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51.
Neide Vieira Carlos Bessa Ana J. Rodrigues Paulo Marques Fung-Yi Chan Ana Xavier de Carvalho Margarida Correia-Neves Nuno Sousa 《Cellular and molecular life sciences : CMLS》2018,75(11):2027-2044
The sorting nexins family of proteins (SNXs) plays pleiotropic functions in protein trafficking and intracellular signaling and has been associated with several disorders, namely Alzheimer’s disease and Down’s syndrome. Despite the growing association of SNXs with neurodegeneration, not much is known about their function in the nervous system. The aim of this work was to use the nematode Caenorhabditis elegans that encodes in its genome eight SNXs orthologs, to dissect the role of distinct SNXs, particularly in the nervous system. By screening the C. elegans SNXs deletion mutants for morphological, developmental and behavioral alterations, we show here that snx-3 gene mutation leads to an array of developmental defects, such as delayed hatching, decreased brood size and life span and reduced body length. Additionally, ?snx-3 worms present increased susceptibility to osmotic, thermo and oxidative stress and distinct behavioral deficits, namely, a chemotaxis defect which is independent of the described snx-3 role in Wnt secretion. ?snx-3 animals also display abnormal GABAergic neuronal architecture and wiring and altered AIY interneuron structure. Pan-neuronal expression of C. elegans snx-3 cDNA in the ?snx-3 mutant is able to rescue its locomotion defects, as well as its chemotaxis toward isoamyl alcohol. Altogether, the present work provides the first in vivo evidence of the SNX-3 role in the nervous system. 相似文献
52.
Sara Canato João D. Santos Ana S. Carvalho Kerman Aloria Margarida D. Amaral Rune Matthiesen André O. Falcao Carlos M. Farinha 《Cellular and molecular life sciences : CMLS》2018,75(24):4495-4509
Misfolded F508del-CFTR, the main molecular cause of the recessive disorder cystic fibrosis, is recognized by the endoplasmic reticulum (ER) quality control (ERQC) resulting in its retention and early degradation. The ERQC mechanisms rely mainly on molecular chaperones and on sorting motifs, whose presence and exposure determine CFTR retention or exit through the secretory pathway. Arginine-framed tripeptides (AFTs) are ER retention motifs shown to modulate CFTR retention. However, the interactions and regulatory pathways involved in this process are still largely unknown. Here, we used proteomic interaction profiling and global bioinformatic analysis to identify factors that interact differentially with F508del-CFTR and F508del-CFTR without AFTs (F508del-4RK-CFTR) as putative regulators of this specific ERQC checkpoint. Using LC–MS/MS, we identified kinesin family member C1 (KIFC1) as a stronger interactor with F508del-CFTR versus F508del-4RK-CFTR. We further validated this interaction showing that decreasing KIFC1 levels or activity stabilizes the immature form of F508del-CFTR by reducing its degradation. We conclude that the current approach is able to identify novel putative therapeutic targets that can be ultimately used to the benefit of CF patients. 相似文献
53.
This study offers a detailed analysis of an episode of the popularization of astronomy which took place in Portugal, a peripheral country of Europe, and occurring in the early twentieth century. The episode was driven by the 28 May 1900 total solar eclipse which was seen on the Iberian Peninsula (Portugal and Spain). Instead of focusing on one of the ends of the popularization process, we analyze the circulation of knowledge among scientists and the public, contrast the aims of the various expeditions, professional and amateur, which took place on Portuguese soil, analyze their repercussions in the Portuguese astronomical landscape, and the different ways used by the Portuguese political elite and astronomical community to successfully appropriate this astronomical event to serve their varied agendas, political, social and scientific. In this episode of public enthusiasm for science, a central figure emerged in the network of the official commission, professional and amateur communities and the ‘general public’: Frederico Tomás Oom (1864–1930), an astronomer of the Lisbon Astronomical Observatory. This paper aims to illustrate the different layers of the circulation process, and at proving that the popularization of science was not a unidirectional process from scientists to lay people nor did it serve only a particular agenda, be it political, social or scientific. 相似文献
54.
Cotton RG; Human Variome Project Appelbe W Auerbach AD Becker K Bodmer W Boone DJ Boulyjenkov V Brahmachari S Brody L Brookes A Brown AF Byers P Cantu JM Cassiman JJ Claustres M Concannon P Cotton RG den Dunnen JT Flicek P Gibbs R Hall J Hasler J Katz M Kwok PY Laradi S Lindblom A Maglott D Marsh S Masimirembwa CM Minoshima S de Ramirez AM Pagon R Ramesar R Ravine D Richards S Rimoin D Ring HZ Scriver CR Sherry S Shimizu N Stein L Tadmouri GO Taylor G Watson M 《Nature genetics》2007,39(4):433-436
Lists of variations in genomic DNA and their effects have been kept for some time and have been used in diagnostics and research. Although these lists have been carefully gathered and curated, there has been little standardization and coordination, complicating their use. Given the myriad possible variations in the estimated 24,000 genes in the human genome, it would be useful to have standard criteria for databases of variation. Incomplete collection and ascertainment of variants demonstrates a need for a universally accessible system. These and other problems led to the World Heath Organization-cosponsored meeting on June 20-23, 2006 in Melbourne, Australia, which launched the Human Variome Project. This meeting addressed all areas of human genetics relevant to collection of information on variation and its effects. Members of each of eight sessions (the clinic and phenotype, the diagnostic laboratory, the research laboratory, curation and collection, informatics, relevance to the emerging world, integration and federation and funding and sustainability) developed a number of recommendations that were then organized into a total of 96 recommendations to act as a foundation for future work worldwide. Here we summarize the background of the project, the meeting and its recommendations. 相似文献
55.
Nocentini S Reginensi D Garcia S Carulla P Moreno-Flores MT Wandosell F Trepat X Bribian A del Río JA 《Cellular and molecular life sciences : CMLS》2012,69(10):1689-1703
Newly generated olfactory receptor axons grow from the peripheral to the central nervous system aided by olfactory ensheathing
cells (OECs). Thus, OEC transplantation has emerged as a promising therapy for spinal cord injuries and for other neural diseases.
However, these cells do not present a uniform population, but instead a functionally heterogeneous population that exhibits
a variety of responses including adhesion, repulsion, and crossover during cell–cell and cell–matrix interactions. Some studies
report that the migratory properties of OECs are compromised by inhibitory molecules and potentiated by chemical gradients.
Here, we demonstrated that rodent OECs express all the components of the Nogo receptor complex and that their migration is
blocked by myelin. Next, we used cell tracking and traction force microscopy to analyze OEC migration and its mechanical properties
over myelin. Our data relate the decrease of traction force of OEC with lower migratory capacity over myelin, which correlates
with changes in the F-actin cytoskeleton and focal adhesion distribution. Lastly, OEC traction force and migratory capacity
is enhanced after cell incubation with the Nogo receptor inhibitor NEP1-40. 相似文献
56.
57.
Johansson ME Ambort D Pelaseyed T Schütte A Gustafsson JK Ermund A Subramani DB Holmén-Larsson JM Thomsson KA Bergström JH van der Post S Rodriguez-Piñeiro AM Sjövall H Bäckström M Hansson GC 《Cellular and molecular life sciences : CMLS》2011,68(22):3635-3641
In discussions on intestinal protection, the protective capacity of mucus has not been very much considered. The progress in the last years in understanding the molecular nature of mucins, the main building blocks of mucus, has, however, changed this. The intestinal enterocytes have their apical surfaces covered by transmembrane mucins and the whole intestinal surface is further covered by mucus, built around the gel-forming mucin MUC2. The mucus of the small intestine has only one layer, whereas the large intestine has a two-layered mucus where the inner, attached layer has a protective function for the intestine, as it is impermeable to the luminal bacteria. 相似文献
58.
Kozyrev SV Abelson AK Wojcik J Zaghlool A Linga Reddy MP Sanchez E Gunnarsson I Svenungsson E Sturfelt G Jönsen A Truedsson L Pons-Estel BA Witte T D'Alfonso S Barrizzone N Danieli MG Gutierrez C Suarez A Junker P Laustrup H Francisca González-Escribano M Martin J Abderrahim H Alarcón-Riquelme ME 《Nature genetics》2008,40(4):484
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