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Functional genomics

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https://www.readbyqxmd.com/read/28927115/wee1-inhibition-by-mk1775-as-a-single-agent-therapy-inhibits-ovarian-cancer-viability
#1
Minghui Zhang, Donye Dominguez, Siqi Chen, Jie Fan, Lei Qin, Alan Long, Xia Li, Yi Zhang, Huirong Shi, Bin Zhang
Wee1-like protein kinase (WEE1) physiologically serves a key function in maintaining the integrity of the cell genome through mediating the activation of cyclin-dependent kinase (CDK)1 and CDK2. Increased expression of WEE1 has been associated with the poor prognosis of patients with ovarian cancer. The present study aimed at examining the in vitro and in vivo antitumor activity of MK1775, a potent pharmacological inhibitor of WEE1, as a single agent against ovarian cancer cells. The cytotoxicity of MK1775 was examined in a panel of tumor cells using MTT in vitro...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28926997/effects-of-cellular-methylation-on-transgene-expression-and-site-specific-integration-of-adeno-associated-virus
#2
Diptiman Chanda, Jonathan A Hensel, Jerome T Higgs, Rajat Grover, Niroop Kaza, Selvarangan Ponnazhagan
DNA methylation is a major epigenetic event that affects not only cellular gene expression but that also has the potential to influence bacterial and viral DNA in their host-dependent functions. Adeno-associated virus (AAV) genome contains a high degree of CpG sequences capable of methylation in its terminal repeat sequences, which are the sole elements retained in AAV-based vectors used in gene therapy. The present study determined the influence of methylation status of the host cell on wild type (wt) AAV integration and recombinant (r) AAV transgene expression in HeLa cells...
September 18, 2017: Genes
https://www.readbyqxmd.com/read/28926993/satellite-dna-an-evolving-topic
#3
REVIEW
Manuel A Garrido-Ramos
Satellite DNA represents one of the most fascinating parts of the repetitive fraction of the eukaryotic genome. Since the discovery of highly repetitive tandem DNA in the 1960s, a lot of literature has extensively covered various topics related to the structure, organization, function, and evolution of such sequences. Today, with the advent of genomic tools, the study of satellite DNA has regained a great interest. Thus, Next-Generation Sequencing (NGS), together with high-throughput in silico analysis of the information contained in NGS reads, has revolutionized the analysis of the repetitive fraction of the eukaryotic genomes...
September 18, 2017: Genes
https://www.readbyqxmd.com/read/28926971/mini-review-the-contribution-of-intermediate-phenotypes-to-gxe-effects-on-disorders-of-body-composition-in-the-new-omics-era
#4
REVIEW
Edna J Nava-Gonzalez, Esther C Gallegos-Cabriales, Irene Leal-Berumen, Raul A Bastarrachea
Studies of gene-environment (GxE) interactions describe how genetic and environmental factors influence the risk of developing disease. Intermediate (molecular or clinical) phenotypes (IPs) are traits or metabolic biomarkers that mediate the effects of gene-environment influences on risk behaviors. Functional systems genomics discovery offers mechanistic insights into how DNA variations affect IPs in order to detect genetic causality for a given disease. Disorders of body composition include obesity (OB), Type 2 diabetes (T2D), and osteoporosis (OSTP)...
September 17, 2017: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/28926843/the-genetic-basis-of-delayed-puberty
#5
S R Howard, Leo Dunkel
<br>The genetic control of puberty remains an important but mostly unanswered question. Late pubertal timing affects over 2% of adolescents and is associated with adverse health outcomes including short stature, reduced bone mineral density and compromised psychosocial health. Self-limited delayed puberty (DP) is a highly heritable trait, which often segregates in an autosomal dominant pattern; however, its neuroendocrine pathophysiology and genetic regulation remain unclear. Some insights into the genetic mutations that lead to familial DP have come from sequencing genes known to cause GnRH deficiency, most recently via next generation sequencing, and others from large-scale genome wide association studies in the general population...
September 18, 2017: Neuroendocrinology
https://www.readbyqxmd.com/read/28926812/isotope-and-microbiome-data-provide-complementary-information-to-identify-natural-nitrate-attenuation-processes-in-groundwater
#6
Elena Hernández-Del Amo, Anna Menció, Frederic Gich, Josep Mas-Pla, Lluís Bañeras
Natural attenuation processes alleviate the impact of fertilization practices on groundwater resources. Therefore, identifying the occurrence of denitrification has become a requirement for water quality management. Several approaches are useful for this purpose, such as isotopic and microbiological methods, each of them providing distinct but complementary information about denitrification reactions, attenuation rates and their occurrence in the aquifer. In this paper, we investigate the contribution of both approaches to describe denitrification in a consolidated rock aquifer (limestone and marls), with a porosity related to fracture networks located in the northeastern sector of the Osona basin (NE Spain)...
September 16, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28926624/molecular-characterization-expression-analysis-and-heterologous-expression-of-two-translationally-controlled-tumor-protein-genes-from-cucumis-sativus
#7
Xiang Nan Meng, Qiu Min Chen, Hai Yan Fan, Tie Feng Song, Na Cui, Ju Yong Zhao, Shu Min Jia, Ke Xin Meng
The translationally controlled tumor protein (TCTP) is a family of abundant and ubiquitous proteins involved in several important primary functions. Cucumbers harbor two TCTP genes, CsTCTP1 and CsTCTP2; however, their functional roles remain unclear. In this study, we isolated CsTCTP1 and CsTCTP2 (XP-004134215 and XP-004135602, respectively) promoters, full-length cDNA and genomic sequences from Cucumis sativus. Bioinformatics analysis, containing cis-acting elements, structural domains, phylogenetic tree and conserved motifs, suggested the conservation and divergence of CsTCTP1 and CsTCTP2, thus providing knowledge regarding their functions...
2017: PloS One
https://www.readbyqxmd.com/read/28926604/a-novel-class-of-chemicals-that-react-with-abasic-sites-in-dna-and-specifically-kill-b-cell-cancers
#8
Shanqiao Wei, Madusha L W Perera, Ramin Sakhtemani, Ashok S Bhagwat
Most B cell cancers overexpress the enzyme activation-induced deaminase at high levels and this enzyme converts cytosines in DNA to uracil. The constitutive expression of this enzyme in these cells greatly increases the uracil content of their genomes. We show here that these genomes also contain high levels of abasic sites presumably created during the repair of uracils through base-excision repair. We further show that three alkoxyamines with an alkyne functional group covalently link to abasic sites in DNA and kill immortalized cell lines created from B cell lymphomas, but not other cancers...
2017: PloS One
https://www.readbyqxmd.com/read/28926587/functional-characterization-of-zebrafish-orthologs-of-the-human-beta-3-glucosyltransferase-b3glct-gene-mutated-in-peters-plus-syndrome
#9
Eric Weh, Hideyuki Takeuchi, Sanaa Muheisen, Robert S Haltiwanger, Elena V Semina
Peters Plus Syndrome (PPS) is a rare autosomal recessive disease characterized by ocular defects, short stature, brachydactyly, characteristic facial features, developmental delay and other highly variable systemic defects. Classic PPS is caused by loss-of-function mutations in the B3GLCT gene encoding for a β3-glucosyltransferase that catalyzes the attachment of glucose via a β1-3 glycosidic linkage to O-linked fucose on thrombospondin type 1 repeats (TSRs). B3GLCT was shown to participate in a non-canonical ER quality control mechanism; however, the exact molecular processes affected in PPS are not well understood...
2017: PloS One
https://www.readbyqxmd.com/read/28926430/targeting-histone-methylation-in-cancer
#10
Michael T McCabe, Helai P Mohammad, Olena Barbash, Ryan G Kruger
Most, if not all, human cancers exhibit altered epigenetic signatures that promote aberrant gene expression that contributes to cellular transformation. Historically, attempts to pharmacologically intervene in this process have focused on DNA methylation and histone acetylation. More recently, genome-wide studies have identified histone and chromatin regulators as one of the most frequently dysregulated functional classes in a wide range of cancer types. These findings have provided numerous potential therapeutic targets including many that affect histone methylation...
September 2017: Cancer Journal
https://www.readbyqxmd.com/read/28926145/a-crispr-reimagining-new-twists-and-turns-of-crispr-beyond-the-genome-engineering-revolution
#11
Robert J Plummer, Yi Guo, Ying Peng
Despite its explosive applications in genome engineering, CRISPR (Clustered Regularly Interspersed Short Palindromic Repeats) has been developed into a versatile tool beyond its well-known nuclease function. In this prospect article, we summarize a few exciting "off-label" applications of CRISPR including manipulating DNA sequences, visualizing chromosomal loci in living cells, and modulating transcription and chromatin structures. These novel applications will likely elevate CRISPR tools into yet another level of sophistication and diversity, leading to many more exciting cell biological discoveries...
September 19, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28926110/pacap-and-pac1r-are-differentially-expressed-in-motor-cortex-of-amyotrophic-lateral-sclerosis-patients-and-support-survival-of-ipsc-derived-motor-neurons
#12
Gabriele Bonaventura, Rosario Iemmolo, Agata Grazia D'Amico, Valentina La Cognata, Erminio Costanzo, Mario Zappia, Velia D'Agata, Francesca Luisa Conforti, Eleonora Aronica, Sebastiano Cavallaro
Amyotrophic lateral sclerosis (ALS) is a fatal and disabling neurodegenerative disease characterized by upper and lower motor neurons depletion. In our previous work, comprehensive genomic profiling of 41 motor cortex samples enabled to discriminate controls from sporadic ALS patients, and segregated these latter into two distinct subgroups (SALS1 and SALS2), each associated with different deregulated genes. In the present study, we focused our attention on two of them, Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) and its type 1 receptor (PAC1R), and validated the results of the transcriptome experiments by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), immunohistochemistry and western blot analysis...
September 19, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28925997/precision-annotation-of-digital-samples-in-ncbi-s-gene-expression-omnibus
#13
Dexter Hadley, James Pan, Osama El-Sayed, Jihad Aljabban, Imad Aljabban, Tej D Azad, Mohamad O Hadied, Shuaib Raza, Benjamin Abhishek Rayikanti, Bin Chen, Hyojung Paik, Dvir Aran, Jordan Spatz, Daniel Himmelstein, Maryam Panahiazar, Sanchita Bhattacharya, Marina Sirota, Mark A Musen, Atul J Butte
The Gene Expression Omnibus (GEO) contains more than two million digital samples from functional genomics experiments amassed over almost two decades. However, individual sample meta-data remains poorly described by unstructured free text attributes preventing its largescale reanalysis. We introduce the Search Tag Analyze Resource for GEO as a web application (http://STARGEO.org) to curate better annotations of sample phenotypes uniformly across different studies, and to use these sample annotations to define robust genomic signatures of disease pathology by meta-analysis...
September 19, 2017: Scientific Data
https://www.readbyqxmd.com/read/28925810/ube3a-mediated-regulation-of-imprinted-genes-and-epigenome-wide-marks-in-human-neurons
#14
S Jesse Lopez, Keith Dunaway, M Saharul Islam, Charles Mordaunt, Annie Vogel Ciernia, Makiko Meguro-Horike, Shin-Ichi Horike, David J Segal, Janine LaSalle
The dysregulation of genes in neurodevelopmental disorders that lead to social and cognitive phenotypes is a complex, multilayered process involving both genetics and epigenetics. Parent-of-origin effects of deletion and duplication of the 15q11-q13 locus leading to Angelman, Prader-Willi, and Dup15q syndromes are due to imprinted genes, including UBE3A, which is maternally expressed exclusively in neurons. UBE3A encodes a ubiquitin E3 ligase protein with multiple downstream targets, including RING1B, which in turn monoubiquitinates histone variant H2A...
September 19, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28925527/one-gene-two-proteins-coordinated-production-of-a-copper-chaperone-by-differential-transcript-formation-and-translational-frameshifting-in-escherichia-coli
#15
Steffen Lorenz Drees, Birgit Klinkert, Stefan Helling, Dominik Fabian Beyer, Katrin Marcus, Franz Narberhaus, Mathias Lübben
Programmed ribosomal frameshifting (PRF) is a translational anomaly causing the ribosome to shift into an alternative reading frame. PRFs are common in viral genomes, using a single nucleotide sequence to code for two proteins in overlapping frames. In bacteria and eukaryota, PRFs are less frequent. We report on a PRF in the copper detoxification system of Escherichia coli where a metallochaperone is generated out of the first 69 amino acids and a C-terminal out-of-frame glycine of the gene copA. copA besides codes for the P1B -ATPase CopA, a membrane-integral protein and principal interaction target of the chaperone...
September 19, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28925507/-epigallocatechin-3-gallate-and-ezh2-inhibitor-gsk343-have-similar-inhibitory-effects-and-mechanisms-of-action-on-colorectal-cancer-cells
#16
Le Ying, Feng Yan, Bryan R G Williams, Ping Xu, Xin Li, Yueling Zhao, Yiqun Hu, Yuefei Wang, Dakang Xu, Jing Dai
Epigallocatechin-3-gallate (EGCG) is a type of catechin. It exhibits excellent antioxidant effects and anti-tumor activities for cancer chemoprevention. The mechanism of anti-tumor effects of EGCG on different cancers has been studied for the past few decades, but remains controversial. To investigate the potential role that EGCG may play in the epigenetic regulation of colorectal cancer (CRC) cell line, we integrated bioinformatics analysis with experimental validation. We found that levels of the enhancer of zeste homolog 2 (EZH2) were significantly higher in CRC tissues compared to normal adjacent tissues, based on the Genomic Data Commons (GDC) data portal...
September 19, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28925404/ing5-activity-in-self-renewal-of-glioblastoma-stem-cells-via-calcium-and-follicle-stimulating-hormone-pathways
#17
F Wang, A Y Wang, C Chesnelong, Y Yang, A Nabbi, S Thalappilly, V Alekseev, K Riabowol
Stem cell-like brain tumor initiating cells (BTICs) cause recurrence of glioblastomas, with BTIC 'stemness' affected by epigenetic mechanisms. The ING family of epigenetic regulators (ING1-5) function by targeting histone acetyltransferase (HAT) or histone deacetylase complexes to the H3K4me3 mark to alter histone acetylation and subsequently, gene expression. Here we find that ectopic expression of ING5, the targeting subunit of HBO1, MOZ and MORF HAT complexes increases expression of the Oct4, Olig2 and Nestin stem cell markers, promotes self-renewal, prevents lineage differentiation and increases stem cell pools in BTIC populations...
September 18, 2017: Oncogene
https://www.readbyqxmd.com/read/28925401/endogenous-androgen-receptor-proteomic-profiling-reveals-genomic-subcomplex-involved-in-prostate-tumorigenesis
#18
S Stelloo, E Nevedomskaya, Y Kim, L Hoekman, O B Bleijerveld, T Mirza, L F A Wessels, W M van Weerden, A F M Altelaar, A M Bergman, W Zwart
Androgen receptor (AR) is a key player in prostate cancer development and progression. Here we applied immunoprecipitation mass spectrometry of endogenous AR in LNCaP cells to identify components of the AR transcriptional complex. In total, 66 known and novel AR interactors were identified in the presence of synthetic androgen, most of which were critical for AR-driven prostate cancer cell proliferation. A subset of AR interactors required for LNCaP proliferation were profiled using chromatin immunoprecipitation assays followed by sequencing, identifying distinct genomic subcomplexes of AR interaction partners...
September 18, 2017: Oncogene
https://www.readbyqxmd.com/read/28925399/dock4-promotes-loss-of-proliferation-in-glioblastoma-progenitor-cells-through-nuclear-beta-catenin-accumulation-and-subsequent-mir-302-367-cluster-expression
#19
D N Debruyne, L Turchi, F Burel-Vandenbos, M Fareh, F Almairac, V Virolle, D Figarella-Branger, N Baeza-Kallee, P Lagadec, V Kubiniek, P Paquis, D Fontaine, M-P Junier, H Chneiweiss, T Virolle
Glioblastomas (GBM) are lethal primitive brain tumours characterized by a strong intra-tumour heterogeneity. We observed in GBM tissues the coexistence of functionally divergent micro-territories either enriched in more differentiated and non-mitotic cells or in mitotic undifferentiated OLIG2 positive cells while sharing similar genomic abnormalities. Understanding the formation of such functionally divergent micro-territories in glioblastomas (GBM) is essential to comprehend GBM biogenesis, plasticity and to develop therapies...
September 18, 2017: Oncogene
https://www.readbyqxmd.com/read/28924976/spontaneous-generation-of-a-novel-foetal-human-retinal-pigment-epithelium-rpe-cell-line-available-for-investigation-on-phagocytosis-and-morphogenesis
#20
Zhihua Shao, Haiyun Wang, Xuejian Zhou, Baosen Guo, Xuehu Gao, Zengrong Xiao, Meng Liu, Jihong Sha, Chunlian Jiang, Yuping Luo, Zhixue Liu, Siguang Li
OBJECTIVES: Primary retinal pigment epithelium (RPE) cells have a limited capacity to re-establish epithelial morphology and to maintain native RPE function in vitro, and all commercially available RPE cell lines have drawbacks of morphology or function; therefore, the establishment of new RPE cell lines with typical characteristics of RPE would be helpful in further understanding of their physiological and pathological mechanisms. Here, we firstly report a new spontaneously generated RPE line, fhRPE-13A, from a 13-week aborted foetus...
September 18, 2017: Cell Proliferation
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