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排序方式: 共有118条查询结果,搜索用时 416 毫秒
61.
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Jacobien J Hoogerwerf Gerritje JW van der Windt Dana C Blok Arie J Hoogendijk Alex F de Vos Cornelis van ‘t Veer Sandrine Florquin Koichi S Kobayashi Richard A Flavell Tom van der Poll 《Molecular medicine (Cambridge, Mass.)》2012,18(1):1067-1075
Pneumonia is a common cause of morbidity and mortality and the most frequent source of sepsis. Bacteria that try to invade normally sterile body sites are recognized by innate immune cells through pattern recognition receptors, among which toll-like receptors (TLRs) feature prominently. Interleukin-1 receptor (IL-1R)–associated kinase (IRAK)-M is a proximal inhibitor of TLR signaling expressed by epithelial cells and macrophages in the lung. To determine the role of IRAK-M in host defense against bacterial pneumonia, IRAK-M-deficient (IRAK-M−/−) and normal wild-type (WT) mice were infected intranasally with Klebsiella pneumoniae. IRAK-M mRNA was upregulated in lungs of WT mice with Klebsiella pneumonia, and the absence of IRAK-M resulted in a strongly improved host defense as reflected by reduced bacterial growth in the lungs, diminished dissemination to distant body sites, less peripheral tissue injury and better survival rates. Although IRAK-M−/− alveolar macrophages displayed enhanced responsiveness toward intact K. pneumoniae and Klebsiella lipopolysaccharide (LPS) in vitro, IRAK-M−/− mice did not show increased cytokine or chemokine levels in their lungs after infection in vivo. The extent of lung inflammation was increased in IRAK-M−/− mice shortly after K. pneumoniae infection, as determined by semiquantitative scoring of specific components of the inflammatory response in lung tissue slides. These data indicate that IRAK-M impairs host defense during pneumonia caused by a common gram-negative respiratory pathogen. 相似文献
63.
Antibodies directed to citrullinated proteins (anti-cyclic citrullinated peptide) are highly specific for rheumatoid arthritis (RA). Recent data suggest that the antibodies may be involved in the disease process of RA and that several RA-associated genetic factors might be functionally linked to RA via modulation of the production of anti-cyclic citrullinated peptide antibodies or citrullinated antigens. 相似文献
64.
McCool JD Long E Petrosino JF Sandler HA Rosenberg SM Sandler SJ 《Molecular microbiology》2004,53(5):1343-1357
Many recombination, DNA repair and DNA replication mutants have high basal levels of SOS expression as determined by a sulAp-lacZ reporter gene system on a population of cells. Two opposing models to explain how the SOS expression is distributed in these cells are: (i) the 'Uniform Expression Model (UEM)' where expression is evenly distributed in all cells or (ii) the 'Two Population Model (TPM)' where some cells are highly induced while others are not at all. To distinguish between these two models, a method to quantify SOS expression in individual bacterial cells was developed by fusing an SOS promoter (sulAp) to the green fluorescent protein (gfp) reporter gene and inserting it at attlambda on the Escherichia coli chromosome. It is shown that the fluorescence in sulAp-gfp cells is regulated by RecA and LexA. This system was then used to distinguish between the two models for several mutants. The patterns displayed by priA, dnaT, recG, uvrD, dam, ftsK, rnhA, polA and xerC mutants were explained best by the TPM while only lexA (def), lexA3 (ind-) and recA defective mutants were explained best by the UEM. These results are discussed in a context of how the processes of DNA replication and recombination may affect cells in a population differentially. 相似文献
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66.
Lee ER McCool KW Murdoch FE Fritsch MK 《The Journal of biological chemistry》2006,281(30):21162-21172
Embryonic stem (ES) cells are pluripotent cells capable of unlimited self-renewal and differentiation into the three embryonic germ layers under appropriate conditions. Mechanisms for control of the early period of differentiation, involving exit from the pluripotent state and lineage commitment, are not well understood. An emerging concept is that epigenetic histone modifications may play a role during this early period. We have found that upon differentiation of mouse ES cells by removal of the cytokine leukemia inhibitory factor, there is a global increase in coupled histone H3 phosphorylation (Ser-10)-acetylation (Lys-14) (H3 phosphoacetylation). We show that this occurs through activation of both the extracellular signal-regulated kinase (ERK) and p38 MAPK signaling pathways. Early ES cell differentiation is delayed using pharmacological inhibitors of the ERK and p38 pathways. One common point of convergence of these pathways is the activation of the mitogen- and stress-activated protein kinase 1 (MSK1). We show here that MSK1 is the critical mediator of differentiation-induced H3 phosphoacetylation using both the chemical inhibitor H89 and RNA interference. Interestingly, inhibition of H3 phosphoacetylation also alters gene expression during early differentiation. These results point to an important role for both epigenetic histone modifications and kinase pathways in modulating early ES differentiation. 相似文献
67.
McCool F. D.; Kelly K. B.; Loring S. H.; Greaves I. A.; Mead J. 《Journal of applied physiology》1986,61(3):1114-1119
To make estimates of ventilation from measurements of body surface movements in unrestrained subjects, we measured changes in linear dimensions and cross-sectional areas of the rib cage (RC) and abdomen (AB) of six healthy unrestrained subjects during a variety of maneuvers. RC and AB anteroposterior diameters and abdominal length in the cephalocaudal axis (axial displacement) were measured with magnetometers, and RC and AB cross-sectional areas were measured with a respiratory inductance plethysmograph. Flow was measured at the mouth with a pneumotachograph and integrated electrically to give volume. Volume and body surface measurements were analyzed by multiple linear regression. Addition of the axial measurements to either the anteroposterior dimensions or cross-sectional areas of RC and AB improved estimates of tidal volume in all subjects (P less than 0.01). With measurements of axial displacement and cross-sectional area of the RC and AB, tidal volume could be reliably estimated to within 20% of actual ventilation. We conclude that measurement of axial displacements improves estimates of ventilation in unrestrained subjects. 相似文献
68.
Rat bone marrow cells have been separated on the basis of their sedimentation at unit gravity. The cell population most responsive to erythropoietin in vitro was found to have a sedimentation velocity of about 6.6 mm/hr. In the process of becoming hemoglobin-synthesizing cells, it undergoes cell division and its sedimentation velocity decreases to 3.9 mm/hr and then to 2.1 mm/hr, the sedimentation velocity of mature red blood cells. 相似文献
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70.
The Gram-positive pathogen Bacillus anthracis grows in characteristic chains of individual, rod-shaped cells. Here, we report the cell-separating activity of BslO, a putative N-acetylglucosaminidase bearing three N-terminal S-layer homology (SLH) domains for association with the secondary cell wall polysaccharide (SCWP). Mutants with an insertional lesion in the bslO gene exhibit exaggerated chain lengths, although individual cell dimensions are unchanged. Purified BslO complements this phenotype in trans, effectively dispersing chains of bslO-deficient bacilli without lysis and localizing to the septa of vegetative cells. Compared with the extremely long chain lengths of csaB bacilli, which are incapable of binding proteins with SLH-domains to SCWP, bslO mutants demonstrate a chaining phenotype that is intermediate between wild-type and csaB. Computational simulation suggests that BslO effects a non-random distribution of B. anthracis chain lengths, implying that all septa are not equal candidates for separation. 相似文献