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https://www.readbyqxmd.com/read/29161447/dna-polymerase-beta-participates-in-dna-end-joining
#1
Sreerupa Ray, Gregory Breuer, Michelle DeVeaux, Daniel Zelterman, Ranjit Bindra, Joann B Sweasy
DNA double strand breaks (DSBs) are one of the most deleterious lesions and if left unrepaired, they lead to cell death, genomic instability and carcinogenesis. Cells combat DSBs by two pathways: homologous recombination (HR) and non-homologous end-joining (NHEJ), wherein the two DNA ends are re-joined. Recently a back-up NHEJ pathway has been reported and is referred to as alternative NHEJ (aNHEJ), which joins ends but results in deletions and insertions. NHEJ requires processing enzymes including nucleases and polymerases, although the roles of these enzymes are poorly understood...
November 17, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29156763/elas1-induces-apoptotic-death-in-adenocarcinoma-du145-and-squamous-cell-carcinoma-sas-cancer-cells-but-not-in-normal-kd-cells
#2
Toshihiro Uchihashi, Kaori Ota, Yusuke Yabuno, Shouichi Ohno, Kohshiro Fukushima, Yoko Naito, Mikihiko Kogo, Norikazu Yabuta, Hiroshi Nojima
We previously reported that an ELAS1 peptide containing 29 amino acids induces apoptotic death in U2OS human osteosarcoma cells following DNA double-strand break insults. Here, we show that ELAS1 also caused apoptosis in prostate adenocarcinoma DU145 cells and tongue squamous-cell carcinoma SAS cells. ELAS1 appears to be safe because it induced apoptosis only in cancer cells, not in normal KD cells. Because the effect of ELAS1 is dependent on increased stability of p53 and enhanced phosphorylation of p53-S46, we exogenously expressed wild-type p53 protein to fully promote ELAS1-mediated induction of apoptosis in SAS cells...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29149412/the-translationally-controlled-tumor-protein-and-the-cellular-response-to-ionizing-radiation-induced-dna-damage
#3
Jie Zhang, Grace Shim, Sonia M de Toledo, Edouard I Azzam
The absorption of ionizing radiation by living cells can directly disrupt atomic structures, producing chemical and biological changes. It can also act indirectly through radiolysis of water, thereby generating reactive chemical species that may damage nucleic acids, proteins, and lipids. Together, the direct and indirect effects of radiation initiate a series of biochemical and molecular signaling events that may repair the damage or culminate in permanent physiological changes or cell death. In efforts to gain insight into the mechanisms underlying these effects, we observed a prominent upregulation of the Translationally Controlled Tumor Protein (TCTP) in low dose/low dose rate (137)Cs γ-irradiated cells that was associated with adaptive responses that reduced chromosomal damage to a level lower than what occurs spontaneously...
2017: Results and Problems in Cell Differentiation
https://www.readbyqxmd.com/read/29148426/stabilization-and-structural-analysis-of-a-membrane-associated-hiapp-aggregation-intermediate
#4
Diana C Rodriguez Camargo, Kyle J Korshavn, Alexander Jussupow, Kolio Raltchev, David Goricanec, Markus Fleisch, Riddhiman Sarkar, Kai Xue, Michaela Aichler, Gabriele Mettenleiter, Axel Karl Walch, Carlo Camilloni, Franz Hagn, Bernd Reif, Ayyalusamy Ramamoorthy
Membrane-assisted amyloid formation is implicated in human diseases, and many of the aggregating species accelerate amyloid formation and induce cell death. While structures of membrane-associated intermediates would provide tremendous insights into the pathology and aid in the design of compounds to potentially treat the diseases, it has not been feasible to overcome the challenges posed by the cell membrane. Here we use NMR experimental constraints to solve the structure of a type-2 diabetes related human islet amyloid polypeptide intermediate stabilized in nanodiscs...
November 17, 2017: ELife
https://www.readbyqxmd.com/read/29142132/identification-of-a-small-molecule-that-compromises-the-structural-integrity-of-viroplasms-and-rotavirus-double-layered-particles
#5
Catherine Eichwald, Giuditta De Lorenzo, Elisabeth M Schraner, Guido Papa, Michela Bollati, Paolo Swuec, Matteo de Rosa, Mario Milani, Eloise Mastrangelo, Mathias Ackermann, Oscar R Burrone, Francesca Arnoldi
Despite the availability of two attenuated vaccines, rotavirus (RV) gastroenteritis remains an important cause of mortality among children in developing countries causing about 215,000 infant deaths annually. Currently, there are no specific antiviral therapies available. RV is a non-enveloped virus with a segmented double-stranded RNA genome. Viral genome replication and assembly of transcriptionally active double-layered particles (DLPs) take place in cytoplasmic viral structures called viroplasms. In this study, we describe strong impairment of the early stages of RV replication induced by a small molecule known as RNA polymerase III inhibitor, ML-60218 (ML)...
November 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29141658/thioredoxin-mitigates-radiation-induced-hematopoietic-stem-cell-injury-in-mice
#6
Pasupathi Sundaramoorthy, Qinhong Wang, Zhihong Zheng, Yiqun Jiao, Benny J Chen, Phuong L Doan, Nelson J Chao, Yubin Kang
BACKGROUND: Radiation exposure poses a significant threat to public health. Hematopoietic injury is one of the major manifestations of acute radiation sickness. Protection and/or mitigation of hematopoietic stem cells (HSCs) from radiation injury is an important goal in the development of medical countermeasure agents (MCM). We recently identified thioredoxin (TXN) as a novel molecule that has marked protective and proliferative effects on HSCs. In the current study, we investigated the effectiveness of TXN in rescuing mice from a lethal dose of total body radiation (TBI) and in enhancing hematopoietic reconstitution following a lethal dose of irradiation...
November 15, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29137877/immune-analysis-of-radium-223-in-patients-with-metastatic-prostate-cancer
#7
Joseph W Kim, Min Sun Shin, Youna Kang, Insoo Kang, Daniel P Petrylak
BACKGROUND: Radium223 (Ra223) delivers high-energy radiation to osteoblastic metastasis of prostate cancer, resulting in irreparable double-stranded DNA damage. The effects of Ra223 on CD8+ T cell subsets in patients with prostate cancer is unknown. PATIENTS AND METHODS: Fifteen men with metastatic prostate cancer with clinical indication for Ra223 without any autoimmune or immune deficiency conditions were enrolled. Patients received a course of Ra223 50 kBq/kg...
October 24, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/29133371/turnip-mosaic-virus-counteracts-selective-autophagy-of-the-viral-silencing-suppressor-hcpro
#8
Anders Hafrén, Suayib Üstün, Anton Hochmuth, Steingrim Svenning, Terje Johansen, Daniel Hofius
Autophagy is a conserved intracellular degradation pathway and has emerged as a key mechanism of antiviral immunity in metazoans, including the selective elimination of viral components. In turn, some animal viruses are able to escape and modulate autophagy for enhanced pathogenicity. Whether host autophagic responses and viral countermeasures play similar roles in plant-virus interactions is not well understood. Here, we have identified selective autophagy as antiviral pathway during plant infection with turnip mosaic virus (TuMV), a positive-stranded RNA potyvirus...
November 13, 2017: Plant Physiology
https://www.readbyqxmd.com/read/29132682/-biomarkers-of-radiation-induced-dna-repair-processes
#9
REVIEW
Alexis Vallard, Chloé Rancoule, Jean-Baptiste Guy, Sophie Espenel, Sylvie Sauvaigo, Claire Rodriguez-Lafrasse, Nicolas Magné
The identification of DNA repair biomarkers is of paramount importance. Indeed, it is the first step in the process of modulating radiosensitivity and radioresistance. Unlike tools of detection and measurement of DNA damage, DNA repair biomarkers highlight the variations of DNA damage responses, depending on the dose and the dose rate. The aim of the present review is to describe the main biomarkers of radiation-induced DNA repair. We will focus on double strand breaks (DSB), because of their major role in radiation-induced cell death...
November 10, 2017: Bulletin du Cancer
https://www.readbyqxmd.com/read/29129525/multicenter-evaluation-of-the-clinical-utility-of-laparoscopy-assisted-ercp-in-patients-with-roux-en-y-gastric-bypass
#10
Ali M Abbas, Andrew T Strong, David L Diehl, Brian C Brauer, Iris H Lee, Rebecca Burbridge, Jaroslav Zivny, Jennifer T Higa, Marcelo Falcão, Ihab I El Hajj, Paul Tarnasky, Brintha K Enestvedt, Alexander R Ende, Adarsh M Thaker, Rishi Pawa, Priya Jamidar, Kartik Sampath, Eduardo Guimarães Hourneaux de Moura, Richard S Kwon, Alejandro L Suarez, Murad Aburajab, Andrew Y Wang, Mohammad H Shakhatreh, Vivek Kaul, Lorna Kang, Thomas E Kowalski, Rahul Pannala, Jeffrey Tokar, A Aziz Aadam, Demetrios Tzimas, Mihir S Wagh, Peter V Draganov, M D The LA-Ercp Research Group Jeffrey Ponsky, Bruce D Greenwald, Lance T Uradomo, Alyson A McGhan, Shahrad Hakimian, Andrew Ross, Stuart Sherman, Benjamin L Bick, Christopher E Forsmark, Dennis Yang, Anand Gupte, Shailendra Chauhan, Steven J Hughes, Karen Saks, Gennadiy Bakis, Adam W Templeton, Michael Saunders, Alireza Sedarat, John A Evans, Thiruvengadam Muniraj, Timothy B Gardner, Almino C Ramos, Marco Aurelio Santo, Andrew Nett, Gregory A Coté, B Joseph Elmunzer, Kulwinder S Dua, Michael J Nosler, Daniel S Strand, Paul Yeaton, Shivangi Kothari, Asad Ullah, Pushpak Taunk, Patrick Brady, Haim Pinkas, Ashley L Faulx, Haroon Shahid, Jordan Holmes, Davinderbir Pannu, Srinadh Komanduri, Juan Carlos Bucobo, Harry Dhaliwal, Alaa Rostom, Brent W Acker
BACKGROUND AND AIMS: The obesity epidemic has led to increased use of Roux-en-Y gastric bypass (RYGB). These patients have an increased incidence of pancreaticobiliary diseases yet standard ERCP is not possible due to surgically altered gastroduodenal anatomy. Laparoscopic-ERCP (LA-ERCP) has been proposed as an option but supporting data are derived from single center small case-series. Therefore, we conducted a large multicenter study to evaluate the feasibility, safety, and outcomes of LA-ERCP...
November 9, 2017: Gastrointestinal Endoscopy
https://www.readbyqxmd.com/read/29125965/death-by-self-mutilation-after-oral-cannabis-consumption
#11
Clemence Delteil, Caroline Sastre, Marie-Dominique Piercecchi, Catherine Faget-Agius, Marc Deveaux, Pascal Kintz, Marc-Antoine Devooght, George Leonetti, Christophe Bartoli, Anne-Laure Pélissier-Alicot
Major self-mutilation (amputation, castration, self-inflicted eye injuries) is frequently associated with psychiatric disorders and/or substance abuse. A 35-year-old man presented with behavioral disturbances of sudden onset after oral cannabis consumption and major self-mutilation (attempted amputation of the right arm, self-enucleation of both eyes and impalement) which resulted in death. During the enquiry, four fragments of a substance resembling cannabis resin were seized at the victim's home. Autopsy confirmed that death was related to hemorrhage following the mutilations...
November 2, 2017: Legal Medicine
https://www.readbyqxmd.com/read/29117179/a-mutation-in-the-viral-sensor-2-5-oligoadenylate-synthetase-2-causes-failure-of-lactation
#12
Samantha R Oakes, David Gallego-Ortega, Prudence M Stanford, Simon Junankar, Wendy Wing Yee Au, Zoya Kikhtyak, Anita von Korff, Claudio M Sergio, Andrew M K Law, Lesley E Castillo, Stephanie L Allerdice, Adelaide I J Young, Catherine Piggin, Belinda Whittle, Edward Bertram, Matthew J Naylor, Daniel L Roden, Jesse Donovan, Alexei Korennykh, Christopher C Goodnow, Moira K O'Bryan, Christopher J Ormandy
We identified a non-synonymous mutation in Oas2 (I405N), a sensor of viral double-stranded RNA, from an ENU-mutagenesis screen designed to discover new genes involved in mammary development. The mutation caused post-partum failure of lactation in healthy mice with otherwise normally developed mammary glands, characterized by greatly reduced milk protein synthesis coupled with epithelial cell death, inhibition of proliferation and a robust interferon response. Expression of mutant but not wild type Oas2 in cultured HC-11 or T47D mammary cells recapitulated the phenotypic and transcriptional effects observed in the mouse...
November 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29113972/localized-synchrotron-irradiation-of-mouse-skin-induces-persistent-systemic-genotoxic-and-immune-responses
#13
Jessica Ventura, Pavel N Lobachevsky, Jason S Palazzolo, Helen Forrester, Nicole M Haynes, Alesia Ivashkevich, Andrew W Stevenson, Christopher J Hall, Andreas Ntargaras, Vasilis Kotsaris, Gerasimos Ch Pollakis, Gianna Potsi, Konstantinos Skordylis, Georgia Terzoudi, Ioannis S Pateras, Vassilis G Gorgoulis, Alexandros G Georgakilas, Carl N Sprung, Olga A Martin
The importance of nontargeted (systemic) effects of ionizing radiation is attracting increasing attention. Exploiting synchrotron radiation generated by the Imaging and Medical Beamline at the Australian Synchrotron, we studied radiation-induced nontargeted effects in C57BL/6 mice. Mice were locally irradiated with a synchrotron X-ray broad beam and a multiplanar microbeam radiotherapy beam. To assess the influence of the beam configurations and variations in peak dose and irradiated area in the response of normal tissues outside the irradiated field at 1 and 4 days after irradiation, we monitored oxidatively induced clustered DNA lesions (OCDL), DNA double-strand breaks (DSB), apoptosis, and the local and systemic immune responses...
November 7, 2017: Cancer Research
https://www.readbyqxmd.com/read/29107689/semi-synthetic-salinomycin-analogs-exert-cytotoxic-activity-against-human-colorectal-cancer-stem-cells
#14
Johannes Klose, Sarah Kattner, Björn Borgström, Claudia Volz, Thomas Schmidt, Martin Schneider, Stina Oredsson, Daniel Strand, Alexis Ulrich
Salinomycin, a polyether antibiotic, is a well-known inhibitor of human cancer stem cells. Chemical modification of the allylic C20 hydroxyl of salinomycin has enabled access to synthetic analogs that display increased cytotoxic activity compared to the native structure. The aim of this study was to investigate the activity of a cohort of C20-O-acyl analogs of salinomycin on human colorectal cancer cell lines in vitro. Two human colorectal cancer cell lines (SW480 and SW620) were exposed to three C20-O-acylated analogs and salinomycin...
October 28, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29107146/nabi-a-novel-%C3%AE-sheet-breaker-inhibits-a%C3%AE-aggregation-and-neuronal-toxicity-therapeutic-implications-for-alzheimer-s-disease
#15
Ja-Young Jang, Hyangshuk Rhim, Seongman Kang
Amyloid beta (Aβ) aggregates are an important therapeutic target for Alzheimer's disease (AD), a fatal neurodegenerative disease. To date, AD still remains a big challenge due to no effective treatments. Based on the property that Aβ aggregates have the cross-β-structure, a common structural feature in amyloids, we systemically designed the Aβ-aggregation inhibitor that maintains Aβ-interacting ability but removes toxic part from SOD1 (superoxide dismutase 1)-G93A. We identified NABi (Natural Aβ Binder and Aβ-aggregation inhibitor) composed of β2-3 strands, a novel breaker of Aβ aggregation, which does not self-aggregate and has no cytotoxicity at all...
January 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29106790/phytoestrogen-alpha-zearalanol-attenuate-endoplasmic-reticulum-stress-to-against-cultured-rat-hippocampal-neurons-apoptotic-death-induced-by-amyloid-beta25-35
#16
(no author information available yet)
OBJECTIVE: Our previous studies demonstrated both phytoestrogen α-zearalanol (α-ZAL) and estrogen is effective decrease Alzheimer's disease (AD)-like apoptotic neuron death, but α-ZAL showed significantly less side-effect on breast and endometrial tissue compared to estrogen, it suggested that α-ZAL can be used as a potential substitute for estrogen. However, the molecular mechanism by which α-ZAL prevents neuron damage remains unclear. Growing evidence suggests that endoplasmic reticulum (ER) stress plays an important role in the process of cell apoptosis in AD; in addition, our published data indicated that α-ZAL possessed the potential ability to stabilize ER function...
October 6, 2017: Neuro Endocrinology Letters
https://www.readbyqxmd.com/read/29098631/formation-and-repair-of-dna-protein-crosslink-damage
#17
REVIEW
Naeh L Klages-Mundt, Lei Li
DNA is constantly exposed to a wide array of genotoxic agents, generating a variety of forms of DNA damage. DNA-protein crosslinks (DPCs)-the covalent linkage of proteins with a DNA strand-are one of the most deleterious and understudied forms of DNA damage, posing as steric blockades to transcription and replication. If not properly repaired, these lesions can lead to mutations, genomic instability, and cell death. DPCs can be induced endogenously or through environmental carcinogens and chemotherapeutic agents...
October 30, 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/29094262/the-methuselah-effect-the-pernicious-impact-of-unreported-deaths-on-old-age-mortality-estimates
#18
Dan A Black, Yu-Chieh Hsu, Seth G Sanders, Lynne Steuerle Schofield, Lowell J Taylor
We examine inferences about old-age mortality that arise when researchers use survey data matched to death records. We show that even small rates of failure to match respondents can lead to substantial bias in the measurement of mortality rates at older ages. This type of measurement error is consequential for three strands in the demographic literature: (1) the deceleration in mortality rates at old ages; (2) the black-white mortality crossover; and (3) the relatively low rate of old-age mortality among Hispanics, often called the "Hispanic paradox...
November 1, 2017: Demography
https://www.readbyqxmd.com/read/29091070/enhancement-of-radiosensitivity-of-oral-carcinoma-cells-by-iodinated-chlorin-p6-copper-complex-in-combination-with-synchrotron-x-ray-radiation
#19
Paromita Sarbadhikary, Alok Dube
The combination of synchrotron X-ray radiation and metal-based radiosensitizer is a novel form of photon activation therapy which offers the advantage of treating malignant tumors with greater efficacy and higher precision than conventional radiation therapy. In this study the anticancer cytotoxic efficacy of a new chlorophyll derivative, iodinated chlorin p6 copper complex (ICp6-Cu), combined with synchrotron X-ray radiation (8-10 keV) in two human oral cancer cell lines is explored. Pre-treatment of cells with 20 µM and 30 µM ICp6-Cu for 3 h was found to enhance the X-ray-induced cytotoxicity with sensitization enhancement ratios of 1...
November 1, 2017: Journal of Synchrotron Radiation
https://www.readbyqxmd.com/read/29081676/possible-involvement-of-ros-generation-in-vorinostat-pretreatment-induced-enhancement-of-the-antibacterial-activity-of-ciprofloxacin
#20
Majed M Masadeh, Karem H Alzoubi, Sayer I Al-Azzam, Ahlam M Al-Buhairan
The mechanism underlying ciprofloxacin action involves interference with transcription and replication of bacterial DNA and, thus, the induction of double-strand breaks in DNA. It also involves elevated oxidative stress, which might contribute to bacterial cell death. Vorinostat was shown to induce oxidative DNA damage. The current work investigated a possible interactive effect of vorinostat on ciprofloxacin-induced cytotoxicity against a number of reference bacteria. Standard bacterial strains were Escherichia coli ATCC 35218, Staphylococcus aureus ATCC29213, Pseudomonas aeruginosa ATCC 9027, Staphylococcus epidermidis ATCC 12228, Acinetobacter baumannii ATCC 17978, Proteus mirabilis ATCC 12459, Klebsiella pneumoniae ATCC 13883, methicillin-resistant Staphylococcus aureus (MRSA) (ATCC 43300), and Streptococcus pneumoniae (ATCC 25923)...
2017: Clinical Pharmacology: Advances and Applications
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