99,066 research outputs found
Thermoresponsive Behaviors of Poly(oxypropylene)-amidoamine Functionalized Carbon Nanotubes
No full textDifferential roles of the microRNA let-7 in C. elegans tissue development
Full text linkThe organs and tissues of the human body comprise of an astonishing variety of cells as different in morphology and function as muscle cells and neurons. Amazingly, despite their different protein contents, they largely contain the identical genomic information. In order to understand the processes that enable this differentiation, we need to determine the underlying regulatory mechanisms. A very recent discovery in this context was the posttranscriptional regulation of gene expression by microRNAs (miRNAs). miRNAs are small RNA molecules that mediate translational repression and degradation of mRNA transcripts through partial complementarity to their 3’ untranslated region (UTR) . Among the first miRNAs to be identified, let-7 stands out for its high conservation in sequence and developmental functions in development throughout the animal kingdom. During my PhD, I studied the role of let-7 in Caenorhabditis elegans in the context of two distinct processes of tissue development, namely differentiation of the epidermis (called hypodermis), and morphogenesis of the vulva. The functions of the let-7 miRNA in formation of the adult cuticle have been extensively studied and are well understood. let-7 controls differentiation of specific, mitotically active epidermal cells by inducing cell cycle exit, fusion, and switch to an adult specific transcriptional program upon repression of targets such as lin-41, daf-12, hbl-1 and let-60/ras. I set out to identify novel interactors of let-7 in a genome-wide RNAi screen for suppression of the lethal let-7 bursting phenotype. Candidates were then verified using fluorescence-based reporter systems for onset of hypodermis differentiation and intensity of repression of a known target. Thereby, I was able to validate a whole set of novel members of the let-7 network, comprising genes downstream in the pathway as well as potential regulators of let-7 activity. Notably, both groups of repressors contain factors required for cell cycle progression and mitosis, which indicates an active crosstalk between let-7 and the cell-cycle machinery. In a second project, I explored the molecular basis for the prominent let-7 vulval bursting phenotype. Despite the absence of overproliferation or any other obvious phenotype in vulval morphogenesis, I was able to show that let-7 activity is required in the vulva, and that its major function in this context is repression of a single target, namely lin-41. Disruption of let-7 binding to lin-41 through modification of the let-7 complementary sites by CRISPR/Cas9 mediated genome editing suffices to trigger the bursting phenotype, proving that repression of a single target is the key function of the miRNA in this context. In summary, my work shows that while both differentiation of hypodermis as well as vulval integrity are mediated through repression of lin-41, the downstream effect of this regulation seem to differ, suggesting that let-7 can be wired to control distinct processes depending on the cellular context. With respect to the latest findings both in C. elegans as well as in mammals, it will be interesting to determine if this depends on differential molecular functions of LIN-41 in the two tissues
Spatial Chow-Lin Methods for Data Completion in Econometric Flow Models
Full text linkFlow data across regions can be modeled by spatial econometric models, see LeSage and Pace (2009). Recently, regional studies became interested in the aggregation and disaggregation of flow models, because trade data cannot be obtained at a disaggregated level but data are published on an aggregate level. Furthermore, missing data in disaggregated flow models occur quite often since detailed measurements are often not possible at all observation points in time and space. In this paper we develop classical and Bayesian methods to complete flow data. The Chow and Lin (1971) method was developed for completing disaggregated incomplete time series data. We will extend this method in a general framework to spatially correlated flow data using the cross-sectional Chow-Lin method of Polasek et al. (2009). The missing disaggregated data can be obtained either by feasible GLS prediction or by a Bayesian (posterior) predictive density.Missing values in spatial econometrics, MCMC, non-spatial Chow-Lin (CL) and spatial Chow-Lin (SCL) methods, spatial internal flow (SIF) models, origin and destination (OD) data
Anomalous temperature-driven magnetization switching in CoxNi1?x/Cu(1 0 0) binary alloy films
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IL-4 Modulates Lipopolysaccharide-mediated Nitric Oxide and IL-6 Release via Inhibition of the Extracelular Signal-regulated Kinases, p38 Mitogen-activated Protein Kinase and Protein Kinase C.
No full textThe LIN-2/LIN-7/LIN-10 Complex Mediates Basolateral Membrane Localization of the C. elegans EGF Receptor LET-23 in Vulval Epithelial Cells
No full textAbstractIn C. elegans, the LET-23 receptor tyrosine kinase is localized to the basolateral membranes of polarized vulval epithelial cells. lin-2, lin-7, and lin-10 are required for basolateral localization of LET-23, since LET-23 is mislocalized to the apical membrane in lin-2, lin-7, and lin-10 mutants. Yeast two-hybrid, in vitro binding, and in vivo coimmunoprecipitation experiments show that LIN-2, LIN-7, and LIN-10 form a protein complex. Furthermore, compensatory mutations in lin-7 and let-23 exhibit allele-specific suppression of apical mislocalization and signaling-defective phenotypes. These results present a mechanism for basolateral localization of LET-23 receptor tyrosine kinase by direct binding to the LIN-2/LIN-7/LIN-10 complex. Each of the binding interactions within this complex is conserved, suggesting that this complex may also mediate basolateral localization in mammals
Conjugated linoleic acid concentration as affected by lactic cultures and added linoleic acid.
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