Bile acids have been reported as important cofactors promoting human and murine norovirus (NoV) infections in cell culture. The underlying mechanisms are not resolved. Through the use of chemical shift perturbation (CSP) NMR experiments, we identified a low-affinity bile acid binding site of a human GII.4 NoV strain. Long-timescale MD simulations reveal the formation of a ligand-accessible binding pocket of flexible shape, allowing the formation of stable viral coat protein–bile acid complexes in agreement with experimental CSP data. CSP NMR experiments also show that this mode of bile acid binding has a minor influence on the binding of histo-blood group antigens and vice versa. STD NMR experiments probing the binding of bile acids to virus-like particles of seven different strains suggest that low-affinity bile acid binding is a common feature of human NoV and should therefore be important for understanding the role of bile acids as cofactors in NoV infection. 相似文献
Nutritional research is currently entering the field of personalized nutrition, to a large extent driven by major technological breakthroughs in analytical sciences and biocomputing. An efficient launching of the personalized approach depends on the ability of researchers to comprehensively monitor and characterize interindividual variability in the activity of the human gastrointestinal tract. This information is currently not available in such a form. This review therefore aims at identifying and discussing published data, providing evidence on interindividual variability in the processing of the major nutrients, i.e., protein, fat, carbohydrates, vitamins, and minerals, along the gastrointestinal tract, including oral processing, intestinal digestion, and absorption. Although interindividual variability is not a primary endpoint of most studies identified, a significant number of publications provides a wealth of information on this topic for each category of nutrients. This knowledge remains fragmented, however, and understanding the clinical relevance of most of the interindividual responses to food ingestion described in this review remains unclear. In that regard, this review has identified a gap and sets the base for future research addressing the issue of the interindividual variability in the response of the human organism to the ingestion of foods. 相似文献
Obesity is a risk factor for Alzheimer’s disease (AD), but underlying mechanisms are not clear. We analyzed peripheral clearance of amyloid β (Aβ) in overweight mice because its systemic elimination may impact brain Aβ load, a major landmark of AD pathology. We also analyzed whether circulating insulin-like growth factor I (IGF-I) intervenes in the effects of overweight as this growth factor modulates brain Aβ clearance and is increased in the serum of overweight mice. Overweight mice showed increased Aβ accumulation by the liver, the major site of elimination of systemic Aβ, but unaltered brain Aβ levels. We also found that Aβ accumulation by hepatocytes is stimulated by IGF-I, and that mice with low serum IGF-I levels show reduced liver Aβ accumulation—ameliorated by IGF-I administration, and unchanged brain Aβ levels. In the brain, IGF-I favored the association of its receptor (IGF-IR) with the Aβ precursor protein (APP), and at the same time, stimulated non-amyloidogenic processing of APP in astrocytes, as indicated by an increased sAPPα/sAPPβ ratio after IGF-I treatment. Since serum IGF-I enters into the brain in an activity-dependent manner, we analyzed in overweight mice the effect of brain activation by environmental enrichment (EE) on brain IGF-IR phosphorylation and its association to APP, as a readout of IGF-I activity. After EE, significantly reduced brain IGF-IR phosphorylation and APP/IGF-IR association were found in overweight mice as compared to lean controls. Collectively, these results indicate that a high-fat diet influences peripheral clearance of Aβ without affecting brain Aβ load. Increased serum IGF-I likely contributes to enhanced peripheral Aβ clearance in overweight mice, without affecting brain Aβ load probably because its brain entrance is reduced. 相似文献
Two-dimensional (2D) nanomaterials have attracted a great deal of attention since the discovery of graphene in 2004, due to their intriguing physicochemical properties and wide-ranging applications in catalysis, energy-related devices, electronics and optoelectronics. To maximize the potential of 2D nanomaterials for their technological applications, controlled assembly of 2D nanobulding blocks into integrated systems is critically needed. This mini review summarizes the reported strategies of 2D materials-based assembly into integrated functional nanostructures, from in-situ assembly method to post-synthesis assembly. The applications of 2D assembled integrated structures are also covered, especially in the areas of energy, electronics and sensing, and we conclude with discussion on the remaining challenges and potential directions in this emerging field.
In aerospace industry, tapping is the prime choice for hole threading in jet aero-engine turbine components. Taps are not usually resharpened, unlike other 相似文献
The air-surface exchange of mercury (Hg) was measured, using a dynamic polycarbonate flux chamber, for soils with low or "background" Hg concentrations (<0.1 mg/kg) at eleven locations across the contiguous United States. Sampling locations included agricultural, desert, grassland, mixed and pine forest ecosystems (n=1326 soil flux measurements at 46 individual sites). An overall soil Hg flux of 0.9+/-0.2 ng/m2/h for these background soils was obtained by averaging the means for the different locations. Soil Hg fluxes were significantly lower in dark conditions than in the light for all but the grassland sites. Mean inlet air Hg concentrations were 1.0+/-0.1 ng/m3 in the dark and 1.3+/-0.2 ng/m3 in the light. Soil temperature inside and outside of the chamber, air temperature, relative humidity, and irradiance were measured concurrently with soil Hg flux. Soil-air Hg exchange was weakly predicted by environmental variables (R2 from 0.07 to 0.52). For a single location, flux was better correlated with soil moisture than other measured environmental parameters, suggesting that soil moisture might be an important driver for Hg emissions from background soils. In addition, based on data collected we suggest some quality control measures for use of Tekran 2537A analyzers when measuring low mercury fluxes. Using basic scaling procedures, we roughly estimate that natural emissions from soils in the contiguous U.S. release approximately 100 Mg/yr of Hg to the atmosphere. 相似文献
Residues of the herbicide glyphosate (N-phosphonomethylglicine) and its main metabolite, aminomethylphosphonic acid (AMPA), were determined in a forest soil in north-west Spain, previously treated with 5 and 8 l ha(-1) of glyphosate. Both products were monitored in the solid and liquid soil phases for an 8-week period after the treatment. Soil samples were extracted by KH2PO4. Concentrated extracts and liquid phase samples were derivatized with 9-fluorenylmethyl chloroformate (FMOC) before determination by HPLC using an anion exchange column and spectrofluorometric detection. The treated soil peaked at 6.9 microg g(-1) of glyphosate, whereas soil water samples peaked at 0.74 microg ml(-1) of glyphosate. One month after the treatment, both glyphosate and AMPA concentrations in soil and water samples were almost negligible. AMPA peaked at 0.77 microg ml(-1) in soil water samples. Glyphosate and AMPA exhibited high vertical mobility in the treated soil, quickly reaching high concentrations in subsurface horizons where the degradation is slower. 相似文献
A suite of 30 primarily estrogenic organic wastewater contaminants was measured in several influent/effluent wastewater samples from four municipal wastewater treatment plants and effluents from one bleached kraft pulp mill (BKME) using an ultra-trace analytical method based on gas chromatography-high resolution mass spectroscopy (GC-HRMS). In vitro recombinant yeast assay detection of the estrogenic equivalent (EEq) on whole and solid phase extracted (SPE) and fractionated wastewater was also performed. 19-norethindrone was the most frequently detected and abundant (26-224 ng/L) of all the synthetic estrogens/progesterones in the influent samples. 17alpha-ethinylestradiol was the more frequently detected synthetic estrogen/progesterone in the effluents occurring at or below 5 ng/L with some sporadic occurrences of up to 178 ng/L. The greatest levels of steroidal estrogens in municipal effluents were E1>E2>E3 which were all <20 ng/L. Nonylphenol and di(2-ethylhexyl) phthalate were found to be the highest non-steroidal synthetic compounds surveyed in both municipal influent and effluent samples, both occurring at 6-7 microg/L in municipal effluents. BKME contained relatively large amounts of the plant sterol stigmasterol (4 microg/L) but low amounts of fecal sterols, and steroidal estrogens (E2 only at 6 ng/L) when compared to the municipal effluents. In vitro EEq in the wastewater surveyed ranged from 9-106 ng E2/L and ranked from municipal influent>municipal effluent approximately BKME, with most of the estrogenicity fractionating in the 100% methanol SPE fraction followed by a secondary amount in the diethyl ether (for municipal) or methyl-tert butyl ether (for BKME) SPE fractions. Most correlations between chemical and in vitro estrogenic equivalency were weak (p>0.05 in most cases). Unexpected inverse correlations between in vitro estrogenic activity and concentrations of the estrogenic contaminant bisphenol A were found which likely contributed to the weakness of these correlations. A modified toxicity identification and evaluation procedure was continued with the SPE extracts from the more potent 100% methanol SPE fractions of municipal effluent. High performance liquid chromatography band elution retention times, based on in vitro estrogen detection, indicated that steroidal estrogens such as E2 were responsible for most of the estrogenicity of the samples. Subsequent collection and GC-MS analysis of active bands did not confirm the presence of steroidal estrogens, but expanded the possibility of phthalate esters (i.e. dibutyl phthalate) and natural sterols (i.e. beta-sitosterol) contributing to the overall estrogenic load. 相似文献