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Dr. Cynthia Bulik is a clinical psychologist and one of the world's leading experts on eating disorders. She is the Founding Director of the University of North Carolina Center of Excellence for Eating Disorders and also the founder director of the Centre for Eating Disorders Innovation at Karolinska Institutet in Stockholm, Sweden. Dr. Bulik is Distinguished Professor of Eating Disorders in the Department of Psychiatry at UNC, Professor of Nutrition in the Gillings School of Global Public Health, and Professor of Medical Epidemiology and Biostatistics at Karolinska Institute. Dr Bulik has received numerous awards for her pioneering work, including Lifetime Achievement Awards from the National Eating Disorders Association, the Academy for Eating Disorders, and the International Society of Psychiatric Genetics. She has written over 750 scientific papers, and several books aimed at educating the public about eating disorders. Currently, Dr. Bulik's focus is in the reconceptualization of eating disorders as being a metabo-psychiatric diseases. Food Junkies is keen to explore this interest in how metabolic disease plays a role in disordered eating: can this construct be the common ground to start to understand the muddy waters between eating disorders and food addiction? In This Episode, You'll Learn:
Matters Microbial #91: You Are What Your Genes Feed Your Microbiome May 16, 2025 Today, Dr. Emily Davenport, Assistant Professor in the Department of Biology and Huck Institutes of the Life Sciences at Penn State University, joins the #QualityQuorum to tell us about the research her team does, studying how our own genes impact our microbiomes. Host: Mark O. Martin Guest: Emily Davenport Subscribe: Apple Podcasts, Spotify Become a patron of Matters Microbial! Links for this episode A description of GWAS (“Genome Wide Association Study”). Here is an introductory video about the concept. An explainer on organoids. An essay about the diversity of the host microbiome (i.e. is there a “healthy” microbiome?). An article of the work of Dr. Sarkis Mazamian on how individual host genes and bacterial genes can impact the microbiome. A nice write up for Dr. Mazamian's work showing how host genes and bacterial genes can work together…or not. An oldish video of how the infant microbiome develops over time by Dr. Rob Knight's research group. An article on the same topic from Dr. Ruth Ley. An essay on the mucosal microbiota, rather than the fecal microbiome. An interesting member of the human microbiome, Akkermansia that might be related to obesity. Another interesting member of the human microbiome, Bifidobacterium, which appears to be associated with host lactose metabolism. Yes, there is a Giant Microbes plush toy. An overview of the impact of host genetics on the microbiome by Dr. Davenport. A definition of heritability. An overview of the Hutterites and how their study has advanced genetics. An explainer of the power of twin studies in genetics. A fascinating article about ancient dental plaque microbiome by Dr. Davenport and others. Dr. Davenport's faculty website. Dr. Davenport's research group website. Intro music is by Reber Clark Send your questions and comments to mattersmicrobial@gmail.com
BUFFALO, NY — April 29, 2025 — A new #research paper was #published in Aging (Aging-US) Volume 17, Issue 3, on March 20, 2025, titled “Inhibition of the metalloprotease ADAM19 as a novel senomorphic strategy to ameliorate gut permeability and senescence markers by modulating senescence-associated secretory phenotype (SASP).” Researchers, led by first author Sudipta Bar and corresponding authors Amit Sharma and Pankaj Kapahi from the Buck Institute for Research on Aging, have found that the enzyme ADAM19 plays an important role in regulating aging in cells and inflammation in the gut. Their study shows that blocking ADAM19 reduced gut damage and inflammation in fruit flies, mice, and human cells. This discovery points to a new possible way to treat gut disorders related to aging by reducing the harmful signals from senescent (aging) cells. As individuals age, DNA damage can lead to the accumulation of senescent cells, contributing to tissue damage. These are cells that stop dividing and release harmful inflammatory substances called the senescence-associated secretory phenotype (SASP). In this study, researchers used fruit flies to search for genes involved in radiation-related gut damage. They identified a gene called meltrin, which is similar to human ADAM19. When meltrin was turned off, the flies had less gut leakage, less inflammation, and fewer signs of cellular aging. “Through an unbiased genome-wide association study (GWAS) utilizing 156 strains from the Drosophila Genetic Reference Panel (DGRP), we identified meltrin (the drosophila orthologue of mammalian ADAM19) as a potential modulator of the senescence-associated secretory phenotype (SASP).” To test if these results applied beyond flies, the team inhibited ADAM19 in mice using a drug called batimastat. Mice treated with the drug after chemotherapy exposure had stronger gut barriers and lower levels of inflammatory markers. The findings extended to human cell cultures, where ADAM19 inhibition reduced signs of cellular aging, including the expression of SASP proteins and β-galactosidase, a classic aging marker. Importantly, this approach does not kill aging cells like many 'senolytic' therapies but instead reduces the harmful substances they release, making it a potential "senomorphic" strategy. The study also showed that ADAM19 helps release certain SASP proteins by cutting them at the cell surface, suggesting a direct role in regulating inflammatory signals. Through proteomic analysis, the team identified 12 SASP proteins that were significantly reduced when ADAM19 was blocked. Many of these proteins are linked to inflammation, immune response, and tissue remodeling in diseases such as inflammatory bowel disease and Crohn's disease. This connection underlines the relevance of the findings for treating chronic gut disorders in aging populations. By targeting ADAM19, researchers may have found a new way to protect gut health and lower inflammation caused by aging cells. This study offers a promising path for creating treatments that maintain healthy tissues without having to destroy aging cells, which could benefit people with gut damage related to aging or medical treatments. DOI - https://doi.org/10.18632/aging.206224 Corresponding authors - Amit Sharma - amit.sharma@sens.org, and Pankaj Kapahi - pkapahi@buckinstitute.org Video short - https://www.youtube.com/watch?v=dRfxQ20O2fQ Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts To learn more about the journal, please visit our website at https://www.Aging-US.com. MEDIA@IMPACTJOURNALS.COM
This week, we explore the genetics behind the production of antinuclear antibodies (ANA) in individuals without clinical autoimmune disease, using data from the All of Us registry. Our guest, Dr. Mehmet Hocaoglu shares insights into the significance of understanding ANA positivity and its potential genetic underpinnings, highlighting how large-scale genome-wide association studies (GWAS) can predict susceptibility to autoimmune conditions. We cover the study's methodology, the unique All of Us dataset, and the complexities of genetic analysis. Dr. Hocaoglu also discusses his personal journey in rheumatology research, offering advice for aspiring researchers, especially international medical graduates (IMGs).
Welcome to the Olink® Proteomics in Proximity podcast! Below are some useful resources mentioned in this episode: Olink® Reveal, accessible NGS-based proteomics for every lab: https://olink.com/products/olink-revealOlink tools and software· Olink® Explore 3072, the platform utilized by the UK Biobank to measure ~3000 proteins in plasma: https://olink.com/products-services/explore/· Olink® Explore HT, Olink's most advanced solution for high-throughput biomarker discovery, measuring 5400+ proteins simultaneously with a streamlined workflow and industry-leading specificity: https://olink.com/products-services/exploreht/ UK Biobank Pharma Proteomics Project (UKB-PPP), one of the world's largest scientific studies of blood protein biomarkers conducted to date, https://www.ukbiobank.ac.uk/learn-more-about-uk-biobank/news/uk-biobank-launches-one-of-the-largest-scientific-studies Subscribe to the podcast on your favorite player or app:Apple Podcasts: https://apple.co/3T0YbSm Spotify Podcasts: https://open.spotify.com/show/2sZ2wxO... Google Podcasts: https://podcasts.google.com/feed/aHR0... Amazon Music: https://music.amazon.com/podcasts/d97... Podcast Addict: https://podcastaddict.com/podcast/409... Deezer: https://www.deezer.com/show/5178787 Player FM: https://player.fm/series/series-3396598 In case you were wondering, Proteomics in Proximity refers to the principle underlying Olink technology called the Proximity Extension Assay (PEA). More information about the assay and how it works can be found here: https://bit.ly/3Rt7YiY For any questions regarding information Olink Proteomics, please email us ...
Welcome to the Olink® Proteomics in Proximity podcast! Below are some useful resources mentioned in this episode: Olink tools and software· Olink® Explore 3072, the platform utilized by the UK Biobank to measure ~3000 proteins in plasma: https://olink.com/products-services/explore/· Olink® Explore HT, Olink's most advanced solution for high-throughput biomarker discovery, measuring 5400+ proteins simultaneously with a streamlined workflow and industry-leading specificity: https://olink.com/products-services/exploreht/ UK Biobank Pharma Proteomics Project (UKB-PPP), one of the world's largest scientific studies of blood protein biomarkers conducted to date, https://www.ukbiobank.ac.uk/learn-more-about-uk-biobank/news/uk-biobank-launches-one-of-the-largest-scientific-studies Press release and news story from UK Biobank:https://www.ukbiobank.ac.uk/learn-more-about-uk-biobank/news/launch-of-world-s-most-significant-protein-study-set-to-usher-in-new-understanding-for-medicine https://www.ukbiobank.ac.uk/learn-more-about-uk-biobank/news/dataset-of-thousands-of-proteins-marks-landmark-step-for-research-into-human-health https://www.ukbiobank.ac.uk/learn-more-about-uk-biobank/news/uk-biobank-launches-one-of-the-largest-scientific-studies News stories:Today Programme – Professor Rory Collins live on programme, timestamp 02:36:37 Times – ‘Game-changing' study of blood proteins will help fight disease Independent – World's largest proteins study ‘invaluable' for understanding disease – experts Daily Mail – How Alzheimer's could be diagnosed a DECADE earlier following huge study of blood proteins Mirror – New blood test reveals risk of developing different diseases in 'new frontier of science' Science – Seeking disease insights, UK Biobank launches largest study of human proteinsTechnology Networks – UK Biobank Launches Largest Proteomics Study for Disease Research Chemical and Engineering News – Pharma firms team up to study UK proteomics data Links to referred episodes: • Evan – Episode 20: https://share.transistor.fm/s/f795811e https://open.spotify.com/episode/6lv5GA8hZCgDvujlBltS9f?si=36a29e6cfa4b4fae https://podcasts.apple.com/us/podcast/how-proteomics-is-shaping-pharma-strategies/id1645900688?i=1000635040581 • Chris – Episode 16: https://share.transistor.fm/s/255ad207 https://open.spotify.com/episode/0oe0S6zI8cryUtgZTjGlRq?si=8a7b0323b1364b96 https://podcasts.apple.com/us/podcast/interview-about-the-uk-biobank-with-dr-christopher-whelan/id1645900688?i=1000622521524 Subscribe to the podcast on your favorite player or app:Apple Podcasts: https://apple.co/3T0YbSm Spotify Podcasts: https://open.spotify.com/show/2sZ2wxO... Google Podcasts: https://podcasts.google.com/feed/aHR0... Amazon Music:
At-home DNA tests are everywhere, but what can your DNA tell you about your risk for developing serious diseases like cancer? Returning guest Dr. Joel Evans from Genetype and The Center for Functional Medicine explains how a polygenic risk score may help optimize your future. During this episode you'll learn about: This week's guest: Dr. Joel Evans, OB-GYN and functional medicine doctor [0:55] How to use polygenic risk scores, a powerful disease prediction tool [2:45] What are SNPs (single nucleotide polymorphisms)? [5:57] Breakthrough genome-wide association studies (GWAS) [7:15] From GWAS to PRS: Polygenic risk scores show genetic predisposition to disease [10:55] How polygenic risk scores compare to popular DNA test kits [13:14] Who may benefit from getting their polygenic risk score measured? [17:22] Questions from the community If I score high on polygenic risk for something like cancer, does that mean I will get cancer? [22:22] How much do polygenic risk tests cost? Are they worth the cost? [26:49] Are polygenic risk scores the same as ancestry DNA tests? [28:55] How do polygenic risk scores work? Are they secure? Do I need to worry about privacy? [30:02] How can I use my polygenic risk score to optimize my health? [33:21] Resources to topics mentioned in this episode: Learn more about Dr. Joel Evan's work on polygenic risk scores at Genetype and The Center For Functional Medicine Discover more ways to test your health at home with Thorne Assess Your Biological Age With Thorne's Biological Age Health Panel How It Works: Health Panel Blood Draw What Can A Microbiome Test Tell You That A Genetic Test Can't? How Does Thorne's Biological Age Panel Work? Products mentioned in this episode: Biological Age Health Panel, Essential Health Panel, Advanced Health Panel Subscribe to More Content Subscribe to the show wherever you listen to podcasts so you never miss an episode. You can also learn more about the topics in the episode by checking out the latest news, videos, and stories on Thorne's Take 5 Daily blog.
In this episode of the Food Junkies Podcast, Dr. Vera Tarman sits down with Dr. Amelia Scott Barrett, a Stanford-trained neurologist and migraine expert with over 30 years of experience. Dr. Barrett shares her professional insights and personal journey with migraines, exploring their genetic basis, root causes, and treatment options. This comprehensive conversation covers everything from diet and hormonal influences to toxins and integrative medicine approaches. Dr. Barrett founded Migraine Relief Code, an online platform offering integrative tools for migraine sufferers, and has a popular 2023 TED Talk on migraines. She advocates for addressing migraines early, focusing on root causes rather than just masking symptoms. What You'll Learn in This Episode: Migraine Basics and Misconceptions: The key differences between migraines and tension headaches. Why many people with migraines are undiagnosed or misdiagnosed. Understanding “migraine brain” and the importance of early intervention. Root Causes of Migraines: Nutrients: How deficiencies in essential nutrients like omega-3s and vitamin D impact brain health. Gut Health: The link between leaky gut, inflammation, and migraine triggers. Toxins: How environmental toxins impair mitochondria and contribute to chronic pain. Hormones and Adrenals: The role of stress, cortisol depletion, and hormonal fluctuations in migraines. Diet and Lifestyle Tips: The importance of balancing blood sugar to reduce migraine frequency. How processed foods and sugar impact migraines and mimic addictive eating patterns. Why a ketogenic or whole-food, plant-based diet may help manage symptoms. The role of alcohol and endocrine disruptors in triggering migraines. Integrative Approaches to Treatment: Biohacking tools are used to monitor and shift the body from "fight or flight" to recovery mode. Why a personalized recovery plan addressing underlying issues is critical. The benefits and limitations of medications, injections, and other pharmaceutical treatments. Research and Future Directions: The emerging role of genomic research and precision medicine in migraine treatment. How toxins and processed foods contribute to broader neurological conditions. Follow Dr. Amelia Scott Barrett: Website: Migraine Relief Code Free Migraine Masterclass YouTube Channel: Dr. Amelia Scott Barrett Download her eBook: The Food Code Referenced Topics: Watch Dr. Barrett's 2023 TED Talk on migraines. Learn about genome-wide association studies (GWAS) and their impact on migraine genetics. Explore her online courses for navigating precision medicine and migraine recovery. Let's Connect: Email: foodjunkiespodcast@gmail.com Follow Sweet Sobriety for updates on workshops, conferences, and recovery tools. Thank You for Listening! We're grateful to have you on this journey. Remember: Recovery is about progress, perseverance, and connection. You've got this!
Dr. Jesse Crayle is a clinical neuromuscular fellow in the Department of Neurology at Washington University in St. Louis and Dr. Evadnie Rampersaud is a Principal Bioinformatics Research Scientist at St. Jude Children's Research Hospital. They will be discussing their publication “Genetic Associations With an Amyotrophic Lateral Sclerosis Reversal Phenotype.”
Welcome to the Olink® Proteomics in Proximity podcast! Below are some useful resources mentioned in this episode: Olink tools and softwareOlink® Explore 3072, the platform utilized by the UK Biobank to measure ~3000 proteins in plasma: https://olink.com/products-services/explore/Olink® Explore HT, Olink's most advanced solution for high-throughput biomarker discovery, measuring 5400+ proteins simultaneously with a streamlined workflow and industry-leading specificity: https://olink.com/products-services/exploreht/ UK Biobank Pharma Proteomics Project (UKB-PPP), one of the world's largest scientific studies of blood protein biomarkers conducted to date, https://www.ukbiobank.ac.uk/learn-more-about-uk-biobank/news/uk-biobank-launches-one-of-the-largest-scientific-studies Research articlesThe support of human genetic evidence for approved drug indicationsMatthew R Nelson et al, Nature Genetics 2015https://www.nature.com/articles/ng.3314 Proteomic aging clock predicts mortality and risk of common age-related diseases in diverse populationsM. Austin Argentieri et al, Nature Medicine 2024https://www.nature.com/articles/s41591-024-03164-7 Plasma protein-based organ-specific aging and mortality models unveil diseases as accelerated aging of organismal systemsLudger J.E. Goeminne et al, Cell Metabolism 2024, in presshttps://www.sciencedirect.com/science/article/abs/pii/S1550413124004017?via%3Dihub Plasma proteomic associations with genetics and health in the UK BiobankBenjamin B. Sun et, Nature 2023https://www.nature.com/articles/s41586-023-06592-6 Rare variant associations with plasma protein levels in the UK BiobankRyan S. Dhindsa; Nature 2023https://www.nature.com/articles/s41586-023-06547-x Disease prediction with multi-omics and biomarkers empowers case–control genetic discoveries in the UK BiobankManik Garg, Nature Genetics, 2024https://www.nature.com/articles/s41588-024-01898-1 China Kadoorie Biobank: https://www.ckbiobank.org/publicationsPublications: https://www.ckbiobank.org/publications Subscribe to the podcast on your favorite player or app:Apple Podcasts: https://apple.co/3T0YbSm Spotify Podcasts: https://open.spotify.com/show/2sZ2wxO... Google Podcasts: https://podcasts.google.com/feed/aHR0... Amazon Music: https://music.amazon.com/podcasts/d97... Podcast Addict:
In this episode, we welcome Dr. Eric Fauman, Executive Director and Head of Computational Biology in the Internal Medicine Research Unit at Pfizer. Eric and Patrick discuss facilitating efficient identification of potential drug targets and the role of artificial intelligence in genetics research and drug discovery. Please note that Eric has kindly shared some interesting research that was mentioned in the podcast. It is pasted at the end of the show notes.
研究領域物換星移，隨著新的研究領域誕生，也有研究領域慢慢淡出人們的視野。而有些曾經冷門的領域，則因為技術進步、新的科學發現，回歸眾人追逐的研究熱點。神經膠質細胞（Neural progenitor cells, NPCs）就是這樣的領域，隨著近年對神經退化疾病的重視，以及全基因組關聯研究（GWAS）的發現指引，原本被認為扮演輔助角色的神經膠質細胞，一躍成為熱門的藥物標的。 本集的訪談邀請到蔡蕙歆博士，他將會介紹神經膠質細胞在神經系統的功能，以及這一群「和神經細胞一樣重要」的細胞，在神經退化疾病領域的進展。此外，蕙歆也會和我們分享他如何轉換領域、挑戰自我，從學界教職跳到業界，從基礎研究進到臨床試驗開發。他也和我們分享管理腦庫的特別經歷、和面對公司人事異動、冷門領域找工作的心法。他談論如何調適心態，應對多變的環境，在職涯中展現的彈性和適應力。相信蕙歆的分享，對於現在面臨嚴峻景氣的求職者，與在職場打拼探索屬於自己的道路的大家，會非常有助益。
This episode went live on World Menopause Day.Menopause is an inevitable aspect of life for half of the global population, but one that requires far more study. New genomic insights could empower women with better reproductive choices and insights into likely future health.In this episode, I talk with Dr Stasa Stankovic. She has a PhD in Genomic Medicine from Cambridge University, and is on a mission to reshape the future of women's health by developing, and eventually commercialising, prediction tools and next generation therapeutics for female reproductive disorders.We discuss the complexities of female reproductive health, particularly focusing on ovarian ageing and menopause. We also explore the genetic factors influencing menopause timing, and the importance of understanding reproductive health beyond fertility.Stasa shares her collaborative work on large-scale genomics, using samples from the UK Biobank to conduct genome-wide association studies (GWAS). These have highlighted many genes associated with menopause and thus pave the way for potential new diagnostic techniques and therapeutic interventions to give women greater control of their reproductive health.Menopause affects every woman, but also indirectly impacts husbands, partners, colleagues and friends. The work Stasa and her colleagues are doing will have implications not just for women but for all of us.“We need to empower women with knowledge.” – Stasa Stankovic You'll hear about:01:37 - Stasa's area of research04:14 - Why the science behind menopause is so important07:36 - The ovarian reserve and what that means12:26 - Contributing factors to menopause17:24 - The key findings of the genome-wide association (GWAS) study21:21 - Getting the right targets for intervention27:05 - The challenge of finding animal models for menopause28:22 - Turning lab science into commercial science31:40 - Stasa on the choices that women have38:38 - Is gene intervention possible? Connect with Stasa:LinkedIn - https://www.linkedin.com/in/stasa-stankovic-93723a137/ OvartiX - https://ovartix.com/ Connect with me:LinkedIn: https://www.linkedin.com/in/markdavison100/ If you need any lab equipment:Grant Instruments: https://www.grantinstruments.com/ Grant Instruments on LinkedIn: https://www.linkedin.com/company/grant-instruments-cambridge-ltd/
BUFFALO, NY- October 15, 2024 – A new #research paper was #published on the #cover of Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science), Volume 16, Issue 19 on October 12, 2024, entitled, “A proteomics approach to study mouse long bones: examining baseline differences and mechanical loading-induced bone formation in young-adult and old mice.” As noted in the abstract, bone mass declines with age, and the anabolic effects of skeletal loading decrease. While much research has focused on gene transcription, how bone ages and loses its mechanoresponsiveness at the protein level remains unclear. In their paper, researchers Christopher J. Chermside-Scabbo, John T. Shuster, Petra Erdmann-Gilmore, Eric Tycksen, Qiang Zhang, R. Reid Townsend, and Matthew J. Silva from Washington University School of Medicine and Washington University in St. Louis, Missouri, describe how they developed a novel proteomics approach and conducted paired mass spectrometry and RNA-seq analyses on tibias from young-adult (5-month) and old (22-month) mice. The researchers report the first correlation estimate between the bone proteome and transcriptome (Spearman ρ = 0.40). While this is consistent with findings from other tissues, it suggests that only a relatively low amount of variation in protein levels is explained by variation in transcript levels. Of the 71 shared targets that differed with age, eight were associated with bone mineral density in previous GWAS, including the understudied targets Asrgl1 and Timp2. Using complementary RNA in situ hybridization, the researchers confirmed that Asrgl1 and Timp2 showed reduced expression in osteoblasts/osteocytes in aged bones. Additionally, they found evidence of reduced TGF-beta signaling with aging, particularly Tgfb2. The researchers also identified proteomic changes following mechanical loading, noting that at the protein level, bone differed more with age than with loading, and aged bone exhibited fewer loading-induced changes. "Overall, our findings underscore the need for complementary protein-level assays in skeletal biology research.” DOI - https://doi.org/10.18632/aging.206131 Corresponding author - Christopher J. Chermside-Scabbo - ccherms@wustl.edu Video short - https://www.youtube.com/watch?v=xm6o7gWH8p4 Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206131 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, bone, mechanical loading, proteomics, RNA-seq/transcriptomics About Aging-US The mission of the journal is to understand the mechanisms surrounding aging and age-related diseases, including cancer as the main cause of death in the modern aged population. The journal aims to promote 1) treatment of age-related diseases by slowing down aging, 2) validation of anti-aging drugs by treating age-related diseases, and 3) prevention of cancer by inhibiting aging. (Cancer and COVID-19 are age-related diseases.) Please visit our website at https://www.Aging-US.com and connect with us: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM
This week, Patrick welcomes President and CEO of The Jackson Laboratory, Lon Cardon. They discuss the rise of genome-wide association studies (GWAS) and how they changed the face of genetics research and why Lon took the plunge and moved from academia to industry in an era when it was an unpopular choice. Plus, they cover the future of disease taxonomy and why data sharing remains vital to the field of genetics.
In this week's episode of the Everything Epigenetics podcast, I'm joined by Dr. Charles Breeze, an expert in computational epigenetics. We talk about his inspiring journey into the field of epigenetics, his trailblazing research on kidney function across diverse ethnic groups, and the innovative tools he's developed to push the boundaries of epigenetic research.Dr. Breeze shares how his fascination with the complex interaction between environmental and genetic factors shaped his path into epigenetics. This passion led him to focus on understanding why certain populations are at higher risk for diseases like chronic kidney disease. His work has uncovered insights into the disparities in kidney disease risk among different ethnic groups, shedding light on genetic and environmental factors that had previously been overlooked.To address the challenges of inclusivity and precision in epigenetic studies, Dr. Breeze developed specialized tools that enhance the accuracy of Epigenome-Wide Association Studies (EWAS). These tools aim to improve how we analyze the impact of genetics and environment on health, helping researchers study epigenetic patterns across populations more effectively. His contributions are making it easier to identify how factors like diet, stress, and pollution affect gene expression, paving the way for more inclusive and equitable health research.Dr. Breeze earned his Ph.D. in computational epigenetics and genomics from University College London, where he was a Marie Curie fellow. He has also worked at top institutions like the University of Oxford, the European Bioinformatics Institute, and the Altius Institute for Biomedical Sciences in Seattle. There, he led the analysis and creation of important mouse genome data. Dr. Breeze has developed bioinformatics tools like eFORGE and FORGE2, which help analyze data from studies on how genes and the environment affect health (EWAS and GWAS). Dr. Breeze is a member of the Encyclopedia of DNA Elements (ENCODE) and the International Human Epigenome Consortium (IHEC).You'll learn about: - Dr. Breeze's early interest in genomics, sparked by reading "Genome" by Matthew Ridley - His significant findings from the 2021 study titled “Epigenome-wide association study of kidney function identifies trans-ethnic and ethnic-specific loci,” which revealed ethnic disparities in kidney function - The challenges faced in epigenetic research due to the lack of diversity in reference data and how this impacts research outcomes - Proposed solutions to increase diversity in epigenomic data, including community involvement and targeted data generation - How his bioinformatics tools, eFORGE and FORGE2, assist researchers in understanding the complex data from EWAS and GWAS studies - His future research directions, including studies on kidney cancer and the expansion of pathway analysis toolsSupport the showWhere to Find Us:Instagram Twitter Facebook Follow us on:Apple Podcast Spotify YouTube Visit our website for more information and resources: everythingepigenetics.com Thank you for joining us at the Everything Epigenetics Podcast and remember you have control over your Epigenetics, so tune in next time to learn more about how to harness this knowledge for your benefit.
Kris and David are guestless as we discuss the week that was August 26-September 3, 2000, a Patreon request from Ted Bell, who dropped the $25 for us to cover this week. Topics of discussion include:Changes coming for the WWF creative staff, which comes at an interesting time because....Raw and Smackdown focusing on Triple H and Chyna interacting on TV for the first time in almost a year, which angers their onscreen significant others, Stephanie McMahon and Eddie Guerrero. We talk about how insane this all was, how it seemed like it was building towards a Triple H/Chyna reunion, and why we think it only lasted one week of TV before being dropped cold.SummerSlam 2000, which features the WWF's first-ever TLC match with Edge and Christian vs. The Dudley Boyz vs. The Hardy Boyz, as well as Shane McMahon being a maniac and Kurt Angle finishing the main event with a concussion among lots of other news and notes.Kazushi Sakuraba dislocating Renzo Gracie's elbow at Pride 10, which was quite the newsworthy show in general, as it also featured the infamous “Petey, my heart!” fight with Ken Shamrock quitting against Kazuyuki Fujita.Atsushi Onita returning to AJPW while Masahiro Chono vs. Masa Fuchi at the Budokan officially kicked off the AJPW vs. NJPW feud.Otto Wanz folding his CWA promotion in Austria.Fishman losing his mask at the infamous debacle of a super show from GWAS in Mexico, which he never got paid for.Night two of ECW's debut weekend at the Hammerstein Ballroom in NYC as they put on what was arguably their last great show.WCW, of course..featuring VINCE RUSSO IN THE DESERT, plus Mike Awesome becoming That 70's Guy, Paul Orndorff being jacked as hell while starting his feud with the Natural Born Thrillers, Kevin Nash eating some Korean, and tons more insanity.This one is damn wild and a CAN'T-MISS SHOW!!!Timestamps:0:00:00 WWF2:20:54 Int'l: Pride FC, AJPW, NJPW, BJPW, FMW, Jd', LLPW, AustraliaWF tour, CWA folds, GWAS, Tijuana, & Puerto Rico TV ratings3:34:22 Other USA: ECW, Midnight Express, Ron Fuller-Terry Landel feud, MemphisCW, Power Pro, & XPW4:07:35 WCWTo support the show and get access to exclusive rewards like special members-only monthly themed shows, go to our Patreon page at Patreon.com/BetweenTheSheets and become an ongoing Patron. Becoming a Between the Sheets Patron will also get you exclusive access to not only the monthly themed episode of Between the Sheets, but also access to our new mailbag segment, a Patron-only chat room on Slack, and anything else we do outside of the main shows!If you're looking for the best deal on a VPN service—short for Virtual Private Network, it helps you get around regional restrictions as well as browse the internet more securely—then Private Internet Access is what you've been looking for. Not only will using our link help support Between The Sheets, but you'll get a special discount, with prices as low as $1.98/month if you go with a 40 month subscription. With numerous great features and even a TV-specific Android app to make streaming easier, there is no better choice if you're looking to subscribe to WWE Network, AEW Plus, and other region-locked services.For the best in both current and classic indie wrestling streaming, make sure to check out IndependentWrestling.tv and use coupon code BTSPOD for a free 5 day trial! (You can also go directly to TinyURL.com/IWTVsheets to sign up that way.) If you convert to a paid subscriber, we get a kickback for referring you, allowing you to support both the show and the indie scene.To subscribe, you can find us on iTunes, Google Play, and just about every other podcast app's directory, or you can also paste Feeds.FeedBurner.com/BTSheets into your favorite podcast app using whatever “add feed manually” option it has.Support this podcast at — https://redcircle.com/between-the-sheets/donationsAdvertising Inquiries: https://redcircle.com/brands
Kris and David are guestless as we discuss the week that was August 26-September 3, 2000, a Patreon request from Ted Bell, who dropped the $25 for us to cover this week. Topics of discussion include:Changes coming for the WWF creative staff, which comes at an interesting time because....Raw and Smackdown focusing on Triple H and Chyna interacting on TV for the first time in almost a year, which angers their onscreen significant others, Stephanie McMahon and Eddie Guerrero. We talk about how insane this all was, how it seemed like it was building towards a Triple H/Chyna reunion, and why we think it only lasted one week of TV before being dropped cold.SummerSlam 2000, which features the WWF's first-ever TLC match with Edge and Christian vs. The Dudley Boyz vs. The Hardy Boyz, as well as Shane McMahon being a maniac and Kurt Angle finishing the main event with a concussion among lots of other news and notes.Kazushi Sakuraba dislocating Renzo Gracie's elbow at Pride 10, which was quite the newsworthy show in general, as it also featured the infamous “Petey, my heart!” fight with Ken Shamrock quitting against Kazuyuki Fujita.Atsushi Onita returning to AJPW while Masahiro Chono vs. Masa Fuchi at the Budokan officially kicked off the AJPW vs. NJPW feud.Otto Wanz folding his CWA promotion in Austria.Fishman losing his mask at the infamous debacle of a super show from GWAS in Mexico, which he never got paid for.Night two of ECW's debut weekend at the Hammerstein Ballroom in NYC as they put on what was arguably their last great show.WCW, of course..featuring VINCE RUSSO IN THE DESERT, plus Mike Awesome becoming That 70's Guy, Paul Orndorff being jacked as hell while starting his feud with the Natural Born Thrillers, Kevin Nash eating some Korean, and tons more insanity.This one is damn wild and a CAN'T-MISS SHOW!!!Timestamps:0:00:00 WWF2:20:54 Int'l: Pride FC, AJPW, NJPW, BJPW, FMW, Jd', LLPW, AustraliaWF tour, CWA folds, GWAS, Tijuana, & Puerto Rico TV ratings3:34:22 Other USA: ECW, Midnight Express, Ron Fuller-Terry Landel feud, MemphisCW, Power Pro, & XPW4:07:35 WCWTo support the show and get access to exclusive rewards like special members-only monthly themed shows, go to our Patreon page at Patreon.com/BetweenTheSheets and become an ongoing Patron. Becoming a Between the Sheets Patron will also get you exclusive access to not only the monthly themed episode of Between the Sheets, but also access to our new mailbag segment, a Patron-only chat room on Slack, and anything else we do outside of the main shows!If you're looking for the best deal on a VPN service—short for Virtual Private Network, it helps you get around regional restrictions as well as browse the internet more securely—then Private Internet Access is what you've been looking for. Not only will using our link help support Between The Sheets, but you'll get a special discount, with prices as low as $1.98/month if you go with a 40 month subscription. With numerous great features and even a TV-specific Android app to make streaming easier, there is no better choice if you're looking to subscribe to WWE Network, AEW Plus, and other region-locked services.For the best in both current and classic indie wrestling streaming, make sure to check out IndependentWrestling.tv and use coupon code BTSPOD for a free 5 day trial! (You can also go directly to TinyURL.com/IWTVsheets to sign up that way.) If you convert to a paid subscriber, we get a kickback for referring you, allowing you to support both the show and the indie scene.To subscribe, you can find us on iTunes, Google Play, and just about every other podcast app's directory, or you can also paste Feeds.FeedBurner.com/BTSheets into your favorite podcast app using whatever “add feed manually” option it has.Support this podcast at — https://redcircle.com/between-the-sheets/donationsAdvertising Inquiries: https://redcircle.com/brands
Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: [LDSL#0] Some epistemological conundrums, published by tailcalled on August 8, 2024 on LessWrong. This post is also available on my Substack. When you deal with statistical science, causal inference, measurement, philosophy, rationalism, discourse, and similar, there's some different questions that pop up, and I think I've discovered that there's a shared answer behind a lot of the questions that I have been thinking about. In this post, I will briefly present the questions, and then in a followup post I will try to give my answer for them. Why are people so insistent about outliers? A common statistical method is to assume an outcome is due to a mixture of observed factors and unobserved factors, and then model how much of an effect the observed factors have, and attribute all remaining variation to unobserved factors. And then one makes claims about the effects of the observed factors. But some people then pick an outlier and demand an explanation for that outlier, rather than just accepting the general statistical finding: In fact, aren't outliers almost by definition anti-informative? No model is perfect, so there's always going to be cases we can't model. By insisting on explaining all those rare cases, we're basically throwing away the signal we can model. A similar point applies to reading the news. Almost by definition, the news is about uncommon stuff like terrorist attacks, rather than common stuff like heart disease. Doesn't reading such things invert your perception, such that you end up focusing on exactly the least relevant things? Why isn't factor analysis considered the main research tool? Typically if you have a ton of variables, you can perform a factor analysis which identifies a set of variables which explain a huge chunk of variation across those variables. If you are used to performing factor analysis, this feels like a great way to get an overview over the subject matter. After all, what could be better than knowing the main dimensions of variation? Yet a lot of people think of factor analysis as being superficial and uninformative. Often people insist that it only yields aggregates rather than causes, and while that might seem plausible at first, once you dig into it enough, you will see that usually the factors identified are actually causal, so that can't be the real problem. A related question is why people tend to talk in funky discrete ways when careful quantitative analysis generally finds everything to be continuous. Why do people want clusters more than they want factors? Especially since cluster models tend to be more fiddly and less robust. Why do people want "the" cause? There's a big gap between how people intuitively view causal inference (often searching for "the" cause of something), versus how statistics views causal inference. The main frameworks for causal inference in statistics are Rubin's Potential Outcomes framework and Pearl's DAG approach, and both of these view causality as a function from inputs to outputs. In these frameworks, causality is about functional input/output relationships, and there are many different notions of causal effects, not simply one canonical "cause" of something. Why are people dissatisfied with GWAS? In genome-wide association searches, researchers use statistics to identify alleles that are associated with specific outcomes of interest (e.g. health, psychological characteristics, SES outcomes). They've been making consistent progress over time, finding tons of different genetic associations and gradually becoming able to explain more and more variance between people. Yet GWAS is heavily criticized as "not causal". While there are certain biases that can occur, those biases are usually found to be much smaller than seems justified by these critiques. So what gives? What value does qualitative r...
A vida segue. Gwas https://x.com/el_gwaso / https://www.youtube.com/channel/UCw5rys5957XS2ZgpmoFRvFA Músicas: Metrô - A gota suspensa
Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: Superbabies: Putting The Pieces Together, published by sarahconstantin on July 12, 2024 on LessWrong. This post was inspired by some talks at the recent LessOnline conference including one by LessWrong user "Gene Smith". Let's say you want to have a "designer baby". Genetically extraordinary in some way - super athletic, super beautiful, whatever. 6'5", blue eyes, with a trust fund. Ethics aside[1], what would be necessary to actually do this? Fundamentally, any kind of "superbaby" or "designer baby" project depends on two steps: 1.) figure out what genes you ideally want; 2.) create an embryo with those genes. It's already standard to do a very simple version of this two-step process. In the typical course of in-vitro fertilization (IVF), embryos are usually screened for chromosomal abnormalities that would cause disabilities like Down Syndrome, and only the "healthy" embryos are implanted. But most (partially) heritable traits and disease risks are not as easy to predict. Polygenic Scores If what you care about is something like "low cancer risk" or "exceptional athletic ability", it won't be down to a single chromosomal abnormality or a variant in a single gene. Instead, there's typically a statistical relationship where many genes are separately associated with increased or decreased expected value for the trait. This statistical relationship can be written as a polygenic score - given an individual's genome, it'll crunch the numbers and spit out an expected score. That could be a disease risk probability, or it could be an expected value for a trait like "height" or "neuroticism." Polygenic scores are never perfect - some people will be taller than the score's prediction, some shorter - but for a lot of traits they're undeniably meaningful, i.e. there will be a much greater-than-chance correlation between the polygenic score and the true trait measurement. Where do polygenic scores come from? Typically, from genome-wide association studies, or GWAS. These collect a lot of people's genomes (the largest ones can have hundreds of thousands of subjects) and personal data potentially including disease diagnoses, height and weight, psychometric test results, etc. And then they basically run multivariate correlations. A polygenic score is a (usually regularized) multivariate regression best-fit model of the trait as a function of the genome. A polygenic score can give you a rank ordering of genomes, from "best" to "worst" predicted score; it can also give you a "wish list" of gene variants predicted to give a very high combined score. Ideally, "use a polygenic score to pick or generate very high-scoring embryos" would result in babies that have the desired traits to an extraordinary degree. In reality, this depends on how "good" the polygenic scores are - to what extent they're based on causal vs. confounded effects, how much of observed variance they explain, and so on. Reasonable experts seem to disagree on this.[2] I'm a little out of my depth when it comes to assessing the statistical methodology of GWAS studies, so I'm interested in another question - even assuming you have polygenic score you trust, what do you do next? How do you get a high-scoring baby out of it? Massively Multiplexed, Body-Wide Gene Editing? Not So Much, Yet. "Get an IVF embryo and gene-edit it to have the desired genes" (again, ethics and legality aside)[3] is a lot harder than it sounds. First of all, we don't currently know how to make gene edits simultaneously and abundantly in every tissue of the body. Recently approved gene-editing therapies like Casgevy, which treats sickle-cell disease, are operating on easy mode. Sickle-cell disease is a blood disorder; the patient doesn't have enough healthy blood cells, so the therapy consists of an injection of the patient's own blood cells which h...
In this episode of The Crop Science Podcast Show, Dr. Samuel Fernandes, assistant professor of agricultural statistics and quantitative genetics at the University of Arkansas, discusses the evolving field of plant breeding. Dr. Fernandes elaborates on the importance of quantitative genetics, machine learning, and data science integration in enhancing crop yields and stability. Listen now to gain expert knowledge and stay at the forefront of crop production advancements."The integration of statistical models and data science in plant breeding helps us develop stable cultivars across different environments."(00:00) Introduction (03:10) Multi-Omics in plant breeding(04:40) Importance of quantitative genetics(10:27) Bridging data and farm application(16:00) AI applications in crop science(24:18) Breakthroughs in plant breeding(29:00) Final three questionsMeet the guest: Dr. Samuel Fernandes is an Assistant Professor of Agricultural Statistics and Quantitative Genetics at the University of Arkansas. Specializing in quantitative genetics, plant breeding, and genomics, he has significant research experience from the University of Illinois Urbana-Champaign, focusing on genomic selection and GWAS in biomass sorghum. He holds a Ph.D. and a Master's in Genetics and Plant Breeding from the Federal University of Lavras and a Bachelor's in Agronomy from the University of Brasilia. Dr. Fernandes uses statistical models and data science to enhance crop yields.The Crop Science Podcast Show is trusted and supported by the innovative companies:- KWS- CNH RemanAre you ready to unleash the podcasting potential of your company? wisenetix.co/custom-podcast
The majority of children and adolescents experience headache, with pooled estimates suggesting that approximately 60% of youth are affected. Migraine and tension-type headache are the leading cause of neurologic disability among children and adolescents 10 years and older. In this episode, Allison Weathers, MD, FAAN speaks with Serena Orr, MD, MSc, FRCPC, author of the article “Headache in Children and Adolescents,” in the Continuum® April 2024 Headache issue. Dr. Weathers is a Continuum® Audio interviewer and an associate chief medical information officer at Cleveland Clinic in Cleveland, Ohio. Dr. Orr is an assistant professor in the departments of Pediatrics, Community Health Sciences, and Clinical Neurosciences at Cumming School of Medicine, University of Calgary and a pediatric neurologist at Alberta Children's Hospital in Calgary, Alberta, Canada. Additional Resources Read the article: Headache in Children and Adolescents Subscribe to Continuum: continpub.com/Spring2024 Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the American Academy of Neurology: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Guest: @SerenaLOrr Transcript Dr Jones: This is Dr. Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology. Thank you for joining us on Continuum Audio, a companion podcast to the journal. Continuum Audio features conversations with the guest editors and authors of Continuum, who are the leading experts in their fields. Subscribers to the Continuum journal can read the full article or listen to verbatim recordings of the article by visiting the link in the show notes. Subscribers also have access to exclusive audio content not featured on the podcast. As an ad-free journal entirely supported by subscriptions, if you're not already a subscriber, we encourage you to become one. For more information on subscribing, please visit the link in the show notes. AAN members, stay tuned after the episode to hear how you can get CME for listening. Dr Weathers: This is Dr. Allison Weathers. Today, I'm interviewing Dr. Serena Orr on pediatric headache, which is part of the April 2024 Continuum issue on headache. Dr. Orr is an Assistant Professor at the University of Calgary, and a Pediatric Neurologist at Alberta Children's Hospital in Calgary, Alberta, Canada. Welcome to the podcast. So, thank you, Dr. Orr, for taking the time to speak with me about this fantastic article that covers such an important topic – headache in the pediatric population, in children and adolescents. First, I'd love to start by learning a little bit about you. Where do you practice, and how did you get interested in this topic? I love learning more about the authors of these incredible articles and how they became interested in their fields. So, you know, pediatric neurology is already a pretty subspecialized area of medicine – how did you become interested even further subspecializing in headache? Dr Orr: Well, thank you for the invitation. Nice to meet you, Dr. Weathers. I'm Serena Orr. I'm a clinician-scientist, pediatric neurologist, and headache specialist based in Canada at the Alberta Children's Hospital in Calgary, Alberta, just outside of the Rockies. I'm really passionate about headache medicine. I think I came to it because it allowed me to marry my interests in neurology and psychology together. I did my undergraduate studies at McGill in psychology and really wanted to take a biopsychosocial approach to my practice. The first child neurology patient I ever saw was a child who was experiencing migraine and having a lot of disability from it, with lots of impacts on her life - and I really saw an opportunity to take a holistic approach to the patient and marry my interests in neuroscience, neurology, and psychology together. So, I'm very excited to talk to you today about this topic that I'm really passionate about and that I think is underserved – um, hopefully get more people excited about it. Dr Weathers: But so great, and I'm sure we will do that just based on how excited I was just reading your article. So, I always like to start, actually, with what you feel is the most important clinical message of your article. What is your biggest takeaway you want to leave our listeners with? Dr Orr: Yeah, well I think this is a really big topic in neurology. So, if you look at the reasons for consulting a child neurologist, headache falls into the top three. 60% of youth experience headache in youth. If we look at what presents to neurology in terms of headache, the majority is migraine – and so that's a big focus of this article, because anywhere between a half to 88% of headache consultations in neurology are for migraine. And as I kind of alluded to in discussing my interests in this area, you know, it's really important to take a biopsychosocial approach to managing any chronic pain disorder, including migraine and headache disorders. Another big takeaway point from the article is that - specific to pediatric headache - there's really high placebo response rates that we're still trying to understand and grapple with in the field, and I think this underscores the importance in really doing patient-centered care and ensuring that you're educating patients and families about the level of evidence that we have about the placebo response rates and engaging in shared decision-making when you're choosing treatments together. So, I think those would be the main take-home points. Dr Weathers: I think both really critical. And I think even without – I'll put my plug in – even without the placebo effect, I think that shared decision-making is such an important concept for all of us in neurology to think about - but I think you make such the important point that with it, it becomes absolutely critical. I want to expand on a concept that you were just talking about. Pediatric headaches are so incredibly common, and you make the point in the article so well that they're one of the leading causes of neurological disability in pediatric patients. They have such a significant impact that really touches all aspects of these children's lives - both at school, how they impact their hobbies - pretty much everything that they do, and these long-reaching impacts. But then you go on to say that pediatric headache remains the most underfunded pediatric disease category when you take into account allocated public research dollars, which was just staggering to me. Why do you think this is? Dr Orr: I think there's a few reasons. So, one of the main reasons, I think, is that headache medicine has been underserved - there haven't been enough people who have gravitated to this field. I think this is rapidly changing as we train more people and show the world how important this topic is and how much exciting translational research is going on. But, historically, this has been a very small subspecialty that's been underserved relative to disease burden (so not enough scientists equals less research funding) - but there's another aspect to this as well. There was a paper published in 2020 by Mirin – who actually looked at research dollars in NIH based on disease burden and whether the diseases were male or female dominant - and found that there's a significant gender bias in research funding. Male-dominant diseases tend to be significantly overfunded relative to female-dominant diseases when you look at disease burden - and if you look at the female-dominant disease table, headache disorders and migraine are in the top three most underfunded disease categories amongst the underfunded female-dominant diseases. That data has been replicated looking at NIH dollars on the pediatric side as well. They didn't look at gender breakdown in the pediatric paper that was published a couple of years ago, but found, actually, that pediatric headache disorders are the most underfunded in terms of NIH research dollars to pediatric diseases – so, top underfunded relative to disease burden. So, yeah, being underserved as a field - and then, I think, gender bias has also played a significant role in what gets funded over time. Dr Weathers: Wow, that is hard to think about. And I think those are really insightful points and ones we really need to think about as we think about the bias in our research and our funding. Why is access to care and treatment for these children and adolescents so important? I know this seems like a super obvious one, but it feels like the answer is actually really much more complex. Dr Orr: Well, there's data to show that earlier diagnosis can lead to better long-term outcomes for youth with migraine - and this is really important, because if you look at the incidence curves for migraine, you see that at least a third, if not more, of incident cases occur before adulthood. We also know there's some GWAS data to show that youth-onset migraine has a higher genetic loading when looking at polygenic risk scores than adult-onset migraine, so people who have migraine onset in youth may be more genetically loaded (that may be important). And we also know that early access to diagnosis and treatment gives them a better long-term prognosis. We know that headache disorders and migraine are associated not only with long-term potential for disability on the physical side, but also increase the risk of psychiatric comorbidities developing over time, so there's really a huge opportunity in accessing a diagnosis and treatment early to improve long-term function - both on the medical side, but also potentially avert poor mental health outcomes - and also diagnose and treat a subset of people with the disease that may be more genetically loaded. We don't know if that impacts outcomes, but potentially, it does. So there's lots of reasons, I think, that we can get in there early and make a big impact – and even for those who it takes a while to find effective treatment for, really having access to education early so that they understand their disease and also ways that they can engage in self-management strategies, I think, is really empowering to the patient and really important (even if we're struggling to find the best medical therapy). Dr Weathers: You laid out a lot of really important reasons, and again, it goes back to the arguments made at the beginning about why it's so important to increase the funding so that this is no longer an area that's underserved, so that we are able to increase the access, and that everybody who needs this kind of care is able to get it. I want to shift a little bit and think about how we diagnose and work up patients who present with a headache. So as a neurologist - and also as a parent - one of the scariest considerations for me is figuring out if a headache is just a headache or if it's a sign of something else (you know, what we think of as a secondary headache disorder). What is your approach to distinguishing between the two? Dr Orr: We take a very clinical approach to diagnosis. We don't have specific biomarkers for different headache disorders, so we're still, you know, relying on a really detailed history and physical exam in order to sort out the diagnosis. As I discussed in the article, really the key first branch point (like you say) is, is this a primary headache disorder or a secondary headache disorder? There's some tools that we can use in practice to try to get at that, I think the most useful of which is the SNOOP tool - it's an acronym that goes over headache, red and orange flags. Every time I write an article where I discuss this, it's expanded to include more red or orange flags (it's in its probably third or fourth iteration now), but there's a nice table in the article that goes over some of these red and orange flags. It includes things like systemic feature (like headache, nuchal rigidity), if there's a history of cancer, if there's associated, you know, headache waking child up in the morning with vomiting - and a variety of features. I have to say the level of evidence for some of the features is relatively low, and our understanding of some of the red flags has changed over time. As one example, we used to think occipital headaches in youth were almost always associated with a secondary headache disorder, but now there's more emerging data to show that it's actually relatively common for youth with migraine to have an occipital location. So, really, using the tool is about kind of putting the whole picture together to try to risk stratify. In the majority of youth who present with recurrent headaches, who don't have any red or orange flags, and who have an unremarkable neurological examination without focal deficits, it typically is such that we don't have to do further investigation - but any red or orange flags (or a combination of them), any focal deficits on exam, would typically be where we would be considering neuroimaging. It's very unusual that we have an indication to do an EEG or large amounts of blood work in youth with headache, but it is context specific - for example, a case presenting with recurrent hemiplegia (you may have Todd's paralysis on the differential and you may want to do an EEG), or in a youth who also has GI symptoms (I picked up some youth with celiac disorder who have chronic headaches as well). So there are specific circumstances where blood work, EEG may be indicated (or obviously lumbar puncture in the case of suspected infection, et cetera), but for the most part, we're really relying on a very thorough history and physical exam to sort out our pretest probability of a secondary headache disorder and whether we need to do neuroimaging and further investigations. Dr Weathers: I think keeping in mind that systematic approach and really working through the algorithm is really reassuring and makes sense that, one, you won't miss something kind of worrisome, but on the other hand, that you're also not doing unnecessary testing, either. Along those lines, what do you think is the easiest mistake to make when treating children and adolescents with headache, and how do you avoid it? Dr Orr: I think the easiest mistake to make is undertreatment. Both for acute and preventive therapies, I often see undertreatment. I think families are often hesitant to give medication to their children, and so I have a lot of families say, “Oh, well, you know we typically wait the attacks out until they get more severe, we try to avoid medication, we use cold compresses, et cetera.” So, explaining to families that acute treatment (of course, we don't want to overuse it) and overusing simple analgesics (NSAIDS) more than three days a week can increase the risk of higher frequency of attacks and medication overuse headache - but undertreatment is a risk, too. And the way I like to explain it to families is in the scientific basis of pain chronification - so I'll say to families, “You know, we have these pain pathways in our brain. If we let them go off for long periods of time, they get stronger (and so that's where we want to get medication in quickly to try to shorten the exposure of the attacks). When you don't do that, those pain pathways may start out like a dirt road - and maybe then you have lots of long attacks, and then it gets paved, and then it becomes a highway.” I find it's a useful way to help families understand the concept of pain chronification and why we want them to treat attacks. The same thing goes for undertreatment on the preventive side. If you know a youth is having frequent attacks that are impacting their life and their ability to function, we really should be thinking about a daily preventive treatment, because we know that pill-based interventions will result in a significant reduction in headache frequency in at least two-thirds of youth - and again, allowing the youth to have frequent attacks contributes to that pain chronification (and explain it to families in a similar way to what I just explained for acute treatment) - but there can be a lot of hesitancy to engage with pill-based treatments, even though we know that they can be helpful. Dr Weathers: I think that's a really powerful point - and I think something we also, frankly, probably tend to do on the adult side as well – but, especially, I could see where there's even probably more hesitancy in children and adolescents (this concern that we're going to overtreat them and then end up inadequately treating, which leads to increased problems). And also goes back to the concept you were talking about earlier about the importance of shared decision-making and really engaging with the patient and their families in the discussion early on to help avoid that, as well to have everybody aware of the benefits and the side effects of all of the different options, I think is so critical. I was also really excited to see you (in the article) write about the importance of a trauma-informed care approach. This is an area I'm really passionate about in my work as a clinical informaticist and how we can leverage the electronic health record to support trauma-informed care and raising awareness of what a patient's triggers may be. Can you explain to our listeners who may not be knowledgeable about this approach what it means, and why you think that this might be applicable to children adolescents with headache? Dr Orr: Thanks for bringing that up. I think it's really important as well. We've done some work in my lab (and many others have as well) to show that there's a relationship between adverse childhood experiences and the development of headache disorders in youth and adults. By adverse childhood experiences, I mean exposure to highly stressful (like toxic stress) environments in early childhood, such as experiencing death of a parent, divorce, abuse, neglect. So, we know that adverse childhood experiences are associated with higher risk of developing migraine and headache disorders, and knowing that and how common these are amongst our patients - really think it's important to advocate for screening all children, adolescents coming in with recurrent headaches for adverse childhood experiences and exposure to trauma, because it really will impact not only how you interact with the patient, but also potentially what you will screen them for on the mental health side. And so providing trauma-informed care, I think - of course we want it to be targeted - but really taking this approach with all patients is actually a good way to think about it, because trauma is very common in our society, and some of the ways that we've measured trauma in the past (like some of the examples that I gave, divorce, death of a parent) are really narrow and don't encompass broader aspects of trauma (like systemic racism and other things that people are experiencing that haven't been adequately measured). So what trauma-informed care is - you know, there's a few core aspects, and one is screening all patients for trauma. The way I do that in clinic is just asking them if they've had any major stressful life events (and then I give a few examples), but there are standardized questionnaires that can be used for this as well. And then really trying to develop a nurturing rapport with the patient - an open listening strategy, asking open-ended questions, being empathic with patients and families - I know we all try to do this, anyway, but really focusing on that, especially in the context of trauma. And then thinking carefully about not only how you're talking to the patient, but how you're approaching them during the physical exam (so, for example, asking permission before touching the patient rather than just diving into the exam to be sensitive to that). And then also recognizing, like I said, that some of the ways that we've conceptualized trauma have been a little bit narrow, and that trauma may occur in context outside of what we traditionally think of. Dr Weathers: Again, I think that's so important and could be certainly much more broadly applied than even just to this one field, but thrilled to see that you're incorporating it into your work and your research (and again, it was discussed in the article) - and, absolutely, I think that the more that we incorporate it as well here, I think, that the better off for all of our patients and the improved care we provide. Moving on from that, I always like to end my interviews on a positive and hopeful note, and so I'd love to hear from you what you're most excited about in the field of pediatric headache. What breakthroughs do you think are coming, or what's giving you the most hope? Dr Orr: There's so much, there's so much exciting stuff going on in our field (and so, you know, I'll have to rein in myself in here), but one thing is there's been an explosion of novel treatment options on the adult migraine side in the last five to ten years, including agents targeted at the CGRP pathway, calcitonin gene-related peptide, some monoclonal antibodies, and receptor antagonists. There's been an explosion of neuromodulation options with now five devices that have various levels of FDA clearance for use in adults and/or youth with migraine. And there are, for most of these devices and novel drugs, either published studies or ongoing research into how they may be used in youth, so I'm hopeful that we will have more treatment options that are evidence based for youth going forward. This is in part due to the Pediatric Research Equity Act that came out a couple of decades ago now that has put requirements for pediatric studies when new drugs are approved by the FDA for adults - so I think that has had an impact, and I'm hopeful that we'll have an expanded treatment landscape in the years to come. There's also a lot of really exciting, more kind of fundamental research going on that I think will help us move the pediatric field forward more rapidly. In the past, we have really often borrowed from what the adult neurologists are doing for adults with headache disorders without really understanding some of the fundamental biological and psychosocial differences between headache disorders onset in youth versus adulthood, and so there is more and more research going on to understand the biology of migraine in youth and some of the risk factors at this age and some of the features that may make youth a little bit different, because it's very rare that youth are just little versions of adults for any disease or problem. And then, you know, I've seen a really large expansion in the number of trainees who are interested in headache medicine since I've entered this field (I've even got one of our residents who's going to do a headache fellowship, which is exciting), and seeing the growth and interest in headache medicine and the number of people being trained really gives me a lot of hope for the future, because there's so much work to be done in this area, and, really, that's where we're going to have the largest impact - is in mentoring and fostering the next generation of headache neurologists. So, there's lots of reasons to be excited, and I would say to the trainees listening that if you want an exciting career where there's lots of opportunity to make impact both clinically on your patients and in terms of educating the next generation and spearheading research initiatives, headache medicine is for you. Dr Weathers: I think that is incredibly inspiring and will hopefully get a lot of our listeners excited about joining this incredible field. Well, thank you for, again, this great article and for all of your time this evening, I've learned so much and really enjoyed speaking with you. Dr Orr: Thank you. Likewise, it was great to have this opportunity. I really enjoyed it. Dr Weathers: Again, today, we've been interviewing Dr. Serena Orr whose article on pediatric headache appears in the most recent issue of Continuum on headache. Be sure to check out Continuum Audio podcasts from this and other issues. And thank you to our listeners for joining today. Dr Monteith: This is Dr. Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practice. And right now, during our Spring Special, all subscriptions are 15% off. Go to Continpub.com/ Spring2024, or use the link in the episode notes, to learn more and take advantage of this great discount. This offer ends June 30, 2024. AAN members: go to the link in the episode notes and complete the evaluation to get CME. Thank you for listening to Continuum Audio.
BUFFALO, NY- April 24, 2024 – A new #researchpaper was #published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 16, Issue 7, entitled, “Using genetics and proteomics data to identify proteins causally related to COVID-19, healthspan and lifespan: a Mendelian randomization study.” The COVID-19 pandemic poses a heavy burden on public health and accounts for substantial mortality and morbidity. Proteins are building blocks of life, but specific proteins causally related to COVID-19, healthspan and lifespan, have not been systematically examined. In this new study, researchers Jie V. Zhao, Minhao Yao, and Zhonghua Liu from The University of Hong Kong and Columbia University conducted a Mendelian randomization study to assess the effects of 1,361 plasma proteins on COVID-19, healthspan and lifespan, using large GWAS of severe COVID-19 (up to 13,769 cases and 1,072,442 controls), COVID-19 hospitalization (32,519 cases and 2,062,805 controls) and SARS-COV2 infection (122,616 cases and 2,475,240 controls), healthspan (n = 300,477) and parental lifespan (~0.8 million of European ancestry). “We included both COVID-19 and healthspan and lifespan in the outcome, because COVID-19 which occurred in recent years reflects a new threat to longevity, whilst healthspan and lifespan reflect overall morbidity and mortality.” The researchers identified 35, 43, and 63 proteins for severe COVID, COVID-19 hospitalization, and SARS-COV2 infection, and 4, 32, and 19 proteins for healthspan, father's attained age, and mother's attained age. In addition to some proteins reported previously, such as SFTPD related to severe COVID-19, the team identified novel proteins involved in inflammation and immunity (such as ICAM-2 and ICAM-5 which affect COVID-19 risk, CXCL9, HLA-DRA and LILRB4 for healthspan and lifespan), apoptosis (such as FGFR2 and ERBB4 which affect COVID-19 risk and FOXO3 which affect lifespan) and metabolism (such as PCSK9 which lowers lifespan). They found 2, 2, and 3 proteins shared between COVID-19 and healthspan/lifespan, such as CXADR and LEFTY2, shared between severe COVID-19 and healthspan/lifespan. Three proteins affecting COVID-19 and seven proteins affecting healthspan/lifespan are targeted by existing drugs. “Our study provided novel insights into protein targets affecting COVID-19, healthspan and lifespan, with implications for developing new treatment and drug repurposing.” DOI - https://doi.org/10.18632/aging.205711 Corresponding authors - Jie V. Zhao - janezhao@hku.hk, and Zhonghua Liu - zl2509@cumc.columbia.edu Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts About Aging-US Aging publishes research papers in all fields of aging research including but not limited, aging from yeast to mammals, cellular senescence, age-related diseases such as cancer and Alzheimer's diseases and their prevention and treatment, anti-aging strategies and drug development and especially the role of signal transduction pathways such as mTOR in aging and potential approaches to modulate these signaling pathways to extend lifespan. The journal aims to promote treatment of age-related diseases by slowing down aging, validation of anti-aging drugs by treating age-related diseases, prevention of cancer by inhibiting aging. Cancer and COVID-19 are age-related diseases. Please visit our website at https://www.Aging-US.com and connect with us: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM
Join us as we welcome back Dr. Veera Rajagopal, a discovery scientist at Regeneron with an interest in human genetics and drug target discovery in neuroscience and psychiatry. If you're a regular listener of The Genetics Podcast, you are likely familiar with Dr. Veera's annual round-up episodes. This year, we are excited to announce quarterly episodes with Dr. Veera, where he and Patrick walk you through the latest developments in genetics, drug discovery, and precision medicine throughout the year. This quarter's episode will focus on non-coding variants and the future of genome-wide association studies (GWAS). Tune in now, and don't forget to check out Veera's substack, GWAS Stories, and his Twitter, @doctorveera.
Dr. Azra Frkatović-Hodžić from Genos Glycoscience Research Laboratory in Zagreb, Croatia, discusses a #research paper she co-authored that was #published by Aging (Aging-US) in Volume 15, Issue 24, entitled, “Mapping of the gene network that regulates glycan clock of ageing.” DOI - https://doi.org/10.18632/aging.205106 Corresponding authors - Azra Frkatović-Hodžić - afrkatovic@genos.hr, and Gordan Lauc - glauc@genos.hr Video - https://www.youtube.com/watch?v=5ExLCMDhpdE Video transcription - https://aging-us.net/2024/03/13/behind-the-study-mapping-of-gene-network-that-regulates-glycan-clock-of-aging/ Abstract Glycans are an essential structural component of immunoglobulin G (IgG) that modulate its structure and function. However, regulatory mechanisms behind this complex posttranslational modification are not well known. Previous genome-wide association studies (GWAS) identified 29 genomic regions involved in regulation of IgG glycosylation, but only a few were functionally validated. One of the key functional features of IgG glycosylation is the addition of galactose (galactosylation), a trait which was shown to be associated with ageing. We performed GWAS of IgG galactosylation (N=13,705) and identified 16 significantly associated loci, indicating that IgG galactosylation is regulated by a complex network of genes that extends beyond the galactosyltransferase enzyme that adds galactose to IgG glycans. Gene prioritization identified 37 candidate genes. Using a recently developed CRISPR/dCas9 system we manipulated gene expression of candidate genes in the in vitro IgG expression system. Upregulation of three genes, EEF1A1, MANBA and TNFRSF13B, changed the IgG glycome composition, which confirmed that these three genes are involved in IgG galactosylation in this in vitro expression system. Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.205106 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, genome-wide association study, glycosylation, glycan clock, immunoglobulin G, CRISPR/dCas9 About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at https://www.Aging-US.com and connect with us: SoundCloud - https://soundcloud.com/Aging-Us Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM
Welcome to the Olink® Proteomics in Proximity podcast! Below are some useful resources mentioned in this episode: UK Biobank Pharma Proteomics Project (UKB-PPP), one of the world's largest scientific studies of blood protein biomarkers conducted to date, https://www.ukbiobank.ac.uk/learn-more-about-uk-biobank/news/uk-biobank-launches-one-of-the-largest-scientific-studies UKB-PPP online resources developed by Nick Lehner and Maria Wörheidehttps://metabolomips.org/ukbbpgwas/ Metabolomics and Proteomics Core in Munich:https://www.helmholtz-munich.de/en/core-facility-overview/metabolomics-and-proteomicshttps://www.helmholtz-munich.de/core-facilitiesStefanie.hauck@helmholtz-munich.de ClinspectM (https://clinspect-m.mscoresys.de/) consortium in the Munich area dedicated to move proteomics forward to clinical applicationMore joint initiatives towards Germany-wide benchmarking and standardized processes are in the making, follow the news on https://www.mscoresys.de/ Research articlesSun, B.B., Chiou, J., Traylor, M. et al. Plasma proteomic associations with genetics and health in the UK Biobank. 2023 Nature, DOI: 10.1038/s41586-023-06592-6 https://www.nature.com/articles/s41586-023-06592-6Petrera A, von Toerne C, Behlr J, et al. Multiplatform Approach for Plasma Proteomics: Complementarity of Olink Proximity Extension Assay Technology to Mass Spectrometry-Based Protein Profiling. (2020) Journal of Proteome Researchhttps://pubs.acs.org/doi/pdf/10.1021/acs.jproteome.0c00641Multicenter Collaborative Study to Optimize Mass Spectrometry Workflows of Clinical Specimens. Kardell O, von Toerne C, Merl-Pham J, König AC, Blindert M, Barth TK, Mergner J, Ludwig C, Tüshaus J, Eckert S, Müller SA, Breimann S, Giesbertz P, Bernhardt AM, Schweizer L, Albrecht V, Teupser D, Imhof A, Kuster B, Lichtenthaler SF, Mann M, Cox J, Hauck SM. J Proteome Res. 2024 Jan 5;23(1):117-129. doi: 10.1021/acs.jproteome.3c00473. Epub 2023 Nov 28. PMID: 38015820 https://pubs.acs.org/doi/10.1021/acs.jproteome.3c00473 Olink tools and softwareOlink® Explore 3072, the platform utilized by the UK Biobank to measure ~3000 proteins in plasma: https://olink.com/products-services/explore/Olink® Explore HT, Olink's most advanced solution for high-throughput biomarker discovery, measuring 5400+ proteins simultaneously with a streamlined workflow and industry-leading specificity: https://olink.com/products-services/exploreht/ Subscribe to the podcast on your favorite player or app:Apple Podcasts: https://apple.co/3T0YbSm Spotify Podcasts: https://open.spotify.com/show/2sZ2wxO... Google Podcasts: https://podcasts.google.com/feed/aHR0... Amazon Music:
A recent GWAS investigation on risk-taking and bisexuality made some assumptions that some experts don't agree with. Learn more about your ad choices. Visit megaphone.fm/adchoices
A recent GWAS investigation on risk-taking and bisexuality made some assumptions that some experts don't agree with. Learn more about your ad choices. Visit megaphone.fm/adchoices
Erratic weather like deluge rain, longer falls, and patches of drought disrupt vinifera's adaptation to long-sustained winters. Jason Londo, Associate Professor of Horticulture in the School of Integrative Plant Sciences at Cornell AgriTech explains how big weather changes in the Pacific North East can cause vines to wake up earlier posing a risk to freeze or frost damage. By researching acclimation and deacclimation, Jason is working to breed and select varieties for enhanced cold resistance, drought resistance, pest resistance, plus good fruit quality. In the future, to reduce inputs in vineyards and increase economic sustainability we need to put the right grape in the right climate. Resources: 135: Cold Hardiness of Grapevines Cold Hardiness prediction model and monitoring website for the Eastern US Foliar Applied Abscisic Acid Increases ‘Chardonnay' Grapevine Bud Freezing Tolerance during Autumn Cold Acclimation Jason Londo Jason Londo's Recent Publications Vitis Underground: NSF-PGRP project looking at rootstock-scion interaction across multiple environments. Vineyard Team Programs: Juan Nevarez Memorial Scholarship - Donate SIP Certified – Show your care for the people and planet Sustainable Ag Expo – The premiere winegrowing event of the year Sustainable Winegrowing On-Demand (Western SARE) – Learn at your own pace Vineyard Team – Become a Member Get More Subscribe wherever you listen so you never miss an episode on the latest science and research with the Sustainable Winegrowing Podcast. Since 1994, Vineyard Team has been your resource for workshops and field demonstrations, research, and events dedicated to the stewardship of our natural resources. Learn more at www.vineyardteam.org. Transcript Craig Macmillan 0:00 Our guest today is Jason Londo. He is Associate Professor of horticulture in the School of integrative Plant Sciences at Cornell agritech. We're gonna talk about some pretty cool stuff today. Thanks for coming on the show. Jason, Jason Londo 0:11 Thank you for having me. Craig Macmillan 0:12 Your work tends to center around identifying things like climate induced disorders, developing medication methods, improving resiliency and sustainability of crops like apples and grapes. How did you become interested in that that's a pretty interesting area. Unknown Speaker 0:26 Originally, I was mostly interested in how plants adapt to stress just in general plants, because they're stuck to the ground that the seed lands on they are forced with so many complicated life's challenges, that it's really amazing what a plant can do in the face of stress. And so my curiosity has always been trying to figure out those strategies. But climate induced part of it is sort of reality striking into my passion, right? We know the climate is shifting, and it is shifting those stresses in a way that our plants can't necessarily respond in the same way that they used to, particularly because of the rate of climate change. So that's how I got interested in this topic, just trying to figure out how plants work when they're stressed out. Craig Macmillan 1:13 And you're interested in plants in general. And then now you're focusing on specific crops, right? Jason Londo 1:18 Yes, indeed, I started out originally working on endangered mints. If you can imagine that. Then I worked on rice. Then I worked on canola and I landed and fruit crops. And so yeah, lots of lots of diversity in those systems. All those plants have different stresses. Craig Macmillan 1:35 They're all different families. I mean, he really jumped around. Jason Londo 1:37 Oh, yeah. One of the coolest things about working in plant stress is plants across different clades evolved different ways of handling maybe the same stress. And you can learn a lot about sort of the limitations of stress response and the advantages and opportunities when you work across a lot of different systems. And so it makes for a tricky CV, because my publications kind of snake all over the place. But from trying to figure out the next strategy or figure out the next experiment, I feel like it's a real positive to have that background. Craig Macmillan 2:13 I want to go back for a second because I think this is an important topic. And you mentioned clade. What is a clade? And how does that apply to looking at plant stress? Jason Londo 2:24 And its most basic a clade is a group of plants that belong to the same sort of evolutionary history, and without getting into the real jargony. And the fights between what makes a species and what doesn't make a species. The basic concept is an evolutionary group. And so when I talk about plant stress strategies and differences between clades if we think about rice, it's a monocot. And so it has a completely different evolutionary lineage from most of our dicot fruit crops. Canola is a dicot it's a mustard. Both rice and canola are typically annualized, maybe sometimes there's a perennial version, when we talk about fruit crops, we're talking about, in my case, grapes and apples, Woody perennials, so dicot species that persists for many, many years. And so the strategies that are successful for for getting through a stressful situation can vary very much by those different life histories. Craig Macmillan 3:24 We're kind of talking about stresses in general, what are particular stresses on things like apples and grapes that you're looking at. Jason Londo 3:29 So in my program, it has a climate adaptation focus. And we all know that the main drivers behind climate change are temperature and precipitation. And here in the northeast, we do have a benefit in that we've got some room to get warm before it gets uncomfortable. And we have plenty of rain. But what we're seeing here is big changes in our winter weather shifts in our phonology. So the spring is coming earlier, the fall is coming later. And then we're also having big changes in precipitation. So little patches of drought, deluge, rain, and so very different from California, where things may be drying out. We're drying out, but in a very episodic sort of pattern. And the systems here are not built on drought management. They're not built so much on water logging either, although we do use tiling in the fields to Drain off excess water. And so when we're talking about climate impacts, here are primarily talking about temperature and shifts in precipitation. I know that you've been looking at cold hardiness. What has been the pattern? What's the change that's happening in the Northeast as far as cold goes? Yeah, so most of my career, as a as a PI has been in cold hardiness and cold stress response in grapes. I spent 10 years at the USDA as a geneticist, particularly diving into this topic, and even in those 10 years years I've seen a major shift in the intensity of our winters they are getting much more mild, but they're also coming very erratic. And so we're having large swings in temperature. I'm sure your listeners are familiar with the concept of a polar vortex we've had enough of them. Now, that is pretty common. When you take a perennial crops like grape, and you put it through winter, it's it's adapted to a long, sustained winter, not a real chaotic, episodic type winter where it gets warm and cold and warm than cold. The the complex molecular components of what tells the grape that it's safe to wake up don't function as well when you have those erratic temperatures. And so we're seeing, in general more mild, which is good for baseline cold hardiness, but also an uptick in sort of chaos. And that's not good for for any form of cold hardiness. And it particularly affects late winter, because the the plants wake up. As they're coming into spring, they respond to heat. And when you have weird weather in that really late winter, early spring, they can wake up too early and then suffer a lot of freeze damage or frost damage if they happen to break bud. Craig Macmillan 6:11 What is the mechanism around freeze damage? I've interviewed some folks from like Michigan and Iowa and Ohio, we don't have freeze damage in California very much Washington, obviously. What are the parameters there? How cold for how long? And what's the actual mechanism of damage to the volume? Jason Londo 6:29 Yeah, great questions. Very complicated questions. Craig Macmillan 6:35 That's why we're here. Jason Londo 6:35 Yeah, yeah. All grapes gain cold hardiness in the winter, regardless of where they are, it's a part of going dormant and making it through winter. The biggest changes that we see in the vine is that the buds will isolate from the vasculature. And so the little connections that come from the xylem and the phloem, into the bud, they actually get clogged up with pectins. And so you have to think of the bud is sort of like a little island tissue, it's not connected to the cane during winter. Once the bud does that it's able to gain cold hardiness and traverse winter. And that process is called acclamation. And so the buds gain a greater and greater ability to survive lower and lower temperatures. We don't know exactly how all of it works. But it's a mixture of making more sugars and making more Ozma protectant inside the buds so that water freezes at lower temperatures and also controlled dehydration. So the more you can dehydrate a tissue, the less likely ice crystals will form in pure water. But and we don't know how they do this. And it's quite magical if you think about it, but they're able to suck out all of this internal water so that it is less and less likely for water to freeze inside the cell. If they can keep the ice crystals from forming inside the cell. We call that cold hardiness that they they are surviving freeze damage, we can measure the temperature that reaches that defense. And you've had other speakers on your show that have talked about cold hardiness. It's called differential thermal analysis. And we basically measure the precise temperature where the water freezes through some tricks of thermodynamics, that cold hardiness failure point changes throughout the whole winter, and it changes by the location that the grape is growing in. What we do know about the system is that it takes oscillating temperatures to gain cold hardiness. So it has to get warm than cold warm than cold, warm than cold and progressively colder in order to ramp down and gain cold hardiness, then it has to stay cold for the cold hardiness to sort of hang out at the maximum cold hardiness. And that maximum cold heartedness is going to differ by region. So here in New York, something like Chardonnay will reach a maximum cold hardiness of maybe negative 27 Celsius. I cannot do the Fahrenheit conversion,. Craig Macmillan 9:00 That's fine. That's fine. Jason Londo 9:03 But say, say negative 27 Fahrenheit, whereas in California, it may not gain more than negative 20. And that's because it just doesn't get pushed. As you go through winter. You go through a whole bunch of other stuff with dormancy chilling our requirement, and that changes the way that the bud responds to temperature. And you enter a phase called Eco dormancy, which is now resistance to freezing based on how cold the vineyard is. And so when you get warm spikes in late winter, when the buds are eco dormant. They think those are a little preview that it's springtime and so they lose their cold heartedness really quickly they start reabsorbing that water, and they'll freeze that warmer and warmer temperatures. And so that's really the most dangerous time in this sort of climate chaos. When you think about winter that late winter period is when the vines are reacting with their adaptive complex for 1000s of years. When it started to warm up. It meant it was spring and now they're starting To think, okay, spring is coming. But we're still in February in New York, maybe in. In California. It's more like it's January and you're getting a warming event. And they all move right towards bud break. And then of course, they can get hit pretty hard by a leak freeze or a frost. Craig Macmillan 10:15 Yeah, exactly. I'm guessing this varies by variety. Jason Londo 10:19 Yes, very much. So, vinifera varieties are typically less hardy than the North American adapted varieties, the, the hybrid varieties is often gets used. I don't particularly like the word hybrid. But these cold climate grapes that have been bred by University of Minnesota and Cornell, they tend to have greater maximum cold hardiness. But they also tend to wake up in the spring much faster. And that's partly because of the genetic background that those hybrids were made from. When you breed with species that come from the far north, like Vitis riparia, those species are adapted to a very short growing season, which means as soon as it's warm enough to start growing, they go for it to try to get through their entire cycle. So now we're starting to see that there are some potential issues with climate change when we think about hybrid varieties that use those those northern species, and that they may be more prone to frost damage in the future. Craig Macmillan 11:15 Oh, really, that's I wouldn't have thought that I would have thought the opposite. So obviously, we have different species. So we have some genetic differences between what I'll call wild grapes or native grapes, the Oh, invasive plant itis vinifera that has been thrown around. What can we learn by looking at the genetics of native North American varieties? Jason Londo 11:38 from a cold hardiness perspective, Craig Macmillan 11:40 cold hardness, just in general drought resistance, pest resistance? Jason Londo 11:44 Well, in general, they're a massive resource for improvement, which depends on who is who's calling a species species. But there may be up to 20 Different wild species in North America. And each of those wild species has a different evolutionary trajectory that has given it the ability to create adaptive gene complexes, that could be useful in viticulture, as we have shifting climate, away from what maybe vinifera likes, hot and dry into further northern latitudes, you know, that if the California industry has to start moving up in latitude or up in altitude, we start integrating different stresses that maybe those vines haven't been exposed to in their evolutionary history, you know, from Europe. And so these wild species just have these potentially novel genes, potentially novel pathways where genes are interacting with one another, that give vines a greater plasticity. And so this concept of plasticity is if you take an individual and you put it in environment a, and it grows to size 10, but you put it in environment B and it grows to size 20. The difference there is the plasticity between those two environments. And we really, if we want sustainable viticulture, what we want to encourage is using cultivars that have maximal plasticity. So as the environment shifts around them, they're still able to give you the same yield the same sugars, the same quality, you know, within a within an error bar anyway, they're the most resilient over time. And incorporating traits and pathways that come from wild grapes can help build that plasticity in the genetic background coming from the European great. Craig Macmillan 13:23 So we're talking about crosses, we're talking about taking a native plant and then vinifera crossing to create something new. You had said that you don't know you don't care for the word hybrid. Why not? That's interesting to me. Jason Londo 13:35 Because it has a negative connotation in the wine drinker. realm, right people think of hybrids as lower quality as not vinifera, so lesser. And I think I'm not an enologists. I'm not a viticulturalists. So I want to be careful on whose toes I mash. But if we're talking about sustainability of a crop through an erratic climate, we can do a lot with vinifera we can we can mitigate climate change a lot with vinifera, but at some point, the inputs may become too much to make it a sustainable crop and then we need to be able to move to adapted varieties. And we can adapt the wine quality from vinifera to climate chaos, by breeding and and selecting for enhanced cold resistance, enhanced drought resistance, enhance pest resistance, and good fruit quality. That's a little bit of a soapbox. But when people say hybrid, it's like lesser, but it's, in my opinion, it's more we're taking something great. And we are increasing its plasticity across the the country across the growing zones. We are giving it a chance to grow in more regions reach more local communities create a bigger fan base. So I get really my hackles got up because there is amazing hybrid based on Climate adapted based wines, and winemakers. And when we use the word hybrid people just automatically in their mind shifted into lesser. And I think that's unfortunate. I think it's something that we need to work actively as an industry against, because a lot of those particular disease resistance traits are coming from wild germ plasm. That is not in the European grape. And we just can't solve all our problems with that one species. Craig Macmillan 15:30 So the kinds of traits that we're talking about these environmental adaptations, or acclamations, these will be polygenic trades, how do you find these? I'm assuming that you're looking for those specific genetic information to say, Yeah, this is the plant that I want to use in my my breeding program. What does that look like? How do you do that? Jason Londo 15:49 So the approaches are very similar to when you're working on single locus traits. And so disease resistance and fruit color are good examples of traits that often can be found in single locus examples, again, would be fruit color, or sort of run one disease resistance, there's a whole bunch of different disease resistance was like polygenic traits can be found the same way, you have to make a cross between two different grapes that have different phenotypes. And so that might be a drug sensitive, and a drought tolerant individual. And you plant out a whole lot of baby grapes 200, 300 progeny from that cross, and then you score them with phenotypes. And with polygenic traits, it's a lot harder to find them sometimes, because in that group of, say, 300, babies, you're not looking for the movement of one gene. In that background, you're looking for maybe the movement of five to 10 different genes. And that means instead of getting a light switch kind of trait, red or white fruit, you're getting a little bit more drought resistant, a whole lot more drought resistant, but there is a gradient, right? When you have a gradient for a phenotype, you need a lot more grape babies in order to get the statistical support to say, hey, this piece of the genome right here, this makes a grape, a little bit more drought resistant. And over here, this piece of the genome does the same thing. And when you put them together, they either add up one plus one, or sometimes they multiply two times two, you use the same approaches, it's typically a little trickier. And you got to kind of do a couple extra years of screening. But it's the same basic playbook to track down those different traits. And we have to do a lot of different phenotypes for drought response, you might be looking for the ability to root deeper, have bigger root masses, you might be looking at bigger hydraulic conductance in the trunk, you might be looking at betters to model control. You might be looking at pyres to model density or lowers to model density, you could be looking at thicker or thinner leaves. So you can imagine if there's lots of ways to be more drought resistant. There's lots of genes that help you in that pursuit. You need a lot of baby grapes in order to find all those little pockets where those genes come together and give you a statistical shift and in the phenotype. Craig Macmillan 18:10 So you're able to identify these are you using something like qualitative trait? Jason Londo 18:13 Exactly. Quantitative trait loci? Craig Macmillan 18:16 Yes, exactly. So that helps speed the process up a little bit. Maybe. Unknown Speaker 18:20 Yeah, so so QTL mapping, quantitative trait loci mapping is the probably the dominant way that we map traits. There's another way called GWAS, genome wide association studies, is built on the same concept where you have a big enough population of either grape babies or in the case of GWAS its diversity. So you'd say, let's say you had 200 Different Vitis riparias instead of 200. Babies, the principle is the same. You are looking for across all of those vines, statistical association between a specific part of the genome and a phenotype to like make it really simple. In 200 babies, grape babies, you want to have enhanced drought resistance. You let's say we take a measurement of carbon isotope concentration and so that carbon isotopes tell you how often the stomates are open, right? So you do an experiment. And you drought stress your plants, and you use carbon isotopes as the phenotype and you say, Okay, this group of 75 individuals, they all shut their stomates right away, and this other group of 125, they kept their stomates open. So then in those two groups, you look at all the genetic markers that are in the background, right, which are like little signposts across the genome. And you say, in this group of 75, which genetic markers do we see over and over and over again, outside of statistical randomness, right? And what that will give you a peek a QTL peak, if you're lucky, right, I'll give you a cue to help you can say hey, right here on chromosome four, every single baby in that pool has a has this set of markers, these five Mark occurs. So there must be a gene, somewhere near these five markers that contribute to closing your stomates. And so then extrapolate that out whatever trait you want to look at how whatever phenotype method you're using, maybe it's not carbon isotope, maybe it's leaf mass, maybe it's node number, I don't know, whatever that screening process is, the concept is the same. You have big enough population, a good genetic marker background, and a phenotype that you can measure. And you can find the statistical associations. Craig Macmillan 20:32 And actually, that reminds me of something, how many chromosomes do grapes have? Jason Londo 20:36 Well, bunch grapes have 19 muscadine. grapes have 20. Craig Macmillan 20:39 That's a lot. Which means that there's a lot of genetic variation in the genome of these plants, then. Jason Londo 20:47 Yeah, if you think about, I mean, grape is sort of a funky beast, because a lot of these varieties that we grow, they're all They're all of the arrays, we grow our clonal. And some of them are 1000s of years old, the same genetic individual from 7000 to 10,000 years ago, we still have around today, in that process, it's it's changed, right? There's mutations that happen in the field all the time. And so even thinking about genetic clones and thinking the idea of Chardonnay being around that long, it's changed in those 7000 years, just naturally. So when you think about comparing two different clones, or two different cultivars, or clones, there's something like 43,000 Different recognized genes in vitis vinifera, that number I can give you in the different wild species, because it varies by species, but roughly 40,000 at those 40,000 genes in a in a single individual, you can have up to two different copies, right. So you could have essentially 80,000 different alleles, then you go across, I don't know, what do we have 12,000 recognized cultivars or something like that? There are something like 60 Grape species. And so now imagine the amount of potential variation you have across that entire gene pool. And so yeah, the genetic diversity within the crop as a whole is incredible. There's a lot of room for improvement. And there's a lot of room for climate adaptation. Just takes a lot of grape babies to figure it out. Craig Macmillan 22:12 And that brings us something else. And that is the the idea of mutation. One of the issues, I think that is a stumbling block, and you mentioned it, there is the consumer, if it's not Cabernet Sauvignon, can't call it Cabernet Sauvignon. I'm not as interesting, which is something that I think we need some help from the marketing world with. Because I agree with you very much. I think if we're going to have wine in the future, we're going to have to start thinking about things other than just the cultivars that we have. Now, can you do the same kind of work with but mutation? Can you take a cane grew from a button, plant that out and look for differences between the same plant? Jason Londo 22:53 Yeah, so you're basically talking about clonal selection clonal selection is practice worldwide by different regions, always with this eye towards making something that we currently have a little bit better or a little bit more unique, right, somatic mutations, random mutations occur in the genetic background all the time. And they often occur in response to stress, which is a really interesting angle, if you think about climate stress. So these mutations happen all the time in the background. Frequently, they will land on pieces of DNA that don't do anything that we know up. I don't want to say that no DNA is unimportant, that there are sections that we don't believe are that important. We call these non coding regions are sometimes introns. When you have a mutation in that area, sometimes there's no effect on the vine at all. And that's happening all the time in the fields. Right now. If you think about all the 1000s to millions of cab sauv vines that are growing in the world, we like to think of them even if you pick a single clone as the same genetic individual. And that is, that's simply not possible. There's so much background mutation going on in those parts of the DNA that don't give us any change in phenotype. There's no way it's all the same. We'd like to simplify it. We'd like to simplify it for our drinking behavior, as well as you know, like our sanity. But yes, you can select for clonal variation. And clonal variation happens all the time when those changes happen to land in a gene producing region, exon or perhaps a promoter or, or even in a transposable element to make a piece of DNA jump around the genome, we get a new clone, you can purposely create clones as well. So it happens naturally, but you can create clones on your own and mutational breeding is something that gets used in a lot of crop species in grapes it doesn't get used as often because it's modifying the base plant, right? So if you take Chardonnay and you want to increase his disease resistance, if it doesn't have a gene that you can break or change that would give it more disease resistance, then you can't create a clone with more disease resistance, right? You're working with a big a base plant that has limitations, but we have So we have a population where this was done it was it was done actually by the USDA by Dr. Amanda Garis. She no longer works for the USDA, but she worked here in Geneva. And they did a project where they took the variety of vignoles, which has a very compact cluster and tends to get a lot of rot. And they took a bunch of dormant canes with the buds, and they put it in a high powered X ray machine at the hospital and blasted it with X rays. What X ray damage does to DNA is it causes breaks between the double strands so all of our DNA and all our genes are wrapped up in in double stranded DNA. And when you do DNA damage with X ray mutagenesis, you break the two strands. And then when they heal themselves back together, it's often imperfect. And so they'll often lose a couple base pairs like there'll be a little piece get that gets nipped out. When you put those two pieces back together and repair, if that landed in exon, you can sometimes change the protein that would have been made by that exon or completely knocked the gene out in its entirety. Creating a clone, you're just doing it faster than nature is doing it on its own. We do it with a hospital X ray machine. And so with this method, they created about 1000 clones of vignoles. And they've made I think 10 selections out of that group that have bigger, looser clusters, so the berries are further spaced out. So they don't get damaged, they don't get as much rot. And I think those are now starting to make their way out into trials. There's an example of a very directed approach to creating a clone to fit fit a very specific viticultural problem that may or may not work for climate adaptation because of the polygenic aspect that you brought up before. Because if you break one gene and a poly genic, adaptive complex, it may not be enough to shift the entire physiology into a recognizably different pattern, it could work to make them less resilient, because you could break something that's really important. But breaking something that's important, but works out for you in the long run is just playing that randomizer lottery a little bit further. So it's doable. It can happen in nature, it can happen on purpose in our hands, but it is trickier for certain traits. Craig Macmillan 27:21 So we're not going to X ray our way out of climate problems, basically, or diseases problems, right? Well, there may not be the right genetic information in the background of vinifera that even if we tried that, we'd have that set of genes that we would need, whereas we would have it in a native, native vine North American vine. Jason Londo 27:42 And just a sheer a sheer number of breaks that you might have to make in order to shift the physiology enough to matter. These climate adaptation pathways are highly networked. They involve hormones, they involve sugar metabolism. And so if you really break something important, it's going to cause a really bad phenotype of death phenotype, you have to nudge the system enough in a specific direction to make a meaningful change. And so, given the complexity of the trade, it makes it harder. I don't want to say anything is impossible. I do think that there would be ways to make vinifera better, more plastic in the environment. I think the potential is there for vinifera to do better in a lot of climates. I don't know if directed mutagenesis is the most efficient way to do it. I mentioned is that random, right, you're breaking double stranded DNA at random, and then it's really healing and there's so many things have to work out for you to hit the right gene, have the right repair, you know, all of that sort of stuff that it's a method, but I don't I wouldn't say it's the most efficient method breeding with wild germ plasm is also a method, the key weakness there is then it's no longer Chardonnay, right from our wine drinking sort of our own personal biases on that situation. We outcross Chardonnay to make it more climate resilient. It's no longer Chardonnay. So it can't be sold as Chardonnay. And that itself creates a market pressure against changing it to something that's more resilient. And I think until the climate imparts an equal level of pain as consumer pressure, we won't get there. I don't think it's a question of if it will happen. It's a question of when. Craig Macmillan 29:23 What kind of projects are you working on currently? You've mentioned experiments and breeding and it's now what do you what do you up to? Jason Londo 29:29 So I have a pretty diverse program climate impacts is all season so we have a lot of winter projects. And we've covered some of that now trying to understand how Acclimation and deaacclimation work and if we can enhance it, we're working with but birth control. So if we could slow down deacclimation and delay by break, we could get around frost damage. And then I'm also working on a really big project is actually coming to an end where we've been looking at what the role of a rootstock is our mapping population concept that we talked about for QTL Mapping, we were talking about the scion, I have a project where we did that with the rootstock. And so we created a mapping population. The only part that is the grape babies is the roots. And we've grafted the same variety onto those roots. And then we're looking at how the different grape baby roots change the scions behavior. A really cool thing about this project is that we've replicated it clonally replicated it and grafted it in three different locations. So we have a vineyard in Missouri, a vineyard in South Dakota and a vineyard here in New York. And so across those three different environments, which are quite different, both in maximum temperature, minimum temperature and precipitation, we're learning so many cool things about what the roots can do to the same scion for your listeners, of course, they know grapes, so they know hopefully enough about grafting and that the rootstock and the scion are two different individuals. And they're mechanically grafted together. From a climate adaptation point of view, what you've done is you've taken an intact and adapted individual, and you've cut its head off, and then you've taken another climate adapted individual, and you've cut its legs off, and you've glued them together, and ask them to perform in the environment, which is just a wild, wild communication question. When the roots are experiencing one environment, and the shoot is experiencing another, how do they communicate? And then how does that affect our grape quality and wine quality? And so we're looking at drought response, can we increase the drought resistance of the Scion, based on the type of root it's on? Can we change the leaf nutrient profile, so the different ions that are taken up from the soil and how they're concentrated in the leaves. And of course, we don't really care about the leaves as much as we care about the fruit, the leaves are easy to work with. And we're even started working on wine quality. And so it looks like across our experiments, we might be able to optimize the rootstock and scion combinations we grow in different climates. To produce specific wind quality attributes, which is really cool. Craig Macmillan 32:00 That is really cool. That is really cool. We're just about out of time. But I want to is there one thing on the on these topics that you would like or recommend to our listeners, or you'd like our listeners to know? Jason Londo 32:11 Oh, well, I think their take home is is that we should all appreciate the new cultivars that come on the scene, whether they be from early regions like the the Eastern caucuses, something that we are not used to having in this country, or its climate adapted varieties that are bred in this country, and grown in these different regions. We need to do our best to open our minds not to does this grape or that grape tastes like cab sauv, or tastes like Chardonnay. But isn't it amazing what this grape tastes like period, because a lot of the the advances in resilience and sustainability that we can get out of either adopting new cultivars, shifting cultivars from climate to climate, or by using hybrid varieties in different regions, all of the benefits that we can get out of growing the right kind of grapes in the right climate, reduces inputs in the vineyard reduces inputs on the ecology. It increases the economic stability of rural communities. And it gives you pride in what the local region can produce. And I guess my take home would be is drink more adapted wines, enjoy them, figure out the nuances. Some of them are not great, but some of them are really great. drink more wine. Craig Macmillan 33:33 Where can people find out more about you and your work? Jason Londo 33:36 So the easiest way is just to Google my name and Cornell and that will take you right to my Cornell page. There's not a lot of information on my Cornell page, and I'm a big procrastinator on my personal website. But you can find my contact information there and certainly get a hold of me directly. If there's anything of interest. I will also send you some links that you can use to take listeners to the Vitis underground project, which is the NSF rootstock project I talked about, I can send you a link to we have a cold hardiness website where we post prediction models that we've built about cold hardiness across most of the Eastern US. We hope to expand that to be nationwide once once I get a stronger computer, but I can send you some links there. Yeah, I would say that that's probably the best places to find information on me and the program here. And if people are in town to come and see Cornell Agrotech and see some of the stuff in the field. Craig Macmillan 34:30 I would love to pay a visit. I've interviewed a number of your colleagues there and there's so much cool stuff going on. really innovative and really groundbreaking feel like we're on the leading edge of a wave that some point is going to break again. Maybe we'll be drinking wines other than the ones we've been drinking. I can see that happening. Anyway. So our guest today was Jason Londo. He's Associate Professor of horticulture in the School of integrative Plant Sciences at Cornell agritech. Thank you. Jason Londo 34:55 Thanks Nearly perfect transcription by https://otter.ai
------------------Support the channel------------ Patreon: https://www.patreon.com/thedissenter PayPal: paypal.me/thedissenter PayPal Subscription 1 Dollar: https://tinyurl.com/yb3acuuy PayPal Subscription 3 Dollars: https://tinyurl.com/ybn6bg9l PayPal Subscription 5 Dollars: https://tinyurl.com/ycmr9gpz PayPal Subscription 10 Dollars: https://tinyurl.com/y9r3fc9m PayPal Subscription 20 Dollars: https://tinyurl.com/y95uvkao ------------------Follow me on--------------------- Facebook: https://www.facebook.com/thedissenteryt/ Twitter: https://twitter.com/TheDissenterYT This show is sponsored by Enlites, Learning & Development done differently. Check the website here: http://enlites.com/ Dr. James Lee is Associate Professor of Psychology, and a member of the Graduate Faculty of Bioinformatics and Computational Biology at the University of Minnesota. In 2012, Dr. Lee earned a Ph.D. from the Department of Psychology at Harvard University. The papers collected in his dissertation cover causal inference, genome-wide association studies, and cognitive-experimental approaches to the study of individual differences. He was a postdoctoral researcher in the Mathematical Biology Section of NIDDK/NIH from 2011 to 2013, working on problems in population and statistical genetics. In this episode, we talk about behavior genetics. We discuss genome-wide association studies (GWAS), and what we can learn from them. We talk about the concept of heritability. We go through traits like educational attainment, IQ, and alcohol and tobacco use. We talk about laypeople's beliefs about the heritability of behavior. Finally, Dr. Lee answers two questions from a patron of the show, about modern education, and causality in behavior genetics. -- A HUGE THANK YOU TO MY PATRONS/SUPPORTERS: PER HELGE LARSEN, JERRY MULLER, HANS FREDRIK SUNDE, BERNARDO SEIXAS, OLAF ALEX, ADAM KESSEL, MATTHEW WHITINGBIRD, ARNAUD WOLFF, TIM HOLLOSY, HENRIK AHLENIUS, JOHN CONNORS, FILIP FORS CONNOLLY, DAN DEMETRIOU, ROBERT WINDHAGER, RUI INACIO, ZOOP, MARCO NEVES, COLIN HOLBROOK, PHIL KAVANAGH, SAMUEL ANDREEFF, FRANCIS FORDE, TIAGO NUNES, FERGAL CUSSEN, HAL HERZOG, NUNO MACHADO, JONATHAN LEIBRANT, JOÃO LINHARES, STANTON T, SAMUEL CORREA, ERIK HAINES, MARK SMITH, JOÃO EIRA, TOM HUMMEL, SARDUS FRANCE, DAVID SLOAN WILSON, YACILA DEZA-ARAUJO, ROMAIN ROCH, DIEGO LONDOÑO CORREA, YANICK PUNTER, ADANER USMANI, CHARLOTTE BLEASE, NICOLE BARBARO, ADAM HUNT, PAWEL OSTASZEWSKI, NELLEKE BAK, GUY MADISON, GARY G HELLMANN, SAIMA AFZAL, ADRIAN JAEGGI, PAULO TOLENTINO, JOÃO BARBOSA, JULIAN PRICE, EDWARD HALL, HEDIN BRØNNER, DOUGLAS FRY, FRANCA BORTOLOTTI, GABRIEL PONS CORTÈS, URSULA LITZCKE, SCOTT, ZACHARY FISH, TIM DUFFY, SUNNY SMITH, JON WISMAN, DANIEL FRIEDMAN, WILLIAM BUCKNER, PAUL-GEORGE ARNAUD, LUKE GLOWACKI, GEORGIOS THEOPHANOUS, CHRIS WILLIAMSON, PETER WOLOSZYN, DAVID WILLIAMS, DIOGO COSTA, ANTON ERIKSSON, CHARLES MOREY, ALEX CHAU, AMAURI MARTÍNEZ, CORALIE CHEVALLIER, BANGALORE ATHEISTS, LARRY D. LEE JR., OLD HERRINGBONE, MICHAEL BAILEY, DAN SPERBER, ROBERT GRESSIS, IGOR N, JEFF MCMAHAN, JAKE ZUEHL, BARNABAS RADICS, MARK CAMPBELL, TOMAS DAUBNER, LUKE NISSEN, KIMBERLY JOHNSON, BENJAMIN GELBART, JESSICA NOWICKI, LINDA BRANDIN, NIKLAS CARLSSON, ISMAËL BENSLIMANE, GEORGE CHORIATIS, VALENTIN STEINMANN, PER KRAULIS, KATE VON GOELER, ALEXANDER HUBBARD, LIAM DUNAWAY, BR, MASOUD ALIMOHAMMADI, JONAS HERTNER, URSULA GOODENOUGH, DAVID PINSOF, SEAN NELSON, MIKE LAVIGNE, JOS KNECHT, ERIK ENGMAN, AND LUCY! A SPECIAL THANKS TO MY PRODUCERS, YZAR WEHBE, JIM FRANK, ŁUKASZ STAFINIAK, TOM VANEGDOM, BERNARD HUGUENEY, CURTIS DIXON, BENEDIKT MUELLER, THOMAS TRUMBLE, KATHRINE AND PATRICK TOBIN, JONCARLO MONTENEGRO, AL NICK ORTIZ, AND NICK GOLDEN! AND TO MY EXECUTIVE PRODUCERS, MATTHEW LAVENDER, SERGIU CODREANU, BOGDAN KANIVETS, ROSEY, AND GREGORY HASTINGS!
In this episode, Marie Sadler talks about her recent Cell Genomics paper, Multi-layered genetic approaches to identify approved drug targets. Previous studies have found that the drugs that target a gene linked to the disease are more likely to be approved. Yet there are many ways to define what it means for a gene to be linked to the disease. Perhaps the most straightforward approach is to rely on the genome-wide association studies (GWAS) data, but that data can also be integrated with quantitative trait loci (eQTL or pQTL) information to establish less obvious links between genetic variants (which often lie outside of genes) and genes. Finally, there's exome sequencing, which, unlike GWAS, captures rare genetic variants. So in this paper, Marie and her colleagues set out to benchmark these different methods against one another. Listen to the episode to find out how these methods work, which ones work better, and how network propagation can improve the prediction accuracy. Links: Multi-layered genetic approaches to identify approved drug targets (Marie C. Sadler, Chiara Auwerx, Patrick Deelen, Zoltán Kutalik) Marie on GitHub Interview with Mariana Mamonova, the Ukrainian marine infantry combat medic who spent 6 months in russian captivity while pregnant Thank you to Jake Yeung, Michael Weinstein, and other Patreon members for supporting this episode.
“Focusing the GWAS Lens on days to flower using latent variable phenotypes derived from global multienvironment trials” with Sandesh Neupane and Derek Wright. Lentil, a pivotal pulse crop, is recognized as an important part of food and nutrition security in the world. It has rich sources of important nutrients, is easy to cook, and thrives well on the farm. Due to its rich dietary benefits, lentil has been introduced to North America, especially in Canada. Originating as a warmer climate crop, domesticated in the Middle East and North Africa, and widely adopted in Southeast Asia, lentil can face adaptation issues in the cooler Canadian climate. This struggle directly impacts flowering, pod-bearing, and overall yield. What precisely are the adaptation constraints hindering lentil introduction in North America? How do varying photoperiods and temperatures exert influence on lentil production? Delving deeper, what genes govern the crop's sensitivity to photoperiods and temperatures? In this episode, Sandesh Neupane and Derek Wright share insights into their research on lentil adaptation and how they dissect the genetic mechanisms orchestrating the photoperiod and temperature sensitivity in lentils with multi-location trials and advanced image-based phenotyping. This groundbreaking work promises to contribute significantly to the breeding of well-suited lentil varieties tailored to thrive in North American conditions. Tune in to learn about: · Lentil and its nutritional value · Lentil's history · The challenges of lentil adaptation in Canada · How the environment affects lentil growth If you would like more information about this topic, this episode's paper is available here: https://doi.org/10.1002/tpg2.20269 This paper is always freely available. Contact us at podcast@sciencesocieties.org or on Twitter @FieldLabEarth if you have comments, questions, or suggestions for show topics, and if you want more content like this don't forget to subscribe. If you'd like to see old episodes or sign up for our newsletter, you can do so here: https://fieldlabearth.libsyn.com/. If you would like to reach out to Derek Wright, you can find him here: derek.wright@usask.ca If you would like to reach out to Sandesh Neupane, you can find him here: sandesh.neupane@usask.ca If you would like to reach out to Om Prakash Ghimire from our Student Spotlight, you can find him here:oghimir@g.clemson.edu Twitter: https://twitter.com/baizalla Resources CEU Quiz: https://web.sciencesocieties.org/Learning-Center/Courses/Course-Detail?productid=%7b66CDC952-F899-EE11-BE37-000D3A32379C%7d Transcripts: https://www.rev.com/transcript-editor/shared/DTO7pupG1PWFmpaCbjNkVKnhQuE9eybRhp_s83uNy5AoLyIlNwjjoi5_3tjqm5lbMxn3ESqOuz1EuC4_GuWmV5Ri604?loadFrom=SharedLink Plant Sciences, Crop Development Centre – University of Saskatchewan: https://agbio.usask.ca/faculty-and-staff/people-pages/kirstin-bett.php#top/ Know Pulse - https://knowpulse.usask.ca/ Thank you to Om Prakash Ghimire for help on the creation of show notes and other assets. Field, Lab, Earth is Copyrighted by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America.
Today, you'll learn about a possible genetic link to vegetarianism, the discovery of a very important ancient woman, and the truth about homework. Genetic Vegetarianism “Going vegetarian? The dietary choice may be influenced by your genes.” by Emily Cooke. 2023. “Genetics of vegetarianism: A genome-wide association study.” by Nabeel R. Yaseen, et al. 2023. “Large-scale GWAS of food liking reveals genetic determinants and genetic correlations with distinct neurophysiological traits.” by Sebastian May-Wilson, et al. 2022. “Shifting Attitudes Towards Meat Consumption: Understanding Vegetarian Statistics.” by Talitha Van Niekerk. 2023. Roman Sarcophagus “‘Exceptional' 1,800-year-old sarcophagus unearthed in France held woman of ‘special status'.” by Sascha Pare. 2023. “Elite Roman man buried with sword may have been ‘restrained' in death.” by Kristina Killgrove. 2023. “The Roman Empire: Rulers, expansion and fall.” by Owen Jarus. 2022. Homework “Is Homework Good for Kids?” by Cara Goodwin, Ph.D. 2023. “Homework and Family Stress: With Consideration of Parents' Self Confidence, Education Level, and Cultural Background.” by Robert M. Pressman, et al. 2015. “Does Homework Improve Academic Achievement? A Synthesis of Research, 1987 - 2003.” by Harris Cooper, et al. 2006. “Physical activity and sedentary behaviors (screen time and homework) among overweight or obese adolescents: a cross-sectional observational study in Yazd, Iran.” by Ali Mohammad Hadianfard, et al. 2021. Hosted on Acast. See acast.com/privacy for more information.
BUFFALO, NY- November 20, 2023 – A new editorial #paper was #published in Oncotarget's Volume 14 on August 30, 2023, entitled, “Predicting the molecular functions of regulatory genetic variants associated with cancer.” Some of inherited human genetic variation can contribute to important phenotypic diversity, such as the varying degrees of individual susceptibility to developing certain health conditions and individual response to therapeutic interventions. To date, over 490,000 genotype-phenotype associations have been discovered through large-scale genome-wide association studies (GWAS); however, molecular functions of most of these discovered GWAS variants remain unknown. In their recent editorial, researchers Jun S. Song and Mohith Manjunath from the University of Illinois at Urbana-Champaign discuss computational methods of genetic analysis using expression quantitative trait loci, frameworks for predicting regulatory genetic functions, application to transcription factors involved in cancer development and progression, and future implications for their methods in cancer research and precision medicine. “There are several technical challenges hindering our understanding [...].” First, the effect size of a typical genetic variant, as measured in terms of the odds ratio of genotype occurrence in case versus control populations, is very small, suggesting that macroscopic systems-level phenotypic differences modulated by each variant may also be small and difficult to detect. Next, most reported variants reside in non-protein-coding regions of the human genome, indicating that they are likely affecting the regulation of some unknown target genes' expression. Finally, the discovered variants may not be functional themselves, but be merely in genetic linkage disequilibrium with other functional variants. “A promising approach to address these challenges is to integrate genomic, epigenomic, transcriptomic and machine learning methods to identify functional genetic variants and characterize their mode of action in regulating target genes.” DOI - https://doi.org/10.18632/oncotarget.28451 Correspondence to - Jun S. Song - songj@illinois.edu Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28451 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, genome-wide association studies, cancer risk, regulatory variants, functional genomics 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, please visit https://www.oncotarget.com and connect with us: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Welcome to the Olink® Proteomics in Proximity podcast! Below are some useful resources mentioned in this episode: Olink tools and software• Olink® Explore 3072, the platform utilized by the UK Biobank to measure ~3000 proteins in plasma: https://olink.com/products-services/explore/• Olink® Explore HT, Olink's most advanced solution for high-throughput biomarker discovery, measuring 5400+ proteins simultaneously with a streamlined workflow and industry-leading specificity: https://olink.com/products-services/exploreht/ UK Biobank Pharma Proteomics Project (UKB-PPP), one of the world's largest scientific studies of blood protein biomarkers conducted to date, https://www.ukbiobank.ac.uk/learn-more-about-uk-biobank/news/uk-biobank-launches-one-of-the-largest-scientific-studies Research articles• Dhindsa, R.S., Burren, O.S., Sun, B.B. et al. Rare variant associations with plasma protein levels in the UK Biobank. 2023 Nature, DOI: 10.1038/s41586-023-06547-xhttps://www.nature.com/articles/s41586-023-06547-x• Sun, B.B., Chiou, J., Traylor, M. et al. Plasma proteomic associations with genetics and health in the UK Biobank. 2023 Nature, DOI: 10.1038/s41586-023-06592-6 https://www.nature.com/articles/s41586-023-06592-6• Ticau S, Sridharan G, Tsour S, et al. Neurofilament Light Chain as a Biomarker of Hereditary Transthyretin-Mediated Amyloidosis 2021 Neurology, DOI: 10.1212/WNL.0000000000011090https://n.neurology.org/content/96/3/e412.long• Zannad F, Ferreira JP, Butler J, et al. Effect of Empagliflozin on Circulating Proteomics in Heart Failure: Mechanistic Insights from the EMPEROR Program. 2022 European Heart Journal, DOI: 10.1093/eurheartj/ehac495 https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehac495/6676779• Eldjarn GH, et al. Large-scale plasma proteomics comparisons through genetics and disease associations. Nature. 2023 Oct;622(7982):348-358. doi: 10.1038/s41586-023-06563-xhttps://www.nature.com/articles/s41586-023-06563-x#Sec44• [PREPRINT] Carrasco-Zanini et al 2023 Proteomic prediction of common and rare diseases MedRxiv https://www.medrxiv.org/content/10.1101/2023.07.18.23292811v1• Michaëlsson E, Lund LH, Hage C, et al. Myeloperoxidase Inhibition Reverses Biomarker Profiles Associated With Clinical Outcomes in HFpEF. 2023 JACC. Heart Failure, DOI: 10.1016/j.jchf.2023.03.002https://www.sciencedirect.com/science/article/pii/S2213177923001257• Girerd N, Levy D, Duarte K, et al. Protein Biomarkers of New-Onset Heart Failure: Insights From the Heart Omics and Ageing Cohort, the Atherosclerosis Risk in Communities Study, and the Framingham Heart Study. 2023 Circulation Heart Failure, DOI: 10.1161/CIRCHEARTFAILURE.122.009694https://www.ahajournals.org/doi/abs/10.1161/CIRCHEARTFAILURE.122.009694Subscribe to the podcast on your favorite player or app:Apple Podcasts: https://apple.co/3T0YbSm Spotify Podcasts: https://open.spotify.com/show/2sZ2wxO... Google Podcasts: https://podcasts.google.com/feed/aHR0... Amazon Music: https://music.amazon.com/podcasts/d97... Podcast Addict: https://podcastaddict.com/podcast/409... Deezer: https://www.deezer.com/show/5178787 Player FM: https://player.fm/series/series-3396598 In case you were wondering, Proteomics in Proximity refers to the principle underlying Olink technology called the Proximity Extension Assay (PEA). More information about the assay and how it works can be found here: https://bit.ly/3Rt7YiY For any questions regarding information about Olink Proteomics, please email us at info@olink.com or visit our website: https://www.olink.com/Interested in a specific podcast topic or guest? Reach out to us at PIP@olink.comWHAT IS PROTEOMICS IN PROXIMITY?Proteomics in Proximity discusses the intersection of proteomics with genomics for drug target discovery, the application of proteomics to reveal disease biomarkers, and current trends in using proteomics to unlock biological mechanisms. Co-hosted by Olink's Cindy Lawley and Sarantis Chlamydas.
Siddhartha Jaiswal, M.D., Ph.D., discusses clonal hematopoiesis and its impact on aging and diseases. Jaiswal highlights the role of genetic variations, focusing on a specific gene, TET2, and its link to clonal expansion. He explains that certain genetic variations can slow clonal expansion, potentially offering insights into treatments or interventions to mitigate its effects. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 39260]
Siddhartha Jaiswal, M.D., Ph.D., discusses clonal hematopoiesis and its impact on aging and diseases. Jaiswal highlights the role of genetic variations, focusing on a specific gene, TET2, and its link to clonal expansion. He explains that certain genetic variations can slow clonal expansion, potentially offering insights into treatments or interventions to mitigate its effects. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 39260]
“Genes and genetic mechanisms contributing to fall armyworm resistance in maize” with Sandra Woolfolk and Leigh Hawkins, research entomologist and molecular biologist (respectively) at USDA-ARS. Fall armyworm is a major pest around the world, causing millions of dollars in damages yearly. However, farmers are not alone in the fight against these invasive creatures, with plant breeders coming alongside to help develop more resistant plants. This episode, Drs. Sandra Woolfolk and Leigh Hawkins discuss their work tracking down the traits that can lead to higher resistance against this frightful pest. Tune in to learn: · What fall armyworms look like · What makes fall armyworms such a scary pest · How DNA, SNPs, and metabolic pathways are like a highway · Which metabolic pathways were the most promising If you would like more information about this topic, this episode's paper is available here: https://doi.org/10.1002/tpg2.20311 This paper is always freely available. Contact us at podcast@sciencesocieties.org or on Twitter @FieldLabEarth if you have comments, questions, or suggestions for show topics, and if you want more content like this don't forget to subscribe. If you'd like to see old episodes or sign up for our newsletter, you can do so here: https://fieldlabearth.libsyn.com/. If you would like to reach out to Sandra, you can find her here: Sandra.Woolfolk@usda.gov If you would like to reach out to Leigh, you can find her here: leigh.hawkins@usda.gov Resources CEU Quiz: Coming soon Transcripts: Coming soon Corn Host Plant Resistance Research Unit: https://www.ars.usda.gov/southeast-area/mississippi-state-ms/crop-science-research-laboratory/corn-host-plant-resistance-research/ Wikipedia: https://en.wikipedia.org/wiki/Fall_armyworm Entomology Department, University of Florida: https://entnemdept.ufl.edu/creatures/field/fall_armyworm.htm Mississippi State Extension Fall Armyworms page: http://extension.msstate.edu/content/fall-armyworms Mississippi State Extension Fall Armyworms in Hayfields and Pastures article: http://extension.msstate.edu/node/7154 USDA-ARS Facebook: https://www.facebook.com/AgriculturalResearchService USDA-ARS LinkedIn: https://www.linkedin.com/company/usda-ars/ FAO Fall Armyworm page: https://www.fao.org/fall-armyworm/en/ USDA Fall Armyworm article: https://www.usda.gov/media/blog/2018/02/26/fall-armyworm-usda-research-lends-hand-international-pest-outbreak Field, Lab, Earth is Copyrighted by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America.
Welcome to the Olink® Proteomics in Proximity podcast! Below are some useful resources from this episode: Published study of primary focusKoprulu M, Carrasco-Zanini J, Wheeler E, Lockhart S, Kerrison ND, Wareham NJ, Pietzner M, Langenberg C. Proteogenomic links to human metabolic diseases. Nat Metab. 2023 Mar;5(3):516-528. doi: 10.1038/s42255-023-00753-7. Epub 2023 Feb 23. Erratum in: Nat Metab. 2023 Mar 19;: PMID: 36823471; PMCID: PMC7614946. https://pubmed.ncbi.nlm.nih.gov/36823471/ Laboratory, first author, and corresponding author of the study· Public Health University Research Institute (PHURI), a multidisciplinary research center to drive personalized healthcare: https://www.qmul.ac.uk/phuri/about/· Mine Koprulu (first author), PhD student, University of Cambridge: https://www.linkedin.com/in/mine-koprulu-497659b9/ · Dr. Claudia Langenberg (corresponding author); Director of PHURI, Queen Mary, University of London; Professor of Computational Medicine, Berlin Institute of Health at Charité: https://www.qmul.ac.uk/phuri/our-people/professor-claudia-langenberg/ Olink tools and software· Olink® Explore 3072, the platform that measured proteins in this study with a next-generation sequencing (NGS) readout: https://olink.com/products-services/explore/ UK Biobank Pharma Proteomics Project (UKB-PPP), one of the world's largest scientific studies of blood protein biomarkers conducted to date, https://www.ukbiobank.ac.uk/learn-more-about-uk-biobank/news/uk-biobank-launches-one-of-the-largest-scientific-studies Genotype-Tissue Expression (GTEx) project, a biobank and open-access database to study tissue-specific gene expression and regulation: https://www.gtexportal.org/home/ European Prospective Investigation into Cancer (EPIC)-Norfolk study, a prospective cohort of middle-aged individuals from Eastern England: https://www.epic-norfolk.org.uk/ Genome Aggregation Database (gnomAD), the largest publicly available collection of population variation from harmonized exome and genome sequencing data: https://gnomad.broadinstitute.org/ Would you like to subscribe to the podcast on your favorite player or app? You can do so here: Apple Podcasts: https://apple.co/3T0YbSm Spotify Podcasts: https://open.spotify.com/show/2sZ2wxO... Google Podcasts: https://podcasts.google.com/feed/aHR0... Amazon Music: https://music.amazon.com/podcasts/d97... Podcast Addict: https://podcastaddict.com/podcast/409... Deezer: https://www.deezer.com/show/5178787 Player FM: https://player.fm/series/series-3396598 In case you were wondering, Proteomics in Proximity refers to the principle underlying Olink technology called the Proximity Extension Assay (PEA). More information about the assay and how it works can be found here: https://bit.ly/3Rt7YiY For any questions regarding information Olink Proteomics, please email us at info@olink.com or visit our website: https://www.olink.com/ WHAT IS PROTEOMICS IN PROXIMITY?Proteomics in Proximity discusses the intersection of proteomics with genomics for drug target discovery, the application of proteomics to reveal disease biomarkers, and current trends in using proteomics to unlock biological mechanisms. Co-hosted by Olink's Cindy Lawley and Sarantis Chlamydas.
BUFFALO, NY- October 25, 2023 – A new editorial perspective was published in Oncotarget's Volume 14 on March 24, 2023, entitled, “Genetic modifiers of p53: opportunities for breast cancer therapies.” Each day our cells encounter a wide range of genomic damage and the p53 protein arbitrates decisions of cell cycle arrest to allow repair of DNA or promote elimination of cells with malignant potential through apoptosis. In this new editorial perspective, researchers Prabin Dhangada Majhi, Aman Sharma and D. Joseph Jerry from the University of Massachusetts, Pioneer Valley Life Sciences Institute and Rays of Hope Center for Breast Cancer Research discuss TP53 mutations. The prevalence of TP53 mutations in nearly all tumors emphasizes its role as a formidable barrier that must be breached to allow oncogenic transformation. Inherited mutations in TP53 are also the primary genetic lesions found in Li-Fraumeni Syndrome (LFS), a familial cancer predisposition characterized by tumors in many tissues. However, tissues are not all equally vulnerable to disruptions in p53 function. Among women with inherited mutations in TP53, breast cancer is by far the most common tumor (Figure 1). Somatic mutations in TP53 are also prevalent in sporadic breast cancers, especially in the triple-negative subtype. The proportion rises to nearly 50% of breast cancers that exhibit impaired function of the p53 pathway based on gene expression signatures as a surrogate biomarker of p53 activity. Therefore, the breast epithelium appears to be uniquely sensitive to alterations in p53 function. “Genomewide association studies (GWAS) have identified over 300 polymorphisms that contribute to breast cancer risk [38–41]. These provide a rich resource of candidate polymorphisms that may modify the consequences of mutations in TP53.” DOI - https://doi.org/10.18632/oncotarget.28387 Correspondence to - D. Joseph Jerry - jjerry@vasci.umass.edu Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28387 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, p53, Li-Fraumeni syndrome, genetic modifiers, breast cancer, DNA repair 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, please visit https://www.oncotarget.com and connect with us: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
PeDRA had the privilege of attending the Symposium on Hidradenitis Suppurativa Advances (SHSA) in Phoenix, AZ in October 2023. During the meeting, PeDRA's Associate Director of Educational Programs interviewed three amazing presenters to discuss the incredible work being done in this space. First up is Lynn Petukhova, PhD, discussing her ground-breaking work in Hidradenitis Suppurativa (HS) genetics and how she harnesses the power of genome-wide association studies (GWAS). Following this, you'll gain insight into more HS research through two poster interviews with MD candidates Nicholas Chiang and Sydney Dong, respectively. For more information on Dr. Petukhova's work, or to submit a case study, please visit the Columbia University Data Science Institute. SHSA is an annual meeting organized by the Hidradenitis Suppurativa Foundation (HSF) to bring experts from around the world to share their experiences with HS.
Welcome to the Olink® Proteomics in Proximity podcast! Below are some useful resources from this episode: Published study of primary focusÁlvez MB, Edfors F, von Feilitzen K, Zwahlen M, Mardinoglu A, Edqvist PH, Sjöblom T, Lundin E, Rameika N, Enblad G, Lindman H, Höglund M, Hesselager G, Stålberg K, Enblad M, Simonson OE, Häggman M, Axelsson T, Åberg M, Nordlund J, Zhong W, Karlsson M, Gyllensten U, Ponten F, Fagerberg L, Uhlén M. Next generation pan-cancer blood proteome profiling using proximity extension assay. Nat Commun. 2023 Jul 18;14(1):4308. doi: 10.1038/s41467-023-39765-y. PMID: 37463882; PMCID: PMC10354027. https://pubmed.ncbi.nlm.nih.gov/37463882/ Laboratory, first author, and corresponding author of the study· SciLifeLab, a collaborative resource for life scientists located in Sweden: https://www.scilifelab.se/· María Bueno Álvez (first author), PhD student, Science for Life Laboratory (SciLifeLab): https://www.linkedin.com/in/mar%C3%ADa-bueno-%C3%A1lvez-33395b192/ · Dr. Mathias Uhlén (corresponding author), Professor of Microbiology, Royal Institute of Technology (KTH), Leader of the Human Protein Atlas, Founding director of the Science for Life Laboratory (SciLifeLab): https://www.kth.se/pro/sysbio/uhlen-group/researchers/mathias-uhlen-1.67763 Olink tools and software· Olink® Explore 1536, the platform that measured proteins in this study with a next-generation sequencing (NGS) readout: https://olink.com/products-services/explore/· Olink® Explore HT, Olink's newest solution for high-throughput biomarker discovery that measures 5300+ proteins simultaneously with minimal sample consumption: https://olink.com/products-services/exploreht/ · Olink® Insight, an open-access resource to accelerate protein biomarker discovery: https://insight.olink.com/ UK Biobank Pharma Proteomics Project (UKB-PPP), one of the world's largest scientific studies of blood protein biomarkers conducted to date· Published article: Styrkarsdottir U, Lund SH, Thorleifsson G, Saevarsdottir S, Gudbjartsson DF, Thorsteinsdottir U, Stefansson K. Cartilage Acidic Protein 1 in Plasma Associates With Prevalent Osteoarthritis and Predicts Future Risk as Well as Progression to Joint Replacements: Results From the UK Biobank Resource. Arthritis Rheumatol. 2023 Apr;75(4):544-552. doi: 10.1002/art.42376. Epub 2022 Dec 28. PMID: 36239377. https://pubmed.ncbi.nlm.nih.gov/36239377/ · UKB-PPP website: https://www.ukbiobank.ac.uk/learn-more-about-uk-biobank/news/uk-biobank-launches-one-of-the-largest-scientific-studies Analysis of UK Biobank proteomics data from cancer patients, with co-authors including Ruth C. Travis, Karl Smith-Byrne, and Joshua R. AtkinsPreprint article: Papier K, Atkins JR, Tong TYN, Gaitskell K, Desai T, Ogamba CF, Parsaeian M, Reeves GK, Mills IG, Key TJ, Smith-Byrne K, Travis RC. Identifying proteomic risk factors for cancer using prospective and exome analyses: 1,463 circulating proteins and risk of 19 cancers in the UK Biobank. medRxiv 2023.07.28.23293330; doi: https://doi.org/10.1101/2023.07.28.23293330. https://www.medrxiv.org/content/10.1101/2023.07.28.23293330v1 U-CAN Biobank, a prospective biobank of cancer patient biomaterial in SwedenGlimelius B, Melin B, Enblad G, Alafuzoff I, Beskow A, Ahlström H, Bill-Axelson A, Birgisson H, Björ O, Edqvist PH, Hansson T, Helleday T, Hellman P, Henriksson K, Hesselager G, Hultdin M, Häggman M, Höglund M, Jonsson H, Larsson C, Lindman H, Ljuslinder I, Mindus S, Nygren P, Pontén F, Riklund K, Rosenquist R, Sandin F, Schwenk JM, Stenling R, Stålberg K, Stålberg P, Sundström C, Thellenberg Karlsson C, Westermark B, Bergh A, Claesson-Welsh L, Palmqvist R, Sjöblom T. U-CAN: a prospective longitudinal collection of biomaterials and clinical information from adult cancer patients in Sweden. Acta Oncol. 2018 Feb;57(2):187-194. doi: 10.1080/0284186X.2017.1337926. Epub 2017 Jun 20. PMID: 28631533. https://pubmed.ncbi.nlm.nih.gov/28631533/ Galleri GRAIL test, a blood-based test that detects a biosignature shared by over 50 cancer types: https://grail.com/galleri-test/ Genotype-Tissue Expression (GTEx) project, a biobank and open-access database to study tissue-specific gene expression and regulation: https://www.gtexportal.org/home/ Human Protein Atlas (HPA), a Swedish-based program with the aim to map all human proteins using an integration of various omics technologies and provide these data freely available to the scientific community: https://www.proteinatlas.org/ Would you like to subscribe to the podcast on your favorite player or app? You can do so here: Apple Podcasts: https://apple.co/3T0YbSm Spotify Podcasts: https://open.spotify.com/show/2sZ2wxO... Google Podcasts: https://podcasts.google.com/feed/aHR0... Amazon Music: https://music.amazon.com/podcasts/d97... Podcast Addict: https://podcastaddict.com/podcast/409... Deezer: https://www.deezer.com/show/5178787 Player FM: https://player.fm/series/series-3396598 In case you were wondering, Proteomics in Proximity refers to the principle underlying Olink Proteomics assay technology called the Proximity Extension Assay (PEA), and more information about the assay and how it works can be found here: https://bit.ly/3Rt7YiY For any questions regarding information Olink Proteomics, please email us at info@olink.com or visit our website: https://www.olink.com/ WHAT IS PROTEOMICS IN PROXIMITY?Proteomics in Proximity discusses the intersection of proteomics with genomics for drug target discovery, the application of proteomics to reveal disease biomarkers, and current trends in using proteomics to unlock biological mechanisms. Co-hosted by Olink's Dale Yuzuki, Cindy Lawley and Sarantis Chlamydas.
The more information you know about your genetics the better, right? This is the idea behind companies like 23andMe, which offer platforms to understand your potential genetic predisposition toward a specific disease. The concept thrives on massive collection of public genetic data, coupled to extensive questionnaires that en masse, generate statistical associations between different genetic variants and various disorders, diseases, behaviors or drug sensitivities. These powerful tools are shaping our understanding of genes and genetic variants that contribute to our physiology, metabolism and psychology, and even aiding in drug discovery. Dr. Joyce Tung, Vice President of Research at 23andMe describes the technology, the evolution of the business, racial disparities, and what the future looks like for public genetic services.
In this episode, Xavier Bonilla has a dialogue with Diana Fleischman about a wide range of topics including polyamory and eugenics. They talk about how evolutionary psychology is a good framework for understanding relationships, patriarchal and matriarchal societies, history of monogamous and polyamorous relationships and jealousy and polyamory. They also talk about the difficult history of eugenics, decoupling bad from the good, polygenic scores, governmental differences with prenatal care, GWAS, and many more topics. Diana Fleischman is an evolutionary psychologist and Associate Research professor at the University of New Mexico. Her research has focused on evolutionary psychology, disgust research, sex differences, animal rights, and eugenics. Website: https://www.dianafleischman.com/Substack: Twitter: @sentientistYou might also like: This is a public episode. If you would like to discuss this with other subscribers or get access to bonus episodes, visit convergingdialogues.substack.com
Related to this podcast's interests in data sharing, this week Jess and Sara talk about common data elements initiatives. These are movements that are hoping to get all of the researchers in the same field or subfield to agree to a given set of assessments, measures, procedures, and/or reporting metrics (Think: Everyone who measures mother's education would ask the same stem question with the same eight category responses, which would be coded and reported in the same way). We'll talk about different types of initiatives, the reasons why proponents think it's a great idea, and what major concerns might come up. Sara also gives us a mini lecture introducing genome-wide association studies. Trust us, it's related! In this episode, we talk about: The NIH Common Data Elements Program: https://heal.nih.gov/data/common-data-elements NIH Common Measures website: https://www.phenxtoolkit.org/ A paper about the NIMH common data elements: Barch, D. M., Gotlib, I. H., Bilder, R. M., Pine, D. S., Smoller, J. W., Brown, C. H., ... & Farber, G. K. (2016). Common measures for National Institute of Mental Health funded research. Biological Psychiatry, 79(12), e91-e96. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4968690/ What's the difference between common measures and common metrics: de Beurs, E., Boehnke, J. R., & Fried, E. I. (2022). Common measures or common metrics? A plea to harmonize measurement results. Clinical Psychology & Psychotherapy, 29(5), 1755-1767. Paper describing the openly available Project KIDS data: Van Dijk, W., Norris, C. U., Al Otaiba, S., Schatschneider, C., & Hart, S. A. (2022). Exploring individual differences in response to reading intervention: Data from Project KIDS (Kids and Individual Differences in Schools). Journal of Open Psychology Data, 10(1). Educational attainment GWAS paper data harmonization appendix: https://static-content.springer.com/esm/art%3A10.1038%2Fs41588-022-01016-z/MediaObjects/41588_2022_1016_MOESM1_ESM.pdf Connect with the podcast on twitter @within_between, or email us letters about developmental science at withinandbetweenpod@gmail.com. More episodes and podcast information at WithinandBetweenPod.com. Follow Dr. Hart on twitter @Saraannhart Follow Dr. Logan on twitter @Jarlogan. Our theme music was composed by Jason Flowers. Our logo was created by Nathan Archer. Recorded July 9, 2023.
View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter's Weekly Newsletter Benoît Arsenault is a research scientist focused on understanding how lifestyle and genetic factors contribute to cardiovascular disease risk. In this episode, the discussion casts a spotlight on Lp(a)—the single most important genetically-inherited trait when it comes to atherosclerotic cardiovascular disease (ASCVD) risk. Benoît explains the biology of Lp(a), how it's inherited, the importance of measuring Lp(a) levels, and the diseases most associated with high Lp(a). He dives into data on the possible treatments for lowering Lp(a) such niacin, statins, and PCSK9 inhibitors, as well as the most exciting new potential therapeutic—antisense oligonucleotides. We discuss: How Benoît came to study Lp(a)—a new marker for cardiovascular risk [3:15]; The relationship between Lp(a) and CVD risk [6:45]; What genome-wide association studies (GWAS) revealed about Lp(a) [16:00]; Clinical tests to measure Lp(a) [22:00]; The biology of Lp(a) [25:45]; How statins lower LDL-cholesterol and why this doesn't work for an Lp(a) [29:15]; The structure of LDL-p and Lp(a) and what makes Lp(a) more atherogenic than an equivalent LDL particle [34:00]; The role of Lp(a) in aortic valve disease [42:45]; How greater numbers of Lp(a) particles are associated with increased risk of disease [48:00]; The genetics and inheritance of Lp(a) and how and when to measure Lp(a) levels [52:00]; Niacin and other proposed therapies to lower Lp(a), apoB, and CVD risk [1:00:45]; Why awareness of Lp(a) among physicians remains low despite the importance of managing risk factors for ASCVD [1:14:00]; The variability of disease in patients with high Lp(a) [1:19:00]; Diseases most associated with high Lp(a) [1:26:30]; The biology of PCSK9 protein, familial hypercholesterolemia, and the case for inhibiting PCSK9 [1:35:00]; The variability in PCSK9 inhibitors' ability to lower Lp(a) and why we need more research on individuals with high levels of Lp(a) [1:50:30]; Peter's approach to managing patients with high Lp(a), and Benoît's personal approach to managing his risk [1:54:45]; Antisense oligonucleotides—a potential new therapeutic for Lp(a) [1:57:15]; and More. Connect With Peter on Twitter, Instagram, Facebook and YouTube
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