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991.
We have established an in vitro reaction in which heteroduplex DNA formation is dependent on the concerted actions of recA and recBCD proteins, the major components of the recBCD pathway of genetic recombination in vivo. We find that heteroduplex DNA formation requires three distinct enzymatic functions: first, the helicase activity of recBCD enzyme initiates heteroduplex DNA formation by unwinding the linear double-stranded DNA molecule to transiently form single-stranded DNA (ssDNA); second, recA protein traps this ssDNA before it reanneals; third, recA protein catalyzes the pairing of this ssDNA molecule with another homologous ssDNA molecule, followed by the renaturation of these molecules to form heteroduplex DNA. The first two functions should be important to all in vitro reactions involving recA and recBCD proteins, whereas the third will be specific to the DNA substrates used. The rate-limiting step of heteroduplex DNA formation is the trapping by recA protein of the ssDNA produced by recBCD enzyme. A model for this reaction is described.  相似文献   
992.
At least five nonporous sensilla with inflexible sockets (npsensilla) occur on each antenna of both sexes of adult Rhodnius prolixus. Externally the sensillum appears as a short, rounded peg set into a pit surrounded by a depression. A very electron-dense material occurs in the peg lumen and the inner aspect of the pit. Filamentous extensions of this material radiate into the overlying outlets. Each sensillum is innervated by three neurons with unbranched dendrites. Two dendrites extend to the peg tip and distally are covered by a dendritic sheath. The portion of these dendrites within the sheath contains a large number of microtubules. The third dendrite terminates near the base of the dentritic sheath and partially wraps around the other two dendrites. Three sheath cells are associated with each sensillum. Based on similarities in structure with sensilla of known function it is probable that the np-sensilla of R. prolixus are thermo-/hygrosensilla responding to cold, dryness and wetness. The sensilla have a number of structural similarities with insect rectal sheath cells known to absorb atmospheric water by electroosmosis. Possibly this process leads to volumetric alterations of cuticular elements associated with the dendrites and ultimately to mechanotransduction.  相似文献   
993.
In an earlier work using tissue printing method, we found that the PR-10 stress protein was observed in leaf petiole of lupin seedling where lead was not detected (Przymusiński et al. 2001). These results suggested the presence of substance(s) mediating a signal transduction from directly affected cells to distant organs. As the hydrogen peroxide was found to be involved in signal transduction pathway, in the present paper, we analysed the level of H2O2 in the organ of lupin seedlings exposed to Pb2+ with spectrophotometric method and tissue printing technique. It was unequivocally demonstrated that the level of H2O2 and the activity of peroxidase increased in every tested organ of lead-treated lupin seedling. Both the level of H2O2 and the activity of POX were correlated with amount of Pb2+ ions in the cells (Przymusiński et al. 2001) and decreased in tissues more and more distant from the site of metal application. On the other hand, there was no correlation between the histological localization of H2O2 and peroxidase. Our results seem to confirm the hypothesis that H2O2 may act as a signalling substance involved in the induction of PR protein synthesis. It was indicated that there is high degree of correlation between the localization of H2O2 and the histological localization of PR-10 proteins (Przymusiński et al. 2001) in every tested organ of lupin seedling. The presented hypothesis is also supported by the fact that H2O2 and PR-10 proteins are detected in organs and tissues where Pb2+ was not found at all.  相似文献   
994.
995.

Background and Aims

Higher levels of stress impact the prevalence of metabolic syndrome (MetS) and coronary heart disease. The association between MetS, impaired pulmonary function and low level of physical activity is still pending assessment in the subjects exposed to stress. The study aimed to examine whether higher levels of stress might be related to MetS and the plaque presence, as well as whether MetS might affect pulmonary function.

Design and Methods

The study embraced 235 police officers (mean age 40.97 years) from the south of Poland. The anthropometrics and biochemical variables were measured; MetS was diagnosed using the International Diabetes Federation criteria. Computed tomography coronary angiography of coronary arteries, exercise ECG, measurements of brachial flow-mediated dilation, and carotid artery intima-media thickness were completed. In order to measure the self-perception of stress, 10-item Perceived Stress Scale (PSS-10) was applied. Pulmonary function and physical activity levels were also addressed. Multivariate logistic regression analyses were applied to determine the relationships between: 1/ incidence of coronary plaque and MetS per se, MetS components and the number of classical cardiovascular risk factors, 2/ perceived stress and MetS, 3/ MetS and pulmonary function parameters.

Results

Coronary artery atherosclerosis was less associated with MetS (OR = 2.62, 95%CI 1.24–5.52; p = 0.011) than with a co-existence of classical cardiovascular risk factors (OR = 5.67, 95% CI 1.07–29.85, p = 0.03; for 3 risk factors and OR = 9.05; 95% CI 1.24–66.23, p = 0.02; for 6 risk factors, respectively). Perceived stress increased MetS prevalence (OR = 1.07, 95% CI 1.03–1.13; p = 0.03), and impacted coronary plaque prevalence (OR = 1.05, 95% CI 1.001–1.10; p = 0.04). Leisure-time physical activity reduced the chances of developing MetS (OR = 0.98 95% CI 0.96–0.99; p = 0.02). MetS subjects had significantly lower values of certain pulmonary function parameters.

Conclusions

Exposure to job-specific stress among police officers increased the prevalence of MetS and impacted coronary plaque presence. MetS subjects had worse pulmonary function parameters. Early-stage, comprehensive therapeutic intervention may reduce overall risk of cardiovascular events and prevent pulmonary function impairment in this specific occupational population.  相似文献   
996.
997.
Circadian rhythms are common in many cell types but are reported to be lacking in embryonic stem cells. Recent studies have described possible interactions between the molecular mechanism of circadian clocks and the signaling pathways that regulate stem cell differentiation. Circadian rhythms have not been examined well in neural stem cells and progenitor cells that produce new neurons and glial cells during adult neurogenesis. To evaluate circadian timing abilities of cells undergoing neural differentiation, neurospheres were prepared from the mouse subventricular zone (SVZ), a rich source of adult neural stem cells. Circadian rhythms in mPer1 gene expression were recorded in individual spheres, and cell types were characterized by confocal immunofluorescence microscopy at early and late developmental stages in vitro. Circadian rhythms were observed in neurospheres induced to differentiate into neurons or glia, and rhythms emerged within 3–4 days as differentiation proceeded, suggesting that the neural stem cell state suppresses the functioning of the circadian clock. Evidence was also provided that neural stem progenitor cells derived from the SVZ of adult mice are self-sufficient clock cells capable of producing a circadian rhythm without input from known circadian pacemakers of the organism. Expression of mPer1 occurred in high frequency oscillations before circadian rhythms were detected, which may represent a role for this circadian clock gene in the fast cycling of gene expression responsible for early cell differentiation.  相似文献   
998.

Background

The increased use of high sensitivity cardiac troponins (hs-cTn), have made the diagnosis of non-ST elevation myocardial infarction (MI) challenging, especially in complex medical patients, in whom the clinical presentation of MI is nonspecific and multiple comorbidities as well as non-ischemic acute conditions may account for elevated hs-cTn levels. The aim of this study was to assess the frequency of both elevated hs-cTn levels and dynamic changes in hospitalized patients.

Methods and Findings

We conducted a retrospective study identifying all patients hospitalized in the Internal Medicine Division of Rabin Medical Center, Israel between January 2011 to December 2011, for whom at least one hs-cTn T (hs-cTnT) measurement was obtained. Collected data included patient demographics, acute and chronic diagnosis, hs-cTnT and creatinine levels and date of death. Hs-cTnT levels were obtained in 5,696 admissions and was above the 99th percentile (> = 13 ng/L) in 61.6% of the measurements. A relative change of 50% or higher was observed in 24% of the admissions. Among those with elevated hs-cTnT levels, acute coronary syndromes (ACS) accounted for only 6.1% of acute diagnoses. Maximal hs-cTnT levels above 100 ng/L but not dynamic changes discriminated between ACS and non-ACS conditions (positive and negative predictive values of 12% and 96% respectively). The frequency of elevated hs-cTnT levels was age-dependent and over 75% of patients aged >70 years-old had levels above the 99th percentile. Multivariate analysis identified hs-cTnT levels higher than the 99th percentile, as an independent, strong predictor for 30-day mortality (OR 4.58 [2.8, 7.49], p<0.0001).

Conclusions

Elevated hs-cTnT levels together with dynamic changes are frequent findings among hospitalized patients and in most cases, are not related to the ACS diagnosis. These findings highlight the diagnostic challenge of ACS in this complex population. Further studies are needed in order to optimize the use of hs-cTnT measurements in hospitalized patients.  相似文献   
999.
Cerebral arterial myogenic and autoregulatory responses are impaired in Fawn Hooded hypertensive (FHH) rats. Cerebral autoregulatory responses are restored in the congenic rat strain in which a segment of chromosome 1 from the Brown Norway (BN) rat was transferred into the FHH genetic background (FHH.1BN). The impact of this region on cerebral arterial dilator responses remains unknown. Aminopeptidase is a gene that was transferred into the FHH genetic background to generate the FHH.1BN rats and is responsible for degradation of the vasodilator bradykinin. Thus, we hypothesized that FHH rats will have increased aminopeptidase P levels with impaired cerebral arterial responses to bradykinin compared to BN and FHH.1BN rats. We demonstrated higher cerebral arterial expression of aminopeptidase P in FHH compared to BN rats. Accordingly, we demonstrated markedly impaired cerebral arterial dilation to bradykinin in FHH compared to BN rats. Interestingly, aminopeptidase P expression was lower in FHH.1BN compared to FHH rats. Decreased aminopeptidase P levels in FHH.1BN rats were associated with increased cerebral arterial bradykinin-induced dilator responses. Aminopeptidase P inhibition by apstatin improved cerebral arterial bradykinin dilator responses in FHH rats to a level similar to FHH.1BN rats. Unlike bradykinin, cerebral arterial responses to acetylcholine were similar between FHH and FHH.1BN groups. These findings indicate decreased bradykinin bioavailability contributes to impaired cerebral arterial dilation in FHH rats. Overall, these data indicate an important role of aminopeptidase P in the impaired cerebral arterial function in FHH rat.  相似文献   
1000.
High-level fetal (γ) globin expression ameliorates clinical severity of the beta (β) hemoglobinopathies, and safe, orally-bioavailable γ-globin inducing agents would benefit many patients. We adapted a LCR-γ-globin promoter-GFP reporter assay to a high-throughput robotic system to evaluate five diverse chemical libraries for this activity. Multiple structurally- and functionally-diverse compounds were identified which activate the γ-globin gene promoter at nanomolar concentrations, including some therapeutics approved for other conditions. Three candidates with established safety profiles were further evaluated in erythroid progenitors, anemic baboons and transgenic mice, with significant induction of γ-globin expression observed in vivo. A lead candidate, Benserazide, emerged which demonstrated > 20-fold induction of γ-globin mRNA expression in anemic baboons and increased F-cell proportions by 3.5-fold in transgenic mice. Benserazide has been used chronically to inhibit amino acid decarboxylase to enhance plasma levels of L-dopa. These studies confirm the utility of high-throughput screening and identify previously unrecognized fetal globin inducing candidates which can be developed expediently for treatment of hemoglobinopathies.  相似文献   
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