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https://www.readbyqxmd.com/read/28339528/the-utility-of-comprehensive-autoantibody-testing-to-differentiate-connective-tissue-disease-associated-and-idiopathic-interstitial-lung-disease-subgroup-cases
#1
Caroline V Cotton, Lisa G Spencer, Robert P New, Robert G Cooper
Interstitial lung disease (ILD) comprises many heterogeneous disease groups, the largest being CTD-associated and those labelled as idiopathic out of necessity. The mechanisms causing ILD are poorly understood, but most CTD- and idiopathic-ILD cases can respond to immunosuppression, clearly suggesting a pathological role for inflammation. By contrast, corticosteroid immunosuppression causes harm without benefit in the feared idiopathic pulmonary fibrosis, suggesting that inflammation plays little pathological role, and where ILD progresses rapidly to lethal outcome even with anti-fibrotic drug use...
October 20, 2016: Rheumatology
https://www.readbyqxmd.com/read/28335076/fine-mapping-of-chromosome-5p15-33-identifies-novel-lung-cancer-susceptibility-loci-in-han-chinese
#2
Jing Dong, Yang Cheng, Meng Zhu, Yang Wen, Cheng Wang, Yuzhuo Wang, Liguo Geng, Wei Shen, Jia Liu, Zhihua Li, Jiahui Zhang, Hongxia Ma, Juncheng Dai, Guangfu Jin, Zhibin Hu, Hongbing Shen
Genome-wide association studies in European and Asian populations have consistently identified chromosome 5p15.33 as a lung cancer susceptibility region. To investigate further the genetic architecture of common variants in this region, we conducted a two-stage fine-mapping analysis discovered by targeted resequencing of 200 cases and 300 controls individually, and validated in multiethnic lung cancer GWASs with 12,843 cases and 12,639 controls. Two independent variants were identified in approximate conditional analysis with GCTA and consistently validated in lung cancer GWASs in both Asian and European populations...
March 23, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28334541/-autoantibodies-in-systemic-connective-tissue-disease-and-anca-associated-vasculitis-their-relationship-to-interstitial-lung-diseases-and-prognosis
#3
Martina Doubková, Jana Pokorná
Lung disease, including interstitial lung disease (ILD), is a frequent complication of systemic connective tissue disorders (CTD) and ANCA (anti-neutrophil cytoplasmic antibody) associated vasculitis (AAV). Pulmonary manifestations are prognostic factor of CTDs and vasculitis. Autoantibodies assessment is a part of differential diagnosis algorithm of lung diseases. Autoantibodies importance is mainly clinical-diagnostic. Using detection of some autoantibodies it is possible to determine prognosis of lung involvement, especially in CTDs...
2017: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/28331093/structural-characterization-of-hcov-nl63-n-protein
#4
Bozena Szelazek, Wojciech Kabala, Krzysztof Kus, Michal Zdzalik, Aleksandra Twarda-Clapa, Przemyslaw Golik, Michal Burmistrz, Dominik Florek, Benedykt Wladyka, Krzysztof Pyrc, Grzegorz Dubin
Coronaviruses are responsible for upper and lower respiratory tract infections in humans. It is estimated that 1-10% of the population suffers annually from cold-like symptoms related to infection with HCoV-NL63, an alphacoronavirus. The nucleocapsid (N) protein, the major structural component of the capsid, facilitates RNA packing, links the capsid to the envelope and is also involved in multiple other processes including viral replication and evasion of the immune system. Although the role of N protein in viral replication is relatively well described, no structural data are currently available regarding the N proteins of alphacoronaviruses...
March 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28324000/trh-action-is-impaired-in-pituitaries-of-male-igsf1-deficient-mice
#5
Marc-Olivier Turgeon, Tanya L Silander, Denica Doycheva, Xiao-Hui Liao, Marc Rigden, Luisina Ongaro, Xiang Zhou, Sjoerd D Joustra, Jan M Wit, Mike G Wade, Heike Heuer, Samuel Refetoff, Daniel J Bernard
Loss-of-function mutations in the X-linked immunoglobulin superfamily, member 1 (IGSF1) gene cause central hypothyroidism. IGSF1 is a transmembrane glycoprotein of unknown function expressed in TSH-producing thyrotrope cells of the anterior pituitary gland. The protein is co-translationally cleaved, with only its C-terminal domain (CTD) being trafficked to the plasma membrane. Most intragenic IGSF1 mutations in humans map to the CTD. Here, we used CRISPR-Cas9 to introduce a loss-of-function mutation into the IGSF1-CTD in mice...
January 13, 2017: Endocrinology
https://www.readbyqxmd.com/read/28320882/contributions-of-the-n-terminal-and-c-terminal-domains-of-initiation-factor-3-towards-its-functions-in-the-fidelity-of-initiation-and-anti-association-of-the-ribosomal-subunits
#6
Shreya Ayyub, Divya Dobriyal, Umesh Varshney
Initiation factor 3 (IF3) is one of the three conserved prokaryotic translation initiation factors essential for protein synthesis and cellular survival. Bacterial IF3 is composed of a conserved architecture of N- and C- terminal globular domains (NTD and CTD) joined by a linker region. IF3 is a ribosome anti-association factor which also modulates selection of start codon and initiator tRNA. All the functions of IF3 have been attributed to its CTD by in vitro studies. However, in vivo relevance of these findings has not been investigated...
March 20, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28320876/taking-a-step-back-from-back-translocation-an-integrative-view-of-lepa-ef4-s-cellular-function
#7
Jalyce L E Heller, Rajashekhar Kamalampeta, Hans-Joachim Wieden
Protein synthesis, the translation of mRNA into a polypeptide facilitated by the ribosome, is assisted by a variety of protein factors, some of which are GTPases. In addition to four highly conserved and well-understood GTPases with known function, there are also a number of non-canonical GTPases that are implicated in translation but whose functions are not fully understood. LepA/EF4 is one of these non-canonical GTPases. It is highly conserved and present in bacteria, mitochondria and chloroplasts, but its functional role in the cell remains unknown...
March 20, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28300570/idiopathic-interstitial-pneumonia-associated-with-autoantibodies-a-large-case-series-followed-over-one-year
#8
Bridget F Collins, Charles F Spiekerman, Megan A Shaw, Lawrence A Ho, Jennifer Hayes, Carolyn A Spada, Caroline M Stamato, Ganesh Raghu
BACKGROUND: Some patients with autoimmune characteristics and idiopathic interstitial pneumonia (IIP), particularly usual interstitial pneumonia (UIP), do not fit neatly into the category of connective tissue disease associated interstitial lung disease (CTD-ILD), idiopathic pulmonary fibrosis (IPF) or recently proposed yet to be validated criteria for interstitial pneumonia with autoimmune features (IPAF). Outcomes of these patients are unknown. METHODS: Retrospective single center study; ANOVA analyses compared differences in mean change in forced vital capacity (FVC) and diffusion capacity (DLCO) over 1-year among 124 well defined patients (20 AI-ILD [positive autoantibodies with or without symptoms of CTD], 15 IPAF, 36 CTD-ILD, 53 "Lone-IPF" [patients with IPF without any autoantibodies]) RESULTS: 75% of patients with AI-ILD, 33% IPAF, and 33% CTD-ILD had UIP...
March 11, 2017: Chest
https://www.readbyqxmd.com/read/28300396/negative-polarity-helium-charge-transfer-dissociation-tandem-mass-spectrometry-radical-initiated-fragmentation-of-complex-polysulfated-anions
#9
David Ropartz, Pengfei Li, Glen P Jackson, Hélène Rogniaux
This work provides the first use of helium charge transfer dissociation (He-CTD) tandem mass spectrometry (MS/MS) in negative polarity mode. Three sulfated oligosaccharides of natural origin were chosen as representative structures that are difficult to solve by conventional MS/MS approaches. Negative polarity He-CTD provided a full set of structurally informative fragments, which permitted the unambiguous determination of the complete structures of these molecules, including the characterization of labile sulfated functional groups...
March 20, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28291250/site-to-site-interdomain-communication-may-mediate-different-loss-of-function-mechanisms-in-a-cancer-associated-nqo1-polymorphism
#10
Encarnación Medina-Carmona, Jose L Neira, Eduardo Salido, Julian E Fuchs, Rogelio Palomino-Morales, David J Timson, Angel L Pey
Disease associated genetic variations often cause intracellular enzyme inactivation, dysregulation and instability. However, allosteric communication of mutational effects to distant functional sites leading to loss-of-function remains poorly understood. We characterize here interdomain site-to-site communication by which a common cancer-associated single nucleotide polymorphism (c.C609T/p.P187S) reduces the activity and stability in vivo of NAD(P)H:quinone oxidoreductase 1 (NQO1). NQO1 is a FAD-dependent, two-domain multifunctional stress protein acting as a Phase II enzyme, activating cancer pro-drugs and stabilizing p53 and p73α oncosuppressors...
March 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28286152/toxin-production-of-clostridium-difficile-in-sub-mic-of-vancomycin-and-clindamycin-alone-and-in-combination-with-ceftazidime
#11
Ebrahim Rezazadeh Zarandi, Shahla Mansouri, Nouzar Nakhaee, Farhad Sarafzadeh, Mohammad Moradi
Toxin production in Clostridium difficile (C. difficile) is a key process for induction of diarrhea. Several factors such as sub-MIC of antibiotics impact on toxin production. The aim of this research is investigation of sub-minimum inhibitory concentration (sub-MIC) of vancomycin (VAN), clindamycin (CLI) separately and in combination with ceftazidime (CAZ) on toxin production in C. difficile. About ∼10(6) colony forming units (CFU) from 18-h culture of C. difficile ATCC 9689 and clinical isolates A(+)/B(+)/CTD(-), were cultured anaerobically in the pre-reduced medium with appropriate concentration of separated and in combination antibiotics...
March 7, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28283462/real-world-long-term-survival-of-incident-patients-with-pulmonary-arterial-hypertension
#12
P Marques-Alves, R Baptista, A Marinho da Silva, M Pêgo, G Castro
BACKGROUND: Pulmonary arterial hypertension (PAH) is a progressive, fatal disease. Long-term outcomes data are scarce in Portugal. We aimed to estimate survival of newly diagnosed PAH at a Portuguese referral center in the modern management era. METHODS: Between January 2009 and November 2015 all incident PAH cases were consecutively enrolled in a prospective cohort study. Sixty-five patients were followed up for a median of 3.1 [interquartile range 1.7-5.4] years...
March 7, 2017: Revista Portuguesa de Pneumologia
https://www.readbyqxmd.com/read/28281558/allosteric-modulation-of-peroxisomal-membrane-protein-recognition-by-farnesylation-of-the-peroxisomal-import-receptor-pex19
#13
Leonidas Emmanouilidis, Ulrike Schütz, Konstantinos Tripsianes, Tobias Madl, Juliane Radke, Robert Rucktäschel, Matthias Wilmanns, Wolfgang Schliebs, Ralf Erdmann, Michael Sattler
The transport of peroxisomal membrane proteins (PMPs) requires the soluble PEX19 protein as chaperone and import receptor. Recognition of cargo PMPs by the C-terminal domain (CTD) of PEX19 is required for peroxisome biogenesis in vivo. Farnesylation at a C-terminal CaaX motif in PEX19 enhances the PMP interaction, but the underlying molecular mechanisms are unknown. Here, we report the NMR-derived structure of the farnesylated human PEX19 CTD, which reveals that the farnesyl moiety is buried in an internal hydrophobic cavity...
March 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/28279499/tadalafil-in-idiopathic-or-heritable-pulmonary-arterial-hypertension-pah-compared-to-pah-associated-with-connective-tissue-disease
#14
Nazzareno Galiè, Christopher P Denton, Fabio Dardi, Alessandra Manes, Gaia Mazzanti, Baohui Li, Lucio Varanese, Anne Esler, Cathi Harmon, Massimiliano Palazzini
BACKGROUND: The primary objective of this post hoc analysis was to evaluate clinical outcomes of tadalafil in patients with pulmonary arterial hypertension (PAH) associated with connective tissue disease (CTD-PAH) compared with patients with idiopathic/heritable PAH (I/H-PAH) for primary and key secondary efficacy endpoints, and safety. This analysis included adult patients with CTD-PAH or I/H-PAH who participated in the PHIRST and PHIRST-2 studies. METHODS: Patients were randomized 1:1:1:1:1 to tadalafil (2...
February 22, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28274531/an-analysis-of-the-clinical-features-of-lung-cancer-in-patients-with-connective-tissue-diseases
#15
Atsuro Saijo, Masaki Hanibuchi, Hisatsugu Goto, Yuko Toyoda, Toshifumi Tezuka, Yasuhiko Nishioka
BACKGROUND: Patients with connective tissue diseases (CTDs) are at increased risk for lung cancer (LC); interstitial lung disease (ILD) is a common form of organ dysfunction in cases of CTD. However, the influence of ILD on the treatment and prognosis in LC patients with CTD is unclear. METHODS: Between January 2010 and December 2014, 27 patients among all patients with CTD at our institution were diagnosed with primary LC. We retrospectively analyzed the clinical features, treatment modalities, and outcomes of these patients, and evaluated the potential prognostic factors...
March 2017: Respiratory Investigation
https://www.readbyqxmd.com/read/28273146/evaluation-of-an-automated-connective-tissue-disease-screening-assay-in-korean-patients-with-systemic-rheumatic-diseases
#16
Seri Jeong, Heeyoung Yang, Hyunyong Hwang
This study aimed to evaluate the diagnostic utilities of the automated connective tissues disease screening assay, CTD screen, in patients with systemic rheumatic diseases. A total of 1093 serum samples were assayed using CTD screen and indirect immunofluorescent (IIF) methods. Among them, 162 were diagnosed with systemic rheumatic disease, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and mixed connective tissue disease (MCT). The remaining 931 with non-systemic rheumatic disease were assigned to the control group...
2017: PloS One
https://www.readbyqxmd.com/read/28270505/essential-role-of-the-flexible-linker-on-the-conformational-equilibrium-of-bacterial-peroxiredoxin-reductase-for-effective-regeneration-of-peroxiredoxin
#17
Neelagandan Kamariah, Birgit Eisenhaber, Frank Eisenhaber, Gerhard Gruber
Reactive oxygen species (ROS) can damage DNA, proteins, and lipids, so cells have antioxidant systems that regulate ROS. In many bacteria, a dedicated peroxiredoxin reductase, alkyl hydroperoxide reductase subunit F (AhpF), catalyzes the rapid reduction of the redox-active disulfide center of the antioxidant protein peroxiredoxin (AhpC) to detoxify ROS such as hydrogen peroxide, organic hydroperoxide, and peroxynitrite. AhpF is a flexible multi-domain protein that enables a series of electron transfers among the redox centers by accepting reducing equivalents from NADH...
March 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28258643/charge-transfer-dissociation-ctd-of-phosphocholines-gas-phase-ion-ion-reactions-between-helium-cations-and-phospholipid-cations
#18
Pengfei Li, Glen P Jackson
Phospholipid cations formed by electrospray ionization were subjected to excitation and fragmentation by a beam of 6 keV helium cations in a process termed charge transfer dissociation (CTD). The resulting fragmentation pattern in CTD is different from that of conventional collision-induced dissociation (CID), but analogous to that of metastable atom-activated dissociation (MAD) and electron-induced dissociation (EID). Like CID, CTD yields product ions indicative of acyl chain lengths and degrees of unsaturation in the fatty acyl moieties, but also provides additional structural diagnostic information, such as double bond position...
March 4, 2017: Journal of Mass Spectrometry: JMS
https://www.readbyqxmd.com/read/28257838/als-causing-cleavages-of-tdp-43-abolish-its-rrm2-structure-and-unlock-ctd-for-enhanced-aggregation-and-toxicity
#19
Yuanyuan Wei, Liangzhong Lim, Lu Wang, Jianxing Song
Pathological TDP-43 is cleaved into various fragments. Two major groups of ∼35 and ∼25 kDa have enhanced aggregation and cytotoxicity but the underlying mechanisms remain elusive. While the ∼35-kDa fragments contain entire RRM1, RRM2 and C-terminal domain (CTD) with a middle hydrophobic segment flanked by two prion-like regions; the ∼25-kDa one cleaved at Arg208 only consists of the truncated RRM2 and CTD. Remarkably, the 25-kDa fragment was characterized to induce cell death by gain of cytotoxicity and recapitulate pathological features of TDP-43 proteinopathies...
April 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28248323/the-code-and-beyond-transcription-regulation-by-the-rna-polymerase-ii-carboxy-terminal-domain
#20
REVIEW
Kevin M Harlen, L Stirling Churchman
The carboxy-terminal domain (CTD) extends from the largest subunit of RNA polymerase II (Pol II) as a long, repetitive and largely unstructured polypeptide chain. Throughout the transcription process, the CTD is dynamically modified by post-translational modifications, many of which facilitate or hinder the recruitment of key regulatory factors of Pol II that collectively constitute the 'CTD code'. Recent studies have revealed how the physicochemical properties of the CTD promote phase separation in the presence of other low-complexity domains...
March 1, 2017: Nature Reviews. Molecular Cell Biology
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