783 research outputs found
Electron localization in defective ceria films: A study with scanning-tunneling microscopy and density-functional theory
Ponderomotive effects in multiphoton pair production
The Dirac-Heisenberg-Wigner formalism is employed to investigate
electron-positron pair production in cylindrically symmetric but otherwise
spatially inhomogeneous, oscillating electric fields. The oscillation
frequencies are hereby tuned to obtain multiphoton pair production in the
nonperturbative threshold regime. An effective mass as well as a
trajectory-based semi-classical analysis are introduced in order to interpret
the numerical results for the distribution functions as well as for the
particle yields and spectra. The results, including the asymptotic particle
spectra, display clear signatures of ponderomotive forces.Comment: 9 pages, 3 Tables, 3 Figure
microRNA regulation of mammalian target of rapamycin expression and activity controls estrogen receptor function and RAD001 sensitivity
Background:
The AKT/mammalian target of rapamycin (mTOR) signaling pathway is regulated by 17
α
-estradiol (E2)
signaling and mediates E2-induced proliferation and progesterone receptor (PgR) expression in breast cancer.
Methods and results:
Here we use deep sequencing analysis of previously published data from The Cancer
Genome Atlas to demonstrate that expression of a key component of mTOR signaling, rapamycin-insensitive
companion of mTOR (Rictor), positively correlated with an estrogen receptor-
α
positive (ER
α
+
) breast tumor signature.
Through increased microRNA-155 (miR-155) expression in the ER
α
+
breast cancer cells we demonstrate repression
of Rictor enhanced activation of mTOR complex 1 (mTORC1) signaling with both qPCR and western blot.
miR-155-mediated mTOR signaling resulted in deregulated ER
α
signalingbothinculturedcells
in vitro
and in
xenografts
in vivo
in addition to repressed PgR expression and act
ivity.FurthermoreweobservedthatmiR-155
enhanced mTORC1 signaling (observed through western
blot for increased phosphorylation on mTOR S2448) and
induced inhibition of mTORC2 signaling (evident through
repressed Rictor and tuberous sclerosis 1 (TSC1) gene
expression). mTORC1 induced deregulation of E2 signaling was confirmed using qPCR and the mTORC1-specific
inhibitor RAD001. Co-treatment of MCF7 breast cancer cells stably overexpressing miR-155 with RAD001 and E2
restored E2-induced PgR gene expression. RAD001 treatment of SCID/CB17 mice inhibited E2-induced tumorigenesis
of the MCF7 miR-155 overexpressing cell line. Finally we demonstrated a strong positive correlation between Rictor
and PgR expression and a negative correlation with Raptor expression in Luminal B breast cancer samples, a breast
cancer histological subtype known for having an altered ER
α
-signaling pathway.
Conclusions:
miRNA mediated alterations in mTOR and ER
α
signaling establishes a new mechanism for altered
estrogen responses independent of growth factor stimulation
Dual regulation by microRNA-200b-3p and microRNA-200b-5p in the inhibition of epithelial-to-mesenchymal transition in triple-negative breast cancer
Epithelial to mesenchymal transition (EMT) involves loss of an epithelial phenotype and activation of a mesenchymal one. Enhanced expression of genes associated with a mesenchymal transition includes ZEB1/2, TWIST, and FOXC1. miRNAs are known regulators of gene expression and altered miRNA expression is known to enhance EMT in breast cancer. Here we demonstrate that the tumor suppressive miRNA family, miR-200, is not expressed in triple negative breast cancer (TNBC) cell lines and that miR-200b-3p over-expression represses EMT, which is evident through decreased migration and increased CDH1 expression. Despite the loss of migratory capacity following re-expression of miR-200b-3p, no subsequent loss of the conventional miR-200 family targets and EMT markers ZEB1/2 was observed. Next generation RNA-sequencing analysis showed that enhanced expression of pri-miR-200b lead to ectopic expression of both miR-200b-3p and miR-200b-5p with multiple isomiRs expressed for each of these miRNAs. Furthermore, miR-200b-5p was expressed in the receptor positive, epithelial breast cancer cell lines but not in the TNBC (mesenchymal) cell lines. In addition, a compensatory mechanism for miR-200b-3p/200b-5p targeting, where both miRNAs target the RHOGDI pathway leading to non-canonical repression of EMT, was demonstrated. Collectively, these data are the first to demonstrate dual targeting by miR-200b-3p and miR-200b-5p and a previously undescribed role for microRNA processing and strand expression in EMT and TNBC, the most aggressive breast cancer subtype
Incidence and predictors of atrial fibrillation following transcatheter closure of interatrial septal communications using contemporary devices
The Deep Space Network: A Radio Communications Instrument for Deep Space Exploration
The primary purpose of the Deep Space Network (DSN) is to serve as a communications instrument for deep space exploration, providing communications between the spacecraft and the ground facilities. The uplink communications channel provides instructions or commands to the spacecraft. The downlink communications channel provides command verification and spacecraft engineering and science instrument payload data
Genome wide association mapping in <i>Arabidopsis thaliana</i> identifies novel genes involved in linking allyl glucosinolate to altered biomass and defense
A key limitation in modern biology is the ability to rapidly identify genes underlying newly identified complex phenotypes. Genome wide association studies (GWAS) have become an increasingly important approach for dissecting natural variation by associating phenotypes with genotypes at a genome wide level. Recent work is showing that the Arabidopsis thaliana defense metabolite, allyl glucosinolate (GSL), may provide direct feedback regulation, linking defense metabolism outputs to the growth, and defense responses of the plant. However, there is still a need to identify genes that underlie this process. To start developing a deeper understanding of the mechanism(s) that modulate the ability of exogenous allyl GSL to alter growth and defense, we measured changes in plant biomass and defense metabolites in a collection of natural 96 A. thaliana accessions fed with 50 μM of allyl GSL. Exogenous allyl GSL was introduced exclusively to the roots and the compound transported to the leaf leading to a wide range of heritable effects upon plant biomass and endogenous GSL accumulation. Using natural variation we conducted GWAS to identify a number of new genes which potentially control allyl responses in various plant processes. This is one of the first instances in which this approach has been successfully utilized to begin dissecting a novel phenotype to the underlying molecular/polygenic basis
Lipid modulation contributes to heat stress adaptation in peanut
At the cellular level, membrane damage is a fundamental cause of yield loss at high temperatures (HT). We report our investigations on a subset of a peanut (Arachis hypogaea) recombinant inbred line population, demonstrating that the membrane lipid remodeling occurring at HT is consistent with homeoviscous adaptation to maintain membrane fluidity. A major alteration in the leaf lipidome at HT was the reduction in the unsaturation levels, primarily through reductions of 18:3 fatty acid chains, of the plastidic and extra-plastidic diacyl membrane lipids. In contrast, levels of 18:3-containing triacylglycerols (TGs) increased at HT, consistent with a role for TGs in sequestering fatty acids when membrane lipids undergo remodeling during plant stress. Polyunsaturated acyl chains from membrane diacyl lipids were also sequestered as sterol esters (SEs). The removal of 18:3 chains from the membrane lipids decreased the availability of susceptible molecules for oxidation, thereby minimizing oxidative damage in membranes. Our results suggest that transferring 18:3 chains from membrane diacyl lipids to TGs and SEs is a key feature of lipid remodeling for HT adaptation in peanut. Finally, QTL-seq allowed the identification of a genomic region associated with heat-adaptive lipid remodeling, which would be useful for identifying molecular markers for heat tolerance
The ERBB4/HER4 receptor tyrosine kinase regulates gene expression by functioning as a STAT5A nuclear chaperone
In the lactating breast, ERBB4 localizes to the nuclei of secretory epithelium while regulating activities of the signal transducer and activator of transcription (STAT) 5A transcription factor essential for milk-gene expression. We have identified an intrinsic ERBB4 NLS (residues 676–684) within the ERBB4 intracellular domain (4ICD) that is essential for nuclear accumulation of 4ICD. To determine the functional significance of 4ICD nuclear translocation in a physiologically relevant system, we have demonstrated that cotransfection of ERBB4 and STAT5A in a human breast cancer cell line stimulates β-casein promoter activity. Significantly, nuclear localization of STAT5A and subsequent stimulation of the β-casein promoter requires nuclear translocation of 4ICD. Moreover, 4ICD and STAT5A colocalize within nuclei of heregulin β1 (HRG)-stimulated cells and both proteins bind to the endogenous β-casein promoter in T47D breast cancer cells. Together, our results establish a novel molecular mechanism of transmembrane receptor signal transduction involving nuclear cotranslocation of the receptor intracellular domain and associated transcription factor. Subsequent binding of the two proteins at transcription factor target promoters results in activation of gene expression
Gene Expression Profiling and Identification of Resistance Genes to Aspergillus flavus Infection in Peanut through EST and Microarray Strategies
Aspergillus flavus and A. parasiticus infect peanut seeds and produce aflatoxins, which are associated with various diseases in domestic animals and humans throughout the world. The most cost-effective strategy to minimize aflatoxin contamination involves the development of peanut cultivars that are resistant to fungal infection and/or aflatoxin production. To identify peanut Aspergillus-interactive and peanut Aspergillus-resistance genes, we carried out a large scale peanut Expressed Sequence Tag (EST) project which we used to construct a peanut glass slide oligonucleotide microarray. The fabricated microarray represents over 40% of the protein coding genes in the peanut genome. For expression profiling, resistant and susceptible peanut cultivars were infected with a mixture of Aspergillus flavus and parasiticus spores. The subsequent microarray analysis identified 62 genes in resistant cultivars that were up-expressed in response to Aspergillus infection. In addition, we identified 22 putative Aspergillus-resistance genes that were constitutively up-expressed in the resistant cultivar in comparison to the susceptible cultivar. Some of these genes were homologous to peanut, corn, and soybean genes that were previously shown to confer resistance to fungal infection. This study is a first step towards a comprehensive genome-scale platform for developing Aspergillus-resistant peanut cultivars through targeted marker-assisted breeding and genetic engineering
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