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C. David Allis

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https://www.readbyqxmd.com/read/27924077/metabolic-regulation-of-gene-expression-through-histone-acylations
#1
Benjamin R Sabari, Di Zhang, C David Allis, Yingming Zhao
Eight types of short-chain Lys acylations have recently been identified on histones: propionylation, butyrylation, 2-hydroxyisobutyrylation, succinylation, malonylation, glutarylation, crotonylation and β-hydroxybutyrylation. Emerging evidence suggests that these histone modifications affect gene expression and are structurally and functionally different from the widely studied histone Lys acetylation. In this Review, we discuss the regulation of non-acetyl histone acylation by enzymatic and metabolic mechanisms, the acylation 'reader' proteins that mediate the effects of different acylations and their physiological functions, which include signal-dependent gene activation, spermatogenesis, tissue injury and metabolic stress...
December 7, 2016: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/27881822/lowered-h3k27me3-and-dna-hypomethylation-define-poorly-prognostic-pediatric-posterior-fossa-ependymomas
#2
Jill Bayliss, Piali Mukherjee, Chao Lu, Siddhant U Jain, Chan Chung, Daniel Martinez, Benjamin Sabari, Ashley S Margol, Pooja Panwalkar, Abhijit Parolia, Melike Pekmezci, Richard C McEachin, Marcin Cieslik, Benita Tamrazi, Benjamin A Garcia, Gaspare La Rocca, Mariarita Santi, Peter W Lewis, Cynthia Hawkins, Ari Melnick, C David Allis, Craig B Thompson, Arul M Chinnaiyan, Alexander R Judkins, Sriram Venneti
Childhood posterior fossa (PF) ependymomas cause substantial morbidity and mortality. These tumors lack recurrent genetic mutations, but a subset of these ependymomas exhibits CpG island (CpGi) hypermethylation [PF group A (PFA)], implicating epigenetic alterations in their pathogenesis. Further, histological grade does not reliably predict prognosis, highlighting the importance of developing more robust prognostic markers. We discovered global H3K27me3 reduction in a subset of these tumors (PF-ve ependymomas) analogous to H3K27M mutant gliomas...
November 23, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27864305/oncogenic-mechanisms-of-histone-h3-mutations
#3
Daniel N Weinberg, C David Allis, Chao Lu
Recurrent missense mutations in histone H3 were recently reported in pediatric gliomas and soft tissue tumors. Strikingly, these mutations only affected a minority of the total cellular H3 proteins and occurred at or near lysine residues at positions 27 and 36 on the amino-terminal tail of H3 that are subject to well-characterized posttranslational modifications. Here we review recent progress in elucidating the mechanisms by which these mutations perturb the chromatin landscape in cells through their effects on chromatin-modifying machinery, particularly through inhibition of specific histone lysine methyltransferases...
November 18, 2016: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/27855477/recruitment-manoeuvres-for-adults-with-acute-respiratory-distress-syndrome-receiving-mechanical-ventilation
#4
REVIEW
Carol Hodgson, Ewan C Goligher, Meredith E Young, Jennifer L Keating, Anne E Holland, Lorena Romero, Scott J Bradley, David Tuxen
BACKGROUND: Recruitment manoeuvres involve transient elevations in airway pressure applied during mechanical ventilation to open ('recruit') collapsed lung units and increase the number of alveoli participating in tidal ventilation. Recruitment manoeuvres are often used to treat patients in intensive care who have acute respiratory distress syndrome (ARDS), but the effect of this treatment on clinical outcomes has not been well established. This systematic review is an update of a Cochrane review originally published in 2009...
November 17, 2016: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/27836401/novel-bicyclo-3-1-0-hexane-analogs-as-antagonists-of-metabotropic-glutamate-2-3-receptors-for-the-treatment-of-depression
#5
Bruce A Dressman, Eric G Tromiczak, Mark D Chappell, Allie E Tripp, Steven J Quimby, Tatiana Vetman, Adam M Fivush, James Matt, Carlos Jaramillo, Renhua Li, Albert Khilevich, Maria-Jesus Blanco, Stephon C Smith, Mercedes Carpintero, José Eugenio de Diego, Mario Barberis, Susana García-Cerrada, José F Soriano, Jeffrey M Schkeryantz, Jeffrey M Witkin, Keith A Wafford, Wesley Seidel, Thomas Britton, Carl D Overshiner, Xia Li, Xu-Shan Wang, Beverly A Heinz, John T Catlow, Steven Swanson, David Bedwell, Paul L Ornstein, Charles H Mitch
Negative modulators of metabotropic glutamate 2 & 3 receptors demonstrate antidepressant-like activity in animal models and hold promise as novel therapeutic agents for the treatment of major depressive disorder. Herein we describe our efforts to prepare and optimize a series of conformationally constrained 3,4-disubstituted bicyclo[3.1.0]hexane glutamic acid analogs as orthosteric (glutamate site) mGlu2/3 receptor antagonists. This work led to the discovery of a highly potent and efficacious tool compound 18 (hmGlu2 IC50 46±14...
October 25, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27791098/aberrant-h3-3-dynamics-in-nac-promote-vulnerability-to-depressive-like-behavior
#6
Ashley E Lepack, Rosemary C Bagot, Catherine J Peña, Yong-Hwee E Loh, Lorna A Farrelly, Yang Lu, Samuel K Powell, Zachary S Lorsch, Orna Issler, Hannah M Cates, Carol A Tamminga, Henrik Molina, Li Shen, Eric J Nestler, C David Allis, Ian Maze
Human major depressive disorder (MDD), along with related mood disorders, is among the world's greatest public health concerns; however, its pathophysiology remains poorly understood. Persistent changes in gene expression are known to promote physiological aberrations implicated in MDD. More recently, histone mechanisms affecting cell type- and regional-specific chromatin structures have also been shown to contribute to transcriptional programs related to depressive behaviors, as well as responses to antidepressants...
November 1, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27775714/selective-recognition-of-histone-crotonylation-by-double-phd-fingers-of-moz-and-dpf2
#7
Xiaozhe Xiong, Tatyana Panchenko, Shuang Yang, Shuai Zhao, Peiqiang Yan, Wenhao Zhang, Wei Xie, Yuanyuan Li, Yingming Zhao, C David Allis, Haitao Li
Recognition of histone covalent modifications by 'reader' modules constitutes a major mechanism for epigenetic regulation. A recent upsurge of newly discovered histone lysine acylations, such as crotonylation (Kcr), butyrylation (Kbu), and propionylation (Kpr), greatly expands the coding potential of histone lysine modifications. Here we demonstrate that the histone acetylation-binding double PHD finger (DPF) domains of human MOZ (also known as KAT6A) and DPF2 (also known as BAF45d) accommodate a wide range of histone lysine acylations with the strongest preference for Kcr...
December 2016: Nature Chemical Biology
https://www.readbyqxmd.com/read/27768872/chromatin-kinases-act-on-transcription-factors-and-histone-tails-in-regulation-of-inducible-transcription
#8
Steven Z Josefowicz, Miho Shimada, Anja Armache, Charles H Li, Rand M Miller, Shu Lin, Aerin Yang, Brian D Dill, Henrik Molina, Hee-Sung Park, Benjamin A Garcia, Jack Taunton, Robert G Roeder, C David Allis
The inflammatory response requires coordinated activation of both transcription factors and chromatin to induce transcription for defense against pathogens and environmental insults. We sought to elucidate the connections between inflammatory signaling pathways and chromatin through genomic footprinting of kinase activity and unbiased identification of prominent histone phosphorylation events. We identified H3 serine 28 phosphorylation (H3S28ph) as the principal stimulation-dependent histone modification and observed its enrichment at induced genes in mouse macrophages stimulated with bacterial lipopolysaccharide...
October 20, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27608933/producing-a-socially-accountable-medical-school-amee-guide-no-109
#9
Charles Boelen, David Pearson, Arthur Kaufman, James Rourke, Robert Woollard, David C Marsh, Trevor Gibbs
Health systems worldwide are confronted with challenges due to increased demand from their citizens, an aging population, a variety of health risks and limited resources. Key health stakeholders, including academic institutions and medical schools, are urged to develop a common vision for a more efficient and equitable health sector. It is in this environment that Boelen and Heck defined the concept of the "Social Accountability of Medical Schools" - a concept that encourages schools to produce not just highly competent professionals, but professionals who are equipped to respond to the changing challenges of healthcare through re-orientation of their education, research and service commitments, and be capable of demonstrating a positive effect upon the communities they serve...
September 9, 2016: Medical Teacher
https://www.readbyqxmd.com/read/27602905/analysis-of-injury-patterns-and-roles-of-care-in-us-and-israel-militaries-during-recent-conflicts-two-are-better-than-one
#10
Ben Antebi, Avi Benov, Elizabeth A Mann-Salinas, Tuan D Le, Leopoldo C Cancio, Joseph C Wenke, Haim Paran, Avraham Yitzhak, Bader Tarif, Kirby R Gross, David Dagan, Elon Glassberg
BACKGROUND: As new conflicts emerge and enemies evolve, military medical organizations worldwide must adopt the "lessons learned." In this study, we describe roles of care (ROCs) deployed and injuries sustained by both US and Israeli militaries during recent conflicts. The purpose of this collaborative work is facilitate exchange of medical data among allied forces in order to advance military medicine and facilitate strategic readiness for future military engagements that may involve less predictable situations of evacuation and care, such as prolonged field care...
November 2016: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/27510669/distribution-of-plasmid-mediated-quinolone-resistance-in-gram-negative-bacteria-from-a-tertiary-hospital-in-nigeria
#11
David Olusoga Ogbolu, Armstrong Oyebode Alli, Michael C Anorue, Oluwole Adebayo Daini, Afolabi Oluwadun
BACKGROUND: Until recently, mechanisms of resistance to quinolones in Gram-negative bacteria were believed to be only chromosome encoded. However, emergence of plasmid-mediated quinolone resistance (PMQR) has been reported worldwide. AIM: This study investigated distribution of PMQR in Gram-negative bacteria from a tertiary hospital in eastern part of Nigeria. MATERIALS AND METHODS: Seventy-one nonduplicate Gram-negative bacterial isolates of eight species were analyzed for antimicrobial susceptibility, genotypic detection of various PMQRs, typed by random amplified polymorphic DNA (RAPD) and analysis of plasmids present, including replicon typing...
July 2016: Indian Journal of Pathology & Microbiology
https://www.readbyqxmd.com/read/27506785/histone-arginine-methylation-in-cocaine-action-in-the-nucleus-accumbens
#12
Diane M Damez-Werno, HaoSheng Sun, Kimberly N Scobie, Ningyi Shao, Jaclyn Rabkin, Caroline Dias, Erin S Calipari, Ian Maze, Catherine J Pena, Deena M Walker, Michael E Cahill, Ramesh Chandra, Amy Gancarz, Ezekiell Mouzon, Joseph A Landry, Hannah Cates, Mary-Kay Lobo, David Dietz, C David Allis, Ernesto Guccione, Gustavo Turecki, Paola Defilippi, Rachael L Neve, Yasmin L Hurd, Li Shen, Eric J Nestler
Repeated cocaine exposure regulates transcriptional regulation within the nucleus accumbens (NAc), and epigenetic mechanisms-such as histone acetylation and methylation on Lys residues-have been linked to these lasting actions of cocaine. In contrast to Lys methylation, the role of histone Arg (R) methylation remains underexplored in addiction models. Here we show that protein-R-methyltransferase-6 (PRMT6) and its associated histone mark, asymmetric dimethylation of R2 on histone H3 (H3R2me2a), are decreased in the NAc of mice and rats after repeated cocaine exposure, including self-administration, and in the NAc of cocaine-addicted humans...
August 23, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27474439/molecular-basis-for-oncohistone-h3-recognition-by-setd2-methyltransferase
#13
Shuang Yang, Xiangdong Zheng, Chao Lu, Guo-Min Li, C David Allis, Haitao Li
High-frequency point mutations of genes encoding histones have been identified recently as novel drivers in a number of tumors. Specifically, the H3K36M/I mutations were shown to be oncogenic in chondroblastomas and undifferentiated sarcomas by inhibiting H3K36 methyltransferases, including SETD2. Here we report the crystal structures of the SETD2 catalytic domain bound to H3K36M or H3K36I peptides with SAH (S-adenosylhomocysteine). In the complex structure, the catalytic domain adopts an open conformation, with the K36M/I peptide snuggly positioned in a newly formed substrate channel...
July 15, 2016: Genes & Development
https://www.readbyqxmd.com/read/27456839/metabolic-diagnosis-and-medical-prevention-of-calcium-nephrolithiasis-and-its-systemic-manifestations-a-consensus-statement
#14
Giovanni Gambaro, Emanuele Croppi, Fredric Coe, James Lingeman, Orson Moe, Elen Worcester, Noor Buchholz, David Bushinsky, Gary C Curhan, Pietro Manuel Ferraro, Daniel Fuster, David S Goldfarb, Ita Pfeferman Heilberg, Bernard Hess, John Lieske, Martino Marangella, Dawn Milliner, Glen M Preminger, Jose' Manuel Reis Santos, Khashayar Sakhaee, Kemal Sarica, Roswitha Siener, Pasquale Strazzullo, James C Williams
BACKGROUND: Recently published guidelines on the medical management of renal stone disease did not address relevant topics in the field of idiopathic calcium nephrolithiasis, which are important also for clinical research. DESIGN: A steering committee identified 27 questions, which were proposed to a faculty of 44 experts in nephrolithiasis and allied fields. A systematic review of the literature was conducted and 5216 potentially relevant articles were selected; from these, 407 articles were deemed to provide useful scientific information...
July 25, 2016: Journal of Nephrology
https://www.readbyqxmd.com/read/27393093/high-seroprevalence-of-asymptomatic-viral-haemoparasites-among-prospective-blood-donors-in%C3%A2-nigeria
#15
David Olusoga Ogbolu, Oyebode Terry Alli, Itunu Odeleye, Adeolu S Oluremi
OBJECTIVE: To determine the prevalence of viral haemoparasites in prospective Nigerian blood donors. METHODS: Ethical clearance was obtained and informed consent questionnaires were distributed to blood donors to obtain their demographical data. A total of 186 blood donors from LAUTECH Teaching Hospital, Osogbo were tested for hepatitis A virus (HAV), hepatitis B virus (HBV) and hepatitis C virus (HCV) using rapid test kit and enzyme linked immunosorbent assay. RESULTS: The highest prevalence of blood transmitted infections was 182 (97...
July 2016: Asian Pacific Journal of Tropical Medicine
https://www.readbyqxmd.com/read/27355532/seven-year-efficacy-of-rts-s-as01-malaria-vaccine-among-young-african-children
#16
RANDOMIZED CONTROLLED TRIAL
Ally Olotu, Gregory Fegan, Juliana Wambua, George Nyangweso, Amanda Leach, Marc Lievens, David C Kaslow, Patricia Njuguna, Kevin Marsh, Philip Bejon
BACKGROUND: The candidate malaria vaccine RTS,S/AS01 is being evaluated in order to inform a decision regarding its inclusion in routine vaccination schedules. METHODS: We conducted 7 years of follow-up in children who had been randomly assigned, at 5 to 17 months of age, to receive three doses of either the RTS,S/AS01 vaccine or a rabies (control) vaccine. The end point was clinical malaria (temperature of ≥37.5°C and infection with Plasmodium falciparum of >2500 parasites per cubic millimeter)...
June 30, 2016: New England Journal of Medicine
https://www.readbyqxmd.com/read/27346641/the-molecular-hallmarks-of-epigenetic-control
#17
C David Allis, Thomas Jenuwein
Over the past 20 years, breakthrough discoveries of chromatin-modifying enzymes and associated mechanisms that alter chromatin in response to physiological or pathological signals have transformed our knowledge of epigenetics from a collection of curious biological phenomena to a functionally dissected research field. Here, we provide a personal perspective on the development of epigenetics, from its historical origins to what we define as 'the modern era of epigenetic research'. We primarily highlight key molecular mechanisms of and conceptual advances in epigenetic control that have changed our understanding of normal and perturbed development...
August 2016: Nature Reviews. Genetics
https://www.readbyqxmd.com/read/27297938/maximum-load-to-failure-of-high-dose-versus-low-dose-gamma-irradiation-of-anterior-cruciate-ligament-allografts-a-meta-analysis
#18
REVIEW
Alex C DiBartola, Joshua S Everhart, Christopher C Kaeding, Robert A Magnussen, David C Flanigan
BACKGROUND: The objective of this study was to systematically evaluate the existing literature to compare the biomechanical effects of low dose and high dose gamma irradiation on commonly used ACL allografts. METHODS: A systematic search was performed in PubMed, Cumulative Index for Nursing and Allied Health Literature (CINAHL), Cochrane Reviews, SCOPUS, and SportDiscus. Nine studies were identified that met the following inclusion criteria: 1) controlled laboratory study, 2) investigation of standard allografts for anterior cruciate ligament reconstruction (ACLR), 3) gamma irradiation (dose reported) and a negative control group, and 4) mechanical loading (results reported)...
October 2016: Knee
https://www.readbyqxmd.com/read/27259201/greater-than-the-sum-of-parts-complexity-of-the-dynamic-epigenome
#19
REVIEW
Alexey A Soshnev, Steven Z Josefowicz, C David Allis
Information encoded in DNA is interpreted, modified, and propagated as chromatin. The diversity of inputs encountered by eukaryotic genomes demands a matching capacity for transcriptional outcomes provided by the combinatorial and dynamic nature of epigenetic processes. Advances in genome editing, visualization technology, and genome-wide analyses have revealed unprecedented complexity of chromatin pathways, offering explanations to long-standing questions and presenting new challenges. Here, we review recent findings, exemplified by the emerging understanding of crossregulatory interactions within chromatin, and emphasize the pathologic outcomes of epigenetic misregulation in cancer...
June 2, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27228120/worry-among-mexican-american-caregivers-of-community-dwelling-elders
#20
Bronwynne C Evans, David W Coon, Michael J Belyea
This mixed methods, multi-site, National Institute of Nursing Research (NINR)-funded, interdisciplinary, descriptive study aimed to identify expressions of worry in qualitative data obtained from caregiving Mexican American (MA) families assisting older adults. The purpose of this portion of the inquiry was to determine how worry is expressed, what happens to caregivers when they worry, and what adaptive strategies they used. We examined semi-structured interviews completed during six in-home visits with 116 caregivers...
August 2014: Hispanic Journal of Behavioral Sciences
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