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Deletion of a single CTCF motif at the boundary of a chromatin domain with three FGF genes disrupts gene expression and embryonic development

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Developmental Cell 2025年

作者： Chakraborty, Shreeta Wenzlitschke, Nina Anderson, Matthew J. Eraso, Ariel Baudic, Manon Thompson, Joyce J. Evans, Alicia A. Shatford-Adams, Lilly M. Chari, Raj Awasthi, Parirokh Dale, Ryan K. Lewandoski, Mark Petros, Timothy J. Rocha, Pedro P. Unit on Genome Structure and Regulation National Institute of Child Health and Human Development National Institutes of Health Bethesda 20892 MD United States Genetics of Vertebrate Development Section Cancer and Developmental Biology Laboratory National Cancer Institute National Institutes of Health Frederick 21702 MD United States Bioinformatics and Scientific Programming Core National Institute of Child Health and Human Development National Institutes of Health Bethesda 20892 MD United States Laboratory Animal Sciences Program Frederick National Laboratory for Cancer Research Frederick 21702 MD United States Unit on Cellular and Molecular Neurodevelopment National Institute of Child Health and Human Development National Institutes of Health Bethesda 20892 MD United States National Cancer Institute NIH Bethesda 20892 MD United States

Chromatin domains delimited by CTCF can restrict the range of enhancer action. However, disruption of some domain boundaries results in mild gene dysregulation and phenotypes. We tested whether perturbing a domain with multiple developmental regulators would lead to more severe outcomes. We chose a domain with three FGF ligand genes—Fgf3, Fgf4, and Fgf15—that control different murine developmental processes. Heterozygous deletion of a 23.9-kb boundary defined by four CTCF sites led to ectopic interactions of the FGF genes with enhancers active in the brain and induced FGF expression. This caused orofacial clefts, encephalocele, and fully penetrant perinatal lethality. Loss of the single CTCF motif oriented toward the enhancers—but not the three toward the FGF genes—recapitulated these phenotypes. Our works shows that small sequence variants at particular domain boundaries can have a surprisingly outsized effect and must be considered as potential sources of gene dysregulation in development and disease. © 2025

关键词： CTCF epigenetics FGF gene regulation nuclear organization

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From castaways to discoveries: unveiling treasures in skin RNAseq using a novel multidimensional data processing workflow including infection-host dynamics

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Physiological Genomics 2025年第5期57卷 343-356页

作者： Bhargava, Disha Labadie, Alec Hanson-Rios-stutz, Rebecca L. Goodyke, Austin Moses, Ella M. Das, Akansha S. Vanderweele, Sophie Lemon, Janelle V. Cook, Taylor W. Pearson, David Redinger, Joseph M. Caulfield, Adam J. Olivero, Rosemary Foster, Kate Ashack, Kurt Rajasekaran, Surender Bupp, Caleb P. Triche, Timothy J. Krawczyk, Connie M. Chesla, Dave Sims, Matthew D. Hartog, Nicholas L. Prokop, Jeremy W. College of Human Medicine Michigan State University Grand Rapids MI United States Office of Research Corewell Health Grand Rapids MI United States Department of Biology Washington and Jefferson College Washington PA United States Department of Pharmacology and Toxicology Michigan State University East Lansing MI United States Department of Large Animal Clinical Sciences College of Veterinary Medicine Michigan State University East Lansing MI United States School for Environment and Sustainability University of Michigan Ann Arbor MI United States Regional Laboratory Corewell Health Grand Rapids MI United States Infectious Disease Helen DeVos Children’s Hospital Grand Rapids MI United States Dermatology Helen DeVos Children’s Hospital Corewell Health Grand Rapids MI United States Dermatology Associates of West Michigan Grand Rapids MI United States Pediatric Intensive Care Unit Helen DeVos Children’s Hospital Corewell Health Grand Rapids MI United States Medical Genetics Corewell Health Grand Rapids MI United States Center for Epigenetics Van Andel Research Institute Grand Rapids MI United States Department of Metabolism and Nutritional Programming Van Andel Institute Grand Rapids MI United States Section of Infectious Diseases Corewell Health Royal Oak MI United States Allergy and Immunology Corewell Health Grand Rapids MI United States

Defining physiology and methods to measure biological mechanisms is essential. Extensive datasets such as RNA sequencing are used with little analysis of the knowledge gained from the various methodologies. Within this work, we have processed publicly available NCBI RNAseq datasets using a combination of bioinformatics tools for the largest physiological organ, the skin. In many datasets, we identify the quality of the sample, human transcript mapping, the sex of each sample, foreign RNA from bacteria/viruses/protists, and the presence of B/T-cell immune repertoire. Processing 8,274 samples from 132 different experiments for skin samples identifies common flora of skin with elevation of protists (such as Leishmania), bacteria (Staphylococcus, Cutibacterium acnes), and viruses [Human alpha-herpesvirus (HSV), Human papillomavirus (HPV)] that may be involved in physiological differences. We observed samples with the Heilongjiang tick virus, human T-cell leukemia virus type I, and equine infectious anemia virus that likely play pathological roles in physi-ology. Integrating the various biomarkers identified five ideal datasets for skin pathologies that elucidated a novel correlation between the normal skin flora bacterium Bacillus megaterium with major histocompatibility complex (MHC) regulation and the immune repertoire clonal expansion, particularly in patients with hidradenitis suppurativa. Finally, we show that in multiple independent experiments, biological sex is associated with multiple sex chromosome gene differences, highlighting the importance of future work in studying sex differences in skin. Data integrations and multidimensional data mapping are critical for physiological omics advancements, and this work highlights the exciting ability to apply these tools to skin physiology. NEW & NOTEWORTHY Complex bioinformatics mapping to skin RNA sequencing datasets can simultaneously map biological sex, skin-specific genes, bacteria, viruses, protists, and the acqui

关键词： bacteria immune repertoire RNA skin virus

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Novel symmetric numerical methods for solving symmetric mathematical problems

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International Journal of Circuits, Systems and Signal Processing 2021年 15卷 1545-1557页

作者： Ibrahimov, V.R. Mehdiyeva, G.Y.U. Yue, Xiao-Guang Kaabar, Mohammed K.A. Noeiaghdam, Samad Juraev, Davron Aslonqulovich Institute of Control Systems named after Academician A.Huseynov BakuAZ1141 Azerbaijan Computational mathematics Baku State University BakuAZ1148 Azerbaijan Department of Computer Science and Engineering School of Sciences European University Cyprus Nicosia1516 Cyprus Institute of Mathematical Sciences Faculty of Science University of Malaya Kuala Lumpur50603 Malaysia Department of Mathematics and Statistics Washington State University PullmanWA99163 United States Industrial Mathematics Laboratory Baikal School of BRICS Irkutsk National Research Technical University Irkutsk664074 Russia Department of Applied Mathematics and Programming South Ural State University Lenin Prospect 76 Chelyabinsk454080 Russia Department of Natural Science Disciplines Higher Military Aviation School of the Republic of Uzbekistan Karshi City180100 Uzbekistan

—The mathematical model for many problems is arising in different industries of natural science, basically formulated using differential, integral and integro-differential equations. The investigation of these equations is conducted with the help of numerical integration theory. It is commonly known that a class of problems can be solved by applying numerical integration. The construction of the quadrature formula has a direct relation with the computation of definite integrals. The theory of definite integrals is used in geometry, physics, mechanics and in other related subjects of science. In this work, the existence and uniqueness of the solution of above-mentioned equations are investigated. By this way, the domain has been defined in which the solution of these problems is equivalent. All proposed four problems can be solved using one and the same methods. We define some domains in which the solution of one of these problems is also the solution of the other problems. Some stable methods with the degree p © 2021, North Atlantic University Union NAUN. All rights reserved.

关键词： Integrodifferential equations

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Evaluation of the Impact of Various Local Data Caching Configurations on Tier2/Tier3 WLCG Sites 4

Evaluation of the Impact of Various Local Data Caching Confi...

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4th International Workshop on Data Life Cycle in Physics, DLC 2020

作者： Alekseev, Aleksandr Jezequel, Stephane Kiryanov, Andrey Klimentov, Alexei Korchuganova, Tatiana Mitsyn, Valery Oleynik, Danila Smirnov, Serge Zarochentsev, Andrey Nrc ÂKurchatov Instituteâ A- Pnpi Gatchina Russia Saint Petersburg State University Saint Petersburg Russia Brookhaven National Laboratory UptonNY United States Joint Institute for Nuclear Research Dubna Russia National Research Nuclear University MEPhI Moscow Russia Institute for System Programming Ras Moscow Russia University Andres Bello Santiago Chile Plekhanov University of Economy Moscow Russia Laboratoire DâAnnecy de Physique des Particules Annecy France

In this paper, we describe various data caching scenarios test implementation and lessons learned. In particular, we show how local data caches may be configured, deployed, and tested. In our studies, we are using xCache, which is a special type of Xrootd server setup to cache input data for a physics analysis. A relatively large Tier2 storage is used as a primary data source and several geographically distributed smaller WLCG sites configured specifically for this test. All sites are connected to the LHCONE network. The testbed configuration is evaluated using both synthetic tests and real ATLAS computational jobs submitted via the HammerCloud toolkit. The impact and realistic applicability of different local cache configurations is explained, including both the network infrastructure and the configuration of computing nodes. © 2020 CEUR-WS. All rights reserved.

关键词： High energy physics

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Scientific Data Lake for High Luminosity LHC project and other data-intensive particle and astro-particle physics experiments 5

Scientific Data Lake for High Luminosity LHC project and oth...

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5th International Conference on Particle Physics and Astrophysics, ICPPA 2020

作者： Alekseev, A. Kiryanov, A. Klimentov, A. Korchuganova, T. Mitsyn, V. Oleynik, D. Smirnov, A. Smirnov, S. Zarochentsev, A. Compiler Technology Department Ivannikov Institute for System Programming of the Ras Moscow109004 Russia Cloud Technologies and Big Data Analytics Laboratory Plekhanov Russian University of Economics Moscow117997 Russia Atlas Group Universidad Andres Bello Santiago7550196 Chile Department of Computing Resources and Technologies Nrc "kurchatov Institute"-PNPI Gatchina188300 Russia Physics Department Brookhaven National Laboratory UptonNY11973 United States Laboratory of Information Technologies Joint Institute for Nuclear Research Dubna141980 Russia Institute of Nuclear Physics and Engineering National Research Nuclear University MEPhI Moscow115409 Russia Laboratory of Ultra-High Energy Physics Saint Petersburg State University Saint Petersburg198504 Russia

The next phase of LHC Operations-High Luminosity LHC (HL-LHC), which is aimed at ten-fold increase in the luminosity of proton-proton collisions at the energy of 14 TeV, is expected to start operation in 2027-2028 and will deliver an unprecedented scientific data volume of multi-exabyte scale. This amount of data has to be stored and the corresponding storage system should ensure fast and reliable data delivery for processing by scientific groups distributed all over the world. The present LHC computing and data processing model will not be able to provide the required infrastructure growth even taking into account the expected hardware technology evolution. To address this challenge the new state-of-The-Art computing infrastructure technologies are now being developed and are presented here. The possibilities of application of the HL-LHC distributed data handling technique for other particle and astro-particle physics experiments dealing with large-scale data volumes like DUNE, LSST, Belle-II, JUNO, SKAO etc. are also discussed. © Published under licence by IOP Publishing Ltd.

关键词： Luminance

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Functorial string diagrams for reverse-mode automatic differentiation

arXiv

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arXiv 2021年

作者： Alvarez-Picallo, Mario Ghica, Dan R. Sprunger, David Zanasi, Fabio Programming Languages Laboratory Huawei Research Centre 2 Semple Str. EdinburghEH3 8BL United Kingdom Computer Science and University of Birmingham Birmingham EnglandB15 2TT United Kingdom Computer Science University College London London EnglandWC1E 6BT United Kingdom

We enhance the calculus of string diagrams for monoidal categories with hierarchical features in order to capture closed monoidal (and cartesian closed) structure. Using this new syntax we formulate an automatic differentiation algorithm for (applied) simply typed lambda calculus in the style of [Pearlmutter and Siskind 2008] and we prove for the first time its soundness. To give an efficient yet principled implementation of the AD algorithm we define a sound and complete representation of hierarchical string diagrams as a class of hierarchical hypergraphs we call hypernets. Copyright © 2021, The Authors. All rights reserved.

关键词： Graph theory

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Russian DATA LAKE PROTOTYPE AS AN APPROACH towards NATIONAL FEDERATED STORAGE for MEGASCIENCE 9

Russian DATA LAKE PROTOTYPE AS AN APPROACH towards NATIONAL ...

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9th International Conference "Distributed Computing and Grid Technologies in Science and Education", GRID 2021

作者： Alekseev, Aleksandr Kiryanov, Andrey Klimentov, Aleksey Korchuganova, Tatyana Oleynik, Danila Zarochentsev, Anderey NRC "Kurchatov Institute" 1 Akademika Kurchatova sq. Moscow123182 Russia Petersburg Nuclear Physics Institute of NRC "Kurchatov Institute" 1 Orlova Rocha Gatchina 188300 Russia Saint Petersburg State University 7-9 Universitetskaya emb. Saint Petersburg199034 Russia Brookhaven National Laboratory UptonNY United States Ivannikov Institute for System Programming RAS 25 Alexander Solzhenitsyn st. Moscow109004 Russia University Andres Bello Santiago Chile Plekhanov Russian University of Economics 36 Stremyanny lane Moscow117997 Russia Joint Institute for Nuclear Research 6 Joliot-Curie st. Dubna 141980 Russia

A substantial data volume growth will appear with the start of the HL-LHC era. It is not well covered by the current LHC computing model, even taking into account the hardware evolution. The WLCG DOMA project was established to provide data management and storage researches. National data lake r&d's, as a part of the DOMA project, should address the study of possible technology solutions for the organization of intelligent distributed federated storage. This talk will present the current status of the Russian Scientific Data lake prototype and the methodology, which is used for the validation and functional testing of deployed infrastructure. Copyright © 2021 for this paper by its authors. Use permitted under Creative Commons License Attribution 4.0 International (CC BY 4.0).

关键词： Lakes

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Polynomial spline collocation method for solving weakly regular Volterra integral equations of the first kind

arXiv

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arXiv 2021年

作者： Tynda, Aleksandr Noeiaghdam, Samad Sidorov, Denis Higher and Applied Mathematics Department Penza State University Penza440026 Russia Industrial Mathematics Laboratory Baikal School of BRICS Irkutsk National Research Technical University Irkutsk664074 Russia Department of Applied Mathematics and Programming South Ural State University Lenin prospect 76 Chelyabinsk454080 Russia Energy Systems Institute Siberian Branch of Russian Academy of Science Irkutsk664033 Russia Institute of Mathematics and Information Technologies Irkutsk State University Irkutsk664025 Russia

The polynomial spline collocation method is proposed for solution of Volterra integral equations of the first kind with special piecewise continuous kernels. The Gauss-type quadrature formula is used to approximate integrals during the discretization of the proposed projection method. The estimate of accuracy of approximate solution is obtained. Stochastic arithmetics is also used based on the Contrôle et Estimation Stochastique des Arrondis de Calculs (CESTAC) method and the Control of Accuracy and Debugging for Numerical Applications (CADNA) library. Applying this approach it is possible to find optimal parameters of the projective method. The numerical examples are included to illustrate the efficiency of proposed novel collocation *** Codes 45H05, 65R20 © 2021, CC BY.

关键词： Integral equations

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SIRT3-mediated inhibition of FOS through histone H3 deacetylation prevents cardiac fibrosis and inflammation

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Signal Transduction and Targeted Therapy 2020年第1期5卷 2322-2331页

作者： Xavier Palomer MSilvia Román-Azcona Javier Pizarro-Delgado Ana Planavila Francesc Villarroya Brenda Valenzuela-Alcaraz Fátima Crispi Álvaro Sepúlveda-Martínez Irene Miguel-Escalada Jorge Ferrer JFrancisco Nistal Raquel García Mercy MDavidson Emma Barroso Manuel Vázquez-Carrera Department of Pharmacology Toxicology and Therapeutic ChemistryIBUB(Institut de Biomedicina de la Universitat de Barcelona)Research Institute-Pediatric Research InstituteHospital Sant Joan de Déuand CIBER de Diabetes y Enfermedades Metabólicas Asociadas(CIBERDEM)Faculty of Pharmacy and Food SciencesUniversity of BarcelonaBarcelonaSpain Department of Biochemistry and Molecular Biomedicine IBUB and CIBER Fisiopatología de la Obesidad y Nutrición(CIBEROBN)Faculty of BiologyUniversity of BarcelonaBarcelonaSpain aBCNatal-Barcelona Center for Maternal–Fetal and Neonatal Medicine(Hospital Clínic and Hospital Sant Joan de Deu) Institut d’Investigacions Biomèdiques August Pi i SunyerUniversitat de Barcelonaand Center for Biomedical Research on Rare Diseases(CIBER-ER)BarcelonaSpain Genomic Programming of Betacells Laboratory Institut d’Investigacions August Pi i Sunyer(IDIBAPS)and CIBERDEMBarcelonaSpain Section of Epigenomics and Disease Department of Medicineand National Institute for Health Research(NIHR)Imperial Biomedical Research CentreImperial College LondonLondonUK Servicio de Cirugía Cardiovascular Hospital Universitario Marqués de ValdecillaDepartamento de Ciencias Médicas y QuirúrgicasFacultad de MedicinaUniversidad de CantabriaInstituto de Investigación Marqués de Valdecilla(IDIVAL)Centro de Investigación Biomédica en Red Cardiovascular(CIBERCV)Instituto de Salud Carlos IIISantanderSpain Departamento de Fisiología y Farmacología Facultad de MedicinaUniversidad de CantabriaInstituto de Investigación Marqués de Valdecilla(IDIVAL)SantanderSpain Department of Radiation Oncology Columbia UniversityNew YorkNYUSA

Sirtuin 3(SIRT3)is a deacetylase that modulates proteins that control metabolism and protects against oxidative *** of SIRT3 activity has been proposed as a promising therapeutic target for ameliorating metabolic diseases and associated cardiac *** this study,we investigated the role of SIRT3 in inflammation and fibrosis in the heart using male mice with constitutive and systemic deletion of SIRT3 and human cardiac AC16 ***3 knockout mice showed cardiac fibrosis and inflammation that was characterized by augmented transcriptional activity of *** with this,SIRT3 overexpression in human and neonatal rat cardiomyocytes partially prevented the inflammatory and profibrotic response induced by TNF-α.Notably,these effects were associated with a decrease in the mRNA and protein levels of FOS and the DNA-binding activity of ***,we demonstrated that SIRT3 inhibits FOS transcription through specific histone H3 lysine K27 deacetylation at its *** findings highlight an important function of SIRT3 in mediating the often intricate profibrotic and proinflammatory responses of cardiac cells through the modulation of the FOS/AP-1 *** fibrosis and inflammation are crucial in the progression of cardiac hypertrophy,heart failure,and diabetic cardiomyopathy,our results point to SIRT3 as a potential target for treating these diseases.

关键词： SIRT3 inflammation cardiac

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Examining the Effect of Fish Oil Supplementation in Chinese Pregnant Women on Gestation Duration and Risk of Preterm Delivery (vol 149, pg 1942, 2019)

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JOURNAL OF NUTRITION 2019年第11期149卷 2073-2073页

作者： Olsen, S. F. Hansen, H. S. Jensen, B. Sorensen, T., I Centre for Fetal Programming Department of Epidemiology Research Statens Serum Institut Copenhagen Denmark Department of Nutrition Harvard TH Chan School of Public Health Boston MA USA Faculty of Food Science and Nutrition School of Health Sciences University of Iceland Reykjavik Iceland Key Laboratory of Reproduction Regulation of NPFPC SIPPR IRD Fudan University Shanghai China Department of Reproductive Epidemiology and Social Medicine Shanghai Institute of Planned Parenthood Research Shanghai China Faculty of Natural and Health Sciences University of the Faroe Islands Torshavn Faroe Islands School of Public Health Fudan University Shanghai China Nutrition and Food Hygiene Institute School of Public Health Lanzhou University Lanzhou China Shaanxi Health and Family Planning Commission Xi'an China Department of Clinical Epidemiology Aarhus University Hospital Aarhus Denmark

Background Intervention studies have shown that long-chain (LC) n-3 PUFA intake can prolong gestation but the dose−time−effect relations remain unresolved. Objective We examined the effect on gestation duration of 2 doses of supplemental LC n-3 PUFAs. Methods We undertook a 3-group parallel randomized controlled trial in areas of China with low (median: 2.1 g/d) and higher (14.3 g/d) fish intake. Unselected women (median: age, 26.2 y; BMI, 20. kg/m 2 ) were randomly assigned at midgestation to take four 0.72-g identical gelatin capsules per day until the last day of the preterm period (<259 days of gestation), when they were asked to stop. Capsules contained fish oil [high fish oil (HFO) group (60% w/w LC n-3 PUFAs)], a 1:3 mixture of fish oil to olive oil [low fish oil (LFO) group (20%)], or olive oil [control (CON) group (0%)], providing 2.0, 0.5, and 0 g/d of LC n-3 PUFAs, respectively. Habitual fish intake was recorded at baseline. Hazard rate ratios (HRRs) for spontaneous delivery <259 days of gestation and <273 days of gestation across groups were estimated by Cox regression. Results Among 5531 women randomly assigned, 92.5% were included in analyses (1706/1825, 1695/1851, and 1717/1855, respectively). The groups were similar with respect to hazard rates <259 days of gestation [HRR: 1.04 (95% CI: 0.70, 1.53) for LFO compared with CON and 0.90 (95% CI: 0.60, 1.35) for HFO compared with CON], hazard rates <273 days of gestation [HRR: 1.00 (95% CI: 0.86, 1.18) and 0.91 (95% CI: 0.77, 1.07), respectively], and mean gestation durations [differences: 0.2 d (95% CI: −0.5, 0.8) and 0.6 d (95% CI: −0.06, 1.2), respectively]. Inspection of pregnancy survival curves suggested that LC n-3 PUFAs delayed delivery in low fish consumers by 5–10 d and that this effect ceased rapidly after stopping taking the capsules. Conclusion This trial could not substantiate that fish oil prevents preterm birth in Chinese women, possibly because statistical power was too low. This trial wa

关键词： China fish oil gestation duration long-chain n-3 fatty acids pregnancy preterm birth RCT

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