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https://www.readbyqxmd.com/read/28637297/a-role-for-progesterone-regulated-sfrp4-expression-in-uterine-leiomyomas
#1
Meaghan A Delaney, Ying-Wooi Wan, Gyoung-Eun Kim, Chad J Creighton, Margaret G Taylor, Ramya Masand, Andrew Park, Cecilia Valdes, William Gibbons, Zhandong Liu, Matthew L Anderson
Context: Despite progesterone's key role in uterine smooth muscle tumorigenesis, the mechanisms by which it promotes the growth of uterine leiomyomas remain poorly understood. Objective: The aim of this study was to identify novel gene products mediating progesterone's effects in uterine leiomyomas. Design: Gene expression profiling was used to identify putative progesterone-regulated genes differentially expressed in uterine leiomyomas, which were then studied in vitro...
June 14, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28636953/dicer-deficiency-differentially-impacts-microglia-of-the-developing-and-adult-brain
#2
Diana Varol, Alexander Mildner, Thomas Blank, Anat Shemer, Neta Barashi, Simon Yona, Eyal David, Sigalit Boura-Halfon, Yifat Segal-Hayoun, Louise Chappell-Maor, Hadas Keren-Shaul, Dena Leshkowitz, Eran Hornstein, Martin Fuhrmann, Ido Amit, Nicola Maggio, Marco Prinz, Steffen Jung
Microglia seed the embryonic neuro-epithelium, expand and actively sculpt neuronal circuits in the developing central nervous system, but eventually adopt relative quiescence and ramified morphology in the adult. Here, we probed the impact of post-transcriptional control by microRNAs (miRNAs) on microglial performance during development and adulthood by generating mice lacking microglial Dicer expression at these distinct stages. Conditional Dicer ablation in adult microglia revealed that miRNAs were required to limit microglial responses to challenge...
June 20, 2017: Immunity
https://www.readbyqxmd.com/read/28636652/integrative-analysis-of-genomic-alterations-in-triple-negative-breast-cancer-in-association-with-homologous-recombination-deficiency
#3
Masahito Kawazu, Shinya Kojima, Toshihide Ueno, Yasushi Totoki, Hiromi Nakamura, Akiko Kunita, Wei Qu, Jun Yoshimura, Manabu Soda, Takahiko Yasuda, Natsuko Hama, Mihoko Saito-Adachi, Kazuhito Sato, Shinji Kohsaka, Eirin Sai, Masako Ikemura, Shigeru Yamamoto, Tomoko Ogawa, Masashi Fukayama, Keiichiro Tada, Yasuyuki Seto, Shinichi Morishita, Shoichi Hazama, Tatsuhiro Shibata, Yoshihiro Yamashita, Hiroyuki Mano
Triple-negative breast cancer (TNBC) cells do not express estrogen receptors, progesterone receptors, or human epidermal growth factor receptor 2. Currently, apart from poly ADP-ribose polymerase inhibitors, there are few effective therapeutic options for this type of cancer. Here, we present comprehensive characterization of the genetic alterations in TNBC performed by high coverage whole genome sequencing together with transcriptome and whole exome sequencing. Silencing of the BRCA1 gene impaired the homologous recombination pathway in a subset of TNBCs, which exhibited similar phenotypes to tumors with BRCA1 mutations; they harbored many structural variations (SVs) with relative enrichment for tandem duplication...
June 21, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28634715/regulatory-element-based-prediction-identifies-new-susceptibility-regulatory-variants-for-osteoporosis
#4
Shi Yao, Yan Guo, Shan-Shan Dong, Ruo-Han Hao, Xiao-Feng Chen, Yi-Xiao Chen, Jia-Bin Chen, Qing Tian, Hong-Wen Deng, Tie-Lin Yang
Despite genome-wide association studies (GWASs) have identified many susceptibility genes for osteoporosis, it still leaves a large part of missing heritability to be discovered. Integrating regulatory information and GWASs could offer new insights into the biological link between the susceptibility SNPs and osteoporosis. We generated five machine learning classifiers with osteoporosis-associated variants and regulatory features data. We gained the optimal classifier and predicted genome-wide SNPs to discover susceptibility regulatory variants...
June 20, 2017: Human Genetics
https://www.readbyqxmd.com/read/28632001/vasodilator-responsiveness-in-idiopathic-pulmonary-arterial-hypertension-identifying-a-distinct-phenotype-with-distinct-physiology-and-distinct-prognosis
#5
David Langleben, Stylianos Orfanos
Within the cohort of patients suffering from idiopathic pulmonary arterial hypertension (IPAH) is a group that responds dramatically (VR-PAH) to an acute vasodilator challenge and that has excellent long-term hemodynamic improvement and prognosis on high dose calcium channel blockers compared with vasodilator non-responders (VN-PAH). For the purposes of diagnosing VR-PAH, there is to date no test to replace the acute vasodilator challenge. However, recent studies have identified markers that may aid in the identification of VR-PAH, including peripheral blood lymphocyte RNA expression levels of desmogelin-2 and Ras homolog gene family member Q, and plasma levels of provirus integration site for Moloney murine leukemia virus...
June 20, 2017: Pulmonary Circulation
https://www.readbyqxmd.com/read/28631185/the-increased-expression-of-follicle-stimulating-hormone-leads-to-a-decrease-of-fecundity-in-transgenic-large-white-female-pigs
#6
Kai Jiang, Pan Xu, Wanbo Li, Qiang Yang, Longyun Li, Chuanmin Qiao, Huanfa Gong, Hao Zheng, Zhimin Zhou, Hao Fu, Qiuyan Li, Yuyun Xing, Jun Ren
Follicle-stimulating hormone (FSH) is a pituitary gonadotropin regulating reproduction in mammals. Overexpression of the exogenous FSHα/β genes from Chinese Erhualian pigs improved female fecundity of transgenic (TG) mice and male spermatogenesis ability of Large White TG boars. Here, we investigated the impact of the exogenous FSHα/β genes on female reproductive performance of Large White TG pigs. First, we identified the integration site of the exogenous FSHα/β genes at 140,646,456 bp on chromosome 9 in these TG pigs using whole-genome sequencing...
June 19, 2017: Transgenic Research
https://www.readbyqxmd.com/read/28630472/smyd3-promotes-homologous-recombination-via-regulation-of-h3k4-mediated-gene-expression
#7
Yun-Ju Chen, Cheng-Hui Tsai, Pin-Yu Wang, Shu-Chun Teng
SMYD3 is a methyltransferase highly expressed in many types of cancer. It usually functions as an oncogenic protein to promote cell cycle, cell proliferation, and metastasis. Here, we show that SMYD3 modulates another hallmark of cancer, DNA repair, by stimulating transcription of genes involved in multiple steps of homologous recombination. Deficiency of SMYD3 induces DNA-damage hypersensitivity, decreases levels of repair foci, and leads to impairment of homologous recombination. Moreover, the regulation of homologous recombination-related genes is via the methylation of H3K4 at the target gene promoters...
June 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28630415/integrating-genome-and-transcriptome-profiling-for-elucidating-the-mechanism-of-muscle-growth-and-lipid-deposition-in-pekin-ducks
#8
Liyuan Wang, Xiangxiang Li, Jun Ma, Yawen Zhang, Hao Zhang
Muscle growth and lipid deposition are co-ordinately regulated processes. Cherry Valley Pekin duck is a lean-type duck breed with high growth rate, whereas the native Pekin duck of China has high lipid deposition. Phenotypic analysis showed that native Pekin ducks have smaller fibre diameter and larger density in the breast muscle at 3 weeks of age and higher intramuscular fat content at 6 weeks of age than those in Cherry Valley Pekin ducks. We detected 17 positively selected genes (PSGs) by comparing genes mainly involved with muscle organ development, muscle contraction, peroxisome proliferator activated receptor signalling pathway, and fatty acid metabolism...
June 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28630288/intact-pirna-pathway-prevents-l1-mobilization-in-male-meiosis
#9
Simon J Newkirk, Suman Lee, Fiorella C Grandi, Valeriya Gaysinskaya, James M Rosser, Nicole Vanden Berg, Cathryn A Hogarth, Maria C N Marchetto, Alysson R Muotri, Michael D Griswold, Ping Ye, Alex Bortvin, Fred H Gage, Jef D Boeke, Wenfeng An
The PIWI-interacting RNA (piRNA) pathway is essential for retrotransposon silencing. In piRNA-deficient mice, L1-overexpressing male germ cells exhibit excessive DNA damage and meiotic defects. It remains unknown whether L1 expression simply highlights piRNA deficiency or actually drives the germ-cell demise. Specifically, the sheer abundance of genomic L1 copies prevents reliable quantification of new insertions. Here, we developed a codon-optimized L1 transgene that is controlled by an endogenous mouse L1 promoter...
June 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28630177/integrated-genome-and-transcriptome-sequencing-identifies-a-noncoding-mutation-in-the-genome-replication-factor-donson-as-the-cause-of-microcephaly-micromelia-syndrome
#10
Gilad D Evrony, Dwight R Cordero, Jun Shen, Jennifer N Partlow, Timothy W Yu, Rachel E Rodin, R Sean Hill, Michael E Coulter, Anh-Thu N Lam, Divya Jayaraman, Dianne Gerrelli, Diana G Diaz, Chloe Santos, Victoria Morrison, Antonella Galli, Ulrich Tschulena, Stefan Wiemann, M Jocelyne Martel, Betty Spooner, Steven C Ryu, Princess C Elhosary, Jillian M Richardson, Danielle Tierney, Christopher A Robinson, Rajni Chibbar, Dana Diudea, Rebecca Folkerth, Sheldon Wiebe, A James Barkovich, Ganeshwaran H Mochida, James Irvine, Edmond G Lemire, Patricia Blakley, Christopher A Walsh
While next-generation sequencing has accelerated the discovery of human disease genes, progress has been largely limited to the "low hanging fruit" of mutations with obvious exonic coding or canonical splice site impact. In contrast, the lack of high-throughput, unbiased approaches for functional assessment of most noncoding variants has bottlenecked gene discovery. We report the integration of transcriptome sequencing (RNA-seq), which surveys all mRNAs to reveal functional impacts of variants at the transcription level, into the gene discovery framework for a unique human disease, microcephaly-micromelia syndrome (MMS)...
June 19, 2017: Genome Research
https://www.readbyqxmd.com/read/28627677/integrated-analysis-of-the-potential-roles-of-mirna%C3%A2-mrna-networks-in-triple-negative-breast-cancer
#11
Huiru Zhu, Meiyu Dai, Xiaoli Chen, Xiang Chen, Shini Qin, Shengming Dai
Triple negative breast cancer (TNBC) is a type of breast cancer where the tumor cells are negative for the estrogen, progesterone and human epidermal growth factor 2 receptors. To date, expression profiling of microRNA (miRNA/miR) and mRNA sequences have been widely applied for the diagnosis of TNBC. In the present study, an integrated analysis of miRNA‑mRNA profiling arrays was performed. A total of five dysregulated miRNAs in patients with TNBC were identified, including upregulated miR‑558 expression and downregulated miR‑320d‑1, miR‑548v, miR‑99a and miR‑21 expression...
June 9, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28627406/multi-omics-facilitated-variable-selection-in-cox-regression-model-for-cancer-prognosis-prediction
#12
Cong Liu, Xujun Wang, Georgi Z Genchev, Hui Lu
Motivation New developments in high-throughput genomic technologies have enabled the measurement of diverse types of omics biomarkers in a cost-efficient and clinically-feasible manner. Developing computational methods and tools for analysis and translation of such genomic data into clinically-relevant information is an ongoing and active area of investigation. For example, several studies have utilized an unsupervised learning framework to cluster patients by integrating omics data. Despite such recent advances, predicting cancer prognosis using integrated omics biomarkers remains a challenge...
June 13, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28626364/ex-vivo-generation-of-genetically-modified-macrophages-from-human-induced-pluripotent-stem-cells
#13
Mania Ackermann, Alexandra Kuhn, Jessica Kunkiel, Sylvia Merkert, Ulrich Martin, Thomas Moritz, Nico Lachmann
BACKGROUND: Pluripotent stem cells, including induced pluripotent stem cells (iPSCs), have the capacity to differentiate towards all three germ layers and have been highlighted as an attractive cell source for the field of regenerative medicine. Thus, stable expression of therapeutic transgenes in iPSCs, as well as thereof derived progeny of hematopoietic lineage, may lay the foundation for innovative cell replacement therapies. METHODS: We have utilized human iPSC lines genetically modified by lentiviral vector technology or targeted integration of reporter genes to evaluate transgene expression during hematopoietic specification and differentiation towards macrophages...
June 2017: Transfusion Medicine and Hemotherapy
https://www.readbyqxmd.com/read/28625995/novel-antibiotic-resistance-determinants-from-agricultural-soil-exposed-to-antibiotics-widely-used-in-human-medicine-and-animal-farming
#14
Calvin Ho-Fung Lau, Kalene van Engelen, Stephen Gordon, Justin Renaud, Edward Topp
Antibiotic resistance has emerged globally as one of the biggest threats to human and animal health. Although the excessive use of antibiotics is recognized for accelerating the selection for resistance, there is a growing body of evidence suggesting that natural environments are "hotspots" for the development of both ancient and contemporary resistance mechanisms. Given that pharmaceuticals can be entrained onto agricultural land through anthropogenic activities, this could be a potential driver for the emergence and dissemination of resistance in soil bacteria...
June 16, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28625833/colorectal-cancer-cell-line-proteomes-are-representative-of-primary-tumors-and-predict-drug-sensitivity
#15
Jing Wang, Dmitri Mouradov, Xiaojing Wang, Robert N Jorissen, Matthew C Chambers, Lisa J Zimmerman, Suhas Vasaikar, Christopher G Love, Shan Li, Kym Lowes, Karl-Johan Leuchowius, Helene Jousset, Janet Weinstock, Christopher Yau, John Mariadason, Zhiao Shi, Yuguan Ban, Xi Chen, Robert J C Coffey, Robbert J C Slebos, Antony W Burgess, Daniel C Liebler, Bing Zhang, Oliver M Sieber
BACKGROUND AND AIMS: Proteomics holds promise for individualizing cancer treatment. We analyzed to what extent the proteomic landscape of human colorectal cancer (CRC) is maintained in established CRC cell lines and the utility of proteomics for predicting therapeutic responses. METHODS: Proteomic and transcriptomic analyses were performed on 44 CRC cell lines, compared against primary CRCs (n=95) and normal tissues (n=60), and integrated with genomic and drug sensitivity data...
June 15, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28624520/dissecting-the-chloroplast-proteome-of-chickpea-cicer-arietinum-l-provides-new-insights-into-classical-and-non-classical-functions
#16
Nilesh Vikram Lande, Pratigya Subba, Pragya Barua, Dipak Gayen, T S Keshava Prasad, Subhra Chakraborty, Niranjan Chakraborty
Chloroplast, the energy organelle unique to plant cells, is a dynamic entity which integrates an array of metabolic pathways and serves as first level for energy conversion for the entire ecological hierarchy. Increasing amount of sequence data and evolution of mass spectrometric approaches has opened up new avenues for opportune exploration of the global proteome of this organelle. In our study, we aimed at generation of a comprehensive catalogue of chloroplast proteins in a grain legume, chickpea and provided a reference proteome map...
June 14, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28624210/low-dose-gene-therapy-for-murine-pku-using-episomal-naked-dna-vectors-expressing-pah-from-its-endogenous-liver-promoter
#17
Hiu Man Grisch-Chan, Andrea Schlegel, Tanja Scherer, Gabriella Allegri, Raphael Heidelberger, Panagiota Tsikrika, Marco Schmeer, Martin Schleef, Cary O Harding, Johannes Häberle, Beat Thöny
Limited duration of transgene expression, insertional mutagenesis, and size limitations for transgene cassettes pose challenges and risk factors for many gene therapy vectors. Here, we report on physiological expression of liver phenylalanine hydroxylase (PAH) by delivery of naked DNA/minicircle (MC)-based vectors for correction of homozygous enu2 mice, a model of human phenylketonuria (PKU). Because MC vectors lack a defined size limit, we constructed a MC vector expressing a codon-optimized murine Pah cDNA that includes a truncated intron and is under the transcriptional control of a 3...
June 16, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28623590/integration-of-genome-wide-tf-binding-and-gene-expression-data-to-characterize-gene-regulatory-networks-in-plant-development
#18
Dijun Chen, Kerstin Kaufmann
Key transcription factors (TFs) controlling the morphogenesis of flowers and leaves have been identified in the model plant Arabidopsis thaliana. Recent genome-wide approaches based on chromatin immunoprecipitation (ChIP) followed by high-throughput DNA sequencing (ChIP-seq) enable systematic identification of genome-wide TF binding sites (TFBSs) of these regulators. Here, we describe a computational pipeline for analyzing ChIP-seq data to identify TFBSs and to characterize gene regulatory networks (GRNs) with applications to the regulatory studies of flower development...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28622513/comprehensive-and-integrative-genomic-characterization-of-hepatocellular-carcinoma
#19
(no author information available yet)
Liver cancer has the second highest worldwide cancer mortality rate and has limited therapeutic options. We analyzed 363 hepatocellular carcinoma (HCC) cases by whole-exome sequencing and DNA copy number analyses, and we analyzed 196 HCC cases by DNA methylation, RNA, miRNA, and proteomic expression also. DNA sequencing and mutation analysis identified significantly mutated genes, including LZTR1, EEF1A1, SF3B1, and SMARCA4. Significant alterations by mutation or downregulation by hypermethylation in genes likely to result in HCC metabolic reprogramming (ALB, APOB, and CPS1) were observed...
June 15, 2017: Cell
https://www.readbyqxmd.com/read/28621677/genome-wide-methylome-and-chromatin-interactome-identify-abnormal-enhancer-to-be-risk-factor-of-breast-cancer
#20
Yuan Wang, Da-Peng Hao, Jing-Jing Li, Li Wang, Li-Jun Di
Enhancer is critical cis regulatory elements in gene expression. To understand whether and how the aberrant enhancer activation may contribute to cancer risk, the differentially methylated enhancers (eDMRs) in normal and malignant breast tissues were identified and analyzed. By incorporating genome-wide chromatin interaction, integrated analysis of eDMRs and target gene expression identified 1,272 enhancer-promoter pairs. Surprisingly, two functionally distinct groups of genes were identified in these pairs, one showing better correlation to enhancer methylation (eRGs) and the other showing better correlation to promoter methylation (pRGs), and the former group is functionally enriched with cancer related genes...
June 2, 2017: Oncotarget
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