Podcasts about Nature Genetics

O SciCast mergulhou no universo fascinante dessas espécies que encantam pessoas ao redor do mundo. No entanto, por trás dessa beleza, há um custo ecossocial significativo. A exploração desenfreada, a falta de reprodução em cativeiro e o impacto na biodiversidade são temas urgentes que precisam ser discutidos. Conversamos como a aquariofilia afeta os ecossistemas de água doce e salgada, além de explorar as condições de trabalho das comunidades envolvidas na coleta desses peixes. Além disso, discutimos o papel dos governos e o que pode ser feito para tornar essa indústria mais sustentável. Patronato do SciCast: 1. Patreon SciCast 2. Apoia.se/Scicast 3. Nos ajude via Pix também, chave: contato@scicast.com.br ou acesse o QRcode: Sua pequena contribuição ajuda o Portal Deviante a continuar divulgando Ciência! Contatos: contato@scicast.com.br https://twitter.com/scicastpodcast https://www.facebook.com/scicastpodcast https://instagram.com/scicastpodcast Fale conosco! E não esqueça de deixar o seu comentário na postagem desse episódio! Expediente: Produção Geral: Tarik Fernandes e André Trapani Equipe de Gravação: Tarik Fernandes, Bruno Saito, Caio Ferreira, Rita Kujawski, Marcelo Pedraz Citação ABNT: Scicast #643: Peixes Ornamentais e Aquarismo. Locução: Tarik Fernandes, Bruno Saito, Caio Ferreira, Rita Kujawski, Marcelo Pedraz. [S.l.] Portal Deviante, 10/05/2025. Podcast. Disponível em: https://www.deviante.com.br/podcasts/scicast-643 Imagem de capa: Referências e Indicações Agostinho, A. A. (2010). Fisheries management in the Upper Paraná River. Aquatic Veterinary Society. (2021). Aquatic animal health: Challenges and solutions. Balon, E. K. (1975). Reproductive guilds of fishes. Chapman, L. J., Chapman, C. A., & Kaufman, L. (2006). Hypoxia tolerance in African fishes. Journal of Fish Biology, 68(1), 1-22. Environmental Science & Technology. (2020). Ecotoxicology of heavy metals in freshwater ecosystems. Environmental Science & Technology, 54(12), 12345-12356. IBAMA. (2022). Relatório de monitoramento de fauna silvestre. Instituto Brasileiro do Meio Ambiente e dos Recursos Naturais Renováveis. IUCN. (2023). Red List of Threatened Species. International Union for Conservation of Nature. https://www.iucnredlist.org Marine Ecology Progress Series. (2019). Cyanide fishing and its impacts on coral reefs. Marine Ecology Progress Series, 621, 1-15. Marine Policy. (2020). Cyanide fishing in the Indo-Pacific: Impacts and solutions. Marine Policy, 118, 103987. Nature Genetics. (2018). The zebrafish genome project. Nature Genetics, 50(3), 345-356. Projeto Piaba. (2023). Dados de manejo comunitário no Rio Negro. https://www.projetopiaba.org Revista FAPESP. (2021). O mercado de peixes ornamentais no Brasil. Revista FAPESP, 300, 45-50. Statista. (2023). Global ornamental fish market size. https://www.statista.com Transparência Brasil. (2023). Ligações entre parlamentares e exportadores de peixes ornamentais. https://www.transparencia.org.br University of Florida. (2021). Mortality rates in ornamental fish trade. Journal of Aquatic Animal Health, 33(2), 123-134. WWF. (2021). Ornamental fisheries and sustainable practices. World Wildlife Fund. https://www.worldwildlife.org Zootaxa. (2021). Taxonomic challenges in ornamental killifishes. Zootaxa, 5000(1), 1-20. Sugestões de filmes: Wild Caught: Aquarium Fish Trade of Amazon A saga do Piabeiro The Dark Hobby Into the Amazon - Discovering Wild Fish The End of The Line See omnystudio.com/listener for privacy information.

The Ag Net News Hour's Lorre Boyer and Nick Papagni, “The AgMeter” started out the show by discussing the significant impact of tariffs on agriculture, particularly the 10% blanket tariffs and the 90-day delay on reciprocal tariffs for countries willing to negotiate. China's tariffs have risen to 125% on US imports. The US exports were valued at $176 billion last year, supporting over 1 million jobs. The trade deficit has increased to nearly $50 billion from $0 in four years. Secretary of Agriculture Brooke Rollins emphasized the need for fair trade deals and highlighted the President's efforts to ensure farmers are treated fairly in international negotiations. The discussion on Ag Net News Hour focused on Brooke Rollins' speech on trade, highlighting the high tariffs on US products, such as a 700% tariff on rice. They reviewed the Trump administration's efforts to support farmers and criticized other countries' tariffs. They also discussed the Food Security and Farm Protection Act, which aims to combat California's Proposition 12, a law setting minimum space requirements for animal raising. The bill, introduced by Senator Joni Ernst (R-IA), aims to prevent states from interfering with interstate commerce. Additionally, research on bird flu led by California scientists was mentioned, emphasizing its impact on the state's dairy industry. The University of California Davis, in collaboration with international researchers, has created the first detailed map of gene regulation in chickens, which could help breed birds resistant to diseases like avian influenza. The study, published in Nature Genetics, analyzed over 100 chicken breeds and 28 tissues. This research is crucial amidst the ongoing bird flu outbreak, which has affected over a million birds and spread to dairy cows, particularly in California. The conversation also touched on the importance of supporting local agriculture, the upcoming citrus event in Florida, and the seasonal shifts in agricultural production, emphasizing the need to promote local growers and the resilience of the agricultural sector.

Pulmonary Fibrosis. A debilitating disease that restricts a person's lung capacity, controllable with drug therapies, but it's only “cure” is a double lung transplant. Researchers at TGen have released the results of a study that investigated the disease on a cellular level. Using advanced spatial transcriptomics, they identified hidden disease markers in seemingly healthy lung tissue—offering hope for earlier, more personalized treatments. Targeting these early disruptions could improve lung function and outcomes. With current PF treatments only slowing decline, this discovery, published in Nature Genetics, marks a step toward preventing irreversible damage. In this episode of TGen Talks, Nicholas Banovich, Ph.D., discusses the Nature Genetics finding and the new spatial map of gene expression in lung cells. Instead of blending tissue together and analyzing it, scientists can now examine individual cells and pinpoint where molecular changes happen. We'll break down what this means, how it's done, and why it could change the way we study lung disease.

durée : 00:05:27 - Avec sciences - par : Alexandre Morales - Une équipe Toulousaine a montré qu'un champignon aurait transmis une part de son patrimoine génétique à un ancêtre commun à toutes les plantes terrestres. Leurs résultats sont à retrouver dans Nature Genetics.

* List of Discoveries Squeezing Evolution: Did you know that dinosaurs ate rice before rice evolved? That turtle shells existed forty million years before turtle shells began evolving? That insects evolved tongues for eating from flowers 70 million years before flowers evolved? And that birds appeared before birds evolved? The fossil record is a wonderful thing. And more recently, only a 40,000-year squeeze, Neanderthal had blood types A, B, and O, shocking evolutionists but expected to us here at Real Science Radio! Sit back and get ready to enjoy another instant classic, today's RSR "list show" on Evolution's Big Squeeze! Our other popular list shows include: - scientists doubting Darwin - evidence against whale evolution - problems with 'the river carved the canyon' - carbon 14 everywhere it shouldn't be - dinosaur still-soft biological tissue - solar system formation problems - evidence against the big bang - evidence for the global flood - genomes that just don't fit - and our list of not so old things! (See also rsr.org/sq2 and rsr.org/sq3!) * Evolution's Big Squeeze: Many discoveries squeeze the Darwinian theory's timeframe and of course without a workable timeframe there is no workable theory. Examples, with their alleged (and falsified) old-earth timeframes, include: - Complex skeletons existed 9 million years before they were thought to have evolved, before even the "Cambrian explosion".- Butterflies existed 10 million years before they were thought to have evolved. - Parrots existed "much earlier than had been thought", in fact, 25 million years before they were thought to have evolved. - Cephalopod fossils (squids, cuttlefish, etc.) appear 35 million years before they were able to propagate. - Turtle shells 40 million years before turtle shells began evolving - Trees began evolving 45 million years before they were thought to evolve - Spores appearing 50 million years before the plants that made them (not unlike footprints systematically appearing "millions of years before" the creatures that made them, as affirmed by Dr. Marcus Ross, associate professor of geology). - Sponges existed 60 million years before they were believed to have evolved. - Dinosaurs ate rice before it evolved Example - Insect proboscis (tongue) in moths and butterflies 70 million years before previously believed has them evolving before flowers. - Arthropod brains fully developed with central nervous system running to eyes and appendages just like modern arthropods 90 million years earlier than previously known (prior to 2021, now, allegedly 310mya) - 100 million years ago and already a bird - Fossil pollen pushes back plant evolution 100 million years. - Mammalian hair allegedly 100-million-years-old show that, "the morphology of hair cuticula may have remained unchanged throughout most of mammalian evolution", regarding the overlapping cells that lock the hair shaft into its follicle. - Piranha-like flesh-eating teeth (and bitten prey) found pushing back such fish 125 million years earlier than previously claimed   - Shocking organic molecules in "200 million-years-old leaves" from ginkgoes and conifers show unexpected stasis. - Plant genetic sophistication pushed back 200 million years. - Jellyfish fossils (Medusoid Problematica :) 200 million years earlier than expected; here from 500My ago. - Green seaweed 200 million years earlier than expected, pushed back now to a billion years ago!  - The acanthodii fish had color vision 300 million years ago, but then, and wait, Cheiracanthus fish allegedly 388 million years ago already had color vision. - Color vision (for which there is no Darwinian evolutionary small-step to be had, from monochromatic), existed "300 million years ago" in fish, and these allegedly "120-million-year-old" bird's rod and cone fossils stun researchers :) - 400-million-year-old Murrindalaspis placoderm fish "eye muscle attachment, the eyestalk attachment and openings for the optic nerve, and arteries and veins supplying the eyeball" The paper's author writes, "Of course, we would not expect the preservation of ancient structures made entirely of soft tissues (e.g. rods and cone cells in the retina...)." So, check this next item... :) - And... no vertebrates in the Cambrian? Well, from the journal Nature in 2014, a "Lower-Middle Cambrian... primitive fish displays unambiguous vertebrate features: a notochord, a pair of prominent camera-type eyes, paired nasal sacs, possible cranium and arcualia, W-shaped myomeres, and a post-anal tail" Primitive? - Fast-growing juvenile bone tissue, thought to appear in the Cretaceous, has been pushed back 100 million years: "This pushes the origin of fibrolamellar bone in Sauropterygia back from the Cretaceous to the early Middle Triassic..."- Trilobites "advanced" (not the predicted primitive) digestion "525 million" years ago - And there's this, a "530 million year old" fish, "50 million years before the current estimate of when fish evolved" - Mycobacterium tuberculosis 100,000 yr-old MRCA (most recent common ancestor) now 245 million- Fungus long claimed to originate 500M years ago, now found at allegedly 950 Mya (and still biological "the distant past... may have been much more 'modern' than we thought." :) - A rock contained pollen a billion years before plants evolved, according to a 2007 paper describing "remarkably preserved" fossil spores in the French Alps that had undergone high-grade metamorphism - 2.5 billion year old cyanobacteria fossils (made of organic material found in a stromatolite) appear about "200 million years before the [supposed] Great Oxidation Event". - 2.7 billion year old eukaryotes (cells with a nucleus) existed (allegedly) 1 billion years before expected - 3.5 billion year "cell division evidently identical to that of living filamentous prokaryotes." - And even older cyanobacteria! At 220 million years earlier than thought, per Nature's 3.7 billion year old dating of stromatolites! - The universe and life itself (in 2019 with the universe dated a billion, now, no, wait, two billion!, years younger than previously thought, that's not only squeezing biological but also astronomical evolution, with the overall story getting really tight) - Mantis shrimp, with its rudimentary color but advanced UV vision, is allegedly ancient. - Hadrosaur teeth, all 1400 of them, were "more complex than those of cows, horses, and other well-known modern grazers." Professor stunned by the find! (RSR predicts that, by 2030 just to put an end date on it, more fossils will be found from the geologic column that will be more "advanced" as compared to living organisms, just like this hadrosaur and like the allegedly 100M year old hagfish  fossil having more slime glands than living specimens.)  - Trace fossils "exquisitely preserved" of mobile organisms (motility) dated at 2.1 billion years ago, a full 1.5 billion earlier than previously believed - Various multicellular organisms allegedly 2.1 billion years old, show multicellularity 1.5 billion years sooner than long believed   - Pre-sauropod 26,000-pound dinosaur "shows us that even as far back as 200 million years ago, these animals had already become the largest vertebrates to ever walk the Earth." - The Evo-devo squeeze, i.e., evolutionary developmental biology, as with rsr.org/evo-devo-undermining-darwinism. - Extinct Siberian one-horned rhinos coexisted with mankind. - Whale "evolution" is being crushed in the industry-wide "big squeeze". First, geneticist claims whales evolved from hippos but paleontologists say hippos evolved tens of millions of years too late! And what's worse than that is that fossil finds continue to compress the time available for whale evolution. To not violate its own plot, the Darwinist story doesn't start animals evolving back into the sea until the cast includes land animals suitable to undertake the legendary journey. The recent excavation of whale fossils on an island of the Antarctic Peninsula further compresses the already absurdly fast 10 million years to allegedly evolve from the land back to the sea, down to as little as one million years. BioOne in 2016 reported a fossil that is "among the oldest occurrences of basilosaurids worldwide, indicating a rapid radiation and dispersal of this group since at least the early middle Eocene." By this assessment, various techniques produced various published dates. (See the evidence that falsifies the canonical whale evolution story at rsr.org/whales.) * Ancient Hierarchical Insect Society: "Thanks to some well-preserved remains, researchers now believe arthropod social structures have been around longer than anyone ever imagined. The encased specimens of ants and termites recently studied date back [allegedly] 100 million years." Also from the video about "the bubonic plague", the "disease is well known as a Middle Ages mass killer... Traces of very similar bacteria were found on [an allegedly] 20-million-year-old flea trapped in amber." And regarding "Caribbean lizards... Even though they are [allegedly] 20 million years old, the reptiles inside the golden stones were not found to differ from their contemporary counterparts in any significant way. Scientists attribute the rarity [Ha! A rarity or the rule? Check out rsr.org/stasis.] to stable ecological surroundings." * Squeezing and Rewriting Human History: Some squeezing simply makes aspects of the Darwinian story harder to maintain while other squeezing contradicts fundamental claims. So consider the following discoveries, most of which came from about a 12-month period beginning in 2017 which squeeze (and some even falsify) the Out-of-Africa model: - find two teeth and rewrite human history with allegedly 9.7 million-year-old teeth found in northern Europe (and they're like Lucy, but "three times older") - date blue eyes, when humans first sported them, to as recently as 6,000 years ago   - get mummy DNA and rewrite human history with a thousand years of ancient Egyptian mummy DNA contradicting Out-of-Africa and demonstrating Out-of-Babel - find a few footprints and rewrite human history with allegedly 5.7 million-year-old human footprints in Crete - re-date an old skull and rewrite human history with a very human skull dated at 325,000 years old and redated in the Journal of Physical Anthropology at about 260,000 years old and described in the UK's Independent, "A skull found in China [40 years ago] could re-write our entire understanding of human evolution." - date the oldest language in India, Dravidian, with 80 derivatives spoken by 214 million people, which appeared on the subcontinent only about 4,500 years ago, which means that there is no evidence for human language for nearly 99% of the time that humans were living in Asia. (Ha! See rsr.org/origin-of-language for the correct explanation.) - sequence a baby's genome and rewrite human history with a 6-week old girl buried in Alaska allegedly 11,500 years ago challenging the established history of the New World. (The family buried this baby girl just beneath their home like the practice in ancient Mesopotamia, the Hebrews who sojourned in Egypt, and in Çatalhöyük in southern Turkey, one of the world's most ancient settlements.) - or was that 130,000? years ago as the journal Nature rewrites human history with a wild date for New World site - and find a jawbone and rewrite human history with a modern looking yet allegedly 180,000-year-old jawbone from Israel which "may rewrite the early migration story of our species" by about 100,000 years, per the journal Science - re-date a primate and lose yet another "missing link" between "Lucy" and humans, as Homo naledi sheds a couple million years off its age and drops from supposedly two million years old to (still allegedly) about 250,000 years old, far too "young" to be the allegedly missing link - re-analysis of the "best candidate" for the most recent ancestor to human beings, Australopithecus sediba, turns out to be a juvenile Lucy-like ape, as Science magazine reports work presented at the American Association of Physical Anthropologists 2017 annual meeting - find skulls in Morocco and "rewrite human history" admits the journal Nature, falsifying also the "East Africa" part of the canonical story - and from the You Can't Make This Stuff Up file, NPR reports in April 2019, Ancient Bones And Teeth Found In A Philippine Cave May Rewrite Human History. :) - Meanwhile, whereas every new discovery requires the materialists to rewrite human history, no one has had to rewrite Genesis, not even once. Yet, "We're not claiming that the Bible is a science textbook. Not at all. For the textbooks have to be rewritten all the time!"  - And even this from Science: "humans mastered the art of training and controlling dogs thousands of years earlier than previously thought."- RSR's Enyart commented on the Smithsonian's 2019 article on ancient DNA possibly deconstructing old myths...  This Smithsonian article about an ancient DNA paper in Science Advances, or actually, about the misuse of such papers, was itself a misuse. The published research, Ancient DNA sheds light on the genetic origins of early Iron Age Philistines, confirmed Amos 9:7 by documenting the European origin of the biblical Philistines who came from the island of Caphtor/Crete. The mainstream media completely obscured this astounding aspect of the study but the Smithsonian actually stood the paper on its head. [See also rsr.org/archaeology.]* Also Squeezing Darwin's Theory: - Evolution happens so slowly that we can't see it, yet - it happens so fast that millions of mutations get fixed in a blink of geologic time AND: - Observing a million species annually should show us a million years of evolution, but it doesn't, yet - evolution happens so fast that the billions of "intermediary" fossils are missing AND: - Waiting for helpful random mutations to show up explains the slowness of evolution, yet - adaption to changing environments is often immediate, as with Darwin's finches Finches Adapt in 17 Years, Not 2.3 Million: Charles Darwin's finches are claimed to have taken 2,300,000 years to diversify from an initial species blown onto the Galapagos Islands. Yet individuals from a single finch species on a U.S. Bird Reservation in the Pacific were introduced to a group of small islands 300 miles away and in at most 17 years, like Darwin's finches, they had diversified their beaks, related muscles, and behavior to fill various ecological niches. So Darwin's finches could diversify in just 17 years, and after 2.3 million more years, what had they evolved into? Finches! Hear this also at rsr.org/lee-spetner and see Jean Lightner's review of the Grants' 40 Years. AND: - Fossils of modern organisms are found "earlier" and "earlier" in the geologic column, and - the "oldest" organisms are increasingly found to have anatomical, proteinaceous, prokaryotic, and eukaryotic sophistication and similarity to "modern" organisms AND: - Small populations are in danger of extinction (yet they're needed to fix mutations), whereas - large populations make it impossible for a mutation to become standard AND: - Mutations that express changes too late in an organism's development can't effect its fundamental body plan, and - mutations expressed too early in an organism's development are fatal (hence among the Enyart sayings, "Like evolving a vital organ, most major hurdles for evolutionary theory are extinction-level events.") AND: - To evolve flight, you'd get bad legs - long before you'd get good wings AND: - Most major evolutionary hurdles appear to be extinction-level events- yet somehow even *vital* organs evolve (for many species, that includes reproductive organs, skin, brain, heart, circulatory system, kidney, liver, pancreas, stomach, small intestines, large intestines, lungs -- which are only a part of the complex respiration system) AND: - Natural selection of randomly taller, swifter, etc., fish, mammals, etc. explains evolution yet - development of microscopic molecular machines, feedback mechanisms, etc., which power biology would be oblivous to what's happening in Darwin's macro environment of the entire organism AND: - Neo-Darwinism suggests genetic mutation as the engine of evolution yet - the there is not even a hypothesis for modifying the vast non-genetic information in every living cell including the sugar code, electrical code, the spatial (geometric) code, and the epigenetic code AND: - Constant appeals to "convergent" evolution (repeatedly arising vision, echolocation, warm-bloodedness, etc.) - undermine most Darwinian anatomical classification especially those based on trivialities like odd or even-toed ungulates, etc. AND: - Claims that given a single species arising by abiogenesis, then - Darwinism can explain the diversification of life, ignores the science of ecology and the (often redundant) biological services that species rely upon AND: - humans' vastly superior intelligence indicates, as bragged about for decades by Darwinists, that ape hominids should have the greatest animal intelligence, except that - many so-called "primitive" creatures and those far distant on Darwin's tee of life, exhibit extraordinary rsr.org/animal-intelligence even to processing stimuli that some groups of apes cannot AND: - Claims that the tree of life emerges from a single (or a few) common ancestors - conflict with the discoveries of multiple genetic codes and of thousands of orphan genes that have no similarity (homology) to any other known genes AND (as in the New Scientist cover story, "Darwin Was Wrong about the tree of life", etc.): - DNA sequences have contradicted anatomy-based ancestry claims - Fossil-based ancestry claims have been contradicted by RNA claims - DNA-based ancestry claims have been contradicted by anatomy claims - Protein-based ancestry claims have been contradicted by fossil claims. - And the reverse problem compared to a squeeze. Like finding the largest mall in America built to house just a kid's lemonade stand, see rsr.org/200 for the astounding lack of genetic diversity in humans, plants, and animals, so much so that it could all be accounted for in just about 200 generations! - The multiplied things that evolved multiple times - Etc. * List of Ways Darwinists Invent their Tree of Life, aka Pop Goes the Weasle – Head and Shoulders, Knees and Toes: Evolutionists change their selection of what evidence they use to show 'lineage', from DNA to fossils to genes to body plans to teeth to many specific anatomical features to proteins to behavior to developmental similarities to habitat to RNA, etc. and to a combination of such. Darwinism is an entire endeavor based on selection bias, a kind of logical fallacy. By anti-science they arbitrarily select evidence that best matches whichever evolutionary story is currently preferred." -Bob E. The methodology used to create the family tree edifice to show evolutionary relationships classifies the descent of organisms based on such attributes as odd-toed and even-toed ungulates. Really? If something as wildly sophisticated as vision allegedly evolved multiple times (a dozen or more), then for cryin' out loud, why couldn't something as relatively simple as odd or even toes repeatedly evolve? How about dinosaur's evolving eggs with hard shells? Turns out that "hard-shelled eggs evolved at least three times independently in dinosaurs" (Nature, 2020). However, whether a genus has an odd or even number of toes, and similar distinctions, form the basis for the 150-year-old Darwinist methodology. Yet its leading proponents still haven't acknowledged that their tree building is arbitrary and invalid. Darwin's tree recently fell anyway, and regardless, it has been known to be even theoretically invalid all these many decades. Consider also bipedalism? In their false paradigm, couldn't that evolve twice? How about vertebrate and non-vertebrates, for that matter, evolving multiple times? Etc., etc., etc. Darwinists determine evolutionary family-tree taxonomic relationships based on numbers of toes, when desired, or on hips (distinguishing, for example, dinosaur orders, until they didn't) or limb bones, or feathers, or genes, or fossil sequence, or neck bone, or..., or..., or... Etc. So the platypus, for example, can be described as evolving from pretty much whatever story would be in vogue at the moment...   * "Ancient" Protein as Advanced as Modern Protein: A book review in the journal Science states, "the major conclusion is reached that 'analyses made of the oldest fossils thus far studied do not suggest that their [allegedly 145-million year-old] proteins were chemically any simpler than those now being produced.'" 1972, Biochemistry of Animal Fossils, p. 125 * "Ancient" Lampreys Just Modern Lampreys with Decomposed Brain and Mouth Parts: Ha! Researches spent half-a-year documenting how fish decay. RSR is so glad they did! One of the lessons learned? "[C]ertain parts of the brain and the mouth that distinguish the animals from earlier relatives begin a rapid decay within 24 hours..." :) * 140-million Year Old Spider Web: The BBC and National Geographic report on a 140-million year old spider web in amber which, as young-earth creationists expect, shows threads that resemble silk spun by modern spiders. Evolutionary scientists on the otherhand express surprise "that spider webs have stayed the same for 140 million years." And see the BBC. * Highly-Credentialed Though Non-Paleontologist on Flowers: Dr. Harry Levin who spent the last 15 years of a brilliant career researching paleontology presents much evidence that flowering plants had to originate not 150 million years ago but more than 300 million years ago. (To convert that to an actual historical timeframe, the evidence indicates flowers must have existed prior to the time that the strata, which is popularly dated to 300 mya, actually formed.) * Rampant Convergence: Ubiquitous appeals to "convergent" evolution (vision, echolocation, warm-bloodedness, icthyosaur/dolphin anatomy, etc.), all allegedly evolving multiple times, undermines anatomical classification based on trivialities like odd or even-toed ungulates, etc. * Astronomy's Big Evolution Squeeze: - Universe a billion, wait, two billion, years younger than thought   (so now it has to evolve even more impossibly rapidly) - Sun's evolution squeezes biological evolution - Galaxies evolving too quickly - Dust evolving too quickly - Black holes evolving too quickly - Clusters of galaxies evolving too quickly. * The Sun's Evolution Squeezes Life's Evolution: The earlier evolutionists claim that life began on Earth, the more trouble they have with astrophysicists. Why? They claim that a few billion years ago the Sun would have been far more unstable and cooler. The journal Nature reports that the Faint young Sun paradox remains for the "Sun was fainter when the Earth was young, but the climate was generally at least as warm as today". Further, our star would shoot out radioactive waves many of which being violent enough to blow out Earth's atmosphere into space, leaving Earth dead and dry like Mars without an atmosphere. And ignoring the fact that powerful computer simulators cannot validate the nebula theory of star formation, if the Sun had formed from a condensing gas cloud, a billion years later it still would have been emitting far less energy, even 30% less, than it does today. Forget about the claimed one-degree increase in the planet's temperature from man-made global warming, back when Darwinists imagine life arose, by this just-so story of life spontaneously generating in a warm pond somewhere (which itself is impossible), the Earth would have been an ice ball, with an average temperature of four degrees Fahrenheit below freezing! See also CMI's video download The Young Sun. * Zircons Freeze in Molten Eon Squeezing Earth's Evolution? Zircons "dated" 4 to 4.4 billion years old would have had to freeze (form) when the Earth allegedly was in its Hadean (Hades) Eon and still molten. Geophysicist Frank Stacey (Cambridge fellow, etc.) has suggested they may have formed above ocean trenches where it would be coolest. One problem is that even further squeezes the theory of plate tectonics requiring it to operate two billion years before otherwise claimed. A second problem (for these zircons and the plate tectonics theory itself) is that ancient trenches (now filled with sediments; others raised up above sea level; etc.) have never been found. A third problem is that these zircons contain low isotope ratios of carbon-13 to carbon-12 which evolutionists may try to explain as evidence for life existing even a half-billion years before they otherwise claim. For more about this (and to understand how these zircons actually did form) just click and then search (ctrl-f) for: zircon character. * Evolution Squeezes Life to Evolve with Super Radioactivity: Radioactivity today breaks chromosomes and produces neutral, harmful, and fatal birth defects. Dr. Walt Brown reports that, "A 160-pound person experiences 2,500 carbon-14 disintegrations each second", with about 10 disintergrations per second in our DNA. Worse for evolutionists is that, "Potassium-40 is the most abundant radioactive substance in... every living thing." Yet the percentage of Potassium that was radioactive in the past would have been far in excess of its percent today. (All this is somewhat akin to screws in complex machines changing into nails.) So life would have had to arise from inanimate matter (an impossibility of course) when it would have been far more radioactive than today. * Evolution of Uranium Squeezed by Contrasting Constraints: Uranium's two most abundant isotopes have a highly predictable ratio with 235U/238U equaling 0.007257 with a standard deviation of only 0.000017. Big bang advocates claim that these isotopes formed in distant stellar cataclysms. Yet that these isotopes somehow collected in innumerable small ore bodies in a fixed ratio is absurd. The impossibility of the "big bang" explanation of the uniformity of the uranium ratio (rsr.org/bb#ratio) simultaneously contrasts in the most shocking way with its opposite impossibility of the missing uniform distribution of radioactivity (see rsr.org/bb#distribution) with 90% of Earth's radioactivity in the Earth's crust, actually, the continental crust, and even at that, preferentially near granite! A stellar-cataclysmic explanation within the big bang paradigm for the origin of uranium is severely squeezed into being falsified by these contrasting constraints. * Remarkable Sponges? Yes, But For What Reason? Study co-author Dr. Kenneth S. Kosik, the Harriman Professor of Neuroscience at UC Santa Barbara said, "Remarkably, the sponge genome now reveals that, along the way toward the emergence of animals, genes for an entire network of many specialized cells evolved and laid the basis for the core gene logic of organisms that no longer functioned as single cells." And then there's this: these simplest of creatures have manufacturing capabilities that far exceed our own, as Degnan says, "Sponges produce an amazing array of chemicals of direct interest to the pharmaceutical industry. They also biofabricate silica fibers directly from seawater in an environmentally benign manner, which is of great interest in communications [i.e., fiber optics]. With the genome in hand, we can decipher the methods used by these simple animals to produce materials that far exceed our current engineering and chemistry capabilities." Kangaroo Flashback: From our RSR Darwin's Other Shoe program: The director of Australia's Kangaroo Genomics Centre, Jenny Graves, that "There [are] great chunks of the human genome… sitting right there in the kangaroo genome." And the 20,000 genes in the kangaroo (roughly the same number as in humans) are "largely the same" as in people, and Graves adds, "a lot of them are in the same order!" CMI's Creation editors add that "unlike chimps, kangaroos are not supposed to be our 'close relatives.'" And "Organisms as diverse as leeches and lawyers are 'built' using the same developmental genes." So Darwinists were wrong to use that kind of genetic similarity as evidence of a developmental pathway from apes to humans. Hibernating Turtles: Question to the evolutionist: What happened to the first turtles that fell asleep hibernating underwater? SHOW UPDATE Of Mice and Men: Whereas evolutionists used a very superficial claim of chimpanzee and human genetic similarity as evidence of a close relationship, mice and men are pretty close also. From the Human Genome Project, How closely related are mice and humans?, "Mice and humans (indeed, most or all mammals including dogs, cats, rabbits, monkeys, and apes) have roughly the same number of nucleotides in their genomes -- about 3 billion base pairs. This comparable DNA content implies that all mammals [RSR: like roundworms :)] contain more or less the same number of genes, and indeed our work and the work of many others have provided evidence to confirm that notion. I know of only a few cases in which no mouse counterpart can be found for a particular human gene, and for the most part we see essentially a one-to-one correspondence between genes in the two species." * Related RSR Reports: See our reports on the fascinating DNA sequencing results from roundworms and the chimpanzee's Y chromosome! * Genetic Bottleneck, etc: Here's an excerpt from rsr.org/why-was-canaan-cursed... A prediction about the worldwide distribution of human genetic sequencing (see below) is an outgrowth of the Bible study at that same link (aka rsr.org/canaan), in that scientists will discover a genetic pattern resulting from not three but four sons of Noah's wife. Relevant information comes also from mitochondrial DNA (mtDNA) which is not part of any of our 46 chromosomes but resides outside of the nucleus. Consider first some genetic information about Jews and Arabs, Jewish priests, Eve, and Noah. Jews and Arabs Biblical Ancestry: Dr. Jonathan Sarfati quotes the director of the Human Genetics Program at New York University School of Medicine, Dr. Harry Ostrer, who in 2000 said: Jews and Arabs are all really children of Abraham … And all have preserved their Middle Eastern genetic roots over 4,000 years. This familiar pattern, of the latest science corroborating biblical history, continues in Dr. Sarfati's article, Genesis correctly predicts Y-Chromosome pattern: Jews and Arabs shown to be descendants of one man. Jewish Priests Share Genetic Marker: The journal Nature in its scientific correspondence published, Y Chromosomes of Jewish Priests, by scie

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:

The annual meeting of the American Society of Human Genetics (ASHG) is about to start. Here's a sneak-peek of the meeting with Dr. Bruce Gelb who is the current president of ASHG, he is also a researcher at the Icahn School of Medicine in New York City. My co-host --Dr. Mike Fletcher senior editor at Nature Genetics-- and I, asked Bruce Gelb about the meeting but also about some trends such as genetics and inclusion, biobanks, sequencing of the genomes of newborns, exposomics and more. 

Die Themen in den Wissensnachrichten +++ Durch den EU-Emissionshandel ist nicht nur der Ausstoß von CO2 gesunken, sondern auch von anderen Luftschadstoffen +++ Gentest kann besonders frühes Einsetzen der Pubertät vorhersagen +++ Härchen auf der Haut helfen wohl beim Fühlen +++**********Weiterführende Quellen zu dieser Folge:The European Union Emissions Trading System might yield large co-benefits from pollution reduction. PNAS, 01.07.2024Understanding the genetic complexity of puberty timing across the allele frequency spectrum. Nature Genetics, 01.07.2024Packings of Smoothed Polygons. Preprint, arxiv.org, 07.05.2024Archaeological evidence of an ethnographically documented Australian Aboriginal ritual dated to the last ice age. Natur Human Behaviour, 01.07.2024Relations between tactile sensitivity of the finger, arm, and cheek skin over the lifespan showing decline only on the finger. Frontiers in Aging Neuroscience, 02.07.2024Alle Quellen findet ihr hier.**********Ihr könnt uns auch auf diesen Kanälen folgen: Tiktok und Instagram.

Plus Musk Bashes Apple's Strategy (subscribe below) Like this? Get AIDAILY, delivered to your inbox, every weekday. Subscribe to our newsletter at https://aidaily.us Apple Unveils AI Strategy at Developer Conference Apple revealed its AI strategy, "Apple Intelligence," emphasizing personalization and privacy. Key updates include iOS 18's enhanced customization, MacOS Sequoia's iPhone mirroring, and WatchOS 11's new features. The company is also supporting RCS for better messaging with non-Apple devices. CEO Tim Cook and OpenAI's Sam Altman highlighted the advancements Apple's New AI Strategy Could Drive iPhone Upgrades Apple announced its AI strategy, "Apple Intelligence," at its annual developer conference, integrating advanced AI features into its latest devices. The new capabilities, such as image creation and email rewriting, are limited to newer models like the iPhone 15 Pro and Pro Max. This exclusivity may drive consumers to upgrade their devices. Apple Gives Siri a Major AI Makeover At WWDC 2024, Apple unveiled significant updates to Siri, enhancing its naturalness, relevance, and personal context awareness. Siri can now handle speech stumbles, understand context better, and take action across apps using the new App Intents API. These updates aim to make Siri more capable and integrated into users' daily activities. Apple Shares Slip After AI Strategy Unveiling, Musk Criticizes OpenAI Partnership Apple's stock fell during premarket trading after unveiling its "Apple Intelligence" AI strategy at WWDC 2024, which includes a partnership with OpenAI. Tesla's Elon Musk criticized the partnership, calling it a security risk. Wall Street's lukewarm response reflects concerns over Apple's AI capabilities compared to rivals like Google and Microsoft.  Musk Threatens to Ban Apple Devices Over OpenAI Integration Elon Musk threatened to ban Apple devices at his companies if Apple integrates OpenAI at the operating system level, calling it an "unacceptable security violation." This follows Apple's announcement of new AI features and a partnership with OpenAI. Musk criticized Apple's reliance on OpenAI instead of developing its own AI.  AI Uncovers Genetic Insights into Coronary Artery Disease Researchers at Mount Sinai's Icahn School of Medicine used AI to identify rare coding variants in 17 genes linked to coronary artery disease (CAD). Published in Nature Genetics, the study utilized an in silico score derived from machine learning models trained on extensive health records. These findings could lead to new targeted treatments and personalized cardiovascular care.  Kling AI Video Generator Surpasses Competitors with Advanced Features Kling, developed by Chinese tech giant Kuaishou, is gaining attention for its superior AI video generation capabilities. It can create videos up to two minutes long in 1080p resolution, outperforming rivals like Pika and RunwayML. Utilizing advanced 3D reconstruction technology, Kling produces realistic movements and scenes, setting a new standard in AI video creation. --- Send in a voice message: https://podcasters.spotify.com/pod/show/aidaily/message

Uno studio internazionale pubblicato su 'Nature Genetics' sottolinea il ruolo del Dna nella pressione alta. Commentiamo la notizia con il prof. Claudio Borghi, direttore dell'unità operativa di medicina interna al Policlinico Sant'Orsola-Malpighi di Bologna.

Chromatin Accessibility: A new avenue for gene editingHello and welcome to the NanoLSI podcast. Thank you for joining us today. In this episode we feature the latest research by researchers from Nano Life Science Institute (WPI-NanoLSI), Kanazawa University, led by Yusuke Miyanari.The research described in this podcast was published in Nature Genetics in February 2024Kanazawa University NanoLSI websitehttps://nanolsi.kanazawa-u.ac.jp/en/Chromatin Accessibility: A new avenue for gene editingIn a study recently published in Nature Genetics, researchers from Nano Life Science Institute (WPI-NanoLSI) at Kanazawa University explore chromatin accessibility, that is, endogenous access pathways to the genomic DNA, and its use as a tool for gene editing.Our DNA is protected from unwanted external modifications by forming structures called nucleosomes that consist of threads of DNA wound around chunks of special proteins known as histones. This unique coiled shape prevents the access of undesirable molecules to a cell's DNA. However, for vital genetic functions—such as DNA repair—the right set of proteins require access to these DNA fragments. This phenomenon known as ‘chromatin accessibility' involves a privileged set of protein molecules, many of which are still unknown.Now, researchers from Nano Life Science Institute (WPI-NanoLSI) at Kanazawa University, led by Yusuke Miyanari, have used advanced genetic screening methods to unravel chromatin accessibility and its pathways.So how did they go about it?For the investigation the team used a combination of two technologies—CRISPR screening and ATAC-see. While the former is a method to suppress the function of a desired set of genes, the latter is a means to identify which ones are essential for chromatin accessibility. Thus, using this method all genes playing a crucial role in chromatin accessibility could be pinned down.With the help of these assays, novel pathways and individual players involved in chromatin accessibility were uncovered—some playing a positive role and some negative. Of these, one particular protein, TFDP1, showed a negative effect on chromatin accessibility. When it was suppressed, a significant increase in chromatin accessibility was observed, accompanied by nucleosome reduction. A deeper dive into the mechanism of TFDP1 revealed that it functions by regulating the genes responsible for production of certain histone proteins.The team then focused their study towards exploring biotechnological applications of their findings. After suppressing TFDP1, two different approaches were tried. The first approach involved gene editing using the CRISPR/Cas9 tool. This revealed that deletion of TFDP1 made the gene editing process easier. Now, most chromatin accessibility occurs in nucleosome-depleted regions or NDRs. However, by suppressing TFDP1 chromatin accessibility occurred not only in NDRs but across other regions as well. Secondly, the depletion of TFDP1 aided the process of converting regular cells into stem cells, a massive step forward in cellular transformation.This study identified new chromatin accessibility pathways and channels for exploring its potential even further. “Our study shows the significant potential to manipulate chromatin accessibility as a novel strategy to enhance DNA-templated biological applications, including genome editing and cellular reprogramming,” conclude the researchers.ReferenceSatoko Ishii, Taishi Kakizuka, Sung-Joon Park, Ayako Tagawa, Chiaki Sanbo, Hideyuki Tanabe, Yasuyuki Ohkawa, Mahito Nakanishi, Kenta Nakai, Yusuke Miyanari. Genome-wide ATAC-see screening identifies TFDP1 as a modulator of global chromatin accessibility. Nature Genetics, FebNanoLSI Podcast website

GDP Script/ Top Stories for Mar 29th       Publish Date:  Mar 29th           From the Ingles Studio Welcome to the Gwinnett Daily Post Podcast. Today is Friday, March 29th and Happy heavenly Birthday to MLB HOF Cy Young. ***03.29.24 – BIRTHDAY – CY YOUNG*** I'm Bruce Jenkins and here are your top stories presented by Curiosity Lab Bike Race. Two Teens Arrested After Illegal Street Race In Gwinnett Corps of Engineers raising fees at its Lake Lanier parks and boat launches Singleton Road Residents Getting Their Own Pocket Park, Greenway Trail All of this and more is coming up on the Gwinnett Daily Post podcast, and if you are looking for community news, we encourage you to listen daily and subscribe! Break 1: CURIOSITY LAB BIKE RACE   STORY 1: Two Teens Arrested After Illegal Street Race In Gwinnett Two teens were arrested for fleeing from an illegal street racing event in Gwinnett, striking patrol cars in the process. John Anthony Pritchett, 19, faces multiple charges including aggravated assault, kidnapping, and possession of firearms during felonies. Dryan Dradarius Vereen, 18, faces obstruction charges. The incident occurred on March 23, with officers responding to gunshots and people fleeing the scene. Pritchett's stolen Dodge Charger collided with a patrol car, leading to a chase and eventual crash. Firearms were found in the vehicle, reported stolen from DeKalb County. Two female passengers claimed they were unable to exit the vehicle. Fortunately, no officers were injured. STORY 2: Corps of Engineers raising fees at its Lake Lanier parks, boat launches The U.S. Army Corps of Engineers' Mobile District announced a fee increase for using corps-run parks and boat ramps at Lake Lanier. Day use and boat launching fees will rise from $5 to $8 this summer. This adjustment aims to sustain recreational facilities' quality and is part of a broader initiative across all USACE-managed properties. The increase applies specifically to corps-run facilities and excludes those managed by other entities like the Georgia Department of Natural Resources. While the fee hike was approved last year, its implementation was postponed to aid local communities recovering from the pandemic's economic impact. The Corps assures visitors of continued commitment to quality recreation and facility maintenance, inviting inquiries about the fee adjustment. STORY 3: Singleton Road Residents Getting Their Own Pocket Park, Greenway Trail Gwinnett County officials are addressing a lack of nearby recreational options for residents near Indian Trail-Lilburn Road by breaking ground on Singleton Park and a greenway trail. The park, funded by various sources including sales tax funds and grants, aims to provide accessible green space and play amenities. Expected to open in late 2025, it will feature a playground, restroom, and picnic areas. The three-quarter-mile greenway trail will connect Singleton and Dickens Roads, eventually linking to Bryson Park as part of the county's broader greenway trails plan. While promoting walkability, officials also highlight accessibility via public transit. Residents anticipate the park's convenience and benefits, particularly for families in the area lacking outdoor play options.   We have opportunities for sponsors to get great engagement on these shows. Call 770.874.3200 for more info. We'll be right back   Break 2: TOM WAGES   STORY 4: Bill banning puberty blockers for minors languishes alongside other culture war measures During the 2024 Legislative session, two bills concerning transgender issues failed to pass the Georgia House. The bills aimed to restrict transgender children's access to sports teams, restrooms, and puberty-blocking drugs. Despite passing the Senate, the House did not vote on these measures. The bills reflected broader cultural divides, with Republicans supporting them and Democrats opposing. House Speaker Jon Burns emphasized the importance of timing and prioritization in addressing social issues. Proponents of the bills, like Sen. Ben Watson, argued that banning puberty blockers would prevent irreversible decisions for minors. However, opponents, including transgender advocates, highlighted the positive impact of such treatments on mental health and identity affirmation. Another bill addressing student athletes' mental health was also stalled, leaving room for potential reconsideration in future sessions. STORY 5: Immigration crackdown, election law changes go to the governor as other hot-button proposals fizzle The 2024 Legislative session concluded with a flurry of activity, including the failure of several contentious bills. Despite passing the Senate, bills banning puberty blockers for minors and legalizing sports betting did not receive House approval. The last-minute session also saw the passage of bills related to road renaming and property tax relief. However, controversial measures such as an election overhaul and immigration enforcement bills were approved. Additionally, a proposal for a statue honoring Justice Clarence Thomas and efforts to protect the Okefenokee Swamp from mining faced setbacks. While the session ended without certain bills progressing, discussions on key issues, such as Medicaid expansion and environmental protection, are expected to continue.   We'll be back in a moment   Break 3: INGLES 10 – HENRY CO SHERIFFS OFFICE     STORY 6: Targeting immune cells offers hope for preventing breast cancer Researchers at Cambridge University have identified a new pathway for preventing breast cancer by targeting immune cell exhaustion in healthy women with BRCA1 or BRCA2 gene mutations. These mutations increase the risk of breast and ovarian cancer. The study found that immune cells in breast tissue of these women show signs of malfunction, unable to clear out damaged cells that could develop into cancer. This discovery could lead to using existing immunotherapy drugs as early intervention to prevent breast cancer, offering an alternative to risk-reducing surgery. The research, published in Nature Genetics, suggests a potential preventative treatment accessible to all women.   STORY 7: Scientists bust myth that eggs are bad for your heart A new study debunks the myth that eggs are bad for heart health, suggesting concerns about cholesterol levels are unnecessary. The PROSPERITY trial involved 140 patients with or at risk for cardiovascular disease who consumed 12 or more fortified eggs weekly. Results showed no adverse effects on blood cholesterol, with reductions in LDL cholesterol and other heart health markers observed in the fortified egg group. Researchers emphasize that eggs' bad reputation may stem from confusion about egg yolk cholesterol and suggest examining overall dietary habits. They encourage heart disease patients to discuss heart-healthy diets with their doctors.   We'll have final thoughts after this.   Break 4: ATL HEALTH FAIR   Signoff – Thanks again for hanging out with us on today's Gwinnett Daily Post podcast. If you enjoy these shows, we encourage you to check out our other offerings, like the Cherokee Tribune Ledger Podcast, the Marietta Daily Journal, the Community Podcast for Rockdale Newton and Morgan Counties, or the Paulding County News Podcast. Read more about all our stories and get other great content at Gwinnettdailypost.com. Did you know over 50% of Americans listen to podcasts weekly? Giving you important news about our community and telling great stories are what we do. Make sure you join us for our next episode and be sure to share this podcast on social media with your friends and family. Add us to your Alexa Flash Briefing or your Google Home Briefing and be sure to like, follow, and subscribe wherever you get your podcasts. Produced by the BG Podcast Network   Show Sponsors: ingles-markets.com wagesfuneralhome.com henrycountysheriffga.gov gcpsk12.org/about-us/careers acc.org/ATLHealthFair   #NewsPodcast #CurrentEvents #TopHeadlines #BreakingNews #PodcastDiscussion #PodcastNews #InDepthAnalysis #NewsAnalysis #PodcastTrending #WorldNews #LocalNews #GlobalNews #PodcastInsights #NewsBrief #PodcastUpdate #NewsRoundup #WeeklyNews #DailyNews #PodcastInterviews #HotTopics #PodcastOpinions #InvestigativeJournalism #BehindTheHeadlines #PodcastMedia #NewsStories #PodcastReports #JournalismMatters #PodcastPerspectives #NewsCommentary #PodcastListeners #NewsPodcastCommunity #NewsSource #PodcastCuration #WorldAffairs #PodcastUpdates #AudioNews #PodcastJournalism #EmergingStories #NewsFlash #PodcastConversationsSee omnystudio.com/listener for privacy information.

Teaching and Learning: In the Lab featuring Chetan Bettegowda, MD, FAANSDr. Chetan Bettegowda is currently the Jennison and Novak Families Professor of Neurosurgery and Oncology and Vice Chair for Research in the Department of Neurosurgery at the Johns Hopkins University School of Medicine. His clinical focus is on the surgical management of brain tumors and directs and metastatic brain tumor center, meningioma center and trigeminal neuralgia. He directs the Reza Khatib Brain Tumor Center and the Physician Scientist Training Program at Johns Hopkins. As Medical Director of the Ludwig Center for Cancer Genetics and Therapeutics, his laboratory efforts have focused on the applications of cell free tumor derived DNA for the early detection and monitoring of a myriad of cancers. His research has been funded by the Burroughs Wellcome Career Award for Medical Scientists, Doris Duke Clinician Scientist Award, Department of Defense and the National Cancer Institute. He has been recognized with numerous awards including being named the 2022 William Baumgartner Johns Hopkins Physician of the Year. He has published widely with over 250 articles including in journals such as Science, Science Translational Medicine, Nature Genetics, Nature Communications, Cell Reports Medicine and PNAS. 

Dr. Mahdi Sheikh and Dr. David Zaridze join Dr. Shannon Westin to discuss how quitting smoking after diagnosis may impact survival in kidney cancer. TRANSCRIPT  The guest on this podcast episode has no disclosures to declare. Dr. Shannon Westin: Hello everyone, and welcome to another episode of JCO After Hours. This is the podcast where we get in-depth on manuscripts that have been published in the Journal of Clinical Oncology. As always, I'm your host, Shannon Westin, Gynecologic Oncologist and Social Media Editor for the JCO. And I am so excited to be here today. We are going to be discussing the paper, “Smoking Cessation After Diagnosis of Kidney Cancer Is Associated With Reduced Risk of Mortality and Cancer Progression: A Prospective Cohort Study,” which was published in the JCO on March 29, 2023. And this very intriguing paper, I have two of the major authors from this paper. First is Mahdi Sheikh, who is a scientist and epidemiologist at the International Agency for Research on Cancer, the World Health Organization in Lyon, France. Welcome, Dr. Sheikh. Dr. Mahdi Sheikh: Thank you very much, Dr. Westin, and thanks for having us. Dr. Shannon Westin: And then with Dr. Sheikh is Dr. David Zaridze. He is the Director of the Department of Clinical Epidemiology at the N.N. Blokhin Russian Cancer Research Center in Moscow and also the President of the Russian Cancer Society. We are with greatness today. Dr. David Zaridze: Thank you. Thank you very much. Nice to be with you. Dr. Shannon Westin: Very nice to be with the two of you. So, let's get started. I first wanted to just level set. Could one of you review just the overall incidence of kidney cancer and what proportion of patients with kidney cancer are known to be smokers at diagnosis? Dr. David Zaridze: The figures I'm going to present are rates. They are adjusted to standard world population. Why am I saying that? Because in America you sometimes use adjustment to the US population. These figures will be different from what you are accustomed to see. Okay, incidence of kidney cancer in Russia, in men, 14.1 per 100,000. I compare this with the United States of America, men, 16.5. Very small difference. Women in Russia, 8 per 100,000. In the United States of America, 8.8 per 100,000 of population. Exactly the same. Very close. These rates are sort of high-ish, but there are very high rates, for example, in the Czech Republic, where rates are more than 20 and other Central European countries. In Russia, kidney cancer mortality in men is 6 per 100,000. In USA, 3 per 100,000. In women in Russia, 1.9. In the United States, 1.3. I would say that there is a difference in mortality in men, not much in women. The incidence of kidney cancer is increasing in Russia sharply, sharply. Since 1990 it has increased - it's tripled. It increased from 5 per 100,000 in 1990 to 14 per 100,000 in 2019. Mortality is stable or declining. This is suggesting that kidney cancer is overdiagnosed in Russia and probably elsewhere. But this is not a problem of our discussion now. The frequency of the prevalence of smoking in kidney cancer patients. It is estimated that 15% to 20% of patients with kidney cancer smoke. In Russia, we have results only from our study. 18% of patients smoked at admission to our cancer center. Dr. Shannon Westin: Got it. Okay, good. Well, that's really helpful, especially to those of us that don't take care of patients with kidney cancer every day. It helps us just understand. And I guess the next question is what do we know about the impact of tobacco cessation on the risk of kidney cancer? So you were talking about that increasing incidence. How does tobacco cessation impact that? Dr. Mahdi Sheikh: Tobacco smoking is a known risk factor for kidney cancer and an estimated 17% of the kidney cancer burden worldwide can be attributed to tobacco smoking. There is a recent meta-analysis of 56 studies that was published a few years ago that clearly showed a dose-response relationship between smoking and kidney cancer, meaning that the more cigarettes a day you smoke, the risk of kidney cancer will go up. For example, the risk that was shown for five cigarettes per day was 20%. It goes up until 70% for 30 cigarettes per day. And also with a duration, the more years you smoke, the risk for kidney cancer will go higher. However, the good news is that when you quit smoking, there is strong evidence that the risk for developing kidney cancer will be lower compared to if you continue smoking. And there is some evidence that shows again dose-response relationship, meaning that the more years you spend in quitting smoking, the lower your risk would be for developing kidney cancer compared to if you continue smoking. So this is not only about renal cancer or kidney cancer but also true about many other cancer sites as well. Dr. Shannon Westin: Okay, that's super helpful. And then I guess prior to your study that we're about to talk about, did we have any information on what happens when patients quit smoking after their diagnosis? Any limitations to those data that were available? Dr. David Zaridze: You mean the data which was prior our study? You know, the negative effect of smoking after diagnosis has been shown nearly three decades ago. The information exists already for thirty years, but it was largely ignored not only in clinical practice but also in clinical trials. And I have to stress that in clinical trials this information is still ignored. I came across these studies and decided to review them some time ago. All they were case-control studies and to my knowledge, none of them assessed the effect of quitting smoking. I decided to review these studies and included this review in my book, Smoking: A Major Cause of Cancer, which was published in 2012 and was dedicated to Professor Richard Doll's anniversary. In fact, this was a stimulus for the study we are discussing. And in fact, the component of this study we are discussing today was built in and baked into the existing cohort study to which we added the active follow-up component for assessing the changes in smoking habit and disease status. Dr. Mahdi Sheikh: If you review the evidence, before publishing this study just like a few years ago, we find that there are many studies published talking about the effects of smoking cessation on cancer survival. However, as David mentioned when you go deep into these studies, you'll find a lot of limitations. First of all, most of these studies are retrospective studies, which means that either case-control or retrospective course that patients developed the outcome, and then some investigators came to see their records to assess or ask family members before they developed the outcomes. There are a lot of biases with these types of studies. And with the epidemiologic study, perspective study that we did, has less limitations compared to retrospective ones. Another one is that when we go into the study you see, they only assess a small number of patients, small sample size. Some studies just assess 10 smokers, some assess like 30. By this study we try to assess a large number of smokers who quit smoking after diagnosis. Another limitation is that– First, let's see what exposure and what setting we are talking about. We're talking about smoking which is a very dynamic behavior. People quit smoking and they relapse smoking and they quit smoking and so on. So if you access this exposure for only a limited time, for example, for one year, then you may miss what happens after that which results in misclassification of some of the participants. So repeated assessment was not done in other studies that we did here in this study. Another one, you are talking about special setting patients who are diagnosed with cancer. These patients have special circumstances, they have treatments, they have family support, they might go under the stress of cancer, and all these different stages at diagnosis. And most studies that are available, they didn't account for this. They didn't adjust or they didn't try to understand the role of these compounding factors, as we call it in epidemiology, on that, the thing that we're trying to address. And a prospective study, as I said, long follow-up time. Even the very few prospective studies that were available for other cancer sites that have only one year or maximum two years of follow-up with this type of exposure, so it is important to follow them for a long time. Another thing I would say was exposure assessment. Not only did we repeatedly try to assess exposure among participants, but try to call the people– David and his team who did the study in the field, called the participants and tried to ask the family members and sometimes their physicians about their smoking behaviors. When you go to current evidence you see, mostly smoking behavior was assessed using the record that is available like treatment records or patient records, which again has some limitations if you do not assess exposure among qualified participants. Finally, we're talking about a dynamic behavior in the follow-ups. Some people might change smoking. But there is a very important thing, in this study, we also collect at the time of quitting smoking. There's a very important thing in statistics we call Survivorship Bias, meaning that, if you were assessing an exposure doing the follow-up and if you do not pay attention to this, you will assess an exposure that is a proxy of people who lived longer. Meaning that people have enough time, they have a long time, and those who have longer time, will have more time to quit smoking. And then you will be assessing this, actually, not the exposure, but you're only assessing people who quit smoking, and then whatever you assess, you would end up with a beneficial effect. But if you have the time of quitting smoking and follow up and all these statistical things and lower sample size, you are able to account for this very very important bias in epidemiology. Dr. Shannon Westin: Before we go further, I'd love for just a bit of a description of exactly how you laid out your study to really add to where this data are so limited around survival and tobacco cessation. So maybe review the primary/secondary objectives, basic design, just to make sure our listeners are all on the same page. Dr. David Zaridze: The study has classical prospective cohort design that the study, which was basically a basic study, in which the new component was built in. This study used a user's questionnaire-based exposure assessment and molecular epidemiologic approach. I mean that, in addition to the questionnaire approach, we collected blood and tumor tissues for molecular studies. All patients with kidney cancer admitted to the cancer center were interviewed at admission before receiving any treatment. A structured lifestyle questionnaire was used. Participants were asked about their lifetime smoking history which included questions about the duration and frequency of smoking cigarettes, the average number of cigarettes smoked every day. They were also asked about their lifetime history of alcohol drinking. The questions included questions about exposures to carcinogens other than smoking, and health conditions, including chronic kidney diseases, hypertension, diabetes and so on. Height and weight were measured. Today, this study generated and continues to generate plenty of results and papers published in most prestigious journals such as Nature Genetics, for example. So, as you know, we started from 2012, we started the follow up of the cohort members, we were focusing on Moscow residents and the follow-up includes regular annual contacts with the patients personally or via telephone or with patients' household members, etc. Again, we collected information about changes in smoking behavior and disease status. We also used information from the regional cancer registry to confirm the information obtained from patients. The average period of follow up was eight years. And this is quite a long follow-up. Repeated assessment of smoking status reduces the likelihood that exposure to smoking was misclassified. However, regrettably, the self-reported information on smoking was not supported by biochemical tests, for example, by blood cotinine testing. To my knowledge, this is the only prospective cohort study in patients with cancer, not only with kidney cancer that have collected data on participants' smoking status prospectively for quite a long time. The average follow-up time was eight years. Dr. Shannon Westin: That was incredible. That definitely caught my eye. And I was looking, I was like, “Oh, how many did they lose?” And you guys kept 80-100% of the patients. I just was so impressed by that. And now hearing the mechanisms in which you did that, it makes sense. You were very diligent, multiple ways to contact patients and confirm the data. So you really are to be congratulated for the work that you're able to achieve. Dr. Sheikh, I'd love to hear, you talked a little bit about how some of the studies didn't really think about confounding variables. Can you kind of highlight some of the confounding variables that you all controlled for in order to really assess the impact of the cessation on survival? Dr. Mahdi Sheikh: Thanks to the high-quality data and also the large sample size and the way the study was designed, we were able to adjust for a lot of confounding. So we tried to adjust for all these things. So we used three approaches. The first approach was adjustment. When you ran this in the analysis, we tried a statistical model, we tried to adjust for these confounders like age, sex, treatment, socioeconomic status, smoking intensity, alcohol, and other factors. This is one effect, one approach. The second approach was stratification, meaning that we come and see the effect within people who have been diagnosed with only earlier stage tumors to see if the effect among people with earlier stage tumors differs with the effect that we see among people with higher stage tumors. But again, if you read the paper, you see that we saw the protective effects of smoking cessation on both groups of people, those who were diagnosed at earlier stages and those who were diagnosed at later stages. And also heavy smokers or mild to moderate smokers, again, we tried stratified analysis excluding those heavy smokers and saw the effect, again, among those who were light smokers or moderate smokers and also with the heavy smokers. I want to say that we tried all these types of analytical approaches and we really saw the protective effects across all patient subgroups. Finally, I talked again about the survivorship bias. So we used really strict statistical approaches to address this confounding, and because we had the time of quitting, we had the follow up time and all these things. And, again, whatever we did in the study we still could see the effects of smoking and all this is due to the good design, the large sample size, and the good questionnaire data that we have. Dr. Shannon Westin: That's awesome. I think, of course, now let's get to the bottom line. 40% reported that they quit smoking after diagnosis with none relapsing during the time period. And what did you see was the impact on overall survival as well as cancer-specific survival? Dr. Mahdi Sheikh: So we tried several outcomes - overall survival, cancer-specific survival, but also progression-free survival. And then because we had the large sample size we could assess all this. Interestingly, we saw the effect on all the three outcomes that we assessed. So the overall survival was better among those during the quitting time and also the cancer-specific survival was also better and also progression-free survival was better among all these participants. Dr. Shannon Westin: I think most people that have read this paper - and if you haven't read this paper you should run to read it right now - I really was impressed with that kind of clear benefit across cancer-specific mentality across all subgroups regardless of how much they smoked. So I don't know why you get a sense of like, “Oh, if you smoke a little bit you wouldn't see as big of an impact,” but a very clear impact. And I would love to hear why you think smoking negatively impacts these outcomes. How does the cessation help? This is a perfect time for that. Dr. Mahdi Sheikh: When we review the evidence about how smoking cessation may be beneficial for patients, for the survivorship of patients with cancer, we come to five mechanisms that are suggested in the literature. So the first one can be, is suggested, that is altered cancer biology. Smoke and tobacco smoke contain numerous carcinogens and mutagens. So it has been shown that cancer cells that are exposed to tobacco smoke, they may become more aggressive and the risk of metastasis might go higher and also, angiogenesis and all other effects on the biology of cancer cells. So it may affect the cancer cell biology. Another suggested mechanism might be altered immune response. So tobacco smoking affects the immune system and then the immune response among those who are exposed to tobacco might be affected by tobacco smoking. So their response to the cancer cells but also other bacteria, viruses, and other things might be affected as well. The third possible mechanism suggested altered drug metabolism. It has been shown that tobacco smoke and smoking can affect some of the enzymes that have metabolic responsibilities and metabolism of the drugs. So that can affect the washout period for the drug. It might not stay enough in the blood or vice versa as well. It might affect the toxicity. There is some evidence about this. The fourth mechanism suggested is about increasing treating-related complications or treatment-related complications. People who smoke have delayed wound healing, they have more complications, the surgery, the time they spend at the hospital might be longer. And this is also part of which smoking may affect the outcomes that we saw here. And finally, that is we are talking about tobacco smoking and patients with cancer are human beings with all these systems. So we know that smoking causes damage to the cardiovascular system, to the pulmonary system and also to the lungs and other things. So this is why we see different outcomes are affected by cancer. Dr. David Zaridze: I was impressed by the data that exposure to tobacco smoke condensate induces changes in tumor microenvironment. For example, it inhibits formation of interferons, interferon alpha and gamma, inhibits the migration to tumor microenvironment of the immune cells. The number of CD8+ T lymphocytes, T killers, are significantly lower in the tumor microenvironment of current smokers compared to former smokers and never smokers. And even more interestingly, the number of PD-L1+ cells are also lower in the tumor microenvironment of current smokers than former or never smokers. This is probably very important in terms of effectiveness of impairment by smoking of the immunotherapeutic approaches in cancer treatment. Dr. Shannon Westin: That's very important and we know the microenvironment has a huge impact on just the way the cells respond to treatment and develop resistance and so that makes a lot of sense. Okay, well, this has been amazing and I think one thing that you just said just struck me, Dr. Sheikh, that you've obviously shown this in lung cancer and you're looking at this in other cancers. I guess the question is: What should we be doing? How should we be implementing tobacco cessation efforts across all cancer diagnoses to help all patients that have really any diagnosis of cancer? Dr. David Zaridze: Let me first underline the clinical importance of these results. The benefits from quitting smoking are comparable or even superior to those recorded in the clinical trials of modern kidney cancer treatments such as immune checkpoint inhibitors. I refer to the results of pivotal trials in advanced renal cell cancer in the frontline setting and these results were reported at ASCO Meeting 2023 recently in May. If you compare the results of our study with results of these pivotal trials, it is very impressive. It is clear that our findings strengthen the case for making tobacco cessation treatment a standard part of the routine health care for all people with cancer, however, smoking is still quite high in cancer patients. And I would like to quote Peter Shields who is saying that, in the United States,10% to 50% of cancer patients smoke. As far as Russia is concerned, in our study, 80% of kidney cancer patients smoke, and in our lung cancer study, 58% of cancer patients smoke.  The barrier is that the oncologists do not believe or are accepting with a great deal of skepticism the results of our study. They don't believe the idea that anything else besides surgical, radiological, or medical treatment could improve the outlook of cancer patients. It's difficult for them to apprehend. Many of them think that smoking cessation after diagnosis is simply a waste of time. Many patients simply don't know that smoking cessation after diagnosis may be beneficial for them. In addition, they are pessimistic and they feel discouraged to quit smoking, as they might think it is too late. I would like to quote my favorite quote: “Smoking cessation treatment has to become the fourth pillar of cancer treatment, one that could affect cancer treatment outcomes as powerfully as surgery, chemotherapy, or radiation therapy.” This is Dr. Fiore, 2019. Dr. Shannon Westin: Thank you so much. And Dr. Sheikh, anything to add there around cessation efforts? Dr. Mahdi Sheikh: As we saw the results of these studies that smoking cessation is feasible and it is accessible at a minimum cost for many patients, it should really be integrated in the  management of patients with cancer. It is feasible, it is cheap, it is accessible. But unfortunately, when we review the evidence we see that only less than half of the physicians, like around 40% of physicians, send the patients to tobacco smoking cessation services. And even some do not discuss this issue. And as David mentioned, they do not know the effect of smoking cessation. So when you go through these studies to find the major barriers, in addition to what David had mentioned, we find two important points. First one is lack of education or experience in providing tobacco cessation interventions among those who deal with patients with cancer. So they do not have the education. And second is lack of available resources for referrals. Now we're not only talking about the United States but also many other countries even high-income countries, we do not see the resources for referrals on smoking cessation services in cancer care settings. The take home message probably from this study and also from these barriers, would be for three groups. First, for the policymakers, we would recommend sustainable funding should be dedicated to tobacco cessation services. As we saw, the effect is huge and seems to be a very big effect and it is cheap so why not implement this smoking cessation service within cancer care settings.  And the second one, tobacco treatment training programs for healthcare providers. This is also very, very important that we try to implement this training program in the curriculum of healthcare providers, especially those who deal with cancers and tobacco-related outcomes. And also for physicians, we recommend that physicians should assess and address tobacco use in all patients with cancer. They should talk about this topic and also show the benefits of quitting smoking. And patients with cancer who smoke should be supported to stop smoking at any time and each visit after diagnosis is not like some time pass, as we saw, all patient subgroups could benefit from smoking cessation. This is important.  But something also very, very important that we shouldn't forget that cancer itself causes a lot of fear and anxiety and stress. And smoking cessation sometimes may be associated with stress and more anxiety. So it is very, very important to think about this point and provide the psychosocial support to patients who quit smoking. Sometimes they may relapse just because of the fear and anxiety they have. So it's not only showing the evidence, but also supporting these patients, telling them how to do that and also supporting them emotionally and also psychosocially. And finally for the patients, I would like to give this message that we see and we know that it is never too late to quit smoking. As David said, patients may feel like, “It is too late now I've developed cancers,” but no, it's really not too late. And if you quit smoking at any time after diagnosis, you would benefit a lot from smoking cessation. Dr. David Zaridze: In the United States there are guidelines, several guidelines for smoking cessation, specifically for cancer patients because smoking cessation in cancer patients is very different from smoking cessation in general population. In the general population, we more or less succeeded, I would say, and we have to look now at this direction to the smoking cessation in cancer patients. And this is a message to WHO, that countries, members of WHO, based on the recommendation guidelines of WHO, develop their own specific guidelines for smoking cessation in cancer patients. And that should be used in all cancer clinics and that should be a must, absolutely important part of anti-cancer treatment. And as I already told, it should be the fourth pillar in cancer treatment, as treatment, as surgery, chemotherapy and radiation. Dr. Shannon Westin: Thank you both. That was such a great discussion, and I hope that we've convinced everyone that this is a critical effort that they need to be addressing every day.  I just want to thank everyone who listened. This has been "Smoking Cessation after Diagnosis of Kidney Cancers Associated with Reduced Risk of Mortality and Cancer Progression: A Prospective Cohort Study", again published in the JCO on March 29, 2023. Thank you guys again for listening to JCO After Hours. Please check out our other podcast offerings. You can check them out on the website or wherever you get your podcasts and let us know what you think about the podcast on Twitter. Dr. David Zaridze: Thank you. Dr. Mahdi Sheikh: Thank you very much.  The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.   Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.  

We got a special episode of Too T3rpd this week. It's another spin-off episode with a comedian! Donovan and DietRosinT chat with Comedian Ronaldo Mercado. We talk to Ronaldo about his comedy origins. gives some comedy advice, talks about some big moments in Ronaldos career and much more! On this weeks episode our flower sponsor is We Supply Medical! They supplied us with some Grape Crinkle Berry x Sour Stomper flower bred by Force of Nature Genetics and cultivated by We Supply Medical. You can find We Supply Medical:On instagram: @we_supply-medical-caregiversYou can find Ronaldo:Instagram: @ronaldosuckssYouTube: @rifflaughloveFollow Too T3rpd on Instagram  Check out our videos on our Too T3rpd YouTube channel  Leave voicemails/text to our Too T3rpd hotline (314) 399-9711Sign up for our Patreon: https://www.patreon.com/TOOT3RPD Follow Donovan @Donovan2408 on all socialsFollow Tyler @somesocialst on instagram Follow Eddie @stl_kush_culture on all socialsSupport the show

This episode follows 2 Kidney Cancer expert Urologists in understanding Kidney tumors from diagnosis to treatment options.  Guest:   John L. Gore, M.D. Professor of Urology, Professor of Surgery, Health Services Researcher, University of Washington. Urologist, surgeon, clinician, researcher, educator and expert in clinical care guidelines and outcomes. Dr. Gore is the PI of a large pragmatic trial in bladder cancer, and a quality of care expert. He previously served as the American Urological Association (AUA) representative to the National Quality Forum, which endorses national health care performance measures, and has been on guidelines panels for the National Comprehensive Cancer Network (NCCN) for kidney cancer, and the AUA for bladder cancer.   Brian Shuch, MD is the Director of the Kidney Cancer Program and the Alvin & Carrie Meinhardt Endowed Chair in Kidney Cancer Research. He completed his urology training at UCLA followed by a Urologic Oncology Fellowship at the National Cancer Institute. He is an accomplished surgeon (open/laparoscopic/robotic surgery and percutaneous ablations) and clinical/translational researcher. He serves in leadership positions within various kidney cancer research organizations such as SWOG and the Society of Urologic Oncology. He is recognized as an expert in the genetics of kidney cancer and runs a translational research program with over 140 peers reviewed publications including primary research published in prestigious journals such as Nature, Nature Genetics, Proceedings of the National Academy of Sciences, Journal of Clinical Oncology, and Clinical Cancer Research. He is one of the few clinicians to bring bench science to the bedside in an upcoming therapeutic clinical trial for metastatic kidney cancer.   During This Episode We Discuss: The types of Kidney Cancer   Non cancerous kidney cysts (benign) versus cancerous kidney cysts,   Solid kidney tumors, benign and malignant   Diagnosis of kidney cancers: Imaging and Biopsy   Risk factors for kidney cancers   Genomics of kidney cancer   Treatment of kidney cancer: Localized and Metastatic Quotes (Tweetables) Back in the olden days we used to talk about the triad of three symptoms people associated with kidney cancer. Those three symptoms were hematuria or blood in the urine, palpable mass, and flank pain. Realistically in 2023 this triad happens less than 1% of the time. What has changed is that there is a much higher frequency of use of imaging to diagnose problems in our bodies. Kidney cancer is one of the fastest growing cancer types in terms of it's incidence, because of incidental detection.                                                                                  Dr Gore   Regarding tumor size, it all depends on the scenario.The larger the lesion the more concerning it is for cancer, but even a 1 cm tumor can have some aggressive elements. There is not an absolute size where you say that a tumor below this threshold cannot be a cancer.                                                                                Dr Shuch Most kidney cancers are what we would call sporadic, in that it occurs in the absence of known risk factors. The 2 biggest risk factors that are more behavioral are smoking and obesity.                                                                                 Dr Gore                                                                                Recommended Resources:   KCA: Kidney Cancer Association www.kidneycancer.org   Kidney Can www.kidneycan.org   KC Cure  www.kccure.org   American Cancer Society   Fred Hutchinson   UCLA

Join Af as he learns about the incredible advances in DNA manipulation with Kevin Davies, the author of Editing Humanity: The CRISPR Revolution and the New Era of Genome Editing. Kevin has 30+ years in science publishing as an editor of leading academic journals (with Nature Genetics, Nature and Cell Press); in trade publishing (Bio-IT World), and as a publisher (C&EN). In 2018, he spearheaded the launch of The CRISPR Journal, published by Mary Ann Liebert Inc. His books include "The $1,000 Genome"​ (Free Press, 2010), "Cracking the Genome" (Free Press, 2001), and "Breakthrough: The Race for the Breast Cancer Gene." Kevin is the founding editor of Nature Genetics, the first offshoot from Nature. He holds an undergraduate degree in Biochemistry from Oxford University and a PhD in molecular genetics from the University of London.

On episode 150, we welcome Dr. Mikkael Sekeres to discuss the social and political climate that fostered the necessity to create the FDA, medical charlatans and the history of pseudo-medicine, the necessity of clinical trials for creating safe and effective medications, why anecdotal evidence isn't equivalent to scientific validation, the FDA's decision to remove the breast cancer indication for the drug Avastin and Genentech's decision to fight it, Mikkael's personal experience during that hearing while a member of the jury, the public's distrust of the FDA and where it stems from, Genentech spin-doctoring data to make their case for the safety and efficacy of Avastin, why mostly harmful medications should be removed from circulation if proven so, and how the FDA decides on which drugs to approve and which ones to recommend removing. Dr. Mikkael A. Sekeres is Professor of Medicine and Chief of the Division of Hematology at the Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, and former Chair of the Oncologic Drugs Advisory Committee of the FDA. He is the author or co-author of over 400 manuscripts and 650 abstracts published in leading journals such as NEJM, Blood, Journal of Clinical Oncology, Nature Genetics, Cancer Cell, Journal of the National Cancer Institute, Journal of Clinical Investigation, PLoS One, and Leukemia. A regular contributor to the Well section of the New York Times, has authored 8 books, including When Blood Breaks Down: Life Lessons from Leukemia and his newest book, available now, is called Drugs and the FDA: Safety, Efficacy, and the Public's Trust. | Mikkael Sekeres | ► Website | https://bit.ly/3UetF8h ► Twitter | https://twitter.com/MikkaelSekeres ► Drugs and the FDA Book | https://amzn.to/3Df18IA Where you can find us: | Seize The Moment Podcast | ► Facebook | https://www.facebook.com/SeizeTheMoment ► Twitter | https://twitter.com/seize_podcast ► Instagram | https://www.instagram.com/seizethemoment ► TikTok | https://www.tiktok.com/@seizethemomentpodcast ► Patreon | https://www.patreon.com/user?u=32208666

In this episode of the Epigenetics Podcast, we caught up with John Rinn from the University of Colorado in Boulder to talk about his work on the role of lncRNAs in gene expression and nuclear organization. The Rinn Lab pioneered the approach of screening the human genome for long noncoding RNAs (lncRNAs). More recently, the lab has shifted focus from measuring the number of lncRNAs to finding lncRNAs that have a distinct biological function in human health and disease. One example of such a lncRNA is FIRRE, which is present in all animals, however the sequence is not conserved, except for in primates. FIRRE contains many interesting features, such as repeat sequences and CTCF binding sites. In absence of FIRRE, defects in the immune system can be observed and also some brain defects may also be observed.   References Carter, T., Singh, M., Dumbovic, G., Chobirko, J. D., Rinn, J. L., & Feschotte, C. (2022). Mosaic cis-regulatory evolution drives transcriptional partitioning of HERVH endogenous retrovirus in the human embryo. eLife, 11, e76257. Advance online publication. https://doi.org/10.7554/eLife.76257 Long, Y., Hwang, T., Gooding, A. R., Goodrich, K. J., Rinn, J. L., & Cech, T. R. (2020). RNA is essential for PRC2 chromatin occupancy and function in human pluripotent stem cells. Nature Genetics, 52(9), 931–938. https://doi.org/10.1038/s41588-020-0662-x Kelley, D., & Rinn, J. (2012). Transposable elements reveal a stem cell-specific class of long noncoding RNAs. Genome biology, 13(11), R107. https://doi.org/10.1186/gb-2012-13-11-r107 Khalil, A. M., Guttman, M., Huarte, M., Garber, M., Raj, A., Rivea Morales, D., Thomas, K., Presser, A., Bernstein, B. E., van Oudenaarden, A., Regev, A., Lander, E. S., & Rinn, J. L. (2009). Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression. Proceedings of the National Academy of Sciences, 106(28), 11667–11672. https://doi.org/10.1073/pnas.0904715106 Guttman, M., Amit, I., Garber, M., French, C., Lin, M. F., Feldser, D., Huarte, M., Zuk, O., Carey, B. W., Cassady, J. P., Cabili, M. N., Jaenisch, R., Mikkelsen, T. S., Jacks, T., Hacohen, N., Bernstein, B. E., Kellis, M., Regev, A., Rinn, J. L., & Lander, E. S. (2009). Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature, 458(7235), 223–227. https://doi.org/10.1038/nature07672   Related Episodes The Role of lncRNAs in Tumor Growth and Treatment (Sarah Diermeier) The Role of Small RNAs in Transgenerational Inheritance in C. elegans (Oded Rechavi) Chromatin Structure and Dynamics at Ribosomal RNA Genes (Tom Moss)   Contact Active Motif on Twitter Epigenetics Podcast on Twitter Active Motif on LinkedIn Active Motif on Facebook Email: podcast@activemotif.com

What are 3 golden rules of clinical care? And what really drives Dr. John McGrath, who has received numerous awards, including the exclusive and prestigious Fothergill Gold medal by the London Medical Society? The answers might surprise you. This conversation also touches on the ethos of medicine. Dr. John McGrath is Head of Department, St John's Institute of Dermatology. He is Professor of Molecular Dermatology and head of the Genetic Skin Disease Group. He qualified from Guy's Hospital in 1985, having trained in dermatology and dermatopathology at St. John's Institute of Dermatology in London. He is a recent President of the European Society for Dermatological Research, serves on the editorial board of 9 international journals, and is the section editor for genetics for the Journal of Investigative Dermatology. He has published over 400 manuscripts, including reports of mutations in Nature Genetics. His group discovered mutant genes in lipoid proteinosis, Kindler syndrome, AEC syndrome, OC syndrome and many others. Read more about Dr. McGrath at https://www.kcl.ac.uk/people/john-mcgrath. 

#crispr #geneticediting #editinghumanity #biotech CRISPR- EDITING HUMANITY'S FUTURE & RE-IMAGINING HEALTHCARE Kevin Davies is a renowned British science journalist and the executive editor of The CRISPR Journal Plus Nature Genetics. He has authored various books such as Breakthrough: The Race to Find the Breast Cancer Gene in the early 1990s Cracking the Genome, which details the dramatic story of one of the greatest scientific feats ever accomplished: the mapping of the human genome The $1,000 Genome, DNA: The Story of the Genetic Revolution And his most recent release, Editing Humanity: The CRISPR Revolution and the New Era of Genome Editing, for which he won a Guggenheim Fellowship for science writing in 2017. Kevin studied at Oxford University and moved to the US in 1987 after earning his Ph.D. in genetics. He is the founding editor of the Nature Genetics journal and Bio-IT World magazine, former editor-in-chief of Cell Press, and the first publisher of C&EN, the weekly magazine of the American Chemical Society. https://www.linkedin.com/in/kevin-davies-52b912 https://twitter.com/kevinadavies Watch our highest viewed videos: 1-India;s 1st Quantum Computer- https://youtu.be/ldKFbHb8nvQDR R VIJAYARAGHAVAN - PROF & PRINCIPAL INVESTIGATOR AT TIFR 2-Breakthrough in Age Reversal- -https://youtu.be/214jry8z3d4DR HAROLD KATCHER - CTO NUGENICS RESEARCH 3-Head of Artificial Intelligence-JIO - https://youtu.be/q2yR14rkmZQShailesh Kumar 4-STARTUP FROM INDIA AIMING FOR LEVEL 5 AUTONOMY - SANJEEV SHARMA CEO SWAAYATT ROBOTS -https://youtu.be/Wg7SqmIsSew 5-TRANSHUMANISM & THE FUTURE OF MANKIND - NATASHA VITA-MORE: HUMANITY PLUS -https://youtu.be/OUIJawwR4PY 6-MAN BEHIND GOOGLE QUANTUM SUPREMACY - JOHN MARTINIS -https://youtu.be/Y6ZaeNlVRsE 7-1000 KM RANGE ELECTRIC VEHICLES WITH ALUMINUM AIR FUEL BATTERIES - AKSHAY SINGHAL -https://youtu.be/cUp68Zt6yTI 8-Garima Bharadwaj Chief Strategist IoT & AI at Enlite Research -https://youtu.be/efu3zIhRxEY 9-BANKING 4.0 - BRETT KING FUTURIST, BESTSELLING AUTHOR & FOUNDER MOVEN -https://youtu.be/2bxHAai0UG0 10-E-VTOL & HYPERLOOP- FUTURE OF INDIA"S MOBILITY- SATYANARAYANA CHAKRAVARTHY -https://youtu.be/ZiK0EAelFYY 11-NON-INVASIVE BRAIN COMPUTER INTERFACE - KRISHNAN THYAGARAJAN -https://youtu.be/fFsGkyW3xc4 12-SATELLITES THE NEW MULTI-BILLION DOLLAR SPACE RACE - MAHESH MURTHY -https://youtu.be/UarOYOLUMGk Connect & Follow us at: https://in.linkedin.com/in/eddieavil https://in.linkedin.com/company/change-transform-india https://www.facebook.com/changetransformindia/ https://twitter.com/intothechange https://www.instagram.com/changetransformindia/ Listen to the Audio Podcast at: https://anchor.fm/transform-impossible https://podcasts.apple.com/us/podcast/change-i-m-possibleid1497201007?uo=4 https://open.spotify.com/show/56IZXdzH7M0OZUIZDb5mUZ https://www.breaker.audio/change-i-m-possible https://www.google.com/podcasts?feed=aHR0cHM6Ly9hbmNob3IuZm0vcy8xMjg4YzRmMC9wb2RjYXN0L3Jzcw Kindly Subscribe to CHANGE- I M POSSIBLE - youtube channel www.youtube.com/ctipodcast

Soutenir et s'abonner à NeurosapiensDans cet épisode, nous allons aborder ensemble le sujet de l'intelligence et plus spécifiquement du haut potentiel intellectuel.Cet épisode sera découpé en 3 grands thèmes. Pour commencer, on se fera un petit mémo sur l'intelligence. Ce qu'elle est, ce qu'elle n'est pas. Ce qu'on sait sur l'intelligence aujourd'hui en neurosciences. Ensuite, nous ferons un focus sur le haut potentiel actuel où nous décortiquerons les mythes et les réalités.L'Instagram de Confidences de Psy :https://www.instagram.com/confidencesdepsy/Production, animation, réalisation et illustration : Anaïs RouxInstagram : https://www.instagram.com/neurosapiens.podcast/neurosapiens.podcast@gmail.comMusique d'intro KEEP ON GOINGMusique proposée par La Musique LibreJoakim Karud - Keep On Going : https://youtu.be/lOfg0jRqaA8Joakim Karud : https://soundcloud.com/joakimkarudSOURCESG. E. Gignac et al., Brain volume and intelligence : The moderating role of intelligence measurement quality, Intelligence, vol. 64, pp. 18-29, 2017.K. H. Lee et al., Neural correlates of superior intelligence : Stronger recruitment of posterior parietal cortex, Neuroimage, vol. 29, pp. 578-586, 2006.S. Sniekers et al., Genome-wide association meta-analysis of 78,308 individuals identifies new loci and genes influencing human intelligence, Nature Genetics, vol. 49, pp. 1107, 2017.D. Zabaneh et al., A genome-wide association study for extremely high intelligence, Molecular Psychiatry, vol. 23, pp. 1226-1232, 2018.F. Schmiedek et al., Within-person structures of daily cognitive performance cannot be inferred from between-person structures of cognitive abilities, PeerJ Preprints, vol. 7, 7:e27576v1, 2019. Voir Acast.com/privacy pour les informations sur la vie privée et l'opt-out. Become a member at https://plus.acast.com/s/neurosapiens.

Se han identificado nuevos factores de riesgo asociados al alzhéimer, concretamente 75 factores, según publica la revista 'Nature Genetics'. Se trata de un hallazgo de gran relevancia para la investigación, ya que 42 de los factores identificados no se habían relacionado antes con la enfermedad. Así, los resultados abren nuevas vías para el tratamiento y el diagnóstico de la enfermedad.   Escuchar audio

For the low, low price of $15.95 on Amazon, you can purchase a little spray bottle of pheromones that supposedly will trigger "animal attraction" in your partner. But is it true??? Pheromones are a well-known system of communicating territory, alarms, and sexual needs to other animals but is this system present in humans? We know that smell is an important component of sexual attraction and arousal but human beings seem to lack both the organ and brain region needed to process pheromone information. But maybe???If you're curious, come and listen to learn a little bit more about what's happening upstairs!Please rate, review, and subscribe and if you have any questions, comments, concerns, queries, or complaints, please email me at neuroscienceamateurhour@gmail.com or DM me at NeuroscienceAmateurHour on Instagram.Citations and relevant pictures are below:Jimenez J, Hughes K, Alaks G, Graham L, Lacy R. An experimental study of inbreeding depression in a natural habitat. Science. 1994;266(5183):271-273. doi:10.1126/science.7939661Keverne EB. The Vomeronasal Organ. Science. 1999;286(5440):716-720. doi:10.1126/science.286.5440.716Kang N, Baum MJ, Cherry JA. Different Profiles of Main and Accessory Olfactory Bulb Mitral/Tufted Cell Projections Revealed in Mice Using an Anterograde Tracer and a Whole-Mount, Flattened Cortex Preparation. Chemical Senses. 2010;36(3):251-260. doi:10.1093/chemse/bjq120Wang L, Zhang Z, Chen J, et al. Cell-Type-Specific Whole-Brain Direct Inputs to the Anterior and Posterior Piriform Cortex. Frontiers in Neural Circuits. 2020;14. doi:10.3389/fncir.2020.00004‌Wedekind, C., Seebeck, T., Bettens, F. and Paepke, A. J. MHC-dependent mate preferences in humans. Proceedings of the Royal Society of London Series B. 1995: 260: 245-249Meredith M. Human Vomeronasal Organ Function: A Critical Review of Best and Worst Cases. Chemical Senses. 2001;26(4):433-445. doi:10.1093/chemse/26.4.433D'Aniello B, Semin GR, Scandurra A, Pinelli C. The Vomeronasal Organ: A Neglected Organ. Frontiers in Neuroanatomy. 2017;11. doi:10.3389/fnana.2017.00070Rodriguez I, Greer CA, Mok MY, Mombaerts P. A putative pheromone receptor gene expressed in human olfactory mucosa. Nature Genetics. 2000;26(1):18-19. doi:10.1038/79124Verhaeghe J, Gheysen R, Enzlin P. Pheromones and their effect on women's mood and sexuality. Facts, Views & Vision in ObGyn. 2013;5(3):189-195. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3987372/Miller SL, Maner JK. Scent of a Woman. Psychological Science. 2009;21(2):276-283. doi:10.1177/0956797609357733Support the show (https://www.patreon.com/neuroscienceamateurhour)

ADHD -  attention deficit hyperactivity disorder - is a condition characterized by differences in brain development and brain activity that affect attention, the ability to sit still, and impulse control. It affects millions of children and adults and has far-reaching effects on the lives and well-being of these individuals. And yet we still don't know what going on!Is it genetic? Is it environmental? Come and listen to learn a little bit more about the neuroscience of ADHD and what's going on in your head. Please rate, review, and subscribe and if you have any questions, comments, concerns, queries, or complaints, please email me at neuroscienceamateurhour@gmail.com or DM me at NeuroscienceAmateurHour on Instagram.Citations and relevant pictures below:Demontis D, Walters RK, Martin J, et al. Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder. Nature Genetics. 2018;51(1):63-75. doi:10.1038/s41588-018-0269-7Faraone SV, Larsson H. Genetics of attention deficit hyperactivity disorder. Molecular Psychiatry. 2018;24(4). doi:10.1038/s41380-018-0070-0Froehlich TE, Anixt JS, Loe IM, Chirdkiatgumchai V, Kuan L, Gilman RC. Update on Environmental Risk Factors for Attention-Deficit/Hyperactivity Disorder. Current Psychiatry Reports. 2011;13(5):333-344. doi:10.1007/s11920-011-0221-3Oscar Berman M, Blum K, Chen TJ, et al. Attention-deficit-hyperactivity disorder and reward deficiency syndrome. Neuropsychiatric Disease and Treatment. 2008;4(5):893. doi:10.2147/ndt.s2627Quist JF, Barr CL, Schachar R, et al. The serotonin 5-HT1B receptor gene and attention deficit hyperactivity disorder. Molecular Psychiatry. 2003;8(1):98-102. doi:10.1038/sj.mp.4001244Zulauf CA, Sprich SE, Safren SA, Wilens TE. The Complicated Relationship Between Attention Deficit/Hyperactivity Disorder and Substance Use Disorders. Current Psychiatry Reports. 2014;16(3). doi:10.1007/s11920-013-0436-6Tomasi D, Volkow ND, Wang R, et al. Dopamine Transporters in Striatum Correlate with Deactivation in the Default Mode Network during Visuospatial Attention. Rustichini A, ed. PLoS ONE. 2009;4(6):e6102. doi:10.1371/journal.pone.0006102Ritalin Poses Cognitive Risks to Those Without ADHD. Pharmacy Times. https://www.pharmacytimes.com/view/ritalin-poses-cognitive-risks-to-those-without-adhdSupport the show (https://www.patreon.com/neuroscienceamateurhour)

A perda do olfato (anosmia) ou do paladar (ageusia) estão entre os primeiros e mais frequentes sintomas da COVID-19. Porém, os mecanismos que levam a estas perdas não são claros e os sintomas não estão presentes em todas as pessoas positivadas. Para avaliar esta variabilidade de efeitos, um artigo da Nature Genetics realizou um estudo de associação genética ampla (GWAS) comparando indivíduos positivos para o SARS-CoV-2, que relataram perda de olfato ou paladar, com indivíduos que não relataram perda de olfato ou paladar. Os resultados demonstraram que os genes UGT2A1 e UGT2A2 apresentam uma modificação de base única (SNP) no DNA, que pode levar à perda de olfato ou paladar. A ideia é que pessoas que apresentem uma timina tem maior risco de perder olfato ou paladar, do que pessoas que apresentam uma citosina na mesma posição. Este locus genético rs7688383 do cromossomo 4, também esta associado com a preferência por sabor de sorvete e com o ato de fumar tabaco. Como os genes UGT2A1 e UGT2A2 produzem proteínas, que estão envolvidas na eliminação de odorantes na cavidade nasal, a ideia agora é compreender por qual mecanismo estas alterações genéticas podem levar à perda do olfato ou paladar. Então Vem Cienciar conosco! *The UGT2A1/UGT2A2 locus is associated with COVID-19-related loss of smell or taste. Nature Genetics fev/2022. https://www.nature.com/articles/s41588-021-00986-w.pdf

In this episode of the Epigenetics Podcast, we caught up with Yad Ghavi-Helm from the Institut de Génomique Functionnelle de Lyon to talk about her work on enhancer-promoter interactions during development. The Laboratory of Yad Ghavi-Helm focuses on how developmental genes are regulated by enhancers. Their work shows that developmental genes are often regulated by more than one enhancer and that those enhancers can often be located many kilobases away on the linear chromosome. Furthermore, their research also indicates that the interactions between promoters and their respective enhancers are usually established before the expression of the target gene is switched on, and that those interactions are generally stable during embryogenesis. In addition, those stable interactions seem to coincide with paused RNA Pol II being located at those promoters before gene activation. References Ghavi-Helm, Y., Michaut, M., Acker, J., Aude, J.-C., Thuriaux, P., Werner, M., & Soutourina, J. (2008). Genome-wide location analysis reveals a role of TFIIS in RNA polymerase III transcription. Genes & Development, 22(14), 1934–1947. https://doi.org/10.1101/gad.471908 Ghavi-Helm, Y., Klein, F. A., Pakozdi, T., Ciglar, L., Noordermeer, D., Huber, W., & Furlong, E. E. M. (2014). Enhancer loops appear stable during development and are associated with paused polymerase. Nature, 512(7512), 96–100. https://doi.org/10.1038/nature13417 Ghavi-Helm, Y., Jankowski, A., Meiers, S., Viales, R. R., Korbel, J. O., & Furlong, E. E. M. (2019). Highly rearranged chromosomes reveal uncoupling between genome topology and gene expression. Nature Genetics, 51(8), 1272–1282. https://doi.org/10.1038/s41588-019-0462-3   Related Episodes Ultraconserved Enhancers and Enhancer Redundancy (Diane Dickel) Unraveling Mechanisms of Chromosome Formation (Job Dekker) Biophysical Modeling of 3-D Genome Organization (Leonid Mirny)   Contact Active Motif on Twitter Epigenetics Podcast on Twitter Active Motif on LinkedIn Active Motif on Facebook Email: podcast@activemotif.com

Kevin Davies is a renowned British science journalist and the executive editor of The CRISPR Journal, based in New York. His literary career began with Breakthrough: The Race to Find the Breast Cancer Gene in the early 1990s, followed by Cracking the Genome, which details the dramatic story of one of the greatest scientific feats ever accomplished: the mapping of the human genome. His other titles include the $1,000 Genome, DNA: The Story of the Genetic Revolution, and his most recent release, Editing Humanity: The CRISPR Revolution and the New Era of Genome Editing, for which he won a Guggenheim Fellowship for science writing in 2017. Kevin studied at Oxford University and moved to the US in 1987 after earning his Ph.D. in genetics. He is the founding editor of the Nature Genetics journal and Bio-IT World magazine, former editor-in-chief of Cell Press, and the first publisher of C&EN, the weekly magazine of the American Chemical Society. In today's episode, Kevin elaborates on his career trajectory and explains why he believes that hanging up his lab coat was the best decision he ever made. We also touch on the common themes that run through his books, some of the challenges scientific publishers and editors face, and the importance of promoting the work of women scientists. We also cover vectors, CRISPR babies, the cost of gene therapy, and so much more! Make sure not to miss this fascinating discussion with the remarkable Kevin Davies. “How we turn this stunning 21st-century medicine into therapies that are affordable is going to be a Nobel Prize-winning discovery if anybody can crack that one.” — @KevinADavies Key Points From This Episode: Kevin's career trajectory and his so-called “desperate” shift to science journalism. How Kevin believes the field of genetics has evolved since he was a geneticist in the 1980s. Learn about the impetus behind the Nature Genetics journal and The CRISPR Journal. What motivated Kevin to write Breakthrough, including a meeting with Mary-Claire King. Three elements in all of his books: genetics, medical or societal impact, and personal drama. Hanging up his lab coat to join Nature and the access to authors that it afforded him. Kevin reflects on the demographic representation and “race to the finish line” issues in scientific publishing and the burden editors face. The lens through which Nobel Prizes are considered and how it can shift perspectives. The importance of promoting women in science, who have traditionally been overlooked. How Kevin's book, Editing Humanity, coincided with Doudna and Charpentier making history as the first two women to share a Nobel Prize. Stanley Qi's role in the CRISPR story, which Kevin calls an “unsung contribution.” Speculation and trepidation surrounding vectors: Kevin shares some new thinking. Germline genome editing, CRISPR babies, He Jiankui, and controversy in Hong Kong. Learn more about the exponential cost of gene therapies and gene editing drugs.

Prof Kumaramanickavel works on ocular genomics - primarily involved in gene mapping, mutational screening and association studies including genome-wide in complex and Mendelian ophthalmic diseases. Was involved in glaucoma, diabetic retinopathy and pediatric epidemiological and genetic projects comprising of 35,000 subjects. Was a key member of a successful ocular gene mapping team at New Zealand. Later, joined the Department of Genetics at Sankara Nethralaya, India and worked for over a decade and where he was elevated as executive officer (Medical) and Deputy Director of Research. He has done genetic counselling for over 10,000 patients and teaches medical and ophthalmic genetics. He graduated in medicine (MBBS) from the University of Madras, Madras Medical College, India and subsequently graduated in MD (Physiology). As Fogarty Visiting Associate, Dr. James Fielding Hejtmancik trained him in the Ophthalmic Genetics & Clinical Services Branch, National Eye Institute, National Institute of Health, USA. He was a Research Fellow, Ocular Gene Mapping Laboratory, Department of Biochemistry, University of Otago, New Zealand, where Dr. Michael John Denton trained him. During the same period at Otago, Dr. Robert F Mueller trained him in genetic counselling. Currently, he is the Research Director at two premier ophthalmic institutions of India – (a) Narayana Nethralaya, Bangalore and (a) Aditya Jyot Eye Hospital, Mumbai. He is a visiting faculty at the National Eye Institute, USA; Chinese University of Hong Kong and several universities in China and India. He has received funding for research projects from DBT, DST, ICMR, CSIR (all Government of India), National Institutes of Health, USA, INSERM, France and other private funding agencies. He has over 90 peer-reviewed publications including articles in Nature Genetics. He is a recognized PhD guide in various universities in India and across the world.

C. Jimmy Lin, MD, Ph.D., MHS is the Chief Scientific Officer (CSO) at Freenome, working on the early diagnosis of cancers. Previously, he was the CSO, Oncology at Natera (NASDAQ: NTRA), where he has led the development of new diagnostic technologies for cancer.Jimmy is also a 2016 Senior TED Fellow and Founder & President of Rare Genomics Institute, the world's first platform to enable any community to leverage cutting-edge biotechnology to advance understanding of any rare disease.Previously, Jimmy led the ClinOmics program in the Genetics Branch of the National Cancer Institute (NIH/NCI). Prior to this, he led the computational analysis of the first-ever exome sequencing studies of cancer at Johns Hopkins and was a research instructor at Washington University in St. Louis. He has numerous publications in Science, Nature, Cell, Nature Genetics, and Nature Biotechnology, and has been featured in Forbes, Bloomberg, Wall Street Journal, New York Times, Washington Post, BBC, TIME, and the Huffington Post.Learn more about Jimmy at DrJimmyLin.com and RareGenomics.org.

Desert Horse-Grant is a world leader in facilitating the translation of discoveries from the lab to the clinical environment, being recently named by Modern Healthcare as one of the year's Top 25 Innovators. She launched the UCLA Health Innovation Challenge, a seed funding program that recognizes and scales innovative therapeutic, digital and device solutions as well as patient experience and performance excellence efforts. In 2019, the U.S. Secretary of Commerce announced Desert and colleagues recipients of a prestigious national i6 Challenge grant to support Regional Innovation Strategies. She and her team's pioneering work to develop Oncoscope, a novel biotool on the analysis and visualization of linked molecular and clinical cancer data, was recognized with a social impact award by GitHub and published in Nature Genetics in 2018.

Publishing is a complex world of skewed macro-level challenges including access to high-impact journals, lack of equity within journal publication processes, and monopolization by reputable journals; as well as micro-level barriers such as navigating manuscript production, language, journal selection, and fees. Two editors-in-chief, Seye and Orli, shed some light on these processes, and offer unique perspectives, and advice including pursuing publications with a “healthy dose of disrespect” and endeavoring to reach out to editors with your questions and concerns.Guest informationProf. Seye Abimbola is a senior lecturer at the University of Sydney, where he studies health system governance and epistemic justice in global health. He is also the current Prince Claus Chair in Equity and Development at Utrecht University and the editor in chief of BMJ Global Health. Connect with Seye on Twitter @seyeabimbola, and to learn more about his work, visit: https://www.sydney.edu.au/medicine-health/about/our-people/academic-staff/seye-abimbola.htmlDr. Orli G. Bahcall, Editor-in-Chief of Cell Genomics, has over 17 years of editorial experience, previously serving as genetics and genomics editor at Nature and Nature Genetics and Chief Editor of Nature Reviews Genetics. Orli brings with her to Cell Genomics a love of science, a passion for collaborative research, and a commitment to openness and transparency in research, as well as in the editorial and review processes. Orli received her Ph.D. in epidemiology and mathematical modeling from Imperial College, London, her MS from Oxford University as a Marshall Scholar, and her BS from the Massachusetts Institute of Technology. Connect with Orli on Twitter @obahcall. To learn more about her work, visit:https://www.cell.com/cell-genomics/home or her LinkedIn page: www.linkedin.com/in/orli-bahcall-6b81b11a3ResourcesScholary Kitchen blog (https://scholarlykitchen.sspnet.org/2021/01/28/open-access-and-global-south-it-is-more-than-a-matter-of-inclusion/ )Support open access in global south (https://www.research4life.org/news/open-access-inclusive-as-it-wants-to-be/)Challenges in open access (https://www.enago.com/academy/challenges-in-growth-of-open-access-publishing/)BMJ benefits of open access(https://www.bmj.com/company/openaccess/open-access-faq/)Is the staggeringly profitable business of scientific publishing bad for science? (https://www.theguardian.com/science/2017/jun/27/profitable-business-scientific-publishing-bad-for-science)Big publishers, bigger profits (https://core.ac.uk/download/pdf/304667847.pdf)Barriers to publishing (https://bmcmedresmethodol.biomedcentral.com/articles/10.1186/s12874-017-0371-z)Language barriers (https://pubrica.com/academy/journal-selection/english-language-as-a-barrier-to-publish-in-high-impact-factor-journals-quick-tips-to-overcome/)Global inclusivity report 2020 (https://www.emeraldgrouppublishing.com/global-2020-inclusivity-report)AcknowledgmentsEditing by Mariana Vaz, https://www.marianacpvaz.com/Research: Nagehan Ramazanoglu; Alice MatimbaProducers: Christine Boinett (Creator and Executive producer), Alice Matimba (Senior Producer), Isabela Malta (Producer and Research Lead), Emmanuela Oppong (Producer), Nagehan Ramazanoglu (Producer), Catherine Holmes (Marketing Lead).Host: Alice Matimba & Emmanuela OppongMedia and Marketing: Catherine HolmesMusic: https://freesound.org/s/477388/Contact usEmail: enquiries@yourdigimentor.netTwitter: @mentor_podcastSupportWCS: https://www.wellcomeconnectingscience.org/WSI: https://www.sanger.ac.ukSESH: https://www.seshglobal.org/

In this episode of the Epigenetics Podcast, we caught up with Marieke Oudelaar from the Max Planck Institute for Biophysical Chemistry to talk about her work on chromatin organization during development and disease. Marieke Oudelaar and her team focus on on developing high-resolution Chromosome Conformation Capture (3C) based techniques, like low-input Capture-C, Tri-C, and Tiled-C. Those techniques are then used in combination with other genomic techniques, genetic perturbations, and computational approaches to investigate the 3D structure of chromatin in development and disease. The team focused on the interplay between genome organisation and regulation during mammalian differentiation, and how perturbations in these processes contribute to human disease, including cancer.   References Oudelaar, A. M., Davies, J. O. J., Downes, D. J., Higgs, D. R., & Hughes, J. R. (2017). Robust detection of chromosomal interactions from small numbers of cells using low-input Capture-C. Nucleic Acids Research, 45(22), e184–e184. https://doi.org/10.1093/nar/gkx1194 Oudelaar, A. M., Davies, J. O. J., Hanssen, L. L. P., Telenius, J. M., Schwessinger, R., Liu, Y., Brown, J. M., Downes, D. J., Chiariello, A. M., Bianco, S., Nicodemi, M., Buckle, V. J., Dekker, J., Higgs, D. R., & Hughes, J. R. (2018). Single-allele chromatin interactions identify regulatory hubs in dynamic compartmentalized domains. Nature Genetics, 50(12), 1744–1751. https://doi.org/10.1038/s41588-018-0253-2 Oudelaar, A. M., Beagrie, R. A., Gosden, M., de Ornellas, S., Georgiades, E., Kerry, J., Hidalgo, D., Carrelha, J., Shivalingam, A., El-Sagheer, A. H., Telenius, J. M., Brown, T., Buckle, V. J., Socolovsky, M., Higgs, D. R., & Hughes, J. R. (2020). Dynamics of the 4D genome during in vivo lineage specification and differentiation. Nature Communications, 11(1), 2722. https://doi.org/10.1038/s41467-020-16598-7 Aljahani, A., Hua, P., Karpinska, M. A., Quililan, K., Davies, J. O. J., & Oudelaar, A. M. (2021). Analysis of sub-kilobase chromatin topology reveals nano-scale regulatory interactions with variable dependence on cohesin and CTCF [Preprint]. Genomics. https://doi.org/10.1101/2021.08.10.455796   Related Episodes Hi-C and Three-Dimensional Genome Sequencing (Erez Lieberman Aiden) Unraveling Mechanisms of Chromosome Formation (Job Dekker) Ultraconserved Enhancers and Enhancer Redundancy (Diane Dickel)   Contact Active Motif on Twitter Epigenetics Podcast on Twitter Active Motif on LinkedIn Active Motif on Facebook Email: podcast@activemotif.com

In this episode of the Epigenetics Podcast, we caught up with Marnie Blewitt from the Walter and Eliza Hall Institute of Medical Research to talk about her work on the role of SMCHD1 in Development and Disease. The Laboratory of Marnie Blewitt focuses finding inhibitors or activators for the epigenetic regulator SMCHD1. Marnie Blewitt identified and characterized this protein during her PhD and the findings were published in 2008 in Nature Genetics. Since then, she and her team were able to investigate the function of this protein further. By doing so, they showed the involvement of SMCHD1 in cancer and several other diseases. Currently the lab is screening for small molecules that can act as inhibitors or activators of SMCHD1 the former as potential treatments for facioscapulohumeral muscular dystrophy, the latter for Prader Willi and Schaaf-Yang syndromes, both of which have no current targeted treatments.   References Blewitt, M. E., Gendrel, A.-V., Pang, Z., Sparrow, D. B., Whitelaw, N., Craig, J. M., Apedaile, A., Hilton, D. J., Dunwoodie, S. L., Brockdorff, N., Kay, G. F., & Whitelaw, E. (2008). SmcHD1, containing a structural-maintenance-of-chromosomes hinge domain, has a critical role in X inactivation. Nature Genetics, 40(5), 663–669. https://doi.org/10.1038/ng.142 Leong, H. S., Chen, K., Hu, Y., Lee, S., Corbin, J., Pakusch, M., Murphy, J. M., Majewski, I. J., Smyth, G. K., Alexander, W. S., Hilton, D. J., & Blewitt, M. E. (2013). Epigenetic Regulator Smchd1 Functions as a Tumor Suppressor. Cancer Research, 73(5), 1591–1599. https://doi.org/10.1158/0008-5472.CAN-12-3019 Gordon, C. T., Xue, S., Yigit, G., Filali, H., Chen, K., Rosin, N., Yoshiura, K., Oufadem, M., Beck, T. J., McGowan, R., Magee, A. C., Altmüller, J., Dion, C., Thiele, H., Gurzau, A. D., Nürnberg, P., Meschede, D., Mühlbauer, W., Okamoto, N., … Reversade, B. (2017). De novo mutations in SMCHD1 cause Bosma arhinia microphthalmia syndrome and abrogate nasal development. Nature Genetics, 49(2), 249–255. https://doi.org/10.1038/ng.3765   Related Episodes Epigenetics and X-Inactivation (Edith Heard) Biophysical Modeling of 3-D Genome Organization (Leonid Mirny) Unraveling Mechanisms of Chromosome Formation (Job Dekker)   Contact Active Motif on Twitter Epigenetics Podcast on Twitter Active Motif on LinkedIn Active Motif on Facebook Email: podcast@activemotif.com

In this episode of the Epigenetics Podcast, we caught up with Efrat Shema from the Weizmann Institute of Science to talk about her work on Single Molecule Imaging of chromatin, and the analysis of nucleosomes circulating in plasma. In ChIP-Seq experiments the peak you get as a read out represents an average over, most often, millions of cells. Furthermore, one often does not know if that peak represents one or more than one nucleosome. If you then want to study multiple marks at the same time, the question remains: do those modifications occur at the same time, in the same cell? The Laboratory of Efrat Shema works on answering those questions by developing methods to study the modification patterns on single nucleosomes with single molecule imaging. With that it is possible to study single nucleosomes in a high throughout manner to identify the modifications they are decorated with. A subsequent sequencing step makes it possible to identify the genomic location of that nucleosome.   References Shema, E., Bernstein, B. E., & Buenrostro, J. D. (2019). Single-cell and single-molecule epigenomics to uncover genome regulation at unprecedented resolution. Nature Genetics, 51(1), 19–25. https://doi.org/10.1038/s41588-018-0290-x Shema, E., Jones, D., Shoresh, N., Donohue, L., Ram, O., & Bernstein, B. E. (2016). Single-molecule decoding of combinatorially modified nucleosomes. Science, 352(6286), 717–721. https://doi.org/10.1126/science.aad7701 Shema, E., Kim, J., Roeder, R. G., & Oren, M. (2011). RNF20 Inhibits TFIIS-Facilitated Transcriptional Elongation to Suppress Pro-oncogenic Gene Expression. Molecular Cell, 42(4), 477–488. https://doi.org/10.1016/j.molcel.2011.03.011 Shema, E., Tirosh, I., Aylon, Y., Huang, J., Ye, C., Moskovits, N., Raver-Shapira, N., Minsky, N., Pirngruber, J., Tarcic, G., Hublarova, P., Moyal, L., Gana-Weisz, M., Shiloh, Y., Yarden, Y., Johnsen, S. A., Vojtesek, B., Berger, S. L., & Oren, M. (2008). The histone H2B-specific ubiquitin ligase RNF20/hBRE1 acts as a putative tumor suppressor through selective regulation of gene expression. Genes & Development, 22(19), 2664–2676. https://doi.org/10.1101/gad.1703008   Related Episodes ATAC-Seq, scATAC-Seq and Chromatin Dynamics in Single-Cells (Jason Buenrostro) Investigating the Dynamics of Epigenetic Plasticity in Cancer with Single Cell Technologies (Céline Vallot) The Past, Present, and Future of Epigenetics (Joe Fernandez, founder of Active Motif)   Contact Active Motif on Twitter Epigenetics Podcast on Twitter Active Motif on LinkedIn Active Motif on Facebook Email: podcast@activemotif.com

This week Harry is joined by Kevin Davies, author of the 2020 book Editing Humanity: The CRISPR Revolution and the New Era of Genome Editing. CRISPR—an acronym for Clustered Regularly Interspaced Short Palindromic Repeats—consists of DNA sequences that evolved to help bacteria recognize and defend against viral invaders, as a kind of primitive immune system. Thanks to its ability to precisely detect and cut other DNA sequences, CRISPR has spread to labs across the world in the nine years since Jennifer Doudna and Emmanuel Charpentier published a groundbreaking 2012 Science paper describing how the process works. The Nobel Prize committee recognized the two scientists for the achievement in 2020, one day after Davies' book came out. The book explains how CRISPR was discovered, how it was turned into an easily programmable tool for cutting and pasting stretches of DNA, how most of the early pioneers in the field have now formed competing biotech companies, and how the technology is being used to help patients today—and in at least one famous case, misused. Today's interview covers all of that ground and more.Davies is a PhD geneticist who has spent most of his career in life sciences publishing. After his postdoc with Harvey Lodish at the Whitehead Institute, Davies worked as an assistant editor at Nature, the founding editor of Nature Genetics (Nature's first spinoff journal), editor-in-chief at Cell Press, founding editor-in-chief of the Boston-based publication Bio-IT World, and publisher of Chemical & Engineering News. In 2018 he helped to launch The CRISPR Journal, where he is the executive editor. Davies' previous books include Breakthrough (1995) about the race to understand the BRCA1 breast cancer gene, Cracking the Genome (2001) about the Human Genome Project, The $1,000 Genome (2010) about next-generation sequencing companies, and DNA (2017), an updated version of James Watson's 2004 book, co-authored with Watson and Andrew Berry.Please rate and review MoneyBall Medicine on Apple Podcasts! Here's how to do that from an iPhone, iPad, or iPod touch:1. Open the Podcasts app on your iPhone, iPad, or Mac. 2. Navigate to the page of the MoneyBall Medicine podcast. You can find it by searching for it or selecting it from your library. 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Your review may not be immediately visible.Full TranscriptHarry Glorikian: I'm Harry Glorikian, and this is MoneyBall Medicine, the interview podcast where we meet researchers, entrepreneurs, and physicians who are using the power of data to improve patient health and make healthcare delivery more efficient. You can think of each episode as a new chapter in the never-ending audio version of my 2017 book, “MoneyBall Medicine: Thriving in the New Data-Driven Healthcare Market.” If you like the show, please do us a favor and leave a rating and review at Apple Podcasts.Harry Glorikian: We talk a lot on the show about how computation and data are changing the way we develop new medicines and the way we deliver healthcare. Some executives in the drug discovery business speak of the computing and software side of the business as the “dry lab” —to set it apart from the “wet labs” where scientists get their hands dirty working with actual cells, tissues, and reagents.But the thing is, recent progress on the wet lab side of biotech has been just as amazing as progress in areas like machine learning. And this week, my friend Kevin Davies is here to talk about the most powerful tool to come along in the last decade, namely, precise gene editing using CRISPR.Of course, CRISPR-based gene editing has been all over the news since Jennifer Doudna and Emmanuel Charpentier published a groundbreaking Science paper in 2012 describing how the process works in the lab. That work earned them a Nobel Prize in medicine just eight years later, in 2020.But what's not as well-known is the story of how CRISPR was discovered, how it was turned into an easily programmable tool for cutting and pasting stretches of DNA, how most of the early pioneers in the field have now formed competing biotech companies, and how the technology is being used to help patients today—and in at least one famous case, misused.Kevin put that whole fascinating story together in his 2020 book Editing Humanity. And as the executive editor of The CRISPR Journal, the former editor-in-chief of Bio-IT World, the founding editor at Nature Genetics, and the author of several other important books about genomics, Kevin is one of the best-placed people in the world to tell that story. Here's our conversation.Harry Glorikian: Kevin, welcome to the show. Kevin Davies: Great to see you again, Harry. Thanks for having me on.Harry Glorikian: Yeah, no, I mean, I seem to be saying this a lot lately, it's been such a long time since, because of this whole pandemic, nobody's really seeing anybody on a regular basis. I want to give everybody a chance to hear about, you had written this book called Editing Humanity, which is, you know, beautifully placed behind you for, for product placement here. But I want to hear, can you give everybody sort of an overview of the book and why you feel that this fairly technical laboratory tool called CRISPR is so important that you needed to write a book about it?Kevin Davies: Thank you. Yes. As you may know, from some of my previous “bestsellers” or not, I've written about big stories in genetics because that's the only thing I'm remotely qualified to write about. I trained as a human geneticist in London and came over to do actually a pair of post-docs in the Boston area before realizing my talents, whatever they might be, certainly weren't as a bench researcher. So I had to find another way to stay in science but get away from the bench and hang up the lab coats.So moving into science publishing and getting a job with Nature and then launching Nature Genetics was the route for me. And over the last 30 years, I've written four or five books that have all been about, a) something big happening in genomics, b) something really big that will have both medical and societal significance, like the mapping and discovery of the BRCA1 breast cancer gene in the mid-90s, the Human Genome Project at the turn of the century, and then the birth and the dawn of consumer genetics and personalized medicine with The $1,000 Genome. And the third ingredient I really look for if I'm trying to reach a moderately, significantly large audience is for the human elements. Who are they, the heroes and the anti heroes to propel the story? Where is the human drama? Because, you know, we all love a good juicy, gossipy piece of story and rating the good guys and the bad guys. And CRISPR, when it first really took off in 2012, 2013 as a gene editing tool a lot of scientists knew about this. I mean, these papers are being published in Science in particular, not exactly a specialized journal, but I was off doing other things and really missed the initial excitement, I'm embarrassed to say. It was only a couple of years later, working on a sequel to Jim Watson's DNA, where I was tasked with trying to find and summarize the big advances in genomic technology over the previous decade or whatever, that I thought, well, this CRISPR thing seems to be taking off and the Doudnas and the Charpentiers are, you know, winning Breakthrough Prizes and being feted by celebrities. And it's going on 60 Minutes. They're going to make a film with the Rock, Dwayne Johnson. What the heck is going on. And it took very little time after that, for me to think, you know, this is such an exciting, game-changing disruptive technology that I've got to do two things. I've gotta, a) write a book and b) launch a journal, and that's what I did. And started planning at any rate in sort of 2016 and 17. We launched the CRISPR Journal at the beginning of 2018. And the book Editing Humanity came out towards the end of 2020. So 2020, literally one day before the Nobel Prize—how about that for timing?—for Doudna and Charpentier for chemistry last year. Harry Glorikian: When I think about it, I remember working with different companies that had different types of gene editing technology you know, working with some particularly in the sort of agriculture space, cause it a little bit easier to run faster than in the human space. And you could see what was happening, but CRISPR now is still very new. But from the news and different advances that are happening, especially here in the Boston area, you know, it's having some real world impacts. If you had to point to the best or the most exciting example of CRISPR technology helping an actual patient, would you say, and I've heard you say it, Victoria Gray, I think, would be the person that comes to mind. I've even, I think in one of your last interviews, you said something about her being, you know, her name will go down in history. Can you explain the technology that is helping her and what some of the similar uses of CRISPR might be?Kevin Davies: So the first half of Editing Humanity is about the heroes of CRISPR, how we, how scientists turned it from this bizarre under-appreciated bacterial antiviral defense system and leveraged it and got to grips with it, and then figured out ways to turn it into a programmable gene editing technology. And within a year or two of that happening that the classic Doudna-Charpentier paper came out in the summer of 2012. Of course the first wave of biotech companies were launched by some of the big names, indeed most of the big names in CRISPR gene editing hierarchies. So Emmanuel Charpentier, Nobel Laureate, launched CRISPR Therapeutics, Jennifer Doudna co-founded Editas Medicine with several other luminaries. That didn't go well for, for reasons of intellectual property. So she withdrew from Editas and became a co-founder of Intellia Therapeutics as well as her own company, Caribou, which just went public, and Feng Zhang and others launched Editas Medicine. So we had this sort of three-way race, if you will, by three CRISPR empowered gene editing companies who all went public within the next two or three years and all set their sights on various different genetic Mendelian disorders with a view to trying to produce clinical success for this very powerful gene editing tool. And so, yes, Victoria Gray is the first patient, the first American patient with sickle cell anemia in a trial that is being run by CRISPR Therapeutics in close association with Vertex Pharmaceuticals. And that breakthrough paper, as I think many of your listeners will know, came out right at the end of 2020 published in the New England Journal of Medicine. Doesn't get much more prestigious than that. And in the first handful of patients that CRISPR Therapeutics have edited with a view to raising the levels of fetal hemoglobin, fetal globin, to compensate for the defective beta globin that these patients have inherited, the results were truly spectacular.And if we fast forward now to about two years after the initial administration, the initial procedures for Victoria Gray and some of her other volunteer patients, the results still look as spectacular. Earlier this year CRISPR Therapeutics put out of sort of an update where they are saying that the first 20 or 24 patients that they have dosed with sickle cell and beta thallasemia are all doing well. There've been little or no adverse events. And the idea of this being a once and done therapy appears very well founded. Now it's not a trivial therapy. This is ex-vivo gene editing as obviously rounds of chemotherapy to provide the room for the gene edited stem cells to be reimplanted into the patient. So this is not an easily scalable or affordable or ideal system, but when did we, when will we ever able to say we've pretty much got a cure for sickle cell disease? This is an absolutely spectacular moment, not just for CRISPR, but for medicine, I think, overall. And Victoria Gray, who's been brilliantly profiled in a long running series on National Public Radio, led by the science broadcaster Rob Stein, she is, you know, we, we can call her Queen Victoria, we can call it many things, but I really hope that ,it's not just my idea, that she will be one of those names like Louise Brown and other heroes of modern medicine, that we look and celebrate for decades to come.So the sickle cell results have been great, and then much more recently, also in the New England Journal, we have work led by Intellia Therapeutics, one of the other three companies that I named, where they've been also using CRISPR gene editing, but they've been looking at a rare liver disease, a form of amyloidosis where a toxic protein builds up and looking to find ways to knock out the production of that abnormal gene.And so they've been doing in vivo gene editing, really using CRISPR for the first time. It's been attempted using other gene editing platforms like zinc fingers, but this is the first time that I think we can really say and the New England Journal results prove it. In the first six patients that have been reported remarkable reductions in the level of this toxic protein far, not far better, but certainly better than any approved drugs that are currently on the market. So again, this is a very, very exciting proof of principle for in vivo gene editing, which is important, not just for patients with this rare liver disorder, but it really gives I think the whole field and the whole industry enormous confidence that CRISPR is safe and can be used for a growing list of Mendelian disorders, it's 6,000 or 7,000 diseases about which we know the root genetic cause, and we're not going to tackle all of them anytime soon, but there's a list of ones that now are within reach. And more and more companies are being launched all the time to try and get at some of these diseases.So as we stand here in the summer of 2021, it's a really exciting time. The future looks very bright, but there's so much more to be done. Harry Glorikian: No, we're just at the beginning. I mean, I remember when I first saw this, my first question was off target effects, right? How are we going to manage that? How are they going to get it to that place that they need to get it to, to have it to that cell at that time, in the right way to get it to do what it needs to do. And you know, all these sorts of technical questions, but at the same time, I remember I'm going to, trying to explain this to my friends. I'm like, “You don't understand, this can change everything.” And now a high school student, I say this to people and they look at me strangely, a high school student can order it and it shows up at your house.Kevin Davies: Yeah, well, this is why I think, and this is why one reason why CRISPR has become such an exciting story and receives the Nobel Prize eight years after the sort of launch publication or the first demonstration of it as a gene editing tool. It is so relatively easy to get to work. It's truly become a democratized or democratizing technology. You don't need a million-dollar Illumina sequencer or anything. And so labs literally all around the world can do basic CRISPR experiments. Not everyone is going to be able to launch a clinical trial. But the technology is so universally used, and that means that advances in our understanding of the mechanisms, new tools for the CRISPR toolbox new pathways, new targets, new oftware, new programs, they're all coming from all corners of the globe to help not just medicine, but many other applications of CRISPR as well.Harry Glorikian: Yeah. I always joke about like, there, there are things going on in high school biology classes now that weren't, available, when I was in college and even when we were in industry and now what used to take an entire room, you can do on a corner of a lab bench.Kevin Davies: Yeah. Yeah. As far as the industry goes we mentioned three companies. But you know, today there's probably a dozen or more CRISPR based or gene editing based biotech companies. More undoubtedly are going to be launched before the end of this year. I'm sure we'll spend a bit of time talking about CRISPR 2.0, it seems too soon to be even thinking about a new and improved version of CRISPR, but I think there's a lot of excitement around also two other Boston-based companies, Beam Therapeutics in Cambridge and Verve Therapeutics both of which are launching or commercializing base editing. So base editing is a tool developed from the lab of David Lu of the Broad Institute [of MIT and Harvard]. And the early signs, again, this technology is only five or six years old, but the early signs of this are incredibly promising. David's team, academic team, had a paper in Nature earlier this year, really reporting successful base editing treatment of sickle cell disease in an animal model, not by raising the fetal globin levels, which was sort of a more indirect method that is working very well in the clinic, but by going right at the point mutation that results in sickle cell disease and using given the chemical repertoire of base editing.Base editing is able to make specific single base changes. It can't do the full repertoire of single base changes. So there are some limitations on researchers' flexibility. So they were unable to flip the sickle cell variant back to the quote unquote wild type variants, but the change they were able to make is one that they can live with, we can live with because it's a known benign variant, a very rare variant that has been observed in other, in rare people around the world. So that's completely fine. It's the next best thing. And so that looks very promising. Beam Therapeutics, which is the company that David founded or co-founded is trying a related approach, also going right at the sickle cell mutation. And there are other companies, including one that Matthew Porteus has recently founded and has gone public called Graphite Bio.So this is an exciting time for a disease sickle cell disease that has been woefully neglected, I think you would agree, both in terms of basic research, funding, medical prioritization, and medical education. Now we have many, many shots on goal and it doesn't really, it's not a matter of one's going to win and the others are going to fall by the wayside. Just like we have many COVID vaccines. We'll hopefully have many strategies for tackling sickle cell disease, but they are going to be expensive. And I think you know the economics better than I do. But I think that is the worry, that by analogy with gene therapies that have been recently approved, it's all, it's really exciting that we can now see the first quote, unquote cures in the clinic. That's amazingly exciting. But if the price tag is going to be $1 million or $2 million when these things are finally approved, if and when, that's going to be a rather deflating moment. But given the extraordinary research resources that the CRISPRs and Intellias and Beams and Graphites are pouring into this research, obviously they've got to get some return back on their investment so that they can plow it back into the company to develop the next wave of of gene editing therapies. So you know, it's a predicament Harry Glorikian: One of these days maybe I have to have a show based on the financial parts of it. Because there's a number of different ways to look at it. But just for the benefit of the listeners, right, who may not be experts, how would you explain CRISPR is different from say traditional gene therapies. And is CRISPR going to replace older methods of, of gene therapy or, or will they both have their place? Kevin Davies: No, I think they'll both have their place. CRISPR and, and these newer gene editing tools, base editing and another one called prime editing, which has a company behind it now called Prime Medicine, are able to affect specific DNA changes in the human genome.So if you can target CRISPR, which is an enzyme that cuts DNA together with a little program, the GPS signal is provided in the form of a short RNA molecule that tells the enzyme where to go, where to go in the genome. And then you have a couple of strategies. You can either cut the DNA at the appropriate target site, because you want to inactivate that gene, or you just want to scramble the sequence because you want to completely squash the expression of that gene. Or particularly using the newer forms of gene editing, like base editing, you can make a specific, a more nuanced, specific precision edit without, with one big potential advantage in the safety profile, which is, you're not completely cutting the DNA, you're just making a nick and then coaxing the cell's natural repair systems to make the change that you sort of you're able to prime.So there are many diseases where this is the way you want to go, but that does not in any way invalidate the great progress that we're making in traditional gene therapy. So for example today earlier today I was recording an interview or for one of my own programs with Laurence Reid, the CEO of Decibel Therapeutics, which is looking at therapies for hearing loss both genetic and other, other types of hearing disorders.And I pushed him on this. Aren't you actually joinomg with the gene editing wave? And he was very circumspect and said, no, we're very pleased, very happy with the results that we're getting using old fashioned gene replacement therapy. These are recessive loss of function disorders. And all we need to do is get the expression of some of the gene back. So you don't necessarily need the fancy gene editing tools. If you can just use a an AAV vector and put the healthy gene back into the key cells in the inner ear. So they're complimentary approaches which is great.Harry Glorikian: So, you know, in, in this podcast, I try to have a central theme when I'm talking to people. The relationships of big data, computation, advances in new drugs, and other ways to keep people healthy. So, you know, like question-wise, there's no question in my mind that the whole genomics revolution that started in the ‘90s, and I was happy to be at Applied Biosystems when we were doing that, would have been impossible in the absence of the advances in computing speed and storage in the last three decades. I think computing was the thing that held up the whole human genome, which gave us the book of life that CRISPR is now allowing us to really edit. But I wonder if you could bring us sort of up-to-date and talk about the way CRISPR and computation are intertwined. What happens when you combine precision of an editing tool like CRISPR with the power of machine learning and AI tools to find meaning and patterns in that huge genetic ball? Kevin Davies: Yeah. Well, yeah. I'm got to tread carefully here, but I think we are seeing papers from some really brilliant labs that are using some of the tools that you mentioned. AI and machine learning with a view to better understanding and characterizing some of the properties and selection criteria of some of these gene editing tools. So you mentioned earlier Harry, the need to look out for safety and minimize the concern of off-target effects. So I think by using some of these some algorithms and AI tools, researchers have made enormous strides in being able to design the programmable parts of the gene editing constructs in such a way that you increase the chances that they're going to go to the site that you want them to go to, and nnot get hung up latching onto a very similar sequence that's just randomly cropped up on the dark side of the genome, across the nucleus over there. You don't want that to happen. And I don't know that anybody would claim that they have a failsafe way to guarantee that that could never happen. But the you know, the clinical results that we've seen and all the preclinical results are showing in more and more diseases that we've got the tools and learned enough now to almost completely minimize these safety concerns. But I think everyone, I think while they're excited and they're moving as fast as they can, they're also doing this responsibly. I mean, they, they have to because no field, gene therapy or gene editing really wants to revisit the Jesse Gelsinger tragedy in 1999, when a teenage volunteer died in volunteering for a gene therapy trial at Penn of, with somebody with a rare liver disease. And of course that, that setback set back the, entire field of gene therapy for a decade. And it's really remarkable that you know, many of the sort of pioneers in the field refuse to throw in the towel, they realized that they had to kind of go back to the drawing board, look at the vectors again, and throw it out. Not completely but most, a lot of the work with adenoviruses has now gone by the wayside. AAV is the new virus that we hear about. It's got a much better safety profile. It's got a smaller cargo hold, so that's one drawback, but there are ways around that. And the, the explosion of gene therapy trials that we're seeing now largely on the back of AAV and now increasingly with, with non-viral delivery systems as well is, is very, very gratifying. And it's really delivery. I think that is now the pain point. Digressing from your question a little bit, but delivery, I think is now the big challenge. It's one thing to contemplate a gene therapy for the eye for rare hereditary form of blindness or the ear. Indeed those are very attractive sites and targets for some of these early trials because of the quantities that you need to produce. And the localization, the, the physical localization, those are good things. Those help you hit the target that you want to. But if you're contemplating trying something for Duchenne muscular dystrophy or spinal muscular atrophy, or some of the diseases of the brain, then you're going to need much higher quantities particularly for muscular disorders where, you run into now other challenges, including, production and manufacturing, challenges, and potentially safeguarding and making sure that there isn't an immune response as well. That's another, another issue that is always percolating in the background.But given where we were a few years ago and the clinical progress that we've talked about earlier on in the show it, I think you can safely assume that we've collectively made enormous progress in, in negating most, if not all of these potential safety issues.Harry Glorikian: No, you know, it's funny, I know that people will say like, you know, there was a problem in this and that. And I look at like, we're going into uncharted territories and it has to be expected that you just…you've got people that knew what they were doing. All of these people are new at what they are doing. And so you have to expect that along the way everything's not going to go perfectly. But I don't look at it as a negative. I look at it as, they're the new graduating class that's going to go on and understand what they did right. Or wrong, and then be able to modify it and make an improvement. And, you know, that's what we do in science. Kevin Davies: Well, and forget gene editing—in any area of drug development and, and pharmaceutical delivery, things don't always go according to plan. I'm sure many guests on Moneyball Medicine who have had to deal with clinical trial failures and withdrawing drugs that they had all kinds of high hopes for because we didn't understand the biology or there was some other reaction within, we didn't understand the dosing. You can't just extrapolate from an animal model to humans and on and on and on. And so gene editing, I don't think, necessarily, should be held to any higher standard. I think the CRISPR field has already in terms of the sort of market performance, some of the companies that we've mentioned, oh my God, it's been a real roller coaster surprisingly, because every time there's been a paper published in a prominent journal that says, oh my God, there's, there's a deletion pattern that we're seeing that we didn't anticipate, or we're seeing some immune responses or we're seeing unusual off target effects, or we're seeing P53 activation and you know, those are at least four off the top of my head. I'm sure there've been others. And all had big transient impact on the financial health of these companies. But I think that was to be expected. And the companies knew that this was just an overreaction. They've worked and demonstrated through peer review publications and preclinical and other reports that these challenges have been identified, when known about, pretty much completely have been overcome or are in the process of being overcome.So, you know, and we're still seeing in just traditional gene therapy technologies that have been around for 15, 20 years. We're still seeing reports of adverse events on some of those trials. So for gene editing to have come as far as it's common, to be able to look at these two big New England Journal success stories in sickle cell and ATTR amyloidosis, I don't think any very few, except the most ardent evangelists would have predicted we'd be where we are just a few years ago. [musical transition]Harry Glorikian: I want to pause the conversation for a minute to make a quick request. If you're a fan of MoneyBall Medicine, you know that we've published dozens of interviews with leading scientists and entrepreneurs exploring the boundaries of data-driven healthcare and research. And you can listen to all of those episodes for free at Apple Podcasts, or at my website glorikian.com, or wherever you get your podcasts.There's one small thing you can do in return, and that's to leave a rating and a review of the show on Apple Podcasts. It's one of the best ways to help other listeners find and follow the show.If you've never posted a review or a rating, it's easy. All you have to do is open the Apple Podcasts app on your smartphone, search for MoneyBall Medicine, and scroll down to the Ratings & Reviews section. Tap the stars to rate the show, and then tap the link that says Write a Review to leave your comments. It'll only take a minute, but it'll help us out immensely. Thank you! And now back to the show.[musical transition]Harry Glorikian:One of your previous books was called The $1,000 Genome. And when you published that back in 2010, it was still pretty much science fiction that it might be possible to sequence someone's entire genome for $1,000. But companies like Illumina blew past that barrier pretty quickly, and now people are talking about sequencing individual genome for just a few hundred dollars or less. My question is, how did computing contribute to the exponential trends here. And do you wish you'd called your book The $100 Genome?Kevin Davies: I've thought about putting out a sequel to the book, scratching out the 0's and hoping nobody would notice. Computing was yes, of course, a massive [deal] for the very first human genome. Remember the struggle to put that first assembly together. It's not just about the wet lab and pulling the DNA sequences off the machines, but then you know, the rapid growth of the data exposure and the ability to store and share and send across to collaborators and put the assemblies together has been critical, absolutely critical to the development of genomics.I remember people were expressing shock at the $1,000 genome. I called the book that because I heard Craig Venter use that phrase in public for the first time in 2002. And I had just recently published Cracking the Genome. And we were all still recoiling at the billions of dollars it took to put that first reference genome sequence together. And then here's Craig Venter, chairing a scientific conference in Boston saying what we need is the $1,000 genome. And I almost fell off my chair. “what are you? What are you must you're in, you're on Fantasy Island. This is, there's no way we're going to get, we're still doing automated Sanger sequencing. God bless Fred Sanger. But how on earth are you going to take that technology and go from billions of dollars to a couple of thousand dollars. This is insanity.” And that session we had in 2002 in Boston. He had a local, a little episode of America's Got Talent and he invited half a dozen scientists to come up and show what they had. And George Church was one of them. I think Applied Biosystems may have given some sort of talk during that session. And then a guy, a young British guy from a company we'd never heard of called Celexa showed up and showed a couple of pretty PowerPoint slides with colored beads, representing the budding DNA sequence on some sort of chip. I don't know that he showed any data. It was all very pretty and all very fanciful. Well guess what? They had the last laugh. Illumina bought that company in 2006. And as you said, Harry you know, I think when, when they first professed to have cracked the $1,000 dollar genome barrier, a few people felt they needed a pinch of salt to go along with that. But I think now, yeah, we're, we're, we're well past that. And there are definitely outfits like BGI, the Beijing Genomics Institute being one of them, that are touting new technologies that can get us down to a couple of hundred. And those were such fun times because for a while there Illumina had enormous competition from companies like 454 and Helicose and PacBio. And those were fun heady times with lots and lots of competition. And in a way, Illumina's had it a little easy, I think over the last few years, but with PacBio and Oxford Nanopore gaining maturity both, both in terms of the technology platforms and their business strategy and growth, I think Illumina' gonna start to feel a little bit more competition in the long read sequence space. And one is always hearing whispers of new companies that may potentially disrupt next-gen sequencing. And that would be exciting because then we'd have an excuse to write another book. Harry Glorikian: Well, Kevin, start writing because I actually think we're there. I think there are a number of things there and you're right, I think Illumina has not had to bring the price down as quickly because there hasn't been competition. And you know, when I think about the space is, if you could do a $60 genome, right, it starts to become a rounding error. Like what other business models and opportunities now come alive? And those are the things that excite me. All right. But so, but you have a unique position as editor of the journal of CRISPR and the former editor of a lot of prominent, you know, publications, Nature Genetics, Bio-IT World, Chemical & Engineering News. Do you think that there's adequate coverage of the biological versus the computing side of it? Because I, I have this feeling that the computing side still gets a little overlooked and underappreciated. Kevin Davies: I think you're right. I mean I think at my own company Genetic Engineering News, we still have such deep roots in the wet lab vision and version of biotechnology that it takes a conscious effort to look and say, you know, that's not where all the innovation is happening. Bio-IT World, which you mentioned is interesting because we launched that in 2002. It was launched by the publisher IDG, best-known from MacWorld and ComputerWorld and this, this whole family of high-tech publications.And we launched in 2002 was a very thick glossy print magazine. And ironically, you know, we just couldn't find the advertising to sustain that effort, at least in the way that we'd envisioned it. And in 2006 and 2007, your friend and mine Phillips Kuhl, the proprietor of Cambridge Healthtech Institute, kind of put us out of our misery and said, you know what I'll, take the franchise because IDG just didn't know what to do with it anymore. But what he really wanted was the trade show, the production. And even though at the magazine eventually we fell on our sword and eventually put it out of its misery, the trade show went from strength to strength and it'll be back in Boston very soon because he had the vision to realize there is a big need here as sort of supercomputing for life sciences.And it's not just about the raw high-performance computing, but it's about the software, the software tools and data sharing and management. And it's great to go back to that show and see the, you know, the Googles and Amazons and yeah, all the big household names. They're all looking at this because genome technology, as we've discussed earlier has been one of the big growth boom areas for, for their services and their products.Harry Glorikian: Right. I mean, well, if you look at companies like Tempus, right. When I talked to Joel Dudley over there on the show it's, they want to be the Amazon AWS piping for all things genomic analysis. Right. So instead of creating it on your own and building a, just use their platform, basically, so it's definitely a growth area. And at some point, if you have certain disease states, I don't see how you don't get you know, genomic sequencing done, how a physician even today in oncology, how anybody can truly prescribe with all the drugs that are being approved that have, you know, genomic biomarkers associated with them and not use that data.Kevin Davies: On a much lower, lo-fi scale, as I've been doing a lot of reading about sickle cell disease lately, it's clear that a lot of patients who are, of course, as you, as you know, as your listeners know, are mostly African-American because the disease arose in Africa and the carrier status gives carriers a huge health advantage in warding off malaria. So the gene continues to stay, stay high in in frequency. Many African-American patients would benefit from some generic drugs that are available in this country that provide some relief, but aren't aware of it and maybe their physicians aren't completely aware of it either. Which is very sad. And we've neglected the funding of this disease over many decades, whereas a disease like cystic fibrosis, which affects primarily white people of Northern European descent that receives far more funding per capita, per head, than than a disease like sickle cell does. But hopefully that will begin to change as we see the, the potential of some of these more advanced therapies.I think as far as your previous comment. I think one of the big challenges now is how we tackle common diseases. I think we're making so much progress in treating rare Mendelian diseases and we know thousands of them. But it's mental illness and asthma and diabetes you know, diseases that affect millions of people, which have a much more complicated genetic and in part environmental basis.And what can we learn, to your point about having a full genome sequence, what can we glean from that that will help the medical establishment diagnose and treat much more common diseases, not quite as simple as just treating a rare Mendelian version of those diseases? So that's, I think going to be an important frontier over the next decade.Harry Glorikian: Yeah. It's complicated. I think you're going to see as we get more real-world data that's organized and managed well, along with genomic data, I think you'll be able to make more sense of it. But some of these diseases are quite complicated. It's not going to be find one gene, and it's going to give you that answer.But I want to go back to, you can't really talk about CRISPR without talking about this specter of germline editing. And a big part of your book is about this firestorm of criticism and condemnation around, you know, the 2018 when the Chinese researcher He Jankui, I think I said it correctly.Yep.Kevin Davies: He Jankui is how I say it. Close. Harry Glorikian: He announced that he had created twin baby girls with edits to their genomes that were intended to make them immune to HIV, which sort of like—that already made me go, what? But the experiment was, it seems, unauthorized. It seems that, from what I remember, the edits were sloppy and the case spurred a huge global discussion about the ethics of using CRISPR to make edits that would be inherited by future generations. Now, where are we in that debate now? I mean, I know the National Academy of Sciences published a list of criteria, which said, don't do that. Kevin Davies: It was a little more nuanced than that. It wasn't don't do that. It was, there is a very small window through which we could move through if a whole raft of criteria are met. So they, they refuse to say hereditary genome editing should be banned or there should be a moratorium. But they said it should not proceed until we do many things. One was to make sure it is safe. We can't run before we can walk. And by that, I mean, we've got to first demonstrate—because shockingly, this hasn't been done yet—that genome editing can be done safely in human embryos. And in the last 18 months there've been at least three groups, arguably the three leading groups in terms of looking at genetic changes in early human embryos, Kathy Niakan in London, Shoukhrat Mitalipov in Oregon, and Dieter Egli in New York, who all at roughly the same time published and reports that said, or posted preprints at least that said, when we attempt to do CRISPR editing experiments in very early human embryos, we're seeing a mess. We're seeing a slew of off-target and even on-target undesirable edits.And I think that says to me, we don't completely understand the molecular biology of DNA repair in the early human embryo. It may be that there are other factors that are used in embryogenesis that are not used after we're born. That's speculation on my part. I may be wrong. But the point is we still have a lot to do to understand, even if we wanted to.And even if everybody said, “Here's a good case where we should pursue germline editing,” we've gotta be convinced that we can do it safely. And at the moment, I don't think anybody can say that. So that's a huge red flag.But let's assume, because I believe in the power of research, let's assume that we're going to figure out ways to do this safely, or maybe we say CRISPR isn't the right tool for human embryos, but other tools such as those that we've touched on earlier in the show base editing or prime editing, or maybe CRISPR 3.0 or whatever that is right now to be published somewhere. [Let's say ] those are more safe, more precise tools. Then we've got to figure out well, under what circumstances would we even want to go down this road? And the pushback was quite rightly that, well, we already have technologies that can safeguard against families having children with genetic diseases. It's called IVF and pre-implantation genetic diagnosis. So we can select from a pool of IVF embryos. The embryos that we can see by biopsy are safe and can therefore be transplanted back into the mother, taken to term and you know, a healthy baby will emerge.So why talk about gene editing when we have that proven technology? And I think that's a very strong case, but there are a small number of circumstances in which pre-implantation genetic diagnosis will simply not work. And those are those rare instances where a couple who want to have a biological child, but have both of them have a serious recessive genetic disease. Sickle cell would be an obvious case in point. So two sickle cell patients who by definition carry two copies of the sickle cell gene, once I have a healthy biological child preimplantation genetic diagnosis, it's not going to help them because there are no healthy embryos from whatever pool that they produce that they can select. So gene editing would be their only hope in that circumstance. Now the National Academy's report that you cited, Harry, did say for serious diseases, such as sickle cell and maybe a few others they could down the road potentially see and condone the use of germline gene editing in those rare cases.But they're going to be very rare, I think. It's not impossible that in an authorized approved setting that we will see the return of genome editing, but that's okay. Of course you can can issue no end of blue ribbon reports from all the world's experts, and that's not going to necessarily prevent some entrepreneur whose ethical values don't align with yours or mine to say, “You know what, there's big money to be made here. I'm going offshore and I'm going to launch a CRISPR clinic and you know, who's going to stop me because I'll be out of the clutches of the authorities.” And I think a lot of people are potentially worried that that scenario might happen. Although if anyone did try to do that, the scientific establishment would come down on them like a ton of bricks. And there'll be a lot of pressure brought to bear, I think, to make sure that they didn't cause any harm.Harry Glorikian: Yeah. It's funny. I would like to not call them entrepreneurs. I like entrepreneurs. I'd like to call them a rogue scientist. Kevin Davies: So as you say, there's the third section of four in Editing Humanity was all about the He Jankui debacle or saga. I had flown to Hong Kong. It's a funny story. I had a little bit of money left in my travel budget and there were two conferences, one in Hong Kong and one in China coming up in the last quarter of 2018. So I thought, well, okay, I'll go to one of them. And I just narrowed, almost a flip of a coin, I think. Okay, let's go to the Hong Kong meeting.It's a bioethics conference since I don't expect it to be wildly exciting, but there are some big speakers and this is an important field for the CRISPR Journal to monitor. So I flew there literally, you know, trying to get some sleep on the long flights from New York and then on landing, turn on the phone, wait for the new wireless signal provider to kick in. And then Twitter just explode on my feed as this very, very astute journalists at MIT Technology Review, Antonio Regalado, had really got the scoop of the century by identifying a registration on a Chinese clinical trial website that he and only he had the foresight and intelligence to sort of see. He had met He Jankui in an off the record meeting, as I described in the book, about a month earlier. A spider sense was tingling. He knew something was up and this was the final clue. He didn't know at that time that the Lulu and Nana, the CRISPR babies that you mentioned, had actually been born, but he knew that there was a pregnancy, at least one pregnancy, from some of the records that he'd seen attached to this registration document. So it was a brilliant piece of sleuthing. And what he didn't know is that the Asociated Press chief medical writer Marilynm Marchion had confidentially been alerted to the potential upcoming birth of these twins by an American PR professional who was working with He Jankui in Shenzhen. So she had been working on an embargoed big feature story that He Jankui and his associates hoped would be the definitive story that would tell the world, we did this quote unquote, “responsibly and accurately, and this is the story that you can believe.” So that story was posted within hours.And of course the famous YouTube videos that He Jankui had recorded announcing with some paternal pride that he had ushered into the world these two gene edited, children, screaming and crying into the world as beautiful babies I think was [the phrase]. And he thought that he was going to become famous and celebrated and lauded by not just the Chinese scientific community, but by the world community for having the ability and the bravery to go ahead and do this work after Chinese researchers spent the previous few years editing human embryos. And he was persuaded that he had to present his work in Hong Kong, because he'd set off such a such an extraordinary firestorm. And I think you've all seen now you're the clips of the videos of him nervously walking onto stage the muffled, the silence, or the only sound in the front row, the only sound in the big auditorium at Hong Kong university—[which] was absolutely packed to the rim, one side of the auditorium was packed with press photographers, hundreds of journalists and cameras clicking—and the shutters clattering was the only, that was the applause that he got as he walked on stage.And to his credit, he tried to answer the questions directly in the face of great skepticism from the audience. The first question, which was posed by David Liu, who had traveled all the way there, who just asked him simply, “What was the unmet medical need that you are trying to solve with this reckless experiment? There are medical steps that you can do, even if the couple that you're trying to help has HIV and you're trying to prevent this from being passed on. There are techniques that you can use sperm washing being one of them. That is a key element of the IVF process to ensure that the no HIV is transmitted.”But he was unable to answer the question in terms of I'm trying to help a family. He'd already moved out and was thinking far, far bigger. Right? And his naiveté was shown in the manuscript that he'd written up and by that point submitted to Nature, excerpts of which were leaked out sometime later.So he went back to Shenzhen and he was put under house arrest after he gave that talk in Hong Kong. And about a year later was sentenced to three years in jail. And so he's, to the best of my knowledge that's where he is. But I often get asked what about the children? As far as we know, there was a third child born about six months later, also gene-edited. We don't even know a name for that child, let alone anything about their health. So one hopes that somebody in the Chinese medical establishment is looking after these kids and monitoring them and doing appropriate tests. The editing, as you said, was very shoddily performed. He knocked out the gene in question, but he did not mimic the natural 32-base deletion in this gene CCR5 that exists in many members of the population that confers, essentially, HIV resistance. So Lulu and Nana on the third child are walking human experiments, sad to say. This should never have been done. Never should have been attempted. And so we hope that he hasn't condemned them to a life of, you know, cancer checkups and that there were no off-target effects. They'll be able to live, hopefully, with this inactivated CCR5 gene, but it's been inactivated in a way that I don't think any, no other humans have ever been recorded with such modifications. So we, we really hope and pray that no other damage has been done. Harry Glorikian: So before we end, I'd love to give you the chance to speculate on the future of medicine in light of CRISPR. Easy, fast, inexpensive genome sequencing, give us access to everybody's genetic code, if they so choose. Machine learning and other forms of AI are helping understand the code and trace interactions between our 20,000 genes. And now CRISPR gives us a way to modify it. So, you know, it feels like [we have] almost everything we need to create, you know, precise, targeted, custom cures for people with genetic conditions. What might be possible soon, in your view? What remaining problems need to be solved to get to this new area of medicine? Kevin Davies: If you know the sequence that has been mutated to give rise to a particular disease then in principle, we can devise a, some sort of gene edit to repair that sequence. It may be flipping the actual base or bases directly, or maybe as we saw with the first sickle cell trial, it's because we understand the bigger genetic pathway. We don't have to necessarily go after the gene mutation directly, but there may be other ways that we can compensate boost the level of a compensating gene.But I think we, we should be careful not to get too carried away. As excited as I am—and hopefully my excitement comes through in Editing Humanity—but for every company that we've just mentioned, you know, you can go on their website and look at their pipeline. And so Editas might have maybe 10 diseases in its cross hairs. And CRISPR [Therapeutics] might have 12 diseases. And Intellia might have 14 diseases and Graphite has got maybe a couple. And Beam Therapeutics has got maybe 10 or 12. And Prime Medicine will hasn't listed any yet, but we'll hopefully have a few announced soon. And so I just reeled off 50, 60, less than a hundred. And some of these are gonna work really, really well. And some are going to be either proven, ineffective or unviable economically because the patient pool is too small. And we've got, how many did we say, 6,000 known genetic diseases. So one of the companies that is particularly interesting, although they would admit they're in very early days yet, is Verve Therapeutics. I touched on them earlier because they're looking at to modify a gene called PCSK9 that is relevant to heart disease and could be a gene modification that many people might undergo because the PCSK9 gene may be perfectly fine and the sequence could be perfectly normal, but we know that if we re remove this gene, levels of the bad cholesterol plummet, and that's usually a good thing as far as heart management goes. So that's an interesting, very interesting study case study, I think, to monitor over the coming years, because there's a company looking at a much larger patient pool potentially than just some of these rare syndromes with unpronounceable names. So the future of CRISPR and gene editing is very bright. I think one of the lessons I took away from CRISPR in Editing Humanity is, looking at the full story, is how this technology, this game-changing gene-editing technology, developed because 25 years ago, a handful of European microbiologists got really interested in why certain microbes were thriving in a salt lake in Southeastern Spain. This is not exactly high-profile, NIH-must-fund-this research. There was a biological question that they wanted to answer. And the CRISPR repeats and the function of those repeats fell out of that pure curiosity, just science for science's sake. And so it's the value of basic investigator-driven, hypothesis-driven research that led to CRISPR being described and then the function of the repeats.And then the story shifted to a yogurt company in Europe that was able to experimentally show how having the right sequence within the CRISPR array could safeguard their cultures against viral infection. And then five years of work people in various groups started to see, were drawn to this like moths to a flame. Jennifer Doudna was intrigued by this from a tip-off from a coffee morning discussion with a Berkeley faculty colleagues, Jill Banfield, a brilliant microbiologist in her own. And then she met meets Emmanuelle Charpentier in Puerto Rico at a conference, and they struck up a friendship and collaboration over the course of an afternoon. And that, why should that have worked? Well, it did, because a year later they're publishing in Science. So it's serendipity and basic research. And if that can work for CRISPR, then I know that there's another technology beginning to emerge from somewhere that may, yet trump CRISPR.And I think the beauty of CRISPR is its universal appeal. And the fact is, it's drawn in so many people, it could be in Japan or China or South Korea or parts of Europe or Canada or the U.S. or South America. Somebody is taking the elements of CRISPR and thinking well, how can we improve it? How can we tweak it?And so this CRISPR toolbox is being expanded and modified and updated all the time. So there's a hugely exciting future for genome medicine. And you know, whether it's a new form of sequencing or a new form of synthetic biology, you know, hopefully your show is going to be filled for many years to come with cool, talented, young energetic entrepreneurs who've developed more cool gadgets to work with our genome and other genomes as well. We haven't even had time to talk about what this could do for rescuing the wooly mammoth from extinction. So fun things, but maybe, maybe another time. Harry Glorikian: Excellent. Well, great to have you on the show. Really appreciate the time. I hope everybody got a flavor for the enormous impact this technology can have. Like you said, we talked about human genome, but there's so many other genomic applications of CRISPR that we didn't even touch. Kevin Davies: Yup. Yup. So you have to read the book. Harry Glorikian: Yeah. I will look forward to the next book. So, great. Thank you so much. Kevin Davies: Thanks for having me on the show, Harry. All the best.Harry Glorikian: Take care.Harry Glorikian: That's it for this week's show. You can find past episodes of MoneyBall Medicine at my website, glorikian.com, under the tab “Podcast.” And you can follow me on Twitter at hglorikian.  Thanks for listening, and we'll be back soon with our next interview.

In this episode of the Epigenetics Podcast, we caught up with Ali Shilatifard from Northwestern University to talk about his work on targeting COMPASS to cure childhood leukemia. The Shilatifard Lab studies childhood leukemia and how it can potentially be treated using epigenetic targets. The team focuses on is SET1/COMPASS, a histone H3 lysine4 methylase. Ali Shilatifard was able to purify and identify its activity, with results published in 2001 in PNAS. This protein complex is conserved from yeast to drosophila to humans. Surprisingly, the Shilatifard Team could show that the catalytic activity of COMPASS is not necessary for viability of drosophila. Furthermore, they found that catalytic activity was not the decisive feature of the complex, but rather its role in the context of chromatin structure, in particular a protein domain that only spans 80 amino acids within the 4000 amino acid protein.   References Miller, T., Krogan, N. J., Dover, J., Erdjument-Bromage, H., Tempst, P., Johnston, M., Greenblatt, J. F., & Shilatifard, A. (2001). COMPASS: A complex of proteins associated with a trithorax-related SET domain protein. Proceedings of the National Academy of Sciences, 98(23), 12902–12907. https://doi.org/10.1073/pnas.231473398 Lin, C., Garruss, A. S., Luo, Z., Guo, F., & Shilatifard, A. (2013). The RNA Pol II Elongation Factor Ell3 Marks Enhancers in ES Cells and Primes Future Gene Activation. Cell, 152(1–2), 144–156. https://doi.org/10.1016/j.cell.2012.12.015 Wang, L., Zhao, Z., Ozark, P. A., Fantini, D., Marshall, S. A., Rendleman, E. J., Cozzolino, K. A., Louis, N., He, X., Morgan, M. A., Takahashi, Y., Collings, C. K., Smith, E. R., Ntziachristos, P., Savas, J. N., Zou, L., Hashizume, R., Meeks, J. J., & Shilatifard, A. (2018). Resetting the epigenetic balance of Polycomb and COMPASS function at enhancers for cancer therapy. Nature Medicine, 24(6), 758–769. https://doi.org/10.1038/s41591-018-0034-6 Morgan, M. A. J., & Shilatifard, A. (2020). Reevaluating the roles of histone-modifying enzymes and their associated chromatin modifications in transcriptional regulation. Nature Genetics, 52(12), 1271–1281. https://doi.org/10.1038/s41588-020-00736-4   Related Episodes Cancer and Epigenetics (David Jones) Transcription and Polycomb in Inheritance and Disease (Danny Reinberg) Epigenetic Mechanisms of Aging and Longevity (Shelley Berger)   Contact Active Motif on Twitter Epigenetics Podcast on Twitter Active Motif on LinkedIn Active Motif on Facebook Email: podcast@activemotif.com

The Fitness of Nature for Mankind featuring Biologist Michael Denton Watch this presentation at- https://youtu.be/9SL_xqSvWqU 36,385 views Discovery Science 123K subscribers Renowned author and biologist Michael Denton gives a new expression to what he calls the “medieval synthesis” of knowledge about life, now enjoying a “Reconquista” thanks to modern science. In charming and lyrical yet rigorous fashion, Denton reviews the intelligent design evidence detailed in his books, including the most recent, The Miracle of the Cell. Join him as he explores the myriad of ways nature is fit not just for life, but for human life. Denton is author of the new book "The Miracle of the Cell" (2020) as well as many other books such as "Nature's Destiny," "Fire-Maker," "The Wonder of Water," and "Evolution: Still a Theory in Crisis." You will never think of nature in the same way after you watch this presentation! Dr. Denton's new book The Miracle of the Cell [https://www.discovery.org/store/produ...] provides compelling evidence that long before life emerged on our planet, the design of the carbon-based cell was foreshadowed in the order of nature, in the exquisite fitness of the laws of nature for this foundational unit of all life on Earth. Nowhere is this fitness more apparent than in the properties of the key atomic constituents of the cell. Each of the atoms of life — including carbon, hydrogen, oxygen, and nitrogen, as well as several metal elements — features a suite of unique properties fine-tuned to serve highly specific, indispensable roles in the cell. Moreover, some of these properties are specifically fit for essential roles in the cells of advanced aerobic organisms like ourselves. Author Michael Denton is a Senior Fellow with Discovery Institute's Center for Science and Culture. He holds an MD from Bristol University and a PhD in biochemistry from King's College in London. His previous books include Evolution: A Theory in Crisis and Nature's Destiny: How the Laws of Biology Reveal Purpose in the Universe. He has published his work in Nature, Nature Genetics, BioSystems, Human Genetics, and Biology and Philosophy. Be sure to check out these related videos: Marcos Eberlin: Earth as the “Presidential Suite” of the Universe https://youtu.be/dFrOWEWHWZg Water, Ultimate Giver of Life, Points to Intelligent Design https://youtu.be/e2i0g1sL-X4 Conversations with William Dembski–Information All the Way Down https://youtu.be/BnVss3QseCw ============================ The Discovery Science News Channel is the official Youtube channel of Discovery Institute's Center for Science & Culture. The CSC is the institutional hub for scientists, educators, and inquiring minds who think that nature supplies compelling evidence of intelligent design. The CSC supports research, sponsors educational programs, defends free speech, and produce articles, books, and multimedia content. For more information visit https://www.discovery.org/id/ http://www.evolutionnews.org/ http://www.intelligentdesign.org/ Follow us on Facebook and Twitter: Twitter: @discoverycsc Facebook: https://www.facebook.com/discoverycsc/ Visit other Youtube channels connected to the Center for Science & Culture Discovery Institute: https://www.youtube.com/user/Discover... Dr. Stephen C. Meyer: https://www.youtube.com/user/DrStephe... The Magician's Twin - CS Lewis & Evolution: https://www.youtube.com/user/cslewisweb Darwin's Heretic - Alfred Russel Wallce: https://www.youtube.com/user/AlfredRW... HELP ACU SPREAD THE WORD!   Ways to subscribe to the American Conservative University Podcast Click here to subscribe via Apple Podcasts Click here to subscribe via RSS You can also subscribe via Stitcher FM Player Podcast Addict Tune-in Podcasts Pandora Look us up on Amazon Prime   If you like this episode head on over to Apple Podcasts and kindly leave us a rating, a review and subscribe! People find us through our good reviews.   FEEDBACK- You can ask your questions, make comments, submit ideas for shows and lots more. Let your voice be heard. Email us at americanconservativeuniversity@americanconservativeuniversity.com     Help CSI Stamp Out Slavery In Sudan Join us in our effort to free over 350 slaves. Listeners to the Eric Metaxas Show will remember our annual effort to free Christians who have been enslaved for simply acknowledging Jesus Christ as their Savior. As we celebrate the birth of Christ this Christmas, join us in giving new life to brothers and sisters in Sudan who have enslaved as a result of their faith. https://csi-usa.org/metaxas   https://csi-usa.org/slavery/   Typical Aid for the Enslaved A ration of sorghum, a local nutrient-rich staple food A dairy goat A “Sack of Hope,” a survival kit containing essential items such as tarp for shelter, a cooking pan, a water canister, a mosquito net, a blanket, a handheld sickle, and fishing hooks. Release celebrations include prayer and gathering for a meal, and medical care for those in need. The CSI team provides comfort, encouragement, and a shoulder to lean on while they tell their stories and begin their new lives. Thank you for your compassion  Giving the Gift of Freedom and Hope to the Enslaved South Sudanese

The Fitness of Nature for Mankind featuring Biologist Michael Denton Watch this presentation at- https://youtu.be/9SL_xqSvWqU 36,385 views Discovery Science 123K subscribers Renowned author and biologist Michael Denton gives a new expression to what he calls the “medieval synthesis” of knowledge about life, now enjoying a “Reconquista” thanks to modern science. In charming and lyrical yet rigorous fashion, Denton reviews the intelligent design evidence detailed in his books, including the most recent, The Miracle of the Cell. Join him as he explores the myriad of ways nature is fit not just for life, but for human life. Denton is author of the new book "The Miracle of the Cell" (2020) as well as many other books such as "Nature's Destiny," "Fire-Maker," "The Wonder of Water," and "Evolution: Still a Theory in Crisis." You will never think of nature in the same way after you watch this presentation! Dr. Denton's new book The Miracle of the Cell [https://www.discovery.org/store/produ...] provides compelling evidence that long before life emerged on our planet, the design of the carbon-based cell was foreshadowed in the order of nature, in the exquisite fitness of the laws of nature for this foundational unit of all life on Earth. Nowhere is this fitness more apparent than in the properties of the key atomic constituents of the cell. Each of the atoms of life — including carbon, hydrogen, oxygen, and nitrogen, as well as several metal elements — features a suite of unique properties fine-tuned to serve highly specific, indispensable roles in the cell. Moreover, some of these properties are specifically fit for essential roles in the cells of advanced aerobic organisms like ourselves. Author Michael Denton is a Senior Fellow with Discovery Institute's Center for Science and Culture. He holds an MD from Bristol University and a PhD in biochemistry from King's College in London. His previous books include Evolution: A Theory in Crisis and Nature's Destiny: How the Laws of Biology Reveal Purpose in the Universe. He has published his work in Nature, Nature Genetics, BioSystems, Human Genetics, and Biology and Philosophy. Be sure to check out these related videos: Marcos Eberlin: Earth as the “Presidential Suite” of the Universe https://youtu.be/dFrOWEWHWZg Water, Ultimate Giver of Life, Points to Intelligent Design https://youtu.be/e2i0g1sL-X4 Conversations with William Dembski–Information All the Way Down https://youtu.be/BnVss3QseCw ============================ The Discovery Science News Channel is the official Youtube channel of Discovery Institute's Center for Science & Culture. The CSC is the institutional hub for scientists, educators, and inquiring minds who think that nature supplies compelling evidence of intelligent design. The CSC supports research, sponsors educational programs, defends free speech, and produce articles, books, and multimedia content. For more information visit https://www.discovery.org/id/ http://www.evolutionnews.org/ http://www.intelligentdesign.org/ Follow us on Facebook and Twitter: Twitter: @discoverycsc Facebook: https://www.facebook.com/discoverycsc/ Visit other Youtube channels connected to the Center for Science & Culture Discovery Institute: https://www.youtube.com/user/Discover... Dr. Stephen C. Meyer: https://www.youtube.com/user/DrStephe... The Magician's Twin - CS Lewis & Evolution: https://www.youtube.com/user/cslewisweb Darwin's Heretic - Alfred Russel Wallce: https://www.youtube.com/user/AlfredRW... HELP ACU SPREAD THE WORD!   Ways to subscribe to the American Conservative University Podcast Click here to subscribe via Apple Podcasts Click here to subscribe via RSS You can also subscribe via Stitcher FM Player Podcast Addict Tune-in Podcasts Pandora Look us up on Amazon Prime   If you like this episode head on over to Apple Podcasts and kindly leave us a rating, a review and subscribe! People find us through our good reviews.   FEEDBACK- You can ask your questions, make comments, submit ideas for shows and lots more. Let your voice be heard. Email us at americanconservativeuniversity@americanconservativeuniversity.com     Help CSI Stamp Out Slavery In Sudan Join us in our effort to free over 350 slaves. Listeners to the Eric Metaxas Show will remember our annual effort to free Christians who have been enslaved for simply acknowledging Jesus Christ as their Savior. As we celebrate the birth of Christ this Christmas, join us in giving new life to brothers and sisters in Sudan who have enslaved as a result of their faith. https://csi-usa.org/metaxas   https://csi-usa.org/slavery/   Typical Aid for the Enslaved A ration of sorghum, a local nutrient-rich staple food A dairy goat A “Sack of Hope,” a survival kit containing essential items such as tarp for shelter, a cooking pan, a water canister, a mosquito net, a blanket, a handheld sickle, and fishing hooks. Release celebrations include prayer and gathering for a meal, and medical care for those in need. The CSI team provides comfort, encouragement, and a shoulder to lean on while they tell their stories and begin their new lives. Thank you for your compassion  Giving the Gift of Freedom and Hope to the Enslaved South Sudanese

Flestir þekkja það að borða skötu á Þorláksmessu, en fæstir tengja skötuát við sumarið, nema kannski Ásmundur Friðriksson sem hefur undanfarin ár staðið fyrir skötumessu að sumri í þeim tilgangi að afla fjár til góðra málefna. Skötumessan í ár fer fram á morgun og við slógum á þráðinn til Ásmundar og forvitnuðumst aðeins um þessa óhefðbundnu skötuveislu. Hnúðlaxi hefur fjölgað í íslenskum ám undanfarin ár og þeir sem til þekkja segja að eiga megi von á enn meiri aukningu í ár. En hvað er hnúðlax og af hverju er hann ekki velkomin í árnar? Hjörleifur Finnsson ráðgjafi í umhverfisvernd hefur rannsakað stjórnun framandi tegunda á Íslandi út frá hnúðlaxinum og hann var á línunni hjá okkur að vestan og sagði okkur meira af stöðunni. Guðrún Bjarnadóttir hefur rekið jurtalitunar vinnustofuna Hespuhúsið um nokkurra ára skeið, fyrst í Borgarfirði og nú í Ölfusinu. Auk þess að lita garn og taka á móti gestum hefur hún fært út kvíarnar og gaf út jurtalitapúsl fyrir síðustu jól sem sló í gegn og nú hefur hún gefið út Flóruspilið. Við heyrum í Guðrúnu og forvitnumst um verkefni Hespuhússins. Í gær kom út grein í vefútgáfu vísindaritsins Nature Genetics þar sem vísindamenn Íslenskrar erfðagreiningar sýna hvernig 243 erfðabreytileikar, þar af 64 áður óþekktir, hafa áhrif á stærð barna við fæðingu, annars vegar í erfðamengi móður og hins vegar í gegnum erfðamengi fósturs. Tengsl fæðingarþyngdar við sjúkdóma hafa lengi verið þekkt en deilt hefur verið um hversu mikið þau tengjast erfðaþáttum einstaklingsins og að hversu miklu leyti þau tengjast aðstæðum fósturs á meðgöngu og þar með erfðaþáttum móður. Þau Kári Stefánsson og Valgerður Steinþórsdóttir frá Íslenskri erfðagreiningu komu til okkar og fræddu okkur um þetta mál. Íslenska sumarið hefur verið gott víða undanfarið, en því miður ekki alls staðar. Sigurður Þ. Ragnarsson, kallaður Siggi stormur frá því hann sinnti starfi veðurfréttamanns á Stöð2 fyrir nokkrum árum, var á línunni hjá okkur. Á Facebook síðu Sigga má sjá pælingar hans um ýmislegt sem tengist veðrinu. Við ræddum við hann þar sem hann er í Borgarfirðinum og spurðum hvort hann sér nokkuð í kortunum um að þau landssvæði sem hafi verið sumarsvelt hingað til fái líka að njóta? Tónlist: Hipsumhaps - Á hnjánum. Jet Black Joe og Sigríður Guðnadóttir - Freedom. E.L.O. - Dont bring me down. Unnsteinn Manuel - Lúser. Roxette - Sleeping in my car. Jón Jónsson - Gefðu allt sem þú átt. Stjórnin - Hleypum gleðinni inn. Sigurður Guðmundsson - Kartöflur. Police - Wrapped around your fingers.

Flestir þekkja það að borða skötu á Þorláksmessu, en fæstir tengja skötuát við sumarið, nema kannski Ásmundur Friðriksson sem hefur undanfarin ár staðið fyrir skötumessu að sumri í þeim tilgangi að afla fjár til góðra málefna. Skötumessan í ár fer fram á morgun og við slógum á þráðinn til Ásmundar og forvitnuðumst aðeins um þessa óhefðbundnu skötuveislu. Hnúðlaxi hefur fjölgað í íslenskum ám undanfarin ár og þeir sem til þekkja segja að eiga megi von á enn meiri aukningu í ár. En hvað er hnúðlax og af hverju er hann ekki velkomin í árnar? Hjörleifur Finnsson ráðgjafi í umhverfisvernd hefur rannsakað stjórnun framandi tegunda á Íslandi út frá hnúðlaxinum og hann var á línunni hjá okkur að vestan og sagði okkur meira af stöðunni. Guðrún Bjarnadóttir hefur rekið jurtalitunar vinnustofuna Hespuhúsið um nokkurra ára skeið, fyrst í Borgarfirði og nú í Ölfusinu. Auk þess að lita garn og taka á móti gestum hefur hún fært út kvíarnar og gaf út jurtalitapúsl fyrir síðustu jól sem sló í gegn og nú hefur hún gefið út Flóruspilið. Við heyrum í Guðrúnu og forvitnumst um verkefni Hespuhússins. Í gær kom út grein í vefútgáfu vísindaritsins Nature Genetics þar sem vísindamenn Íslenskrar erfðagreiningar sýna hvernig 243 erfðabreytileikar, þar af 64 áður óþekktir, hafa áhrif á stærð barna við fæðingu, annars vegar í erfðamengi móður og hins vegar í gegnum erfðamengi fósturs. Tengsl fæðingarþyngdar við sjúkdóma hafa lengi verið þekkt en deilt hefur verið um hversu mikið þau tengjast erfðaþáttum einstaklingsins og að hversu miklu leyti þau tengjast aðstæðum fósturs á meðgöngu og þar með erfðaþáttum móður. Þau Kári Stefánsson og Valgerður Steinþórsdóttir frá Íslenskri erfðagreiningu komu til okkar og fræddu okkur um þetta mál. Íslenska sumarið hefur verið gott víða undanfarið, en því miður ekki alls staðar. Sigurður Þ. Ragnarsson, kallaður Siggi stormur frá því hann sinnti starfi veðurfréttamanns á Stöð2 fyrir nokkrum árum, var á línunni hjá okkur. Á Facebook síðu Sigga má sjá pælingar hans um ýmislegt sem tengist veðrinu. Við ræddum við hann þar sem hann er í Borgarfirðinum og spurðum hvort hann sér nokkuð í kortunum um að þau landssvæði sem hafi verið sumarsvelt hingað til fái líka að njóta? Tónlist: Hipsumhaps - Á hnjánum. Jet Black Joe og Sigríður Guðnadóttir - Freedom. E.L.O. - Dont bring me down. Unnsteinn Manuel - Lúser. Roxette - Sleeping in my car. Jón Jónsson - Gefðu allt sem þú átt. Stjórnin - Hleypum gleðinni inn. Sigurður Guðmundsson - Kartöflur. Police - Wrapped around your fingers.

Haemophilia is a genetic condition which is characterised by one of the blood clotting factors, usually encoded for on the X chromosome, not being encoded for properly for various reasons- whether it's a mobile genetic element inserting itself into the gene or a simple mutation. On the show today, we describe the cause and symptoms of haemophilia, as well as using the case study of Queen Victoria to show that new mutations are a surprisingly common root cause... Sources for this episode: 1) Francioli, L. C., et al. (2015), Genome-wide patterns and properties of de novo mutations in humans. Nature Genetics 47(7): 822- 826. 2) Mannucci, P. M. and Tuddenham, E. G. D. (2001), The Haemophilias- From Royal Genes to Gene Therapy. The New England Journal of Medicine 344(23): 1773- 1779. 3) Thain, M. and Hickman, M. (2014), Dictionary of Biology (Eleventh Edition). London: Penguin Books Ltd. 4) Author unknown, The Haemophilia Society (date unknown), Bleeding Disorders > Haemophilia (online) [Accessed 08/04/2021]. 5) Author unknown, Wikipedia (date unknown), Factor VIII (online) [Accessed 08/04/2021]. 6) Author unknown, Wikipedia (date unknown), Queen Victoria (online) [Accessed 08/04/2021].

In this episode of the Epigenetics Podcast, we caught up with Diane Dickel from Lawrence Berkeley National Laboratory to talk about her work on ultraconserved enhancers and enhancer redundancy. Diane Dickel and her co-workers study non-coding regions of the genome that harbor distant-acting transcriptional regulatory regions, called enhancers. Enhancers have been shown to be critical for normal embryonic development, implying evolutional conservation. Diane Dickel and her team try to identify and characterize enhancers at a genomic scale. Their efforts include the use of CRISPR/CAS9 to mutate enhancer sequences in order to understand sequence dependent functional relevance. In this episode we discuss the function of ultraconserved enhancers, what ultraconservation actually means, how enhancer redundancy works and how Diane Dickel dealt with a failed PhD project.   References Dickel, D. E., Ypsilanti, A. R., Pla, R., Zhu, Y., Barozzi, I., Mannion, B. J., Khin, Y. S., Fukuda-Yuzawa, Y., Plajzer-Frick, I., Pickle, C. S., Lee, E. A., Harrington, A. N., Pham, Q. T., Garvin, T. H., Kato, M., Osterwalder, M., Akiyama, J. A., Afzal, V., Rubenstein, J. L. R., … Visel, A. (2018). Ultraconserved Enhancers Are Required for Normal Development. Cell, 172(3), 491-499.e15. https://doi.org/10.1016/j.cell.2017.12.017 Gorkin, D. U., Barozzi, I., Zhao, Y., Zhang, Y., Huang, H., Lee, A. Y., Li, B., Chiou, J., Wildberg, A., Ding, B., Zhang, B., Wang, M., Strattan, J. S., Davidson, J. M., Qiu, Y., Afzal, V., Akiyama, J. A., Plajzer-Frick, I., Novak, C. S., … Ren, B. (2020). An atlas of dynamic chromatin landscapes in mouse fetal development. Nature, 583(7818), 744–751. https://doi.org/10.1038/s41586-020-2093-3 Snetkova, V., Ypsilanti, A. R., Akiyama, J. A., Mannion, B. J., Plajzer-Frick, I., Novak, C. S., Harrington, A. N., Pham, Q. T., Kato, M., Zhu, Y., Godoy, J., Meky, E., Hunter, R. D., Shi, M., Kvon, E. Z., Afzal, V., Tran, S., Rubenstein, J. L. R., Visel, A., … Dickel, D. E. (2021). Ultraconserved enhancer function does not require perfect sequence conservation. Nature Genetics, 53(4), 521–528. https://doi.org/10.1038/s41588-021-00812-3   Related Episodes Identification of Functional Elements in the Genome (Bing Ren) Epigenetic Reprogramming During Mammalian Development (Wolf Reik) Unraveling Mechanisms of Chromosome Formation (Job Dekker)   Contact Active Motif on Twitter Epigenetics Podcast on Twitter Active Motif on LinkedIn Active Motif on Facebook Email: podcast@activemotif.com

Prof John McGrath is Professor of Molecular Dermatology, Lead of the Genetic Skin Disease Group and Head of the St John's Institute of Dermatology in London. Professor McGrath is also a recent President of the European Society for Dermatological Research. He is internationally renowned within dermatology, and an expert in Epidermolysis Bullosa.  He also reported the first mutations in hemidesmosomes and desmosomes which was published in Nature Genetics and in fact one of the diseases is named after him – McGrath's syndrome. In this episode we ask him about: His career Dermatology Research Advice for medical students and young doctors   For comments, collaboration or feedback, contact us via email or Twitter. Email: medspirepodcast@gmail.com Twitter: @medspirepodcast  

Derrière cette question a priori saugrenue, se cache un réel sujet de recherche sur lequel se sont penchés des chercheurs de plusieurs laboratoires à travers le monde. Fruit de leur collaboration, leurs résultats ont été publiés en avril 2021 dans la revue Nature Genetics. See acast.com/privacy for privacy and opt-out information.

The paper we discuss is Psychiatric Genomics Consortium. Genome-Wide Association Study Identifies 30 Loci Associated with Bipolar Disorder. Nature Genetics 2019; 51:793-803.Here's an incredibly helpful review on understanding genome wide association studies (GWAS): TA Pearson and TA Manolio. How to Interpret a Genome-Wide Association Study. JAMA 2008; 299(11):1335-1344.Find out more about the Psychiatric Genomics Consortium. 

Learn about the science of sourdough starters; and why identical twins aren’t so identical after all. Then, play along at home as we test your podcast knowledge with this month’s Curiosity Challenge trivia game.  Study of sourdough from around the world shows location doesn't matter for its microbes by Cameron Duke Intercontinental study sheds light on the microbial life of sourdough. (2021). EurekAlert! https://www.eurekalert.org/pub_releases/2021-01/ncsu-iss012621.php Kiniry, L. (2020). Why San Francisco does sourdough best. Bbc.com.  http://www.bbc.com/travel/story/20200402-why-san-francisco-does-sourdough-best Landis, E. A., Oliverio, A. M., McKenney, E. A., Nichols, L. M., Kfoury, N., Biango-Daniels, M., Shell, L. K., Madden, A. A., Shapiro, L., Shravya Sakunala, Kinsey Drake, Robbat, A., Booker, M., Dunn, R. R., Fierer, N., & Wolfe, B. E. (2021, January 26). The diversity and function of sourdough starter microbiomes. ELife; eLife Sciences Publications, Ltd. https://elifesciences.org/articles/61644 Identical twins aren't so identical after all by Steffie Drucker Jarry, J. (2021, January 24). Identical Twins Are Not Identical. Office for Science and Society. McGill University. https://www.mcgill.ca/oss/article/general-science/identical-twins-are-not-identical  Guardian staff reporter. (2021, January 8). Identical twins are not so identical, study suggests. The Guardian; The Guardian. https://www.theguardian.com/science/2021/jan/08/identical-twins-are-not-so-identical-study-suggests  Machemer, T. (2021, January 13). Many Identical Twins Actually Have Slightly Different DNA. Smithsonian Magazine; Smithsonian Magazine. https://www.smithsonianmag.com/smart-news/identical-twins-can-have-slightly-different-dna-180976736/  ‌Nicoletta Lanese. (2021, January 7). Identical twins don’t share 100% of their DNA. Livescience.com; Live Science. https://www.livescience.com/identical-twins-dont-share-all-dna.html  Jonsson, H., Magnusdottir, E., et. al. (2021). Differences between germline genomes of monozygotic twins. Nature Genetics, 53(1), 27–34. https://doi.org/10.1038/s41588-020-00755-1  Episodes referenced in Curiosity Challenge Trivia game: Chronotypes: https://www.curiositydaily.com/why-does-february-have-28-days/  Ants on stilts: https://www.curiositydaily.com/why-scientists-made-ants-walk-on-stilts/  Smellicopter: https://www.curiositydaily.com/the-dark-ages-werent-really-dark/ Subscribe to Curiosity Daily to learn something new every day with Cody Gough and Ashley Hamer. You can also listen to our podcast as part of your Alexa Flash Briefing; Amazon smart speakers users, click/tap “enable” here: https://www.amazon.com/Curiosity-com-Curiosity-Daily-from/dp/B07CP17DJY  See omnystudio.com/listener for privacy information.

FDA 批准一种新型的单抗-药物偶联物治疗乳腺癌JAMA 乳腺癌筛查时，简易乳房MRI与数字乳房合成技术哪一种好？Science子刊 能快速诊断癌症的便携式细胞分析仪-CytoPAN曲妥珠单抗-德鲁替康（trastuzumab deruxtecan）曲妥珠单抗-德鲁替康（trastuzumab deruxtecan）是一种HER-2单抗、偶联拓扑异构酶1抑制剂的药物。2019年12月，曲妥珠单抗-德鲁替康（trastuzumab deruxtecan）被FDA批准用于治疗HER2阳性的、经治疗的乳腺癌。《DESTINY-Breast01研究：曲妥珠单抗-德鲁替康经治疗的HER2阳性乳腺癌的2期临床研究》New England Journal of Medicine，2020年2月 (1)这项2部分的、开放标签、单组、多中心、2期研究，评估了184名、HER2阳性的、转移性乳腺癌患者，使用曲妥珠单抗德鲁替康的疗效。研究第一部分，使用了3种不同剂量，以确定推荐剂量；在第二部分中，评估了推荐剂量的有效性和安全性。曲妥珠单抗德鲁替康的推荐剂量为5.4mg/kg。随访11.1个月后，患者的中位缓解时间为14.8个月，中位无进展生存时间为16.4个月。在研究中，最常见的严重不良事件是中性粒细胞计数减少、贫血和恶心。结论：曲妥珠单抗-德鲁替康在HER2阳性的、转移性乳腺癌患者中，显示出持久的抗肿瘤活性。除了恶心和骨髓抑制，治疗组还观察到间质性肺病，因此用药过程中需监测肺部情况。避孕法避孕法主要包括激素避孕和非激素避孕。激素避孕药包括雌-孕激素避孕药和单纯孕激素避孕药；可采用口服、注射、皮下植入剂、透皮贴剂、子宫避孕器或阴道避孕器等方式给药。非激素避孕法主要包括：输卵管阻断、含铜宫内避孕器、避孕套。《回顾性研究：避孕法类型是否影响痤疮的发病率和严重程度》Obstetrics and Gynecology，2020年5月 (2)皮肤科医生常开出复方口服避孕药用于治疗痤疮，这项回顾性队列研究，目的是比较各种避孕法使用1年内，对痤疮的发病率和严重程度的影响。研究共大约337,000名避孕法的新使用者（年龄12～40岁），2%～8%出现新发痤疮，年轻女性的发病率较高。研究发现复方口服避孕药相比，含铜宫内节育器的痤疮发生风险比为1.14，含孕酮的宫内节育器的痤疮风险比1.09，这些女性新发痤疮后的就诊率略高。21,000名患有痤疮病史的女性，使用含铜宫内节育器和含孕酮的节育器后，从外用药转换成口服四环素类抗生素的可能性更高（风险比分别为1.44和1.34）。结论：复方口服避孕药似乎痤疮风险相对较小，各种避孕法之间绝对差异也很小。 《回顾性研究：产后即刻行皮下植入依托孕烯植入剂避孕，与静脉血栓栓塞的关系》Obstetrics and Gynecology，2020年6月 (3)来自贝勒大学医学院的研究人员，对分娩后30天内皮下植入依托孕烯植入剂的妇女与未植入的妇女的再入院率进行了比较，旨在明确这种避孕方法是否增加静脉血栓的风险。在338万余名产妇中，排除有静脉血栓栓塞史或抗凝治疗史的产妇，共8369名产妇在分娩住院期间接受了皮下植入避孕。研究发现，依托孕烯避孕的产妇和没有避孕的产妇的静脉血栓栓塞再入院率没有差异；而且糖尿病、血栓性血友病、系统性红斑狼疮和剖宫产的发生率在组间无差异。统计发现，接受避孕植入的产妇更年轻、收入更低、吸烟者更多、高血压、围产期感染或产后出血发生率也较高；在对这些混杂因素进行调整后，静脉血栓栓塞发生率的风险比为1.81，没有统计学差异（95%可信区间0.44 - -7.45）。结论：分娩后立即接受依托孕烯避孕植入物避孕，没有增加静脉血栓发生率。《对照研究：依托孕烯避孕植入物使用者不良出血模式的治疗》Obstetrics and Gynecology，2020年8月 (4)依托孕烯避孕植入物的主要副作用是阴道不规则出血，该研究的目的是评价短程使用他莫西芬是否有效。这个研究的前90天，这是一个双盲、随机、对照试验中，研究纳入112名植入依托孕烯避孕植入物后反复阴道出血的女性，随机双盲入组他莫昔芬10mg bid组或安慰剂组，连续治疗7天。然后，参与者进入下一个90天的开放标签研究，如果需要每30天可以接受最多3个疗程的他莫西芬，在此期间，参与者使用短信记录每天的流血情况。双盲对照期间，他莫西芬组报告在最初90天内阴道连续不出血的天数比安慰剂组少9.8天（P=0.001)；在开放标签阶段，服用他莫西芬的女性得到了类似的疗效。在随机对照期，他莫西芬组参与者的满意度也更高。结论：短疗程的他莫昔芬减少了问题性出血，提高了使用者的满意度。《随机对照研究：新型的宫内节育器的2期临床研究》Obsteteric & Gynecology，2020年4月 (5)这种新型的宫内节育器，支架含有镍钛合金，铜仅位于靠近子宫角和子宫颈内口的位置，含有的铜和镍钛合金的剂量都很小；而且设计时为了方便放置，自带细线。因此，这种宫内节育器可能减少与铜相关的子宫痉挛和出血。在这项为期36个月2期研究中，纳入了286名女性，评价了总共5,640个月经周期的妊娠情况。宫内节育器的平均使用时间为2.7年；37.8%的女性使用该宫内节育器的时间达到36个月。在使用宫内节育器的第1年，每个月经周期的平均出血天数从7.6天（第1个月经周期）减少至5.2天（第13个月经周期）。主要不良反应是出血、疼痛。结论：这种新型的宫内节育器有效性高，且耐受性好。《系统回顾：延长宫内节育器使用时间的有效性和安全性》American Journal of Obstetrics and Gynecology，2020年7月 (6)文章系统地回顾了关于宫内节育器超过批准的有效时间后，是否仍能有效和安全的避孕。研究纳入了2篇关于含铜宫内节育器（批准有效期10年）和4篇关于左炔诺孕酮宫内节育器（批准有效期为5年）的研究。研究发现，左炔诺孕酮宫内节育器在第6和第7年合并妊娠率为0.02/100人年(95%置信区间，0.00-0.29)。超期使用后，每年不良事件发生率、或因不良事件取环的比率为0- 3.7/100。对于含铜宫内节育器，11年和12年的合并妊娠率为0.0/100人年(95%可信区间为0-0.8)；在此期间，不良事件年发生率为0-4.6/100人。结论：左炔诺孕酮宫内节育器和含铜宫内节育器，延长使用的前两年的妊娠率、不良事件率、因副作用取出率都是很低的；但这些数据在数量和质量上都是有限的，不建议推广。乳腺癌的筛查乳腺癌的筛查首先需要对风险进行分层。没有卵巢癌、腹膜癌、乳腺癌个人史或家族史，没有遗传基因突变，10-30岁之间没有接受过胸部放疗的女性属于低危人群；有以上病史的女性属于高危。美国癌症协会建议女性45岁开始接受每年一次的钼靶筛查，55岁以后每两年一次。筛查方式：钼靶是首选，高危女性可使用MRI联合钼靶。《横向研究：简易乳房MRI与数字乳房合成技术在筛查致密乳房女性中乳腺癌的比较》JAMA，2020年2月 (7)乳腺密度高的女性患乳腺癌的风险增加，研究旨在比较简易乳房MRI和数字乳房合成技术对致密乳腺患者的筛查效果。共1516名女性参与了研究，平均年龄54岁。队列中，有17名浸润性乳腺癌和6名原位导管癌。MRI检测出全部17名浸润性乳腺癌和5名原位导管癌；数字合成技术仅检测出7例浸润性乳腺癌和2例原位癌。MRI敏感度为95.7%、特异性为86.7%；数字合成技术灵敏度为39.1%，特异性为97.4%（P=0.001，P

FDA 批准一种新型的单抗-药物偶联物治疗乳腺癌JAMA 乳腺癌筛查时，简易乳房MRI与数字乳房合成技术哪一种好？Science子刊 能快速诊断癌症的便携式细胞分析仪-CytoPAN曲妥珠单抗-德鲁替康（trastuzumab deruxtecan）曲妥珠单抗-德鲁替康（trastuzumab deruxtecan）是一种HER-2单抗、偶联拓扑异构酶1抑制剂的药物。2019年12月，曲妥珠单抗-德鲁替康（trastuzumab deruxtecan）被FDA批准用于治疗HER2阳性的、经治疗的乳腺癌。《DESTINY-Breast01研究：曲妥珠单抗-德鲁替康经治疗的HER2阳性乳腺癌的2期临床研究》New England Journal of Medicine，2020年2月 (1)这项2部分的、开放标签、单组、多中心、2期研究，评估了184名、HER2阳性的、转移性乳腺癌患者，使用曲妥珠单抗德鲁替康的疗效。研究第一部分，使用了3种不同剂量，以确定推荐剂量；在第二部分中，评估了推荐剂量的有效性和安全性。曲妥珠单抗德鲁替康的推荐剂量为5.4mg/kg。随访11.1个月后，患者的中位缓解时间为14.8个月，中位无进展生存时间为16.4个月。在研究中，最常见的严重不良事件是中性粒细胞计数减少、贫血和恶心。结论：曲妥珠单抗-德鲁替康在HER2阳性的、转移性乳腺癌患者中，显示出持久的抗肿瘤活性。除了恶心和骨髓抑制，治疗组还观察到间质性肺病，因此用药过程中需监测肺部情况。避孕法避孕法主要包括激素避孕和非激素避孕。激素避孕药包括雌-孕激素避孕药和单纯孕激素避孕药；可采用口服、注射、皮下植入剂、透皮贴剂、子宫避孕器或阴道避孕器等方式给药。非激素避孕法主要包括：输卵管阻断、含铜宫内避孕器、避孕套。《回顾性研究：避孕法类型是否影响痤疮的发病率和严重程度》Obstetrics and Gynecology，2020年5月 (2)皮肤科医生常开出复方口服避孕药用于治疗痤疮，这项回顾性队列研究，目的是比较各种避孕法使用1年内，对痤疮的发病率和严重程度的影响。研究共大约337,000名避孕法的新使用者（年龄12～40岁），2%～8%出现新发痤疮，年轻女性的发病率较高。研究发现复方口服避孕药相比，含铜宫内节育器的痤疮发生风险比为1.14，含孕酮的宫内节育器的痤疮风险比1.09，这些女性新发痤疮后的就诊率略高。21,000名患有痤疮病史的女性，使用含铜宫内节育器和含孕酮的节育器后，从外用药转换成口服四环素类抗生素的可能性更高（风险比分别为1.44和1.34）。结论：复方口服避孕药似乎痤疮风险相对较小，各种避孕法之间绝对差异也很小。 《回顾性研究：产后即刻行皮下植入依托孕烯植入剂避孕，与静脉血栓栓塞的关系》Obstetrics and Gynecology，2020年6月 (3)来自贝勒大学医学院的研究人员，对分娩后30天内皮下植入依托孕烯植入剂的妇女与未植入的妇女的再入院率进行了比较，旨在明确这种避孕方法是否增加静脉血栓的风险。在338万余名产妇中，排除有静脉血栓栓塞史或抗凝治疗史的产妇，共8369名产妇在分娩住院期间接受了皮下植入避孕。研究发现，依托孕烯避孕的产妇和没有避孕的产妇的静脉血栓栓塞再入院率没有差异；而且糖尿病、血栓性血友病、系统性红斑狼疮和剖宫产的发生率在组间无差异。统计发现，接受避孕植入的产妇更年轻、收入更低、吸烟者更多、高血压、围产期感染或产后出血发生率也较高；在对这些混杂因素进行调整后，静脉血栓栓塞发生率的风险比为1.81，没有统计学差异（95%可信区间0.44 - -7.45）。结论：分娩后立即接受依托孕烯避孕植入物避孕，没有增加静脉血栓发生率。《对照研究：依托孕烯避孕植入物使用者不良出血模式的治疗》Obstetrics and Gynecology，2020年8月 (4)依托孕烯避孕植入物的主要副作用是阴道不规则出血，该研究的目的是评价短程使用他莫西芬是否有效。这个研究的前90天，这是一个双盲、随机、对照试验中，研究纳入112名植入依托孕烯避孕植入物后反复阴道出血的女性，随机双盲入组他莫昔芬10mg bid组或安慰剂组，连续治疗7天。然后，参与者进入下一个90天的开放标签研究，如果需要每30天可以接受最多3个疗程的他莫西芬，在此期间，参与者使用短信记录每天的流血情况。双盲对照期间，他莫西芬组报告在最初90天内阴道连续不出血的天数比安慰剂组少9.8天（P=0.001)；在开放标签阶段，服用他莫西芬的女性得到了类似的疗效。在随机对照期，他莫西芬组参与者的满意度也更高。结论：短疗程的他莫昔芬减少了问题性出血，提高了使用者的满意度。《随机对照研究：新型的宫内节育器的2期临床研究》Obsteteric & Gynecology，2020年4月 (5)这种新型的宫内节育器，支架含有镍钛合金，铜仅位于靠近子宫角和子宫颈内口的位置，含有的铜和镍钛合金的剂量都很小；而且设计时为了方便放置，自带细线。因此，这种宫内节育器可能减少与铜相关的子宫痉挛和出血。在这项为期36个月2期研究中，纳入了286名女性，评价了总共5,640个月经周期的妊娠情况。宫内节育器的平均使用时间为2.7年；37.8%的女性使用该宫内节育器的时间达到36个月。在使用宫内节育器的第1年，每个月经周期的平均出血天数从7.6天（第1个月经周期）减少至5.2天（第13个月经周期）。主要不良反应是出血、疼痛。结论：这种新型的宫内节育器有效性高，且耐受性好。《系统回顾：延长宫内节育器使用时间的有效性和安全性》American Journal of Obstetrics and Gynecology，2020年7月 (6)文章系统地回顾了关于宫内节育器超过批准的有效时间后，是否仍能有效和安全的避孕。研究纳入了2篇关于含铜宫内节育器（批准有效期10年）和4篇关于左炔诺孕酮宫内节育器（批准有效期为5年）的研究。研究发现，左炔诺孕酮宫内节育器在第6和第7年合并妊娠率为0.02/100人年(95%置信区间，0.00-0.29)。超期使用后，每年不良事件发生率、或因不良事件取环的比率为0- 3.7/100。对于含铜宫内节育器，11年和12年的合并妊娠率为0.0/100人年(95%可信区间为0-0.8)；在此期间，不良事件年发生率为0-4.6/100人。结论：左炔诺孕酮宫内节育器和含铜宫内节育器，延长使用的前两年的妊娠率、不良事件率、因副作用取出率都是很低的；但这些数据在数量和质量上都是有限的，不建议推广。乳腺癌的筛查乳腺癌的筛查首先需要对风险进行分层。没有卵巢癌、腹膜癌、乳腺癌个人史或家族史，没有遗传基因突变，10-30岁之间没有接受过胸部放疗的女性属于低危人群；有以上病史的女性属于高危。美国癌症协会建议女性45岁开始接受每年一次的钼靶筛查，55岁以后每两年一次。筛查方式：钼靶是首选，高危女性可使用MRI联合钼靶。《横向研究：简易乳房MRI与数字乳房合成技术在筛查致密乳房女性中乳腺癌的比较》JAMA，2020年2月 (7)乳腺密度高的女性患乳腺癌的风险增加，研究旨在比较简易乳房MRI和数字乳房合成技术对致密乳腺患者的筛查效果。共1516名女性参与了研究，平均年龄54岁。队列中，有17名浸润性乳腺癌和6名原位导管癌。MRI检测出全部17名浸润性乳腺癌和5名原位导管癌；数字合成技术仅检测出7例浸润性乳腺癌和2例原位癌。MRI敏感度为95.7%、特异性为86.7%；数字合成技术灵敏度为39.1%，特异性为97.4%（P=0.001，P

Essential Tremor Treated With High-Intensity Focused UltrasoundDr. Michael Kaplitt is the first doctor in New York to use high-intensity focused ultrasound [HIFU] to relieve a patient's Essential Tremor - ET. The procedure is part of a new clinical trial testing the use of this technology to eliminate the source of tremors in a completely non-invasive way. Dr. Kaplitt and his neurosurgical team, along with Dr. Levi Chazen from Radiology and Dr. Harini Sarva from Neurology, were able to watch as the patient's tremor diminished visibly during the procedure. [http://corebrainjournal.com/221 (Listen to his patient Steve) here at CBJ as he tells you what it felt like coming out of HIFU treatment.] Essential tremor may be mild in some individuals, but in others, it can become debilitating over time. The tremors, which are often most severe in the hands, can interfere with everyday activities such as eating, drinking, writing or tying shoelaces. Patient Experience with Dr. Kaplitt's TeamWe asked for this interview after working with For a previous CBJ report from a healed golfer-patient treated by Dr. Kaplitt with HIFU listen here: http://corebrainjournal.com/221 (CBJ/221). This Ultrasound tool and the Tremor Treatment Team at Weill Cornell Brain & Spine is simply amazing. Current treatment options for ET include medication as well as Deep-Brain Stimulation (DBS), which involves implanting a battery-operated neurotransmitter under the collarbone connected to a wire that runs up the length of the neck into the scalp, where it is guided to the brain through a small hole in the skull. The tip of this wire sends the electrical impulses generated by the neurotransmitter into the precise spot in the brain that regulates the activity of the key circuits in essential tremor. In a phrase, brain surgery. http://weillcornellbrainandspine.org/faculty/michael-kaplitt-md-phd (Michael Kaplitt MD, Ph.D.,) and the Weill Cornell team are also national leaders in the use of DBS for essential tremor, Parkinson's disease, epilepsy and a variety of other disorders for more than 15 years. Listen up as Dr. Kaplitt discusses with us this remarkable new, non-invasive procedure to correct ET without brain surgery. - And he answers some of my questions about Parkinson's as well. Photo by https://unsplash.com/photos/_WKIsAKTaOU?utm_source=unsplash&utm_medium=referral&utm_content=creditCopyText (Nathan Dumlao) on https://unsplash.com/search/photos/spill?utm_source=unsplash&utm_medium=referral&utm_content=creditCopyText (Unsplash) Additional Research WorkDr. Kaplitt has pioneered human gene therapy for neurodegenerative disorders, having performed as a student the first rodent study that used the adeno-associated virus (AAV) vehicle for gene transfer to the brain. He performed the world's first human gene therapy procedure for Parkinson's disease and more recently helped to guide the first successful randomized, double-blind, sham-controlled trial of this experimental treatment, which was the first positive trial of this kind for gene therapy in any http://weillcornellbrainandspine.org/faculty/michael-kaplitt-md-phd (brain disorder). On The Psychiatric SideHe is also pioneering the development of novel deep brain stimulation treatments for psychiatric conditions, including refractory drug addiction. Dr. Kaplitt is an internationally recognized expert in the science of gene therapy and molecular neurobiology, and his current focus is to understand molecular disease mechanisms and develop novel molecular therapies for Parkinson's disease, depression, addiction, and pain. He has published over 100 articles and has edited two books on these subjects, with publications from his lab appearing in the most prestigious international journals, including Science, Science Translational Medicine, Nature Genetics, Nature Medicine, Proceedings of the National Academy of Science and Lancet. His basic science lab has...