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https://www.readbyqxmd.com/read/28646802/dampness-can-promote-the-influenza-a-virus-and-worsen-its-prognosis-by-upregulating-the-tlr7-signaling-pathway
#1
Deng Li, Xu Huachong, Pang Peng, Zheng Ke, Nie Jiao, Wu Xianlin, Yu Bin, Chen Jia, Chen Xiaoyin
Context • Outbreaks of the influenza A virus (IAV) are increasingly recognized as a global public health issue, affecting a large proportion of the world's population. A number of studies have provided epidemiologic evidence that dampness and mold are consistently associated with multiple allergic and respiratory effects, but they focused on dampness-related pathogenic microorganisms leading to allergy rather than the dampness itself. Objective • The current study intended to examine the effects of a damp environment on the promotion of the IAV and determine the adverse effects on its prognosis through upregulation of the toll-like receptor 7 (TLR7)-signaling pathway in the lung...
June 23, 2017: Alternative Therapies in Health and Medicine
https://www.readbyqxmd.com/read/28646652/influenza-a-virus-cap-snatches-host-rnas-based-on-their-abundance-early-after-infection
#2
Dorota Sikora, Lynda Rocheleau, Earl G Brown, Martin Pelchat
The influenza A virus RNA polymerase cleaves the 5' ends of host RNAs and uses these RNA fragments as primers for viral mRNA synthesis. We performed deep sequencing of the 5' host-derived ends of the eight viral mRNAs of influenza A/Puerto Rico/8/1934 (H1N1) virus in infected A549 cells, and compared the population to those of A/Hong Kong/1/1968 (H3N2) and A/WSN/1933 (H1N1). In the three strains, the viral RNAs target different populations of host RNAs. Host RNAs are cap-snatched based on their abundance, and we found that RNAs encoding proteins involved in metabolism are overrepresented in the cap-snatched populations...
June 21, 2017: Virology
https://www.readbyqxmd.com/read/28646274/population-pharmacokinetic-modeling-of-diltiazem-in-chinese-renal-transplant-recipients
#3
Xiao-Feng Guan, Dai-Yang Li, Wen-Jun Yin, Jun-Jie Ding, Ling-Yun Zhou, Jiang-Lin Wang, Rong-Rong Ma, Xiao-Cong Zuo
BACKGROUND AND OBJECTIVES: Diltiazem is a benzothiazepine calcium blocker and widely used in renal transplant patients since it improves the level of tacrolimus or cyclosporine A concentration. Several population pharmacokinetic (PopPK) models had been established for cyclosporine A and tacrolimus but no specific PopPK model was established for diltiazem. The aim of the study is to develop a PopPK model for diltiazem in renal transplant recipients and provide relevant pharmacokinetic parameters of diltiazem for further pharmacokinetic interaction study...
June 23, 2017: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28646117/cyclin-dependent-kinase-9-is-a-novel-specific-molecular-target-in-adult-t-cell-leukemia-lymphoma
#4
Tomoko Narita, Takashi Ishida, Asahi Ito, Ayako Masaki, Shiori Kinoshita, Susumu Suzuki, Hisashi Takino, Takashi Yoshida, Masaki Ri, Shigeru Kusumoto, Hirokazu Komatsu, Kazunori Imada, Yuetsu Tanaka, Takaori-Kondo Akifumi, Hiroshi Inagaki, Arne Scholz, Philip Lienau, Taruho Kuroda, Ryuzo Ueda, Shinsuke Iida
Cyclin-dependent kinase 9 (CDK9), a subunit of the positive transcription elongation factor b (P-TEFb) complex, regulates gene transcription elongation by phosphorylating the carboxy-terminal domain (CTD) of RNA polymerase II (RNAPII).  The deregulation of CDK9/P-TEFb has important implications for many cancer types.  BAY 1143572 is a novel and highly selective CDK9/P-TEFb inhibitor currently being investigated in phase I studies. We evaluated the therapeutic potential of BAY 1143572 in adult T-cell leukemia/lymphoma (ATL)...
June 23, 2017: Blood
https://www.readbyqxmd.com/read/28646110/the-mcm2-7-interacting-domain-of-human-mini-chromosome-maintenance-10-mcm10-protein-is-important-for-stable-chromatin-association-and-origin-firing
#5
Masako Izumi, Takeshi Mizuno, Ken-Ichiro Yanagi, Kazuto Sugimura, Katsuzumi Okumura, Naoko Imamoto, Tomoko Abe, Fumio Hanaoka
The protein mini-chromosome maintenance 10 (Mcm10) was originally identified as an essential yeast protein in the maintenance of mini-chromosome plasmids. Subsequently, Mcm10 has been shown to be required for both initiation and elongation during chromosomal DNA replication. However, it is not fully understood how the multiple functions of Mcm10 are coordinated or how Mcm10 interacts with other factors at replication forks. Here, we identified and characterized the Mcm2-7-interacting domain in human Mcm10. The interaction with Mcm2-7 required the Mcm10 domain that contained amino acids 530-655, which overlapped with the domain required for the stable retention of Mcm10 on chromatin...
June 22, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28645739/mir-1224-inhibits-cell-proliferation-in-acute-liver-failure-by-targeting-the-antiapoptotic-gene-nfib
#6
Sanchari Roy, Heike Bantel, Franziska Wandrer, Anne Theres Schneider, Jeremie Gautheron, Mihael Vucur, Frank Tacke, Christian Trautwein, Tom Luedde, Christoph Roderburg
BACKGROUND AND AIMS: Patient outcome in acute liver failure (ALF) is crucially determined by the appropriate balance between cell death and compensatory cell proliferation. MicroRNAs (miRNAs) - small non-coding RNAs that function as guide molecules in RNA silencing - have evolved as crucial mediators of nearly all developmental and pathological processes including physiology and disease of the liver. We investigated the role of miR-1224 during ALF. METHODS: We measured miR-1224 in livers of mice in various acute liver disease murine models and in ALF patients using quantitative real-time polymerase chain reaction...
June 20, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28645632/adjuvant-chemotherapy-guided-by-molecular-profiling-and-improved-outcomes-in-early-stage-non-small-cell-lung-cancer
#7
Gavitt A Woodard, Sue X Wang, Johannes R Kratz, Clara T Zoon-Besselink, Chun-Yuan Chiang, Matthew A Gubens, Thierry M Jahan, Collin M Blakely, Kirk D Jones, Michael J Mann, David M Jablons
INTRODUCTION: Many early stage non-small-cell lung cancer (NSCLC) patients who are not considered candidates for adjuvant treatment according to current guidelines do harbor occult metastasis, and have disease recurrence despite complete resection. Although National Comprehensive Cancer Network (NCCN) guidelines suggest clinicopathologic characteristics to identify high-risk patients for adjuvant intervention, molecular profiling more accurately predicts 5-year survival. Early evidence of clinical benefit from application of this molecular-based management strategy, however, has not been reported...
May 31, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28645479/impact-of-the-nap-1-strain-on-disease-severity-mortality-and-recurrence-of-healthcare-associated-clostridium-difficile-infection
#8
Karri A Bauer, Jessica E W Johnston, Eric Wenzler, Debra A Goff, Charles H Cook, Joan-Miquel Balada-Llasat, Preeti Pancholi, Julie E Mangino
OBJECTIVES: Studies are conflicting regarding the association of the North American pulsed-field gel electrophoresis type 1 (NAP1) strain in Clostridium difficile infection (CDI) and outcomes. We evaluated the association of NAP1 with healthcare-associated CDI disease severity, mortality, and recurrence at our academic medical center. METHODS: Healthcare-associated CDI cases were identified from November 1, 2011 through January 31, 2013. Multivariable regression models were used to evaluate the associations of NAP1 with severe disease (based on the Hines VA severity score index), mortality, and recurrence...
June 20, 2017: Anaerobe
https://www.readbyqxmd.com/read/28645378/preparation-of-stable-nitrogen-mustard-dna-interstrand-cross-link-analogs-for-biochemical-and-cell-biological-studies
#9
Alejandra Castaño, Upasana Roy, Orlando D Schärer
Nitrogen mustards (NMs) react with two bases on opposite strands of a DNA duplex to form a covalent linkage, yielding adducts called DNA interstrand cross-links (ICLs). This prevents helix unwinding, blocking essential processes such as replication and transcription. Accumulation of ICLs causes cell death in rapidly dividing cells, especially cancer cells, making ICL-forming agents like NMs valuable in chemotherapy. However, the repair of ICLs can contribute to chemoresistance through a number of pathways that remain poorly understood...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28645375/current-and-emerging-assays-for-studying-the-primer-synthesis-activities-of-dna-primases
#10
Thomas A Guilliam, Aidan J Doherty
Primases play a crucial role in the initiation of DNA synthesis during replication by de novo synthesis of short RNA or DNA "primers." In recent years, evidence has accumulated which expands the essential roles of primases to include, not only the initiation of replication but also other critical roles in DNA metabolism, including damage tolerance and repair. Despite the broadening roles for these enzymes, the methods used to identify and characterize primase activities are limited. Historically, biochemical analysis of primases has been based on the synthesis of radioactively labeled primers and their detection on denaturing polyacrylamide gels...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28645374/reconstituted-system-for-the-examination-of-repair-dna-synthesis-in-homologous-recombination
#11
Youngho Kwon, James M Daley, Patrick Sung
In homologous recombination (HR), DNA polymerase δ-mediated DNA synthesis occurs within the displacement loop (D-loop) that is made by the recombinase Rad51 in conjunction with accessory factors. We describe in this chapter the reconstitution of the D-loop and repair DNA synthesis reactions using purified Saccharomyces cerevisiae HR (Rad51, RPA, and Rad54) and DNA replication (PCNA, RFC, and DNA polymerase δ) proteins and document the role of the Pif1 helicase in DNA synthesis via a migrating DNA bubble intermediate...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28645373/strategies-and-methods-of-transcription-coupled-repair-studies-in-vitro-and-in-vivo
#12
Vitaly Epshtein, Venu Kamarthapu, Evgeny Nudler
Transcription-coupled repair (TCR) serves an important role in preserving genome integrity and maintaining fidelity of replication. Coupling transcription to DNA repair requires a coordinated action of several factors, including transcribing RNA polymerase and various transcription modulators and repair proteins. To study TCR in molecular detail, it is important to employ defined protein complexes in vitro and defined genetic backgrounds in vivo. In this chapter, we present methods to interrogate various aspects of TCR at different stages of repair...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28645267/a-rapid-and-quantitative-method-to-detect-human-circulating-tumor-cells-in-a-preclinical-animal-model
#13
Shih-Hsin Tu, Yi-Chen Hsieh, Li-Chi Huang, Chun-Yu Lin, Kai-Wen Hsu, Wen-Shyang Hsieh, Wei-Ming Chi, Chia-Hwa Lee
BACKGROUND: As cancer metastasis is the deadliest aspect of cancer, causing 90% of human deaths, evaluating the molecular mechanisms underlying this process is the major interest to those in the drug development field. Both therapeutic target identification and proof-of-concept experimentation in anti-cancer drug development require appropriate animal models, such as xenograft tumor transplantation in transgenic and knockout mice. In the progression of cancer metastasis, circulating tumor cells (CTCs) are the most critical factor in determining the prognosis of cancer patients...
June 23, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28645155/features-of-genomic-organization-in-a-nucleotide-resolution-molecular-model-of-the-escherichia-coli-chromosome
#14
William C Hacker, Shuxiang Li, Adrian H Elcock
We describe structural models of the Escherichia coli chromosome in which the positions of all 4.6 million nucleotides of each DNA strand are resolved. Models consistent with two basic chromosomal orientations, differing in their positioning of the origin of replication, have been constructed. In both types of model, the chromosome is partitioned into plectoneme-abundant and plectoneme-free regions, with plectoneme lengths and branching patterns matching experimental distributions, and with spatial distributions of highly-transcribed chromosomal regions matching recent experimental measurements of the distribution of RNA polymerases...
June 22, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28645088/risk-based-screening-combined-with-a-pcr-based-test-for-group-b-streptococci-diminishes-the-use-of-antibiotics-in-laboring-women
#15
Mohammed R Khalil, Niels Uldbjerg, Poul B Thorsen, Birgitte Henriksen, Jens K Møller
OBJECTIVE: To assess the performance of a polymerase chain reaction - group B streptococci test (PCR-GBS test) - in deciding antibiotic prophylaxis in term laboring women. STUDY DESIGN: In this observational study, we enrolled 902 unselected Danish term pregnant women. During labor, midwives obtained vaginal swabs that were used for both GBS cultures (reference standard) and for the PCR-GBS test. Furthermore, we recorded the presence of risk factors for EOGBS (Early Onset Group B Streptococcal disease): (1) Bacteriuria during current pregnancy, (2) Prior infant with EOGBS (3) Temperature above 38...
June 9, 2017: European Journal of Obstetrics, Gynecology, and Reproductive Biology
https://www.readbyqxmd.com/read/28645008/effect-of-microrna-129-5p-targeting-hmgb1-rage-signaling-pathway-on-revascularization-in-a-collagenase-induced-intracerebral-hemorrhage-rat-model
#16
Xin-Long Ma, Shu-Ya Li, Feng Shang
BACKGROUND: This study aimed at exploring the effect of microRNA-129-5p (miR-129-5p) targeting high mobility group box-1 (HMGB1)-receptor for advanced glycation end-products (RAGE) signaling pathway on the revascularization in a collagenase-induced intracerebral hemorrhage (ICH) rat model. METHODS: OX26-pGFAP-IL, an immunoliposome expressing miR-129-5p was constructed. The collagenase-induced ICH rat models were successfully established by 96 Sprague Dawley (SD) rats, which were categorized into the sham group, ICH group, miR-129-5p group, negative control (NC) group, ethyl pyruvate (EP, an inhibitor of HMGB1) group and N-benzyl-4-chloro-N-cyclohe-xylbenzamide (FPS-ZM1, a RAGE receptor antagonist) group...
June 20, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28645007/activation-of-the-pi3k-akt-pathway-promotes-neuroprotection-of-the-%C3%AE-opioid-receptor-agonist-against-cerebral-ischemia-reperfusion-injury-in-rat-models
#17
Mei-Rong Lv, Bin Li, Ming-Guang Wang, Fan-Guo Meng, Jian-Jun Yu, Feng Guo, Ye Li
The central objective was to identify the role of the PI3K-Akt activation pathway on the neuroprotection of δ-opioid receptor agonist (DADLE) against cerebral ischemia-reperfusion (I/R) injury in a rat model. Fifty-five male Sprague-Dawley (SD) rats were included to establish a middle cerebral artery occlusion (MCAO) model which were then divided into the sham, MCAO, LY294002 (MCAO+DADLE+LY294002 [inhibitor of PI3K-Akt pathway]), DADLE (MCAO+DADLE) and DMSO (MCAO+DADLE+DMSO [dimethyl sulphoxide]) groups. The cerebral infarction (CI) volume and nerve cell apoptosis was determined using TTC and TUNEL staining...
June 20, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28645004/amplified-detection-of-hepatitis-b-virus-using-an-electrochemical-dna-biosensor-on-a-nanoporous-gold-platform
#18
Laleh Enayati Ahangar, Masoud A Mehrgardi
In the present study, a nanoporous gold platform was applied for the amplified detection of Hepatitis B virus (HBV) by an electrochemical DNA biosensor. Ferrocene as a redox reporter was covalently attached to the DNA probe and its electrochemical signal was recorded as the biosensor response. For real samples, DNA was firstly extracted from blood of patients and then amplified by polymerase chain reaction (PCR) for 5cycles. Sensitivity of this biosensor was enhanced by using nanoporous gold electrode, therefore this sensor can discriminate the genome of HBV in real sample with low PCR cycles...
June 15, 2017: Bioelectrochemistry
https://www.readbyqxmd.com/read/28644872/helicobacter-pylori-gene-silencing-in-vivo-demonstrates-urease-is-essential-for-chronic-infection
#19
Aleksandra W Debowski, Senta M Walton, Eng-Guan Chua, Alfred Chin-Yen Tay, Tingting Liao, Binit Lamichhane, Robyn Himbeck, Keith A Stubbs, Barry J Marshall, Alma Fulurija, Mohammed Benghezal
Helicobacter pylori infection causes chronic active gastritis that after many years of infection can develop into peptic ulceration or gastric adenocarcinoma. The bacterium is highly adapted to surviving in the gastric environment and a key adaptation is the virulence factor urease. Although widely postulated, the requirement of urease expression for persistent infection has not been elucidated experimentally as conventional urease knockout mutants are incapable of colonization. To overcome this constraint, conditional H...
June 23, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28644739/treatment-of-hepatitis-c-with-new-fixed-dose-combinations
#20
Vicente Soriano
The advent of oral direct-acting antivirals (DAA) has revolutionized the hepatitis C virus (HCV) therapeutic landscape providing cure rates over 90%. However, a subset of patients remains at higher risk for treatment failure, including those infected with: i) genotype 3 and cirrhosis; ii) resistance-associated substitutions (RAS) occurring either as natural polymorphisms or selected after prior DAA failure; and iii) poor drug adherence associated with social disabilities (homeless, psychiatric illnesses, injection drug use, alcoholism, etc...
June 23, 2017: Expert Opinion on Pharmacotherapy
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