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https://www.readbyqxmd.com/read/28431219/genetic-analysis-of-%C3%AE-synuclein-3-untranslated-region-and-its-corresponding-micrornas-in-relation-to-parkinson-s-compared-to-dementia-with-lewy-bodies
#1
Lidia Tagliafierro, Omolara-Chinue Glenn, Madison E Zamora, Thomas G Beach, Randy L Woltjer, Michael W Lutz, Ornit Chiba-Falek
INTRODUCTION: The α-synuclein (SNCA) gene has been implicated in the etiology of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). METHODS: A computational analysis of SNCA 3' untranslated region to identify potential microRNA (miRNA) binding sites and quantitative real-time PCR to determine their expression in isogenic induced pluripotent stem cell-derived dopaminergic and cholinergic neurons as a model of PD and DLB, respectively, were performed. In addition, we performed a deep sequencing analysis of the SNCA 3' untranslated region of autopsy-confirmed cases of PD, DLB, and normal controls, followed by genetic association analysis of the identified variants...
April 18, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28431045/water-table-drawdown-shapes-the-depth-dependent-variations-in-prokaryotic-diversity-and-structure-in-zoige-peatlands
#2
Qiuping Zhong, Huai Chen, Liangfeng Liu, Yixin He, Dan Zhu, Lin Jiang, Wei Zhan, Ji Hu
Microbial communities are important to ecosystem function and sensitive to hydrological dynamics. However, we lack predictable knowledge about how soil microorganisms respond to water table drawdown in different depths. This research used high-throughput sequencing method to determine the responses of prokaryotic communities to the changes of water table and depth on Zoige peatlands. Our results showed that water table drawdown reduced alpha diversity indices (observed species, Shannon diversity and Chao1 richness) of prokaryotic communities...
April 18, 2017: FEMS Microbiology Ecology
https://www.readbyqxmd.com/read/28430977/deep-mining-heterogeneous-networks-of-biomedical-linked-data-to-predict-novel-drug-target-associations
#3
Nansu Zong, Hyeoneui Kim, Victoria Ngo, Olivier Harismendy
Motivation: A heterogeneous network topology possessing abundant interactions between biomedical entities has yet to be utilized in similarity-based methods for predicting drug-target associations based on the array of varying features of drugs and their targets. Deep learning reveals features of vertices of a large network that can be adapted in accommodating the similarity-based solutions to provide a flexible method of drug-target prediction. Results: We propose a similarity-based drug-target prediction method that enhances existing association discovery methods by using a topology-based similarity measure...
April 18, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28430949/capturing-non-local-interactions-by-long-short-term-memory-bidirectional-recurrent-neural-networks-for-improving-prediction-of-protein-secondary-structure-backbone-angles-contact-numbers-and-solvent-accessibility
#4
Rhys Heffernan, Yuedong Yang, Kuldip Paliwal, Yaoqi Zhou
Motivation: The accuracy of predicting protein local and global structural properties such as secondary structure and solvent accessible surface area has been stagnant for many years because of the challenge of accounting for non-local interactions between amino acid residues that are close in three-dimensional structural space but far from each other in their sequence positions. All existing machine-learning techniques relied on a sliding window of 10-20 amino acid residues to capture some "short to intermediate" non-local interactions...
April 18, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28429829/molecular-adaptation-in-the-world-s-deepest-living-animal-insights-from-transcriptome-sequencing-of-the-hadal-amphipod-hirondellea-gigas
#5
Yi Lan, Jin Sun, Renmao Tian, Douglas H Bartlett, Runsheng Li, Yue Him Wong, Weipeng Zhang, Jian-Wen Qiu, Ting Xu, Li-Sheng He, Harry G Tabata, Pei-Yuan Qian
The Challenger Deep in the Mariana Trench is the deepest point in the oceans of our planet. Understanding how animals adapt to this harsh environment characterized by high hydrostatic pressure, food-limited, dark, and cold is of great scientific interest. Of the animals dwelling in the Challenger Deep, amphipods have been captured using baited traps. In the present study, we sequenced the transcriptome of the amphipod Hirondellea gigas collected at a depth of 10,929 m from the East Pond of the Challenger Deep...
April 21, 2017: Molecular Ecology
https://www.readbyqxmd.com/read/28429724/clonal-evolution-in-myelodysplastic-syndromes
#6
Pedro da Silva-Coelho, Leonie I Kroeze, Kenichi Yoshida, Theresia N Koorenhof-Scheele, Ruth Knops, Louis T van de Locht, Aniek O de Graaf, Marion Massop, Sarah Sandmann, Martin Dugas, Marian J Stevens-Kroef, Jaroslav Cermak, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Satoru Miyano, Theo de Witte, Nicole M A Blijlevens, Petra Muus, Gerwin Huls, Bert A van der Reijden, Seishi Ogawa, Joop H Jansen
Cancer development is a dynamic process during which the successive accumulation of mutations results in cells with increasingly malignant characteristics. Here, we show the clonal evolution pattern in myelodysplastic syndrome (MDS) patients receiving supportive care, with or without lenalidomide (follow-up 2.5-11 years). Whole-exome and targeted deep sequencing at multiple time points during the disease course reveals that both linear and branched evolutionary patterns occur with and without disease-modifying treatment...
April 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28428977/19th-workshop-of-the-international-stroke-genetics-consortium-april-28-29-2016-boston-massachusetts-usa-2016-001-mri-defined-cerebrovascular-genomics-the-charge-consortium
#7
S Debette, Y Saba, D Vojinovic, X Jian, H Adams, G Chauhan, M Sargurupremraj, S Kaffashian, J Ding, J C Bis, P Nyquist, K Mather, C Van Duijn, L J Launer, M A Ikram, H Schmidt, W T Longstreth, M Fornage, S Seshadri
The CHARGE consortium is an investigator-initiated collaboration to facilitate meta-analyses of genome-wide association studies (GWAS) and genomic analyses based on next generation sequencing (NGS), among multiple large and well-phenotyped population-based cohort studies around the world (http://www.chargeconsortium.com). Within the neuro-CHARGE working group, we are presenting an update of ongoing genomic studies on MRI-markers of cerebrovascular disease. Large population-based studies have shown that the burden of cerebrovascular disease extends far beyond that of clinical stroke...
March 2017: Neurology. Genetics
https://www.readbyqxmd.com/read/28428345/proliferation-of-primary-human-hepatocytes-and-prevention-of-hepatitis-b-virus-reinfection-efficiently-deplete-nuclear-cccdna-in-vivo
#8
Lena Allweiss, Tassilo Volz, Katja Giersch, Janine Kah, Giuseppina Raffa, Joerg Petersen, Ansgar W Lohse, Concetta Beninati, Teresa Pollicino, Stephan Urban, Marc Lütgehetmann, Maura Dandri
OBJECTIVE: The stability of the covalently closed circular DNA (cccDNA) in nuclei of non-dividing hepatocytes represents a key determinant of HBV persistence. Contrarily, studies with animal hepadnaviruses indicated that hepatocyte turnover can reduce cccDNA loads but knowledge on the proliferative capacity of HBV-infected primary human hepatocytes (PHHs) in vivo and the fate of cccDNA in dividing PHHs is still lacking. This study aimed to determine the impact of human hepatocyte division on cccDNA stability in vivo...
April 20, 2017: Gut
https://www.readbyqxmd.com/read/28428261/ebf2-transcriptionally-regulates-brown-adipogenesis-via-the-histone-reader-dpf3-and-the-baf-chromatin-remodeling-complex
#9
Suzanne N Shapira, Hee-Woong Lim, Sona Rajakumari, Alexander P Sakers, Jeff Ishibashi, Matthew J Harms, Kyoung-Jae Won, Patrick Seale
The transcription factor early B-cell factor 2 (EBF2) is an essential mediator of brown adipocyte commitment and terminal differentiation. However, the mechanisms by which EBF2 regulates chromatin to activate brown fat-specific genes in adipocytes were unknown. ChIP-seq (chromatin immunoprecipitation [ChIP] followed by deep sequencing) analyses in brown adipose tissue showed that EBF2 binds and regulates the activity of lineage-specific enhancers. Mechanistically, EBF2 physically interacts with the chromatin remodeler BRG1 and the BAF chromatin remodeling complex in brown adipocytes...
April 20, 2017: Genes & Development
https://www.readbyqxmd.com/read/28427571/targeted-deep-sequencing-reveals-high-diversity-and-variable-dominance-of-bloom-forming-cyanobacteria-in-eutrophic-lakes
#10
Yongguang Jiang, Peng Xiao, Yang Liu, Jiangxin Wang, Renhui Li
Cyanobacterial blooms in eutrophic lakes are severe environmental problems worldwide. To characterize the spatiotemporal heterogeneity of cyanobacterial blooms, a high-throughput method is necessary for the specific detection of cyanobacteria. In this study, the cyanobacterial composition of three eutrophic waters in China (Taihu Lake, Dongqian Lake, and Dongzhen Reservoir) was determined by pyrosequencing the cpcBA intergenic spacer (cpcBA-IGS) of cyanobacteria. A total of 2585 OTUs were obtained from the normalized cpcBA-IGS sequence dataset at a distance of 0...
April 2017: Harmful Algae
https://www.readbyqxmd.com/read/28427202/clinical-implications-of-genomic-profiles-in-metastatic-breast-cancer-with-a-focus-on-tp53-and-pik3ca-the-most-frequently-mutated-genes
#11
Ji-Yeon Kim, Eunjin Lee, Kyunghee Park, Woong-Yang Park, Hae Hyun Jung, Jin Seok Ahn, Young-Hyuck Im, Yeon Hee Park
Breast cancer (BC) has been genetically profiled through large-scale genome analyses. However, the role and clinical implications of genetic alterations in metastatic BC (MBC) have not been evaluated. Therefore, we conducted whole-exome sequencing (WES) and RNA-Seq of 37 MBC samples and targeted deep sequencing of another 29 MBCs. We evaluated somatic mutations from WES and targeted sequencing and assessed gene expression and performed pathway analysis from RNA-Seq. In this analysis, PIK3CA was the most commonly mutated gene in estrogen receptor (ER)-positive BC, while in ER-negative BC, TP53 was the most commonly mutated gene (p = 0...
March 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28426742/multiple-components-of-pka-and-tgf-%C3%AE-pathways-are-mutated-in-pseudomyxoma-peritonei
#12
Lilli Saarinen, Pirjo Nummela, Alexandra Thiel, Rainer Lehtonen, Petrus Järvinen, Heikki Järvinen, Lauri A Aaltonen, Anna Lepistö, Sampsa Hautaniemi, Ari Ristimäki
Pseudomyxoma peritonei (PMP) is a subtype of mucinous adenocarcinoma mainly restricted to the peritoneal cavity and most commonly originating from the appendix. The genetic background of PMP is poorly understood and no targeted treatments are currently available for this fatal disease. While RAS signaling pathway is affected in most if not all PMP cases and over half of them also have a mutation in the GNAS gene, other genetic alterations and affected pathways are, to a large degree, poorly known. In this study, we sequenced whole coding genome of nine PMP tumors and paired normal tissues in order to identify additional, commonly mutated genes and signaling pathways affected in PMP...
2017: PloS One
https://www.readbyqxmd.com/read/28424610/characterizing-brain-iron-deposition-in-patients-with-subcortical-vascular-mild-cognitive-impairment-using-quantitative-susceptibility-mapping-a-potential-biomarker
#13
Yawen Sun, Xin Ge, Xu Han, Wenwei Cao, Yao Wang, Weina Ding, Mengqiu Cao, Yong Zhang, Qun Xu, Yan Zhou, Jianrong Xu
The presence and pattern of iron accumulation in subcortical vascular mild cognitive impairment (svMCI) and their effects on cognition have rarely been investigated. We aimed to examine brain iron deposition in svMCI subjects using quantitative susceptibility mapping (QSM). Moreover, we aimed to investigate the correlation between brain iron deposition and the severity of cognitive impairment as indicated by z-scores. We recruited 20 subcortical ischemic vascular disease (SIVD) patients who fulfilled the criteria for svMCI...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28424332/improving-genetic-diagnosis-in-mendelian-disease-with-transcriptome-sequencing
#14
Beryl B Cummings, Jamie L Marshall, Taru Tukiainen, Monkol Lek, Sandra Donkervoort, A Reghan Foley, Veronique Bolduc, Leigh B Waddell, Sarah A Sandaradura, Gina L O'Grady, Elicia Estrella, Hemakumar M Reddy, Fengmei Zhao, Ben Weisburd, Konrad J Karczewski, Anne H O'Donnell-Luria, Daniel Birnbaum, Anna Sarkozy, Ying Hu, Hernan Gonorazky, Kristl Claeys, Himanshu Joshi, Adam Bournazos, Emily C Oates, Roula Ghaoui, Mark R Davis, Nigel G Laing, Ana Topf, Peter B Kang, Alan H Beggs, Kathryn N North, Volker Straub, James J Dowling, Francesco Muntoni, Nigel F Clarke, Sandra T Cooper, Carsten G Bönnemann, Daniel G MacArthur
Exome and whole-genome sequencing are becoming increasingly routine approaches in Mendelian disease diagnosis. Despite their success, the current diagnostic rate for genomic analyses across a variety of rare diseases is approximately 25 to 50%. We explore the utility of transcriptome sequencing [RNA sequencing (RNA-seq)] as a complementary diagnostic tool in a cohort of 50 patients with genetically undiagnosed rare muscle disorders. We describe an integrated approach to analyze patient muscle RNA-seq, leveraging an analysis framework focused on the detection of transcript-level changes that are unique to the patient compared to more than 180 control skeletal muscle samples...
April 19, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28424201/pik3ca-mutations-contribute-to-acquired-cetuximab-resistance-in-metastatic-colorectal-cancer-patients
#15
Jian Ming Xu, Yan Wang, You-Liang Wang, Yan Wang, Tao Liu, Ming Ni, Man-Sheng Li, Li Lin, Fei-Jiao Ge, Chun Gong, Jun-Yan Gu, Ru Jia, He-Fei Wang, Yu Ling Chen, Rong-Rui Liu, Chuan-Hua Zhao, Zhao-Li Tan, Yang Jin, Yunping Zhu, Shuji Ogino, Zhi Rong Qian
<p>Mutations in KRAS are considered to be the main drivers of acquired resistance to epidermal growth factor receptor (EGFR) blockade in patients with metastatic colorectal cancer (mCRC). However, the potential roles of other genes downstream of the EGFR signaling pathway in conferring acquired resistance has not been extensively investigated.</p> <br /><br />Experimental Design: <p>Using circulating tumor DNA (ctDNA) from patients with mCRC and with acquired cetuximab resistance, we developed a targeted amplicon ultra-deep sequencing method to screen for low-abundance somatic mutations in a panel of genes that encode components of the EGFR signaling pathway...
April 19, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28424085/the-within-host-population-dynamics-of-mycobacterium-tuberculosis-vary-with-treatment-efficacy
#16
Andrej Trauner, Qingyun Liu, Laura E Via, Xin Liu, Xianglin Ruan, Lili Liang, Huimin Shi, Ying Chen, Ziling Wang, Ruixia Liang, Wei Zhang, Wang Wei, Jingcai Gao, Gang Sun, Daniela Brites, Kathleen England, Guolong Zhang, Sebastien Gagneux, Clifton E Barry, Qian Gao
BACKGROUND: Combination therapy is one of the most effective tools for limiting the emergence of drug resistance in pathogens. Despite the widespread adoption of combination therapy across diseases, drug resistance rates continue to rise, leading to failing treatment regimens. The mechanisms underlying treatment failure are well studied, but the processes governing successful combination therapy are poorly understood. We address this question by studying the population dynamics of Mycobacterium tuberculosis within tuberculosis patients undergoing treatment with different combinations of antibiotics...
April 19, 2017: Genome Biology
https://www.readbyqxmd.com/read/28423717/non-homologous-end-joining-induced-alterations-in-dna-methylation-a-source-of-permanent-epigenetic-change
#17
Brittany Allen, Antonio Pezone, Antonio Porcellini, Mark T Muller, Michal M Masternak
In addition to genetic mutations, epigenetic revision plays a major role in the development and progression of cancer; specifically, inappropriate DNA methylation or demethylation of CpG residues may alter the expression of genes that promote tumorigenesis. We hypothesize that DNA repair, specifically the repair of DNA double strand breaks (DSB) by Non-Homologous End Joining (NHEJ) may play a role in this process. Using a GFP reporter system inserted into the genome of HeLa cells, we are able to induce targeted DNA damage that enables the cells, after successfully undergoing NHEJ repair, to express WT GFP...
March 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423565/identification-and-characterization-of-l1-specific-endo-sirnas-essential-for-early-embryonic-development-in-pig
#18
Heng Zhang, Jilong Liu, Yurong Tai, Xiaolei Zhang, Jiaming Zhang, Shichao Liu, Jiawei Lv, Zhonghua Liu, Qingran Kong
Small noncoding RNAs (sncRNAs) play important roles in RNA interference (RNAi). In addition to microRNA (miRNA) and Piwi-interacting RNA (piRNA), one key member of sncRNAs group is endogenous small interfering RNA (endo-siRNA). Some studies do show the role of endo-siRNAs in Dicer and/or Ago mutants, however, the biological functions of specific endo-siRNAs remains mostly unanswered. In the study, we have performed a comparative analysis of endo-siRNAs present in porcine sperms, oocytes and zygotes, identified by deep sequencing and bioinformatics analysis...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28422344/use-of-blood-pool-agents-with-steady-state-mri-to-assess-the-vascular-system
#19
Avnesh S Thakor, John Chung, Premal Patel, Anthony Chan, Amdad Ahmed, Graeme McNeil, David M Liu, Bruce Forster, Darren Klass
Over the past two decades there have been significant advances in the use of magnetic resonance imaging (MRI) to assess the vascular system. New imaging sequences and improvements in magnet design have enabled the creation of higher spatial resolution images. MRI is now a viable alternative imaging modality when compared to both invasive angiography and computed tomographic angiography. The use of blood pool agents has further facilitated the use of MR angiography (MRA); their high molecular weight allows for lower doses of contrast medium administration while their prolonged presence in the blood stream allows for repeated high-quality volumetric imaging of both the arterial and venous circulation...
April 19, 2017: Journal of Magnetic Resonance Imaging: JMRI
https://www.readbyqxmd.com/read/28421416/emergence-of-ctnnb1-mutation-at-acquired-resistance-to-kit-inhibitor-in-metastatic-melanoma
#20
J Cho, S Y Kim, Y J Kim, M H Sim, S T Kim, N K D Kim, K Kim, W Park, J H Kim, K-T Jang, J Lee
PURPOSE: The KIT inhibitor, imatinib, has shown promising efficacy in patients with KIT-mutated melanoma; however, acquisition of resistance to imatinib occurs rapidly in the majority of patients. The mechanisms of acquired resistance to imatinib in melanoma remain unclear. METHODS: We analyzed biopsy samples from paired baseline and post-treatment tumor lesions in one patient with KIT-mutated melanoma who had had an initial objective tumor regression in response to imatinib treatment followed by disease progression 8 months later...
April 18, 2017: Clinical & Translational Oncology
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