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https://www.readbyqxmd.com/read/29150481/identification-of-pleiotropic-cancer-susceptibility-variants-from-genome-wide-association-studies-reveals-functional-characteristics
#1
Yi-Hsuan Wu, Rebecca E Graff, Michael N Passarelli, Joshua D Hoffman, Elad Ziv, Thomas J Hoffmann, John S Witte
BACKGROUND: There exists compelling evidence that some genetic variants are associated with the risk of multiple cancer sites (i.e., pleiotropy). However, the biological mechanisms through which the pleiotropic variants operate are unclear. METHODS: We obtained all cancer risk associations from the National Human Genome Research Institute-European Bioinformatics Institute GWAS Catalog, and correlated cancer risk variants were clustered into groups. Pleiotropic variant groups and genes were functionally annotated...
November 17, 2017: Cancer Epidemiology, Biomarkers & Prevention
https://www.readbyqxmd.com/read/29150048/dna-dependent-protein-kinase-modulates-the-anti-cancer-properties-of-silver-nanoparticles-in-human-cancer-cells
#2
Hui Kheng Lim, Resham Lal Gurung, M Prakash Hande
Silver nanoparticles (Ag-np) were reported to be toxic to eukaryotic cells. These potentially detrimental effects of Ag-np can be advantageous in experimental therapeutics. They are currently being employed to enhance the therapeutic efficacy of cancer drugs. In this study, we demonstrate that Ag-np treatment trigger the activation of DNA-PKcs and JNK pathway at selected doses, presumably as a physiologic response to DNA damage and repair in normal and malignant cells. Ag-np altered the telomere dynamics by disrupting the shelterin complex located at the telomeres and telomere lengths...
December 2017: Mutation Research
https://www.readbyqxmd.com/read/29149597/structural-basis-for-shelterin-bridge-assembly
#3
Jin-Kwang Kim, Jinqiang Liu, Xichan Hu, Clinton Yu, Kyle Roskamp, Banumathi Sankaran, Lan Huang, Elizabeth A Komives, Feng Qiao
Telomere elongation through telomerase enables chromosome survival during cellular proliferation. The conserved multifunctional shelterin complex associates with telomeres to coordinate multiple telomere activities, including telomere elongation by telomerase. Similar to the human shelterin, fission yeast shelterin is composed of telomeric sequence-specific double- and single-stranded DNA-binding proteins, Taz1 and Pot1, respectively, bridged by Rap1, Poz1, and Tpz1. Here, we report the crystal structure of the fission yeast Tpz1(475-508)-Poz1-Rap1(467-496) complex that provides the structural basis for shelterin bridge assembly...
November 16, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29149592/dynamics-under-the-telomeric-bridge
#4
Sabrina Pisano, Eric Gilson, Marie-Josèphe Giraud-Panis
In this issue of Molecular Cell, Kim et al. (2017) have studied the structure and organization of the shelterin protein complex protecting telomeres in Schizosaccharomyces pombe and humans and discovered an allosteric structural transition that drives the formation of the shelterin complex and participates in telomere length regulation.
November 16, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29149257/eleven-telomere-epigenetic-clock-and-biomarker-composite-quantifications-of-biological-aging-do-they-measure-the-same-thing
#5
Daniel W Belsky, Terrie E Moffitt, Alan A Cohen, David L Corcoran, Morgan E Levine, Joseph A Prinz, Jonathan Schaefer, Karen Sugden, Benjamin Williams, Richie Poulton, Avshalom Caspi
The geroscience hypothesis posits that therapies to slow biological processes of aging can prevent disease and extend healthy years of life. To test such "gero-protective" therapies in humans, outcome measures are needed that can assess extension of disease-free lifespan. This need has spurred development of different methods to quantify biological aging. But different methods have not been systematically compared in the same humans. We implemented seven methods to quantify biological aging using repeated-measures physiological and genomic data in 964 middle-aged humans in the Dunedin Study...
November 15, 2017: American Journal of Epidemiology
https://www.readbyqxmd.com/read/29149205/kir-content-genotypes-associate-with-carriage-of-hepatitis-b-surface-antigen-e-antigen-and-hbv-viral-load-in-gambians
#6
Louis-Marie Yindom, Maimuna Mendy, Christopher Bodimeade, Caroline Chambion, Peter Aka, Hilton C Whittle, Sarah L Rowland-Jones, Robert Walton
BACKGROUND: Hepatocellular carcinoma (HCC) causes over 800,000 deaths worldwide annually, mainly in low income countries, and incidence is rising rapidly in the developed world with the spread of hepatitis B (HBV) and C (HCV) viruses. Natural Killer (NK) cells protect against viral infections and tumours by killing abnormal cells recognised by Killer-cell Immunoglobulin-like Receptors (KIR). Thus genes and haplotypes encoding these receptors may be important in determining both outcome of initial hepatitis infection and subsequent chronic liver disease and tumour formation...
2017: PloS One
https://www.readbyqxmd.com/read/29149047/new-insights-into-phasmatodea-chromosomes
#7
Thomas Liehr, Olesya Buleu, Tatyana Karamysheva, Alexander Bugrov, Nikolai Rubtsov
Currently, approximately 3000 species of stick insects are known; however, chromosome numbers, which range between 21 and 88, are known for only a few of these insects. Also, centromere banding staining (C-banding) patterns were described for fewer than 10 species, and fluorescence in situ hybridization (FISH) was applied exclusively in two Leptynia species. Interestingly, 10-25% of stick insects (Phasmatodea) are obligatory or facultative parthenogenetic. As clonal and/or bisexual reproduction can affect chromosomal evolution, stick insect karyotypes need to be studied more intensely...
November 17, 2017: Genes
https://www.readbyqxmd.com/read/29148828/increased-cellular-aging-by-3-years-of-age-in-latino-preschool-children-who-consume-more-sugar-sweetened-beverages-a-pilot-study
#8
Janet M Wojcicki, Rosalinda Medrano, Jue Lin, Elissa Epel
BACKGROUND: Previous studies in adults and older children find that sugar-sweetened beverage (SSB) consumption increases risk for obesity and cellular aging, as measured by leukocyte telomere length (LTL). METHODS: In a previously described, San Francisco-based Latino birth cohort, where telomere length was measured at birth, we evaluate the relationship between beverage consumption (including SSB and 100% fruit juice), obesity, and LTL at 2-3 years old, as well as change in LTL from birth...
November 17, 2017: Childhood Obesity
https://www.readbyqxmd.com/read/29148767/role-of-the-benzodioxole-group-in-the-interactions-between-the-natural-alkaloids-chelerythrine-and-coptisine-and-the-human-telomeric-g-quadruplex-dna-a-multiapproach-investigation
#9
F Papi, M Ferraroni, R Rigo, S Da Ros, C Bazzicalupi, C Sissi, P Gratteri
The binding properties toward the human telomeric G-quadruplex of the two natural alkaloids coptisine and chelerythrine were studied using spectroscopic techniques, molecular modeling, and X-ray diffraction analysis. The results were compared with reported data for the parent compounds berberine and sanguinarine. Spectroscopic studies showed modest, but different rearrangements of the DNA-ligand complexes, which can be explained considering particular stereochemical features for these alkaloids, in spite of the similarity of their skeletons...
November 17, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/29146545/werner-syndrome-wrn-gene-variants-and-their-association-with-altered-function-and-age-associated-diseases
#10
REVIEW
Michel Lebel, Raymond J Monnat
Werner syndrome (WS) is a heritable autosomal recessive human disorder characterized by the premature onset of several age-associated pathologies including cancer. The protein defective in WS patients, WRN, is encoded by a member of the human RECQ gene family that contains both a DNA exonuclease and a helicase domain. WRN has been shown to participate in several DNA metabolic pathways including DNA replication, recombination and repair, as well as telomere maintenance and transcription modulation. Here we review base pair-level genetic variation that has been documented in WRN, with an emphasis on non-synonymous coding single nucleotide polymorphisms (SNPs) and their associations with anthropomorphic features, longevity and disease risk...
November 13, 2017: Ageing Research Reviews
https://www.readbyqxmd.com/read/29145644/paf1-and-ctr9-core-components-of-the-paf1-complex-maintain-low-levels-of-telomeric-repeat-containing-rna
#11
Joana Rodrigues, David Lydall
The conserved PAF1 complex (Cdc73, Paf1, Ctr9, Leo1 and Rtf1, in yeast), binds RNA pol II, and affects levels of many RNAs. Although PAF1 is a complex, there is evidence that different components perform different functions. In yeast, Cdc73, Paf1 and Ctr9 maintain normal telomerase RNA (TLC1) levels and affect telomere length. Here we report a new connection between the PAF1 complex and telomere biology. We show that Paf1 and Ctr9 maintain low telomere repeat containing RNA (TERRA) levels while Cdc73, Leo1 and Rtf1 have lesser effects...
November 14, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29145503/zinc-sulfate-contributes-to-promote-telomere-length-extension-via-increasing-telomerase-gene-expression-telomerase-activity-and-change-in-the-tert-gene-promoter-cpg-island-methylation-status-of-human-adipose-derived-mesenchymal-stem-cells
#12
Raheleh Farahzadi, Ezzatollah Fathi, Seyed Alireza Mesbah-Namin, Nosratollah Zarghami
The use of mesenchymal stem cells (MSCs) for cell therapy and regenerative medicine has received widespread attention over the past few years, but their application can be complicated by factors such as reduction in proliferation potential, the senescent tendency of the MSCs upon expansion and their age-dependent decline in number and function. It was shown that all the mentioned features were accompanied by a reduction in telomerase activity and telomere shortening. Furthermore, the role of epigenetic changes in aging, especially changes in promoter methylation, was reported...
2017: PloS One
https://www.readbyqxmd.com/read/29144994/gene-pathways-associated-with-mitochondrial-function-oxidative-stress-and-telomere-length-are-differentially-expressed-in-the-liver-of-rats-fed-lifelong-on-virgin-olive-sunflower-or-fish-oils
#13
Alfonso Varela-Lopez, María Patricia Pérez-López, César Luis Ramirez-Tortosa, Maurizio Battino, Sergio Granados-Principal, María Del Carmen Ramirez-Tortosa, Julio José Ochoa, Laura Vera-Ramirez, Francesca Giampieri, José Luis Quiles
This study investigates the effect of lifelong intake of different fat sources rich in monounsaturated (virgin olive oil), n6 polyunsaturated (sunflower oil) or n3 polyunsaturated (fish oil) fatty acids in the aged liver. Male Wistar rats fed lifelong on diets differing in the fat source were killed at 6 and at 24 months of age. Liver histopathology, mitochondrial ultrastructure, biogenesis, oxidative stress, mitochondrial electron transport chain, relative telomere length and gene expression profiles were studied...
September 20, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/29144820/pheochromocytoma-a-genetic-and-diagnostic-update
#14
Leilani B Mercado-Asis, Katherine I Wolf, Ivana Jochmanova, David Taïeb
OBJECTIVE: Pheochromocytomas and paragangliomas (PPGLs) are neuroendocrine tumors derived from adrenal or extra-adrenal locations, respectively. Upon suspicion of PPGL, specific metabolomic, molecular, biochemical, imaging, and histopathological studies are performed to prove, localize, treat, and monitor disease progression. Recently, improved diagnostic tools allow physicians to accurately diagnose PPGL, even in patients presenting with small (less than 1 cm) or biochemically silent tumors, which previously delayed proper detection and treatment...
November 16, 2017: Endocrine Practice
https://www.readbyqxmd.com/read/29143804/telomeres-and-telomerase-in-hematopoietic-dysfunction-prognostic-implications-and-pharmacological-interventions
#15
REVIEW
Theresa Vasko, Andrea Kaifie, Matthias B Stope, Thomas Kraus, Patrick Ziegler
Leukocyte telomere length (TL) has been suggested as a marker of biological age in healthy individuals, but can also reflect inherited and acquired hematopoietic dysfunctions or indicate an increased turnover of the hematopoietic stem and progenitor cell compartment. In addition, TL is able to predict the response rate of tyrosine kinase inhibitor therapy in chronic myeloid leukemia (CML), indicates clinical outcomes in chronic lymphocytic leukemia (CLL), and can be used as screening tool for genetic sequencing of selected genes in patients with inherited bone marrow failure syndromes (BMFS)...
October 28, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29143441/cellular-aging-dynamics-after-acute-malaria-infection-a-12-month-longitudinal-study
#16
Muhammad Asghar, Victor Yman, Manijeh Vafa Homann, Klara Sondén, Ulf Hammar, Dennis Hasselquist, Anna Färnert
Accelerated cellular aging and reduced lifespan have recently been shown in birds chronically infected with malaria parasites. Whether malaria infection also affects cellular aging in humans has not been reported. Here, we assessed the effect of a single acute Plasmodium falciparum malaria infection on cellular aging dynamics in travelers prospectively followed over one year in Sweden. DNA and RNA were extracted from venous blood collected at the time of admission and repeatedly up to one year. Telomere length was measured using real-time quantitative PCR, while telomerase activity and CDKN2A expression were measured by reverse transcriptase (RT)-qPCR...
November 16, 2017: Aging Cell
https://www.readbyqxmd.com/read/29143121/telomere-length-of-gallbladder-epithelium-is-shortened-in-patients-with-congenital-biliary-dilatation-measurement-by-quantitative-fluorescence-in-situ-hybridization
#17
Yuto Aoki, Junko Aida, Youichi Kawano, Ken-Ichi Nakamura, Naotaka Izumiyama-Shimomura, Naoshi Ishikawa, Tomio Arai, Yoshiharu Nakamura, Nobuhiko Taniai, Eiji Uchida, Kaiyo Takubo, Toshiyuki Ishiwata
BACKGROUND: Congenital biliary dilatation (CBD) is a congenital malformation involving both dilatation of the extrahepatic bile duct and pancreaticobiliary maljunction. Persistent reflux of pancreatic juice injures the biliary tract mucosa, resulting in chronic inflammation and higher rates of carcinogenesis in the biliary tract, including the gallbladder. Telomeres are repetitive DNA sequences located at the ends of chromosomes. Chromosomal instability due to telomere dysfunction plays an important role in the carcinogenesis of many organs...
November 15, 2017: Journal of Gastroenterology
https://www.readbyqxmd.com/read/29141207/distinct-terb1-domains-regulate-different-protein-interactions-in-meiotic-telomere-movement
#18
Jingjing Zhang, Zhaowei Tu, Yoshinori Watanabe, Hiroki Shibuya
Meiotic telomeres attach to the nuclear envelope (NE) and drive the chromosome movement required for the pairing of homologous chromosomes. The meiosis-specific telomere proteins TERB1, TERB2, and MAJIN are required to regulate these events, but their assembly processes are largely unknown. Here, we developed a germ-cell-specific knockout mouse of the canonical telomere-binding protein TRF1 and revealed an essential role for TRF1 in directing the assembly of TERB1-TERB2-MAJIN. Further, we identified a TERB2 binding (T2B) domain in TERB1 that is dispensable for the TRF1-TERB1 interaction but is essential for the subsequent TERB1-TERB2 interaction and therefore for telomere attachment to the NE...
November 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/29141206/role-of-the-pif1-pcna-complex-in-pol-%C3%AE-dependent-strand-displacement-dna-synthesis-and-break-induced-replication
#19
Olga Buzovetsky, Youngho Kwon, Nhung Tuyet Pham, Claire Kim, Grzegorz Ira, Patrick Sung, Yong Xiong
The S. cerevisiae Pif1 helicase functions with DNA polymerase (Pol) δ in DNA synthesis during break-induced replication (BIR), a conserved pathway responsible for replication fork repair and telomere recombination. Pif1 interacts with the DNA polymerase processivity clamp PCNA, but the functional significance of the Pif1-PCNA complex remains to be elucidated. Here, we solve the crystal structure of PCNA in complex with a non-canonical PCNA-interacting motif in Pif1. The structure guides the construction of a Pif1 mutant that is deficient in PCNA interaction...
November 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/29138179/association-between-leukocyte-telomere-length-and-the-risk-of-incident-atrial-fibrillation-the-framingham-heart-study
#20
Laila Staerk, Biqi Wang, Kathryn L Lunetta, Robert H Helm, Darae Ko, Jason A Sherer, Patrick T Ellinor, Steven A Lubitz, David D McManus, Ramachandran S Vasan, Emelia J Benjamin, Ludovic Trinquart
BACKGROUND: Advancing age is a prominent risk factor for atrial fibrillation (AF). Shorter telomere length is a biomarker of biological aging, but the link between shorter telomere length and increased risk of AF remains unclear. We examined the association between shorter leukocyte telomere length (LTL) and incident AF. METHODS AND RESULTS: We included AF-free participants from the observational Framingham Heart Study Offspring cohort from 1995 to 1998, who had LTL measurements...
November 14, 2017: Journal of the American Heart Association
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