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https://www.readbyqxmd.com/read/28433648/repeated-threat-without-direct-harm-alters-metabolic-capacity-in-select-regions-that-drive-defensive-behavior
#1
D J Kim, A S Lee, A A Yttredahl, R Gómez-Rodríguez, B J Anderson
To understand the behavioral consequences of intermittent anticipatory stress resulting from threats without accompanying physiological challenges, we developed a semi-naturalistic rodent housing and foraging environment that can include threats that are unpredictable in timing. Behavior is automatically recorded while rats forage for food or water. Over three weeks, the threats have been shown to elicit risk assessment behaviors, increase defensive burying and increase adrenal gland weight. To identify brain regions activated by this manipulation, we measured cytochrome c oxidase (COX), which is tightly coupled to neural activity...
April 19, 2017: Neuroscience
https://www.readbyqxmd.com/read/28433553/identification-and-validation-of-micrornas-directly-regulating-the-udp-glucuronosyltransferase-1a-subfamily-enzymes-by-a-functional-genomics-approach
#2
Ioannis Papageorgiou, Michael H Court
Posttranscriptional repression of UDP-glucuronosyltransferase (UGT) 1A expression by microRNAs (miRNAs) may be an important mechanism underlying interindividual variability in drug glucuronidation. Furthermore, the UGT1A 3'-UTR shared by all UGT1A enzymes is polymorphic, containing three linked SNPs (rs10929303, rs1042640, and rs8330) that could influence miRNA binding. The aim of this study was to identify the complete complement of miRNAs that could regulate UGT1A expression through binding to the reference and/or common variant UGT1A 3'-UTR...
April 19, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28433327/replacing-antibodies-with-modified-dna-aptamers-in-vaccine-potency-assays
#3
Jeremiah J Trausch, Mary Shank-Retzlaff, Thorsten Verch
Vaccine in vitro potency assays are vital regulatory tests that are used to confirm the presence and concentration of an antigen of interest in a form that directly or indirectly relates to protective activity in patients. Current assays come in many forms, but they almost exclusively use antibody reagents for selective detection of the target antigen. Antibodies provide specific recognition of vaccine antigens but also exhibit drawbacks such as stability limitations, cost, and lot-to-lot variation, which can make it challenging to maintain the reagent throughout the lifetime of the vaccine...
April 19, 2017: Vaccine
https://www.readbyqxmd.com/read/28433102/the-genetics-of-wilson-disease
#4
Irene J Chang, Si Houn Hahn
Wilson disease (WD) is an autosomal-recessive disorder of hepatocellular copper deposition caused by pathogenic variants in the copper-transporting gene, ATP7B. Early detection and treatment are critical to prevent lifelong neuropsychiatric, hepatic, and systemic disabilities. Due to the marked heterogeneity in age of onset and clinical presentation, the diagnosis of Wilson disease remains challenging to physicians today. Direct sequencing of the ATP7B gene is the most sensitive and widely used confirmatory testing method, and concurrent biochemical testing improves diagnostic accuracy...
2017: Handbook of Clinical Neurology
https://www.readbyqxmd.com/read/28432787/presynaptic-morphology-and-vesicular-composition-determine-vesicle-dynamics-in-mouse-central-synapses
#5
Laurent Guillaud, Dimitar Dimitrov, Tomoyuki Takahashi
Transport of synaptic vesicles (SVs) in nerve terminals is thought to play essential roles in maintenance of neurotransmission. To identify factors modulating SV movements, we performed real-time imaging analysis of fluorescently labeled SVs in giant calyceal and conventional hippocampal terminals. Compared with small hippocampal terminals, SV movements in giant calyceal terminals were faster, longer and kinetically more heterogeneous. Morphological maturation of giant calyceal terminals was associated with an overall reduction in SV mobility and displacement heterogeneity...
April 22, 2017: ELife
https://www.readbyqxmd.com/read/28432359/role-of-the-ion-channel-extracellular-collar-in-ampa-receptor-gating
#6
Maria V Yelshanskaya, Samaneh Mesbahi-Vasey, Maria G Kurnikova, Alexander I Sobolevsky
AMPA subtype ionotropic glutamate receptors mediate fast excitatory neurotransmission and are implicated in numerous neurological diseases. Ionic currents through AMPA receptor channels can be allosterically regulated via different sites on the receptor protein. We used site-directed mutagenesis and patch-clamp recordings to probe the ion channel extracellular collar, the binding region for noncompetitive allosteric inhibitors. We found position and substitution-dependent effects for introduced mutations at this region on AMPA receptor gating...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28432356/a-role-of-human-rnase-p-subunits-rpp29-and-rpp21-in-homology-directed-repair-of-double-strand-breaks
#7
Enas R Abu-Zhayia, Hanan Khoury-Haddad, Noga Guttmann-Raviv, Raphael Serruya, Nayef Jarrous, Nabieh Ayoub
DNA damage response (DDR) is needed to repair damaged DNA for genomic integrity preservation. Defective DDR causes accumulation of deleterious mutations and DNA lesions that can lead to genomic instabilities and carcinogenesis. Identifying new players in the DDR, therefore, is essential to advance the understanding of the molecular mechanisms by which cells keep their genetic material intact. Here, we show that the core protein subunits Rpp29 and Rpp21 of human RNase P complex are implicated in DDR. We demonstrate that Rpp29 and Rpp21 depletion impairs double-strand break (DSB) repair by homology-directed repair (HDR), but has no deleterious effect on the integrity of non-homologous end joining...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28432336/structure-function-analysis-of-the-dna-binding-domain-of-a-transmembrane-transcriptional-activator
#8
Andreas Schlundt, Sophie Buchner, Robert Janowski, Thomas Heydenreich, Ralf Heermann, Jürgen Lassak, Arie Geerlof, Ralf Stehle, Dierk Niessing, Kirsten Jung, Michael Sattler
The transmembrane DNA-binding protein CadC of E. coli, a representative of the ToxR-like receptor family, combines input and effector domains for signal sensing and transcriptional activation, respectively, in a single protein, thus representing one of the simplest signalling systems. At acidic pH in a lysine-rich environment, CadC activates the transcription of the cadBA operon through recruitment of the RNA polymerase (RNAP) to the two cadBA promoter sites, Cad1 and Cad2, which are directly bound by CadC...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28432123/an-amphipathic-%C3%AE-helix-directs-palmitoylation-of-the-large-intracellular-loop-of-the-sodium-calcium-exchanger
#9
Fiona Plain, Samitha Dilini Congreve, Rachel Sue Zhen Yee, Jennifer Kennedy, Jacqueline Howie, Chien-Wen Kuo, Niall Fraser, William Fuller
The electrogenic sodium/calcium exchanger (NCX) mediates bidirectional calcium transport controlled by the transmembrane sodium gradient. NCX inactivation occurs in the absence of phosphatidylinositol 4,5-bisphosphate (PIP2), and is facilitated by palmitoylation of a single cysteine at position 739 within NCX's large intracellular loop. The aim of this investigation was to identify the structural determinants of NCX1 palmitoylation. Full-length NCX1 (FL-NCX1) and a YFP fusion protein of the NCX1 large intracellular loop (YFP-NCX1) were expressed in HEK cells...
April 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28432121/the-lon-protease-like-domain-in-the-bacterial-reca-paralog-rada-is-required-for-dna-binding-and-repair
#10
Masao Inoue, Kenji Fukui, Yuki Fujii, Noriko Nakagawa, Takato Yano, Seiki Kuramitsu, Ryoji Masui
Homologous recombination (HR) plays an essential role in the maintenance of genome integrity. RecA/Rad51 paralogs have been recognized as an important factor of HR. Among them, only one bacterial RecA/Rad51 paralog - RadA - is involved in HR as an accessory factor of RecA recombinase. RadA has a unique Lon protease-like domain (LonC) at its C-terminus, in addition to a RecA-like ATPase domain. Unlike Lon protease, RadA's LonC domain does not show protease activity but is still essential for RadA-mediated DNA repair...
April 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28432120/two-glycosaminoglycan-binding-domains-of-the-mouse-cytomegalovirus-encoded-chemokine-mck-2-are-critical-for-oligomerization-of-the-full-length-protein
#11
Sergio M Pontejo, Philip M Murphy
Chemokines are essential for antimicrobial host defenses and tissue repair. Herpesviruses and poxviruses also encode chemokines, copied from their hosts and repurposed for multiple functions, including immune evasion. The CC chemokine MCK-2 encoded by mouse cytomegalovirus (MCMV) has an atypical structure consisting of a classic chemokine domain N-terminal to a second unique domain, resulting from the splicing of MCMV ORFs m131 and m129. MCK-2 is essential for full MCMV infectivity in macrophages and for persistent infection in the salivary gland...
April 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28432080/npm1-directs-piddosome-dependent-caspase-2-activation-in-the-nucleolus
#12
Kiyohiro Ando, Melissa J Parsons, Richa B Shah, Chloé I Charendoff, Sheré L Paris, Peter H Liu, Sara R Fassio, Brittany A Rohrman, Ruth Thompson, Andrew Oberst, Samuel Sidi, Lisa Bouchier-Hayes
The PIDDosome (PIDD-RAIDD-caspase-2 complex) is considered to be the primary signaling platform for caspase-2 activation in response to genotoxic stress. Yet studies of PIDD-deficient mice show that caspase-2 activation can proceed in the absence of PIDD. Here we show that DNA damage induces the assembly of at least two distinct activation platforms for caspase-2: a cytoplasmic platform that is RAIDD dependent but PIDD independent, and a nucleolar platform that requires both PIDD and RAIDD. Furthermore, the nucleolar phosphoprotein nucleophosmin (NPM1) acts as a scaffold for PIDD and is essential for PIDDosome assembly in the nucleolus after DNA damage...
April 21, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28431990/a-common-polymorphism-decreases-lrp1-mrna-stability-and-is-associated-with-increased-plasma-factor-viii-levels
#13
Jiann-Der Lee, Kuang-Ming Hsiao, Pey-Jium Chang, Chih-Cheng Chen, Ya-Wen Kuo, Yen-Chu Huang, Huan-Lin Hsu, Ya-Hui Lin, Chih-Ying Wu, Ying-Chih Huang, Meng Lee, Chia-Yu Hsu, Yi-Ting Pan, Chih-Yu Kuo, Chun-Hsien Lin
The low-density lipoprotein receptor-related protein 1 (LRP1) gene is associated with increased levels of plasma factor VIII (FVIII). We aimed to explore eight functional genetic LRP1 variants for their potential roles in regulating FVIII levels and acute ischemic stroke (AIS). This genetic association study enrolled 192 patients with AIS and 134 controls. There were no significant differences in the genetic frequency of the eight functional single-nucleotide polymorphisms (SNPs) between the control and AIS groups...
April 18, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28431866/circulating-micrornas-signature-correlates-with-positive-18-f-fluorodeoxyglucose-positron-emission-tomography-in-patients-with-abdominal-aortic-aneurysm
#14
Audrey Courtois, Betty Nusgens, Nancy Garbacki, Roland Hustinx, Pierre Gomez, Jean-Olivier Defraigne, Alain C Colige, Natzi Sakalihasan
BACKGROUND: Prediction of abdominal aortic aneurysm (AAA) rupture is a challenging issue. Small noncoding microRNAs (miRNAs) are potent regulators of gene expression and are considered as valuable circulating biomarkers. Recently, [(18)F]fluorodeoxyglucose (FDG) uptake detected by positron emission tomography (PET) in AAA was correlated with cellular and molecular alterations involved in wall instability and its potential rupture. Our study aimed at identifying circulating miRNAs correlated with a positive PET that could help discriminate patients at high risk of rupture...
April 18, 2017: Journal of Vascular Surgery
https://www.readbyqxmd.com/read/28431851/ultraviolet-c-light-as-a-means-of-disinfecting-anesthesia-workstations
#15
Matthew Nottingham, Gene Peterson, Christopher Doern, Michelle Doll, Nadia Masroor, Kakotan Sanogo, Michael Stevens, Gonzalo Bearman
BACKGROUND: Anesthesia workstations (AWs) are a reservoir for pathogenic organisms potentially associated with surgical site infections. This study examined the effectiveness of the Tru-D SmartUVC device (Tru-D LLC, Nashville, TN) on bioburden reduction (BR) on AWs. METHODS: Strips of tissue inoculated with a known concentration of either Staphylococcus aureus, Enterococcus faecalis, or Acinetobacter sp were placed on 22 high-touch surfaces of an AW. Half of the AW surfaces received direct ultraviolet (UV) light exposure and half received indirect exposure...
April 18, 2017: American Journal of Infection Control
https://www.readbyqxmd.com/read/28431346/caged-gammarus-as-biomonitors-identifying-thresholds-of-toxic-metal-bioavailability-that-affect-gammarid-densities-at-the-french-national-scale
#16
Alexandre Ciliberti, Arnaud Chaumot, Rémi Recoura-Massaquant, André Chandesris, Adeline François, Marina Coquery, Martial Ferréol, Olivier Geffard
Bioaccumulated concentrations of toxic elements in biomonitor invertebrate species have already been used to successfully link metal bioavailability and impairments of stream macroinvertebrate communities at the scale of the watershed. However, implementing this empirical comparative approach at a greater spatial scale remains a challenge due to the diversity of biogeographical contexts encompassed by regional and national scales. We showed in previous studies that the use of standard organisms caged permits the use of a common biomonitor over a far greater geographical range, while limiting the influence of confounding factors on levels of bioavailable contamination...
April 17, 2017: Water Research
https://www.readbyqxmd.com/read/28431140/performance-of-the-patient-reported-outcomes-measurement-information-system-29-in-scleroderma-a-scleroderma-patient-centered-intervention-network-cohort-study
#17
Linda Kwakkenbos, Brett D Thombs, Dinesh Khanna, Marie-Eve Carrier, Murray Baron, Daniel E Furst, Karen Gottesman, Frank van den Hoogen, Vanessa L Malcarne, Maureen D Mayes, Luc Mouthon, Warren R Nielson, Serge Poiraudeau, Robert Riggs, Maureen Sauvé, Fredrick Wigley, Marie Hudson, Susan J Bartlett
Objective.: The Patient-Reported Outcomes Measurement Information System (PROMIS)-29 assesses seven health-related quality of life domains plus pain intensity. The objective was to examine PROMIS-29v2 validity and explore clinical associations in patients with SSc. Methods.: English-speaking SSc patients in the Scleroderma Patient-centered Intervention Network Cohort from 26 sites in Canada, the USA and the UK completed the PROMIS-29v2 between July 2014 and November 2015...
April 18, 2017: Rheumatology
https://www.readbyqxmd.com/read/28431042/cis-regulatory-divergence-in-gene-expression-between-two-thermally-divergent-yeast-species
#18
Xueying C Li, Justin C Fay
Gene regulation is a ubiquitous mechanism by which organisms respond to their environment. While organisms are often found to be adapted to the environments they experience, the role of gene regulation in environmental adaptation is not often known. In this study, we examine divergence in cis-regulatory effects between two Saccharomyces species, S. cerevisiae and S. uvarum, that have substantially diverged in their thermal growth profile. We measured allele specific expression (ASE) in the species' hybrid at three temperatures, the highest of which is lethal to S...
April 14, 2017: Genome Biology and Evolution
https://www.readbyqxmd.com/read/28431023/safety-and-efficacy-of-the-sofia-6f-plus-distal-access-reperfusion-catheter-in-the-endovascular-treatment-of-acute-ischemic-stroke
#19
Hussain Shallwani, Hakeem J Shakir, Leonardo Rangel-Castilla, Jason M Davies, Ashish Sonig, Mithun G Sattur, Bernard R Bendok, Kenneth V Snyder, Adnan H Siddiqui, Elad I Levy
BACKGROUND: Neuroendovascular intervention has become a key treatment option for acute ischemic stroke. The Sofia (6F) PLUS catheter was designed for neurovascular access for diagnostic or therapeutic interventions. OBJECTIVE: To report the first series describing use of the Sofia PLUS intermediate/distal access reperfusion catheter in the treatment of acute ischemic stroke. METHODS: In this retrospective study, 41 stroke cases were identified in which the catheter was utilized for thrombolysis/thrombectomy...
April 19, 2017: Neurosurgery
https://www.readbyqxmd.com/read/28430981/central-nervous-system-glp-1-receptors-regulate-islet-hormone-secretion-and-glucose-homeostasis-in-male-rats
#20
Lene Jessen, Eric P Smith, Yvonne Ulrich-Lai, James P Herman, Randy J Seeley, Darleen Sandoval, David D'Alessio
The glucagon-like peptide 1 (GLP-1) system plays an important role in blood glucose regulation, in great part through coordinate control of insulin and glucagon secretion. These effects are generally attributed to GLP-1 produced in peripheral sites, principally the intestine. GLP-1 is also produced in hindbrain neurons that signal through GLP-1 receptors (GLP-1r) expressed in brain regions involved in metabolic regulation. GLP-1 in the central nervous system (CNS) induces satiety, visceral illness, and stress responses...
April 18, 2017: Endocrinology
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