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https://www.readbyqxmd.com/read/27923055/a-novel-rrm3-function-in-restricting-dna-replication-via-an-orc5-binding-domain-is-genetically-separable-from-rrm3-function-as-an-atpase-helicase-in-facilitating-fork-progression
#1
Salahuddin Syed, Claus Desler, Lene J Rasmussen, Kristina H Schmidt
In response to replication stress cells activate the intra-S checkpoint, induce DNA repair pathways, increase nucleotide levels, and inhibit origin firing. Here, we report that Rrm3 associates with a subset of replication origins and controls DNA synthesis during replication stress. The N-terminal domain required for control of DNA synthesis maps to residues 186-212 that are also critical for binding Orc5 of the origin recognition complex. Deletion of this domain is lethal to cells lacking the replication checkpoint mediator Mrc1 and leads to mutations upon exposure to the replication stressor hydroxyurea...
December 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27922635/increased-plasma-levels-of-circulating-cell-free-mitochondrial-dna-in-suicide-attempters-associations-with-hpa-axis-hyperactivity
#2
D Lindqvist, J Fernström, C Grudet, L Ljunggren, L Träskman-Bendz, L Ohlsson, Å Westrin
Preclinical data suggest that chronic stress may cause cellular damage and mitochondrial dysfunction, potentially leading to the release of mitochondrial DNA (mtDNA) into the bloodstream. Major depressive disorder has been associated with an increased amount of mtDNA in leukocytes from saliva samples and blood; however, no previous studies have measured plasma levels of free-circulating mtDNA in a clinical psychiatric sample. In this study, free circulating mtDNA was quantified in plasma samples from 37 suicide attempters, who had undergone a dexamethasone suppression test (DST), and 37 healthy controls...
December 6, 2016: Translational Psychiatry
https://www.readbyqxmd.com/read/27921220/increased-cell-free-mitochondrial-dna-is-a-marker-of-ongoing-inflammation-and-better-neurocognitive-function-in-virologically-suppressed-hiv-infected-individuals
#3
Josué Pérez-Santiago, Michelli F De Oliveira, Susanna R Var, Tyler R C Day, Steven P Woods, Sara Gianella, Sanjay R Mehta
Cell-free mitochondrial DNA (mtDNA) is a highly immunogenic molecule that is associated with several inflammatory conditions and with neurocognitive impairment during untreated HIV infection. Here, we investigate how cell-free mtDNA in cerebrospinal fluid (CSF) is associated with inflammation, neuronal damage, and neurocognitive functioning in the context of long-term suppressive antiretroviral therapy (ART). We quantified the levels of cell-free mtDNA in the CSF from 41 HIV-infected individuals with completely suppressed HIV RNA levels in blood plasma (<50 copies/mL) by droplet digital PCR...
December 5, 2016: Journal of Neurovirology
https://www.readbyqxmd.com/read/27920533/effect-of-inserted-spacer-in-hepatic-cell-penetrating-multifunctional-peptide-component-on-the-dna-intracellular-delivery-of-quaternary-complexes-based-on-modular-design
#4
Luchen Zhang, Zhenbo Li, Fangli Sun, Yuhong Xu, Zixiu Du
A safe and efficient quaternary gene delivery system (named Q-complexes) was constructed based on self-assembly of molecules through noncovalent bonds. This system was formulated through the cooperation and competing interactions of cationic liposomes, multifunctional peptides, and DNA, followed by coating hyaluronic acid on the surface of the ternary complexes. The multifunctional peptide was composed of two functional domains: penetrating hepatic tumor-targeted cell moiety (KRPTMRFRYTWNPMK) and a wrapping gene sequence (polyarginine 16)...
2016: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/27919866/mitochondrial-dna-haplogroups-influence-the-risk-of-incident-knee-osteoarthritis-in-oai-and-check-cohorts-a-meta-analysis-and-functional-study
#5
Mercedes Fernández-Moreno, Angel Soto-Hermida, María E Vázquez-Mosquera, Estefanía Cortés-Pereira, Sara Relaño, Tamara Hermida-Gómez, Sonia Pértega, Natividad Oreiro-Villar, Carlos Fernández-López, Rafael Garesse, Francisco J Blanco, Ignacio Rego-Pérez
OBJECTIVE: To evaluate the influence of the mitochondrial DNA (mtDNA) haplogroups in the risk of incident knee osteoarthritis (OA) and to explain the functional consequences of this association to identify potential diagnostic biomarkers and therapeutic targets. METHODS: Two prospective cohorts contributed participants. The osteoarthritis initiative (OAI) included 2579 subjects of the incidence subcohort, and the cohort hip and cohort knee (CHECK) included 635, both with 8-year follow-up...
December 5, 2016: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/27919736/effect-of-morin-5-sulfonic-acid-sodium-salt-on-the-expression-of-apoptosis-related-proteins-caspase-3-bax-and-bcl-2-due-to-the-mercury-induced-oxidative-stress-in-albino-rats
#6
Rantham Subramaniam Venkatesan, Abdul Majeeth Mohamed Sadiq
Many environmental contaminants have been reported to disturb the pro-oxidant or antioxidant balance of the cells by inducing oxidative stress. Oxidative stress mediated by the HgCl2 induces DNA, protein and lipid oxidation resulted in necrosis or apoptosis, or both. Currently flavonoids are being emerging topic and reported to have antiviral, anti-inflammatory, anti- tumor and antioxidant activities. Morin is one of the flavonoid protects the cells from oxygen free radical damage and scavenges the free radicals and metals and also heals the injured cells commercially...
December 2, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27918552/hmyh-and-hmth1-cooperate-for-survival-in-mismatch-repair-defective-t-cell-acute-lymphoblastic-leukemia
#7
S Eshtad, Z Mavajian, S G Rudd, T Visnes, J Boström, M Altun, T Helleday
hMTH1 is an 8-oxodGTPase that prevents mis-incorporation of free oxidized nucleotides into genomic DNA. Base excision and mismatch repair pathways also restrict the accumulation of oxidized lesions in DNA by removing the mis-inserted 8-oxo-7,8-dihydro-2'-deoxyguanosines (8-oxodGs). In this study, we aimed to investigate the interplay between hMYH DNA glycosylase and hMTH1 for cancer cell survival by using mismatch repair defective T-cell acute lymphoblastic leukemia (T-ALL) cells. To this end, MYH and MTH1 were silenced individually or simultaneously using small hairpin RNAs...
December 5, 2016: Oncogenesis
https://www.readbyqxmd.com/read/27917702/effectiveness-of-pegaspargase-gemcitabine-and-oxaliplatin-p-gemox-chemotherapy-combined-with-radiotherapy-in-newly-diagnosed-stage-ie-to-iie-nasal-type-extranodal-natural-killer-t-cell-lymphoma
#8
Wen Wei, Ping Wu, Li Li, Zhi-Hui Zhang
PURPOSE: Extranodal natural killer/T-cell lymphoma (ENKTL), nasal-type, is a distinct subtype of non-Hodgkin lymphoma. ENKTL is sensitive to radiotherapy, but the prognosis is poorer than those of other types of early stage lymphoma. To date, optimal treatment strategies for patients with early stage ENKTL have not been fully defined. METHODS: We retrospectively investigated the efficacy and safety of pegaspargase, gemcitabine, and oxaliplatin (P-GEMOX) combined with different dose radiotherapy (RT) in the treatment of 35 newly diagnosed, stage IE to IIE ENKTL patients at our institution from October 2011 to September 2015...
December 5, 2016: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/27917701/design-synthesis-mtt-assay-dna-interaction-studies-of-platinum-ii-complexes
#9
Miral V Lunagariya, Khyati P Thakor, Bhargav N Waghela, Foram U Vaidya, Chadramani Pathak, Mohan N Patel
The square planar Pt(II) complexes of the type [Pt(L(n))(Cl2)] (where L(n) = L(1-3) = thiophene-2-carboxamide derivatives and L(4-6) = thiophene-2-carbothioamide derivatives) have been synthesized and characterized by physicochemical and various spectroscopic studies. MIC method was employed to inference the antibacterial potency of complexes in reference to free ligands and metal salt. Characteristic binding constant (Kb) and binding mode of complexes with calf thymus DNA (CT-DNA) were determined using absorption titration (0...
December 4, 2016: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/27916887/cucumber-metallothionein-like-2-csmtl2-exhibits-metal-binding-properties
#10
Yu Pan, Yanglu Pan, Junpeng Zhai, Yan Xiong, Jinhua Li, Xiaobing Du, Chenggang Su, Xingguo Zhang
We identified a novel member of the metallothionein (MT) family, Cucumis sativus metallothionein-like 2 (CsMTL2), by screening a young cucumber fruit complementary DNA (cDNA) library. The CsMTL2 encodes a putative 77-amino acid Class II MT protein that contains two cysteine (Cys)-rich domains separated by a Cys-free spacer region. We found that CsMTL2 expression was regulated by metal stress and was specifically induced by Cd(2+) treatment. We investigated the metal-binding characteristics of CsMTL2 and its possible role in the homeostasis and/or detoxification of metals by heterologous overexpression in Escherichia coli cells...
November 30, 2016: Genes
https://www.readbyqxmd.com/read/27915499/first-trimester-contingent-screening-for-trisomies-21-18-13-is-this-model-cost-efficient-and-feasible-in-pubblic-health-system
#11
Enrico Colosi, Valentina D'Ambrosio, Enrico Periti
PURPOSE: To evaluate the effectiveness of three different first trimester screening models for trisomies 21, 18 and 13, in terms of detection rate, invasive test rate and final costs. MATERIAL AND METHODS: We analyzed the distribution of risk for trisomies 21, 18 and 13 in a population of 20.831 singleton pregnancies based on maternal age, fetal heart rate, nuchal translucency, free beta human chorionic gonadotropin and pregnancy associated plasma protein A (Combined test)...
December 5, 2016: Journal of Maternal-fetal & Neonatal Medicine
https://www.readbyqxmd.com/read/27915165/re-assessing-gallium-67-as-a-therapeutic-radionuclide
#12
Muhamad F Bin Othman, Nabil R Mitry, Valerie J Lewington, Philip J Blower, Samantha Y A Terry
INTRODUCTION: Despite its desirable half-life and low energy Auger electrons that travel further than for other radionuclides, (67)Ga has been neglected as a therapeutic radionuclide. Here, (67)Ga is compared with Auger electron emitter (111)In as a potential therapeutic radionuclide. METHODS: Plasmid pBR322 studies allowed direct comparison between (67)Ga and (111)In (1MBq) in causing DNA damage, including the effect of chelators (EDTA and DTPA) and the effects of a free radical scavenger (DMSO)...
October 29, 2016: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/27913835/preventive-dna-vaccination-against-cea-expressing-tumors-with-anti-idiotypic-scfv6-c4-dna-in-cea-expressing-transgenic-mice
#13
Priscila M A Denapoli, Bianca F Zanetti, Adara A Dos Santos, Jane Z de Moraes, Sang W Han
Carcinoembryonic antigen (CEA) is expressed during embryonic life and in low level during adult life. Consequently, the CEA is recognized by the immune system as a self-antigen and thus CEA-expressing tumors are tolerated. Previously, we constructed a single chain variable fragment using the 6.C4 (scFv6.C4) hybridoma cell line, which gave rise to antibodies able to recognize CEA when C57/Bl6 mice were immunized. Here, the scFv6.C4 ability to prevent the CEA-expressing tumor growth was assessed in CEA-expressing transgenic mice CEA2682...
December 2, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27908784/cisplatin-induced-mitochondrial-dysfunction-is-associated-with-impaired-cognitive-function-in-rats
#14
Naomi Lomeli, Kaijun Di, Jennifer Czerniawski, John F Guzowski, Daniela A Bota
PURPOSE: Chemotherapy-related cognitive impairment (CRCI) is commonly reported following the administration of chemotherapeutic agents and comprises a wide variety of neurological problems. No effective treatments for CRCI are currently available. Here we examined the mechanisms involving cisplatin-induced hippocampal damage following cisplatin administration in a rat model and in cultured rat hippocampal neurons and neural stem/progenitor cells (NSC). We also assessed the protective effects of the antioxidant, N-acetylcysteine in mitigating these damages...
November 28, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27908619/correlation-of-dna-repair-gene-polymorphisms-with-clinical-outcome-in-patients-with-locally-advanced-non-small-cell-lung-cancer-receiving-induction-chemotherapy-followed-by-surgery
#15
Mariacarmela Santarpia, Jose Luis Ramirez, Itziar de Aguirre, Pilar Garrido, Maria Pérez Cano, Cristina Queralt, Jose Luis Gonzalez-Larriba, Amelia Insa, Mariano Provencio, Dolores Isla, Carlos Camps, Remei Blanco, Teresa Moran, Rafael Rosell
OBJECTIVE: The aim of this study was to evaluate whether xeroderma pigmentosum group D (XPD) and ribonucleotide reductase subunit M1 (RRM1) polymorphisms influenced clinical outcome in patients with stage IIIA-B non-small-cell lung cancer (NSCLC) treated with neoadjuvant gemcitabine/cisplatin/docetaxel followed by surgery. MATERIALS AND METHODS: A total of 109 patients with stage IIIA and IIIB NSCLC were prospectively genotyped to examine a potential association between XPD 312 (aspartic acid [Asp]/asparagine [Asn]), XPD 751 (lysine [Lys]/glutamine [Gln]), and RRM1 (-37 C/A) polymorphisms with response and survival...
November 9, 2016: Clinical Lung Cancer
https://www.readbyqxmd.com/read/27908304/the-role-and-diagnostic-value-of-cell-free-dna-in-systemic-lupus-erythematosus
#16
REVIEW
Anna Truszewska, Bartosz Foroncewicz, Leszek Pączek
Cell-free DNA (cfDNA) represents a small fraction of total DNA pool that circulates freely in the blood both in normal and pathological conditions. Data indicate that cfDNA plays an important role in the pathogenesis of systemic lupus erythematosus (SLE) and hypomethylation may be crucial for its immunogenic properties. Although differences in quantification methodology hinder the comparison of results between the studies, it appears that levels of cfDNA are abnormally elevated in SLE patients and correlate with various antibody titers, but not with disease activity...
November 14, 2016: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/27906860/liquid-biopsy-for-early-detection-of-lung-cancer
#17
Paul Hofman
PURPOSE OF REVIEW: The possibility of complete recovery for a lung cancer patient depends on very early diagnosis, as it allows total surgical resection. Screening for this cancer in a high-risk population can be performed using a radiological approach, but this holds a certain number of limitations. Liquid biopsy could become an alternative and complementary screening approach to chest imaging for early diagnosis of lung cancer. RECENT FINDINGS: Several circulating biomarkers indicative of lung cancer can be investigated in blood, such as circulating tumor cells, circulating free nucleic acids (RNA and DNA) and proteins...
January 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/27906459/integrative-genomic-analysis-identifies-ancestry-related-expression-quantitative-trait-loci-on-dna-polymerase-%C3%AE-and-supports-the-association-of-genetic-ancestry-with-survival-disparities-in-head-and-neck-squamous-cell-carcinoma
#18
Meganathan P Ramakodi, Karthik Devarajan, Elizabeth Blackman, Denise Gibbs, Danièle Luce, Jacqueline Deloumeaux, Suzy Duflo, Jeffrey C Liu, Ranee Mehra, Rob J Kulathinal, Camille C Ragin
BACKGROUND: African Americans with head and neck squamous cell carcinoma (HNSCC) have a lower survival rate than whites. This study investigated the functional importance of ancestry-informative single-nucleotide polymorphisms (SNPs) in HNSCC and also examined the effect of functionally important genetic elements on racial disparities in HNSCC survival. METHODS: Ancestry-informative SNPs, RNA sequencing, methylation, and copy number variation data for 316 oral cavity and laryngeal cancer patients were analyzed across 178 DNA repair genes...
December 1, 2016: Cancer
https://www.readbyqxmd.com/read/27905522/circulating-cell-free-dna-telomere-length-and-bilirubin-in-the-vienna-active-ageing-study-exploratory-analysis-of-a-randomized-controlled-trial
#19
Anela Tosevska, Bernhard Franzke, Marlene Hofmann, Immina Vierheilig, Barbara Schober-Halper, Stefan Oesen, Oliver Neubauer, Barbara Wessner, Karl-Heinz Wagner
Telomere length (TL) in blood cells is widely used in human studies as a molecular marker of ageing. Circulating cell-free DNA (cfDNA) as well as unconjugated bilirubin (UCB) are dynamic blood constituents whose involvement in age-associated diseases is largely unexplored. To our knowledge, there are no published studies integrating all three parameters, especially in individuals of advanced age. Here we present a secondary analysis from the Vienna Active Aging Study (VAAS), a randomized controlled intervention trial in institutionalized elderly individuals (n = 101)...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27905097/novel-biomarkers-in-primary-breast-core-biopsies-to-predict-poor-response-to-neoadjuvant-chemotherapy-and-appearance-of-metastases
#20
Anna Novell, Serafin Morales, Joan Valls, Maria José Panadés, Antonieta Salud, Edelmiro Iglesias, Felip Vilardell, Xavier Matias-Guiu, Antonio Llombart-Cussac
Drug resistance has been one of the major obstacles limiting the success of cancer chemotherapy. In two thirds of breast cancer patients, large (>1cm) residual tumors are present after neoadjuvant chemotherapy (NCT). The residual tumor and involved nodes have been indicators of relapse and survival very important in breast cancer. The goal of this preliminary study was to assess the predictive significance of a panel of molecular biomarkers, related with the response to treatment or drug resistance to NCT, as determined on the diagnostic tumor...
December 1, 2016: Histology and Histopathology
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