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991.
992.
Ethylenediaminetetraacetate (EDTA) is currently the most abundant organic pollutant due to its recalcitrance and extensive use. Only a few bacteria can degrade it, using EDTA monooxygenase (EmoA) to initiate the degradation. EmoA is an FMNH2‐dependent monooxygenase that requires an NADH:FMN oxidoreductase (EmoB) to provide FMNH2 as a cosubstrate. Although EmoA has been identified from Chelativorans (ex. Mesorhizobium) sp. BNC1, its catalytic mechanism is unknown. Crystal structures of EmoA revealed a domain‐like insertion into a TIM‐barrel, which might serve as a flexible lid for the active site. Docking of MgEDTA2− into EmoA identified an intricate hydrogen bond network connected to Tyr71, which should potentially lower its pKa. Tyr71, along with nearby Glu70 and a peroxy flavin, facilitates a keto‐enol transition of the leaving acetyl group of EDTA. Further, for the first time, the physical interaction between EmoA and EmoB was observed by ITC, molecular docking and enzyme kinetic assay, which enhanced both EmoA and EmoB activities probably through coupled channelling of FMNH2.  相似文献   
993.
This study examined the effects of Lactobacillus acidophilus ATCC 43121 (LAB) on cholesterol metabolism in hypercholesterolemia-induced rats. Four treatment groups of rats (n = 9) were fed experimental diets: normal diet, normal diet+LAB (2 x 10(6) CFU/day), hypercholesterol diet (0.5% cholesterol, w/w), and hypercholesterol diet + LAB. Body weight, feed intake, and feed efficiency did not differ among the four groups. Supplementation with LAB reduced total serum cholesterol (25%) and VLDL + IDL + LDL cholesterol (42%) in hypercholesterol diet groups, although hepatic tissue cholesterol and lipid contents were not changed. In the normal diet group, cholesterol synthesis (HMG-CoA reductase expression), absorption (LDL receptor expression), and excretion via bile acids (cholesterol 7 alpha-hydroxylase expression) were increased by supplementation with LAB, and increased cholesterol absorption and decreased excretion were found in the hypercholesterol diet group. Total fecal acid sterols excretion was increased by supplementation with LAB. With proportional changes in both normal and hypercholesterol diet groups, primary bile acids (cholic and chenodeoxycholic acids) were reduced, and secondary bile acids (deoxycholic and lithocholic acids) were increased. Fecal neutral sterol excretion was not changed by LAB. In this experiment, the increase in insoluble bile acid (lithocholic acid) reduced blood cholesterol level in rats fed hypercholesterol diets supplemented with LAB. Thus, in the rat, L. acidophilus ATCC 43121 is more likely to affect deconjugation and dehydroxylation during cholesterol metabolism than the assimilation of cholesterol into cell membranes.  相似文献   
994.
3,4-Dihydroquinazoline analogues substituted by N-methyl-N-(5-pyrrolidinopentyl)amine at the 2-position were synthesized and their blocking effects were evaluated for T- and N-type calcium channels. Compound 11b (KYS05080), compared to mibefradil (IC50=1.34+/-0.49 microM), was about 5-fold potent (IC50=0.26+/-0.01 microM) for T-type calcium channel (alpha1G) blocking and its selectivity of T/N-type was also improved (7.5 versus 1.4 of mibefradil).  相似文献   
995.
Structural genomics projects are determining the three-dimensional structure of proteins without full characterization of their function. A critical part of the annotation process involves appropriate knowledge representation and prediction of functionally important residue environments. We have developed a method to extract features from sequence, sequence alignments, three-dimensional structure, and structural environment conservation, and used support vector machines to annotate homologous and nonhomologous residue positions based on a specific training set of residue functions. In order to evaluate this pipeline for automated protein annotation, we applied it to the challenging problem of prediction of catalytic residues in enzymes. We also ranked the features based on their ability to discriminate catalytic from noncatalytic residues. When applying our method to a well-annotated set of protein structures, we found that top-ranked features were a measure of sequence conservation, a measure of structural conservation, a degree of uniqueness of a residue's structural environment, solvent accessibility, and residue hydrophobicity. We also found that features based on structural conservation were complementary to those based on sequence conservation and that they were capable of increasing predictor performance. Using a family nonredundant version of the ASTRAL 40 v1.65 data set, we estimated that the true catalytic residues were correctly predicted in 57.0% of the cases, with a precision of 18.5%. When testing on proteins containing novel folds not used in training, the best features were highly correlated with the training on families, thus validating the approach to nonhomologous catalytic residue prediction in general. We then applied the method to 2781 coordinate files from the structural genomics target pipeline and identified both highly ranked and highly clustered groups of predicted catalytic residues.  相似文献   
996.
997.
Objective: Retinol binding protein‐4 (RBP4) has been reported to impair insulin sensitivity throughout the body. We investigated the relationship between serum RBP4 levels and adiposity indices as well as metabolic risk variables. Research Methods and Procedure: We recruited a total of 102 healthy women 21 to 67 years old. We assessed body composition by computed tomography and divided the study population into four groups based on body weight and visceral fat area (non‐obese without visceral adiposity, non‐obese with visceral adiposity, obese without visceral adiposity, and obese with visceral adiposity). Serum RBP4 levels were measured by radioimmunoassay. Results: Despite similar levels of total body fat, non‐obese women had lower systolic blood pressure, total cholesterol, triglyceride (TG), low‐density lipoprotein (LDL)‐cholesterol levels, insulin resistance indices, and RBP4 levels than non‐obese women with visceral adiposity and had higher high‐density lipoprotein‐cholesterol levels. Similarly, obese women without visceral adiposity had lower blood pressure, total cholesterol, TG levels, insulin resistance indices, and RBP4 levels than obese women with visceral adiposity. In addition, despite having increased body fat, obese women without visceral adiposity had lower TGs, insulin resistance indices, and serum RBP4 levels than non‐obese women with visceral adiposity. By step‐wise multiple regression analysis, visceral fat areas and LDL‐cholesterol levels independently affected RBP4 levels. Discussion: We determined that serum RBP4 levels are independently associated with visceral fat and LDL‐cholesterol levels. These results suggest that, irrespective of body weight, visceral obesity is an independent predictor of serum RBP4 levels, and RBP4 may represent a link between visceral obesity and cardiovascular disease.  相似文献   
998.
Lee  Suyeon  Ha  Ji-Hye  Moon  Duk-Soo  Youn  Soyoung  Kim  Changnam  Park  Boram  Kim  Myong-Jae  Kim  Hyo-Won  Chung  Seockhoon 《Sleep and biological rhythms》2019,17(3):277-285
Sleep and Biological Rhythms - We evaluated the sleep environment factors that influence children’s sleep, and the relationship between co-sleeping and parenting stress and parents’...  相似文献   
999.
Perovskite solar cells are one of the most promising photovoltaic technologies, although their molecular level design and stability toward environmental factors remain a challenge. Layered 2D Ruddlesden–Popper perovskite phases feature an organic spacer bilayer that enhances their environmental stability. Here, the concept of supramolecular engineering of 2D perovskite materials is demonstrated in the case of formamidinium (FA) containing A2FAn?1PbnI3n+1 formulations by employing (adamantan‐1‐yl)methanammonium (A) spacers exhibiting propensity for strong Van der Waals interactions complemented by structural adaptability. The molecular design translates into desirable structural features and phases with different compositions and dimensionalities, identified uniquely at the atomic level by solid‐state NMR spectroscopy. For A2FA2Pb3I10, efficiencies exceeding 7% in mesoscopic device architectures without any additional treatment or use of antisolvents for ambient temperature film deposition are achieved. This performance improvement over the state‐of‐the‐art FA‐based 2D perovskites is accompanied by high operational stability under humid ambient conditions, which illustrates the utility of the approach in perovskite solar cells and sets the basis for advanced supramolecular design in the future.  相似文献   
1000.
Silibinin is a polyphenolic flavonoid compound isolated from milk thistle (Silybum marianum), with known hepatoprotective, anticarcinogenic, and antioxidant effects. Herein, we show that silibinin inhibits receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis from RAW264.7 cells as well as from bone marrow-derived monocyte/macrophage cells in a dose-dependent manner. Silibinin has no effect on the expression of RANKL or the soluble RANKL decoy receptor osteoprotegerin (OPG) in osteoblasts. However, we demonstrate that silibinin can block the activation of NF-κB, c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein (MAP) kinase, and extracellular signal-regulated kinase (ERK) in osteoclast precursors in response to RANKL. Furthermore, silibinin attenuates the induction of nuclear factor of activated T cells (NFAT) c1 and osteoclast-associated receptor (OSCAR) expression during RANKL-induced osteoclastogenesis. We demonstrate that silibinin can inhibit TNF-α-induced osteoclastogenesis as well as the expression of NFATc1 and OSCAR. Taken together, our results indicate that silibinin has the potential to inhibit osteoclast formation by attenuating the downstream signaling cascades associated with RANKL and TNF-α.  相似文献   
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