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1.
Clémence L. Gamblin émilie J.-L. Hardy Fran?ois J.-M. Chartier Nicolas Bisson Patrick Laprise 《The Journal of cell biology》2014,204(4):487-495
During epithelial cell polarization, Yurt (Yrt) is initially confined to the lateral membrane and supports the stability of this membrane domain by repressing the Crumbs-containing apical machinery. At late stages of embryogenesis, the apical recruitment of Yrt restricts the size of the apical membrane. However, the molecular basis sustaining the spatiotemporal dynamics of Yrt remains undefined. In this paper, we report that atypical protein kinase C (aPKC) phosphorylates Yrt to prevent its premature apical localization. A nonphosphorylatable version of Yrt dominantly dismantles the apical domain, showing that its aPKC-mediated exclusion is crucial for epithelial cell polarity. In return, Yrt counteracts aPKC functions to prevent apicalization of the plasma membrane. The ability of Yrt to bind and restrain aPKC signaling is central for its role in polarity, as removal of the aPKC binding site neutralizes Yrt activity. Thus, Yrt and aPKC are involved in a reciprocal antagonistic regulatory loop that contributes to segregation of distinct and mutually exclusive membrane domains in epithelial cells. 相似文献
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Joyce S. F. D. de Almeida Teobaldo R. Cuya Guizado Ana P. Guimarães Teodorico C. Ramalho Arlan S. Gonçalves Martijn C. de Koning 《Journal of biomolecular structure & dynamics》2016,34(12):2632-2642
In the present work, we performed docking and molecular dynamics simulations studies on two groups of long-tailored oximes designed as peripheral site binders of acetylcholinesterase (AChE) and potential penetrators on the blood brain barrier. Our studies permitted to determine how the tails anchor in the peripheral site of sarin-inhibited human AChE, and which aminoacids are important to their stabilization. Also the energy values obtained in the docking studies corroborated quite well with the experimental results obtained before for these oximes. 相似文献
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J. H. D. Bassett A. A. J. Pannett S. A. Forbes R. V. Thakker M. McCarthy A. P. Read B. T. Teh C. Larsson S. Kytölä J. Leisti P. Salmela G. Weber S. Giraud C. X. Zhang A. Calender J. W. M. Höppener H. K. Ploos van Amstel C. J. M. Lips K. Kas W. J. M. Van de Ven P. Gaudray 《Human genetics》1997,100(5-6):657-665
Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterised by tumours of the parathyroids,
pancreas and anterior pituitary. The MEN1 gene has been localised to a 2-Mb region of chromosome 11q13 by meiotic mapping
studies in MEN1 families. Such studies may have a limited resolution of approximately 1 cM (i.e. 1 Mb) and we have therefore
investigated 96 MEN1 families (40 British, 17 French, 12 Finnish, 7 Swedish, 7 Dutch, 7 North American, 2 Australian, 1 New
Zealand, 1 German, 1 Spanish and 1 Danish) for linkage disequilibrium, in order to facilitate a finer mapping resolution.
We have utilised five microsatellite DNA sequence polymorphisms from the candidate region and have accurately determined their
allele sizes, which ranged from 161 bp to 272 bp. The heterozygosity and number of alleles (given in brackets), respectively,
at the loci were: D11S1883 (76%, 11), D11S457 (55%, 5), PYGM (94%, 18), D11S1783 (10%, 4) and D11S449 (87%, 16). Allelic association
was assessed by Chi-square 2 ×n contingency tables, by Fisher exact 2 ×n contingency tables and by a likelihood-based approach. The results of haplotype analysis revealed 91 different affected haplotypes
in the 96 families, an identical affected haplotype being observed in no more than two families. These results indicate the
absence of an ancestral affected haplotype. Significant linkage disequilibrium (P < 0.005) could be established amongst the microsatellite loci but not between the loci and MEN1 in either the total population
or in any of the geographical sub-populations. The absence of linkage disequilibrium between MEN1 and the polymorphic loci
is probably the result of the occurrence of multiple different disease-causing mutations in MEN1.
Received: 1 April 1997 / Accepted: 25 June 1997 相似文献
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François Blanquart Sylvain Gandon 《Evolution; international journal of organic evolution》2014,68(6):1617-1628
Populations often experience variable conditions, both in time and space. Here we develop a novel theoretical framework to study the evolution of migration under the influence of spatially and temporally variable selection and genetic drift. First, we examine when polymorphism is maintained at a locus under heterogeneous selection, as a function of the pattern of spatial heterogeneity and the migration rate. In a second step, we study how levels of migration evolve under the joint action of kin competition and local adaptation at a polymorphic locus. This analysis reveals the existence of evolutionary bistability, whereby a low or a high migration rate may evolve depending on the initial conditions. Last, we relax several assumptions regarding selection heterogeneity commonly made in previous studies and explore the consequences of more complex spatial and temporal patterns of variability in selection on the evolution of migration. We found that small modifications in the pattern of environmental heterogeneity may have dramatic effects on the evolution of migration. This work highlights the importance of considering more general scenarios of environmental heterogeneity when studying the evolution of life‐history traits in ecologically complex settings. 相似文献
6.
Despite their importance in nano-environmental health and safety, interactions between engineered nanomaterials and microbial life remain poorly characterized. Here, we used the model organism E. coli to study the penetration requirements, subcellular localization, induction of stress responses, and long-term fate of luminescent Mn-doped ZnS nanocrystals fabricated under “green” processing conditions with a minimized ZnS-binding protein. We find that such protein-coated quantum dots (QDs) are unable to penetrate the envelope of unmodified E. coli but readily translocate to the cytoplasm of cells that have been made competent by chemical treatment. The process is dose-dependent and reminiscent of bacterial transformation. Cells that have internalized up to 0.5 μg/mL of nanocrystals do not experience a significant activation of the unfolded protein or SOS responses but undergo oxidative stress when exposed to high QD doses (2.5 μg/mL). Finally, although they are stable in quiescent cells over temperatures ranging from 4 to 42°C, internalized QDs are rapidly diluted by cell division in a process that does not involve TolC-dependent efflux. Taken together, our results suggest that biomimetic QDs based on low toxicity inorganic cores capped by a protein shell are unlikely to cause significant damage to the microbial ecosystem. 相似文献
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