A preliminary study of the metabolic stability of a series of benzoxazinone derivatives as potent neuropeptide Y5 antagonists

The metabolic stability of benzoxazinone derivatives, a potent series of NPY Y5 antagonists, has been investigated. This study resulted in the identification of the structural moieties prone to metabolic transformations and which strongly influenced the in vitro half-life. This provides opportunities to optimize the structure of this new class of NPY Y5 antagonists.     

The O-polysaccharide from the lipopolysaccharide of Providencia stuartii O44 contains L-quinovose, a 6-deoxy sugar rarely occurring in bacterial polysaccharides

The O-polysaccharide (O-antigen) of Providencia stuartii O44:H4 (strain 3768/51) was obtained by mild acid degradation of the lipopolysaccharide and studied by sugar and methylation analyses along with (1)H and (13)C NMR spectroscopy, including 2D (1)H,(1)H COSY, TOCSY, ROESY, and H-detected (1)H,(13)C HSQC, and HMQC-TOCSY experiments. The O-polysaccharide was found to have a branched hexasaccharide repeating unit of the following structure: [Formula: see text].     

Cerebral infarction in diabetes: Clinical pattern,stroke subtypes,and predictors of in-hospital mortality

Background  

To compare the characteristics and prognostic features of ischemic stroke in patients with diabetes and without diabetes, and to determine the independent predictors of in-hospital mortality in people with diabetes and ischemic stroke.     

The structure of the O-polysaccharide from the lipopolysaccharide of Providencia stuartii O57 containing an amide of D-galacturonic acid with L-alanine

The O-polysaccharide (O-antigen) was obtained by mild acid degradation of the lipopolysaccharide of Providencia stuartii O57:H29. Studies by sugar and methylation analyses along with (1)H and (13)C NMR spectroscopy, including two-dimensional (1)H,(1)H COSY, TOCSY, ROESY, H-detected (1)H,(13)C HSQC, and HMBC experiments, showed that the polysaccharide contains an amide of D-galacturonic acid with L-alanine and has the following pentasaccharide repeating unit: [formula: see text]     

Peptergents: peptide detergents that improve stability and functionality of a membrane protein, glycerol-3-phosphate dehydrogenase

Toward enhancing in vitro membrane protein studies, we have utilized small self-assembling peptides with detergent properties ("peptergents") to extract and stabilize the integral membrane flavoenzyme, glycerol-3-phosphate dehydrogenase (GlpD), and the soluble redox flavoenzyme, NADH peroxidase (Npx). GlpD is a six transmembrane spanning redox enzyme that catalyzes the oxidation of glycerol-3-phosphate to dihydroxyacetone phosphate. Although detergents such as n-octyl-beta-D-glucpyranoside can efficiently solubilize the enzyme, GlpD is inactivated within days once reconstituted into detergent micelles. In contrast, peptergents can efficiently extract and solubilize GlpD from native Escherichia coli membrane and maintain its enzymatic activity up to 10 times longer than in traditional detergents. Intriguingly, peptergents also extended the activity of a soluble flavoenzyme, Npx, when used as an additive. Npx is a flavoenzyme that catalyzes the two-electron reduction of hydrogen peroxide to water using a cysteine-sulfenic acid as a secondary redox center. The lability of the peroxidase results from oxidation of the sulfenic acid to the sulfinic or sulfonic acid forms. Oxidation of the sulfenic acid, the secondary redox center, results in inactivation, and this reaction proceeds in vitro even in the presence of reducing agents. Although the exact mechanism by which peptergents influence solution stability of Npx remains to be determined, the positive effects may be due to antioxidant properties of the peptides. Peptide-based detergents can be beneficial for many applications and may be particularly useful for structural and functional studies of membrane proteins due to their propensity to enhance the formation of ordered supramolecular assemblies.     

Endothelial lipase modulates HDL but has no effect on atherosclerosis development in apoE-/- and LDLR-/- mice

Endothelial lipase (EL) is a determinant of high density lipoprotein-cholesterol (HDL-C) level, which is negatively correlated with atherosclerosis susceptibility. We found no difference in aortic atherosclerotic lesion areas between 26-week-old EL+/+ apolipoprotein E-deficient (apoE-/-) and EL-/- apoE-/- mice. To more firmly establish the role of EL in atherosclerosis, we extended our study to EL-/- and EL+/+ low density lipoprotein receptor-deficient (LDLR-/-) mice that were fed a Western diet. Morphometric analysis again revealed no difference in atherosclerosis lesion area between the two groups. Compared with EL+/+ mice, we found increased HDL-C in EL-/- mice with apoE-/- or LDLR-/- background but no difference in macrophage content between lesions of EL-/- and EL+/+ mice in apoE-/- or LDLR-/- background. EL inactivation had no effect on hepatic mRNAs of proteins involved in reverse cholesterol transport. A survey of lipid homeostasis in EL+/+ and EL-/- macrophages revealed that oxidized LDL-induced ABCA1 was attenuated in EL-/- macrophages. This potentially proatherogenic change may have nullified any minor protective increase of HDL in EL-/- mice. Thus, although EL modulated lipoprotein profile in mice, there was no effect of EL inactivation on atherosclerosis development in two hyperlipidemic atherosclerosis-prone mouse models.     

Monitoring the biological activity of the composting process: Oxygen uptake rate (OUR), respirometric index (RI), and respiratory quotient (RQ)

Composting of several organic wastes of different chemical composition (source-separated organic fraction of municipal solid waste, dewatered raw sludge, dewatered anaerobically digested sludge and paper sludge) was carried out under controlled conditions to study the suitability of different biological indexes (oxygen uptake rate, respirometric index, and respiratory quotient) to monitor the biological activity of the composting process. Among the indexes tested, oxygen uptake rate (also referred to as dynamic respirometric index) provided the most reliable values of microbial activity in a compost environment. On the other hand, values of the static respirometric index measured at process temperature, especially in the early stages of the composting process, were significantly lower than those of the dynamic index, which was probably due to oxygen diffusion limitations present in static systems. Both static and dynamic indexes were similar during the maturation phase. Static respirometric index measured at 37 degrees C should not be used with samples obtained during the thermophilic phase, since it resulted in an underestimation of the respiration values. Respiratory quotient presented only slight variations when changing the process temperature or the waste considered, and its use should be restricted to ensure aerobic conditions in the composting matrix.     

Structure of the O-polysaccharide of Providencia alcalifaciens O19

Studies of the O-polysaccharide chain of the lipopolysaccharide (O-antigen) of Providencia alcalifaciens O19 by sugar and methylation analyses along with NMR spectroscopy, including 2D 1H,1H COSY, TOCSY, NOESY and 1H,13C HSQC experiments, showed that the pentasaccharide repeating unit of the polysaccharide has the following structure: [structure: see text] where Fuc3NAc is 3-acetamido-3,6-dideoxygalactose. The unique structure of the O-antigen and serological data are in consistence with classification of this bacterium in a separate Providencia serogroup.     

Structure of the O-polysaccharide of Providencia stuartii O49

The O-specific polysaccharide chain (O-antigen) of the lipopolysaccharide (LPS) of Providencia stuartii O49 was studied using sugar and methylation analyses along with 1H and 13C NMR spectroscopy, including two-dimensional COSY, TOCSY, ROESY, H-detected 1H, 13C HSQC and HMBC experiments. The polysaccharide was found to have the trisaccharide repeating unit with the following structure: -->6)-beta-D-Galp(1-->3)-beta-D-GalpNAc(1-->4)-alpha-D-Galp(1-->