Podcasts about epistasis

Advancements in genomics have accelerated significantly over the past few decades as compute technology has grown exponentially.  Professor Alessandra Ilic and Ricardo Nobre join Tony to talk about their research and how oneAPI is helping them accelerate research in the area of epistasis detection, which in genetics is when the effect of a gene or set of genes is affected by the presences or absence of another set of genes. Guests: Aleksandar Ilic is an Assistant Professor at the IST, University of Lisbon, and a Researcher of INESC-ID, Portugal. His research interests include high-performance and energy-efficient computing and modeling of parallel heterogeneous systems. Ricardo Nobre is a PostDoc researcher at the INESC-ID R&D center in Lisbon/Portugal, as part of the High-Performance Computing Architectures and Systems (HPCAS) research area. His interests include high-performance computing, parallel programming, compilers and machine learning. Aleksandar Ilic Ricardo Nobre   Resources: INESC-ID Achieves 9x Acceleration for Epistasis Disease Detection using oneAPI Tools and Intel Hardware https://www.intel.com/content/www/us/en/developer/articles/case-study/inesc-id-9x-acceleration-for-disease-detection-app.html?wapkw=inesc   Source Code https://github.com/hiperbio   Intel® Advisor https://www.intel.com/content/www/us/en/developer/tools/oneapi/advisor.html   Intel® VTune™ Profiler https://www.intel.com/content/www/us/en/developer/tools/oneapi/vtune-profiler.html   oneAPI https://oneapi.io https://www.intel.com/content/www/us/en/developer/tools/oneapi/overview.html   4th Gen Intel® Xeon® Scalable processors Intel® Data Center GPU Max Series   References: D. Marques, R. Campos, S. Santander-Jiménez, Z. Matveev, L. Sousa and A. Ilic. Unlocking Personalized Healthcare on Modern CPUs/GPUs: Three-way Gene Interaction Study. Paper presented in the 36th IEEE International Parallel & Distributed Processing Symposium (IPDPS) Lyon, France, 2022. DOI: 10.1109/IPDPS53621.2022.00023 R. Nobre, A. Ilic, S. Santander-Jiménez and L. Sousa. Fourth-Order Exhaustive Epistasis Detection for the xPU Era. Paper presented in the 50th International Conference on Parallel Processing (ICPP), Chicago, USA, 2021. DOI: 10.1145/3472456.3472509 D. Marques, A. Ilic, Z. A. Matveev, and L. Sousa. Application-driven Cache-aware Roofline Model. Future Generation Computer Systems 107 (2020): 257-273. DOI: 10.1016/j.future.2020.01.044 Ilic, F. Pratas, and L. Sousa. Cache-aware roofline model: Upgrading the loft. IEEE Computer Architecture Letters 13.1 (2013): 21-24. DOI: 10.1109/L-CA.2013.6   Check out more Intel podcasts at: https://www.intel.com/podcasts

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.29.534821v1?rss=1 Authors: Green, M., Domingos, H. A., Ouzounidis, V., Finlayson, C., Prevo, B., Cheerambathur, D. K. Abstract: Precise control of dendrite branching is essential for the formation of neural circuits, yet the mechanisms that regulate this process remain poorly understood. Here we show that the kinetochore protein KNL-1, known for its role in chromosome-microtubule coupling during mitosis, together with its binding partners, the KMN network, regulate dendritic branching in the C. elegans mechanosensory neuron, PVD, in a cell division independent manner. Neuron-specific degradation of KNL-1 results in excess dendrite branching and fusion events, predisposes PVD to age-dependent degeneration, and impairs animal sensory behavior. Surprisingly, these effects are not attributable to mis-regulation of the microtubule cytoskeleton. Instead, KNL-1 degradation alters the dynamics of F-actin, an established driver of dendrite branching. Epistasis analysis shows that KNL-1 counters the activity of the RacGEF TIAM-1, a downstream effector of dendrite guidance receptors. These findings establish that the microtubule coupling KMN network promotes dendrite branching by regulating the actin cytoskeleton and provide insight into how the cytoskeleton shapes dendritic architecture. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

This is our last episode on genetics, this week we talk about Epistasis. It's a short one but very interesting! Find us on the internet! Our website - Teachmescience.co.ukEmail  - teachmebiologycast@gmail.comTwitter - twitter.com/teachmebiocastInstagram - @teachmebiologycastSupport us - www.buymeacoffee.com/teachmebiologySupport the show

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.11.02.514835v1?rss=1 Authors: Liu, D., Lopez-Paz, C., Li, Y., Zhuang, X., Umen, J. Abstract: Coordination of growth and division in eukaryotic cells is essential for populations of proliferating cells to maintain size homeostasis, but the underlying mechanisms that govern cell size have only been investigated in a few taxa. The green alga Chlamydomonas reinhardtii (Chlamydomonas) proliferates using a multiple fission cell cycle that involves a long G1 phase followed by a rapid series of successive S and M phases (S/M) that produces 2n daughter cells. Two control points show cell-size dependence: Commitment in mid-G1 phase requires attainment of a minimum size to enable at least one mitotic division during S/M, and the S/M control point where mother cell size governs cell division number (n), ensuring that daughter distributions are uniform. tny1 mutants pass Commitment at a smaller size than wild type and undergo extra divisions during S/M phase to produce small daughters, indicating that TNY1 functions to inhibit size-dependent cell cycle progression. TNY1 encodes a cytosolic hnRNP A-related RNA binding protein and is produced once per cell cycle during S/M phase where it is apportioned to daughter cells, and then remains at constant absolute abundance as cells grow, a property known as subscaling. Altering the dosage of TNY1 in heterozygous diploids or through overexpression increased Commitment cell size and daughter cell size, indicating that TNY1 is a limiting factor for both size control checkpoints. Epistasis placed TNY1 function upstream of the retinoblastoma tumor suppressor complex (RBC) and one of its regulators, Cyclin-Dependent Kinase G1 (CDKG1). Moreover, CDKG1 protein and mRNA were found to over-accumulate in tny1 cells suggesting that CDKG1 may be a direct target of repression by TNY1. Our data expand the potential roles of subscaling proteins outside the nucleus and imply a control mechanism that ties TNY1 accumulation to pre-division mother cell size. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

live com Thomas Chi sobre Ativismo Digital https://youtu.be/BN06VfUoIYM C. Brandon Ogbunu on Epistasis & The Primacy of Context in Complex Systems https://pca.st/erj8ste5 Juego de Imperios, Malvinas 1982: colonizados por la Dictadura https://pca.st/ux5l5yms What was the Indus Valley Civilization? Interview with Dr. Adam Green https://pca.st/rekz2w0y The Helsinki neighbourhood leading the way to zero-carbon cities https://www.newscientist.com/article/2314410-the-helsinki-neighbourhood-leading-the-way-to-zero-carbon-cities/ Yayoi ... Read more

Context is king: whether in language, ecology, culture, history, economics, or chemistry. One of the core teachings of complexity science is that nothing exists in isolation — especially when it comes to systems in which learning, memory, or emergent behaviors play a part. Even though this (paradoxically) limits the universality of scientific claims, it also lets us draw analogies between the context-dependency of one phenomenon and others: how protein folding shapes HIV evolution is meaningfully like the way that growing up in a specific neighborhood shapes educational and economic opportunity; the paths through a space of all possible four-letter words are constrained in ways very similar to how interactions between microbes impact gut health; how we make sense both depends on how we've learned and places bounds on what we're capable of seeing.Welcome to COMPLEXITY, the official podcast of the Santa Fe Institute. I'm your host, Michael Garfield, and every other week we'll bring you with us for far-ranging conversations with our worldwide network of rigorous researchers developing new frameworks to explain the deepest mysteries of the universe.This week on Complexity, we talk to Yale evolutionary biologist C. Brandon Ogbunu (Twitter, Google Scholar, GitHub) about the importance of environment to the activity and outcomes of complex systems — the value of surprise, the constraints of history, the virtue and challenge of great communication, and much more. Our conversation touches on everything from using word games to teach core concepts in evolutionary theory, to the ways that protein quality control co-determines the ability of pathogens to evade eradication, to the relationship between human artists, algorithms, and regulation in the 21st Century. Brandon works not just in multiple scientific domains but as the author of a number of high-profile blogs exploring the intersection of science and culture — and his boundaryless fluency shines through in a discussion that will not be contained, about some of the biggest questions and discoveries of our time.If you value our research and communication efforts, please subscribe to Complexity Podcast wherever you prefer to listen, rate and review us at Apple Podcasts, and/or consider making a donation at santafe.edu/give. You'll find plenty of other ways to engage with us at santafe.edu/engage.Thank you for listening!Join our Facebook discussion group to meet like minds and talk about each episode.Podcast theme music by Mitch Mignano.Follow us on social media:Twitter • YouTube • Facebook • Instagram • LinkedInDiscussed in this episode:“I do my science biographically…I find a personal connection to the essence of the question.”– C. Brandon Ogbunugafor on RadioLab"Environment x everything interactions: From evolution to epidemics and beyond"Brandon's February 2022 SFI Seminar (YouTube Video + Live Twitter Coverage)“A Reflection on 50 Years of John Maynard Smith's ‘Protein Space'”C. Brandon Ogbunugafor in GENETICS“Collective Computing: Learning from Nature”David Krakauer presenting at the Foresight Institute in 2021 (with reference to Rubik's Cube research)“Optimal Policies Tend to Seek Power”Alexander Matt Turner, Logan Smith, Rohin Shah, Andrew Critch, Prasad Tadepalli in arXiv“A New Take on John Maynard Smith's Concept of Protein Space for Understanding Molecular Evolution”C. Brandon Ogbunugafor, Daniel Hartl in PLOS Computational Biology“The 300 Most Common Words”by Bruce Sterling“The Host Cell's Endoplasmic Reticulum Proteostasis Network Profoundly Shapes the Protein Sequence Space Accessible to HIV Envelope”Jimin Yoon, Emmanuel E. Nekongo, Jessica E. Patrick, Angela M. Phillips, Anna I. Ponomarenko, Samuel J. Hendel, Vincent L. Butty, C. Brandon Ogbunugafor, Yu-Shan Lin, Matthew D. Shoulders in bioRxiv“Competition along trajectories governs adaptation rates towards antimicrobial resistance”C. Brandon Ogbunugafor, Margaret J. Eppstein in Nature Ecology & Evolution“Scientists Need to Admit What They Got Wrong About COVID”C. Brandon Ogbunugafor in WIRED“Deconstructing higher-order interactions in the microbiota: A theoretical examination”Yitbarek Senay, Guittar John, Sarah A. Knutie, C. Brandon Ogbunugafor in bioRxiv“What Makes an Artist in the Age of Algorithms?”C. Brandon Ogbunugafor in WIREDNot mentioned in this episode but still worth exploring:“Part of what I was getting after with Blackness had to do with authoring ideas that are edgy or potentially threatening. That as a scientist, you can generate ideas in the name of research, in the name of breaking new ground, that may stigmatize you. That may kick you out of the club, so to speak, because you're not necessarily following the herd.”– Physicist Stephon Alexander in an interview with Brandon at Andscape“How Afrofuturism Can Help The World Mend”C. Brandon Ogbunugafor in WIRED“The COVID-19 pandemic amplified long-standing racial disparities in the United States criminal justice system”Brennan Klein, C. Brandon Ogbunugafor, Benjamin J. Schafer, Zarana Bhadricha, Preeti Kori, Jim Sheldon, Nitish Kaza, Emily A. Wang, Tina Eliassi-Rad, Samuel V. Scarpino, Elizabeth Hinton in medRxivAlso mentioned:Simon Conway Morris, Geoffrey West, Samuel Scarpino, Rick & Morty, Stuart Kauffman, Frank Salisbury, Stephen Jay Gould, Frances Arnold, John Vervaeke, Andreas Wagner, Jennifer Dunne, James Evans, Carl Bergstrom, Jevin West, Henry Gee, Eugene Shakhnovich, Rafael Guerrero, Gregory Bateson, Simon DeDeo, James Clerk Maxwell, Melanie Moses, Kathy Powers, Sara Walker, Michael Lachmann, and many others...

Valuing femininity, Vampower amps, mandolin emergencies, and trans representation are part of Hilary's conversation with Amy Mills (Retrofret Vintage Guitars, Couch Slut, Epistasis). Plus, the problem with “most guys.” Huge thanks to this episode's sponsors! http://earthquakerdevices.com (EarthQuaker Devices)- extra special effects pedals made by hand in Akron, OH! http://stompboxsonic.com (Stompbox Sonic)- personalized pedal curation and sales in Somerville, MA! http://holcombguitars.com (Holcomb Guitars)- custom guitars and mobile guitar repair in RI/MA! AMY's BIO Amy Rose Mills is a queer trans woman, photographer, luthier, and musician (among other things) living and working in NYC. AMY'S LINKS https://amyrosemills.com/ (Amy's website) http://instagram.com/rococo_witch (Amy's Instagram) https://www.tiktok.com/@rococo_witch? (Amy's TikTok) https://amyrose.bandcamp.com/album/white-bay (Amy's solo work on Bandcamp) https://couchslut.bandcamp.com/album/take-a-chance-on-rock-n-roll-3 (Couch Slut on Bandcamp) https://crucialblast.bandcamp.com/album/light-through-dead-glass (Epistasis on Bandcamp) http://instagram.com/retrofret (Retrofret on Instagram) MID-RIFF LINKS http://hilarybjones.com/midriffpodcast (Website) http://instagram.com/midriffpodcast (Instagram) http://facebook.com/midriffpodcast (Facebook) https://hilarybjones.us20.list-manage.com/subscribe?u=43bb95b305fb0c7d53fbc8d3a&id=146b44f072 (Newsletter) https://www.hilarybjones.com/blog (Blog)  Thanks for rating/reviewing on https://podcasts.apple.com/us/podcast/mid-riff/id1494997227 (Apple Podcasts)! CREDITS Bumper song: “1” by https://amyrose.bandcamp.com/album/white-bay (Amy Rose) Theme Music: "Hedonism" by https://towanda.bandcamp.com/ (Towanda) Artwork by https://www.juliagualtieri.com/ (Julia Gualtieri)

Epistasis detection holds great promise for the prevention and treatment of diseases such as Alzheimer’s, diabetes and breast cancer. INESC-ID researchers Aleksander Ilic and Rafael Torres Campos are collaborating with other researchers and developers across Portugal through the HiPErBio Project to advance the precision and efficiency of epistasis detection, using oneAPI DevCloud, Intel CPUs and […]

Epistasis detection holds great promise for the prevention and treatment of diseases such as Alzheimer’s, diabetes and breast cancer. INESC-ID researchers Aleksander Ilic and Rafael Torres Campos are collaborating with other researchers and developers across Portugal through the HiPErBio Project to advance the precision and efficiency of epistasis detection, using oneAPI DevCloud, Intel CPUs and […]

Epistasis detection holds great promise for the prevention and treatment of diseases such as Alzheimer’s, diabetes and breast cancer. INESC-ID researchers Aleksander Ilic and Rafael Torres Campos are collaborating with other researchers and developers across Portugal through the HiPErBio Project to advance the precision and efficiency of epistasis detection, using oneAPI DevCloud, Intel CPUs and […]

Is CELEBRITY CULTURE Harmful For Modern Society?? Can Followers Be Comparable To IDOLATERS? Why Is There So Much SELF HATE & JEALOUSY Amongst So Called BLACKS? --- Send in a voice message: https://anchor.fm/bout-dat/message

Episode 66 is going to make all your puppy dreams come true! Beginning with a word nerd moment before completing a Labrador dihybrid cross (1:15). Epistatic interactions don’t always have to be in opposition, as explained in a wheat color dihybrid cross (5:07). Melanie concludes with unit and exam connections (6:13).The Question of the Day asks (7:08) What famous mouse study connects epigenetics, diet and obesity?Thank you for listening to The APsolute RecAP: Biology Edition!(AP is a registered trademark of the College Board and is not affiliated with The APsolute RecAP. Copyright 2021 - The APsolute RecAP, LLC. All rights reserved.)Website:www.theapsoluterecap.comEMAIL:TheAPsoluteRecAP@gmail.comFollow Us:INSTAGRAMTWITTERFACEBOOKYOUTUBE

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.21.348920v1?rss=1 Authors: Nishikawa, K. K., Hoppe, N., Smith, R., Bingman, C., Raman, S. Abstract: Epistasis is a major determinant in the emergence of novel protein function. In allosteric proteins, direct interactions between inducer-binding mutations propagate through the allosteric network, manifesting as epistasis at the level of biological function. Elucidating this relationship between local interactions and their global effects is essential to understanding evolution of allosteric proteins. We integrate computational design, structural and biophysical analysis to characterize the emergence of novel inducer specificity in an allosteric transcription factor. Adaptive landscapes of different inducers of the engineered mutant show that a few strong epistatic interactions constrain the number of viable sequence pathways, revealing ridges in the fitness landscape leading to new specificity. Crystallographic evidence shows a single mutation drives specificity by reshaping the binding pocket. Comparison of biophysical and functional landscapes emphasizes the nonlinear relationship between local inducer affinity and global function (allostery). Our results highlight the functional and evolutionary complexity of allosteric proteins. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.14.339671v1?rss=1 Authors: Morrison, A. J., Wonderlick, D. R., Harms, M. J. Abstract: Non-additivity between mutations--epistasis--profoundly shapes evolution. It can be difficult to understand its mechanistic origins. Here we show that "ensemble epistasis" is likely a universal feature of macromolecules. Using a simple analytical model, we found that epistasis arises when two conditions are met: 1) a macromolecule populates at least three structures and 2) mutations have differential effects on a least two of the inactive structures. To explore the relative magnitude of ensemble epistasis, we performed a virtual deep-mutational scan of the allosteric Ca2+ signaling protein S100A4. We found that 27% of mutation pairs gave ensemble epistasis with a magnitude on the order of thermal fluctuations, 1 kT. We observed many forms of epistasis: magnitude, sign, and reciprocal sign epistasis. Depending on the effector concentration, the same mutation pair could even exhibit different forms of epistasis. The ubiquity of ensembles in biology and its pervasiveness in our dataset suggests that ensemble epistasis may be a universal mechanism of epistasis. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.29.319103v1?rss=1 Authors: Romero-Romero, S., Costas, M., Silva, D.-A., Kordes, S., Rojas-Ortega, E., Guerra, Y., Tapia, C., Shanmugaratnam, S., Rodriguez-Romero, A., Baker, D., Höcker, B., Fernandez-Velasco, D. A. Abstract: The design of stable proteins with custom-made functions is a major goal in biochemistry with practical relevance for our environment and society. High conformational stability lowers protein sensitivity to mutations and changes in the environment; thus, understanding and manipulating protein stability will expand the applications of de novo proteins. Since the ({beta}/)8-barrel or TIM-barrel fold is one of the most common functional scaffolds, in this work we designed a collection of stable de novo TIM barrels (NovoTIMs), using a computational fixed-backbone and modular approach based on improved hydrophobic packing of sTIM11, the first validated de novo TIM barrel. NovoTIMs navigate a region of the stability landscape previously uncharted by natural TIM barrels, with variations spanning 60 degrees in melting temperature and 25 kcal per mol in conformational stability throughout the designs. Significant non-additive or epistatic effects were observed when stabilizing mutations from different regions of the barrel were combined. The molecular basis of epistasis in NovoTIMs appears to be related to the extension of the hydrophobic cores. This study is an important step towards the fine-tuned modulation of protein stability by design. Copy rights belong to original authors. Visit the link for more info

Sidste særsending i denne omgang. Der høres nye udgivelser fra Sverige, Danmark og Japan.Trackliste:Bastian Void - ?Kali Malone - Cast of MindOberlin : ?Minais B - MagnoliaMaria W horn - Epistasis

Relief is a statistical method to perform feature selection. It could be used, for instance, to find genomic loci that correlate with a trait or genes whose expression correlate with a condition. Relief can also be made sensitive to interaction effects (known in genetics as epistasis). In this episode, Trang Lê joins me to talk about Relief and her version of Relief called STIR (STatistical Inference Relief). While traditional Relief algorithms could only rank features and needed a user-supplied threshold to decide which features to select, Trang’s reformulation of Relief allowed her to compute p-values and make the selection process less arbitrary. Links: Paper: STatistical Inference Relief (STIR) feature selection STIR on GitHub Relief on Wikipedia The original Relief paper by Kira and Rendell (1992) Epistasis: what it means, what it doesn’t mean, and statistical methods to detect it in humans

Vincent, Michael, and Michele review highlights of the 2014 General Meeting of the American Society for Microbiology in Boston, MA.

Genome-wide association studies identified a PTGER4 expression-modulating region on chromosome 5p13.1 as Crohn's disease (CD) susceptibility region. The study aim was to test this association in a large cohort of patients with inflammatory bowel disease (IBD) and to elucidate genotypic and phenotypic interactions with other IBD genes. A total of 7073 patients and controls were genotyped: 844 CD and 471 patients with ulcerative colitis and 1488 controls were analyzed for the single nucleotide polymorphisms (SNPs) rs4495224 and rs7720838 on chromosome 5p13.1. The study included two replication cohorts of North American (CD: n = 684; controls: n = 1440) and of German origin (CD: n = 1098; controls: n = 1048). Genotype-phenotype, epistasis and transcription factor binding analyses were performed. In the discovery cohort, an association of rs4495224 (p = 4.10×10⁻⁵; 0.76 [0.67-0.87]) and of rs7720838 (p = 6.91×10⁻⁴; 0.81 [0.71-0.91]) with susceptibility to CD was demonstrated. These associations were confirmed in both replication cohorts. In silico analysis predicted rs4495224 and rs7720838 as essential parts of binding sites for the transcription factors NF-κB and XBP1 with higher binding scores for carriers of the CD risk alleles, providing an explanation of how these SNPs might contribute to increased PTGER4 expression. There was no association of the PTGER4 SNPs with IBD phenotypes. Epistasis detected between 5p13.1 and ATG16L1 for CD susceptibility in the discovery cohort (p = 5.99×10⁻⁷ for rs7720838 and rs2241880) could not be replicated in both replication cohorts arguing against a major role of this gene-gene interaction in the susceptibility to CD. We confirmed 5p13.1 as a major CD susceptibility locus and demonstrate by in silico analysis rs4495224 and rs7720838 as part of binding sites for NF-κB and XBP1. Further functional studies are necessary to confirm the results of our in silico analysis and to analyze if changes in PTGER4 expression modulate CD susceptibility.

Genome-wide association studies identified PTPN2 (protein tyrosine phosphatase, non-receptor type 2) as susceptibility gene for inflammatory bowel diseases (IBD). However, the exact role of PTPN2 in Crohn's disease (CD) and ulcerative colitis (UC) and its phenotypic effect are unclear. We therefore performed a detailed genotype-phenotype and epistasis analysis of PTPN2 gene variants. Genomic DNA from 2131 individuals of Caucasian origin (905 patients with CD, 318 patients with UC, and 908 healthy, unrelated controls) was analyzed for two SNPs in the PTPN2 region (rs2542151, rs7234029) for which associations with IBD were found in previous studies in other cohorts. Our analysis revealed a significant association of PTPN2 SNP rs2542151 with both susceptibility to CD (p = 1.95×10⁻⁵; OR 1.49 [1.34-1.79]) and UC (p = 3.87×10⁻², OR 1.31 [1.02-1.68]). Moreover, PTPN2 SNP rs7234029 demonstrated a significant association with susceptibility to CD (p = 1.30×10⁻³; OR 1.35 [1.13-1.62]) and a trend towards association with UC (p = 7.53×10⁻²; OR 1.26 [0.98-1.62]). Genotype-phenotype analysis revealed an association of PTPN2 SNP rs7234029 with a stricturing disease phenotype (B2) in CD patients (p = 6.62×10⁻³). Epistasis analysis showed weak epistasis between the ATG16L1 SNP rs2241879 and PTPN2 SNP rs2542151 (p = 0.024) in CD and between ATG16L1 SNP rs4663396 and PTPN2 SNP rs7234029 (p = 4.68×10⁻³) in UC. There was no evidence of epistasis between PTPN2 and NOD2 and PTPN2 and IL23R. In silico analysis revealed that the SNP rs7234029 modulates potentially the binding sites of several transcription factors involved in inflammation including GATA-3, NF-κB, C/EBP, and E4BP4. Our data confirm the association of PTPN2 variants with susceptibility to both CD and UC, suggesting a common disease pathomechanism for these diseases. Given recent evidence that PTPN2 regulates autophagosome formation in intestinal epithelial cells, the potential link between PTPN2 and ATG16L1 should be further investigated.

We begin by trying to decide whether it's a good idea or a bad idea for a transport company to use the slogan, "If it's on time, it's a fluke". Turns out you can interpret this in many ways, but don't get all crazy and start denying antecedents, now. We don't go in for logical fallacies. Can you name one important way that trucks are like flatworms? No, that's not it. Nope, wrong again. Don't you know anything about mouth/anuses? Ah, well, if it's any consolation (and it shouldn't be), you're not alone. And you could always try to top John in the dumb-stakes by emailing us with YOUR genetics question (maskedman@limitedappeal.net). Theme music courtesy of General Patton vs. The X-Ecutioners and Ipecac Recordings.

The development of an organism from the fertilized zygote to a multicellular organism is a unidirectional process. It occurs in a spatially and temporally tightly controlled fashion. To understand how the genetic information is interpreted and how the cellular identity is inherited, are major challenges towards the understanding of developmental processes. Epigenetic marks like histone modifications, changes of the protein composition binding to DNA or the remodeling of nucleosomes have been shown to be important for the establishment of tissue-specific transcription profiles. Chromatin immunoprecipitation (ChIP) is a method to investigate the association of proteins to specific genomic loci. In this study, I have established two protocols for ChIP analyses of Xenopus laevis embryos: the In Situ ChIP and the Douncer ChIP. In addition, I have generated several antibodies in collaboration with Dr. Elisabeth Kremmer (GSF München) for ChIP analyses, which were directed against the muscle determination factor MyoD and the Wnt/β-catenin signaling components Lef/Tcf transcription factors Lef1 and Tcf1. While optimizing of the ChIP protocols, I have analyzed successfully the binding of various transcription factors, chromatin remodeling enzymes and histone modifications on genomic loci of key developmental regulators. With the In Situ ChIP, I have shown that the serum response factor SRF interacts predominantly with the actively transcribed myoD gene. Together with other data, this result helps to define a specific role of SRF protein in the stable maintenance of myoD transcription, which is essential for proper muscle differentiation. With the Douncer ChIP protocol, a time course study has been performed in order to understand, when and which histone modification marks appear during muscle cell determination and differentiation on the myoD locus. The temporal and spatial distribution of the analyzed histone modification marks was correlated for the most part with the expected patterns. Furthermore, I have demonstrated that direct binding of the chromatin remodeler CHD4/Mi2-β to the 5' part of the sip1 gene in gastrula stage embryos. This interaction represents a crucial regulatory module, which determines the position along the animal-vegetal axis of the embryo, where the border between the mesodermal and neuroectodermal germ layer will be formed. These examples represent on of the very few successful ChIP applications for the endogenous proteins in young Xenopus embryos, and I hope that my protocols will turn out useful for future investigations of regulatory interactions in this vertebrate model organism.