166,601 research outputs found
Mammalian LIN-7 PDZ proteins associate with beta-catenin at the cell junctions of epithelia and neurons
No full textThe heterotrimeric PDZ complex containing LIN-2, LIN-7 and LIN-10 is known to be involved in the organization of epithelial and neuronal junctions in Caenorhabditis elegans and mammals. We report here that mammalian LIN-7 PDZ proteins form a complex with cadherin and β-catenin in epithelia and neurons. The association of LIN-7 with cadherin and β-catenin is Ca2+ dependent and is mediated by the direct binding of LIN-7 to the C-terminal PDZ target sequence of β-catenin, as demonstrated by means of co-immunoprecipitation experiments and in vitro binding assays with the recombinant glutathione S-transferase:LIN-7A. The presence of β-catenin at the junction is required in order to relocate LIN-7 from the cytosol to cadherin-mediated adhesions, thus indicating that LIN-7 junctional recruitment is β-catenin dependent and that one functional role of the binding is to localize LIN-7. Moreover, when LIN-7 is present at the β-catenin-containing junctions, it determines the accumulation of binding partners, thus suggesting the mechanism by which β-catenin mediates the organization of the junctional domai
Singaporemma bifurcata Lin & Li 2010
No full textSingaporemma bifurcata Lin & Li, 2010 Figures 1A–H, 2A–E, 6F–f, 8A Singaporemma bifurcata Lin & Li, 2010: 26, figs 29–37 Examined material. Topotypes 11♂ 25♀ (NHMSU), CHINA: Guizhou, Suiyang, Wenquan Town, Guihua Village, Hejiao Cave, 28°15´N, 107°17´E, altitude 695 m, 17 April 2015, Y. Lin and H. Yang leg. Diagnosis. With the exception of S. wulongensis, male of S. bifurcata can be distinguished from all other congeners by the embolus with an asymmetrically furcate end (Fig. 6f vs. Fig. 6a–d, 6g –h), and female of S. bifurcata differs by the stubby, sclerotized central process (Fig. 8A vs. Figs. 5C–D, 7A–C, 9A–B). S. bifurcata similar to S. wulongensis in the shape of palpal bulb and the configuration of vulva, but male of S. bifurcata can be distinguished from that of S. wulongensis by the starting position of embolus (Fig. 6F vs. Fig. 6E, the position indicated by the blue arrow) and the unequal length of branches of embolic tip (Fig. 6f vs. Fig. 6e); female of S. bifurcata separated by the smaller, “Ω”-shaped inner vulval plate, and the shorter central process (Fig. 8A vs. Fig. 8B). Description. See Figs 1A–H, 2A–E, 6F–f, 8A and Lin & Li, 2010: 26. Distribution. China (Guizhou) (Fig. 10).Published as part of Yan, Fanhu & Lin, Yucheng, 2018, A review of the spider genus Singaporemma (Araneae: Tetrablemmidae), with the description of a new species, pp. 329-346 in Zootaxa 4392 (2) on page 334, DOI: 10.11646/zootaxa.4392.2.6, http://zenodo.org/record/119544
LIN-2/CASK binds to both ACR-16 and UNC-29 through SH3 domain.
No full text(A) Summary of interactions by Yeast two-hybrid. Strong interaction (++); weak interaction (+), and no interactions (-) were indicated. (B) LIN-2A’s SH3 domain binds the ACR-16’s second intracellular loop (LoopII) in a Yeast two-hybrid assay. Y2HGold cells carrying indicated plasmids (Left) growing on selective media (-Trp/-Leu/-His/-Ade) is shown (Right). (C) LIN-2A’s SH3 domain binds the UNC-29’s second intracellular loop (LoopII) in the Yeast two-hybrid assay. (D-E) FRM-3 do not bind the ACR-16’s second intracellular loop (LoopII) (D) and UNC-29’s second intracellular loop (LoopII) (E) in the Yeast two-hybrid assay. (F-G) LIN-2A binds FRM-3 (F) and its FERM domain (G) requiring its PDZ domain, but not SH3 domain.</p
Differential 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
Quantitative Insights into Developmental Signals and Phenotypes in C. elegans
Full text linkDesign of biomaterials and cellular scaffolds for tissue-engineering applications and regenerative medicine requires a precise understanding of the principles underlying multicellular patterning. Adhesion, migration, division, differentiation, and apoptosis are characteristic cellular behaviors, the engineering of which has the potential to allow creation of custom, multicellular structures. These cellular events occur naturally during embryonic and postembryonic development of multicellular organisms. Development thus offers the opportunity to learn about the design principles and molecular mechanisms that guide cellular patterning.
A key finding in developmental biology is that a limited set of conserved molecular signaling pathways act at multiple times and locations throughout the embryo to introduce cell-fate asymmetries in homogenous populations of cells. In turn, these asymmetries serve as starting points for the patterning of new organs. These signaling pathways interact quantitatively at multiple levels, including signaling cues, post-translational regulation, and gene-regulatory networks, to guide multicellular patterning.
How does the quantitative performance of these signaling networks ensure the intended phenotype pattern? How do changes in the quantitative performance of these networks, possibly over the course of evolution, give rise to new phenotypes? These are the central questions pursued in this thesis.
In order to answer such questions, we used vulva formation in the nematode Caenorhabditis elegans as a model system of cellular patterning. We formulated a mathematical model of the molecular network underlying cellular-fate specification in this system. Computational analysis of this molecular network reveals that cell–cell coupling through lateral LIN-12/Notch signaling amplifies the perception of the gradient in the epidermal-growth-factor-like soluble cue, LIN-3. Thus, the gradient in LIN-3 concentration produces an even steeper difference in LIN-3-mediated intracellular signals between adjoining cells. Such gradient amplification may be particularly important in converting a shallow, graded-specification signal into a spatial pattern of distinct fate choices.
Through quantitative perturbations of interaction strengths between components of the vulval patterning network, we further show that our modeling approach can correctly predict phenotype patterns observed in C. elegans mutation studies. This study generated a framework for quantitative analysis of molecular networks that links quantitative molecular perturbations to patterning outcomes. This framework will prove useful in the analysis of other systems involving cellular fate decisions and in tissue engineering applications where the generation of precise cell patterns is needed. We demonstrate the generality of our approach through an application to evolutionary developmental biology. Since molecular connectivity of the vulva patterning network of several closely related Caenorhabditis species is preserved, we correctly predict the quantitative diversification that must have occurred in this network during species evolution.</p
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
Measurement of the ratio of prompt χ c to J / ψ production in pp collisions at √s = 7 TeV
Full text linkThe prompt production of charmonium χ c and J / ψ states is studied in proton-proton collisions at a centre-of-mass energy of √s = 7 TeV at the Large Hadron Collider. The χ c and J / ψ mesons are identified through their decays χ c → J / ψ γ and J / ψ → μ + μ - using 36 pb - 1 of data collected by the LHCb detector in 2010. The ratio of the prompt production cross-sections for χ c and J / ψ, σ (χ c → J / ψ γ) / σ (J / ψ), is determined as a function of the J / ψ transverse momentum in the range 2 < p T J / ψ < 15 GeV / c. The results are in excellent agreement with next-to-leading order non-relativistic expectations and show a significant discrepancy compared with the colour singlet model prediction at leading order, especially in the low p T J / ψ region
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