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Mrinmoyee Majumder, Reniqua House, Nallasivam Palanisamy, Shuo Qie, Terrence A Day, David Neskey, J Alan Diehl, Viswanathan Palanisamy
[This corrects the article DOI: 10.1371/journal.pgen.1006306.].
October 2016: PLoS Genetics
Mengying Wu, Zhuojia Lin, Xiaonan Li, Xiaoru Xin, Jiahui An, Qidi Zheng, Yuxin Yang, Dongdong Lu
The dysregulation of lncRNAs has increasingly been linked to many human diseases, especially in cancers. Our results demonstrate HULC, MALAT1 and TRF2 are highly expressed in human hepatocellular carcinoma tissues, and HULC plus MALAT1 overexpression drastically promotes the growth of liver cancer stem cells. Mechanistically, both HULC and MALAT1 overexpression enhanced RNA polII, P300, CREPT to load on the promoter region of telomere repeat-binding factor 2(TRF2), triggering the overexpression, phosphorylation and SUMOylation of TRF2...
October 26, 2016: Scientific Reports
Hanseol Kim, Jihye Ryu, Chaeyoung Lee
A genome-wide association study was conducted to identify expression quantitative trait loci (eQTL) for human telomerase.We tested the genetic associations of nucleotide variants with expression of the genes encoding human telomerase reverse transcriptase (hTERT) and telomerase RNA components (TERC) in lymphoblastoid cell lines derived from 373 Europeans.Our results revealed 6 eQTLs associated with hTERT (P < 5 × 10). One eQTL (rs17755753) was located in the intron 1 of the gene encoding R-spondin-3 (RSPO3), a well-known Wnt signaling regulator...
October 2016: Medicine (Baltimore)
Francisco Gomez-Delgado, Javier Delgado-Lista, Javier Lopez-Moreno, Oriol Alberto Rangel-Zuñiga, Juan Francisco Alcala-Diaz, Ana Leon-Acuña, Andreea Corina, Elena Yubero-Serrano, Jose David Torres-Peña, Antonio Camargo, Antonio Garcia-Rios, Javier Caballero, Justo Castaño, Jose M Ordovas, Jose Lopez-Miranda, Pablo Perez-Martinez
BACKGROUND: Leukocyte telomere length (LTL) attrition has been associated with age-related diseases. Telomerase RNA Component (TERC) genetic variants have been associated with LTL; whereas fatty acids (FAs) can interact with genetic factors and influence in aging. We explore whether variability at the TERC gene locus interacts with FA profile and two healthy diets (low-fat diet vs Mediterranean diet [MedDiet]) modulating LTL, glucose metabolism, and inflammation status in coronary heart disease (CHD) patients...
October 5, 2016: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
Muhamed Baljevic, Bogdan Dumitriu, Ju-Whei Lee, Elisabeth M Paietta, Peter H Wiernik, Janis Racevskis, Christina Chen, Eytan M Stein, Robert E Gallagher, Jacob M Rowe, Frederick R Appelbaum, Bayard L Powell, Richard A Larson, Steven E Coutré, Jeffrey Lancet, Mark R Litzow, Selina M Luger, Neal S Young, Martin S Tallman
Telomeres are the capping ends of chromosomes that protect the loss of genetic material and prevent chromosomal instability. In human tissue-specific stem/progenitor cells, telomere length (TL) is maintained by the telomerase complex, which consists of a reverse transcriptase catalytic subunit (TERT) and an RNA template (TERC). Very short telomeres and loss-of-function mutations in the TERT and TERC genes have been reported in acute myeloid leukemia, but the role of telomeres in acute promyelocytic leukemia (APL) has not been well established...
September 16, 2016: Acta Haematologica
Christopher M Evans, Tasha E Fingerlin, Marvin I Schwarz, David Lynch, Jonathan Kurche, Laura Warg, Ivana V Yang, David A Schwartz
Idiopathic pulmonary fibrosis (IPF) is an incurable complex genetic disorder that is associated with sequence changes in 7 genes (MUC5B, TERT, TERC, RTEL1, PARN, SFTPC, and SFTPA2) and with variants in at least 11 novel loci. We have previously found that 1) a common gain-of-function promoter variant in MUC5B rs35705950 is the strongest risk factor (genetic and otherwise), accounting for 30-35% of the risk of developing IPF, a disease that was previously considered idiopathic; 2) the MUC5B promoter variant can potentially be used to identify individuals with preclinical pulmonary fibrosis and is predictive of radiologic progression of preclinical pulmonary fibrosis; and 3) MUC5B may be involved in the pathogenesis of pulmonary fibrosis with MUC5B message and protein expressed in bronchiolo-alveolar epithelia of IPF and the characteristic IPF honeycomb cysts...
October 2016: Physiological Reviews
Mrinmoyee Majumder, Reniqua House, Nallasivam Palanisamy, Shuo Qie, Terrence A Day, David Neskey, J Alan Diehl, Viswanathan Palanisamy
RNA-binding proteins (RBP) regulate numerous aspects of co- and post-transcriptional gene expression in cancer cells. Here, we demonstrate that RBP, fragile X-related protein 1 (FXR1), plays an essential role in cellular senescence by utilizing mRNA turnover pathway. We report that overexpressed FXR1 in head and neck squamous cell carcinoma targets (G-quadruplex (G4) RNA structure within) both mRNA encoding p21 (Cyclin-Dependent Kinase Inhibitor 1A (CDKN1A, Cip1) and the non-coding RNA Telomerase RNA Component (TERC), and regulates their turnover to avoid senescence...
September 2016: PLoS Genetics
Lakshan N Fonseka, Carlos A Tirado
It is expected that 10,460 patients will die from acute myeloid leukemia (AML) in the United States in 2016. Despite progress in clinical management, AML patients still have a 25.9% survival rate in the U.S. Researchers have sought to further understand this hematological malignancy and a number of studies have focused on unveiling the role of telomerase in disease initiation, progression, and maintenance. Though the role of telomerase in diagnosis has remained relatively static, its role in prognosis and treatment has become much clearer...
2016: Journal of the Association of Genetic Technologists
Baris Boyraz, Courtney M Bellomo, Mark D Fleming, Corey S Cutler, Suneet Agarwal
No abstract text is available yet for this article.
September 1, 2016: Blood
Paula Martínez, Gonzalo Gómez-López, David G Pisano, Juana M Flores, Maria A Blasco
RAP1 is one of the components of shelterin, the capping complex at chromosome ends or telomeres, although its role in telomere length maintenance and protection has remained elusive. RAP1 also binds subtelomeric repeats and along chromosome arms, where it regulates gene expression and has been shown to function in metabolism control. Telomerase is the enzyme that elongates telomeres, and its deficiency causes a premature aging in humans and mice. We describe an unanticipated genetic interaction between RAP1 and telomerase...
September 1, 2016: Aging Cell
Sandra Durante, Silvia Vecchiarelli, Annalisa Astolfi, Elisa Grassi, Riccardo Casadei, Donatella Santini, Riccardo Panzacchi, Claudio Ricci, Salvatore Serravalle, Giuseppe Tarantino, Mirella Falconi, Gabriella Teti, Valentina Indio, Andrea Pession, Francesco Minni, Guido Biasco, Mariacristina Di Marco
BACKGROUND: Intraductal papillary mucinous neoplasm (IPMN) is the most common cystic preneoplastic lesion of pancreatic cancer. We used an approach coupling high resolution cytogenetic analysis (Affymetrix Oncoscan FFPE Array) with clinically-oriented bioinformatic interpretation of data to understand the most relevant alterations of precursor lesions at different stages to identify new diagnostic markers. RESULTS: We identified multiple copy number alterations, particularly in lesions with severe dysplasia, with 7 IPMN with low-intermediate dysplasia carrying a nearly normal karyotype and 13 IPMN with complex Karyotype (> 4 alterations), showing high grade dysplasia...
August 22, 2016: Oncotarget
Vanessa Sue Wacleche, Jean-Philippe Goulet, Annie Gosselin, Patricia Monteiro, Hugo Soudeyns, Rémi Fromentin, Mohammad-Ali Jenabian, Shant Vartanian, Steven G Deeks, Nicolas Chomont, Jean-Pierre Routy, Petronela Ancuta
BACKGROUND: Th17 cells are permissive to HIV-1 infection and their depletion from the gut of infected individuals leads to microbial translocation, a major cause for non-AIDS co-morbidities. Most recent evidence supports the contribution of long-lived Th17 cells to HIV persistence during antiretroviral therapy (ART). However, the identity of long-lived Th17 cells remains unknown. RESULTS: Here, we performed an in-depth transcriptional and functional characterization of four distinct Th17 subsets and investigated their contribution to HIV reservoir persistence during ART...
2016: Retrovirology
Annika Scheffold, Inge R Holtman, Sandra Dieni, Nieske Brouwer, Sarah-Fee Katz, Billy Michael Chelliah Jebaraj, Philipp J Kahle, Bastian Hengerer, André Lechel, Stephan Stilgenbauer, Erik W G M Boddeke, Bart J L Eggen, Karl-Lenhard Rudolph, Knut Biber
Parkinson's disease is one of the most common neurodegenerative disorders of the elderly and ageing hence described to be a major risk factor. Telomere shortening as a result of the inability to fully replicate the ends of linear chromosomes is one of the hallmarks of ageing. The role of telomere dysfunction in neurological diseases and the ageing brain is not clarified and there is an ongoing discussion whether telomere shortening is linked to Parkinson's disease. Here we studied a mouse model of Parkinson's disease (Thy-1 [A30P] α-synuclein transgenic mouse model) in the background of telomere shortening (Terc knockout mouse model)...
August 22, 2016: Acta Neuropathologica Communications
Muhammad Ali, Sushil Devkota, Jae-Il Roh, Jaehoon Lee, Han-Woong Lee
Telomerase is a reverse transcriptase that consists of the telomerase RNA component (TERC) and the reverse transcriptase catalytic subunit (TERT) and specializes in the elongation of telomere ends. New evidence suggests that beyond classical telomere maintenance, TERT also possesses telomere length-independent functions that are executed via interaction with other binding proteins. One such reported TERT-interacting proteins is mTOR, a master nutrient sensor that is upregulated in several cancers; however, the physiological implications of the TERT-mTOR interaction in normal cellular processes as well as in tumorigenesis are poorly understood...
September 23, 2016: Biochemical and Biophysical Research Communications
Chad A Newton, Kiran Batra, Jose Torrealba, Julia Kozlitina, Craig S Glazer, Carlos Aravena, Keith Meyer, Ganesh Raghu, Harold R Collard, Christine Kim Garcia
Heterozygous mutations in four telomere-related genes have been linked to pulmonary fibrosis, but little is known about similarities or differences of affected individuals.115 patients with mutations in telomerase reverse transcriptase (TERT) (n=75), telomerase RNA component (TERC) (n=7), regulator of telomere elongation helicase 1 (RTEL1) (n=14) and poly(A)-specific ribonuclease (PARN) (n=19) were identified and clinical data were analysed.Approximately one-half (46%) had a multidisciplinary diagnosis of idiopathic pulmonary fibrosis (IPF); others had unclassifiable lung fibrosis (20%), chronic hypersensitivity pneumonitis (12%), pleuroparenchymal fibroelastosis (10%), interstitial pneumonia with autoimmune features (7%), an idiopathic interstitial pneumonia (4%) and connective tissue disease-related interstitial fibrosis (3%)...
August 18, 2016: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
Shiqi Jie, Mingming Li, Min Gan, Jianyu Zhu, Huaqun Yin, Xueduan Liu
BACKGROUND: Xiangjiang River (Hunan, China) has been contaminated with heavy metal for several decades by surrounding factories. However, little is known about the influence of a gradient of heavy metal contamination on the diversity, structure of microbial functional gene in sediment. To deeply understand the impact of heavy metal contamination on microbial community, a comprehensive functional gene array (GeoChip 5.0) has been used to study the functional genes structure, composition, diversity and metabolic potential of microbial community from three heavy metal polluted sites of Xiangjiang River...
2016: BMC Microbiology
Line Rode, Børge G Nordestgaard, Stig E Bojesen
BACKGROUND: Results regarding telomere length and cancer risk are conflicting. We tested the hypothesis that long telomeres are associated with increased risk of any cancer and specific cancer types in genetic and observational analyses. METHODS: Individuals (N = 95 568) from the Copenhagen City Heart Study and the Copenhagen General Population Study had the telomere length-associated genotypes rs7726159 (TERT), rs1317082 (TERC), and rs2487999 (OBFC1) determined, and 65 176 had telomere length measured...
August 6, 2016: International Journal of Epidemiology
Zeina Soayfane, François Tercé, Michela Cantiello, Horst Robenek, Michel Nauze, Valérie Bézirard, Sophie Allart, Bruno Payré, Florence Capilla, Christel Cartier, Christine Peres, Talal Al Saati, Vassilia Théodorou, David W Nelson, Chi-Liang Eric Yen, Xavier Collet, Christine Coméra
BACKGROUND: Intestinal absorption of dietary lipids involves their hydrolysis in the lumen of proximal intestine as well as uptake, intracellular transport and re-assembly of hydrolyzed lipids in enterocytes, leading to the formation and secretion of the lipoproteins chylomicrons and HDL. In this study, we examined the potential involvement of cytosolic lipid droplets (CLD) whose function in the process of lipid absorption is poorly understood. METHODS: Intestinal lipid absorption was studied in mouse after gavage...
2016: Nutrition & Metabolism
Sara Karami, Younghun Han, Mala Pande, Iona Cheng, James Rudd, Brandon L Pierce, Ellen L Nutter, Fredrick R Schumacher, Zsofia Kote-Jarai, Sara Lindstrom, John S Witte, Shenying Fang, Jiali Han, Peter Kraft, David J Hunter, Fengju Song, Rayjean J Hung, James McKay, Stephen B Gruber, Stephen J Chanock, Angela Risch, Hongbing Shen, Christopher A Haiman, Lisa Boardman, Cornelia M Ulrich, Graham Casey, Ulrike Peters, Ali Amin Al Olama, Andrew Berchuck, Sonja I Berndt, Stephane Bezieau, Paul Brennan, Hermann Brenner, Louise Brinton, Neil Caporaso, Andrew T Chan, Jenny Chang-Claude, David C Christiani, Julie M Cunningham, Douglas Easton, Rosalind A Eeles, Timothy Eisen, Manish Gala, Steven J Gallinger, Simon A Gayther, Ellen L Goode, Henrik Grönberg, Brian E Henderson, Richard Houlston, Amit D Joshi, Sébastien Küry, Mari T Landi, Loic Le Marchand, Kenneth Muir, Polly A Newcomb, Jenny Permuth-Wey, Paul Pharoah, Catherine Phelan, John D Potter, Susan J Ramus, Harvey Risch, Joellen Schildkraut, Martha L Slattery, Honglin Song, Nicolas Wentzensen, Emily White, Fredrik Wiklund, Brent W Zanke, Thomas A Sellers, Wei Zheng, Nilanjan Chatterjee, Christopher I Amos, Jennifer A Doherty
Telomeres cap chromosome ends, protecting them from degradation, double-strand breaks, and end-to-end fusions. Telomeres are maintained by telomerase, a reverse transcriptase encoded by TERT, and an RNA template encoded by TERC. Loci in the TERT and adjoining CLPTM1L region are associated with risk of multiple cancers. We therefore investigated associations between variants in 22 telomere structure and maintenance gene regions and colorectal, breast, prostate, ovarian, and lung cancer risk. We performed subset-based meta-analyses of 204,993 directly-measured and imputed SNPs among 61,851 cancer cases and 74,457 controls of European descent...
December 15, 2016: International Journal of Cancer. Journal International du Cancer
Tal Biron-Shental, Meital Liberman, Michal Elbaz, Ido Laish, Reuven Sharony, Aliza Amiel
OBJECTIVE: Diabetes during pregnancy causes an intrauterine environment that influences lifetime sickness of the mother and the fetus. There is a correlation between diabetes and telomere shortening; however, very little is known about telomere homeostasis in the placenta. We aimed to study the telomerase complex in placentas and in cord blood leukocytes from patients with poorly controlled diabetes. METHODS: Biopsies from 16 third-trimester placentas and cord blood samples from pregnancies complicated with uncontrolled diabetes and from 16 gestational age-matched controls from uncomplicated pregnancies were examined...
August 2016: Placenta
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