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1.
Cholera toxin (CT) stimulated phospholipase activity and caused [3H]arachidonic acid (3H-AA) release in a murine macrophage/monocyte cell line. Pretreatment of cells with dexamethasone, a phospholipase A2 (PLA2) inhibitor, did not affect CT-induced 3H-AA release. In contrast, aspirin, which is an inhibitor of phospholipase C (PLC), blocked CT-induced 3H-AA release and subsequent prostaglandin (PC) synthesis. The inhibitory effect of aspirin was dose dependent, with 4 mM reducing the CT response by approximately 50%. Similarly, inhibition was time dependent, occurring when the drug was added to the culture medium as late as 30 min after CT. Brief exposure (30 min) of the cells to aspirin did not alter their subsequent response to CT, but 3H-AA release from cells exposed to aspirin for 2.5 h was irreversibly inhibited. The data suggested that CT stimulation of AA metabolism may involve increased PLC activity. 相似文献
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Angus Davison †§ Johnny D. S. Birks † Rachael C. Brookes † John E. Messenger† Huw I. Griffiths‡ 《Molecular ecology》2001,10(10):2479-2488
The flora and fauna of Europe are linked by a common biogeographic history, most recently the Pleistocene glaciations that restricted the range of most species to southern refugial populations. Changes in population size and migration, as well as selection, have all left a signature on the genetic differentiation. Thus, three paradigms of postglacial recolonization have been described, inferred from the patterns of DNA differentiation. Yet some species, especially wide-ranging carnivores, exhibit little population structuring between the proposed refugia, although relatively few have been studied due to the difficulty of obtaining samples. Therefore, we investigated mitochondrial variation in pine martens, Martes martes, in order to understand the extent to which they were affected by glacial cycles, and compared the results with an analysis of sequences from polecats, Mustela putorius. A general lack of ancient lineages, and a mismatch distribution that is consistent with an expanding population, is evidence that the present-day M. martes and Mu. putorius in central and northern Europe colonized from a single European refugium following a recent glaciation. There has also been interspecific mitochondrial introgression between M. martes and the sable M. zibellina in Fennoscandia. 相似文献
4.
Studies on the metabolism of steroids in the foetus. Biosynthesis of 6α-hydroxytestosterone in the human foetal liver
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After incubation of testosterone with 105000g microsomes of human foetal liver, 6alpha-hydroxytestosterone was isolated and identified by t.l.c. and g.l.c.-mass spectrometry. This is the first example of 6alpha-hydroxylation of C(19) steroids in the human liver, and the finding is discussed in relation to earlier reports of 6-oxygenated C(19) and C(18) steroids in pregnant women. 相似文献
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Márcia Camargo-De-Morais Marta De Freitas Angela G. De Mattos Nádia Schröder Ana C. Zilles Carla S. F. Lisboa Nice Arteni Armando Barlem Rejane Schierholt Guilherme Zwetsch Carlos A. B. Souza Regina Pessoa-Pureur Carlos A. Netto 《Neurochemical research》1996,21(5):595-602
Neurofilaments subunits (NF-H, NF-M, NF-L) and glial fibrillary acidic protein (GFAP) were investigated in the hippocampus
of rats after distinct periods of reperfusion (1 to 15 days) following 20 min of transient global forebrain ischemia in the
rat. In vitro [14Ca]leucine incorporation was not altered until 48 h after the ischemic insult, however concentration of intermediate filament
subunits significantly decreased in this period. Three days after the insult, leucine incorporation significantly increased
while the concentration NF-H, NF-M, and NF-L were still diminished after 15 days of reperfusion. In vitro incorporation of32P into NF-M and NF-L suffered immediately after ischemia, but returned to control values after two days of reperfusion. GFAP
levels decreased immediately after ischemia but quickly recovered and significantly peaked from 7 to 10 days after the insult.
These results suggest that transient ischemia followed by reperfusion causes proteolysis of intermediate filaments in the
hippocampus, and that proteolysis could be facilitated by diminished phosphorylation levels of NF-M and NF-L. 相似文献
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Katherine Miclau William S. Hambright Johnny Huard Martin J. Stoddart Chelsea S. Bahney 《Aging cell》2023,22(1):e13759
Mesenchymal-derived stromal or progenitor cells, commonly called “MSCs,” have attracted significant clinical interest for their remarkable abilities to promote tissue regeneration and reduce inflammation. Recent studies have shown that MSCs' therapeutic effects, originally attributed to the cells' direct differentiation capacity into the tissue of interest, are largely driven by the biomolecules the cells secrete, including cytokines, chemokines, growth factors, and extracellular vesicles containing miRNA. This secretome coordinates upregulation of endogenous repair and immunomodulation in the local microenvironment through crosstalk of MSCs with host tissue cells. Therapeutic applications for MSCs and their secretome-derived products often involve in vitro monolayer expansion. However, consecutive passaging of MSCs significantly alters their therapeutic potential, inducing a broad shift from a pro-regenerative to a pro-inflammatory phenotype. A consistent by-product of in vitro expansion of MSCs is the onset of replicative senescence, a state of cell arrest characterized by an increased release of proinflammatory cytokines and growth factors. However, little is known about changes in the secretome profile at different stages of in vitro expansion. Some culture conditions and bioprocessing techniques have shown promise in more effectively retaining the pro-regenerative and anti-inflammatory MSC phenotype throughout expansion. Understanding how in vitro expansion conditions influence the nature and function of MSCs, and their associated secretome, may provide key insights into the underlying mechanisms driving these alterations. Elucidating the dynamic and diverse changes in the MSC secretome at each stage of in vitro expansion is a critical next step in the development of standardized, safe, and effective MSC-based therapies. 相似文献
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Chathurika Henpita Rajesh Vyas Chastity L. Healy Tra L. Kieu Aditi U. Gurkar Matthew J. Yousefzadeh Yuxiang Cui Aiping Lu Luise A. Angelini Ryan D. O'Kelly Sara J. McGowan Sanjay Chandrasekhar Rebecca R. Vanderpool Danielle Hennessy-Wack Mark A. Ross Timothy N. Bachman Charles McTiernan Smitha P. S. Pillai Warren Ladiges Mitra Lavasani Johnny Huard Donna Beer-Stolz Claudette M. St. Croix Simon C. Watkins Paul D. Robbins Ana L. Mora Eric E. Kelley Yinsheng Wang Timothy D. O'Connell Laura J. Niedernhofer 《Aging cell》2023,22(4):e13782
Cardiomyopathy is a progressive disease of the myocardium leading to impaired contractility. Genotoxic cancer therapies are known to be potent drivers of cardiomyopathy, whereas causes of spontaneous disease remain unclear. To test the hypothesis that endogenous genotoxic stress contributes to cardiomyopathy, we deleted the DNA repair gene Ercc1 specifically in striated muscle using a floxed allele of Ercc1 and mice expressing Cre under control of the muscle-specific creatinine kinase (Ckmm) promoter or depleted systemically (Ercc1−/D mice). Ckmm-Cre+/−;Ercc1−/fl mice expired suddenly of heart disease by 7 months of age. As young adults, the hearts of Ckmm-Cre+/−;Ercc1−/fl mice were structurally and functionally normal, but by 6-months-of-age, there was significant ventricular dilation, wall thinning, interstitial fibrosis, and systolic dysfunction indicative of dilated cardiomyopathy. Cardiac tissue from the tissue-specific or systemic model showed increased apoptosis and cardiac myocytes from Ckmm-Cre+/-;Ercc1−/fl mice were hypersensitive to genotoxins, resulting in apoptosis. p53 levels and target gene expression, including several antioxidants, were increased in cardiac tissue from Ckmm-Cre+/−;Ercc1−/fl and Ercc1−/D mice. Despite this, cardiac tissue from older mutant mice showed evidence of increased oxidative stress. Genetic or pharmacologic inhibition of p53 attenuated apoptosis and improved disease markers. Similarly, overexpression of mitochondrial-targeted catalase improved disease markers. Together, these data support the conclusion that DNA damage produced endogenously can drive cardiac disease and does so mechanistically via chronic activation of p53 and increased oxidative stress, driving cardiac myocyte apoptosis, dilated cardiomyopathy, and sudden death. 相似文献
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Sessile and vagile organisms differ from one another in some fundamental ways, including methods of resource acquisition and competition. Ant colonies are typically studied as sessile entities, even though a large fraction of ant species frequently relocate their nests in the course of their life history. Little is known about the causes and consequences of nest relocation, but it is likely that the costs and benefits of relocation are driven by nest quality, neighborhood competition, or resource availability. In this paper, we document several cycles of nest relocation in a population of the Central American ant Aphaenogaster araneoides . In our first experiment, we tracked the pattern of relocation, testing whether environmental characteristics and colony demography were associated with relocation behavior. In our second experiment, we manipulated resource availability by adding or subtracting leaf litter, which is known to predict colony growth. We found that colonies relocated their nests once per week on average and colonies often reoccupied nests from which they had once emigrated. Larger colonies relocated more frequently than smaller colonies, and quickly growing colonies utilized a greater number of nests within their home range compared to slowly growing colonies. Relocation events were most likely to occur in periods when vapor pressure deficits were greatest. Nearest neighbor distance and other measures of environmental conditions were not associated with relocation behavior and there was no significant effect of litter removal or supplementation. We found evidence that multiple natural enemies attacked A. araneoides colonies. Based on the demographic correlates of relocation and our rejection of other plausible hypotheses, we propose that nest relocation is driven by the escape from natural enemies. 相似文献
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