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https://www.readbyqxmd.com/read/28346457/confined-space-facilitates-g-quadruplex-formation
#1
Prakash Shrestha, Sagun Jonchhe, Tomoko Emura, Kumi Hidaka, Masayuki Endo, Hiroshi Sugiyama, Hanbin Mao
Molecular simulations suggest that the stability of a folded macromolecule increases in a confined space due to entropic effects. However, due to the interactions between the confined molecular structure and the walls of the container, clear-cut experimental evidence for this prediction is lacking. Here, using DNA origami nanocages, we show the pure effect of confined space on the property of individual human telomeric DNA G-quadruplexes. We induce targeted mechanical unfolding of the G-quadruplex while leaving the nanocage unperturbed...
March 27, 2017: Nature Nanotechnology
https://www.readbyqxmd.com/read/28346225/long-telomeres-protect-against-age-dependent-cardiac-disease-caused-by-notch1-haploinsufficiency
#2
Christina V Theodoris, Foteini Mourkioti, Yu Huang, Sanjeev S Ranade, Lei Liu, Helen M Blau, Deepak Srivastava
Diseases caused by gene haploinsufficiency in humans commonly lack a phenotype in mice that are heterozygous for the orthologous factor, impeding the study of complex phenotypes and critically limiting the discovery of therapeutics. Laboratory mice have longer telomeres relative to humans, potentially protecting against age-related disease caused by haploinsufficiency. Here, we demonstrate that telomere shortening in NOTCH1-haploinsufficient mice is sufficient to elicit age-dependent cardiovascular disease involving premature calcification of the aortic valve, a phenotype that closely mimics human disease caused by NOTCH1 haploinsufficiency...
March 27, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28343765/human-cardiac-progenitor-cells-with-regenerative-potential-can-be-isolated-and-characterized-from-3d-electro-anatomic-guided-endomyocardial-biopsies
#3
Domenico D'Amario, Antonio Maria Leone, Maria Lucia Narducci, Costantino Smaldone, Dalgisio Lecis, Frediano Inzani, Marco Luciani, Andrea Siracusano, Federica La Neve, Melissa Manchi, Gemma Pelargonio, Francesco Perna, Piergiorgio Bruno, Massimo Massetti, Dario Pitocco, Donato Cappetta, Grazia Esposito, Konrad Urbanek, Antonella De Angelis, Francesco Rossi, Roberto Piacentini, Giulia Angelini, Domenica Donatella Li Puma, Claudio Grassi, Elisa De Paolis, Ettore Capoluongo, Valentina Silvestri, Biagio Merlino, Riccardo Marano, Filippo Crea
AIMS: In the present study, we aimed to develop a percutaneous approach and a reproducible methodology for the isolation and expansion of Cardiac Progenitor Cells (CPCs) from EndoMyocardial Biopsies (EMB) in vivo. Moreover, in an animal model of non-ischemic heart failure (HF), we would like to test whether CPCs obtained by this methodology may engraft the myocardium and differentiate. METHODS AND RESULTS: EMB were obtained using a preformed sheath and a disposable bioptome, advanced via right femoral vein in 12 healthy mini pigs, to the right ventricle...
March 1, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28342451/tert-promoter-mutations-in-telomere-biology
#4
REVIEW
Barbara Heidenreich, Rajiv Kumar
Telomere repeats at chromosomal ends, critical to genome integrity, are maintained through an elaborate network of proteins and pathways. Shelterin complex proteins shield telomeres from induction of DNA damage response to overcome end protection problem. A specialized ribonucleic protein, telomerase, maintains telomere homeostasis through repeat addition to counter intrinsic shortcomings of DNA replication that leads to gradual sequence shortening in successive mitoses. The biogenesis and recruitment of telomerase composed of telomerase reverse transcriptase (TERT) subunit and an RNA component, takes place through the intricate machinery that involves an elaborate number of molecules...
January 2017: Mutation Research
https://www.readbyqxmd.com/read/28342200/telomere-length-is-a-critical-determinant-for-survival-in-multiple-myeloma
#5
Sam Hyatt, Rhiannon E Jones, Nicole H Heppel, Julia W Grimstead, Chris Fegan, Graham H Jackson, Robert Hills, James M Allan, Guy Pratt, Chris Pepper, Duncan M Baird
The variable clinical outcomes of Multiple Myeloma (MM) patients are incompletely defined by current prognostication tools. We examined the clinical utility of high-resolution telomere length analysis as a prognostic marker in MM. Cohort stratification, using a previously determined length threshold for telomere dysfunction, revealed that patients with short telomeres had a significantly shorter overall survival (P < 0·0001; HR = 3·4). Multivariate modelling using forward selection identified International Staging System (ISS) stage as the most important prognostic factor, followed by age and telomere length...
March 24, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28341538/the-differential-impact-of-oxytocin-receptor-gene-in-violence-exposed-boys-and-girls
#6
Livia C Merrill, Christopher W Jones, Stacy S Drury, Katherine P Theall
Childhood violence exposure is a prevalent public health problem. Understanding the lasting impact of violence requires an enhanced appreciation for the complex effects of violence across behavioral, physiologic, and molecular outcomes. This subject matched, cross-sectional study of 80 children explored the impact of violence exposure across behavioral, physiologic, and cellular outcomes. Externalizing behavior, diurnal cortisol rhythm, and telomere length (TL) were examined in a community recruited cohort of Black youth...
March 21, 2017: International Journal of Developmental Neuroscience
https://www.readbyqxmd.com/read/28341421/mutations-evolution-and-the-central-role-of-a-self-defined-fitness-function-in-the-initiation-and-progression-of-cancer
#7
Robert A Gatenby, Joel Brown
The origin and progression of cancer is widely viewed as "somatic evolution" driven by the accumulation of random genetic changes. This theoretical model, however, neglects fundamental conditions for evolution by natural selection, which include competition for survival and a local environmental context. Recent observations that the mutational burden in different cancers can vary by 2 orders of magnitude and that multiple mutations, some of which are "oncogenic," are observed in normal tissue suggests these neglected Darwinian dynamics may play a critical role in modifying the evolutionary consequences of molecular events...
March 21, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28340313/linkage-between-mitochondrial-genome-alterations-telomere-length-and-aging-population
#8
Egija Zole, Krista Zadinane, Liana Pliss, Renate Ranka
We studied telomere length (TL) and mitochondrial DNA (mtDNA) copy number variations in individuals from Latvian Caucasian population in different age groups. We showed a positive correlation between TL and mtDNA copy number in individuals of up to 90 years of age; however, this correlation was not observed in the 90-100 years age group. While TL shortened with age and mtDNA content decreased with increasing age, in this study it was observed that mtDNA copy number in nonagenarians was slightly higher than in the 60-89 years age group...
March 24, 2017: Mitochondrial DNA. Part A. DNA Mapping, Sequencing, and Analysis
https://www.readbyqxmd.com/read/28339618/telomere-length-oxidative-stress-inflammation-and-bdnf-levels-in-siblings-of-patients-with-bipolar-disorder-implications-for-accelerated-cellular-aging
#9
Mirela Paiva Vasconcelos-Moreno, Gabriel Rodrigo Fries, Carolina Gubert, Bárbara Tietböhl Martins Quadros Dos Santos, Adam Fijtman, Juliana Sartori, Pamela Ferrari, Lucas Kich Grun, Mariana Migliorini Parisi, Fátima Theresinha Costa Rodrigues Guma, Florencia Maria Barbé-Tuana, Flávio Kapczinski, Adriane Ribeiro Rosa, Lakshmi N Yatham, Marcia Kauer-Sant'Anna
Background: Growing evidence supports the existence of neurobiological trait abnormalities in individuals at genetic risk for bipolar disorder. The aim of this study was to examine potential differences in brain-derived neurotrophic factor, cytokines, oxidative stress, and telomere length markers between patients with bipolar disorder, their siblings, and healthy controls. Methods: Thirty-six patients with bipolar disorder type I, 39 siblings, and 44 healthy controls were assessed...
January 30, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28338837/associations-of-leukocyte-telomere-length-with-aerobic-and-muscular-fitness-in-young-adults
#10
Dylan M Williams, Jessica L Buxton, Marko T Kantomaa, Tuija H Tammelin, Alexandra I F Blakemore, Marjo-Riitta Järvelin
Decline in both telomere length and physical fitness over the life course may contribute to increased risk of several chronic diseases. The relationship between telomere length and aerobic and muscular fitness is not well characterized. We examined whether there are cross-sectional associations of mean relative leukocyte telomere length (LTL) with objective measures of aerobic fitness, muscle strength, and muscle endurance, using data on 31-year-old participants of the Northern Finland Birth Cohort 1966 (n = 4,952-5,205, varying by exposure-outcome analysis)...
March 1, 2017: American Journal of Epidemiology
https://www.readbyqxmd.com/read/28338779/telomere-length-and-ccl11-levels-are-associated-with-gray-matter-volume-and-episodic-memory-performance-in-schizophrenia-evidence-of-pathological-accelerated-aging
#11
Leticia Sanguinetti Czepielewski, Raffael Massuda, Bruna Panizzutti, Lucas Kich Grun, Florencia María Barbé-Tuana, Antonio Lucio Teixeira, Deanna M Barch, Clarissa S Gama
Schizophrenia (SZ) is associated with increased somatic morbidity and mortality, in addition to cognitive impairments similar to those seen in normal aging, which may suggest that pathological accelerated aging occurs in SZ. Therefore, we aim to evaluate the relationships of age, telomere length (TL), and CCL11 (aging and inflammatory biomarkers, respectively), gray matter (GM) volume and episodic memory performance in individuals with SZ compared to healthy controls (HC). One hundred twelve participants (48 SZ and 64 HC) underwent clinical and memory assessments, structural MRI, and had their peripheral blood drawn for biomarkers analysis...
February 22, 2017: Schizophrenia Bulletin
https://www.readbyqxmd.com/read/28338178/the-involvement-of-senescence-induced-by-the-telomere-shortness-in-the-decline-of-osteogenic-differentiation-in-bmscs
#12
C Li, G-J Wei, L Xu, J-S Rong, S-Q Tao, Y-S Wang
OBJECTIVE: BMSC (Bone marrow mesenchymal stem cells) is an important seed cell for the repair of bone and cartilage defect in the tissue engineering. The proliferation rate and differentiation capacity of BMSCs from the old donors were less than that from young donors; however, the related mechanism remained unclear. MATERIALS AND METHODS: Sprague Dawley (SD) rats BMSCs were cultured and treated. Hydrogen peroxide (H2O2) and continual passage of BMSCs were performed to induce senescence...
March 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28337032/drosophila-dyskerin-is-required-for-somatic-stem-cell-homeostasis
#13
Rosario Vicidomini, Arianna Petrizzo, Annamaria di Giovanni, Laura Cassese, Antonella Anna Lombardi, Caterina Pragliola, Maria Furia
Drosophila represents an excellent model to dissect the roles played by the evolutionary conserved family of eukaryotic dyskerins. These multifunctional proteins are involved in the formation of H/ACA snoRNP and telomerase complexes, both involved in essential cellular tasks. Since fly telomere integrity is guaranteed by a different mechanism, we used this organism to investigate the specific role played by dyskerin in somatic stem cell maintenance. To this aim, we focussed on Drosophila midgut, a hierarchically organized and well characterized model for stemness analysis...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28334887/avoidance-of-apobec3b-induced-mutation-by-error-free-lesion-bypass
#14
James I Hoopes, Amber L Hughes, Lauren A Hobson, Luis M Cortez, Alexander J Brown, Steven A Roberts
APOBEC cytidine deaminases mutate cancer genomes by converting cytidines into uridines within ssDNA during replication. Although uracil DNA glycosylases limit APOBEC-induced mutation, it is unknown if subsequent base excision repair (BER) steps function on replication-associated ssDNA. Hence, we measured APOBEC3B-induced CAN1 mutation frequencies in yeast deficient in BER endonucleases or DNA damage tolerance proteins. Strains lacking Apn1, Apn2, Ntg1, Ntg2 or Rev3 displayed wild-type frequencies of APOBEC3B-induced canavanine resistance (CanR)...
March 10, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334836/trypanosoma-brucei-rap1-maintains-telomere-and-subtelomere-integrity-by-suppressing-terra-and-telomeric-rna-dna-hybrids
#15
Vishal Nanavaty, Ranjodh Sandhu, Sanaa E Jehi, Unnati M Pandya, Bibo Li
Trypanosoma brucei causes human African trypanosomiasis and regularly switches its major surface antigen, VSG, thereby evading the host's immune response. VSGs are monoallelically expressed from subtelomeric expression sites (ESs), and VSG switching exploits subtelomere plasticity. However, subtelomere integrity is essential for T. brucei viability. The telomeric transcript, TERRA, was detected in T. brucei previously. We now show that the active ES-adjacent telomere is transcribed. We find that TbRAP1, a telomere protein essential for VSG silencing, suppresses VSG gene conversion-mediated switching...
March 16, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334827/yeast-hrq1-shares-structural-and-functional-homology-with-the-disease-linked-human-recq4-helicase
#16
Cody M Rogers, Joseph Che-Yen Wang, Hiroki Noguchi, Tsuyoshi Imasaki, Yuichiro Takagi, Matthew L Bochman
The five human RecQ helicases participate in multiple processes required to maintain genome integrity. Of these, the disease-linked RecQ4 is the least studied because it poses many technical challenges. We previously demonstrated that the yeast Hrq1 helicase displays similar functions to RecQ4 in vivo, and here, we report the biochemical and structural characterization of these enzymes. In vitro, Hrq1 and RecQ4 are DNA-stimulated ATPases and robust helicases. Further, these activities were sensitive to DNA sequence and structure, with the helicases preferentially unwinding D-loops...
February 25, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334768/repair-of-uv-induced-dna-lesions-in-natural-saccharomyces-cerevisiae-telomeres-is-moderated-by-sir2-and-sir3-and-inhibited-by-yku-sir4-interaction
#17
Laetitia Guintini, Maxime Tremblay, Martin Toussaint, Annie D'Amours, Ralf E Wellinger, Raymund J Wellinger, Antonio Conconi
Ultraviolet light (UV) causes DNA damage that is removed by nucleotide excision repair (NER). UV-induced DNA lesions must be recognized and repaired in nucleosomal DNA, higher order structures of chromatin and within different nuclear sub-compartments. Telomeric DNA is made of short tandem repeats located at the ends of chromosomes and their maintenance is critical to prevent genome instability. In Saccharomyces cerevisiae the chromatin structure of natural telomeres is distinctive and contingent to telomeric DNA sequences...
February 21, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334750/ctc1-mediated-c-strand-fill-in-is-an-essential-step-in-telomere-length-maintenance
#18
Xuyang Feng, Shih-Jui Hsu, Christopher Kasbek, Mary Chaiken, Carolyn M Price
To prevent progressive telomere shortening as a result of conventional DNA replication, new telomeric DNA must be added onto the chromosome end. The de novo DNA synthesis involves elongation of the G-rich strand of the telomere by telomerase. In human cells, the CST complex (CTC1-STN1-TEN1) also functions in telomere replication. CST first aids in duplication of the telomeric dsDNA. Then after telomerase has extended the G-rich strand, CST facilitates fill-in synthesis of the complementary C-strand. Here, we analyze telomere structure after disruption of human CTC1 and demonstrate that functional CST is essential for telomere length maintenance due to its role in mediating C-strand fill-in...
February 23, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334717/a-tandemly-arranged-pattern-of-two-5s-rdna-arrays-in-amolops-mantzorum-anura-ranidae
#19
Ting Liu, Menghuan Song, Yun Xia, Xiaomao Zeng
In an attempt to extend the knowledge of the 5S rDNA organization in anurans, the 5S rDNA sequences of Amolops mantzorum were isolated, characterized, and mapped by FISH. Two forms of 5S rDNA, type I (209 bp) and type II (about 870 bp), were found in specimens investigated from various populations. Both of them contained a 118-bp coding sequence, readily differentiated by their non-transcribed spacer (NTS) sizes and compositions. Four probes (the 5S rDNA coding sequences, the type I NTS, the type II NTS, and the entire type II 5S rDNA sequences) were respectively labeled with TAMRA or digoxigenin to hybridize with mitotic chromosomes for samples of all localities...
March 24, 2017: Cytogenetic and Genome Research
https://www.readbyqxmd.com/read/28334706/repetitive-dna-a-versatile-tool-for-karyotyping-in-festuca-pratensis-huds
#20
Anna Křivánková, David Kopecký, Štěpán Stočes, Jaroslav Doležel, Eva Hřibová
FISH is a useful method to identify individual chromosomes in a karyotype and to discover their structural changes accompanying genome evolution and speciation. DNA probes for FISH should be chromosome specific and/or exhibit specific patterns of distribution along each chromosome. Such probes are not available in many plants including meadow fescue (Festuca pratensis Huds.), an important forage grass species. In the present study, various DNA repeats identified in Illumina shotgun sequences specific to chromosome 4F of F...
March 24, 2017: Cytogenetic and Genome Research
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