts of the world are experiencing drought [00:27:30] and if that can be used in other areas more the better. Yeah. So you have it. An open source and coated in the program language are [inaudible], which is also free and open source. And that's sort of that. One of the ideas too behind it is, is working when working with different communities, you want to make things available. You don't want to create things where you have to have certain software programs that may be more expensive. Um, [00:28:00] so one of the intentions behind that was what can we use out there that is free and open source and virtually anybody anywhere could download it and be able to use it. Speaker 1:Thank you so much, Vickie, for coming in today. So great to hear about your project. We're excited for where we're incented. Speaker 2:Thanks Nick. Speaker 1:And if you'd like to learn more about NASA develop in their other projects, you can check out their youtube page at NASA develop or [00:28:30] you can visit their website at develop dot l a r c. Dot nasa.gov. See acast.com/privacy for privacy and opt-out information.

Background Mucin-1 (MUC1, CD227), more widely known as CA15-3, is an abundantly expressed epithelial cell surface antigen and has evolved to be the most predictive serum tumour marker in breast cancer. PankoMab-GEX™, which is currently being evaluated for its therapeutic efficacy in a phase IIb clinical trial, is a glyco-optimized anti-MUC1 antibody specifically recognizing a tumour-associated MUC1 epitope (TA-MUC1). The current study aimed to analyse the immunoreactivity of PankoMabGEX™ and its correlation with established clinico-pathological variables including 10-year and overall survival in a large cohort of breast cancer patients. Methods Breast cancer tissue sections (n = 227) underwent a standardized immunohistochemical staining protocol for TA-MUC1 by using PankoMab-GEX™ as a primary antibody. The staining was evaluated by two independent observers and quantified by applying the IR-score. Results TA-MUC1 as detected by PankoMab-GEX™ was identified in 74.9% of breast cancer tissue sections. Patients were subdivided according to the subcellular localisation of TA-MUC1 and cases classified as mem-PankoMab-GEX™ (solely membranous) positive, cyt-PankoMab-GEX™ (solely cytoplasmic) positive, double positive or as completely negative were compared regarding their survival. Herein mem-PankoMab-GEX™-positive patients performed best, while double-negative ones presented with a significantly shortened survival. Positivity for mem-PankoMab-GEX™ as well as a double-negative immunophenotype turned out to be independent prognosticators for survival. Conclusions This is the first study to report on PankoMab-GEX™ in a large panel of breast cancer patients. The PankoMab-GEX™ epitope TA-MUC1 could be identified in the majority of cases and was found to be an independent prognosticator depending on its subcellular localisation. Since TA-MUC1 is known to be highly immunogenic cancers staining positive for PankoMab-GEX™ might be more compromised by host anti-tumour immune defence. Further, the observations reported here might be fundamental for selecting patients to undergo PankoMab-GEX™-containing chemotherapy protocols.

Hintergrund und Zielsetzung: Die aktuelle TNM-Klassifikation berücksichtigt bis dato nicht die tatsächliche Tumorlast bei mehrherdigen Mammakarzinomen. Neuere Daten weisen darauf hin, dass mehrherdige Karzinome im Vergleich zu einherdigen Karzinomen bei identischem TNM-Stadium eine schlechtere Prognose hinsichtlich Gesamtüberleben und Rezidivauftreten haben. Ziel dieser Studie war es, mögliche Unterschiede in der Tumorbiologie von ein- und mehrherdigen Mammakarzinomen zu evaluieren. Material und Methoden: Wir verglichen retrospektiv 57 einherdige mit 55 mehrherdigen Mammakarzinompatientinnen. Aus diesem Gesamtkollektiv isolierten wir eine Matched-Pair-Gruppe mit 46 Patientinnen, deren Kollektive hinsichtlich Tumorgröße, Grading und Lymphknotenstatus übereinstimmten. Die Paraffinschnitte jeder Patientin wurden immunhistochemisch auf die Expression von E-Cadherin, Beta Catenin und Mucin-1 untersucht. Ergebnisse: Die E-Cadherin-Expression war bei den mehrherdigen Mammakarzinomen signifikant reduziert gegenüber den einherdigen Karzinomen (Gesamtkollektiv: p

Brian Button discusses a feedback mechanism for insuring the proper hydration of airway mucus.

Background: Mucin-1 is known to be over-expressed by various human carcinomas and is shed into the circulation where it can be detected in patient's serum by specific anti-Mucin-1 antibodies, such as the tumour marker assays CA 15-3 and CA 27.29. The prognostic value of Mucin-1 expression in ovarian carcinoma remains uncertain. One aim of this study was to compare the concentrations of Mucin-1 in a cohort of patients with either benign or malignant ovarian tumours detected by CA 15-3 and CA 27.29. Another aim of this study was to evaluate Mucin-1 expression by immunohistochemistry in a different cohort of ovarian carcinoma patients with respect to grade, stage and survival. Methods: Patients diagnosed with and treated for ovarian tumours were included in the study. Patient characteristics, histology including histological subtype, tumour stage, grading and follow-up data were available from patient records. Serum Mucin-1 concentrations were measured with ELISA technology detecting CA 15-3 and CA 27.29, Mucin-1 tissue expression was determined by immunohistochemistry using the VU4H5 and VU3C6 anti-Mucin-1 antibodies. Statistical analysis was performed by using SPSS 18.0. Results: Serum samples of 118 patients with ovarian tumours were obtained to determine levels of Mucin-1. Median CA 15-3 and CA 27.29 concentrations were significantly higher in patients with malignant disease (p < 0.001) than in patients with benign disease. Paraffin-embedded tissue of 154 patients with ovarian carcinoma was available to determine Mucin-1 expression. The majority of patients presented with advanced stage disease at primary diagnosis. Median follow-up time was 11.39 years. Immunohistochemistry results for VU4H5 showed significant differences with respect to tumour grade, FIGO stage and overall survival. Patients with negative expression had a mean overall survival of 9.33 years compared to 6.27 years for patients with positive Mucin-1 expression. Conclusions: This study found significantly elevated Mucin-1 serum concentrations in ovarian carcinoma patients as compared to those women suffering from benign ovarian diseases. However, it needs to be noted that Mucin-1 concentrations in carcinoma patients showed a rather high variability. Results from immunohistochemistry indicate that Mucin-1 has a prognostic relevance in ovarian carcinomas when evaluating the expression by VU4H5 antibody.

Thu, 24 Mar 2011 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/12909/ https://edoc.ub.uni-muenchen.de/12909/1/Lapa_Constantin_Frederik_Victor.pdf Lapa, Constantin ddc:610, ddc:600, Medizinische

Aim: PankoMab is a novel antibody that recognizes a tumor-specific epitope of Mucin 1 (MUC1). The aim of this study was the evaluation of PankoMab as a potential diagnostic tool and its comparison with two established antibodies against MUC1 in human ductal breast cancer. Materials and Methods: Breast carcinomas were obtained from 82 patients. MUC1 expression and hormone receptor status were determined by immunohistochemistry of paraffin-embedded material. Results: PankoMab revealed strong correlation to hormone receptor expression. DF3 showed no correlation with grading, lymph node involvement and/or estrogen receptor (ER) expression. In the subgroup of lymph node-positive and ER-negative tumors, we saw a significantly reduced DF3 staining in G3 tumors compared to G2 tumors. VU-4-H5 showed increased staining intensity in correlation with increased grading. In addition, we also identified a significantly higher expression of the VU-4-H5 epitope in lymph node-positive carcinomas compared to carcinomas without lymph node involvement. Conclusion: PankoMab revealed strong correlation to hormone receptor expression in ductal carcinoma of the breast. VU-4-H5 showed increased staining intensity in correlation with increased grading and lymph node involvement. PankoMab and VU-4-H5 staining could be a useful combination in ductal breast cancer prognosis by immunohistochemistry.

This week news that men talk as much as women, cosmetics from jellyfish, songbirds "greatest-tits", a breathtaking asthma breakthrough and a gene-screen for bowel cancer. We also uncover the cause of contagious yawns, probe the brain basis of epilepsy and manic depression, and uncover a brain region responsible for out of body experiences. Plus, in Kitchen Science, Ben and Dave find out why the raisins always rise to the top of the cereal box. Like this podcast? Please help us by supporting the Naked Scientists

This week news that men talk as much as women, cosmetics from jellyfish, songbirds "greatest-tits", a breathtaking asthma breakthrough and a gene-screen for bowel cancer. We also uncover the cause of contagious yawns, probe the brain basis of epilepsy and manic depression, and uncover a brain region responsible for out of body experiences. Plus, in Kitchen Science, Ben and Dave find out why the raisins always rise to the top of the cereal box. Like this podcast? Please help us by supporting the Naked Scientists

Some biliary proteins (pronucleators) seem to be essential factors for cholesterol crystal formation and crystal growth in bile. A recent study suggests that fibronectin is such a pronucleator in bile. Fibronectin also seems to closely interact with intestinal mucin. Since biliary mucin plays an important role in gallstone formation, such an interaction in bile may be of relevance in cholesterol gallstone formation. To more clearly elucidate the role of fibronectin in cholesterol gallstone disease, we measured the concentration of fibronectin in native bile of cholesterol gallstone patients and checked its influence on the cholesterol nucleation time of model bile. We further looked for a molecular interaction between biliary fibronectin and gallbladder mucin. We found that fibronectin is present in gallbladder bile of gallstone patients in low concentrations (2.6 +/- 1.2 micrograms/ml). Bile fibronectin did not interact with gallbladder mucin. Moreover, in a wide range of concentrations fibronectin had no influence on the nucleation time of model bile. We conclude that fibronectin does not seem to play a major role in cholesterol gallstone disease.