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https://www.readbyqxmd.com/read/28538984/accuracy-of-medical-claims-for-identifying-cardiovascular-and-bleeding-events-after-myocardial-infarction-a-secondary-analysis-of-the-translate-acs-study
#1
Patricia O Guimarães, Arun Krishnamoorthy, Lisa A Kaltenbach, Kevin J Anstrom, Mark B Effron, Daniel B Mark, Patrick L McCollam, Linda Davidson-Ray, Eric D Peterson, Tracy Y Wang
Importance: Pragmatic clinical trial designs have proposed the use of medical claims data to ascertain clinical events; however, the accuracy of billed diagnoses in identifying potential events is unclear. Objectives: To compare the 1-year cumulative incidences of events when events were identified by medical claims vs by physician adjudication and to assess the accuracy of bill-identified events using physician adjudication as the criterion standard. Design, Setting, and Participants: This post hoc analysis of a clinical trial assessed the medical claims forms and records for all rehospitalizations at 233 US hospitals within 1 year of the index acute myocardial infarction (MI) of 12 365 patients enrolled in the Treatment With Adenosine Diphosphate Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary Syndrome (TRANSLATE-ACS) study between April 1, 2010, and October 31, 2012...
May 24, 2017: JAMA Cardiology
https://www.readbyqxmd.com/read/28538164/post-translational-regulation-of-plant-immunity
#2
REVIEW
John Withers, Xinnian Dong
Plants have evolved multi-layered molecular defense strategies to protect against pathogens. Plant immune signaling largely relies on post-translational modifications (PTMs) to induce rapid alterations of signaling pathways to achieve a response that is appropriate to the type of pathogen and infection pressure. In host cells, dynamic PTMs have emerged as powerful regulatory mechanisms that cells use to adjust their immune response. PTM is also a virulence strategy used by pathogens to subvert host immunity through the activities of effector proteins secreted into the host cell...
May 21, 2017: Current Opinion in Plant Biology
https://www.readbyqxmd.com/read/28534506/lsd1-demethylates-hif1%C3%AE-to-inhibit-hydroxylation-and-ubiquitin-mediated-degradation-in-tumor-angiogenesis
#3
J-Y Lee, J-H Park, H-J Choi, H-Y Won, H-S Joo, D-H Shin, M K Park, B Han, K P Kim, T J Lee, C M Croce, G Kong
Lysine-specific demethylase 1 (LSD1), which has been considered as a potential therapeutic target in human cancer, has been known to regulate many biological functions through its non-histone substrates. Although LSD1-induced hypoxia-inducible factor alpha (HIF1α) demethylation has recently been proposed, the effect of LSD1 on the relationship between HIF1α post-translational modifications (PTMs) and HIF1α-induced tumor angiogenesis remains to be elucidated. Here, we identify a new methylation site of the HIF1α protein antagonized by LSD1 and the interplay between HIF1α protein methylation and other PTMs in regulating tumor angiogenesis...
May 22, 2017: Oncogene
https://www.readbyqxmd.com/read/28533144/discovery-of-two-p-superfamily-conotoxins-lt9a-and-lt9b-with-different-modifications-on-voltage-sensitive-sodium-channels
#4
Lei Wang, Junliang Liu, Zhenghua Ren, Yu Chen, Anlong Xu
In this work, two P-superfamily conotoxins, lt9a and lt9b, were purified and characterized from the crude venom of Conus litteratus. The amino acid sequences of lt9a and lt9b were determined by the Edman degradation method. It has been suggested that both lt9a and lt9b are produced from the precursor encoded by the gene Lt9.1. During the conotoxin maturation process, different post-translational modifications occurred between lt9a and lt9b. Conotoxin lt9b was predicted to have two prolines that underwent hydroxylation and one glutamate that underwent carboxylation, while lt9a had no hydroxyproline and carboxyglutamate residue...
May 19, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28533032/design-and-synthesis-of-an-immobilized-metal-affinity-chromatography-and-metal-oxide-affinity-chromatography-hybrid-material-for-improved-phosphopeptide-enrichment
#5
Da-Song Yang, Xi-Ying Ding, Hong-Ping Min, Bo Li, Meng-Xiang Su, Miao-Miao Niu, Bin Di, Fang Yan
Reversible phosphorylation of proteins is one of the most important post-translational modifications, while the detection of phosphopeptides is difficult due to their low abundance and the signal suppression of nonphosphorylated peptides. Therefore, selective enrichment of phosphopeptides from highly complicated mixtures is vital for MS-based phosphoproteome analysis. Despite various strategies have been developed, there is no single method that is capable of providing full coverage of the whole phosphoproteome...
May 10, 2017: Journal of Chromatography. A
https://www.readbyqxmd.com/read/28533023/the-rna-modification-n-6-methyladenosine-and-its-implications-in-human-disease
#6
REVIEW
Pedro J Batista
Impaired gene regulation lies at the heart of many disorders, including developmental diseases and cancer. Furthermore, the molecular pathways that control gene expression are often the target of cellular parasites, such as viruses. Gene expression is controlled through multiple mechanisms that are coordinated to ensure the proper and timely expression of each gene. Many of these mechanisms target the life cycle of the RNA molecule, from transcription to translation. Recently, another layer of regulation at the RNA level involving RNA modifications has gained renewed interest of the scientific community...
May 19, 2017: Genomics, Proteomics & Bioinformatics
https://www.readbyqxmd.com/read/28530711/a-combinatorial-screen-of-the-cloud-uncovers-a-synergy-targeting-the-androgen-receptor
#7
Marco P Licciardello, Anna Ringler, Patrick Markt, Freya Klepsch, Charles-Hugues Lardeau, Sara Sdelci, Erika Schirghuber, André C Müller, Michael Caldera, Anja Wagner, Rebecca Herzog, Thomas Penz, Michael Schuster, Bernd Boidol, Gerhard Dürnberger, Yasin Folkvaljon, Pär Stattin, Vladimir Ivanov, Jacques Colinge, Christoph Bock, Klaus Kratochwill, Jörg Menche, Keiryn L Bennett, Stefan Kubicek
Approved drugs are invaluable tools to study biochemical pathways, and further characterization of these compounds may lead to repurposing of single drugs or combinations. Here we describe a collection of 308 small molecules representing the diversity of structures and molecular targets of all FDA-approved chemical entities. The CeMM Library of Unique Drugs (CLOUD) covers prodrugs and active forms at pharmacologically relevant concentrations and is ideally suited for combinatorial studies. We screened pairwise combinations of CLOUD drugs for impairment of cancer cell viability and discovered a synergistic interaction between flutamide and phenprocoumon (PPC)...
May 22, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28529622/ires-mediated-protein-translation-overcomes-suppression-by-the-p14arf-tumor-suppressor-protein
#8
Song Xi, Ming Zhao, Si Wang, Ling Ma, Shensen Wang, Xianling Cong, Ruth A Gjerset, Rebecca C Fitzgerald, Yinghui Huang
Internal ribosome entry sites (IRES elements) have attracted interest in cancer gene therapy because they can be used in the design of gene transfer vectors that provide bicistronic co-expression of two transgene products under the control of a single promoter. Unlike cellular translation of most mRNAs, a process that requires a post-translational 5' modification of the mRNA known as the cap structure, IRES-mediated translation is independent of the cap structure. The cellular conditions that may intervene to modulate IRES-mediated, cap-independent versus cap-dependent translation, however, remain poorly understood, although they could be critical to the choice of gene transfer vectors...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28529348/different-stationary-phase-selectivities-and-morphologies-for-intact-protein-separations
#9
REVIEW
A Astefanei, I Dapic, M Camenzuli
The central dogma of biology proposed that one gene encodes for one protein. We now know that this does not reflect reality. The human body has approximately 20,000 protein-encoding genes; each of these genes can encode more than one protein. Proteins expressed from a single gene can vary in terms of their post-translational modifications, which often regulate their function within the body. Understanding the proteins within our bodies is a key step in understanding the cause, and perhaps the solution, to disease...
2017: Chromatographia
https://www.readbyqxmd.com/read/28529077/plmd-an-updated-data-resource-of-protein-lysine-modifications
#10
Haodong Xu, Jiaqi Zhou, Shaofeng Lin, Wankun Deng, Ying Zhang, Yu Xue
Post-translational modifications (PTMs) occurring at protein lysine residues, or protein lysine modifications (PLMs), play critical roles in regulating biological processes. Due to the explosive expansion of the amount of PLM substrates and the discovery of novel PLM types, here we greatly updated our previous studies, and presented a much more integrative resource of protein lysine modification database (PLMD). In PLMD, we totally collected and integrated 284,780 modification events in 53,501 proteins across 176 eukaryotes and prokaryotes for up to 20 types of PLMs, including ubiquitination, acetylation, sumoylation, methylation, succinylation, malonylation, glutarylation, glycation, formylation, hydroxylation, butyrylation, propionylation, crotonylation, pupylation, neddylation, 2-hydroxyisobutyrylation, phosphoglycerylation, carboxylation, lipoylation and biotinylation...
May 3, 2017: Journal of Genetics and Genomics, Yi Chuan Xue Bao
https://www.readbyqxmd.com/read/28528988/ubiquitin-dependent-regulation-of-stem-cell-biology
#11
REVIEW
Achim Werner, Andrew G Manford, Michael Rape
The growth of a metazoan body relies on a series of highly coordinated cell-fate decisions by stem cells which can undergo self-renewal, reversibly enter a quiescent state, or terminally commit to a cell specification program. To guide their decisions, stem cells make frequent use of ubiquitylation, a post-translational modification that can affect the activity, interaction landscape, or stability of stem cell proteins. In this review we discuss novel findings that have provided insight into ubiquitin-dependent mechanisms of stem cell control and revealed how an essential and highly conserved protein modification can shape metazoan development...
May 18, 2017: Trends in Cell Biology
https://www.readbyqxmd.com/read/28528441/herpesvirus-latency-on-the-importance-of-positioning-oneself
#12
Patrick Lomonte
The nucleus is composed of multiple compartments and domains, which directly or indirectly influence many cellular processes including gene expression, RNA splicing and maturation, protein post-translational modifications, and chromosome segregation. Nuclear-replicating viruses, especially herpesviruses, have co-evolved with the cell, adopting strategies to counteract and eventually hijack this hostile environment for their own benefit. This allows them to persist in the host for the entire life of an individual and to ensure their maintenance in the target species...
2017: Advances in Anatomy, Embryology, and Cell Biology
https://www.readbyqxmd.com/read/28528271/exploring-binding-characteristics-and-the-related-competition-of-different-protein-bound-uremic-toxins
#13
Olivier Deltombe, Henriette de Loor, Griet Glorieux, Annemieke Dhondt, Wim Van Biesen, Björn Meijers, Sunny Eloot
Little is known about potential differences in binding characteristics of protein-bound uremic toxins (PBUTs) in patients with chronic kidney disease (CKD) versus healthy controls. The question arises whether eventual differences are attributed to (i) the elevated levels of competing uremic toxins, and/or (ii) post-translational modifications of albumin. We evaluated the binding characteristics of hippuric acid (HA), indole-3-acetic acid (IAA), indoxyl sulfate (IS), and p-cresylsulfate (pCS) by deriving a binding curve in three distinct conditions: (i) serum from healthy controls (healthy serum), (ii) blank serum from hemodialysis patients (blank HD serum; i...
May 17, 2017: Biochimie
https://www.readbyqxmd.com/read/28527406/the-relevance-of-ki-calculation-for-bi-substrate-enzymes-illustrated-by-kinetic-evaluation-of-a-novel-lysine-k-acetyltransferase-8-inhibitor
#14
Hannah Wapenaar, Thea van den Bosch, Niek G J Leus, Petra E van der Wouden, Nikolaos Eleftheriadis, Jos Hermans, Gebremedhin Solomon Hailu, Dante Rotili, Antonello Mai, Alexander Dömling, Rainer Bischoff, Hidde J Haisma, Frank J Dekker
Histone acetyltransferases (HATs) are important mediators of epigenetic post-translational modifications of histones that play important roles in health and disease. A disturbance of these modifications can result in disease states, such as cancer or inflammatory diseases. Inhibitors of HATs (HATi) such as lysine (K) acetyltransferase 8 (KAT8), could be used to study the epigenetic processes in diseases related to these enzymes or to investigate HATs as therapeutic targets. However, the development of HATi is challenged by the difficulties in kinetic characterization of HAT enzymes and their inhibitors to enable calculation of a reproducible inhibitory potency...
May 5, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28526919/antibodies-to-post-translationally-modified-insulin-as-a-novel-biomarker-for-prediction-of-type-1-diabetes-in-children
#15
Rocky Strollo, Chiara Vinci, Nicola Napoli, Paolo Pozzilli, Johnny Ludvigsson, Ahuva Nissim
AIMS/HYPOTHESIS: We have shown that autoimmunity to insulin in type 1 diabetes may result from neoepitopes induced by oxidative post-translational modifications (oxPTM). Antibodies specific to oxPTM-insulin (oxPTM-INS-Ab) are present in most newly diagnosed individuals with type 1 diabetes and are more common than autoantibodies to native insulin. In this study, we investigated whether oxPTM-INS-Ab are present before clinical onset of type 1 diabetes, and evaluated the ability of oxPTM-INS-Ab to identify children progressing to type 1 diabetes...
May 20, 2017: Diabetologia
https://www.readbyqxmd.com/read/28526911/dynamics-of-post-translationally-modified-histones-during-barley-pollen-embryogenesis-in-the-presence-or-absence-of-the-epi-drug-trichostatin-a
#16
Pooja Pandey, Diaa S Daghma, Andreas Houben, Jochen Kumlehn, Michael Melzer, Twan Rutten
Improving pollen embryogenesis. Despite the agro-economic importance of pollen embryogenesis, the mechanisms underlying this process are still poorly understood. We describe the dynamics of chromatin modifications (histones H3K4me2, H3K9ac, H3K9me2, and H3K27me3) and chromatin marks (RNA polymerase II CDC phospho-Ser5, and CENH3) during barley pollen embryogenesis. Immunolabeling results show that, in reaction to stress, immature pollen rapidly starts reorganizing several important chromatin modifications indicative of a change in cell fate...
May 19, 2017: Plant Reproduction
https://www.readbyqxmd.com/read/28526709/acetylation-of-mitochondrial-proteins-by-gcn5l1-promotes-enhanced-fatty-acid-oxidation-in-the-heart
#17
Dharendra Thapa, Manling Zhang, Janet R Manning, Danielle Guimarães, Michael Stoner, Robert M O'Doherty, Sruti Shiva, Iain Scott
Lysine acetylation is a reversible post-translational modification, and is particularly important in the regulation of mitochondrial metabolic enzymes. Acetylation uses acetyl-CoA derived from fuel metabolism as a co-factor, thereby linking nutrition to metabolic activity. In this study, we investigated how mitochondrial acetylation status in the heart is controlled by food intake, and how these changes affect mitochondrial metabolism. We found that there was a significant increase in cardiac mitochondrial protein acetylation in mice fed a long-term high fat diet, and that this change correlated with an increase in the abundance of the mitochondrial acetyltransferase-related protein GCN5L1...
May 19, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28526583/the-connexin-43-c-terminus-a-tail-of-many-tales
#18
REVIEW
Edward Leithe, Marc Mesnil, Trond Aasen
Connexins are chordate gap junction channel proteins that, by enabling direct communication between the cytosols of adjacent cells, create a unique cell signalling network. Gap junctional intercellular communication (GJIC) has important roles in controlling cell growth and differentiation and in tissue development and homeostasis. Moreover, several non-canonical connexin functions unrelated to GJIC have been discovered. Of the 21 members of the human connexin family, connexin 43 (Cx43) is the most widely expressed and studied...
May 16, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28526562/new-intracellular-activities-of-matrix-metalloproteinases-shine-in-the-moonlight
#19
REVIEW
Parker G Jobin, Georgina S Butler, ChristopherM Overall
Adaption of a single protein to perform multiple independent functions facilitates functional plasticity of the proteome allowing a limited number of protein-coding genes to perform a multitude of cellular processes. Multifunctionality is achievable by post-translational modifications and by modulating subcellular localization. Matrix metalloproteinases (MMPs), classically viewed as degraders of the extracellular matrix (ECM) responsible for matrix protein turnover, are more recently recognized as regulators of a range of extracellular bioactive molecules including chemokines, cytokines, and their binders...
May 16, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28525736/a-flick-of-the-tail-keeps-the-circadian-clock-in-line
#20
Rajesh Narasimamurthy, David M Virshup
Circadian clocks signal and adapt to an ever-changing world by juggling a panoply of transcriptional and post-translational modifications. In this issue of Molecular Cell, Gustafson et al. (2017) report an additional requirement for accurate timekeeping, a cis/trans conformational flicker in the transcriptional activation domain of the core clock protein BMAL1.
May 18, 2017: Molecular Cell
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