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https://www.readbyqxmd.com/read/28099038/an-exome-sequencing-study-to-assess-the-role-of-rare-genetic-variation-in-pulmonary-fibrosis
#1
Slavé Petrovski, Jamie L Todd, Michael T Durheim, Quanli Wang, Jason W Chien, Fran L Kelly, Courtney Frankel, Caroline M Mebane, Zhong Ren, Joshua Bridgers, Thomas J Urban, Colin D Malone, Ashley Finlen Copeland, Christie Brinkley, Andrew S Allen, Thomas O'Riordan, John G McHutchison, Scott M Palmer, David B Goldstein
RATIONALE: Idiopathic pulmonary fibrosis (IPF) is an increasingly recognized, often fatal lung disease of unknown etiology. OBJECTIVES: The aim of this study was to use whole-exome sequencing to improve our understanding of the genetic architecture of pulmonary fibrosis. METHODS: We performed a case-control exome-wide collapsing analysis including 262 unrelated individuals with pulmonary fibrosis; clinically classified as IPF according to ATS/ERS/JRS/ALAT guidelines (81...
January 18, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28096444/single-molecule-fret-rosetta-reveals-rna-structural-rearrangements-during-human-telomerase-catalysis
#2
Joseph W Parks, Kalli Kappel, Rhiju Das, Michael D Stone
Maintenance of telomeres by telomerase permits continuous proliferation of rapidly dividing cells, including the majority of human cancers. Despite its direct biomedical significance, the architecture of the human telomerase complex remains unknown. Generating homogeneous telomerase samples has presented a significant barrier to developing improved structural models. Here we pair single-molecule Förster resonance energy transfer (smFRET) measurements with Rosetta modeling to map the conformations of the essential telomerase RNA core domain within the active ribonucleoprotein...
February 2017: RNA
https://www.readbyqxmd.com/read/28068329/the-primacy-of-nf1-loss-as-the-driver-of-tumorigenesis-in-neurofibromatosis-type-1-associated-plexiform-neurofibromas
#3
A Pemov, H Li, R Patidar, N F Hansen, S Sindiri, S W Hartley, J S Wei, A Elkahloun, S C Chandrasekharappa, J F Boland, S Bass, J C Mullikin, J Khan, B C Widemann, M R Wallace, D R Stewart
Neurofibromatosis type 1 (NF1) is a common tumor-predisposition disorder due to germline mutations in the tumor suppressor gene NF1. A virtually pathognomonic finding of NF1 is the plexiform neurofibroma (PN), a benign, likely congenital tumor that arises from bi-allelic inactivation of NF1. PN can undergo transformation to a malignant peripheral nerve sheath tumor, an aggressive soft-tissue sarcoma. To better understand the non-NF1 genetic contributions to PN pathogenesis, we performed whole-exome sequencing, RNASeq profiling and genome-wide copy-number determination for 23 low-passage Schwann cell cultures established from surgical PN material with matching germline DNA...
January 9, 2017: Oncogene
https://www.readbyqxmd.com/read/28064387/the-role-of-histone-modifications-and-telomere-alterations-in-the-pathogenesis-of-diffuse-gliomas-in-adults-and-children
#4
REVIEW
Julieann Lee, D A Solomon, Tarik Tihan
Genetic profiling is an increasingly useful tool for sub-classification of gliomas in adults and children. Specific gene mutations, structural rearrangements, DNA methylation patterns, and gene expression profiles are now recognized to define molecular subgroups of gliomas that arise in distinct anatomic locations and patient age groups, and also provide a better prediction of clinical outcomes for glioma patients compared to histologic assessment alone. Understanding the role of these distinctive genetic alterations in gliomagenesis is also important for the development of potential targeted therapeutic interventions...
January 7, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28058238/sedentary-behavior-physical-activity-and-cardiorespiratory-fitness-on-leukocyte-telomere-length
#5
Meghan K Edwards, Paul D Loprinzi
Background: Emerging work is starting to investigate the cumulative effects of moderate-to-vigorous physical activity (MVPA), sedentary behavior and cardiorespiratory fitness on health. The objective of this study was to examine the cumulative and independent associations of MVPA, sedentary behavior and cardiorespiratory fitness on leukocyte telomere length (LTL). Methods: Data from the 1999-2002 National Health and Nutrition Examination Survey (NHANES) were used (N = 1868 adults 20+ years); analyzed in 2016...
2017: Health Promotion Perspectives
https://www.readbyqxmd.com/read/28055114/quantitative-analysis-of-cellular-senescence-in-culture-and-in-vivo
#6
Jing Zhao, Heike Fuhrmann-Stroissnigg, Aditi U Gurkar, Rafael R Flores, Akaitz Dorronsoro, Donna B Stolz, Claudette M St Croix, Laura J Niedernhofer, Paul D Robbins
Cellular senescence refers to the irreversible growth arrest of normally dividing cells in response to various types of stress. Cellular senescence is induced by telomere shortening due to repeated cell division, which causes a DNA damage response, as well as genotoxic, oxidative, and inflammatory stress. Strong mitogenic signaling, such as oncogene activation, also drives cells into a senescent state. Senescent cells express a specific subset of genes, termed the senescence-associated secretory phenotype (SASP), including pro-inflammatory factors, growth factors, and matrix metalloproteinases, which together promote non-cell autonomous, secondary senescence...
January 5, 2017: Current Protocols in Cytometry
https://www.readbyqxmd.com/read/28052260/telomere-recognition-and-assembly-mechanism-of-mammalian-shelterin
#7
Fabian Erdel, Katja Kratz, Smaranda Willcox, Jack D Griffith, Eric C Greene, Titia de Lange
Shelterin is a six-subunit protein complex that plays crucial roles in telomere length regulation, protection, and maintenance. Although several shelterin subunits have been studied in vitro, the biochemical properties of the fully assembled shelterin complex are not well defined. Here, we characterize shelterin using ensemble biochemical methods, electron microscopy, and single-molecule imaging to determine how shelterin recognizes and assembles onto telomeric repeats. We show that shelterin complexes can exist in solution and primarily locate telomeric DNA through a three-dimensional diffusive search...
January 3, 2017: Cell Reports
https://www.readbyqxmd.com/read/28050263/peculiarities-of-yeasts-and-human-telomerase-rnas-processing
#8
M P Rubtsova, D P Vasilkova, Yu V Naraykina, O A Dontsova
Telomerase is one of the major components of the telomeres -- linear eukaryotic chromosome ends - maintenance system. Linear chromosomes are shortened during each cell division due to the removal of the primer used for DNA replication. Special repeated telomere sequences at the very ends of linear chromosomes prevent the deletion of genome information caused by primer removal. Telomeres are shortened at each replication round until it becomes critically short and is no longer able to protect the chromosome in somatic cells...
October 2016: Acta Naturae
https://www.readbyqxmd.com/read/28046023/a-model-to-investigate-single-strand-dna-responses-in-g1-human-cells-via-a-telomere-targeted-nuclease-deficient-crispr-cas9-system
#9
Remco P Crefcoeur, Omar Zgheib, Thanos D Halazonetis
DNA replication stress has the potential to compromise genomic stability and, therefore, cells have developed elaborate mechanisms to detect and resolve problems that may arise during DNA replication. The presence of single-stranded DNA (ssDNA) is often associated with DNA replication stress and serves as a signal for both checkpoint and repair responses. In this study, we exploited a CRISPR-Cas9 system to induce regions of ssDNA in the genome. Specifically, single-guide RNAs bearing sequence complementarity to human telomeric repeats, were used to target nuclease-deficient Cas9 (dCas9) to telomeres...
2017: PloS One
https://www.readbyqxmd.com/read/28039025/common-variants-of-human-tert-and-terc-genes-and-susceptibility-to-sporadic-alzheimers-disease
#10
D Scarabino, E Broggio, G Gambina, F Pelliccia, R M Corbo
Studies investigating telomere length in association with cognitive decline, dementia, and sporadic Alzheimer's disease (AD) have frequently found shorter telomeres to be associated with the development of AD and telomerase expression with pathological processes in AD. Human telomerase is constituted by two components: the telomerase reverse transcriptase (TERT) and the telomerase RNA component (TERC). Genetic variation at the two loci has been investigated in relation to telomere length, longevity, and common diseases of advanced age, but not in relation to AD...
December 27, 2016: Experimental Gerontology
https://www.readbyqxmd.com/read/28038469/polyunsaturated-fatty-acids-ameliorate-aging-via-redox-telomere-antioncogene-axis
#11
Jingnan Chen, Yan Wei, Xinyu Chen, Jingjing Jiao, Yu Zhang
Polyunsaturated fatty acids (PUFA), a group of nourishing and health-promoting nutrients, ameliorate age-related chronic diseases. However, how PUFA especially n-3 PUFA exert anti-aging functions remains poorly understood. Here we link fish oil, docosahexaenoic acid (DHA) and arachidonic acid (AA) to the aging etiology via a redox-telomere-antioncogene axis based on D-galactose-induced aging mice. Both fish oil and PUFA enhanced hepatic superoxide dismutase (SOD) and catalase activities and cardiac SOD activities within the range of 18%-46%, 26%-65% and 19%-58%, respectively, whereas reduced cerebral monoamine oxidase activity, plasma F2-isoprostane level and cerebral lipid peroxidation level by 56%-90%, 20%-79% and 16%-54%, respectively...
December 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/28029664/depressive-symptoms-and-salivary-telomere-length-in-a-probability-sample-of-middle-aged-and-older-adults
#12
Mark A Whisman, Emily D Richardson
OBJECTIVES: To examine the association between depressive symptoms and salivary telomere length in a probability sample of middle-aged and older adults, and to evaluate age and sex as potential moderators of this association and test whether this association was incremental to potential confounds. METHODS: Participants were 3,609 individuals from the 2008 wave of the Health and Retirement Study. Telomere length assays were performed using quantitative real-time polymerase chain reaction on DNA extracted from saliva samples...
August 30, 2016: Psychosomatic Medicine
https://www.readbyqxmd.com/read/28027556/overexpression-of-tp53-tp53i3-and-birc5-alterations-of-gene-regulation-of-apoptosis-and-aging-of-human-immune-cells-in-a-remote-period-after-radiation-exposure
#13
I N Ilienko, D A Bazyka
OBJECTIVE: To identify a contributive role of changes in gene regulation of apoptosis and telomere length at tran scriptional and translational levels to the formation of radiation induced effects in immune system. PATIENTS AND METHODS: Study groups included 310 Chornobyl (Chornobyl) cleanup workers (dose of external expo sure (360.82 ± 32.3) mSv; age 58.9 ± 0.6 (M ± SD) years) and control (n = 77; age (52.9 ± 0.64) (M ± SD) years). Expression of CD95, phosphatidylserine receptors, bcl2 and p53 proteins was studied by flow cytometry; the relative expression (RQ) of BAX, BIRC5, FASLG, MADD, MAPK14, TP53, TP53I3, TERT, TERF1, TERF2 genes was performed using 7900 HT Fast RT PCR System and TagMan technology...
December 2016: Problemy Radiat︠s︡iĭnoï Medyt︠s︡yny Ta Radiobiolohiï
https://www.readbyqxmd.com/read/28027549/damage-of-chromosoms-under-irradiation-of-human-blood-lymphocytes-and-development-of-bystander-effect
#14
O V Shemetun
OBJECTIVE: the research the distribution of radiation induced damages among chromosomes and their bands in irra diated in vitro human blood lymphocytes and in unirradiated bystander cells.Material and methods of research: cultivation of human peripheral blood lymphocytes by semi micromethod D.A. Hungerford, modeling of radiation induced bystander effect in mixed cultures consisting of irradiated in vitro and non irradiated blood lymphocytes from persons of different gender, GTG staining of metaphase chromosomes and their cytogenetic analysis...
December 2016: Problemy Radiat︠s︡iĭnoï Medyt︠s︡yny Ta Radiobiolohiï
https://www.readbyqxmd.com/read/28027420/sex-differences-in-leukocyte-telomere-length-in-a-free-living-mammal
#15
R L Watson, E J Bird, S Underwood, R V Adams, J Fairlie, K Watt, E Salvo-Chirnside, J G Pilkington, J M Pemberton, T N McNeilly, H Froy, D H Nussey
Mounting evidence suggests that average telomere length reflects previous stress and predicts subsequent survival across vertebrate species. In humans, leukocyte telomere length (LTL) is consistently shorter during adulthood in males than females, although the causes of this sex difference and its generality to other mammals remain unknown. Here we measured LTL in a cross sectional sample of free-living Soay sheep and found shorter telomeres in males than females in later adulthood (>3 years of age), but not in early life...
December 27, 2016: Molecular Ecology
https://www.readbyqxmd.com/read/28007578/nmr-based-model-of-human-telomeric-repeat-g-quadruplex-in-complex-with-2-4-6-triarylpyridine-family-ligand
#16
Abdelaziz Kerkour, Jean-Louis Mergny, Gilmar F Salgado
G-quadruplexes (G4) are one of the several different forms of non-canonical DNA structures that can occur in our genome. Their existence is thought to be implicated in important biological functions such as positive and negative transcription regulation or telomeric extension. The human telomeric sequence G4 formed by repetitive nucleotide sequences (T2AG3) at each chromosome end is an important example of intramolecular G4. Knowing the atomic details for different families of ligands targeting G-quadruplex structures hypothetically found in the telomeric repeat it is an important step for rational drug design...
December 19, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27995640/genotoxic-risk-of-ethyl-paraben-could-be-related-to-telomere-shortening
#17
F Finot, A Kaddour, L Morat, I Mouche, N Zaguia, C Cuceu, D Souverville, S Négrault, O Cariou, A Essahli, N Prigent, J Saul, F Paillard, L Heidingsfelder, P Lafouge, M Al Jawhari, W M Hempel, M El May, B Colicchio, A Dieterlen, E Jeandidier, L Sabatier, J Clements, R M'Kacher
The ability of parabens to promote the appearance of multiple cancer hallmarks in breast epithelium cells provides grounds for regulatory review of the implication of the presence of parabens in human breast tissue. It is well documented that telomere dysfunction plays a significant role in the initiation of genomic instability during carcinogenesis in human breast cancer. In the present study, we evaluated the genotoxic effect of ethyl 4-hydroxybenzoate (ethyl-paraben), with and without metabolic activation (S9), in studies following OECD guidelines...
December 20, 2016: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/27986793/a-snp-based-linkage-map-of-the-arctic-charr-salvelinus-alpinus-genome-provides-insights-into-the-diploidization-process-after-whole-genome-duplication
#18
Cameron M Nugent, Anne A Easton, Joseph D Norman, Moira M Ferguson, Roy G Danzmann
Diploidization, which follows whole genome duplication events, does not occur evenly across the genome. In salmonid fishes, certain pairs of homeologous chromosomes preserve tetraploid loci in higher frequencies towards the telomeres due to residual tetrasomic inheritance. Research suggests this occurs only in homeologous pairs where one chromosome arm has undergone a fusion event. We present a linkage map for Arctic charr (Salvelinus alpinus), a salmonid species with relatively fewer chromosome fusions. Genotype by sequencing identified 19,418 SNPs and a linkage map consisting of 4508 markers was constructed from a subset of high quality SNPs and microsatellite markers that were used to anchor the new map to previous versions...
December 16, 2016: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/27979878/implications-of-telomeres-and-telomerase-in-endometrial-pathology
#19
REVIEW
D K Hapangama, A Kamal, G Saretzki
BACKGROUND: Eukaryotic chromosomal ends are linear and are protected by nucleoprotein complexes known as telomeres. The complex structural anatomy and the diverse functions of telomeres as well as the unique reverse transcriptase enzyme, telomerase that maintains telomeres are under intensive scientific scrutiny. Both are involved in many human diseases including cancer, but also in ageing and chronic disease such as diabetes. Their intricate involvement in many cellular processes and pathways is being dynamically deciphered in many organs including the endometrium...
December 15, 2016: Human Reproduction Update
https://www.readbyqxmd.com/read/27977688/regulation-of-the-human-telomerase-gene-tert-by-telomere-position-effect-over-long-distances-tpe-old-implications-for-aging-and-cancer
#20
Wanil Kim, Andrew T Ludlow, Jaewon Min, Jerome D Robin, Guido Stadler, Ilgen Mender, Tsung-Po Lai, Ning Zhang, Woodring E Wright, Jerry W Shay
Telomerase is expressed in early human development and then becomes silenced in most normal tissues. Because ~90% of primary human tumors express telomerase and generally maintain very short telomeres, telomerase is carefully regulated, particularly in large, long-lived mammals. In the current report, we provide substantial evidence for a new regulatory control mechanism of the rate limiting catalytic protein component of telomerase (hTERT) that is determined by the length of telomeres. We document that normal, young human cells with long telomeres have a repressed hTERT epigenetic status (chromatin and DNA methylation), but the epigenetic status is altered when telomeres become short...
December 2016: PLoS Biology
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