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https://www.readbyqxmd.com/read/28087624/tissue-specific-regulation-of-alternative-polyadenylation-represses-expression-of-neuronal-ankyrin-isoform-in-c-elegans-epidermal-development
#1
Fei Chen, Andrew D Chisholm, Yishi Jin
Differential mRNA polyadenylation plays an important role in shaping the neuronal transcriptome. In C. elegans, several ankyrin isoforms are produced from the unc-44 locus through alternative polyadenylation. Here, we identify a key role for an intronic polyadenylation site (PAS) in temporal- and tissue-specific regulation of UNC-44/ankyrin isoforms. Removing an intronic PAS results in ectopic expression of the neuronal ankyrin isoform in non-neural tissues. This mis-expression underlies epidermal developmental defects in mutants of the conserved tumor suppressor death-associated protein kinase, dapk-1 We previously reported that the use of this intronic PAS depends on the nuclear polyadenylation factor SYDN-1, which inhibits the RNA polymerase II CTD phosphatase SSUP-72...
January 13, 2017: Development
https://www.readbyqxmd.com/read/28087622/calmodulin-limits-pathogenic-na-channel-persistent-current
#2
Haidun Yan, Chaojian Wang, Steven O Marx, Geoffrey S Pitt
Increased "persistent" current, caused by delayed inactivation, through voltage-gated Na(+) (NaV) channels leads to cardiac arrhythmias or epilepsy. The underlying molecular contributors to these inactivation defects are poorly understood. Here, we show that calmodulin (CaM) binding to multiple sites within NaV channel intracellular C-terminal domains (CTDs) limits persistent Na(+) current and accelerates inactivation across the NaV family. Arrhythmia or epilepsy mutations located in NaV1.5 or NaV1.2 channel CTDs, respectively, reduce CaM binding either directly or by interfering with CTD-CTD interchannel interactions...
January 13, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28086753/better-care-provided-to-patients-with-tuberculosis-at-county-designated-tb-hospitals-ctd-compared-to-non-ctds-in-rural-china
#3
Li Yuan, Hui Zhang, Changming Zhou, Weili Jiang, Qi Zhao, Xu Biao
BACKGROUND: The primary unit of tuberculosis (TB) medical care in China is the county TB dispensary or county designated hospital (CTD), where patients can receive free diagnosis and treatment. However, a substantial number of patients seek their anti-TB treatment from general health facilities (Non-CTDs). This study aimed to investigate the first anti-TB treatment experience and choice of health facilities of retreated TB patients and their determinants. METHODS: A cross-sectional study was conducted in Jiangsu, Shandong and Sichuan provinces...
January 13, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28077651/bromodomain-containing-4-brd4-couples-nf%C3%AE%C2%BAb-rela-with-airway-inflammation-and-the-irf-rig-i-amplification-loop-in-respiratory-syncytial-virus-infection
#4
Bing Tian, Jun Yang, Yingxin Zhao, Teodora Ivanciuc, Hong Sun, Roberto P Garofalo, Allan R Brasier
: The airway mucosa expresses protective interferon (IFN) and inflammatory cytokines in response to Respiratory Syncytial Virus (RSV) infection. In this study, we examine the role of bromodomain containing 4 (BRD4) in mediating this innate immune response in human small airway epithelial cells. We observe that RSV induces BRD4 to complex with NFκB/RelA. BRD4 is functionally required for expression of the NFκB-dependent inflammatory gene regulatory network (GRN), including the IFN Response Factor (IRFs)-1 and -7 that mediate a cross-talk pathway for RIG-I upregulation...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28067802/stabilization-of-nucleosomes-by-histone-tails-and-by-fact-revealed-by-spfret-microscopy
#5
Maria E Valieva, Nadezhda S Gerasimova, Kseniya S Kudryashova, Anastasia L Kozlova, Mikhail P Kirpichnikov, Qi Hu, Maria Victoria Botuyan, Georges Mer, Alexey V Feofanov, Vasily M Studitsky
A correct chromatin structure is important for cell viability and is tightly regulated by numerous factors. Human protein complex FACT (facilitates chromatin transcription) is an essential factor involved in chromatin transcription and cancer development. Here FACT-dependent changes in the structure of single nucleosomes were studied with single-particle Förster resonance energy transfer (spFRET) microscopy using nucleosomes labeled with a donor-acceptor pair of fluorophores, which were attached to the adjacent gyres of DNA near the contact between H2A-H2B dimers...
January 6, 2017: Cancers
https://www.readbyqxmd.com/read/28066922/x-ray-crystal-structure-of-the-n-terminal-region-of-moloney-murine-leukemia-virus-integrase-and-its-implications-for-viral-dna-recognition
#6
Rongjin Guan, Sriram Aiyer, Marie L Cote, Rong Xiao, Mei Jiang, Thomas B Acton, Monica J Roth, Gaetano T Montelione
The retroviral integrase (IN) carries out the integration of a dsDNA copy of the viral genome into the host DNA, an essential step for viral replication. All IN proteins have three general domains, the N-terminal domain (NTD), the catalytic core domain (CCD), and the C-terminal domain (CTD). The NTD includes an HHCC zinc finger-like motif, which is conserved in all retroviral IN proteins. Two crystal structures of Moloney murine leukemia virus (M-MuLV) IN N-terminal region (NTR) constructs that both include an N-terminal extension domain (NED, residues 1-44) and an HHCC zinc-finger NTD (residues 45-105), in two crystal forms are reported...
January 9, 2017: Proteins
https://www.readbyqxmd.com/read/28053878/microparticle-subpopulations-are-potential-markers-of-disease-progression-and-vascular-dysfunction-across-a-spectrum-of-connective-tissue-disease
#7
E M McCarthy, D Moreno-Martinez, F L Wilkinson, N J McHugh, I N Bruce, J D Pauling, M Y Alexander, B Parker
OBJECTIVE: Microparticles (MPs) are membrane-bound vesicles derived from vascular and intravascular cells such as endothelial cells (EMPs) and platelets (PMPs). We investigated EMP and PMP numbers across a spectrum of autoimmune rheumatic diseases (AIRDs) with the aim of comparing the levels of, and relationship between, EMPs and PMPs. METHODS: Patients with Systemic Lupus Erythematosus (SLE) (n = 24), Systemic Sclerosis (SSc) (n = 24), Primary Raynauds Phenomenon (RP) (n = 17) and "other CTD" (n = 15) (Primary Sjogrens Syndrome, UCTD or MCTD) as well as 15 healthy controls were recruited...
June 2017: BBA Clinical
https://www.readbyqxmd.com/read/28050603/new-open-conformation-of-smyd3-implicates-conformational-selection-and-allostery
#8
Nicholas Spellmon, Xiaonan Sun, Wen Xue, Joshua Holcomb, Srinivas Chakravarthy, Weifeng Shang, Brian Edwards, Nualpun Sirinupong, Chunying Li, Zhe Yang
SMYD3 plays a key role in cancer cell viability, adhesion, migration and invasion. SMYD3 promotes formation of inducible regulatory T cells and is involved in reducing autoimmunity. However, the nearly "closed" substrate-binding site and poor in vitro H3K4 methyltransferase activity have obscured further understanding of this oncogenically related protein. Here we reveal that SMYD3 can adopt an "open" conformation using molecular dynamics simulation and small-angle X-ray scattering. This ligand-binding-capable open state is related to the crystal structure-like closed state by a striking clamshell-like inter-lobe dynamics...
2017: AIMS Biophysics
https://www.readbyqxmd.com/read/28049537/imperforated-cor-triatriatum-dexter-in-a-dog-with-concurrent-caudal-vena-cava-wall-mineralization
#9
Tetyda Paulina Dobak, Gregory Starrak, Kathleen Linn, Elisabeth Christine Roberston Snead
BACKGROUND: Cor triatriatum dexter (CTD) is a rare congenital cardiac malformation with various manifestations and has been sporadically described in dogs. Clinically the dogs present with nonspecific signs of right heart failure or Budd-Chiari-like syndrome. Other associated concurrent cardiovascular anomalies are commonly reported. Diagnosis and full characterization of this complex malformation requires careful investigation and often a multimodal imaging approach. CASE PRESENTATION: A 10-week-old, male intact, Golden Retriever was presented with clinical signs of stunted growth, anorexia, and progressive ascites...
January 3, 2017: Acta Veterinaria Scandinavica
https://www.readbyqxmd.com/read/28045091/ctcf-interacts-with-the-lytic-hsv-1-genome-to-promote-viral-transcription
#10
Fengchao Lang, Xin Li, Olga Vladimirova, Benxia Hu, Guijun Chen, Yu Xiao, Vikrant Singh, Danfeng Lu, Lihong Li, Hongbo Han, J M A S P Wickramasinghe, Sheryl T Smith, Chunfu Zheng, Qihan Li, Paul M Lieberman, Nigel W Fraser, Jumin Zhou
CTCF is an essential chromatin regulator implicated in important nuclear processes including in nuclear organization and transcription. Herpes Simplex Virus-1 (HSV-1) is a ubiquitous human pathogen, which enters productive infection in human epithelial and many other cell types. CTCF is known to bind several sites in the HSV-1 genome during latency and reactivation, but its function has not been defined. Here, we report that CTCF interacts extensively with the HSV-1 DNA during lytic infection by ChIP-seq, and its knockdown results in the reduction of viral transcription, viral genome copy number and virus yield...
January 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28039187/initial-combination-therapy-with-ambrisentan-and-tadalafil-in-connective-tissue-disease-associated-pulmonary-arterial-hypertension-ctd-pah-subgroup-analysis-from-the-ambition-trial
#11
John Gerry Coghlan, Nazzareno Galiè, Joan Albert Barberà, Adaani E Frost, Hossein-Ardeschir Ghofrani, Marius M Hoeper, Masataka Kuwana, Vallerie V McLaughlin, Andrew J Peacock, Gérald Simonneau, Jean-Luc Vachiéry, Christiana Blair, Hunter Gillies, Karen L Miller, Julia H N Harris, Jonathan Langley, Lewis J Rubin
BACKGROUND: Patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH), in particular systemic sclerosis (SSc), had an attenuated response compared with idiopathic PAH in most trials. Thus, there is uncertainty regarding the benefit of PAH-targeted therapy in some forms of CTD-PAH. OBJECTIVE: To explore the safety and efficacy of initial combination therapy with ambrisentan and tadalafil versus ambrisentan or tadalafil monotherapy in patients with CTD-PAH and SSc-PAH enrolled in the AMBITION trial...
December 30, 2016: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28034630/defect-of-fe-s-cluster-binding-by-dna-polymerase-%C3%AE-in-yeast-suppresses-uv-induced-mutagenesis-but-enhances-dna-polymerase-%C3%AE-dependent-spontaneous-mutagenesis
#12
E I Stepchenkova, E R Tarakhovskaya, H M Siebler, Y I Pavlov
Eukaryotic genomes are duplicated by a complex machinery, utilizing high fidelity replicative B-family DNA polymerases (pols) α, δ and ε. Specialized error-prone pol ζ, the fourth B-family member, is recruited when DNA synthesis by the accurate trio is impeded by replication stress or DNA damage. The damage tolerance mechanism dependent on pol ζ prevents DNA/genome instability and cell death at the expense of increased mutation rates. The pol switches occurring during this specialized replication are not fully understood...
December 9, 2016: DNA Repair
https://www.readbyqxmd.com/read/28031513/double-intertrochanteric-osteotomy-for-trochanteric-overgrowth-and-a-short-femoral-neck-in-adolescents
#13
Turgut Akgül, Cengiz Şen, Halil İbrahim Balci, Gökhan Polat
PURPOSE: To review the outcome of Wagner double intertrochanteric osteotomy for trochanteric overgrowth and a short femoral neck in 7 adolescents. METHODS: Records of one male and 6 females aged 15 to 20 years who underwent modified Wagner osteotomy for trochanteric overgrowth and a short femoral neck by a single senior surgeon were reviewed. The diagnoses were coxa vara (n=2), developmental dysplasia of the hip (n=3), Leg-Calve-Perthes (n=1), and proximal femoral focal deficiency (n=1)...
December 2016: Journal of Orthopaedic Surgery
https://www.readbyqxmd.com/read/28031456/a-novel-motif-for-s-adenosyl-l-methionine-binding-by-the-ribosomal-rna-methyltransferase-tlya-from-mycobacterium-tuberculosis
#14
Marta A Witek, Emily G Kuiper, Elizabeth Minten, Emily K Crispell, Graeme L Conn
Capreomycin is a potent ribosome-targeting antibiotic that is an essential component of current antituberculosis treatments, particularly in the case of multi-drug resistant Mycobacterium tuberculosis (Mtb). Optimal capreomycin binding and Mtb ribosome inhibition requires ribosomal RNA (rRNA) methylation in both ribosome subunits by TlyA (Rv1694), an enzyme with dual 2'-O-methytransferase and putative hemolytic activities. Despite TlyA's important role in capreomycin sensitivity and identification of inactivating mutations in the corresponding Mtb gene tylA which cause resistance to capreomycin, our current structural and mechanistic understanding of TlyA action remains limited...
December 27, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28028307/identification-of-a-rna-seq-based-8-long-non-coding-rna-signature-predicting-survival-in-esophageal-cancer
#15
Qiaowei Fan, Bingrong Liu
BACKGROUND Accumulating evidence suggests the involvement of long non-coding RNAs (lncRNAs) as oncogenic or tumor suppressive regulators in the development of various cancers. In the present study, we aimed to identify a lncRNA signature based on RNA sequencing (RNA-seq) data to predict survival in esophageal cancer. MATERIAL AND METHODS The RNA-seq lncRNA expression data and clinical information were downloaded from The Cancer Genome Atlas (TCGA) database. Differentially expressed lncRNAs were screened out between esophageal cancer and normal tissues...
December 28, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28017589/distinctive-patterns-of-transcription-and-rna-processing-for-human-lincrnas
#16
Margarita Schlackow, Takayuki Nojima, Tomas Gomes, Ashish Dhir, Maria Carmo-Fonseca, Nick J Proudfoot
Numerous long intervening noncoding RNAs (lincRNAs) are generated from the mammalian genome by RNA polymerase II (Pol II) transcription. Although multiple functions have been ascribed to lincRNAs, their synthesis and turnover remain poorly characterized. Here, we define systematic differences in transcription and RNA processing between protein-coding and lincRNA genes in human HeLa cells. This is based on a range of nascent transcriptomic approaches applied to different nuclear fractions, including mammalian native elongating transcript sequencing (mNET-seq)...
January 5, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28002402/structural-basis-of-an-essential-interaction-between-influenza-polymerase-and-pol-ii-ctd
#17
Maria Lukarska, Guillaume Fournier, Alexander Pflug, Patricia Resa-Infante, Stefan Reich, Nadia Naffakh, Stephen Cusack
The heterotrimeric influenza polymerase (FluPol), comprising subunits PA, PB1 and PB2, binds to the conserved 5' and 3' termini (the 'promoter') of each of the eight single-stranded viral RNA (vRNA) genome segments and performs both transcription and replication of vRNA in the infected cell nucleus. To transcribe viral mRNAs, FluPol associates with cellular RNA polymerase II (Pol II), which enables it to take 5'-capped primers from nascent Pol II transcripts. Here we present a co-crystal structure of bat influenza A polymerase bound to a Pol II C-terminal domain (CTD) peptide mimic, which shows two distinct phosphoserine-5 (SeP5)-binding sites in the polymerase PA subunit, accommodating four CTD heptad repeats overall...
December 21, 2016: Nature
https://www.readbyqxmd.com/read/27998507/fatigue-and-psychosocial-variables-in-autoimmune-rheumatic-disease-and-chronic-fatigue-syndrome-a-cross-sectional-comparison
#18
Sheila Ali, Faith Matcham, Katherine Irving, Trudie Chalder
OBJECTIVE: Fatigue is common in autoimmune rheumatic diseases (ARD). This study compared symptom-related cognitions, beliefs, behaviours, quality of sleep, lack of acceptance and distress in participants with ARD such as rheumatoid arthritis (RA), seronegative spondyloarthropathy (SpA), and connective tissue disease (CTD), and participants with chronic fatigue syndrome (CFS). METHODS: 303 participants with RA, SpA, CTD and CFS completed questionnaire measures of fatigue, social adjustment, cognitive-behavioural responses, lack of acceptance, distress and quality of sleep...
January 2017: Journal of Psychosomatic Research
https://www.readbyqxmd.com/read/27989101/overcomes-imatinib-resistance-by-depleting-bcr-abl-in-chronic-myeloid-leukemia
#19
Xiaoyan Sun, Xueting Cai, Jie Yang, Jiao Chen, Caixia Guo, Peng Cao
Cantharidin (CTD) is an active compound isolated from the traditional Chinese medicine blister beetle and displayed anticancer properties against various types of cancer cells. However, little is known about its effect on human chronic myeloid leukemia (CML) cells, including imatinib-resistant CML cells. The objective of this study was to investigate whether CTD could overcome imatinib resistance in imatinib-resistant CML cells and to explore the possible underlying mechanisms associated with the effect. Our results showed that CTD strongly inhibited the growth of both imatinib-sensitive and imatinib-resistant CML cells...
December 2016: Molecules and Cells
https://www.readbyqxmd.com/read/27983596/estrogenic-endocrine-disrupting-chemicals-influencing-nrf1-regulated-gene-networks-in-the-development-of-complex-human-brain-diseases
#20
REVIEW
Mark Preciados, Changwon Yoo, Deodutta Roy
During the development of an individual from a single cell to prenatal stages to adolescence to adulthood and through the complete life span, humans are exposed to countless environmental and stochastic factors, including estrogenic endocrine disrupting chemicals. Brain cells and neural circuits are likely to be influenced by estrogenic endocrine disruptors (EEDs) because they strongly dependent on estrogens. In this review, we discuss both environmental, epidemiological, and experimental evidence on brain health with exposure to oral contraceptives, hormonal therapy, and EEDs such as bisphenol-A (BPA), polychlorinated biphenyls (PCBs), phthalates, and metalloestrogens, such as, arsenic, cadmium, and manganese...
December 13, 2016: International Journal of Molecular Sciences
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