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Chen-Chen Li, Juan Hu, Mengfei Lu, Chun-Yang Zhang
Human telomerase is responsible for the maintenance of chromosome end structures and is a valuable biomarker for malignant growth. However, the accurate measurement of telomerase activity at the single-cell level has remained a great challenge. Here we develop a simple quantum dot (QD)-based electrochemical biosensor for stripping voltammetric detection of telomerase activity at the single-cell level. We designed a thiol-modified capture DNA which may be immobilized on the gold electrode by the gold-sulfur bond...
September 13, 2018: Biosensors & Bioelectronics
Yongsoon Kim, YoungJoon Park, JoonYeon Hwang, KyuBum Kwack
Reproduction is an important biological process. However, studies of human reproduction at the molecular level are limited due to the difficulty of performing in vivo studies. Hence, a mechanistic understanding of human reproduction remains still poor. Thus, it is important to use an alternative model organism for mechanistic studies of human reproduction. In this study, we used the nematode Caenorhabditis elegans as a model for studying human reproduction and identified 61 human and 535 worm reproductive genes through a combination of comparative genomic and Gene Ontology (GO) analyses...
September 21, 2018: Physiological Genomics
Anirban Ray, Tiffany Rene Oliver, Pinku Halder, Upamanyu Pal, Sumantra Sarkar, Supratim Dutta, Sujay Ghosh
Consanguineous marriage was examined as a risk factor for Down syndrome birth. We genotyped Down syndrome family trios using short tandem repeat markers on 21q-to interpret the parental and meiotic stage of origin of errors as well as to record recombination profile along long arm of chromosome 21. We then compared nonconsanguineous (N = 811) group with-the consanguineous (N =157) marriages. We report for the first time that consanguineous marriage is associated with an increased risk for nondisjunction of chromosome 21 in oocytes-during the second meiotic division...
September 21, 2018: American Journal of Medical Genetics. Part A
Pallabi Sengupta, Nilanjan Banerjee, Tanaya Roychowdhury, Anindya Dutta, Samit Chattopadhyay, Subhrangsu Chatterjee
c-MYC proto-oncogene harbours a transcription-inhibitory quadruplex-forming scaffold (Pu27) upstream P1 promoter providing anti-neoplastic therapeutic target. Previous reports showed the binding profile of human Cathelicidin peptide (LL37) and telomeric G-quadruplex. Here, we truncated the quadruplex-binding domain of LL37 to prepare a small library of peptides through site-specific amino acid substitution. We investigated the intracellular selectivity of peptides for Pu27 over other oncogenic quadruplexes and their role in c-MYC promoter repression by dual-luciferase assays...
September 17, 2018: Nucleic Acids Research
Carly L Geronimo, Saurabh P Singh, Roberto Galletto, Virginia A Zakian
Pif1 family DNA helicases are conserved from bacteria to humans and have critical and diverse functions in vivo that promote genome integrity. Pif1 family helicases share a 23 amino acid region, called the Pif1 signature motif (SM) that is unique to this family. To determine the importance of the SM, we did mutational and functional analysis of the SM from the Saccharomyces cerevisiae Pif1 (ScPif1). The mutations deleted portions of the SM, made one or multiple single amino acid changes in the SM, replaced the SM with its counterpart from a bacterial Pif1 family helicase and substituted an α-helical domain from another helicase for the part of the SM that forms an α helix...
September 19, 2018: Nucleic Acids Research
Galina M Viryasova, Nina G Dolinnaya, Ekaterina A Golenkina, Tatjana V Gaponova, Mikhail B Viryasov, Yulia M Romanova, Galina F Sud'ina
Human polymorphonuclear leukocytes (PMNLs, neutrophils) play a major role in the immune response to bacterial and fungal infections and eliminate pathogens through phagocytosis. During phagocytosis of microorganisms, the 5-lipoxygenase (5-LOX) pathway is activated resulting in generation of leukotrienes, which mediate host defense. In this study, a library of oligodeoxyribonucleotides (ODNs) with varying numbers of human telomeric repeats (d(TTAGGG)n ) and their analogues with phosphorothioate internucleotide linkages and single-nucleotide substitutions was designed...
September 21, 2018: Journal of Biomolecular Structure & Dynamics
Nannan Yang, Megan C McDonald, Peter S Solomon, Andrew W Milgate
A new and dominant R gene Stb19 is identified from a soft wheat cultivar 'Lorikeet' and was mapped on the distal region of chromosome 1DS. Two tightly linked KASP markers were also discovered and validated for molecular-assisted breeding programs. A new R gene, designated as Stb19, provides resistance to Zymoseptoria tritici in wheat. This new dominant gene resides on the short arm of chromosome 1D, exhibiting complete resistance to three Z. tritici isolates, WAI332, WAI251, and WAI161, at the seedling stage...
September 20, 2018: TAG. Theoretical and Applied Genetics. Theoretische und Angewandte Genetik
Rima Manafi Shabestari, Fatemeh Alikarami, Davood Bashash, Mostafa Paridar, Majid Safa
Dysregulated expression of miRNAs can play a vital role in pathogenesis of leukemia. The shortened telomere length, and elevated telomerase activity in acute promyelocytic leukemia cells are mainly indicative of extensive proliferative activity. This study aimed to investigate the effect of overexpression of miR-138 on telomerase activity, and cell proliferation of acute promyelocytic leukemia NB4 cells. MiR-138 was overexpressed in NB4 cells using GFP hsa-miR-138-expressing lentiviruses. hTERT mRNA and protein expression levels were assessed by qRT-PCR and western blot analysis...
2018: International Journal of Molecular and Cellular Medicine
Mrithunjay Rathore, Jessy Abraham
Telomeres, the repetitive sequences that protect the ends of chromosomes, help to maintain genomic integrity and are of key importance to human health. Telomeres progressively shorten throughout life and a number of studies have shown shorter telomere length to be associated with lifestyle disorders. Previous studies also indicate that yoga and lifestyle-based intervention have significant role on oxidative DNA damage and cellular aging. However, very few publications investigate telomere stability and its implication from the point of view of asana, pranayama, and meditation...
September 2018: International Journal of Yoga
Xiaojuan Bai
Biomarkers of aging are a biological parameter that can predict the functional status of an individual in the absence of disease and can be used to better predict morbidity and mortality, compared to using the chronological age alone. Most of aging biomarkers were gene, molecules, and protein, which were found in basic scientific researches, such as telomeres, proteomics, cytokines, etc. However, it is almost impossible for single biomarkers to fully reveal the mechanism of aging. Because of the complexity of aging process, the biomarkers of aging may need to be composed of multiple genes, proteins, and metabolites...
2018: Advances in Experimental Medicine and Biology
Chensheng Ma, Ruth Chau Ting Chan, Chris Tsz-Leung Chan, Allen Ka-Wa Wong, Bowie Po-Yee Chung, Wai-Ming Kwok
I-motifs are tetraplex DNAs known to be stable at acidic pH. The structure of i-motifs is important in DNA nanotechnology while i-motif forming sequences with consecutive cytosines (Cs) are abundant throughout the human genome. There is however little information on structure of C-rich DNAs at the physiologically relevant neutral condition. The electron dynamics of i-motifs, crucial to both the biology and material applications, also remains largely unexplored. In this work, we report a combined femtosecond and nanosecond broadband time-resolved fluorescence (TRF) and steady state fluorescence investigation on homo-oligomer dC20, a human telomeric sequence (HTS) 5'-dC3(TA2C3)3 and its analog performed with different excitation at both acidic and neutral pH...
September 19, 2018: Chemistry, An Asian Journal
Yukun Zhu, Xuewen Liu, Xuelu Ding, Fei Wang, Xin Geng
Aging is a biological process characterized by a progressive functional decline in tissues and organs, which eventually leads to mortality. Telomeres, the repetitive DNA repeat sequences at the end of linear eukaryotic chromosomes protecting chromosome ends from degradation and illegitimate recombination, play a crucial role in cell fate and aging. Due to the mechanism of replication, telomeres shorten as cells proliferate, which consequently contributes to cellular senescence and mitochondrial dysfunction...
September 18, 2018: Biogerontology
Di Liu, Xinyan Xu, Junmiao Wen, Liyi Xie, Junhua Zhang, Yuxin Shen, Guoliang Jiang, Jiayan Chen, Min Fan
Purpose / Objectives . Primary small cell esophageal carcinoma (SCEC) represents a rare and aggressive malignancy without any prospective clinical trial or established treatment strategy at present. Although previous studies have indicated similarities between SCEC and small cell lung cancer (SCLC) in terms of their clinical manifestations, pathology, and morphology, very little genetic information is available on this highly malignant tumor. At present, patients with SCEC are staged and treated according to the guidelines established for SCLC...
2018: Stem Cells International
Gianluca Storci, Sabrina De Carolis, Fabiola Olivieri, Massimiliano Bonafè
Inflamm-aging depicts the progressive activation of the innate immune system that accompanies human aging. Its role as a disease-predisposing condition has been proposed, but its molecular basis is still poorly understood. A wealth of literature conveys that, particularly upon stress, nuclear and mitochondrial genomes are released into the cytoplasmic and extracellular compartments. Cytoplasmic (cy) and cell-free (cf) DNA pools trigger inflammation and innate immunity at local and systemic level. In particular, cyDNA plays a crucial role in the phenomenon of cell senescence and in the cognate pro-inflammatory secretome...
September 15, 2018: Seminars in Immunology
Jacqueline A Brosnan-Cashman, Ming Yuan, Mindy K Graham, Anthony J Rizzo, Kaylar M Myers, Christine Davis, Rebecca Zhang, David M Esopi, Eric H Raabe, Charles G Eberhart, Christopher M Heaphy, Alan K Meeker
Cancers must maintain their telomeres at lengths sufficient for cell survival. In several cancer subtypes, a recombination-like mechanism termed alternative lengthening of telomeres (ALT), is frequently used for telomere length maintenance. Cancers utilizing ALT often have lost functional ATRX, a chromatin remodeling protein, through mutation or deletion, thereby strongly implicating ATRX as an ALT suppressor. Herein, we have generated functional ATRX knockouts in four telomerase-positive, ALT-negative human glioma cell lines: MOG-G-UVW, SF188, U-251 and UW479...
2018: PloS One
Niko Välimäki, Heli Kuisma, Annukka Pasanen, Oskari Heikinheimo, Jari Sjöberg, Ralf Bützow, Nanna Sarvilinna, Hanna-Riikka Heinonen, Jaana Tolvanen, Simona Bramante, Tomas Tanskanen, Juha Auvinen, Terhi Piltonen, Amjad Alkodsi, Rainer Lehtonen, Eevi Kaasinen, Kimmo Palin, Lauri A Aaltonen
Uterine leiomyomas (ULs) are benign tumors that are a major burden to women's health. A genome-wide association study on 15,453 UL cases and 392,628 controls was performed, followed by replication of the genomic risk in six cohorts. Effects of the risk alleles were evaluated in view of molecular and clinical characteristics. 22 loci displayed a genome-wide significant association. The likely predisposition genes could be grouped to two biological processes. Genes involved in genome stability were represented by TERT, TERC, OBFC1 - highlighting the role of telomere maintenance - TP53 and ATM ...
September 18, 2018: ELife
Li Wang, Hongying Zhao, Yingqi Xu, Jing Li, Chunyu Deng, Yulan Deng, Jing Bai, Xia Li, Yun Xiao, Yunpeng Zhang
Copy number alterations (CNAs) of lincRNAs act as one of important mechanisms in disrupting lincRNA expression which may play critical roles during tumorigenesis in lung adenocarcinoma (LUAD). The copy number alterations of lincRNAs can mark the spectrum of cancer progression and may serve as biomarkers for prognosis in LUAD, however it is rarely studied. We analyzed RNASeq data for 488 LUAD patients from TCGA portal and 58 healthy subjects to identify prognostic lincRNAs predictive of patient survival. Computational analysis entailing integration of expression and copy number alteration data revealed five prognostic lincRNAs: RBPMS-AS1, TDRKH-AS1, LINC00578, RP11-470M17...
September 18, 2018: International Journal of Cancer. Journal International du Cancer
Ryo Gouko, Manabu Onuma, Takahiro Eitsuka, Masafumi Katayama, Kouhei Takahashi, Kiyotaka Nakagawa, Miho Inoue-Murayama, Tohru Kiyono, Tomokazu Fukuda
Tsushima leopard cat is the subspecies of Amur cats, and it is classified as the most highest class of critically endangered animals. Although the protection activity is highly recognized, the number of animals is decreasing due to the human activity and invasion of domestic cats and infectious disease. In this study, we succeeded primary culture of normal fibroblasts derived from the Tsushima leopard cat (Prionailurus bengalensis euptilurus). Furthermore, we introduced the human derived mutant Cyclin Dependent Kinase 4, Cyclin D1, and telomere reverse transcriptase...
September 17, 2018: Cytotechnology
Gillian V Pepper, Melissa Bateson, Daniel Nettle
Telomeres have been proposed as a biomarker that integrates the impacts of different kinds of stress and adversity into a common currency. There has as yet been no overall comparison of how different classes of exposure associate with telomeres. We present a meta-analysis of the literature relating telomere measures to stresses and adversities in humans. The analysed dataset contained 543 associations from 138 studies involving 402 116 people. Overall, there was a weak association between telomere variables and exposures (greater adversity, shorter telomeres: r = -0...
August 2018: Royal Society Open Science
Doorgesh Sharma Jokhun, Yuqing Shang, G V Shivashankar
Genome regulatory programs such as telomere functioning require extracellular signals to be transmitted from the microenvironment to the nucleus and chromatin. Although the cytoskeleton has been shown to directly transmit stresses, we show that the intrinsically dynamic nature of the actin cytoskeleton is important in relaying extracellular signals to telomeres. Interestingly, this mechanical pathway not only transmits physical stimuli but also chemical stimuli. The cytoskeletal network continuously reorganizes and applies dynamic forces on the nucleus and feeds into the regulation of telomere dynamics...
August 29, 2018: Biophysical Journal
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