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https://www.readbyqxmd.com/read/28731405/pro-death-nmda-receptor-signaling-is-promoted-by-the-glun2b-c-terminus-independently-of-dapk1
#1
Jamie McQueen, Tomas J Ryan, Sean McKay, Katie Fm Marwick, Paul E Baxter, Sarah M Carpanini, Thomas M Wishart, Thomas H Gillingwater, Jean C Manson, David Ja Wyllie, Seth Gn Grant, Barry McColl, Noboru Komiyama, Giles E Hardingham
Aberrant NMDA receptor (NMDAR) activity contributes to several neurological disorders, but direct antagonism is poorly tolerated therapeutically. The GluN2B cytoplasmic C-terminal domain (CTD) represents an alternative therapeutic target since it potentiates excitotoxic signaling. The key GluN2B CTD-centred event in excitotoxicity is proposed to involve its phosphorylation at Ser-1303 by DAPK1, that is blocked by a neuroprotective cell-permeable peptide mimetic of the region. Contrary to this model, we find that excitotoxicity can proceed without increased Ser-1303 phosphorylation, and is unaffected by DAPK1 deficiency in vitro or following ischemia in vivo...
July 21, 2017: ELife
https://www.readbyqxmd.com/read/28731030/cryo-em-structure-and-biochemical-analysis-reveal-the-basis-of-the-functional-difference-between-human-pi3kc3-c1-and-c2
#2
Meisheng Ma, Jun-Jie Liu, Yan Li, Yuwei Huang, Na Ta, Yang Chen, Hua Fu, Ming-Da Ye, Yuehe Ding, Weijiao Huang, Jia Wang, Meng-Qiu Dong, Li Yu, Hong-Wei Wang
Phosphatidylinositol 3-phosphate (PI3P) plays essential roles in vesicular trafficking, organelle biogenesis and autophagy. Two class III phosphatidylinositol 3-kinase (PI3KC3) complexes have been identified in mammals, the ATG14L complex (PI3KC3-C1) and the UVRAG complex (PI3KC3-C2). PI3KC3-C1 is crucial for autophagosome biogenesis, and PI3KC3-C2 is involved in various membrane trafficking events. Here we report the cryo-EM structures of human PI3KC3-C1 and PI3KC3-C2 at sub-nanometer resolution. The two structures share a common L-shaped overall architecture with distinct features...
July 21, 2017: Cell Research
https://www.readbyqxmd.com/read/28723227/extended-release-guanfacine-does-not-show-a-large-effect-on-tic-severity-in-children-with-chronic-tic-disorders
#3
Tanya K Murphy, Thomas V Fernandez, Barbara J Coffey, Omar Rahman, Allison Gavaletz, Camille E Hanks, Caitlin S Tillberg, Laura Ibanez Gomez, Denis G Sukhodolsky, Lily Katsovich, Lawrence Scahill
OBJECTIVE: To evaluate the tolerability, safety, and preliminary efficacy of extended-release guanfacine in children with chronic tic disorders, including Tourette's disorder (collectively referred to as CTD). METHODS: This was a multisite, 8-week, randomized, double-blind, placebo-controlled trial. The primary outcome measure was the Yale Global Tic Severity Scale (YGTSS) total score. Key secondary outcomes included the Improvement item of Clinical Global Impressions-Improvement (CGI-I) scale and the Tic Symptom Self-report (TSSR)...
July 19, 2017: Journal of Child and Adolescent Psychopharmacology
https://www.readbyqxmd.com/read/28720099/association-between-genome-wide-copy-number-variation-and-arsenic-induced-skin-lesions-a-prospective-study
#4
Muhammad G Kibriya, Farzana Jasmine, Faruque Parvez, Maria Argos, Shantanu Roy, Rachelle Paul-Brutus, Tariqul Islam, Alauddin Ahmed, Muhammad Rakibuz-Zaman, Justin Shinkle, Vesna Slavkovich, Joseph H Graziano, Habibul Ahsan
BACKGROUND: Exposure to arsenic in drinking water is a global health problem and arsenic-induced skin lesions are hallmark of chronic arsenic toxicity. We and others have reported germline genetic variations as risk factors for such skin lesions. The role of copy number variation (CNV) in the germline DNA in this regard is unknown. METHODS: From a large prospectively followed-up cohort, exposed to arsenic, we randomly selected 2171 subjects without arsenic-induced skin lesions at enrollment and genotyped their whole blood DNA samples on Illumina Cyto12v2...
July 18, 2017: Environmental Health: a Global Access Science Source
https://www.readbyqxmd.com/read/28717830/a-review-of-drug-induced-liver-injury-databases
#5
REVIEW
Guangwen Luo, Yiting Shen, Lizhu Yang, Aiping Lu, Zheng Xiang
Drug-induced liver injuries have been a major focus of current research in drug development, and are also one of the major reasons for the failure and withdrawal of drugs in development. Drug-induced liver injuries have been systematically recorded in many public databases, which have become valuable resources in this field. In this study, we provide an overview of these databases, including the liver injury-specific databases LiverTox, LTKB, Open TG-GATEs, LTMap and Hepatox, and the general databases, T3DB, DrugBank, DITOP, DART, CTD and HSDB...
July 17, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28717148/human-ribosomal-p1-p2-heterodimer-represents-an-optimal-docking-site-for-ricin-a-chain-with-a-prominent-role-for-p1-c-terminus
#6
Przemysław Grela, Xiao-Ping Li, Patrycja Horbowicz, Monika Dźwierzyńska, Marek Tchórzewski, Nilgun E Tumer
The eukaryotic P-stalk contains two P1-P2 protein dimers with a conserved C- terminal domain (CTD) critical for the interaction with external factors. To understand the role of the individual CTD of human P1/P2 proteins, we examined the interaction of reconstituted human P-protein complexes and C-terminally truncated forms with ricin A chain (RTA), which binds to the stalk to depurinate the sarcin/ricin loop (SRL). The interaction between P-protein complexes and RTA was examined by surface plasmon resonance, isothermal titration calorimetry, microscale thermophoresis and bio-layer interferometry...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28715108/ivermectin-activates-girk-channels-in-a-pip2-dependent-g%C3%AE-%C3%AE-independent-manner-and-an-amino-acid-residue-at-the-slide-helix-governs-the-activation
#7
I-Shan Chen, Michihiro Tateyama, Yuko Fukata, Motonari Uesugi, Yoshihiro Kubo
Ivermectin (IVM) is a widely used antiparasitic drug in humans and pets which activates glutamate-gated Cl(-) channel in parasites. It is also known that IVM binds to the transmembrane domains (TMs) of several ligand-gated channels, such as Cys-loop receptors and P2X receptors. In this study, we found that the G-protein-gated inwardly rectifying K(+) (GIRK) channel is activated by IVM directly. By electrophysiological recordings in Xenopus oocytes, we observed that IVM activates GIRK channel in a phosphatidylinositol-4,5-biphosphate (PIP2 )-dependent manner, and that the IVM-mediated GIRK activation is independent of Gβγ ...
July 17, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28714502/insights-into-the-rna-binding-mechanism-of-human-l1-orf1p-a-molecular-dynamics-study
#8
Muthukumaran Rajagopalan, Sangeetha Balasubramanian, Amutha Ramaswamy
The recognition and binding of nucleic acids by ORF1p, an L1 retrotransposon protein, have not yet been clearly understood due to the lack of structural knowledge. The present study attempts to identify the probable single-stranded RNA binding pathway of trimeric ORF1p using computational methods like ligand mapping methodology combined with molecular dynamics simulations. Using the ligand mapping methodology, the possible RNA interacting sites on the surface of the trimeric ORF1p were identified. The crystal structure of the ORF1p timer and an RNA molecule of 29 nucleotide bases in length were used to generate the structure of the ORF1p complex based on information on predicted binding sites as well as the functional states of the CTD...
July 17, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28711408/biochemical-characteristics-of-newborns-with-carnitine-transporter-defect-identified-by-newborn-screening-in-california
#9
N M Gallant, K Leydiker, Y Wilnai, C Lee, F Lorey, L Feuchtbaum, H Tang, J Carter, G M Enns, S Packman, H J Lin, W R Wilcox, S D Cederbaum, J E Abdenur
Carnitine transporter defect (CTD; also known as systemic primary carnitine deficiency; MIM 212140) is due to mutations in the SLC22A5 gene and leads to extremely low carnitine levels in blood and tissues. Affected individuals may develop early onset cardiomyopathy, weakness, or encephalopathy, which may be serious or even fatal. The disorder can be suggested by newborn screening. However, markedly low newborn carnitine levels can also be caused by conditions unrelated to CTD, such as the low carnitine levels often associated with normal pregnancies and some metabolic disorders occurring in the mother...
July 8, 2017: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/28708999/splicing-activation-by-rbfox-requires-self-aggregation-through-its-tyrosine-rich-domain
#10
Yi Ying, Xiao-Jun Wang, Celine K Vuong, Chia-Ho Lin, Andrey Damianov, Douglas L Black
Proteins of the Rbfox family act with a complex of proteins called the Large Assembly of Splicing Regulators (LASR). We find that Rbfox interacts with LASR via its C-terminal domain (CTD), and this domain is essential for its splicing activity. In addition to LASR recruitment, a low-complexity (LC) sequence within the CTD contains repeated tyrosines that mediate higher-order assembly of Rbfox/LASR and are required for splicing activation by Rbfox. This sequence spontaneously aggregates in solution to form fibrous structures and hydrogels, suggesting an assembly similar to the insoluble cellular inclusions formed by FUS and other proteins in neurologic disease...
July 13, 2017: Cell
https://www.readbyqxmd.com/read/28704913/treatment-of-connective-tissue-disease-associated-interstitial-lung-disease-the-pulmonologist-s-point-of-view
#11
REVIEW
So-My Koo, Soo-Taek Uh
Interstitial lung disease (ILD) occurs in 15% of patients with collagen vascular disease (CVD), referred to as connective tissue disease (CTD). Despite advances in management strategies, ILD continues to be a significant cause of mortality in patients with CVD-associated ILD (CTD-ILD). There is a lack of randomized, clinical trials assessing pharmacological agents for CTD-ILD, except in cases of ILD-associated systemic sclerosis (SSc). This may be due to the lack of CTD cases available, the difficulty of histological confirmation of ILD, and the various types of CTD and ILD...
July 2017: Korean Journal of Internal Medicine
https://www.readbyqxmd.com/read/28693159/cantharidin-alters-the-expression-of-genes-associated-with-the-nkg2d-associated-immune-response-in-tsgh-8301-human-bladder-carcinoma-cells
#12
Jehn-Hwa Kuo, An-Cheng Huang, Jen-Jyh Lin, Kuang-Chi Lai, Rick Sai-Chuen Wu, Jiun-Long Yang, Bin-Chuan Ji, Mei-Due Yang, Yung-Lin Chu, Jing-Gung Chung
Cantharidin (CTD) is a natural toxin in beetles of the Mylabris genus (blister beetle), which has been revealed to induce cell death in various types of human cancer cells. However, to the best of our knowledge, no previous studies have investigated the effect of CTD on the expression of genes and their associated signaling pathways in human bladder carcinoma cells. In the present study, CTD-induced cell morphological changes and apoptosis were observed using phase-contrast microscopy and the terminal deoxynucleotidyl transferase dUTP nick end labeling assay, respectively, in TSGH-8301 human bladder carcinoma cells...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28686733/the-short-mrna-isoform-of-the-immunoglobulin-superfamily-member-1-gene-encodes-an-intracellular-glycoprotein
#13
Ying Wang, Emilie Brûlé, Tanya Silander, Beata Bak, Sjoerd D Joustra, Daniel J Bernard
Mutations in the immunoglobulin superfamily, member 1 gene (IGSF1/Igsf1) cause an X-linked form of central hypothyroidism. The canonical form of IGSF1 is a transmembrane glycoprotein with 12 immunoglobulin (Ig) loops. The protein is co-translationally cleaved into two sub-domains. The carboxyl-terminal domain (CTD), which contains the last 7 Ig loops, is trafficked to the plasma membrane. Most pathogenic mutations in IGSF1 map to the portion of the gene encoding the CTD. IGSF1/Igsf1 encodes a variety of transcripts...
2017: PloS One
https://www.readbyqxmd.com/read/28677248/identification-of-suitable-reference-genes-during-the-formation-of-chlamydospores-in-clonostachys-rosea-67-1
#14
Jun Zhang, Zhanbin Sun, Shidong Li, Manhong Sun
Clonostachys rosea is a potential biocontrol fungus that can produce highly resistant chlamydospores under specific conditions. To investigate the genes related to chlamydospore formation, we identified reliable reference genes for quantification of gene expression in C. rosea 67-1 during sporulation. In this study, nine reference genes, actin (ACT), elongation factor 1 (EF1), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), histone (HIS), RNA polymerase II CTD phosphatase Fcp1 (RPP), succinate-semialdehyde dehydrogenase (SSD), TATA-binding protein (TBP), ubiquitin (UBQ), and ubiquitin-conjugating enzyme (UCE), were selected and cloned from 67-1, and their expression stability during chlamydospore formation was determined using reverse transcription quantitative PCR and assessed using the software geNorm, NormFinder and BestKeeper...
July 5, 2017: MicrobiologyOpen
https://www.readbyqxmd.com/read/28669632/regulation-of-the-equilibrium-between-closed-and-open-conformations-of-annexin-a2-by-n-terminal-phosphorylation-and-s100a4-binding
#15
Péter Ecsédi, Bence Kiss, Gergő Gógl, László Radnai, László Buday, Kitti Koprivanacz, Károly Liliom, Ibolya Leveles, Beáta Vértessy, Norbert Jeszenői, Csaba Hetényi, Gitta Schlosser, Gergely Katona, László Nyitray
Annexin A2 (ANXA2) has a versatile role in membrane-associated functions including membrane aggregation, endo- and exocytosis, and it is regulated by post-translational modifications and protein-protein interactions through the unstructured N-terminal domain (NTD). Our sequence analysis revealed a short motif responsible for clamping the NTD to the C-terminal core domain (CTD). Structural studies indicated that the flexibility of the NTD and CTD are interrelated and oppositely regulated by Tyr24 phosphorylation and Ser26Glu phosphomimicking mutation...
June 21, 2017: Structure
https://www.readbyqxmd.com/read/28667747/lack-of-response-to-intravenous-sodium-thiosulfate-in-three-cases-of-extensive-connective-tissue-disease-associated-calcinosis-cutis
#16
P Song, N M Fett, J Lin, J F Merola, M Costner, R A Vleugels
Dystrophic calcinosis cutis is a debilitating condition of calcium salt deposition in the skin often occurring in association with connective tissue disease (CTD). Available treatments for calcinosis cutis are unsatisfactory, but given the recent use of topical and intralesional sodium thiosulfate (STS) to treat calcifying disorders, we sought to describe the use of intravenous (IV) STS for CTD-associated dystrophic calcinosis cutis. We report three patients with longstanding and extensive CTD-associated calcinosis cutis treated with IV STS after having failed multiple prior therapies...
July 1, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/28666014/radiologic-pleuroparenchymal-fibroelastosis-like-lesion-in-connective-tissue-disease-related-interstitial-lung-disease
#17
Yasunori Enomoto, Yutaro Nakamura, Thomas V Colby, Takeshi Johkoh, Hiromitsu Sumikawa, Koji Nishimoto, Katsuhiro Yoshimura, Sayomi Matsushima, Yoshiyuki Oyama, Hironao Hozumi, Masato Kono, Tomoyuki Fujisawa, Noriyuki Enomoto, Naoki Inui, Toshihide Iwashita, Takafumi Suda
BACKGROUND: Radiologic pleuroparenchymal fibroelastosis (PPFE)-like lesion including pulmonary apical cap can be occasionally observed in clinical settings. However, the significance of radiologic PPFE-like lesion is unclear in connective tissue disease (CTD)-related interstitial lung disease (ILD). MATERIALS AND METHODS: A total of 113 patients with CTD-related ILD were enrolled and assessed for radiologic PPFE-like lesion, which was defined as bilateral, upper lobe, and subpleural dense consolidations with or without pleural thickening on chest high-resolution computed tomography...
2017: PloS One
https://www.readbyqxmd.com/read/28663408/a-long-term-follow-up-study-of-the-clinical-and-radiographic-outcome-of-distal-trochanteric-transfer-in-legg-calv%C3%A3-perthes-disease-following-varus-derotational-osteotomy
#18
N Shohat, R Gilat, R Shitrit, Y Smorgick, Y Beer, G Agar
AIMS: To assess the long-term effect of distal trochanteric transfer (DTT) on the clinical and radiographic outcomes of patients with Legg-Calvé-Perthes' disease (LCPD) following a varus derotational osteotomy (VDRO). PATIENTS AND METHODS: For this single centre cross-sectional retrospective study we analysed the data of 22 patients (24 hips) with LCPD who had greater trochanteric overgrowth (GTO), following a VDRO performed in our institution between 1959 and 1983...
July 2017: Bone & Joint Journal
https://www.readbyqxmd.com/read/28658626/functional-dissection-of-the-pol-v-largest-subunit-ctd-in-rna-directed-dna-methylation
#19
Jered M Wendte, Jeremy R Haag, Jasleen Singh, Anastasia McKinlay, Olga M Pontes, Craig S Pikaard
Plant multisubunit RNA polymerase V (Pol V) transcription recruits Argonaute-small interfering RNA (siRNA) complexes that specify sites of RNA-directed DNA methylation (RdDM) for gene silencing. Pol V's largest subunit, NRPE1, evolved from the largest subunit of Pol II but has a distinctive C-terminal domain (CTD). We show that the Pol V CTD is dispensable for catalytic activity in vitro yet essential in vivo. One CTD subdomain (DeCL) is required for Pol V function at virtually all loci. Other CTD subdomains have locus-specific effects...
June 27, 2017: Cell Reports
https://www.readbyqxmd.com/read/28648480/a-10-year-institutional-experience-with-open-branched-graft-reconstruction-of-aortic-aneurysms-in-connective-tissue-disorders-versus-degenerative-disease
#20
Caitlin W Hicks, Jennifer Lue, Natalia O Glebova, Bryan A Ehlert, James H Black
OBJECTIVE: Aortic reconstruction for complex thoracoabdominal aortic aneurysms (TAAAs) can be challenging, especially in patients with connective tissue disorders (CTDs) in whom tissue fragility is a major concern. Branched graft reconstruction is a more complex operation compared with inclusion patch repair of the aorta but is frequently necessary in patients with CTDs or other pathologies because of anatomic reasons. We describe our institutional experience with open branched graft reconstruction of aortic aneurysms and compare outcomes for patients with CTDs vs degenerative pathologies...
June 22, 2017: Journal of Vascular Surgery
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