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Telomere d

Ke-Zheng Dai, James C Ryan, Christian Naper, John T Vaage
Early studies indicate that rats may have a repertoire of MHC class Ib-reactive Ly49 stimulatory receptors capable of mounting memory-like NK cell alloresponses. In this article, we provide molecular and functional evidence for this assumption. Pairs of Ly49 receptors with sequence similarities in the lectin-like domains, but with opposing signaling functions, showed specificity for ligands with class Ia-like structural features encoded from the first telomeric MHC class Ib gene cluster, RT1-CE , which is syntenic with the H2-D/H2-L/H2-Q cluster in mice...
March 12, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Sylwia Kedziora, Vamsi K Gali, Rosemary H C Wilson, Kate R M Clark, Conrad A Nieduszynski, Shin-Ichiro Hiraga, Anne D Donaldson
The Rif1 protein negatively regulates telomeric TG repeat length in the budding yeast Saccharomyces cerevisiae, but how it prevents telomere over-extension is unknown. Rif1 was recently shown to control DNA replication by acting as a Protein Phosphatase 1 (PP1)-targeting subunit. Therefore, we investigated whether Rif1 controls telomere length by targeting PP1 activity. We find that a Rif1 mutant defective for PP1 interaction causes a long-telomere phenotype, similar to that of rif1Δ cells. Tethering PP1 at a specific telomere partially substitutes for Rif1 in limiting TG repeat length, confirming the importance of PP1 in telomere length control...
February 26, 2018: Nucleic Acids Research
Saumya R Bollam, Michael E Berens, Harshil D Dhruv
PURPOSE OF REVIEW: High-throughput genomic sequencing has identified alterations in the gene encoding human telomerase reverse transcriptase (TERT) as points of interest for elucidating the oncogenic mechanism of multiple different cancer types, including gliomas. In gliomas, the TERT promoter mutation (TPM) and resultant overexpression of TERT are observed mainly in the most aggressive (primary glioblastoma/grade IV astrocytoma) and the least aggressive (grade II oligodendroglioma) cases...
March 10, 2018: Current Neurology and Neuroscience Reports
Quinn A Conklin, Brandon G King, Anthony P Zanesco, Jue Lin, Anahita B Hamidi, Jennifer J Pokorny, María Jesús Álvarez-López, Marta Cosín-Tomás, Colin Huang, Perla Kaliman, Elissa S Epel, Clifford D Saron
A growing body of evidence suggests that meditation training may have a range of salubrious effects, including improved telomere regulation. Telomeres and the enzyme telomerase interact with a variety of molecular components to regulate cell-cycle signaling cascades, and are implicated in pathways linking psychological stress to disease. We investigated the effects of intensive meditation practice on these biomarkers by measuring changes in telomere length (TL), telomerase activity (TA), and telomere-related gene (TRG) expression during a 1-month residential Insight meditation retreat...
March 5, 2018: Brain, Behavior, and Immunity
D D Zhdanov, Yu A Gladilina, M V Pokrovskaya, S S Aleksandrova, D V Grishin, O V Podobed, N N Sokolov
The effect of apoptotic endonuclease EndoG on alternative splicing of mRNA of human telomerase catalytic subunit hTERT (human telomerase reverse transcriptase) and telomerase activity in normal human lymphocytes were studied. Human CD4+ , CD8+ , B, and NK cells were transfected with a plasmid pEndoG-GFP containing EndoG gene or control plasmid pGFP. The levels of mRNA of EndoG or hTERT splicing variants were analyzed by real-time PCR. Protein content was assessed by Western blotting. Telomerase activity was measured by the telomere repeats amplification protocol...
March 5, 2018: Bulletin of Experimental Biology and Medicine
M K Islam, P J M Jackson, D E Thurston, K M Rahman
We report a series of novel methylene-linked bis-phenylbenzimidazoles intercalators that stabilize telomeric DNA/RNA hybrid (tDRH) structures by up to 7.2 °C at a 1 μM ligand concentration while having negligible affinity for DNA/DNA duplexes, although with a low affinity for quadruplex DNA. We have used molecular modelling studies to rationalize this selectivity, concluding that the methylene spacer between the terminal benzimidazole and phenylene moieties plays a key role in facilitating the bis-intercalating process...
March 2, 2018: Organic & Biomolecular Chemistry
D Valerio, A Luddi, V De Leo, D Labella, S Longobardi, P Piomboni
STUDY QUESTION: Are cohesins SA1/SA2 and the NAD-dependent deacetylase SIRT1 involved in telomere homeostasis of cumulus cells and thus eligible as biomarkers of follicular physiology and ovarian aging? SUMMARY ANSWER: SA1/SA2 cohesins and SIRT1 are associated with telomere length in cumulus cells and may be eligible biomarkers of follicular physiology and ovarian aging. WHAT IS KNOWN ALREADY: In somatic cells, cohesins SA1/SA2 mediate sister chromatid cohesion at the telomere termini (for SA1) and along chromatid arms (for SA2)...
February 22, 2018: Human Reproduction
Jun-Qin Qiao, Zhao-Ming Cao, Chao Liang, Hong-Juan Chen, Wei-Juan Zheng, Hong-Zhen Lian
Polymorphism is inherent for G-quadruplexes (G4s), and the different structural forms are important for the participation in different biological functions of telomeres. A lot of progress has been made in the exploration of G4 polymorphism. However, quick separation and reliable assessment methods for different conformations of G4 are still very few. In this work, the polymorphism of three sequences d[(G3 T)3 G3 ], d[(G3 C)3 G3 ] and d[(G3 T)4 ] annealed in six different solutions were investigated by means of reversed-phase high performance liquid chromatography (RP-HPLC), liquid chromatography-mass spectrometry (LC-MS), fluorescence spectroscopy, circular dichroism spectroscopy, together with native-polyacrylamide gel electrophoresis...
February 12, 2018: Journal of Chromatography. A
Kumar Padmapriya, Ritu Barthwal
Plant derived small molecules, which interact with and stabilize G-quadruplex DNA, act as inhibitors of telomere elongation and oncogene expression in humans. The inhibition of telomerase enzyme has immense potential since it is over expressed in most cancer cells. Interaction of palmatine, an antitumor alkaloid, to parallel G-quadruplex DNA, [d(TTGGGGT)]4 and [d(TTAGGGT)]4 , has been investigated using Nuclear Magnetic Resonance (NMR), fluorescence and Circular Dichroism (CD) spectroscopy. Titrations were monitored by recording1 H and31 P NMR spectra and solution structure of palmatine-[d(TTGGGGT)]4 complex was obtained by restrained Molecular Dynamics (rMD) simulations using distance restraints from 2D NOESY spectra...
February 20, 2018: Biochimie
Shankar Shastry, Olga Steinberg-Neifach, Neal Lue, Michael D Stone
Telomerase is a specialized enzyme that maintains telomere length by adding DNA repeats to chromosome ends. The catalytic protein subunit of telomerase utilizes the integral telomerase RNA to direct telomere DNA synthesis. The telomerase essential N-terminal (TEN) domain is required for enzyme function; however, the precise mechanism of the TEN domain during catalysis is not known. We report a single-molecule study of dynamic TEN-induced conformational changes in its nucleic acid substrates. The TEN domain from the yeast Candida parapsilosis (Cp) exhibits a strong binding preference for double-stranded nucleic acids, with particularly high affinity for an RNA-DNA hybrid mimicking the template-product complex...
February 21, 2018: Nucleic Acids Research
M Vera-Rodriguez, A Diez-Juan, J Jimenez-Almazan, S Martinez, R Navarro, V Peinado, A Mercader, M Meseguer, D Blesa, I Moreno, D Valbuena, C Rubio, C Simon
STUDY QUESTION: What is the origin and composition of cell-free DNA in human embryo spent culture media? SUMMARY ANSWER: Cell-free DNA from human embryo spent culture media represents a mix of maternal and embryonic DNA, and the mixture can be more complex for mosaic embryos. WHAT IS KNOWN ALREADY: In 2016, ~300 000 human embryos were chromosomally and/or genetically analyzed using preimplantation genetic testing for aneuploidies (PGT-A) or monogenic disorders (PGT-M) before transfer into the uterus...
February 20, 2018: Human Reproduction
Jonathan K Alder, Vidya Sagar Hanumanthu, Margaret A Strong, Amy E DeZern, Susan E Stanley, Clifford M Takemoto, Ludmilla Danilova, Carolyn D Applegate, Stephen G Bolton, David W Mohr, Robert A Brodsky, James F Casella, Carol W Greider, J Brooks Jackson, Mary Armanios
Telomere length (TL) predicts the onset of cellular senescence in vitro but the diagnostic utility of TL measurement in clinical settings is not fully known. We tested the value of TL measurement by flow cytometry and FISH (flowFISH) in patients with mutations in telomerase and telomere maintenance genes. TL had a discrete and reproducible normal range with definable upper and lower boundaries. While TL above the 50th age-adjusted percentile had a 100% negative predictive value for clinically relevant mutations, the lower threshold in mutation carriers was age-dependent, and adult mutation carriers often overlapped with the lowest decile of controls...
February 20, 2018: Proceedings of the National Academy of Sciences of the United States of America
Benilson S Rodrigues, Rafael Kretschmer, Ricardo J Gunski, Analia D V Garnero, Patricia C M O'Brien, Malcolm Ferguson-Smith, Edivaldo H C de Oliveira
Tyrannidae is the largest family of Passeriformes in the Neotropical region. However, despite an interesting chromosomal diversity, there are only few cytogenetic studies of this family, and most of these are based on conventional cytogenetics. Hence, we analyzed here the chromosomal diversity and karyotypical evolution of this group by chromosome painting in 3 different species - Pitangus sulphuratus, Serpophaga subcristata, and Satrapa icterophrys - and make comparisons with previous data. In addition to chromosome painting with Gallus gallus (GGA) and Leucopternis albicollis (LAL) probes, karyotypes were analyzed by conventional staining, C-banding, and FISH with 18S rDNA and telomeric probes...
February 21, 2018: Cytogenetic and Genome Research
Kumar Padmapriya, Ritu Barthwal
Plant derived small molecules, which interact with and stabilize G-quadruplex DNA, act as inhibitors of telomere elongation and oncogene expression in humans. The inhibition of telomerase enzyme has immense potential since it is over expressed in most cancer cells. Interaction of palmatine, an antitumor alkaloid, to parallel G-quadruplex DNA, [d(TTGGGGT)]4 and [d(TTAGGGT)]4 , has been investigated using Nuclear Magnetic Resonance (NMR), fluorescence and Circular Dichroism (CD) spectroscopy. Titrations were monitored by1 H and31 P NMR spectra and solution structure of palmatine-[d(TTGGGGT)]4 complex was obtained by restrained Molecular Dynamics (rMD) simulations using distance restraints from 2D NOESY spectra...
February 16, 2018: Biochimie
Yun J Sung, Thomas W Winkler, Lisa de Las Fuentes, Amy R Bentley, Michael R Brown, Aldi T Kraja, Karen Schwander, Ioanna Ntalla, Xiuqing Guo, Nora Franceschini, Yingchang Lu, Ching-Yu Cheng, Xueling Sim, Dina Vojinovic, Jonathan Marten, Solomon K Musani, Changwei Li, Mary F Feitosa, Tuomas O Kilpeläinen, Melissa A Richard, Raymond Noordam, Stella Aslibekyan, Hugues Aschard, Traci M Bartz, Rajkumar Dorajoo, Yongmei Liu, Alisa K Manning, Tuomo Rankinen, Albert Vernon Smith, Salman M Tajuddin, Bamidele O Tayo, Helen R Warren, Wei Zhao, Yanhua Zhou, Nana Matoba, Tamar Sofer, Maris Alver, Marzyeh Amini, Mathilde Boissel, Jin Fang Chai, Xu Chen, Jasmin Divers, Ilaria Gandin, Chuan Gao, Franco Giulianini, Anuj Goel, Sarah E Harris, Fernando Pires Hartwig, Andrea R V R Horimoto, Fang-Chi Hsu, Anne U Jackson, Mika Kähönen, Anuradhani Kasturiratne, Brigitte Kühnel, Karin Leander, Wen-Jane Lee, Keng-Hung Lin, Jian 'an Luan, Colin A McKenzie, He Meian, Christopher P Nelson, Rainer Rauramaa, Nicole Schupf, Robert A Scott, Wayne H H Sheu, Alena Stančáková, Fumihiko Takeuchi, Peter J van der Most, Tibor V Varga, Heming Wang, Yajuan Wang, Erin B Ware, Stefan Weiss, Wanqing Wen, Lisa R Yanek, Weihua Zhang, Jing Hua Zhao, Saima Afaq, Tamuno Alfred, Najaf Amin, Dan Arking, Tin Aung, R Graham Barr, Lawrence F Bielak, Eric Boerwinkle, Erwin P Bottinger, Peter S Braund, Jennifer A Brody, Ulrich Broeckel, Claudia P Cabrera, Brian Cade, Yu Caizheng, Archie Campbell, Mickaël Canouil, Aravinda Chakravarti, Ganesh Chauhan, Kaare Christensen, Massimiliano Cocca, Francis S Collins, John M Connell, Renée de Mutsert, H Janaka de Silva, Stephanie Debette, Marcus Dörr, Qing Duan, Charles B Eaton, Georg Ehret, Evangelos Evangelou, Jessica D Faul, Virginia A Fisher, Nita G Forouhi, Oscar H Franco, Yechiel Friedlander, He Gao, Bruna Gigante, Misa Graff, C Charles Gu, Dongfeng Gu, Preeti Gupta, Saskia P Hagenaars, Tamara B Harris, Jiang He, Sami Heikkinen, Chew-Kiat Heng, Makoto Hirata, Albert Hofman, Barbara V Howard, Steven Hunt, Marguerite R Irvin, Yucheng Jia, Roby Joehanes, Anne E Justice, Tomohiro Katsuya, Joel Kaufman, Nicola D Kerrison, Chiea Chuen Khor, Woon-Puay Koh, Heikki A Koistinen, Pirjo Komulainen, Charles Kooperberg, Jose E Krieger, Michiaki Kubo, Johanna Kuusisto, Carl D Langefeld, Claudia Langenberg, Lenore J Launer, Benjamin Lehne, Cora E Lewis, Yize Li, Sing Hui Lim, Shiow Lin, Ching-Ti Liu, Jianjun Liu, Jingmin Liu, Kiang Liu, Yeheng Liu, Marie Loh, Kurt K Lohman, Jirong Long, Tin Louie, Reedik Mägi, Anubha Mahajan, Thomas Meitinger, Andres Metspalu, Lili Milani, Yukihide Momozawa, Andrew P Morris, Thomas H Mosley, Peter Munson, Alison D Murray, Mike A Nalls, Ubaydah Nasri, Jill M Norris, Kari North, Adesola Ogunniyi, Sandosh Padmanabhan, Walter R Palmas, Nicholette D Palmer, James S Pankow, Nancy L Pedersen, Annette Peters, Patricia A Peyser, Ozren Polasek, Olli T Raitakari, Frida Renström, Treva K Rice, Paul M Ridker, Antonietta Robino, Jennifer G Robinson, Lynda M Rose, Igor Rudan, Charumathi Sabanayagam, Babatunde L Salako, Kevin Sandow, Carsten O Schmidt, Pamela J Schreiner, William R Scott, Sudha Seshadri, Peter Sever, Colleen M Sitlani, Jennifer A Smith, Harold Snieder, John M Starr, Konstantin Strauch, Hua Tang, Kent D Taylor, Yik Ying Teo, Yih Chung Tham, André G Uitterlinden, Melanie Waldenberger, Lihua Wang, Ya X Wang, Wen Bin Wei, Christine Williams, Gregory Wilson, Mary K Wojczynski, Jie Yao, Jian-Min Yuan, Alan B Zonderman, Diane M Becker, Michael Boehnke, Donald W Bowden, John C Chambers, Yii-Der Ida Chen, Ulf de Faire, Ian J Deary, Tõnu Esko, Martin Farrall, Terrence Forrester, Paul W Franks, Barry I Freedman, Philippe Froguel, Paolo Gasparini, Christian Gieger, Bernardo Lessa Horta, Yi-Jen Hung, Jost B Jonas, Norihiro Kato, Jaspal S Kooner, Markku Laakso, Terho Lehtimäki, Kae-Woei Liang, Patrik K E Magnusson, Anne B Newman, Albertine J Oldehinkel, Alexandre C Pereira, Susan Redline, Rainer Rettig, Nilesh J Samani, James Scott, Xiao-Ou Shu, Pim van der Harst, Lynne E Wagenknecht, Nicholas J Wareham, Hugh Watkins, David R Weir, Ananda R Wickremasinghe, Tangchun Wu, Wei Zheng, Yoichiro Kamatani, Cathy C Laurie, Claude Bouchard, Richard S Cooper, Michele K Evans, Vilmundur Gudnason, Sharon L R Kardia, Stephen B Kritchevsky, Daniel Levy, Jeff R O'Connell, Bruce M Psaty, Rob M van Dam, Mario Sims, Donna K Arnett, Dennis O Mook-Kanamori, Tanika N Kelly, Ervin R Fox, Caroline Hayward, Myriam Fornage, Charles N Rotimi, Michael A Province, Cornelia M van Duijn, E Shyong Tai, Tien Yin Wong, Ruth J F Loos, Alex P Reiner, Jerome I Rotter, Xiaofeng Zhu, Laura J Bierut, W James Gauderman, Mark J Caulfield, Paul Elliott, Kenneth Rice, Patricia B Munroe, Alanna C Morrison, L Adrienne Cupples, Dabeeru C Rao, Daniel I Chasman
Genome-wide association analysis advanced understanding of blood pressure (BP), a major risk factor for vascular conditions such as coronary heart disease and stroke. Accounting for smoking behavior may help identify BP loci and extend our knowledge of its genetic architecture. We performed genome-wide association meta-analyses of systolic and diastolic BP incorporating gene-smoking interactions in 610,091 individuals. Stage 1 analysis examined ∼18.8 million SNPs and small insertion/deletion variants in 129,913 individuals from four ancestries (European, African, Asian, and Hispanic) with follow-up analysis of promising variants in 480,178 additional individuals from five ancestries...
March 1, 2018: American Journal of Human Genetics
A Schrader, G Crispatzu, S Oberbeck, P Mayer, S Pützer, J von Jan, E Vasyutina, K Warner, N Weit, N Pflug, T Braun, E I Andersson, B Yadav, A Riabinska, B Maurer, M S Ventura Ferreira, F Beier, J Altmüller, M Lanasa, C D Herling, T Haferlach, S Stilgenbauer, G Hopfinger, M Peifer, T H Brümmendorf, P Nürnberg, K S J Elenitoba-Johnson, S Zha, M Hallek, R Moriggl, H C Reinhardt, M-H Stern, S Mustjoki, S Newrzela, P Frommolt, M Herling
T-cell prolymphocytic leukemia (T-PLL) is a rare and poor-prognostic mature T-cell malignancy. Here we integrated large-scale profiling data of alterations in gene expression, allelic copy number (CN), and nucleotide sequences in 111 well-characterized patients. Besides prominent signatures of T-cell activation and prevalent clonal variants, we also identify novel hot-spots for CN variability, fusion molecules, alternative transcripts, and progression-associated dynamics. The overall lesional spectrum of T-PLL is mainly annotated to axes of DNA damage responses, T-cell receptor/cytokine signaling, and histone modulation...
February 15, 2018: Nature Communications
Nicole M Foley, Graham M Hughes, Zixia Huang, Michael Clarke, David Jebb, Conor V Whelan, Eric J Petit, Frédéric Touzalin, Olivier Farcy, Gareth Jones, Roger D Ransome, Joanna Kacprzyk, Mary J O'Connell, Gerald Kerth, Hugo Rebelo, Luísa Rodrigues, Sébastien J Puechmaille, Emma C Teeling
Understanding aging is a grand challenge in biology. Exceptionally long-lived animals have mechanisms that underpin extreme longevity. Telomeres are protective nucleotide repeats on chromosome tips that shorten with cell division, potentially limiting life span. Bats are the longest-lived mammals for their size, but it is unknown whether their telomeres shorten. Using >60 years of cumulative mark-recapture field data, we show that telomeres shorten with age in Rhinolophus ferrumequinum and Miniopterus schreibersii , but not in the bat genus with greatest longevity, Myotis ...
February 2018: Science Advances
E Vakonaki, K Tsiminikaki, S Plaitis, P Fragkiadaki, D Tsoukalas, I Katsikantami, G Vaki, M N Tzatzarakis, D A Spandidos, A M Tsatsakis
Telomeres are repeated 5'-TTAGGG-3' sequences at the end of chromosomes, which maintain genomic stability. Their length is related to a number of diseases that affect humans. Apart from cancer, cardiovascular diseases, diabetes and other, telomere length has been associated with chronic diseases. Chronic mental illness includes various types of mental disorders with the most common being depression, schizophrenia and stress-anxiety. The aim of this review is to summarize the current state of knowledge on the role of telomeres in these disorders and to compare telomere length variations in patients receiving medication and patients not taking treatment...
February 2018: Biomedical Reports
Miten Jain, Sergey Koren, Karen H Miga, Josh Quick, Arthur C Rand, Thomas A Sasani, John R Tyson, Andrew D Beggs, Alexander T Dilthey, Ian T Fiddes, Sunir Malla, Hannah Marriott, Tom Nieto, Justin O'Grady, Hugh E Olsen, Brent S Pedersen, Arang Rhie, Hollian Richardson, Aaron R Quinlan, Terrance P Snutch, Louise Tee, Benedict Paten, Adam M Phillippy, Jared T Simpson, Nicholas J Loman, Matthew Loose
We report the sequencing and assembly of a reference genome for the human GM12878 Utah/Ceph cell line using the MinION (Oxford Nanopore Technologies) nanopore sequencer. 91.2 Gb of sequence data, representing ∼30× theoretical coverage, were produced. Reference-based alignment enabled detection of large structural variants and epigenetic modifications. De novo assembly of nanopore reads alone yielded a contiguous assembly (NG50 ∼3 Mb). We developed a protocol to generate ultra-long reads (N50 > 100 kb, read lengths up to 882 kb)...
January 29, 2018: Nature Biotechnology
Shenghan Lai, Christopher M Heaphy, Anthony J Rizzo, David D Celentano, Gary Gerstenblith, Ji Li, Richard D Moore, Glenn Treisman, Shaoguang Chen, Parker Foster, Thomas Kickler, Hong Lai
BACKGROUND: Although cocaine use may induce/accelerate HIV-associated comorbidities in HIV-infected individuals on antiretroviral therapy (ART), and that HIV itself may accelerate aging, the issue of whether cocaine use plays a role in HIV-associated aging in HIV-infected cocaine users has not been reported. The goals of this study were (1) to explore factor(s) associated with peripheral blood leukocyte telomere length, a marker of cellular replicative history, and telomere shortening in HIV-infected individuals, and (2) to assess whether cocaine use plays a role in accelerating telomere shortening in cocaine users with HIV infection...
February 2, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
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