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https://www.readbyqxmd.com/read/28749535/inhibition-of-histone-deacetylases-sensitizes-egfr-tki-resistant-non-small-cell-lung-cancer-cells-to-erlotinib-in-vitro-and-in-vivo
#1
Weiwei Yu, Weiqiang Lu, Guoliang Chen, Feixiong Cheng, Hui Su, Yihua Chen, Mingyao Liu, Xiufeng Pang
BACKGROUND AND PURPOSE: Intrinsic and/or acquired resistance of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) commonly occurs in patients with non-small-cell lung cancer (NSCLC). Here, we develop a combined therapy of histone deacetylase inhibition by a novel HDAC inhibitor, YF454A, with erlotinib to overcome EGFR-TKI resistance in NSCLC. EXPERIMENTAL APPROACH: The sensitization of erlotinib by YF454A was examined in a panel of EGFR-TKI-resistant NSCLC cell lines in vitro and two different erlotinib-resistant NSCLC xenograft mouse models in vivo...
July 27, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28749409/host-response-comparison-of-h1n1-and-h5n1-infected-mice-identifies-two-potential-death-mechanisms
#2
Olivier Leymarie, Léa Meyer, Pierre-Louis Hervé, Bruno Da Costa, Bernard Delmas, Christophe Chevalier, Ronan Le Goffic
Highly pathogenic influenza A viruses (IAV) infections represent a serious threat to humans due to their considerable morbidity and mortality capacities. A good understanding of the molecular mechanisms responsible for the acute lung injury observed during this kind of infection is essential to design adapted therapies. In the current study, using an unbiased transcriptomic approach, we compared the host-responses of mice infected with two different subtypes of IAV: H1N1 vs. H5N1. The host-response comparison demonstrated a clear difference between the transcriptomic profiles of H1N1- and H5N1-infected mice despite identical survival kinetics and similar viral replications...
July 27, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28749043/transcriptome-profiling-reveals-the-immune-response-of-goose-t-cells-under-selenium-stimuli
#3
Nan Cao, Wanyan Li, Bingxin Li, Yunbo Tian, Danning Xu
The goose is an economically important poultry species and a principal natural host of avian viruses. This study aimed to determine the effects of selenium on the immune response of geese. Under selenium stimulation, gene expression profiling was investigated using transcriptome sequencing. The selenoproteins were promoted by selenium stimulation, while the heat shock proteins, interleukin and interferons were mainly down-regulated. After comparison, 2228 differentially expressed genes were primarily involved in immune and environmental response, and infectious disease and genetic information processing related pathways were identified...
July 27, 2017: Animal Science Journal, Nihon Chikusan Gakkaihō
https://www.readbyqxmd.com/read/28749036/advantages-of-rna-seq-compared-to-rna-microarrays-for-transcriptome-profiling-of-anterior-cruciate-ligament-tears
#4
Muhammad Farooq Rai, Eric D Tycksen, Linda J Sandell, Robert H Brophy
Microarrays and RNA-seq are at the forefront of high throughput transcriptome analyses. Since these methodologies are based on different principles there are concerns about the concordance of data between the two techniques. The concordance of RNA-seq and microarrays for genome-wide analysis of differential gene expression has not been rigorously assessed in clinically derived ligament tissues. To demonstrate the concordance between RNA-seq and microarrays and to assess potential benefits of RNA-seq over microarrays, we assessed differences in transcript expression in anterior cruciate ligament (ACL) tissues based on time-from-injury...
July 27, 2017: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/28748452/single-cell-transcriptomics-reveals-gene-signatures-and-alterations-associated-with-aging-in-distinct-neural-stem-progenitor-cell-subpopulations
#5
Zhanping Shi, Yanan Geng, Jiping Liu, Huina Zhang, Liqiang Zhou, Quan Lin, Juehua Yu, Kunshan Zhang, Jie Liu, Xinpei Gao, Chunxue Zhang, Yinan Yao, Chong Zhang, Yi E Sun
Aging associated cognitive decline has been linked to dampened neural stem/progenitor cells (NSC/NPCs) activities manifested by decreased proliferation, reduced propensity to produce neurons, and increased differentiation into astrocytes. While gene transcription changes objectively reveal molecular alterations of cells undergoing various biological processes, the search for molecular mechanisms underlying aging of NSC/NPCs has been confronted by the enormous heterogeneity in cellular compositions of the brain and the complex cellular microenvironment where NSC/NPCs reside...
July 26, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28748213/metabolic-reprogramming-underlies-metastatic-potential-in-an-obesity-responsive-murine-model-of-metastatic-triple-negative-breast-cancer
#6
Ciara H O'Flanagan, Emily L Rossi, Shannon B McDonell, Xuewen Chen, Yi-Hsuan Tsai, Joel S Parker, Jerry Usary, Charles M Perou, Stephen D Hursting
The vast majority of cancer-related deaths are due to metastatic disease, whereby primary tumor cells disseminate and colonize distal sites within the body. Triple negative breast cancer typically displays aberrant Wnt signaling, lacks effective targeted therapies, and compared with other breast cancer subtypes, is more likely to recur and metastasize. We developed a Wnt-driven lung metastasis model of triple negative breast cancer (metM-Wnt(lung)) through serial passaging of our previously described, nonmetastatic, claudin-low M-Wnt cell line...
2017: NPJ Breast Cancer
https://www.readbyqxmd.com/read/28748187/de-novo-assembly-and-characterization-of-cajanus-scarabaeoides-l-thouars-transcriptome-by-paired-end-sequencing
#7
Deepti Nigam, Swati Saxena, G Ramakrishna, Archana Singh, N K Singh, Kishor Gaikwad
Pigeonpea [Cajanus cajan (L.) Millsp.] is a heat and drought resilient legume crop grown mostly in Asia and Africa. Pigeonpea is affected by various biotic (diseases and insect pests) and abiotic stresses (salinity and water logging) which limit the yield potential of this crop. However, resistance to all these constraints is not readily available in the cultivated genotypes and some of the wild relatives have been found to withstand these resistances. Thus, the utilization of crop wild relatives (CWR) in pigeonpea breeding has been effective in conferring resistance, quality and breeding efficiency traits to this crop...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28748001/a-long-range-interactive-dna-methylation-marker-panel-for-the-promoters-of-hoxa9-and-hoxa10-predicts-survival-in-breast-cancer-patients
#8
Seong-Min Park, Eun-Young Choi, Mingyun Bae, Jung Kyoon Choi, Youn-Jae Kim
BACKGROUND: Most DNA cancer methylation markers are based on the transcriptional regulation of the promoter-gene relationship. Recently, the importance of long-range interactions between distal CpGs and target genes has been revealed. Here, we attempted to identify methylation markers for breast cancer that interact with distant genes. RESULTS: We performed integrated analysis using chromatin interactome data, methylome data, transcriptome data, and clinical information for breast cancer from public databases...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28747920/unraveling-key-metabolomic-alterations-in-wheat-embryos-derived-from-freshly-harvested-and-water-imbibed-seeds-of-two-wheat-cultivars-with-contrasting-dormancy-status
#9
Aayudh Das, Dea-Wook Kim, Pramod Khadka, Randeep Rakwal, Jai S Rohila
Untimely rains in wheat fields during harvest season can cause pre-harvest sprouting (PHS), which deteriorates the yield and quality of wheat crop. Metabolic homeostasis of the embryo plays a role in seed dormancy, determining the status of the maturing grains either as dormant (PHS-tolerant) or non-dormant (PHS-susceptible). Very little is known for direct measurements of global metabolites in embryonic tissues of dormant and non-dormant wheat seeds. In this study, physiologically matured and freshly harvested wheat seeds of PHS-tolerant (cv...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28747918/root-knot-and-cyst-nematodes-activate-procambium-associated-genes-in-arabidopsis-roots
#10
Yasuka L Yamaguchi, Reira Suzuki, Javier Cabrera, Satoru Nakagami, Tomomi Sagara, Chika Ejima, Ryosuke Sano, Yuichi Aoki, Rocio Olmo, Tetsuya Kurata, Takeshi Obayashi, Taku Demura, Takashi Ishida, Carolina Escobar, Shinichiro Sawa
Developmental plasticity is one of the most striking features of plant morphogenesis, as plants are able to vary their shapes in response to environmental cues. Biotic or abiotic stimuli often promote organogenesis events in plants not observed under normal growth conditions. Root-knot nematodes (RKNs) are known to parasitize multiple species of rooting plants and to induce characteristic tissue expansion called galls or root-knots on the roots of their hosts by perturbing the plant cellular machinery. Galls contain giant cells (GCs) and neighboring cells, and the GCs are a source of nutrients for the parasitizing nematode...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28747714/transcriptomic-biomarkers-to-discriminate-bacterial-from-nonbacterial-infection-in-adults-hospitalized-with-respiratory-illness
#11
Soumyaroop Bhattacharya, Alex F Rosenberg, Derick R Peterson, Katherine Grzesik, Andrea M Baran, John M Ashton, Steven R Gill, Anthony M Corbett, Jeanne Holden-Wiltse, David J Topham, Edward E Walsh, Thomas J Mariani, Ann R Falsey
Lower respiratory tract infection (LRTI) commonly causes hospitalization in adults. Because bacterial diagnostic tests are not accurate, antibiotics are frequently prescribed. Peripheral blood gene expression to identify subjects with bacterial infection is a promising strategy. We evaluated whole blood profiling using RNASeq to discriminate infectious agents in adults with microbiologically defined LRTI. Hospitalized adults with LRTI symptoms were recruited. Clinical data and blood was collected, and comprehensive microbiologic testing performed...
July 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28747711/a-systems-approach-to-a-spatio-temporal-understanding-of-the-drought-stress-response-in-maize
#12
Zhenyan Miao, Zhaoxue Han, Ting Zhang, Siyuan Chen, Chuang Ma
Crops are often subjected to periods of drought stress during their life cycle. However, how stress response mechanisms contribute to the crosstalk between stress signaling pathways and developmental signaling pathways is still unknown. We built a gene co-expression network from a spatio-temporal transcriptomic map of the drought stress response in maize (Zea mays), profiled from three tissues and four developmental stages and characterized hub genes associated with duplication events, selection, and regulatory networks...
July 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28747667/rna-sequencing-reveals-resistance-of-tlr4-ligand-activated-microglial-cells-to-inflammation-mediated-by-the-selective-jumonji-h3k27-demethylase-inhibitor
#13
Amitabh Das, Sarder Arifuzzaman, Taeho Yoon, Sun Hwa Kim, Jin Choul Chai, Young Seek Lee, Kyoung Hwa Jung, Young Gyu Chai
Persistent microglial activation is associated with the production and secretion of various pro-inflammatory genes, cytokines and chemokines, which may initiate or amplify neurodegenerative diseases. A novel synthetic histone 3 lysine 27 (H3K27) demethylase JMJD3 inhibitor, GSK-J4, was proven to exert immunosuppressive activities in macrophages. However, a genome-wide search for GSK-J4 molecular targets has not been undertaken in microglia. To study the immuno-modulatory effects of GSK-J4 at the transcriptomic level, triplicate RNA sequencing and quantitative real-time PCR analyses were performed with resting, GSK-J4-, LPS- and LPS + GSK-J4-challenged primary microglial (PM) and BV-2 microglial cells...
July 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28747659/porcine-familial-adenomatous-polyposis-model-enables-systematic-analysis-of-early-events-in-adenoma-progression
#14
Tatiana Flisikowska, Monika Stachowiak, Hongen Xu, Alexandra Wagner, Alejandra Hernandez-Caceres, Christine Wurmser, Carolin Perleberg, Hubert Pausch, Anna Perkowska, Konrad Fischer, Dmitrij Frishman, Ruedi Fries, Marek Switonski, Alexander Kind, Dieter Saur, Angelika Schnieke, Krzysztof Flisikowski
We compared gene expression in low and high-grade intraepithelial dysplastic polyps from pigs carrying an APC (1311) truncating mutation orthologous to human APC (1309) , analysing whole samples and microdissected dysplastic epithelium. Gene set enrichment analysis revealed differential expression of gene sets similar to human normal mucosa versus T1 stage polyps. Transcriptome analysis of whole samples revealed many differentially-expressed genes reflecting immune infiltration. Analysis of microdissected dysplastic epithelium was markedly different and showed increased expression in high-grade intraepithelial neoplasia of several genes known to be involved in human CRC; and revealed possible new roles for GBP6 and PLXND1...
July 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28747644/active-nuclear-transcriptome-analysis-reveals-inflammasome-dependent-mechanism-for-early-neutrophil-response-to-mycobacterium-marinum
#15
Amy Kenyon, Daria Gavriouchkina, Jernej Zorman, Giorgio Napolitani, Vincenzo Cerundolo, Tatjana Sauka-Spengler
The mechanisms governing neutrophil response to Mycobacterium tuberculosis remain poorly understood. In this study we utilise biotagging, a novel genome-wide profiling approach based on cell type-specific in vivo biotinylation in zebrafish to analyse the initial response of neutrophils to Mycobacterium marinum, a close genetic relative of M. tuberculosis used to model tuberculosis. Differential expression analysis following nuclear RNA-seq of neutrophil active transcriptomes reveals a significant upregulation in both damage-sensing and effector components of the inflammasome, including caspase b, NLRC3 ortholog (wu: fb15h11) and il1β...
July 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28747643/generation-of-ribosome-imprinted-polymers-for-sensitive-detection-of-translational-responses
#16
Helen A King, Hazim F El-Sharif, Ana M Matia-González, Valentina Iadevaia, Adeola Fowotade, Subrayal M Reddy, André P Gerber
Whilst the profiling of the transcriptome and proteome even of single-cells becomes feasible, the analysis of the translatome, which refers to all messenger RNAs (mRNAs) engaged with ribosomes for protein synthesis, is still an elaborate procedure requiring millions of cells. Herein, we report the generation and use of "smart materials", namely molecularly imprinted polymers (MIPs) to facilitate the isolation of ribosomes and translated mRNAs from merely 1,000 cells. In particular, we show that a hydrogel-based ribosome imprinted polymer could recover ribosomes and associated mRNAs from human, simian and mice cellular extracts, but did not selectively enrich yeast ribosomes, thereby demonstrating selectivity...
July 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28747528/embryo-implantation-evolved-from-an-ancestral-inflammatory-attachment-reaction
#17
Oliver W Griffith, Arun R Chavan, Stella Protopapas, Jamie Maziarz, Roberto Romero, Gunter P Wagner
The molecular changes that support implantation in eutherian mammals are necessary to establish pregnancy. In marsupials, pregnancy is relatively short, and although a placenta does form, it is present for only a few days before parturition. However, morphological changes in the uterus of marsupials at term mimic those that occur during implantation in humans and mice. We investigated the molecular similarity between term pregnancy in the marsupials and implantation in eutherian mammals using the gray short-tailed opossum (Monodelphis domestica) as a model...
July 26, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28747504/targeted-genome-sequencing-reveals-varicella-zoster-virus-open-reading-frame-12-deletion
#18
Randall J Cohrs, Katherine S Lee, Addilynn Beach, Bridget Sanford, Nicholas L Baird, Christina Como, Chiharu Graybill, Dallas Jones, Eden Tekeste, Mitchell Ballard, Xiaomi Chen, David Yalacki, Seth Frietze, Kenneth Jones, Tihana Lenac Rovis, Stipan Jonjić, Jürgen Haas, Don Gilden
The neurotropic herpesvirus varicella zoster virus (VZV) establishes a life-long latent infection in humans following primary infection. The low abundance of VZV nucleic acids in human neurons has hindered an understanding of the mechanisms that regulate viral gene transcription during latency. To overcome this critical barrier, we optimized a targeted capture protocol to enrich VZV DNA and cDNA prior to whole-genome/transcriptome sequence analysis. Since the VZV genome is remarkably stable, it was surprising to detect that VZV32, a VZV laboratory strain with no discernable growth defect in tissue culture, contained a 2158-bp deletion in open reading frame (ORF) 12...
July 26, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28747503/identification-of-vaccinia-virus-replisome-and-transcriptome-proteins-by-ipond-coupled-with-mass-spectrometry
#19
Tatiana G Senkevich, George Katsafanas, Andrea Weisberg, Lisa R Olano, Bernard Moss
Poxviruses replicate within the cytoplasm and encode proteins for DNA and mRNA synthesis. To investigate poxvirus replication and transcription from a new perspective, we incorporated 5-ethynyl-2' -deoxyuridine (EdU) into nascent DNA in cells infected with vaccinia virus (VACV). The EdU-labeled DNA was conjugated to fluor- or biotin-azide and visualized by confocal, super resolution and transmission electron microscopy. Nuclear labeling decreased dramatically after infection, accompanied by intense labeling of cytoplasmic foci...
July 26, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28747473/dissecting-the-contributions-of-time-and-microbe-density-to-variation-in-immune-gene-expression
#20
Ann T Tate, Andrea L Graham
Widespread differential expression of immunological genes is a hallmark of the response to infection in almost all surveyed taxa. However, several challenges remain in the attempt to connect differences in gene expression with functional outcomes like parasite killing and host survival. For example, temporal gene expression patterns are not always monotonic (unidirectional slope), yielding results that qualitatively depend on the time point selected for analysis. They may also be correlated to microbe density, confounding the strength of an immune response and resistance to parasites...
July 26, 2017: Proceedings. Biological Sciences
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