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https://www.readbyqxmd.com/read/28544856/recent-advances-in-connective-tissue-disease-related-interstitial-lung-disease
#1
Atsushi Suzuki, Yasuhiro Kondoh, Aryeh Fischer
Interstitial lung disease (ILD) is a common manifestation of connective tissue disease (CTD). Although the majority of patients with CTD-ILD are stable or slowly progressive, a significant group exhibits a more severe and progressive decline. Interstitial pneumonia with autoimmune features (IPAF) describes the subset of patients with interstitial pneumonia who have features suggesting underlying autoimmunity, but whose features fall short of a clear diagnosis of CTD. Areas covered: In this focused review, we discuss recent advances in early detection, prognostic evaluation, and management of autoimmune forms of ILD...
May 25, 2017: Expert Review of Respiratory Medicine
https://www.readbyqxmd.com/read/28541123/new-exponential-functions-based-on-ct-density-to-estimate-the-percentage-of-liver-that-is-fat
#2
Georgia Keramida, A Michael Peters
OBJECTIVES: In FDG PET/CT, hepatic standardised uptake value (SUV) is reduced through 'signal dilution' by hepatic fat. Maximum SUV (SUVmax) is less affected than mean SUV (SUVmean), so SUVmax/SUVmean correlates with hepatic fat. SUV can be corrected for signal dilution using an equation relating CT density (CTD) to %fat. The objective was to exploit the relationship between SUV indices and CTD to assess the validity of two previously published equations (one linear, one sigmoid) for estimating %fat from CTD, and two new exponential equations...
May 25, 2017: British Journal of Radiology
https://www.readbyqxmd.com/read/28537551/rna-dependent-chromatin-association-of-transcription-elongation-factors-and-pol-ii-ctd-kinases
#3
Sofia Battaglia, Michael Lidschreiber, Carlo Baejen, Phillipp Torkler, Seychelle M Vos, Patrick Cramer
For transcription through chromatin, RNA polymerase (Pol) II associates with elongation factors (EFs). Here we show that many EFs crosslink to RNA emerging from transcribing Pol II in the yeast Saccharomyces cerevisiae. Most EFs crosslink preferentially to mRNAs, rather than unstable non-coding RNAs. RNA contributes to chromatin association of many EFs, including the Pol II serine 2 kinases Ctk1 and Bur1 and the histone H3 methyltransferases Set1 and Set2. The Ctk1 kinase complex binds RNA in vitro, consistent with direct EF-RNA interaction...
May 24, 2017: ELife
https://www.readbyqxmd.com/read/28536523/positive-modulatory-interactions-of-nmda-receptor-glun1-2b-ligand-binding-domains-attenuate-antagonists-activity
#4
Douglas Bledsoe, Ceyhun Tamer, Ivana Mesic, Christian Madry, Bradley G Klein, Bodo Laube, Blaise M Costa
N-methyl D-aspartate receptors (NMDAR) play crucial role in normal brain function and pathogenesis of neurodegenerative and psychiatric disorders. Functional tetra-heteromeric NMDAR contains two obligatory GluN1 subunits and two identical or different non-GluN1 subunits that include six different gene products; four GluN2 (A-D) and two GluN3 (A-B) subunits. The heterogeneity of subunit combination facilities the distinct function of NMDARs. All GluN subunits contain an extracellular N-terminal Domain (NTD) and ligand binding domain (LBD), transmembrane domain (TMD) and an intracellular C-terminal domain (CTD)...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28534504/crystal-structure-of-the-receptor-binding-domain-of-the-spike-glycoprotein-of-human-betacoronavirus-hku1
#5
Xiuyuan Ou, Hongxin Guan, Bo Qin, Zhixia Mu, Justyna A Wojdyla, Meitian Wang, Samuel R Dominguez, Zhaohui Qian, Sheng Cui
Human coronavirus (CoV) HKU1 is a pathogen causing acute respiratory illnesses and so far little is known about its biology. HKU1 virus uses its S1 subunit C-terminal domain (CTD) and not the N-terminal domain like other lineage A β-CoVs to bind to its yet unknown human receptor. Here we present the crystal structure of HKU1 CTD at 1.9 Å resolution. The structure consists of three subdomains: core, insertion and subdomain-1 (SD-1). While the structure of the core and SD-1 subdomains of HKU1 are highly similar to those of other β-CoVs, the insertion subdomain adopts a novel fold, which is largely invisible in the cryo-EM structure of the HKU1 S trimer...
May 23, 2017: Nature Communications
https://www.readbyqxmd.com/read/28529660/biomechanical-considerations-in-slipped-capital-femoral-epiphysis-and-insights-into-prophylactic-fixation
#6
E Leblanc, J M Bellemore, T Cheng, D G Little, O Birke
PURPOSE: Slipped capital femoral epiphysis (SCFE) is a deformity of the proximal femur secondary to widened and unstable physis. In stabilising the slip, gold standard treatments stop growth and involve premature physeal closure, which prevents the remodelling of the acquired deformity and creates a leg length discrepancy that may be significant in younger patients. METHODS: We measured the impact of placing threaded screws across the proximal femoral physis by measuring the centre-trochanteric distance (CTD) and articulo-trochanteric distance (ATD) in participants with or without prophylactic fixation...
April 2017: Journal of Children's Orthopaedics
https://www.readbyqxmd.com/read/28521808/b-cell-repopulation-kinetics-after-rituximab-treatment-in-anca-associated-vasculitides-compared-to-rheumatoid-arthritis-and-connective-tissue-diseases-a-longitudinal-observational-study-on-120-patients
#7
Jens Thiel, Marta Rizzi, Marie Engesser, Ann-Kathrin Dufner, Arianna Troilo, Raquel Lorenzetti, Reinhard E Voll, Nils Venhoff
BACKGROUND: B cell depletion with rituximab (RTX) is approved for treatment of rheumatoid arthritis (RA) and ANCA-associated vasculitides (AAV). Recently, RTX has been shown to be effective in AAV maintenance therapy, but an optimal RTX treatment schedule is unknown and the time to B cell repopulation after RTX has not been studied. METHODS: Retrospective single-center analysis of B cell repopulation in patients with AAV, RA or connective tissue disease (CTD) treated with RTX...
May 18, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28513152/a-molecular-mechanism-for-nonphotochemical-quenching-in-cyanobacteria
#8
Yue Lu, Haijun Liu, Rafael Saer, Veronica L Li, Hao Zhang, Liuqing Shi, Carrie Goodson, Michael L Gross, Robert E Blankenship
The cyanobacterial orange carotenoid protein (OCP) protects photosynthetic cyanobacteria from photodamage by dissipating excess excitation energy collected by phycobilisomes (PBS) as heat. Dissociation of the PBS-OCP complex in vivo is facilitated by another protein known as the fluorescence recovery protein (FRP), which primarily exists as a dimeric complex. We used various mass spectrometry (MS)-based techniques to investigate the molecular mechanism of this FRP-mediated process. FRP in the dimeric state (dFRP) retains its high affinity for the C-terminal domain (CTD) of OCP in the red state (OCP(r))...
May 25, 2017: Biochemistry
https://www.readbyqxmd.com/read/28508461/foxp3-polymorphisms-in-interstitial-lung-disease-among-chinese-han-population-a-genetic-association-study
#9
Jianyu Yao, Tianze Zhang, Lili Zhang, Kaiyu Han, Linyou Zhang
INTRODUCTION: Both genetic and environmental factors are implicated in the pathogenesis of interstitial lung disease (ILD). Single-nucleotide polymorphisms (SNPs) in FOXP3 genes were implicated in the causation of some autoimmune diseases; however, association of these genes and ILD has not been reported. OBJECTIVES: To investigate whether FOXP3 polymorphisms are associated with ILD in a representative Chinese population. METHODS: One hundred and fifty-seven ILD patients and 170 healthy controls were recruited; SNPs were genotyped by the Sequenom MassARRAY platform and SHEsis was used to estimate the haplotype frequencies of SNPs...
May 15, 2017: Clinical Respiratory Journal
https://www.readbyqxmd.com/read/28507178/anti-carbamylated-protein-antibodies-are-detectable-in-various-connective-tissue-diseases
#10
Shuichiro Nakabo, Hajime Yoshifuji, Motomu Hashimoto, Yoshitaka Imura, Ran Nakashima, Kosaku Murakami, Nobuo Kuramoto, Shinji Ito, Junko Satoh, Masao Tanaka, Takao Fujii, Tsuneyo Mimori, Koichiro Ohmura
OBJECTIVE: Anti-carbamylated protein (anti-CarP) antibodies are possible diagnostic biomarkers of anticitrullinated protein antibody (ACPA)-negative rheumatoid arthritis (RA). We aimed to elucidate the prevalence of anti-CarP antibodies in non-RA connective tissue diseases (CTD) because CTD are important in the differential diagnosis of ACPA-negative RA. METHODS: The sera from 266 patients with RA and 616 patients with CTD and 80 healthy controls were examined using an in-house anti-CarP ELISA...
May 15, 2017: Journal of Rheumatology
https://www.readbyqxmd.com/read/28506829/an-asymmetric-dimeric-structure-of-trmj-trna-methyltransferase-from-zymomonas-mobilis-with-a-flexible-c-terminal-dimer
#11
Do-Heon Gu, Mi-Young Park, Jeong-Sun Kim
The tRNA methyltransferase J (TrmJ) and D (TrmD) catalyze the transferring reaction of a methyl group to the tRNA anticodon loop. They commonly have the N-terminal domain (NTD) and the C-terminal domain (CTD). Whereas two monomeric CTDs symmetrically interact with a dimeric NTD in TrmD, a CTD dimer has exhibited an asymmetric interaction with the NTD dimer in the presence of a product. The elucidated apo-structure of the full-length TrmJ from Zymomonas mobilis ZM4 shows a dimeric CTD that asymmetrically interacts with the NTD dimer, thereby distributing non-symmetrical potential charge on the both side of the protein surface...
May 12, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28506463/rna-pol-ii-dynamics-modulate-co-transcriptional-chromatin-modification-ctd-phosphorylation-and-transcriptional-direction
#12
Nova Fong, Tassa Saldi, Ryan M Sheridan, Michael A Cortazar, David L Bentley
Eukaryotic genes are marked by conserved post-translational modifications on the RNA pol II C-terminal domain (CTD) and the chromatin template. How the 5'-3' profiles of these marks are established is poorly understood. Using pol II mutants in human cells, we found that slow transcription repositioned specific co-transcriptionally deposited chromatin modifications; histone H3 lysine 36 trimethyl (H3K36me3) shifted within genes toward 5' ends, and histone H3 lysine 4 dimethyl (H3K4me2) extended farther upstream of start sites...
May 18, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28506081/epidemiological-characteristics-of-chinese-paediatric-traumatic-brain-injury-inpatients
#13
Yunming Li, Fuqin Chen, Junran Zhang, Gang Li, Xiaoguang Yang, Qiang Lu, Xun Xia, Xinyan Zhang, Jun Qiu, Junpeng Zhang, Jihong Zhou, Yongqin Kuang, Jianwen Gu
PRIMARY OBJECTIVE: To investigate the epidemiological characteristics of paediatric inpatients with traumatic brain injury (TBI) in China. RESEARCH DESIGN: The Chinese Trauma Database (CTD), a nationwide register system based on hospital admission data, contains diagnosis and treatment information for trauma inpatients in over 200 military-managed public-service hospitals in China. Using the ICD-9 coding, the data for children with TBI aged 0-17 years between 2001 and 2007 were retrieved...
May 16, 2017: Brain Injury: [BI]
https://www.readbyqxmd.com/read/28504272/sirt1-carboxyl-domain-is-an-atp-repressible-domain-that-is-transferrable-to-other-proteins
#14
Hyeog Kang, Shinichi Oka, Duck-Yeon Lee, Junhong Park, Angel M Aponte, Young-Sang Jung, Jacob Bitterman, Peiyong Zhai, Yi He, Hamed Kooshapur, Rodolfo Ghirlando, Nico Tjandra, Sean B Lee, Myung K Kim, Junichi Sadoshima, Jay H Chung
Sirt1 is an NAD(+)-dependent protein deacetylase that regulates many physiological functions, including stress resistance, adipogenesis, cell senescence and energy production. Sirt1 can be activated by energy deprivation, but the mechanism is poorly understood. Here, we report that Sirt1 is negatively regulated by ATP, which binds to the C-terminal domain (CTD) of Sirt1. ATP suppresses Sirt1 activity by impairing the CTD's ability to bind to the deacetylase domain as well as its ability to function as the substrate recruitment site...
May 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28503830/synthetic-ocp-heterodimers-are-photoactive-and-recapitulate-the-fusion-of-two-primitive-carotenoproteins-in-the-evolution-of-cyanobacterial-photoprotection
#15
Sigal Lechno-Yossef, Matthew R Melnicki, Han Bao, Beronda L Montgomery, Cheryl A Kerfeld
The Orange Carotenoid Protein (OCP) governs photoprotection in the majority of cyanobacteria. It is structurally and functionally modular, comprised of a C-terminal regulatory domain (CTD), an N-terminal effector domain (NTD) and a ketocarotenoid; the chromophore spans the two domains in the ground state and translocates fully into the NTD upon illumination. Using both the canonical OCP1 from Fremyella diplosiphon and the presumably more primitive OCP2 paralog from the same organism, we show that an NTD-CTD heterodimer forms when the domains are expressed as separate polypeptides...
May 15, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28499864/role-of-hepatitis-b-core-protein-in-hbv-transcription-and-recruitment-of-histone-acetyltransferases-to-cccdna-minichromosome
#16
Chun Kong Chong, Ching Yan Serene Cheng, Sin Yi Jasmine Tsoi, Fung-Yu Huang, Fen Liu, Wai-Kay Seto, Ching-Lung Lai, Man-Fung Yuen, Danny Ka-Ho Wong
The hepatitis B core protein (HBc) has been suggested to interact with covalently closed circular DNA (cccDNA) and regulate hepatitis B virus (HBV) transcription. However, direct evidence is lacking. We aimed to identify the specific HBc region(s) responsible for transcription regulation and its interaction with cccDNA. Seventeen mutants with mutations at the four arginine-rich clusters of the HBc carboxyl-terminal domain (CTD) were created. The effect of HBc mutations on the levels of HBV DNA, RNA, and hepatitis B surface antigen (HBsAg) were measured...
May 10, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28497798/phosphorylation-induces-sequence-specific-conformational-switches-in-the-rna-polymerase-ii-c-terminal-domain
#17
Eric B Gibbs, Feiyue Lu, Bede Portz, Michael J Fisher, Brenda P Medellin, Tatiana N Laremore, Yan Jessie Zhang, David S Gilmour, Scott A Showalter
The carboxy-terminal domain (CTD) of the RNA polymerase II (Pol II) large subunit cycles through phosphorylation states that correlate with progression through the transcription cycle and regulate nascent mRNA processing. Structural analyses of yeast and mammalian CTD are hampered by their repetitive sequences. Here we identify a region of the Drosophila melanogaster CTD that is essential for Pol II function in vivo and capitalize on natural sequence variations within it to facilitate structural analysis. Mass spectrometry and NMR spectroscopy reveal that hyper-Ser5 phosphorylation transforms the local structure of this region via proline isomerization...
May 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/28497792/structural-heterogeneity-in-the-intrinsically-disordered-rna-polymerase-ii-c-terminal-domain
#18
Bede Portz, Feiyue Lu, Eric B Gibbs, Joshua E Mayfield, M Rachel Mehaffey, Yan Jessie Zhang, Jennifer S Brodbelt, Scott A Showalter, David S Gilmour
RNA polymerase II contains a repetitive, intrinsically disordered, C-terminal domain (CTD) composed of heptads of the consensus sequence YSPTSPS. The CTD is heavily phosphorylated and serves as a scaffold, interacting with factors involved in transcription initiation, elongation and termination, RNA processing and chromatin modification. Despite being a nexus of eukaryotic gene regulation, the structure of the CTD and the structural implications of phosphorylation are poorly understood. Here we present a biophysical and biochemical interrogation of the structure of the full length CTD of Drosophila melanogaster, which we conclude is a compact random coil...
May 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/28495207/targeting-the-hsp90-c-terminal-domain-to-induce-allosteric-inhibition-and-selective-client-downregulation
#19
Kourtney M Goode, Dino Petrov, Renee E Vickman, Scott A Crist, Pete E Pascuzzi, Tim L Ratliff, V Jo Davisson, Tony R Hazbun
BACKGROUND: Inhibition of Hsp90 is desirable due to potential downregulation of oncogenic clients. Early generation inhibitors bind to the N-terminal domain (NTD) but C-terminal domain (CTD) inhibitors are a promising class because they do not induce a heat shock response. Here we present a new structural class of CTD binding molecules with a unique allosteric inhibition mechanism. METHODS: A hit molecule, NSC145366, and structurally similar probes were assessed for inhibition of Hsp90 activities...
May 8, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28493424/the-dynamic-multisite-interactions-between-two-intrinsically-disordered-proteins
#20
Shaowen Wu, Dongdong Wang, Jin Liu, Yitao Feng, Jingwei Weng, Yu Li, Xin Gao, Jianwei Liu, Wenning Wang
Protein interactions involving intrinsically disordered proteins (IDPs) comprise a variety of binding modes, from the well-characterized folding upon binding to dynamic fuzzy complexes. To date, most studies concern the binding of an IDP to a structured protein, while the interaction between two IDPs is poorly understood. In this study, NMR, smFRET, and molecular dynamics (MD) simulation are combined to characterize the interaction between two IDPs, the C-terminal domain (CTD) of protein 4.1G and the nuclear mitotic apparatus (NuMA) protein...
May 11, 2017: Angewandte Chemie
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