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排序方式: 共有248条查询结果,搜索用时 31 毫秒
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Amber Cathie Gomersall Huy Anh Phan Sylvana Iacuone Song Feng Li Roger W. Parish 《PloS one》2015,10(10)
The p37 protein at the surface of Mycoplasma hyorhinis cells forms part of a high-affinity transport system and has been found associated with animal and human cancers. Here we show in NIH3T3 fibroblasts, p37 rapidly induces the expression of genes implicated in inflammation and cancer progression. This gene activation was principally via the Tlr4 receptor. Activity was lost from p37 when the C-terminal 20 amino acids were removed or the four amino acids specific for the hydrogen bonding of thiamine pyrophosphate had been replaced by valine. Blocking the IL6 receptor or inhibiting STAT3 signalling resulted in increased p37-induced gene expression. Since cancer associated fibroblasts support growth, invasion and metastasis via their ability to regulate tumour-related inflammation, the rapid induction in fibroblasts of pro-inflammatory genes by p37 might be expected to influence cancer development. 相似文献
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The survival of a cell depends on its ability to meet its energy requirements. We hypothesized that the mitochondrial reserve respiratory capacity (RRC) of a cell is a critical component of its bioenergetics that can be utilized during an increase in energy demand, thereby, enhancing viability. Our goal was to identify the elements that regulate and contribute to the development of RRC and its involvement in cell survival. The results show that activation of metabolic sensors, including pyruvate dehydrogenase and AMP-dependent kinase, increases cardiac myocyte RRC via a Sirt3-dependent mechanism. Notably, we identified mitochondrial complex II (cII) as a target of these metabolic sensors and the main source of RRC. Moreover, we show that RRC, via cII, correlates with enhanced cell survival after hypoxia. Thus, for the first time, we show that metabolic sensors via Sirt3 maximize the cellular RRC through activating cII, which enhances cell survival after hypoxia.During normal/unstressed conditions, the cell runs on a fraction of its mitochondrial bioenergetics capacity, where the difference between the maximum respiratory capacity and basal respiratory capacity is referred to as the spare or reserve respiratory capacity (RRC). In the case when energy demand exceeds supply (e.g., an increase in workload or neuronal activity), the RRC has the potential to increase supply, thus, avoiding an ‘ATP crisis''. In accordance, RRC has been shown to correlate with enhanced cell survival1 and, conversely, reduced RRC has been associated with neuronal cell death and disease.2 RRC is a well-recognized phenomenon;3, 4, 5, 6, 7, 8, 9 however, its components or the factors that regulate it remain unknown, or, at best, minimally defined. Not surprisingly, one of the known factors that influence the extent of the RRC is substrate availability.7One potential source of RRC is a regulated increase of substrate entry into the TCA cycle that is synchronized with an increase in the electron transport chain (ETC) activity. Interestingly, mammalian complex II (cII) has the unique characteristic of being a common component that links the TCA cycle and the ETC and its role in cell survival and death is well established. For example, inactivating mutations in the subunit A (SDHA) are associated with Leigh''s syndrome, which is a progressive neurodegenerative disease associated with neuronal cell death.10 Likewise, at least one case report shows that a mutation in cII is associated with heart failure,11 while in Drosophila a mutation in Sdhb causes an increase in ROS production and early mortality.12 In contrast, inhibition of cII during ischemia/reperfusion attenuates ROS-induced damage.13 Indeed, while inhibiting cII has been shown to induce apoptosis,14 it is also recognized as an apoptosis sensor.15 One mechanism that has been described for cII-induced apoptosis involves its disassembly in the low pH environment of distressed cells that results in excessive production of ROS from the Sdha.16, 17 Thus, these results would suggest that a fully assembled cII is critical for cell health and survival, while the disassembled form participates in cell demise. In this report, we show that holo-cII is the source of the RRC, which increases the cells'' resistant to cell death. 相似文献
76.
Rebecca Woodfield Ian Grant UK Biobank Stroke Outcomes Group UK Biobank Follow-Up Outcomes Working Group Cathie L. M. Sudlow 《PloS one》2015,10(10)
Objective
Long-term follow-up of population-based prospective studies is often achieved through linkages to coded regional or national health care data. Our knowledge of the accuracy of such data is incomplete. To inform methods for identifying stroke cases in UK Biobank (a prospective study of 503,000 UK adults recruited in middle-age), we systematically evaluated the accuracy of these data for stroke and its main pathological types (ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage), determining the optimum codes for case identification.Methods
We sought studies published from 1990-November 2013, which compared coded data from death certificates, hospital admissions or primary care with a reference standard for stroke or its pathological types. We extracted information on a range of study characteristics and assessed study quality with the Quality Assessment of Diagnostic Studies tool (QUADAS-2). To assess accuracy, we extracted data on positive predictive values (PPV) and—where available—on sensitivity, specificity, and negative predictive values (NPV).Results
37 of 39 eligible studies assessed accuracy of International Classification of Diseases (ICD)-coded hospital or death certificate data. They varied widely in their settings, methods, reporting, quality, and in the choice and accuracy of codes. Although PPVs for stroke and its pathological types ranged from 6–97%, appropriately selected, stroke-specific codes (rather than broad cerebrovascular codes) consistently produced PPVs >70%, and in several studies >90%. The few studies with data on sensitivity, specificity and NPV showed higher sensitivity of hospital versus death certificate data for stroke, with specificity and NPV consistently >96%. Few studies assessed either primary care data or combinations of data sources.Conclusions
Particular stroke-specific codes can yield high PPVs (>90%) for stroke/stroke types. Inclusion of primary care data and combining data sources should improve accuracy in large epidemiological studies, but there is limited published information about these strategies. 相似文献77.
James Marcus Drymon Katherine E. Schweiss Emily A. Seubert Ryan N. Lehman Toby S. Daly‐Engel Mariah Pfleger Nicole M. Phillips 《Ecology and evolution》2021,11(1):22-28
Human activities in coastal areas are accelerating ecosystem changes at an unprecedented pace, resulting in habitat loss, hydrological modifications, and predatory species declines. Understanding how these changes potentially cascade across marine and freshwater ecosystems requires knowing how mobile euryhaline species link these seemingly disparate systems. As upper trophic level predators, bull sharks (Carcharhinus leucas) play a crucial role in marine and freshwater ecosystem health. Telemetry studies in Mobile Bay, Alabama, suggest that bull sharks extensively use the northern portions of the bay, an estuarine–freshwater interface known as the Mobile‐Tensaw Delta. To assess whether bull sharks use freshwater habitats in this region, environmental DNA surveys were conducted during the dry summer and wet winter seasons in 2018. In each season, 5 × 1 L water samples were collected at each of 21 sites: five sites in Mobile Bay, six sites in the Mobile‐Tensaw Delta, and ten sites throughout the Mobile‐Tombigbee and Tensaw‐Alabama Rivers. Water samples were vacuum‐filtered, DNA extractions were performed on the particulate, and DNA extracts were analyzed with Droplet Digital™ Polymerase Chain Reaction using species‐specific primers and an internal probe to amplify a 237‐base pair fragment of the mitochondrial NADH dehydrogenase subunit 2 gene in bull sharks. One water sample collected during the summer in the Alabama River met the criteria for a positive detection, thereby confirming the presence of bull shark DNA. While preliminary, this finding suggests that bull sharks use less‐urbanized, riverine habitats up to 120 km upriver during Alabama''s dry summer season. 相似文献
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Aeby GS Williams GJ Franklin EC Haapkyla J Harvell CD Neale S Page CA Raymundo L Vargas-Ángel B Willis BL Work TM Davy SK 《PloS one》2011,6(2):e16887
Growth anomalies (GAs) are common, tumor-like diseases that can cause significant morbidity and decreased fecundity in the major Indo-Pacific reef-building coral genera, Acropora and Porites. GAs are unusually tractable for testing hypotheses about drivers of coral disease because of their pan-Pacific distributions, relatively high occurrence, and unambiguous ease of identification. We modeled multiple disease-environment associations that may underlie the prevalence of Acropora growth anomalies (AGA) (n = 304 surveys) and Porites growth anomalies (PGA) (n = 602 surveys) from across the Indo-Pacific. Nine predictor variables were modeled, including coral host abundance, human population size, and sea surface temperature and ultra-violet radiation anomalies. Prevalence of both AGAs and PGAs were strongly host density-dependent. PGAs additionally showed strong positive associations with human population size. Although this association has been widely posited, this is one of the first broad-scale studies unambiguously linking a coral disease with human population size. These results emphasize that individual coral diseases can show relatively distinct patterns of association with environmental predictors, even in similar diseases (growth anomalies) found on different host genera (Acropora vs. Porites). As human densities and environmental degradation increase globally, the prevalence of coral diseases like PGAs could increase accordingly, halted only perhaps by declines in host density below thresholds required for disease establishment. 相似文献
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J. Tyler Youngquist Josh P. Rose Brian F. Pfleger 《Applied microbiology and biotechnology》2013,97(11):5149-5159
Microbially synthesized fatty acids are an attractive platform for producing renewable alternatives to petrochemically derived transportation fuels and oleochemicals. Free fatty acids (FFA) are a direct precursor to many high-value compounds that can be made via biochemical and ex vivo catalytic pathways. To be competitive with current petrochemicals, flux through these pathways must be optimized to approach theoretical yields. Using a plasmid-free, FFA-producing strain of Escherichia coli, a set of chemostat experiments were conducted to gather data for FFA production under phosphate limitation. A prior study focused on carbon-limited conditions strongly implicated non-carbon limitations as a preferred media formulation for maximizing FFA yield. Here, additional data were collected to expand an established kinetic model of FFA production and identify targets for further metabolic engineering. The updated model was able to successfully predict the strain’s behavior and FFA production in a batch culture. The highest yield observed under phosphate-limiting conditions (0.1 g FFA/g glucose) was obtained at a dilution rate of 0.1 h?1, and the highest biomass-specific productivity (0.068 g FFA/gDCW/h) was observed at a dilution rate of 0.25 h?1. Phosphate limitation increased yield (~45 %) and biomass-specific productivity (~300 %) relative to carbon-limited cultivations using the same strain. FFA production under phosphate limitation also led to a cellular maintenance energy ~400 % higher (0.28 g/gDCW/h) than that seen under carbon limitation. 相似文献
80.
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