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111.
112.
Life under multiple extreme conditions: diversity and physiology of the halophilic alkalithermophiles 总被引:1,自引:0,他引:1
Around the world, there are numerous alkaline, hypersaline environments that are heated either geothermally or through intense solar radiation. It was once thought that such harsh environments were inhospitable and incapable of supporting a variety of life. However, numerous culture-dependent and -independent studies revealed the presence of an extensive diversity of aerobic and anaerobic bacteria and archaea that survive and grow under these multiple harsh conditions. This diversity includes the halophilic alkalithermophiles, a novel group of polyextremophiles that require for growth and proliferation the multiple extremes of high salinity, alkaline pH, and elevated temperature. Life under these conditions undoubtedly involves the development of unique physiological characteristics, phenotypic properties, and adaptive mechanisms that enable control of membrane permeability, control of intracellular osmotic balance, and stability of the cell wall, intracellular proteins, and other cellular constituents. This minireview highlights the ecology and growth characteristics of the extremely halophilic alkalithermophiles that have been isolated thus far. Biochemical, metabolic, and physiological properties of the extremely halophilic alkalithermophiles are described, and their roles in resistance to the combined stressors of high salinity, alkaline pH, and high temperature are discussed. The isolation of halophilic alkalithermophiles broadens the physicochemical boundaries for life and extends the boundaries for the combinations of the maximum salinity, pH, and temperature that can support microbial growth. 相似文献
113.
Laussmann MA Passante E Hellwig CT Tomiczek B Flanagan L Prehn JH Huber HJ Rehm M 《The Journal of biological chemistry》2012,287(18):14402-14411
114.
Do Lam AT Axmacher N Fell J Staresina BP Gauggel S Wagner T Olligs J Weis S 《PloS one》2012,7(1):e30009
Memory performance in everyday life is often far from perfect and therefore needs to be monitored and controlled by metamemory evaluations, such as judgments of learning (JOLs). JOLs support monitoring for goal-directed modification of learning. Behavioral studies suggested retrieval processes as providing a basis for JOLs. Previous functional imaging research on JOLs found a dissociation between processes underlying memory prediction, located in the medial prefrontal cortex (mPFC), and actual encoding success, located in the medial temporal lobe. However, JOL-specific neural correlates could not be identified unequivocally, since JOLs were given simultaneously with encoding. Here, we aimed to identify the neurocognitive basis of JOLs, i.e., the cognitive processes and neural correlates of JOL, separate from initial encoding. Using functional magnetic resonance imaging (fMRI), we implemented a face-name paired associative design. In general, we found that actual memory success was associated with increased brain activation of the hippocampi bilaterally, whereas predicted memory success was accompanied by increased activation in mPFC, orbital frontal and anterior cingulate cortices. Masking brain activation during predicted memory success with activation during retrieval success revealed BOLD increases of the mPFC. Our findings indicate that JOLs actually incorporate retrieval processes. 相似文献
115.
Schaab M Kausch H Klammt J Nowicki M Anderegg U Gebhardt R Rose-John S Scheller J Thiery J Kratzsch J 《PloS one》2012,7(4):e34787
Background
The adipokine leptin realizes signal transduction via four different membrane-anchored leptin receptor (Ob-R) isoforms in humans. However, the amount of functionally active Ob-R is affected by constitutive shedding of the extracellular domain via a so far unknown mechanism. The product of the cleavage process the so-called soluble leptin receptor (sOb-R) is the main binding protein for leptin in human blood and modulates its bioavailability. sOb-R levels are differentially regulated in metabolic disorders like type 1 diabetes mellitus or obesity and can, therefore, enhance or reduce leptin sensitivity.Methodology/Principal Findings
To describe mechanisms of Ob-R cleavage and to investigate the functional significance of differential sOb-R levels we established a model of HEK293 cells transiently transfected with different human Ob-R isoforms. Using siRNA knockdown experiments we identified ADAM10 (A Disintegrin And Metalloproteinase 10) as a major protease for constitutive and activated Ob-R cleavage. Additionally, the induction of lipotoxicity and apoptosis led to enhanced shedding shown by increased levels of the soluble leptin receptor (sOb-R) in cell supernatants. Conversely, high leptin concentrations and ER stress reduced sOb-R levels. Decreased amounts of sOb-R due to ER stress were accompanied by impaired leptin signaling and reduced leptin binding.Conclusions
Lipotoxicity and apoptosis increased Ob-R cleavage via ADAM10-dependent mechanisms. In contrast high leptin levels and ER stress led to reduced sOb-R levels. While increased sOb-R concentrations seem to directly block leptin action, reduced amounts of sOb-R may reflect decreased membrane expression of Ob-R. These findings could explain changes of leptin sensitivity which are associated with variations of serum sOb-R levels in metabolic diseases. 相似文献116.
Background
More than 100,000 chemicals are in use but have not been tested for their safety. To overcome limitations in the cancer bioassay several alternative testing strategies are explored. The inability to monitor non-invasively onset and progression of disease limits, however, the value of current testing strategies. Here, we report the application of in vivo imaging to a c-Myc transgenic mouse model of liver cancer for the development of a short-term cancer bioassay.Methodology/Principal Findings
μCT and 18F-FDG μPET were used to detect and quantify tumor lesions after treatment with the genotoxic carcinogen NDEA, the tumor promoting agent BHT or the hepatotoxin paracetamol. Tumor growth was investigated between the ages of 4 to 8.5 months and contrast-enhanced μCT imaging detected liver lesions as well as metastatic spread with high sensitivity and accuracy as confirmed by histopathology. Significant differences in the onset of tumor growth, tumor load and glucose metabolism were observed when the NDEA treatment group was compared with any of the other treatment groups. NDEA treatment of c-Myc transgenic mice significantly accelerated tumor growth and caused metastatic spread of HCC in to lung but this treatment also induced primary lung cancer growth. In contrast, BHT and paracetamol did not promote hepatocarcinogenesis.Conclusions/Significance
The present study evidences the accuracy of in vivo imaging in defining tumor growth, tumor load, lesion number and metastatic spread. Consequently, the application of in vivo imaging techniques to transgenic animal models may possibly enable short-term cancer bioassays to significantly improve hazard identification and follow-up examinations of different organs by non-invasive methods. 相似文献117.
Merkel cell carcinoma (MCC) is a highly aggressive skin cancer with an increasing incidence. The understanding of the molecular carcinogenesis of MCC is limited. Here, we scrutinized the PI3K/AKT pathway, one of the major pathways activated in human cancer, in MCC. Immunohistochemical analysis of 41 tumor tissues and 9 MCC cell lines revealed high levels of AKT phosphorylation at threonine 308 in 88% of samples. Notably, the AKT phosphorylation was not correlated with the presence or absence of the Merkel cell polyoma virus (MCV). Accordingly, knock-down of the large and small T antigen by shRNA in MCV positive MCC cells did not affect phosphorylation of AKT. We also analyzed 46 MCC samples for activating PIK3CA and AKT1 mutations. Oncogenic PIK3CA mutations were found in 2/46 (4%) MCCs whereas mutations in exon 4 of AKT1 were absent. MCC cell lines demonstrated a high sensitivity towards the PI3K inhibitor LY-294002. This finding together with our observation that the PI3K/AKT pathway is activated in the majority of human MCCs identifies PI3K/AKT as a potential new therapeutic target for MCC patients. 相似文献
118.
119.
The prevalence of nonpaternity in human societies is difficult to establish. To obtain a current and fairly unbiased estimate of the nonpaternity rate in Germany, we analysed a dataset consisting of 971 children and their parents in whom human leukocyte antigen (HLA) typing had been carried out in the context of bone marrow transplantation. In this sample, nine exclusions (0.93%) could be identified on the basis of more than 300 HLA-haplotypes defined by four HLA genes. Given this number of exclusions, a maximum likelihood estimate of the nonpaternity rate in the population of 0.94% was obtained with asymptotic 95% confidence limits of 0.33% and 1.55%, respectively. This result is in accordance with recent surveys as well as findings from Switzerland for a comparable sample, and it suggests that earlier estimates of the nonpaternity rate which were often in excess of 10% may have been largely exaggerated. 相似文献
120.
The hyporheic zone in stream ecosystems is a heterogeneous key habitat for species across many taxa. Consequently, it attracts high attention among freshwater scientists, but generally applicable guidelines on sampling strategies are lacking. Thus, the objective of this study was to develop and validate such sampling guidelines. Applying geostatistical analysis, we quantified the spatio-temporal variability of parameters, which characterize the physico-chemical substratum conditions in the hyporheic zone. We investigated eight stream reaches in six small streams that are typical for the majority of temperate areas. Data was collected on two occasions in six stream reaches (development data), and once in two additional reaches, after one year (validation data). In this study, the term spatial variability refers to patch contrast (patch to patch variance) and patch size (spatial extent of a patch). Patch contrast of hyporheic parameters (specific conductance, pH and dissolved oxygen) increased with macrophyte cover (r2 = 0.95, p<0.001), while patch size of hyporheic parameters decreased from 6 to 2 m with increasing sinuosity of the stream course (r2 = 0.91, p<0.001), irrespective of the time of year. Since the spatial variability of hyporheic parameters varied between stream reaches, our results suggest that sampling design should be adapted to suit specific stream reaches. The distance between sampling sites should be inversely related to the sinuosity, while the number of samples should be related to macrophyte cover. 相似文献