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961.
Xing J Koba S Kehoe V Gao Z Rice K King N Sinoway L Li J 《American journal of physiology. Heart and circulatory physiology》2007,293(2):H1190-H1195
During exercise, sympathetic nerve responses are accentuated in heart failure (HF), and this enhances norepinephrine (NE) release and evokes vasoconstriction. Two key pathophysiological responses could contribute to the greater NE release: 1) increased sympathetic nerve discharge and 2) increased NE in the neurovascular junction for a given level of sympathetic discharge. In this report, we focus on the second of these two general issues and test the following hypotheses: 1) in HF for a given level of sympathetic nerve stimulation, NE concentration in the interstitium (an index of neurovascular NE) would be greater, and 2) the greater interstitial NE concentration would be linked to reduced NE uptake. Studies were performed in rats 8-10 wk after induction of myocardial infarction (MI). Interstitial NE samples were collected from microdialysis probes inserted into the hindlimb muscle. Dialysate concentration of NE was determined by the HPLC method. First, interstitial NE concentration increased during electrical stimulation of the lumbar sympathetic nerves in eight control rats. An increase in interstitial NE concentration was significantly greater in 10 rats with severe MI. Additionally, an NE uptake-1 inhibitor (desipramine, 1 microM) was injected into the arterial blood supply of the muscle in six control and eight MI rats. Desipramine increased interstitial NE concentration by 24% in control and by only 3% (P < 0.05 vs. control) in MI rats. In conclusion, given levels of electrical stimulation of the lumbar sympathetic nerve lead to higher interstitial NE concentration in HF. This effect is due, in part, to reduced NE uptake-1 in HF. 相似文献
962.
963.
Wang Y Beck W Deppisch R Marshall SM Hoenich NA Thompson MG 《American journal of physiology. Cell physiology》2007,293(1):C328-C336
Advanced glycation end products (AGE) are substantially elevated in individuals with diabetes and/or chronic kidney disease (CKD). These patients are at greatly increased risk of cardiovascular events. The purpose of this study was to investigate the novel hypothesis that AGE elicit externalization of the platelet membrane phospholipid phosphatidylserine (PS). This contributes to hemostasis through propagation of the coagulation cascade leading to thrombus formation. Platelet-rich plasma (PRP) was prepared by differential centrifugation, and PS externalization was quantified by a fluorescence-activated cell sorter using annexin V-FITC. Human serum albumin (HSA)-AGE was generated by incubating HSA with glucose for 2, 4, or 6 wk, and total HSA-AGE was assessed by fluorescence intensity. The 2-wk HSA-AGE preparation (02 mg/ml) stimulated a concentration-dependent increase in PS externalization in a subpopulation of platelets that was threefold at 2 mg/ml. In contrast, the 4- and 6-wk preparations were maximal at 0.5 mg/ml and fivefold in magnitude. These effects mirrored the change in total HSA-AGE content of the preparations. The PS response was maximal at 10 min and inhibited by the PKC- inhibitor rottlerin and the serotonin [5-hydroxytryptamine (5-HT)]2A/2C receptor antagonist ritanserin in a dose-dependent manner. Moreover, the 5-HT2A/2C receptor agonist 1,2,5-dimethoxy-4-iodophenyl-2-aminopropane mimicked the effect of HSA-AGE on PS externalization. These data demonstrate, for the first time, that HSA-AGE stimulates PS externalization in a subpopulation of platelets via the 5-HT2A/2C receptor. This may have important consequences for platelet involvement in inflammatory responses and the increased cardiovascular risk observed in individuals with diabetes and/or CKD. signal transduction; thrombosis; caspase-3 相似文献
964.
Huntington ND 《Immunology and cell biology》2007,85(7):508-510
Natural killer (NK) cells are important members of the innate immune system being involved in the detection and clearance of transformed or virus-infected cells. The 10th meeting of the Society for Natural Immunity was recently held in Cambridge, UK, where leaders from around the globe gathered to discuss the latest developments and understandings in the field of NK cell biology. Among the topics covered in this meeting were NK cell development, the origin of thymic NK cells, contribution of NK cells to viral infections and subsequent tissue damage, crosstalk between NK cells and other immune cells and the role of NK cells at the foetal-maternal interface. 相似文献
965.
The human kinase gene family is composed of 518 genes that are involved in a diverse spectrum of physiological functions. They are also implicated in a number of diseases and encompass 10% of current drug targets. Contemporary, high-throughput sequencing efforts have identified a rich source of naturally occurring single nucleotide polymorphisms (SNPs) in kinases, a subset of which occur in the coding region of genes (cSNPs) and result in a change in the encoded amino acid sequence (nonsynonymous coding SNP; nscSNPs). What fraction of this naturally occurring variation underlies human disease is largely unknown (uDC), and much of it is assumed not to be disease causing (DC). We pursued a comprehensive computational analysis of the distribution of 1463 nscSNPs and 999 DC nscSNPs within the kinase gene family and have found that DCs are overrepresentated in the kinase catalytic domain and in receptor structures. In addition, the frequencies with which specific amino acid changes occur differ between the DCs and the uDCs, implying different biological characteristics for the two sets of human polymorphisms. Our results provide insights into the sequence and structural phenomena associated with naturally occurring kinase nscSNPs that contribute to human diseases. 相似文献
966.
In this study, we characterize the adaptation of neurons in the cat lateral geniculate nucleus to changes in stimulus contrast and correlations. By comparing responses to high- and low-contrast natural scene movie and white noise stimuli, we show that an increase in contrast or correlations results in receptive fields with faster temporal dynamics and stronger antagonistic surrounds, as well as decreases in gain and selectivity. We also observe contrast- and correlation-induced changes in the reliability and sparseness of neural responses. We find that reliability is determined primarily by processing in the receptive field (the effective contrast of the stimulus), while sparseness is determined by the interactions between several functional properties. These results reveal a number of adaptive phenomena and suggest that adaptation to stimulus contrast and correlations may play an important role in visual coding in a dynamic natural environment. 相似文献
967.
Wang ZY Soanes DM Kershaw MJ Talbot NJ 《Molecular plant-microbe interactions : MPMI》2007,20(5):475-491
The rice blast fungus Magnaporthe grisea infects plants by means of specialized infection structures known as appressoria. Turgor generated in the appressorium provides the invasive force that allows the fungus to breach the leaf cuticle with a narrow-penetration hypha gaining entry to the underlying epidermal cell. Appressorium maturation in M. grisea involves mass transfer of lipid bodies to the developing appressorium, coupled to autophagic cell death in the conidium and rapid lipolysis at the onset of appressorial turgor generation. Here, we report identification of the principal components of lipid metabolism in M. grisea based on genome sequence analysis. We show that deletion of any of the eight putative intracellular triacylglycerol lipase-encoding genes from the fungus is insufficient to prevent plant infection, highlighting the complexity and redundancy associated with appressorial lipolysis. In contrast, we demonstrate that a peroxisomally located multifunctional, fatty acid beta-oxidation enzyme is critical to appressorium physiology, and blocking peroxisomal biogenesis prevents plant infection. Taken together, our results indicate that, although triacylglycerol breakdown in the appressorium involves the concerted action of several lipases, fatty acid metabolism and consequent generation of acetyl CoA are necessary for M. grisea to complete its prepenetration phase of development and enter the host plant. 相似文献
968.
969.
Webber Liao Andrew Collins Matthew Hobbs Mehar S. Khatkar Junhong Luo Frank W. Nicholas 《Mammalian genome》2007,18(5):287-299
We have adapted the Location Database (LDB) map-integration strategy of Morton et al. [Ann Hum Genet 56:223–232] (1992) as
above to create an integrated map for each of several species for which fully annotated genome sequences are not yet available
(sheep, cattle, pig, wallaby), using all types of partial maps for that species, including cytogenetic, linkage, somatic-cell
hybrid, and radiation hybrid maps. An integrated map provides not only predictions of the kilobase location of every locus,
but also predicts locations (in cM) and cytogenetic band locations for every locus. In this way a comprehensive linkage map
and a comprehensive cytogenetic map are created, including all loci, irrespective of whether they have ever been linkage mapped
or physically mapped, respectively. High-resolution physical maps from annotated sequenced species have also been placed alongside
the integrated maps. This has created a powerful tool for comparative genomics. The LDB map-integration strategy has been
extended to make use of zoo-FISH comparative information. It has also been extended to enable the creation of a “virtual”
map for each species not yet sequenced by using mapping data from fully sequenced species. All of the partial maps, together
with the integrated map, for each species have been placed in a database called Comparative Location Database (CompLDB), which
is available for querying, browsing, or download in tabular form at .
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
970.
Shibayama K Wachino J Arakawa Y Saidijam M Rutherford NG Henderson PJ 《Molecular microbiology》2007,64(2):396-406
gamma-Glutamyltranspeptidase (GGT) is a periplasmic enzyme of Helicobacter pylori implicated in its pathogenesis towards mammalian cells. We have cloned and expressed the H. pylori strain 26695 recombinant GGT protein in Escherichia coli and purified it to homogeneity. The purified protein exhibited hydrolysis activity with very high affinities for glutamine and glutathione shown by apparent K(m) values lower than 1 muM. H. pylori cells were unable to take up extracellular glutamine and glutathione directly. Instead, these substances were hydrolysed to glutamate by the action of GGT outside the cells. The glutamate produced was then transported by a Na(+)-dependent reaction into H. pylori cells, where it was mainly incorporated into the TCA cycle and partially utilized as a substrate for glutamine synthesis. These observations show that one of the principle physiological functions of H. pylori GGT is to enable H. pylori cells to utilize extracellular glutamine and glutathione as a source of glutamate. As glutamine and glutathione are important nutrients for maintenance of healthy gastrointestinal tissue, their depletion by the GGT enzyme is hypothesized to account for the damaging of mammalian cells and the pathophysiology of H. pylori. 相似文献