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991.
Silvia Galiani Dominic Waithe Katharina Reglinski Luis Daniel Cruz-Zaragoza Esther Garcia Mathias P. Clausen Wolfgang Schliebs Ralf Erdmann Christian Eggeling 《The Journal of biological chemistry》2016,291(33):16948-16962
Membrane-associated events during peroxisomal protein import processes play an essential role in peroxisome functionality. Many details of these processes are not known due to missing spatial resolution of technologies capable of investigating peroxisomes directly in the cell. Here, we present the use of super-resolution optical stimulated emission depletion microscopy to investigate with sub-60-nm resolution the heterogeneous spatial organization of the peroxisomal proteins PEX5, PEX14, and PEX11 around actively importing peroxisomes, showing distinct differences between these peroxins. Moreover, imported protein sterol carrier protein 2 (SCP2) occupies only a subregion of larger peroxisomes, highlighting the heterogeneous distribution of proteins even within the peroxisome. Finally, our data reveal subpopulations of peroxisomes showing only weak colocalization between PEX14 and PEX5 or PEX11 but at the same time a clear compartmentalized organization. This compartmentalization, which was less evident in cases of strong colocalization, indicates dynamic protein reorganization linked to changes occurring in the peroxisomes. Through the use of multicolor stimulated emission depletion microscopy, we have been able to characterize peroxisomes and their constituents to a yet unseen level of detail while maintaining a highly statistical approach, paving the way for equally complex biological studies in the future. 相似文献
992.
IGFs, IGFBPs, IGF-binding sites and biochemical markers of bone metabolism during differentiation in human pulp fibroblasts 总被引:4,自引:0,他引:4
OBJECTIVE: To investigate the role of the insulin-like growth factors (IGF) system during the differentiation of human pulp-derived fibroblasts (HPF). METHODS: Primary HPF were cultured for 24 days in DMEM medium with IGF-I or IGF-II (50 ng/ml each). Cell growth and morphology, alkaline phosphatase (ALP) activity, the concentration of free deoxypyridinoline (DPD), IGF-I, -II, IGFBP-2 and -3 were studied. The number of (125)I-IGF-I binding sites was estimated by Scatchard analysis. RESULTS: Light-microscopically visible nodules emerged during differentiation. Simultaneously, the ALP activity increased steadily between days 8 and 24, while the DPD concentration decreased by about 50%. The HPF produced high concentrations of IGF-II (2.00-1.30 microg/10(6) cells) but low IGF-I, IGFBP-2. IGFBP-2 was not changed, IGFBP-3 increased by 65% during differentiation. The number of IGF binding sites increased from 8,500 +/- 55 per cell (day 8) up to 22,000 +/- 570 (day 24). CONCLUSION: The increasing number of IGF-binding sites accompanied by alterations in the biochemical bone markers during the differentiation of HPF suggests an autocrine/paracrine role for the IGFs in the formation of dentinal hard tissue. 相似文献
993.
Laura Kehoe Cornelius Senf Carsten Meyer Katharina Gerstner Holger Kreft Tobias Kuemmerle 《Ecography》2017,40(9):1118-1128
Species–area relationships (SARs) provide an avenue to model patterns of species richness and have recently been shown to vary substantially across regions of different climate, vegetation, and land cover. Given that a large proportion of the globe has been converted to agriculture, and considering the large variety in agricultural management practices, a key question is whether global SARs vary across gradients of agricultural intensity. We developed SARs for mammals that account for geographic variation in biomes, land cover and a range of land‐use intensity indicators representing inputs (e.g. fertilizer, irrigation), outputs (e.g. yields) and system‐level measures of intensity (e.g. human appropriation of net primary productivity – HANPP). We systematically compared the resulting SARs in terms of their predictive ability. Our global SAR with a universal slope was significantly improved by the inclusion of any one of the three variable types: biomes, land cover, and land‐use intensity. The latter, in the form of human appropriation of net primary productivity (HANPP), performed as well as biomes and land‐cover in predicting species richness. Other land‐use intensity indicators had a lower predictive ability. Our main finding that land‐use intensity performs as well as biomes and land cover in predicting species richness emphasizes that human factors are on a par with environmental factors in predicting global patterns of biodiversity. While our broad‐scale study cannot establish causality, human activity is known to drive species richness at a local scale, and our findings suggest that this may hold true at a global scale. The ability of land‐use intensity to explain variation in SARs at a global scale had not previously been assessed. Our study suggests that the inclusion of land‐use intensity in SAR models allows us to better predict and understand species richness patterns. 相似文献
994.
995.
Evidence of impaired adipogenesis in insulin resistance 总被引:13,自引:0,他引:13
996.
Fear acquisition and extinction are crucial mechanisms in the etiology and maintenance of anxiety disorders. Moreover, they might play a pivotal role in conveying the influence of genetic and environmental factors on the development of a (more or less) stronger proneness for, or resilience against psychopathology. There are only few insights in the neurobiology of genetically and environmentally based individual differences in fear learning and extinction. In this functional magnetic resonance imaging study, 74 healthy subjects were investigated. These were invited according to 5-HTTLPR/rs25531 (S+ vs. L(A)L(A); triallelic classification) and TPH2 (G(-703)T) (T+ vs. T-) genotype. The aim was to investigate the influence of genetic factors and traumatic life events on skin conductance responses (SCRs) and neural responses (amygdala, insula, dorsal anterior cingulate cortex (dACC) and ventromedial prefrontal cortex (vmPFC)) during acquisition and extinction learning in a differential fear conditioning paradigm. Fear acquisition was characterized by stronger late conditioned and unconditioned responses in the right insula in 5-HTTLPR S-allele carriers. During extinction traumatic life events were associated with reduced amygdala activation in S-allele carriers vs. non-carriers. Beyond that, T-allele carriers of the TPH2 (G(-703)T) polymorphism with a higher number of traumatic life events showed enhanced responsiveness in the amygdala during acquisition and in the vmPFC during extinction learning compared with non-carriers. Finally, a combined effect of the two polymorphisms with higher responses in S- and T-allele carriers was found in the dACC during extinction. The results indicate an increased expression of conditioned, but also unconditioned fear responses in the insula in 5-HTTLPR S-allele carriers. A combined effect of the two polymorphisms on dACC activation during extinction might be associated with prolonged fear expression. Gene-by-environment interactions in amygdala and vmPFC activation may reflect a neural endophenotype translating genetic and adverse environmental influences into vulnerability for or resilience against developing affective psychopathology. 相似文献
997.
Otto Quintus Russe Christine V. Möser Katharina L. Kynast Tanya S. King Katrin Olbrich Sabine Grösch Gerd Geisslinger Ellen Niederberger 《Biochemical and biophysical research communications》2014
AMP-activated kinase is a cellular energy sensor which is activated in stages of increased ATP consumption. Its activation has been associated with a number of beneficial effects such as decreasing inflammatory processes and the disease progress of diabetes and obesity, respectively. Furthermore, AMPK activation has been linked with induction of cell cycle arrest and apoptosis in cancer and vascular cells, indicating that it might have a therapeutic impact for the treatment of cancer and atherosclerosis. However, the impact of AMPK on the proliferation of macrophages, which also play a key role in the formation of atherosclerotic plaques and in inflammatory processes, has not been focused so far. We have assessed the influence of AICAR- and metformin-induced AMPK activation on cell viability of macrophages with and without inflammatory stimulation, respectively. In cells without inflammatory stimulation, we found a strong induction of caspase 3-dependent apoptosis associated with decreased mTOR levels and increased expression of p21. Interestingly, these effects could be inhibited by co-stimulation with bacterial lipopolysaccharide (LPS) but not by other proinflammatory cytokines suggesting that AICAR induces apoptosis via AMPK in a TLR4-pathway dependent manner. 相似文献
998.
Songlei Liu Sukanya Punthambaker Eswar P R Iyer Thomas Ferrante Daniel Goodwin Daniel Fürth Andrew C Pawlowski Kunal Jindal Jenny M Tam Lauren Mifflin Shahar Alon Anubhav Sinha Asmamaw T Wassie Fei Chen Anne Cheng Valerie Willocq Katharina Meyer King-Hwa Ling Conor
K Camplisson Richie E Kohman John Aach Je Hyuk Lee Bruce
A Yankner Edward S Boyden George M Church 《Nucleic acids research》2021,49(10):e58
999.
Oxido-pincer ligands with phenolate-groups [2,6-bis(2-methoxyphenyl)pyridine (LOMe2), 2,6-bis(2-hydroxyphenyl)-pyridine (LOH2), 2,6-bis-(2,4-dimethoxyphenyl)-pyridine (LOMe4)] coordinate to CuII forming binuclear complexes which can be easily and reliably converted into mononuclear species. Their physical properties were analysed using EPR, optical spectroscopy and (spectro-)electrochemical methods. The results were compared to those of related NiII complexes and discussed in view of Cu-containing metalloenzymes. Due to the ligands flexibility the CuII/CuI redox couple exhibits high reversibility, while the ligand-centred oxidation leads to highly reactive phenoxy radicals. Reduction of the LOH2 complex leads to sequential deprotonation. The ligand LOMe4 and the derived complexes show blue luminescence, which can be rationalised from its molecular structure (analysed by XRD). 相似文献
1000.
Jenson Qi Wensheng Lang Edward Giardino Gary W. Caldwell Charles Smith Lisa K. Minor Andrew L. Darrow Gustaaf Willemsens Katharina DeWaepenaert Peter Roevens Joannes T. M. Linders Yin Liang Margery A. Connelly 《Journal of lipid research》2010,51(12):3559-3567
Acyl-CoA:diacylglycerol acyltransferase (DGAT) catalyzes the terminal step in triglyceride (TG) synthesis using diacylglycerol (DAG) and fatty acyl-CoA as substrates. In the liver, the production of VLDL permits the delivery of hydrophobic TG from the liver to peripheral tissues for energy metabolism. We describe here a novel high-content, high-throughput LC/MS/MS-based cellular assay for determining DGAT activity. We treated endogenous DGAT-expressing cells with stable isotope-labeled [13C18]oleic acid. The [13C18]oleoyl-incorporated TG and DAG lipid species were profiled. The TG synthesis pathway assay was optimized to a one-step extraction, followed by LC/MS/MS quantification. Further, we report a novel LC/MS/MS method for tracing hepatic TG synthesis and VLDL-TG secretion in vivo by administering [13C18]oleic acid to rats. The [13C18]oleic acid-incorporated VLDL-TG was detected after one-step extraction without conventional separation of TG and recovery by derivatizing [13C18]oleic acid for detection. Using potent and selective DGAT1 inhibitors as pharmacological tools, we measured changes in [13C18]oleoyl-incorporated TG and DAG and demonstrated that DGAT1 inhibition significantly reduced [13C18]oleoyl-incorporated VLDL-TG. This DGAT1-selective assay will enable researchers to discern differences between the roles of DGAT1 and DGAT2 in TG synthesis in vitro and in vivo. 相似文献