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41.
Jose Córdoba-Chacón Manuel D. Gahete Mario Duran-Prado Ana I. Pozo-Salas María M. Malagón F. Gracia-Navarro Rhonda D. Kineman Raul M. Luque Justo P. Castaño 《Cellular and molecular life sciences : CMLS》2010,67(7):1147-1163
Somatostatin and cortistatin exert multiple biological actions through five receptors (sst1-5); however, not all their effects
can be explained by activation of sst1-5. Indeed, we recently identified novel truncated but functional human sst5-variants,
present in normal and tumoral tissues. In this study, we identified and characterized three novel truncated sst5 variants
in mice and one in rats displaying different numbers of transmembrane-domains [TMD; sst5TMD4, sst5TMD2, sst5TMD1 (mouse-variants)
and sst5TMD1 (rat-variant)]. These sst5 variants: (1) are functional to mediate ligand-selective-induced variations in [Ca2+]i and cAMP despite being truncated; (2) display preferential intracellular distribution; (3) mostly share full-length sst5
tissue distribution, but exhibit unique differences; (4) are differentially regulated by changes in hormonal/metabolic environment
in a tissue- (e.g., central vs. systemic) and ligand-dependent manner. Altogether, our results demonstrate the existence of
new truncated sst5-variants with unique ligand-selective signaling properties, which could contribute to further understanding
the complex, distinct pathophysiological roles of somatostatin and cortistatin. 相似文献
42.
Vanessa Coelho-Santos Renato Socodato Camila Portugal Ricardo A. Leitão Manuel Rito Marcos Barbosa Pierre-Olivier Couraud Ignacio A. Romero Babette Weksler Richard D. Minshall Carlos Fontes-Ribeiro Teresa Summavielle João B. Relvas Ana P. Silva 《Cellular and molecular life sciences : CMLS》2016,73(24):4701-4716
43.
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
44.
45.
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
46.
47.
Frazão C McVey CE Amblar M Barbas A Vonrhein C Arraiano CM Carrondo MA 《Nature》2006,443(7107):110-114
RNA degradation is a determining factor in the control of gene expression. The maturation, turnover and quality control of RNA is performed by many different classes of ribonucleases. Ribonuclease II (RNase II) is a major exoribonuclease that intervenes in all of these fundamental processes; it can act independently or as a component of the exosome, an essential RNA-degrading multiprotein complex. RNase II-like enzymes are found in all three kingdoms of life, but there are no structural data for any of the proteins of this family. Here we report the X-ray crystallographic structures of both the ligand-free (at 2.44 A resolution) and RNA-bound (at 2.74 A resolution) forms of Escherichia coli RNase II. In contrast to sequence predictions, the structures show that RNase II is organized into four domains: two cold-shock domains, one RNB catalytic domain, which has an unprecedented alphabeta-fold, and one S1 domain. The enzyme establishes contacts with RNA in two distinct regions, the 'anchor' and the 'catalytic' regions, which act synergistically to provide catalysis. The active site is buried within the RNB catalytic domain, in a pocket formed by four conserved sequence motifs. The structure shows that the catalytic pocket is only accessible to single-stranded RNA, and explains the specificity for RNA versus DNA cleavage. It also explains the dynamic mechanism of RNA degradation by providing the structural basis for RNA translocation and enzyme processivity. We propose a reaction mechanism for exonucleolytic RNA degradation involving key conserved residues. Our three-dimensional model corroborates all existing biochemical data for RNase II, and elucidates the general basis for RNA degradation. Moreover, it reveals important structural features that can be extrapolated to other members of this family. 相似文献
48.
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
49.
Laurance WF Oliveira AA Laurance SG Condit R Nascimento HE Sanchez-Thorin AC Lovejoy TE Andrade A D'Angelo S Ribeiro JE Dick CW 《Nature》2004,428(6979):171-175
Amazonian rainforests are some of the most species-rich tree communities on earth. Here we show that, over the past two decades, forests in a central Amazonian landscape have experienced highly nonrandom changes in dynamics and composition. Our analyses are based on a network of 18 permanent plots unaffected by any detectable disturbance. Within these plots, rates of tree mortality, recruitment and growth have increased over time. Of 115 relatively abundant tree genera, 27 changed significantly in population density or basal area--a value nearly 14 times greater than that expected by chance. An independent, eight-year study in nearby forests corroborates these shifts in composition. Contrary to recent predictions, we observed no increase in pioneer trees. However, genera of faster-growing trees, including many canopy and emergent species, are increasing in dominance or density, whereas genera of slower-growing trees, including many subcanopy species, are declining. Rising atmospheric CO2 concentrations may explain these changes, although the effects of this and other large-scale environmental alterations remain uncertain. These compositional changes could have important impacts on the carbon storage, dynamics and biota of Amazonian forests. 相似文献
50.
Balbín M Fueyo A Tester AM Pendás AM Pitiot AS Astudillo A Overall CM Shapiro SD López-Otín C 《Nature genetics》2003,35(3):252-257
Matrix metalloproteinases (MMPs) have fundamental roles in tumor progression, but most clinical trials with MMP inhibitors have not shown improvements in individuals with cancer. This may be partly because broad-range inhibitors also reduce host-protective antitumor properties of individual MMPs. We generated mice deficient in collagenase-2 (Mmp8), an MMP mainly produced by neutrophils in inflammatory reactions and detected in some malignant tumors. Loss of Mmp8 did not cause abnormalities during embryonic development or in adult mice. Contrary to previous studies with MMP-deficient mice, however, the absence of Mmp8 strongly increased the incidence of skin tumors in male Mmp8(-/-)mice. Female Mmp8(-/-)mice whose ovaries were removed or were treated with tamoxifen were also more susceptible to tumors compared with wild-type mice. Bone marrow transplantation experiments confirmed that Mmp8 supplied by neutrophils was sufficient to restore the natural protection against tumor development mediated by this protease in male mice. Histopathological analysis showed that mutant mice had abnormalities in the inflammatory response induced by carcinogens. Our study identifies a paradoxical protective role for Mmp8 in cancer and provides a genetic model to evaluate the molecular basis of gender differences in cancer susceptibility. 相似文献