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101.
Döring B Pfitzer G Adam B Liebregts T Eckardt D Holtmann G Hofmann F Feil S Feil R Willecke K 《Cell and tissue research》2007,327(2):333-342
Connexin43 (Cx43) gap-junction channels are highly abundant in intestinal smooth muscle but their functional impact has not
been studied so far. Here, we have aimed to elucidate the functional role of Cx43 in the tunica muscularis of the mouse intestine
in vivo. Transgenic mice with conditional deletion of Cx43 in smooth muscle cells (SMC) were generated. Histological investigations
by immunofluorescence analyses and organ-bath recordings to assess the contractility of intestinal tissue strips were carried
out. Measurements of gastrointestinal transit and of the visceromotor response by utilizing a standardized colorectal distension
model to quantify alterations of visceral sensory function were also performed in SMC-specific Cx43 null mice and control
littermates. Histologically, we found thickening of the tunica muscularis and a 13-fold increase of neutrophil infiltration
of the gastrointestinal wall of SMC-specific Cx43 null mice. These animals also exhibited a decrease of 29% in gastrointestinal
transit time. In contrast, the visceromotor response to a standardized colorectal distension was elevated, as was the contractility
in SMC-specific Cx43 null mice, compared with controls. Thus, SMC-specific ablation of Cx43 in mice leads to morphological
and functional alterations of the intestinal tunica muscularis, to gastrointestinal motor dysfunction and to altered visceral
sensory function.
This study was supported by a grant from the German Research Association (Wi 270/25-1,2) to K.W. and in part by the IFORES
program of the University Hospital, Essen, Germany. 相似文献
102.
Abdelmohsen K Sauerbier E Ale-Agha N Beier J Walter P Galban S Stuhlmann D Sies H Klotz LO 《Biochemical and biophysical research communications》2007,364(2):313-317
Extracellular signal-regulated kinases (ERK) 1 and 2 as well as ERK-5 were previously suggested to phosphorylate connexin-43 and to contribute to the modulation of gap junctional intercellular communication (GJC). Exposure of rat liver epithelial cells to epidermal growth factor (EGF) or the redox cycling and alkylating agent menadione resulted in phosphorylation of connexin-43 and loss in GJC, both of which were abrogated by pharmacological inhibitors of ERK-1/2 activation, if used in concentrations that selectively abrogate phosphorylation of ERK-1/2 but not of ERK-5. Thus, EGF- or menadione-induced loss of GJC is mediated by ERK-1/2 but not ERK-5 in rat liver epithelial cells. 相似文献
103.
This study investigated a marker-assisted introgression programme in Australian Merino sheep. The goal was to introgress an allele with a large negative effect on fibre diameter into a Merino flock possessing medium average fibre diameter. The influence of two factors was explored: the strategy used to select animals from the purebred and backcross line for backcrossing purposes and the use of selection on background markers to accelerate the return to the purebred line''s genome. The results were compared to introgression based on EBVs only. Introgression using EBVs only produced almost the same response in the dollar index as marker-based introgression methods. However, this study did not account for some of the costs associated with implementing the programmes, including the costs of phenotyping and genotyping. Given that the cost of measuring fibre diameter is low, it was concluded that introgression on EBVs only would be the preferred method since the marginal profit of marker-assisted introgression would not be large enough to cover the additional cost of genotyping. In marker-assisted introgression, reciprocal crossing of male and female selection candidates from the backcross and the purebred line was the most advantageous strategy from a practical and profit point of view. Selection for background markers was less profitable in this study than recovering the donor genome by selection on phenotype. 相似文献
104.
Hartl D Latzin P Hordijk P Marcos V Rudolph C Woischnik M Krauss-Etschmann S Koller B Reinhardt D Roscher AA Roos D Griese M 《Nature medicine》2007,13(12):1423-1430
Interleukin-8 (IL-8) activates neutrophils via the chemokine receptors CXCR1 and CXCR2. However, the airways of individuals with cystic fibrosis are frequently colonized by bacterial pathogens, despite the presence of large numbers of neutrophils and IL-8. Here we show that IL-8 promotes bacterial killing by neutrophils through CXCR1 but not CXCR2. Unopposed proteolytic activity in the airways of individuals with cystic fibrosis cleaved CXCR1 on neutrophils and disabled their bacterial-killing capacity. These effects were protease concentration-dependent and also occurred to a lesser extent in individuals with chronic obstructive pulmonary disease. Receptor cleavage induced the release of glycosylated CXCR1 fragments that were capable of stimulating IL-8 production in bronchial epithelial cells via Toll-like receptor 2. In vivo inhibition of proteases by inhalation of alpha1-antitrypsin restored CXCR1 expression and improved bacterial killing in individuals with cystic fibrosis. The cleavage of CXCR1, the functional consequences of its cleavage, and the identification of soluble CXCR1 fragments that behave as bioactive components represent a new pathophysiologic mechanism in cystic fibrosis and other chronic lung diseases. 相似文献
105.
The catalytically inactive precursor of cathepsin D induces apoptosis in human fibroblasts and HeLa cells 总被引:1,自引:0,他引:1
In several reports cathepsin D has been implicated in apoptosis. In some systems the effects of agents considered to be mediated by cathepsin D were inhibited in the presence of pepstatin A, an inhibitor of the enzyme. In other studies the effect of a mutant cathepsin D deprived of activity was indistinguishable from that of the normal enzyme. Here we show that in human fibroblasts and in HeLa cells apoptosis can be induced by microinjecting into cytosol either mature cathepsin D or its inactive precursor procathepsin D. The microinjected precursor remains in the uncleaved form. These results confirm that the proapoptotic effect of cathepsin D in the cytosol is independent of its catalytic activity and suggest that the interaction of cathepsin D with the downstream effector does not involve the active site of the enzyme, since in the proenzyme the active site is masked by the prosequence. 相似文献
106.
Background
Although experimental methods for determining protein structure are providing high resolution structures, they cannot keep the pace at which amino acid sequences are resolved on the scale of entire genomes. For a considerable fraction of proteins whose structures will not be determined experimentally, computational methods can provide valuable information. The value of structural models in biological research depends critically on their quality. Development of high-accuracy computational methods that reliably generate near-experimental quality structural models is an important, unsolved problem in the protein structure modeling. 相似文献107.
108.
Jean-Marie Burel Sébastien Besson Colin Blackburn Mark Carroll Richard K. Ferguson Helen Flynn Kenneth Gillen Roger Leigh Simon Li Dominik Lindner Melissa Linkert William J. Moore Balaji Ramalingam Emil Rozbicki Aleksandra Tarkowska Petr Walczysko Chris Allan Josh Moore Jason R. Swedlow 《Mammalian genome》2015,26(9-10):441-447
109.
110.
Bardan Ghimire Christopher A. Williams G. James Collatz Melanie Vanderhoof John Rogan Dominik Kulakowski Jeffrey G. Masek 《Global Change Biology》2015,21(8):3087-3101
Warmer conditions over the past two decades have contributed to rapid expansion of bark beetle outbreaks killing millions of trees over a large fraction of western United States (US) forests. These outbreaks reduce plant productivity by killing trees and transfer carbon from live to dead pools where carbon is slowly emitted to the atmosphere via heterotrophic respiration which subsequently feeds back to climate change. Recent studies have begun to examine the local impacts of bark beetle outbreaks in individual stands, but the full regional carbon consequences remain undocumented for the western US. In this study, we quantify the regional carbon impacts of the bark beetle outbreaks taking place in western US forests. The work relies on a combination of postdisturbance forest regrowth trajectories derived from forest inventory data and a process‐based carbon cycle model tracking decomposition, as well as aerial detection survey (ADS) data documenting the regional extent and severity of recent outbreaks. We find that biomass killed by bark beetle attacks across beetle‐affected areas in western US forests from 2000 to 2009 ranges from 5 to 15 Tg C yr?1 and caused a reduction of net ecosystem productivity (NEP) of about 6.1–9.3 Tg C y?1 by 2009. Uncertainties result largely from a lack of detailed surveys of the extent and severity of outbreaks, calling out a need for improved characterization across western US forests. The carbon flux legacy of 2000–2009 outbreaks will continue decades into the future (e.g., 2040–2060) as committed emissions from heterotrophic respiration of beetle‐killed biomass are balanced by forest regrowth and accumulation. 相似文献