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https://www.readbyqxmd.com/read/28221367/transcriptomic-analyses-and-leukocyte-telomere-length-measurement-in-subjects-exposed-to-severe-recent-stressful-life-events
#1
N Lopizzo, S Tosato, V Begni, S Tomassi, N Cattane, M Barcella, G Turco, M Ruggeri, M A Riva, C M Pariante, A Cattaneo
Stressful life events occurring in adulthood have been found able to affect mood and behavior, thus increasing the vulnerability for several stress-related psychiatric disorders. However, although there is plenty of clinical data supporting an association between stressful life events in adulthood and an enhanced vulnerability for psychopathology, the underlying molecular mechanisms are still poorly investigated. Thus, in this study we performed peripheral/whole-genome transcriptomic analyses in blood samples obtained from 53 adult subjects characterized for recent stressful life events occurred within the previous 6 months...
February 21, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28218725/treating-cancer-by-targeting-telomeres-and-telomerase
#2
REVIEW
Marko Ivancich, Zachary Schrank, Luke Wojdyla, Brandon Leviskas, Adijan Kuckovic, Ankita Sanjali, Neelu Puri
Telomerase is expressed in more than 85% of cancer cells. Tumor cells with metastatic potential may have a high telomerase activity, allowing cells to escape from the inhibition of cell proliferation due to shortened telomeres. Human telomerase primarily consists of two main components: hTERT, a catalytic subunit, and hTR, an RNA template whose sequence is complimentary to the telomeric 5'-dTTAGGG-3' repeat. In humans, telomerase activity is typically restricted to renewing tissues, such as germ cells and stem cells, and is generally absent in normal cells...
February 19, 2017: Antioxidants (Basel, Switzerland)
https://www.readbyqxmd.com/read/28217994/structure-of-a-stable-g-hairpin
#3
Martin Gajarsky, Martina Lenarcic Zivkovic, Petr Stadlbauer, Bruno Pagano, Radovan Fiala, Jussara Amato, Lubomir Tomaska, Jiri Sponer, Janez Plavec, Lukas Trantirek
In this study, we report the first atomic resolution structure of a stable G-hairpin formed by a natively occurring DNA sequence. An 11-nt-long G-rich DNA oligonucleotide, 5'-d(GTGTGGGTGTG)-3', corresponding to the most abundant sequence motif in irregular telomeric DNA from Saccharomyces cerevisiae (yeast), is demonstrated to adopt a novel type of mixed parallel/antiparallel fold-back DNA structure, which is stabilized by dynamic G:G base pairs that transit between N1-carbonyl symmetric and N1-carbonyl, N7-amino base-pairing arrangements...
February 20, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28217990/telomerase-activity-detection-with-amplification-free-single-molecule-stochastic-binding-assay
#4
Xin Su, Zehao Li, Xinzhong Yan, Lei Wang, Xu Zhou, Lin Wei, Lehui Xiao, Changyuan Yu
Since the elongation of telomeres is associated with tumorigenesis, it is of great interest to develop rapid and high-confidence telomerase activity detection methods for disease diagnosis. Currently, amplification based strategies have been extensively explored for telomerase detection in vitro and in vivo. However, amplification typically associated with poor reproducibility and high background which hamper their further applications particularly for real sample assay. Here, we demonstrated a new amplification-free single molecule imaging method for telomerase activity detection in vitro based on nucleic acid stochastic binding with total internal reflection fluorescence microscopy (TIRFM)...
February 20, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28216227/nek7-protects-telomeres-from-oxidative-dna-damage-by-phosphorylation-and-stabilization-of-trf1
#5
Rong Tan, Satoshi Nakajima, Qun Wang, Hongxiang Sun, Jing Xue, Jian Wu, Sabine Hellwig, Xuemei Zeng, Nathan A Yates, Thomas E Smithgall, Ming Lei, Yu Jiang, Arthur S Levine, Bing Su, Li Lan
Telomeric repeat binding factor 1 (TRF1) is essential to the maintenance of telomere chromatin structure and integrity. However, how telomere integrity is maintained, especially in response to damage, remains poorly understood. Here, we identify Nek7, a member of the Never in Mitosis Gene A (NIMA) kinase family, as a regulator of telomere integrity. Nek7 is recruited to telomeres and stabilizes TRF1 at telomeres after damage in an ATM activation-dependent manner. Nek7 deficiency leads to telomere aberrations, long-lasting γH2AX and 53BP1 foci, and augmented cell death upon oxidative telomeric DNA damage...
February 8, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28216226/nbs1-phosphorylation-status-dictates-repair-choice-of-dysfunctional-telomeres
#6
Rekha Rai, Chunyi Hu, Cayla Broton, Yong Chen, Ming Lei, Sandy Chang
Telomeres employ TRF2 to protect chromosome ends from activating the DNA damage sensor MRE11-RAD50-NBS1 (MRN), thereby repressing ATM-dependent DNA damage checkpoint responses. How TRF2 prevents MRN activation at dysfunctional telomeres is unclear. Here, we show that the phosphorylation status of NBS1 determines the repair pathway choice of dysfunctional telomeres. The crystal structure of the TRF2-NBS1 complex at 3.0 Å resolution shows that the NBS1 429YQLSP433 motif interacts specifically with the TRF2(TRFH) domain...
February 8, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28214534/demographic-phenotypic-and-genetic-characteristics-of-centenarians-in-okinawa-and-honshu-japan-part-2-honshu-japan
#7
REVIEW
Yasumichi Arai, Takashi Sasaki, Nobuyoshi Hirose
The scope and purpose of this review was to summarize the aims, methods, findings, and future of centenarian and (semi)-supercentenarian studies in Japan, particularly those from our own interdisciplinary laboratory. Medically, approximately 97% of centenarians contract chronic diseases including hypertension and gastrointestinal disease; however, they present with few cardiovascular risk factors. The low prevalence of diabetes mellitus and carotid atherosclerotic plaques are peculiarities of centenarians, which could be associated with high adiponectin levels...
February 15, 2017: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/28213353/the-telomere-associated-tzap-protein-limits-telomere-length
#8
(no author information available yet)
TZAP binds preferentially to long telomeres and promotes telomere trimming.
February 17, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28212542/two-stage-genome-wide-association-study-identifies-a-novel-susceptibility-locus-associated-with-melanoma
#9
Katherine J Ransohoff, Wenting Wu, Hyunje G Cho, Harvind C Chahal, Yuan Lin, Hong-Ji Dai, Christopher I Amos, Jeffrey E Lee, Jean Y Tang, David A Hinds, Jiali Han, Qingyi Wei, Kavita Y Sarin
Genome-wide association studies have identified 21 susceptibility loci associated with melanoma. These loci implicate genes affecting pigmentation, nevus count, telomere maintenance, and DNA repair in melanoma risk. Here, we report the results of a two-stage genome-wide association study of melanoma. The stage 1 discovery phase consisted of 4,842 self-reported melanoma cases and 286,565 controls of European ancestry from the 23andMe research cohort and the stage 2 replication phase consisted of 1,804 melanoma cases and 1,026 controls from the University of Texas M...
February 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28209595/prediagnosis-leukocyte-telomere-length-and-risk-of-ovarian-cancer
#10
Meng Yang, Jennifer Prescott, Elizabeth M Poole, Megan S Rice, Laura D Kubzansky, Annika Idahl, Eva Lundin, Immaculata De Vivo, Shelley S Tworoger
Background: The associations between telomere length and cancer risk are equivocal, and none have examined the association between prediagnosis leukocyte telomere length (LTL) and the risk of developing ovarian cancer.Methods: We prospectively measured LTL collected from 442 ovarian cancer cases and 727 controls in the Nurses' Health Studies and the Northern Sweden Health and Disease Study. Cases were matched to one or two controls on age, menopausal status, and date of blood collection. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression...
February 16, 2017: Cancer Epidemiology, Biomarkers & Prevention
https://www.readbyqxmd.com/read/28207952/di-nickel-salphen-complexes-as-binders-of-human-telomeric-dimeric-g-quadruplexes
#11
Ramon Vilar, Chun-Qiong Zhou, Ting-Cong Liao, Zi-Qi Li, Jorge Gonzalez-Garcia, Matthew Reynolds, Min Zou
Three new polyether-tethered di-nickel-salphen complexes (2a-c) have been synthesized and fully characterized by NMR spectroscopy, mass spectrometry and elemental analyses. The binding affinity and selectivity of these complexes and of the parent mono-nickel complex (1) towards dimeric quadruplex DNA have been determined by UV-Vis titrations, fluorescence spectroscopy, CD spectroscopy and electrophoresis. These studies have shown that the di-nickel-salphen complex with the longest polyether linker (2c) has higher binding affinity and selectivity towards dimeric quadruplexes (over monomeric quadruplexes) than the di-nickel-salphen complexes with the shorter polyether linkers (2a and 2b)...
February 16, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28205383/association-between-leukocyte-telomere-length-and-angiogenic-cytokines-in-knee-osteoarthritis
#12
Thitiya Poonpet, Natthaphon Saetan, Aree Tanavalee, Vajara Wilairatana, Pongsak Yuktanandana, Sittisak Honsawek
AIM: The aims of this study were to compare leukocyte relative telomere length (RTL) in knee osteoarthritis (OA) patients and healthy controls and to investigate associations between plasma angiogenic cytokine concentrations and leukocyte RTL. METHOD: Eighty knee OA patients and 60 age-matched controls were enrolled. Leukocyte RTL was assessed using real-time quantitative polymerase chain reaction (qPCR). Angiogenic cytokines were measured by a multiplex immunoassay...
February 16, 2017: International Journal of Rheumatic Diseases
https://www.readbyqxmd.com/read/28202517/tankyrase-binding-protein-tnks1bp1-regulates-actin-cytoskeleton-rearrangement-and-cancer-cell-invasion
#13
Tomokazu Ohishi, Haruka Yoshida, Masamichi Katori, Toshiro Migita, Yukiko Muramatsu, Mao Miyake, Yuichi Ishikawa, Akio Saiura, Shun-Ichiro Iemura, Tohru Natsume, Hiroyuki Seimiya
Tankyrase, a poly(ADP-ribose) polymerase (PARP) that promotes telomere elongation and Wnt/β-catenin signaling, has various binding partners, suggesting that it has as-yet unidentified functions. Here we report that the tankyrase-binding protein TNKS1BP1 regulates actin cytoskeleton and cancer cell invasion, which is closely associated with cancer progression. TNKS1BP1 colocalized with actin filaments and negatively regulated cell invasion. In TNKS1BP1-depleted cells, actin filament dynamics, focal adhesion, and lamellipodia ruffling were increased with activation of the ROCK-LIMK-cofilin pathway...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28202046/highly-predictive-snp-markers-for-efficient-selection-of-the-wheat-leaf-rust-resistance-gene-lr16
#14
Mulualem T Kassa, Frank M You, Colin W Hiebert, Curtis J Pozniak, Pierre R Fobert, Andrew G Sharpe, James G Menzies, D Gavin Humphreys, Nicole Rezac Harrison, John P Fellers, Brent D McCallum, Curt A McCartney
BACKGROUND: Lr16 is a widely deployed leaf rust resistance gene in wheat (Triticum aestivum L.) that is highly effective against the North American Puccinia triticina population when pyramided with the gene Lr34. Lr16 is a seedling leaf rust resistance gene conditioning an incompatible interaction with a distinct necrotic ring surrounding the uredinium. Lr16 was previously mapped to the telomeric region of the short arm of wheat chromosome 2B. The goals of this study were to develop numerous single nucleotide polymorphism (SNP) markers for the Lr16 region and identify diagnostic gene-specific SNP marker assays for marker-assisted selection (MAS)...
February 15, 2017: BMC Plant Biology
https://www.readbyqxmd.com/read/28199314/whole-genome-landscape-of-pancreatic-neuroendocrine-tumours
#15
Aldo Scarpa, David K Chang, Katia Nones, Vincenzo Corbo, Ann-Marie Patch, Peter Bailey, Rita T Lawlor, Amber L Johns, David K Miller, Andrea Mafficini, Borislav Rusev, Maria Scardoni, Davide Antonello, Stefano Barbi, Katarzyna O Sikora, Sara Cingarlini, Caterina Vicentini, Skye McKay, Michael C J Quinn, Timothy J C Bruxner, Angelika N Christ, Ivon Harliwong, Senel Idrisoglu, Suzanne McLean, Craig Nourse, Ehsan Nourbakhsh, Peter J Wilson, Matthew J Anderson, J Lynn Fink, Felicity Newell, Nick Waddell, Oliver Holmes, Stephen H Kazakoff, Conrad Leonard, Scott Wood, Qinying Xu, Shivashankar Hiriyur Nagaraj, Eliana Amato, Irene Dalai, Samantha Bersani, Ivana Cataldo, Angelo P Dei Tos, Paola Capelli, Maria Vittoria Davì, Luca Landoni, Anna Malpaga, Marco Miotto, Vicki L J Whitehall, Barbara A Leggett, Janelle L Harris, Jonathan Harris, Marc D Jones, Jeremy Humphris, Lorraine A Chantrill, Venessa Chin, Adnan M Nagrial, Marina Pajic, Christopher J Scarlett, Andreia Pinho, Ilse Rooman, Christopher Toon, Jianmin Wu, Mark Pinese, Mark Cowley, Andrew Barbour, Amanda Mawson, Emily S Humphrey, Emily K Colvin, Angela Chou, Jessica A Lovell, Nigel B Jamieson, Fraser Duthie, Marie-Claude Gingras, William E Fisher, Rebecca A Dagg, Loretta M S Lau, Michael Lee, Hilda A Pickett, Roger R Reddel, Jaswinder S Samra, James G Kench, Neil D Merrett, Krishna Epari, Nam Q Nguyen, Nikolajs Zeps, Massimo Falconi, Michele Simbolo, Giovanni Butturini, George Van Buren, Stefano Partelli, Matteo Fassan, Kum Kum Khanna, Anthony J Gill, David A Wheeler, Richard A Gibbs, Elizabeth A Musgrove, Claudio Bassi, Giampaolo Tortora, Paolo Pederzoli, John V Pearson, Nicola Waddell, Andrew V Biankin, Sean M Grimmond
The diagnosis of pancreatic neuroendocrine tumours (PanNETs) is increasing owing to more sensitive detection methods, and this increase is creating challenges for clinical management. We performed whole-genome sequencing of 102 primary PanNETs and defined the genomic events that characterize their pathogenesis. Here we describe the mutational signatures they harbour, including a deficiency in G:C > T:A base excision repair due to inactivation of MUTYH, which encodes a DNA glycosylase. Clinically sporadic PanNETs contain a larger-than-expected proportion of germline mutations, including previously unreported mutations in the DNA repair genes MUTYH, CHEK2 and BRCA2...
February 15, 2017: Nature
https://www.readbyqxmd.com/read/28197915/the-role-of-sumoylation-in-senescence
#16
Lyndee L Scurr, Sebastian Haferkamp, Helen Rizos
Cellular senescence is a program initiated by many stress signals including aberrant activation of oncogenes, DNA damage, oxidative lesions and telomere attrition. Once engaged senescence irreversibly limits cellular proliferation and potently prevents tumor formation in vivo. The precise mechanisms driving the onset of senescence are still not completely defined, although the pRb and p53 tumor suppressor pathways converge with the SUMO cascade to regulate cellular senescence. Sumoylation translocates p53 to PML nuclear bodies where it can co-operate with many sumoylated co-factors in a program that activates pRb and favors senescence...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28197807/telomere-length-in-the-gastric-mucosa-after-helicobacter-pylori-eradication-and-its-potential-role-in-the-gastric-carcinogenesis
#17
Tomomitsu Tahara, Sayumi Tahara, Tetsuya Tuskamoto, Noriyuki Horiguchi, Tomohiko Kawamura, Masaaki Okubo, Takamitsu Ishizuka, Mitsuo Nagasaka, Yoshihito Nakagawa, Tomoyuki Shibata, Makoto Kuroda, Naoki Ohmiya
The molecular mechanisms of gastric carcinogenesis after Helicobacter pylori (H. pylori) eradication remain unclear. We examined the telomere length of gastric mucosa samples after successful H. pylori eradication in patients without and those with gastric cancer. Telomere length was measured by the real-time PCR among four different groups of biopsies: gastric body from subjects without history of H. pylori infection (Hp-: n = 23), gastric body from cancer-free subjects after H. pylori eradication (cancer-free body: n = 24), gastric body from early gastric cancer patients diagnosed after H...
February 14, 2017: Clinical and Experimental Medicine
https://www.readbyqxmd.com/read/28196983/genomic-profiling-of-acute-lymphoblastic-leukemia-in-ataxia-telangiectasia-patients-reveals-tight-link-between-atm-mutations-and-chromothripsis
#18
M Ratnaparkhe, M Hlevnjak, T Kolb, A Jauch, K K Maass, F Devens, A Rode, V Hovestadt, A Korshunov, A Pastorczak, W Mlynarski, S Sungalee, J Korbel, J Hoell, U Fischer, T Milde, C Kramm, M Nathrath, K Chrzanowska, E Tausch, M Takagi, T Taga, S Constantini, J Loeffen, J Meijerink, S Zielen, G Gohring, B Schlegelberger, E Maass, R Siebert, J Kunz, A E Kulozik, B Worst, D T Jones, S M Pfister, M Zapatka, P Lichter, A Ernst
Recent developments in sequencing technologies led to the discovery of a novel form of genomic instability, termed chromothripsis. This catastrophic genomic event, involved in tumorigenesis, is characterized by tens to hundreds of simultaneously acquired locally clustered rearrangements on one chromosome. We hypothesized that leukemias developing in individuals with Ataxia Telangiectasia, who are born with two mutated copies of the ATM gene, an essential guardian of genome stability, would show a higher prevalence of chromothripsis due to the associated defect in DNA double-strand break repair...
February 15, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28196871/identification-of-a-transcriptional-activation-domain-in-yeast-repressor-activator-protein-1-rap1-using-an-altered-dna-binding-specificity-variant
#19
Amanda N Johnson, P Anthony Weil
Repressor Activator Protein 1 (Rap1) performs multiple vital cellular functions in the budding yeast Saccharomyces cerevisiae. These include regulation of telomere length, transcriptional repression of both telomere-proximal genes and the silent mating type loci, and transcriptional activation of hundreds of mRNA-encoding genes, including the highly transcribed ribosomal protein- and glycolytic enzyme-encoding genes. Studies of the contributions of Rap1 to telomere length regulation and transcriptional repression have yielded significant mechanistic insights...
February 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28196338/telomerase-and-telomere-biology-in-hematological-diseases-a-new-therapeutic-target
#20
REVIEW
Alessandro Allegra, Vanessa Innao, Giuseppa Penna, Demetrio Gerace, Andrea G Allegra, Caterina Musolino
Telomeres are structures confined at the ends of eukaryotic chromosomes. With each cell division, telomeric repeats are lost because DNA polymerases are incapable to fully duplicate the very ends of linear chromosomes. Loss of repeats causes cell senescence, and apoptosis. Telomerase neutralizes loss of telomeric sequences by adding telomere repeats at the 3' telomeric overhang. Telomere biology is frequently associated with human cancer and dysfunctional telomeres have been proved to participate to genetic instability...
February 7, 2017: Leukemia Research
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