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https://www.readbyqxmd.com/read/28545124/cornet-assigning-function-to-networks-of-co-evolving-residues-by-automated-literature-mining
#1
Tom van den Bergh, Giorgio Tamo, Alberto Nobili, Yifeng Tao, Tianwei Tan, Uwe T Bornscheuer, Remko K P Kuipers, Bas Vroling, René M de Jong, Kalyanasundaram Subramanian, Peter J Schaap, Tom Desmet, Bernd Nidetzky, Gert Vriend, Henk-Jan Joosten
CorNet is a web-based tool for the analysis of co-evolving residue positions in protein super-family sequence alignments. CorNet projects external information such as mutation data extracted from literature on interactively displayed groups of co-evolving residue positions to shed light on the functions associated with these groups and the residues in them. We used CorNet to analyse six enzyme super-families and found that groups of strongly co-evolving residues tend to consist of residues involved in a same function such as activity, specificity, co-factor binding, or enantioselectivity...
2017: PloS One
https://www.readbyqxmd.com/read/28543850/structures-and-kinetics-for-plant-nucleoside-triphosphate-diphosphohydrolases-ntpdases-support-a-domain-motion-catalytic-mechanism
#2
Emma L Summers, Mathew H Cumming, Tifany Oulavallickal, Nick Roberts, Vickery L Arcus
Extracellular nucleoside triphosphate diphosphohydrolases (NTPDases) are enzymes that hydrolyse extracellular nucleotides to the respective monophosphate nucleotides. In the past 20 years, NTPDases belonging to mammalian, parasitic and prokaryotic domains of life have been discovered, cloned and characterized. We reveal the first structures of NTPDases from the legume plant species Trifolium repens (7WC) and Vigna unguiculata subsp. cylindrica (DbLNP). Four crystal structures of 7WC and DbLNP were determined at resolutions between 1...
May 24, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28543193/patterns-of-anaphylaxis-after-diagnostic-work-up-a-follow-up-study-of-226-patients-with-suspected-anaphylaxis
#3
Athamaica Ruiz Oropeza, Carsten Bindslev-Jensen, Sigurd Broesby-Olsen, Thomas Kristensen, Michael Boe Møller, Hanne Vestergaard, Henrik Fomsgaard Kjaer, Susanne Halken, Annmarie Lassen, Charlotte G Mortz
BACKGROUND: Most published studies on anaphylaxis are retrospective or register based. Data on subsequent diagnostic work-up are sparse. We aimed to characterize patients seen with suspected anaphylaxis at the emergency care setting (ECS), after subsequent diagnostic work-up at our Allergy Center (AC). METHODS: Prospective study including patients from the ECS, Odense University Hospital, during May 2013-April 2014. Possible anaphylaxis cases were daily identified based on a broad search profile including history and symptoms in patient records, diagnostic codes and pharmacological treatments...
May 19, 2017: Allergy
https://www.readbyqxmd.com/read/28542178/uncovering-direct-and-indirect-molecular-determinants-of-chromatin-loops-using-a-computational-integrative-approach
#4
Raphaël Mourad, Lang Li, Olivier Cuvier
Chromosomal organization in 3D plays a central role in regulating cell-type specific transcriptional and DNA replication timing programs. Yet it remains unclear to what extent the resulting long-range contacts depend on specific molecular drivers. Here we propose a model that comprehensively assesses the influence on contacts of DNA-binding proteins, cis-regulatory elements and DNA consensus motifs. Using real data, we validate a large number of predictions for long-range contacts involving known architectural proteins and DNA motifs...
May 23, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28539630/functional-characterization-of-the-meiosis-specific-dna-double-strand-break-inducing-factor-spo-11-from-c-elegans
#5
Hsin-Yi Yeh, Sheng-Wei Lin, Yi-Chun Wu, Nei-Li Chan, Peter Chi
The programmed induction of meiotic DNA double-strand breaks (DSBs) by the evolutionarily conserved SPO-11 protein, which is structurally related to archaeal Topo VIA topoisomerases, triggers meiotic recombination. Identification of several meiosis-specific factors that are required for SPO-11-mediated DSB formation raises the question whether SPO-11 alone can cleave DNA. Here, we have developed procedures to express and purify C. elegans SPO-11 in a soluble, untagged, and monodispersed form. Our biochemical and biophysical analyses demonstrate that SPO-11 is monomeric and binds DNA, double-stranded DNA in particular...
May 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28535372/a-brain-region-specific-neural-pathway-regulating-germinal-matrix-angiogenesis
#6
Shang Ma, Devi Santhosh, Peeyush Kumar T, Zhen Huang
Intimate communication between neural and vascular cells is critical for normal brain development and function. Germinal matrix (GM), a key primordium for the brain reward circuitry, is unique among brain regions for its distinct pace of angiogenesis and selective vulnerability to hemorrhage during development. A major neonatal condition, GM hemorrhage can lead to cerebral palsy, hydrocephalus, and mental retardation. Here we identify a brain-region-specific neural progenitor-based signaling pathway dedicated to regulating GM vessel development...
May 22, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28534833/coagulating-colubrids-evolutionary-pathophysiological-and-biodiscovery-implications-of-venom-variations-between-boomslang-dispholidus-typus-and-twig-snake-thelotornis-mossambicanus
#7
Jordan Debono, James Dobson, Nicholas R Casewell, Anthony Romilio, Bin Li, Nyoman Kurniawan, Karine Mardon, Vera Weisbecker, Amanda Nouwens, Hang Fai Kwok, Bryan G Fry
Venoms can deleteriously affect any physiological system reachable by the bloodstream, including directly interfering with the coagulation cascade. Such coagulopathic toxins may be anticoagulants or procoagulants. Snake venoms are unique in their use of procoagulant toxins for predatory purposes. The boomslang (Dispholidus typus) and the twig snakes (Thelotornis species) are iconic African snakes belonging to the family Colubridae. Both species produce strikingly similar lethal procoagulant pathologies. Despite these similarities, antivenom is only produced for treating bites by D...
May 19, 2017: Toxins
https://www.readbyqxmd.com/read/28529483/identification-of-a-novel-allosteric-inhibitory-site-on-tryptophan-hydroxylase-1-enabling-unprecedented-selectivity-over-all-related-hydroxylases
#8
Mike Petrassi, Rob Barber, Celine Be, Sarah Beach, Brian Cox, Anne-Marie D'Souza, Nick Duggan, Martin Hussey, Roy Fox, Peter Hunt, Gabor Jarai, Takatoshi Kosaka, Paul Oakley, Viral Patel, Neil Press, David Rowlands, Clemens Scheufler, Oliver Schmidt, Honnappa Srinivas, Mary Turner, Rob Turner, John Westwick, Alison Wolfreys, Nuzhat Pathan, Simon Watson, Matthew Thomas
Pulmonary arterial hypertension (PAH) has demonstrated multi-serotonin receptor dependent pathologies, characterized by increased tone (5-HT1B receptor) and complex lesions (SERT, 5-HT1B, 5-HT2B receptors) of the pulmonary vasculature together with right ventricular hypertrophy, ischemia and fibrosis (5-HT2B receptor). Selective inhibitors of individual signaling elements - SERT, 5-HT2A, 5HT2B, and combined 5-HT2A/B receptors, have all been tested clinically and failed. Thus, inhibition of tryptophan hydroxylase 1 (TPH1), the rate limiting step in 5-HT synthesis, has been suggested as a more broad, and thereby more effective, mode of 5-HT inhibition...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28526709/acetylation-of-mitochondrial-proteins-by-gcn5l1-promotes-enhanced-fatty-acid-oxidation-in-the-heart
#9
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/28521739/drosophila-melanogaster-positive-transcriptional-elongation-factors-regulate-metabolic-and-sex-biased-expression-in-adults
#10
Haiwang Yang, Denis Basquin, Daniel Pauli, Brian Oliver
BACKGROUND: Transcriptional elongation is a generic function, but is also regulated to allow rapid transcription responses. Following relatively long initiation and promoter clearance, RNA polymerase II can pause and then rapidly elongate following recruitment of positive elongation factors. Multiple elongation complexes exist, but the role of specific components in adult Drosophila is underexplored. RESULTS: We conducted RNA-seq experiments to analyze the effect of RNAi knockdown of Suppressor of Triplolethal and lilliputian...
May 18, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28508891/joint-morphogenetic-cells-in-the-adult-mammalian-synovium
#11
Anke J Roelofs, Janja Zupan, Anna H K Riemen, Karolina Kania, Sharon Ansboro, Nathan White, Susan M Clark, Cosimo De Bari
The stem cells that safeguard synovial joints in adulthood are undefined. Studies on mesenchymal stromal/stem cells (MSCs) have mainly focused on bone marrow. Here we show that lineage tracing of Gdf5-expressing joint interzone cells identifies in adult mouse synovium an MSC population largely negative for the skeletal stem cell markers Nestin-GFP, Leptin receptor and Gremlin1. Following cartilage injury, Gdf5-lineage cells underpin synovial hyperplasia through proliferation, are recruited to a Nestin-GFP(high) perivascular population, and contribute to cartilage repair...
May 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/28507506/differential-regulation-of-pi-4-5-p2-sensitivity-of-kv7-2-and-kv7-3-channels-by-calmodulin
#12
Carolina Gomis-Perez, Maria V Soldovieri, Covadonga Malo, Paolo Ambrosino, Maurizio Taglialatela, Pilar Areso, Alvaro Villarroel
HIGHLIGHTS - Calmodulin-dependent Kv7.2 current density without the need of binding calcium.- Kv7.2 current density increase is accompanied with resistance to PI(4,5)P2 depletion.- Kv7.3 current density is insensitive to calmodulin elevation.- Kv7.3 is more sensitive to PI(4,5)P2 depletion in the presence of calmodulin.- Apo-calmodulin influences PI(4,5)P2 dependence in a subunit specific manner. The identification and understanding of critical factors regulating M-current functional density, whose main components are Kv7...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28501588/oligomeric-structure-of-anabaena-sensory-rhodopsin-in-a-lipid-bilayer-environment-by-combining-solid-state-nmr-and-long-range-deer-constraints
#13
Sergey Milikisiyants, Shenlin Wang, Rachel A Munro, Matthew Donohue, Meaghan E Ward, David Bolton, Leonid S Brown, Tatyana I Smirnova, Vladimir Ladizhansky, Alex I Smirnov
Oligomerization of membrane proteins is common in nature. Here, we combine spin-labeling Double Electron-Electron Resonance (DEER) and solid-state NMR (ssNMR) spectroscopy to refine the structure of an oligomeric integral membrane protein, Anabaena Sensory Rhodopsin (ASR), reconstituted in a lipid environment. An essential feature of such a combined approach is that it provides structural distance restraints spanning a range of ca. 3-60Å, while using the same sample preparation (i.e., mutations, paramagnetic labeling, and reconstitution in lipid bilayers) for both ssNMR and DEER...
May 10, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28496053/chemical-and-structural-biology-of-protein-lysine-deacetylases
#14
Minoru Yoshida, Norio Kudo, Saori Kosono, Akihiro Ito
Histone acetylation is a reversible posttranslational modification that plays a fundamental role in regulating eukaryotic gene expression and chromatin structure/function. Key enzymes for removing acetyl groups from histones are metal (zinc)-dependent and NAD(+)-dependent histone deacetylases (HDACs). The molecular function of HDACs have been extensively characterized by various approaches including chemical, molecular, and structural biology, which demonstrated that HDACs regulate cell proliferation, differentiation, and metabolic homeostasis, and that their alterations are deeply involved in various human disorders including cancer...
2017: Proceedings of the Japan Academy. Series B, Physical and Biological Sciences
https://www.readbyqxmd.com/read/28490634/inflammatory-cytokines-down-regulate-the-barrier-protective-prostasin-matriptase-proteolytic-cascade-early-in-experimental-colitis
#15
Marguerite S Buzza, Tierra A Johnson, Gregory D Conway, Erik W Martin, Subhradip Mukhopadhyay, Terez Shea-Donohue, Toni M Antalis
Compromised gastrointestinal barrier function is strongly associated with the progressive and destructive pathologies of the two main forms of IBD, Ulcerative Colitis (UC) and Crohns disease (CD). Matriptase is a membrane-anchored serine protease encoded by Suppression of Tumorigenicity-14 (ST14) gene, which is critical for epithelial barrier development and homeostasis. Matriptase barrier protective activity is linked with the glycosyl-phosphatidyl-inositol (GPI)-anchored serine protease prostasin, which is a co-factor for matriptase zymogen activation...
May 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28485739/a-decade-of-dna-hybrid-catalysis-from-innovation-to-comprehension
#16
REVIEW
Nicolas Duchemin, Isabelle Heath-Apostolopoulos, Michael Smietana, Stellios Arseniyadis
In a little over a decade, the unique chirality of oligonucleotides has allowed the development of a variety of asymmetric synthetic transformations. The concept lies in embedding an achiral transition metal catalyst in a DNA double helix, which provides the necessary chiral microenvironment to selectively form one enantiomer of a given reaction product. The most recent efforts at unveiling new reactivities have been accompanied by the desire to understand the mechanisms by which the chirality is transferred and the influence of the interaction between DNA and the metallic co-factor on the selectivity...
May 9, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28482142/the-brassinosteroid-receptor-bri1-can-generate-cgmp-enabling-cgmp-dependent-downstream-signaling
#17
Janet I Wheeler, Aloysius Wong, Claudius Marondedze, Arnoud J Groen, Lusisizwe Kwezi, Lubna Freihat, Jignesh Vyas, Misjudeen A Raji, Helen R Irving, Chris Gehring
The brassinosteroid receptor BRASSINOSTEROID INSENSITIVE 1 (BRI1) is a member of the leucine rich repeat receptor like kinase family. The intracellular kinase domain of BRI1 is an active kinase and also encapsulates a guanylate cyclase catalytic centre. Using liquid chromatography tandem mass spectrometry, we confirmed that the recombinant cytoplasmic domain of BRI1 generates pmol amounts of cGMP per μg protein with a preference for magnesium over manganese as a co-factor. Importantly, a functional BRI1 kinase is essential for optimal cGMP generation...
May 8, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28479323/acclimation-of-oxygenic-photosynthesis-to-iron-starvation-is-controlled-by-the-srna-isar1
#18
Jens Georg, Gergana Kostova, Linda Vuorijoki, Verena Schön, Taro Kadowaki, Tuomas Huokko, Desirée Baumgartner, Maximilian Müller, Stephan Klähn, Yagut Allahverdiyeva, Yukako Hihara, Matthias E Futschik, Eva-Mari Aro, Wolfgang R Hess
Oxygenic photosynthesis crucially depends on proteins that possess Fe(2+) or Fe/S complexes as co-factors or prosthetic groups. Here, we show that the small regulatory RNA (sRNA) IsaR1 (Iron-Stress-Activated RNA 1) plays a pivotal role in acclimation to low-iron conditions. The IsaR1 regulon consists of more than 15 direct targets, including Fe(2+)-containing proteins involved in photosynthetic electron transfer, detoxification of anion radicals, citrate cycle, and tetrapyrrole biogenesis. IsaR1 is essential for maintaining physiological levels of Fe/S cluster biogenesis proteins during iron deprivation...
May 22, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28474475/what-happened-to-koch-s-postulates-in-diarrhea
#19
Shamima Sultana, Shafiqul A Sarker, Harald Brüssow
In 1890 Robert Koch has formulated postulates describing what criteria a parasite has to fulfill to qualify as an etiological agent for an infectious disease. Since then Koch's postulates have experienced reformulations by nearly every generation of microbiologists reflecting new discoveries changing the understanding of infectious diseases pathogenesis. The latest addition to this discussion is the role of the host commensal microbiota in turning infections into disease. After an overview of the historical developments of the postulates, we analyzed data on diarrhea etiology from Bangladesh with respect to Koch's postulates...
May 4, 2017: Environmental Microbiology
https://www.readbyqxmd.com/read/28468668/proteomic-anaysis-of-aged-microglia-shifts-in-transcription-bioenergetics-and-nutrient-response
#20
Antwoine Flowers, Harris Bell-Temin, Ahmad Jalloh, Stanley M Stevens, Paula C Bickford
BACKGROUND: Age is the primary risk factor for many diseases. As such, age is a critical co-factor for examination in order to understand the progression and potential intervention in disease progression. Studies examining both the phenotype and transcriptome of aged microglia demonstrated a propensity for the development of a pro-inflammatory phenotype. Less well studied is the concomitant blunting of anti-inflammatory aspects of microglial function with age which also impact plasticity and repair in the CNS...
May 3, 2017: Journal of Neuroinflammation
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