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https://www.readbyqxmd.com/read/29789392/fam35a-associates-with-rev7-and-modulates-dna-damage-responses-of-normal-and-brca1-defective-cells
#1
Junya Tomida, Kei-Ichi Takata, Sarita Bhetawal, Maria D Person, Hsueh-Ping Chao, Dean G Tang, Richard D Wood
To exploit vulnerabilities of tumors, it is urgent to identify associated defects in genome maintenance. One unsolved problem is the mechanism of regulation of DNA double-strand break repair by REV7 in complex with 53BP1 and RIF1, and its influence on repair pathway choice between homologous recombination and non-homologous end-joining. We searched for REV7-associated factors in human cells and found FAM35A, a previously unstudied protein with an unstructured N-terminal region and a C-terminal region harboring three OB-fold domains similar to single-stranded DNA-binding protein RPA, as novel interactor of REV7/RIF1/53BP1...
May 22, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29787529/motor-vehicle-crash-fatalaties-and-undercompensated-care-associated-with-legalization-of-marijuana
#2
Susan Steinemann, Daniel Galanis, Tiffany Nguyen, Walter Biffl
BACKGROUND: Half of U.S. states have legalized medical cannabis (marijuana), some allow recreational use. The economic and public health effects of these policies are still being evaluated. We hypothesized that cannabis legalization was associated with an increase in the proportion of motor vehicle crash fatalities involving cannabis-positive drivers, and that cannabis use is associated with high-risk behavior and poor insurance status. METHODS: Hawaii legalized cannabis in 2000...
May 21, 2018: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/29787441/exome-sequencing-discloses-ionizing-radiation-induced-dna-variants-in-the-genome-of-human-gingiva-fibroblasts
#3
Neetika Nath, Jennifer Esche, Jessica Müller, Lars R Jensen, Matthias Port, Mario Stanke, Lars Kaderali, Harry Scherthan, Andreas W Kuss
Ionizing radiation can induce genomic lesions such as DNA double-strand breaks whose incomplete or faulty repair can result in mutations, which in turn can influence cellular functions and alter the fate of affected cells and organ systems. Ionizing-radiation-induced sequence alterations/mutations occur in a stochastic manner, which contributes to an increased cancer risk in irradiated individuals. Ionizing radiation exposure, and particularly acute doses at high dose rates (as often observed in radiation accidents), induce alterations in the genome that in part will reflect specific characteristics of the DNA damage response and the repair mechanisms involved...
July 2018: Health Physics
https://www.readbyqxmd.com/read/29779790/a-hyperthermophilic-phage-decoration-protein-suggests-common-evolutionary-origin-with-herpesvirus-triplex-proteins-and-an-anti-crispr-protein
#4
Nicholas P Stone, Brendan J Hilbert, Daniel Hidalgo, Kevin T Halloran, Jooyoung Lee, Erik J Sontheimer, Brian A Kelch
Virus capsids are protein shells that protect the viral genome from environmental assaults, while maintaining the high internal pressure of the tightly packaged genome. To elucidate how capsids maintain stability under harsh conditions, we investigated the capsid components of the hyperthermophilic phage P74-26. We determined the structure of capsid protein gp87 and show that it has the same fold as decoration proteins in many other phages, despite lacking significant sequence homology. We also find that gp87 is significantly more stable than mesophilic homologs...
April 26, 2018: Structure
https://www.readbyqxmd.com/read/29778011/bisphenol-a-exposure-through-receipt-handling-and-its-association-with-insulin-resistance-among-female-cashiers
#5
Inae Lee, Sunmi Kim, Ki-Tae Kim, Sungkyoon Kim, Suhyun Park, Hyojin Lee, Yunsun Jeong, Jae-Eun Lim, Hyo-Bang Moon, Kyungho Choi
Bisphenol A (BPA) is one of the most widely used chemicals in various consumer products. In thermal papers such as receipts and tickets, BPA is used as a heat-activated developer. Cashiers are therefore suspected to be a vulnerable group of exposure to BPA, but neither contribution of receipt handling to the total body burden of BPA among cashiers, nor related health effects are well characterized. Female cashiers (n = 54) were recruited from seven retail shops of a major supermarket chain in Korea, and urinary levels of BPA and metabolic syndrome (MetS) related biomarkers were measured...
May 16, 2018: Environment International
https://www.readbyqxmd.com/read/29777529/pharmacokinetics-of-ads-5102-amantadine-extended-release-capsules-administered-once-daily-at-bedtime-for-the-treatment-of-dyskinesia
#6
Robert A Hauser, Rajesh Pahwa, William A Wargin, Cindy J Souza-Prien, Natalie McClure, Reed Johnson, Jack T Nguyen, Rajiv Patni, Gregory T Went
BACKGROUND: Preclinical and clinical studies suggest amantadine immediate-release (IR) may reduce dyskinesia in Parkinson's disease (PD), although higher doses are associated with increased CNS adverse events (AEs). ADS-5102 is an extended release amantadine capsule formulation, designed for once-daily dosing at bedtime (qhs) to provide high concentrations upon waking and throughout the day, with lower concentrations in the evening. The pharmacokinetics (PK) of ADS-5102 were assessed in two phase I studies in healthy subjects, and a blinded, randomized phase II/III dose-finding study in PD patients...
May 18, 2018: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/29775537/amplification-of-dynamic-nuclear-polarization-at-200-ghz-by-arbitrary-pulse-shaping-of-the-electron-spin-saturation-profile
#7
Ilia Kaminker, Songi Han
Dynamic nuclear polarization (DNP) takes center stage in nuclear magnetic resonance (NMR) as a tool to amplify its signal by orders of magnitude through the transfer of polarization from electron to nuclear spins. In contrast to modern NMR and electron paramagnetic resonance (EPR) that extensively rely on pulses for spin manipulation in the time domain, the current mainstream DNP technology exclusively relies on monochromatic continuous wave (CW) irradiation. This study introduces arbitrary phase shaped pulses that constitute a train of coherent chirp pulses in the time domain at 200 GHz (7 Tesla) to dramatically enhance the saturation bandwidth and DNP performance compared to CW DNP, yielding up to 500-fold in NMR signal enhancements...
May 18, 2018: Journal of Physical Chemistry Letters
https://www.readbyqxmd.com/read/29774152/acquisition-of-double-mutation-in-gyra-caused-high-resistance-to-sitafloxacin-in-helicobacter-pylori-after-unsuccessful-eradication-with-sitafloxacin-containing-regimens
#8
Hideki Mori, Hidekazu Suzuki, Juntaro Matsuzaki, Tatsuhiro Masaoka, Takanori Kanai
Background and aim: Although sitafloxacin (STFX)-containing regimens are effective rescue treatments for Helicobacter pylori infection, prevalence of fluoroquinolone resistance in H. pylori has increased rapidly worldwide. The change in resistance levels and gyrA mutations, a major cause of fluoroquinolone resistance, after unsuccessful STFX-containing treatment has not been investigated. Methods: We conducted a retrospective, non-randomized study to compare the minimum inhibitory concentrations (MICs) of STFX and the location of gyrA mutations in H...
April 2018: United European Gastroenterology Journal
https://www.readbyqxmd.com/read/29772737/distal-colon-motor-dysfunction-in-mice-with-chronic-kidney-disease-putative-role-of-uremic-toxins
#9
Elsa Hoibian, Nans Florens, Laetitia Koppe, Hubert Vidal, Christophe O Soulage
Although gastrointestinal complications are a common feature of patients with chronic kidney disease (CKD), the impact of uremia on bowel motility remains poorly understood. The present study was, therefore, designed to investigate the impact of uremia on gut motility. Kidney failure was induced in mice by chemical nephrectomy using an adenine diet (0.25% w/w ). Gastrointestinal transit time and colon motility were explored in vivo and ex vivo . Colons from control mice were incubated with uremic plasma or uremic toxins (urea, indoxyl-sulfate or p-cresyl-sulfate) at concentrations encountered in patients with end-stage renal disease...
May 16, 2018: Toxins
https://www.readbyqxmd.com/read/29772727/why-two-on-the-role-of-a-symmetry-in-negative-supercoiling-of-dna-by-gyrase
#10
REVIEW
Dagmar Klostermeier
Gyrase is a type IIA topoisomerase that catalyzes negative supercoiling of DNA. The enzyme consists of two GyrA and two GyrB subunits. It is believed to introduce negative supercoils into DNA by converting a positive DNA node into a negative node through strand passage: First, it cleaves both DNA strands of a double-stranded DNA, termed the G-segment, and then it passes a second segment of the same DNA molecule, termed the T-segment, through the gap created. As a two-fold symmetric enzyme, gyrase contains two copies of all elements that are key for the supercoiling reaction: The GyrB subunits provide two active sites for ATP binding and hydrolysis...
May 16, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29772275/5c-id-increased-resolution-chromosome-conformation-capture-carbon-copy-with-in-situ-3c-and-double-alternating-primer-design
#11
Ji Hun Kim, Katelyn R Titus, Wanfeng Gong, Jonathan A Beagan, Zhendong Cao, Jennifer E Phillips-Cremins
Mammalian genomes are folded in a hierarchy of compartments, topologically associating domains (TADs), subTADs, and looping interactions. Currently, there is a great need to evaluate the link between chromatin topology and genome function across many biological conditions and genetic perturbations. Hi-C can generate genome-wide maps of looping interactions but is intractable for high-throughput comparison of loops across multiple conditions due to the enormous number of reads (>6 Billion) required per library...
May 14, 2018: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/29771596/safety-tolerability-and-immunogenicity-of-the-expec4v-jnj-63871860-vaccine-for-prevention-of-invasive-extraintestinal-pathogenic-escherichia-coli-disease-a-phase-1-randomized-double-blind-placebo-controlled-study-in-healthy-japanese-participants
#12
Megumi Inoue, Tetsuro Ogawa, Hiroshi Tamura, Yosuke Hagiwara, Yuki Saito, Darren Abbanat, Germie van den Dobbelsteen, Peter Hermans, Stefan Thoelen, Jan Poolman, Patricia Ibarra de Palacios
This Phase 1, randomized, double-blind, placebo-controlled study was conducted to evaluate the safety, tolerability and immunogenicity of different doses of ExPEC4V conjugate vaccine (4-16µg Polysaccharide [PS]/serotype) in healthy Japanese participants, stratified into younger (≥20 to <50 years) or older age groups (≥50 years). Within each age group, participants were randomized to a single vaccination with 1 of 3 dose levels of ExPEC4V (4, 8 and 16 µg PS/serotype) or placebo. Safety and tolerability were the primary objectives; immunogenicity was secondary...
May 17, 2018: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/29770879/no-difference-in-the-graft-shift-between-a-round-and-a-rounded-rectangular-femoral-tunnel-for-anterior-cruciate-ligament-reconstruction-an-experimental-study
#13
Yasushi Takata, Junsuke Nakase, Takeshi Oshima, Kengo Shimozaki, Kazuki Asai, Hiroyuki Tsuchiya
INTRODUCTION: We developed a novel technique of creating a rounded rectangular femoral bone tunnel for anatomical, single-bundle, autologous hamstring tendon anterior cruciate ligament (ACL) reconstruction. Although this tunnel has many advantages, its non-circular shape has raised concerns regarding excessive graft shift within the bone tunnel. This study aimed to compare the graft shift between round and rounded rectangular tunnels using a graft diameter tester for simulating the femoral bone tunnel...
May 16, 2018: Archives of Orthopaedic and Trauma Surgery
https://www.readbyqxmd.com/read/29765528/metabolic-changes-associated-with-metformin-potentiates-bcl-2-inhibitor-venetoclax-and-cdk9-inhibitor-bay1143572-and-reduces-viability-of-lymphoma-cells
#14
Vineela Chukkapalli, Leo I Gordon, Parameswaran Venugopal, Jeffrey A Borgia, Reem Karmali
Metformin exerts direct anti-tumor effects by activating AMP-activated protein kinase (AMPK), a major sensor of cellular metabolism in cancer cells. This, in turn, inhibits pro-survival mTOR signaling. Metformin has also been shown to disrupt complex 1 of the mitochondrial electron transport chain. Here, we explored the lymphoma specific anti-tumor effects of metformin using Daudi (Burkitt), SUDHL-4 (germinal center diffuse large B-cell lymphoma; GC DLBCL), Jeko-1 (Mantle-cell lymphoma; MCL) and KPUM-UH1 (double hit DLBCL) cell lines...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29758184/therapeutic-penetrating-keratoplasty-button-cultures-in-the-mycotic-ulcer-treatment-trial-ii-a-randomized-trial-comparing-oral-voriconazole-vs-placebo
#15
Julie Cho, N Venkatesh Prajna, Prajna Lalitha, Revathi Rajaraman, Tiruvengada Krishnan, Yijie Brittany Lin, Kathryn J Ray, Thomas M Lietman, Jennifer Rose-Nussbaumer
OBJECTIVE: To compare oral voriconazole versus placebo in addition to topical antifungals in the treatment of filamentous fungal keratitis. DESIGN: Non-prespecified, secondary case-control analysis from a multicenter, double-masked, randomized placebo-controlled clinical trial STUDY PARTICIPANTS: Patients with smear-positive filamentous fungal ulcers and visual acuity of 20/400 or worse who eventuated to therapeutic penetrating keratoplasty (TPK). INTERVENTION: Study participants were randomized to oral voriconazole versus oral placebo; all received topical antifungal drops...
May 11, 2018: American Journal of Ophthalmology
https://www.readbyqxmd.com/read/29758119/loss-of-protein-phosphatase-6-in-mouse-keratinocytes-enhances-k-ras-g12d-driven-tumor-promotion
#16
Koreyuki Kurosawa, Yui Inoue, Yoichiro Kakugawa, Yoji Yamashita, Kosuke Kanazawa, Kazuhiro Kishimoto, Miyuki Nomura, Yuki Momoi, Ikuro Sato, Natsuko Chiba, Mai Suzuki, Honami Ogoh, Hidekazu Yamada, Koh Miura, Toshio Watanabe, Nobuhiro Tanuma, Masahiro Tachi, Hiroshi Shima
Here, we address the function of protein phosphatase 6 (PP6) loss on K-ras-initiated tumorigenesis in keratinocytes. To do so, we developed tamoxifen-inducible double mutant (K-rasG12D -expressing and Ppp6c-deficient) mice in which K-rasG12D expression is driven by the cytokeratin 14 (K14) promoter. Doubly-mutant mice showed early onset tumor formation in lip, nipples, external genitalia, anus and palms, and had to be sacrificed by three weeks after induction by tamoxifen, while comparably-treated K-rasG12D -expressing mice did not...
May 14, 2018: Cancer Science
https://www.readbyqxmd.com/read/29757631/understanding-which-residues-of-the-active-site-and-loop-structure-of-a-tyrosine-aminomutase-define-its-mutase-and-lyase-activities
#17
Gayanthi Attanayake, Tyler Walter, Kevin D Walker
Site-directed mutations and substrate analogs were used to gain insights into the branch-point reaction catalyzed by the 3,5-dihydro-5-methylidene-4H-imidazol-4-one (MIO)-tyrosine aminomutase from Oryza sativa ( OsTAM). Exchanging the active residues of ( OsTAM) (Y125C/N446K) for those in a phenylalanine aminomutase TcPAM altered its substrate specificity from tyrosine to phenylalanine. The aminomutase mechanism of ( OsTAM) surprisingly changed nearly exclusively to that of an ammonia lyase making cinnamic acid (>95%) over β-phenylalanine [Biochemistry 55, 3497-3503 (2016)]...
May 14, 2018: Biochemistry
https://www.readbyqxmd.com/read/29755985/single-ring-intermediates-are-essential-for-some-chaperonins
#18
Jay M Bhatt, Adrian S Enriquez, Jinliang Wang, Humberto M Rojo, Sudheer K Molugu, Zacariah L Hildenbrand, Ricardo A Bernal
Chaperonins are macromolecular complexes found throughout all kingdoms of life that assist unfolded proteins reach a biologically active state. Historically, chaperonins have been classified into two groups based on sequence, subunit structure, and the requirement for a co-chaperonin. Here, we present a brief review of chaperonins that can form double- and single-ring conformational intermediates in their protein-folding catalytic pathway. To date, the bacteriophage encoded chaperonins ϕ-EL and OBP, human mitochondrial chaperonin and most recently, the bacterial groEL/ES systems, have been reported to form single-ring intermediates as part of their normal protein-folding activity...
2018: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/29755420/characterization-of-two-novel-bacteriophages-infecting-multidrug-resistant-mdr-acinetobacter-baumannii-and-evaluation-of-their-therapeutic-efficacy-in-vivo
#19
Kyoungeun Cha, Hynu K Oh, Jae Y Jang, Yunyeol Jo, Won K Kim, Geon U Ha, Kwan S Ko, Heejoon Myung
Acinetobacter baumannii is emerging as a challenging nosocomial pathogen due to its rapid evolution of antibiotic resistance. We report characterization of two novel bacteriophages, PBAB08 and PBAB25, infecting clinically isolated, multidrug-resistant (MDR) A. baumannii strains. Both phages belonged to Myoviridae of Caudovirales as their morphology observed under an electron microscope. Their genomes were double stranded linear DNAs of 42,312 base pairs and 40,260 base pairs, respectively. The two phages were distinct from known Acinetobacter phages when whole genome sequences were compared...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29755293/role-of-sequence-variations-in-ahr-gene-towards-modulating-smoking-induced-lung-cancer-susceptibility-in-north-indian-population-a-multiple-interaction-analysis
#20
Sneha Budhwar, Charu Bahl, Siddharth Sharma, Navneet Singh, Digambar Behera
Background: AhR, a ubiquitously expressed ligand-activated transcription factor, upon its encounter with the foreign ligands activates the transcriptional machinery of genes encoding for bio-transformation enzymes like CYP1A1 hence, mediating the metabolism of Poly aromatic hydrocarbons and nitrosamines which account for the maximally found carcinogen in cigarette smoke. Polymorphic variants of AhR play a significant role and are held responsible for disposing the individuals with greater chances of acquiring lung cancer...
May 2018: Current Genomics
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