Lack of effect of nicotine or ethanol on the activity of 11β-hydroxysteroid dehydrogenase type 2

Low birth weight in combination with a large placenta predicts human hypertension. The pathophysiological link remains unclear, but glucocorticoid excess impairs fetal growth and leads to offspring hypertension. A key controller of fetal glucocorticoid exposure and local tissue availability is 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2). The activity of placental 11β-HSD2 correlates with fetal growth in animals and humans. Ethanol abuse and smoking are known to retard fetal growth which may relate to altered glucocorticoid action or dynamics. This study has examined whether nicotine or ethanol modulate glucocorticoid action in the placenta or fetus by inhibiting 11β-HSD2, using clonal cell cultures, freshly isolated dually perfused intact human placentas and placentas from in vivo treated rats. No significant effect on the activity of 11β-HSD2 by pathophysiologically relevant nicotine or ethanol concentrations was observed. The mechanism of action of nicotine and ethanol relevant to reduced fetal growth requires further study.     

A tetravalent dengue nanoparticle stimulates antibody production in mice

Background

Dengue is a major public health problem worldwide, especially in the tropical and subtropical regions of the world. Infection with a single Dengue virus (DENV) serotype causes a mild, self-limiting febrile illness called dengue fever. However, a subset of patients experiencing secondary infection with a different serotype progresses to the severe form of the disease, dengue hemorrhagic fever/dengue shock syndrome. Currently, there are no licensed vaccines or antiviral drugs to prevent or treat dengue infections. Biodegradable nanoparticles coated with proteins represent a promising method for in vivo delivery of vaccines.

Findings

Here, we used a murine model to evaluate the IgG production after administration of inactivated DENV corresponding to all four serotypes adsorbed to bovine serum albumin nanoparticles. This formulation induced a production of anti-DENV IgG antibodies (p < 0.001). However, plaque reduction neutralization assays with the four DENV serotypes revealed that these antibodies have no neutralizing activity in the dilutions tested.

Conclusions

Our results show that while the nanoparticle system induces humoral responses against DENV, further investigation with different DENV antigens will be required to improve immunogenicity, epitope specicity, and functional activity to make this platform a viable option for DENV vaccines.     

Cryoenzymology of β-galactosidase: Effects of cryosolvents

Experimental support for the use of fluid aqueous organic solvent systems and subzero temperatures in mechanistic studies of β-galactosidase is presented. The enzyme was stable and retained catalytic activity and structural integrity in 50% aqueous dimethyl sulfoxide and 60% aqueous methanol at 0°C; at lower temperatures higher concentrations of cosolvent may be successfully used. The effects of dimethyl sulfoxide on the catalytic and structural properties of the enzyme were investigated in detail. For the β-galactoside-catalyzed h ydrolysis ofo-nitrophenyl-β-D-galactoside the value ofk _cat decreased in a linear manner with increasing cosolvent concentration, whereasK _m increased exponentially. The decrease ink _cat paralleled the decrease in water concentration, consistent with rate-limiting hydrolysis of a galactosylenzyme intermediate. The increase inK _m is attributed to less favorable partitioning of the substrate to the active site in the cryosolvent compared to aqueous solution. ThepH*-rate profile for this reaction at 0°C in 50% dimethyl sulfoxide was similar to that in aqueous solution, withpK*₁=5.8 andpK*₂=8.0. Linear Arrhenius plots, with energies of activation of 13.9 and 16.0 kcal mol^?1, respectively, were obtained for the β-galactosidase-catalyzed hydrolysis ofo-nitrophenyl- andp-nitrophenyl-β-D-galactosides in 50% dimethyl sulfoxide at temperatures to ?57°C. Examination of the intrinsic fluorescence and ultraviolet spectra of the enzyme as a function of increasing cosolvent concentration showed no evidence for structural perturbation up to and including 50% dimethyl sulfoxide at 0°C. We conclude that these cryosolvent systems are suitable for mechanistic investigations of β-galactosidase, in particular for trapping intermediates at subzero temperatures.     

澳门鸟类资源调查报告

1989～2009年在澳门山林和沿海滩涂湿地对鸟类进行了调查和记录,共记录鸟类297种,加上文献中记录的3种,整理出澳门鸟类名录共300种,隶属17目56科.其中非雀形目有30科160种,占澳门鸟类总种数的53.33%;雀形目有26科140种,占澳门鸟类种数46.67%.就数量来看,澳门鸟类中的优势种有9种,常见种44种,偶见种96种,稀有种则有151种.白腹海雕Haliaeetus leucogaster属于国家Ⅰ级重点保护野生鸟类.属于国家Ⅱ级重点保护的鸟类有33种.澳门鸟类属于<濒危野生动植物种国际贸易公约,2007>公约附录Ⅰ的有游隼Falco peregrinus peregrinus、小青脚鹬Tringa guttifer和小杓鹬Numenius minutus 3种,属于公约附录Ⅱ的有29种.勺嘴鹬Eurynorhynchus pygmeus被世界自然保护联盟(2009)列入极危(CR)鸟类,黑脸琵鹭Platalea minor和小青脚鹬被列入濒危(EN)鸟类.易危(VU)鸟类有4种,近危(NT)鸟类有5种.本文成果可为今后长期监测和保护澳门鸟类资源提供依据.     

Measuring the translational diffusion coefficients of small DNA molecules by capillary electrophoresis

The apparent translational diffusion coefficients of four 20 base pair (bp) DNA oligonucleotides with different sequences have been measured by capillary electrophoresis, using the stopped migration method. The diffusion coefficients of the four oligomers were equal within experimental error, and averaged (120 +/- 10) x 10(-8) cm(2) s(-1) in 40 mM Tris-acetate-EDTA buffer at 25 degrees C. Since this value is nearly identical to the translational diffusion coefficient determined for a different 20-bp oligomer using other methods, the stopped migration method can accurately measure the diffusion coefficients of small DNA oligomers. The apparent diffusion coefficient of a 118-bp DNA restriction fragment was also measured by the stopped migration method. However, the observed value was approximately 25% larger than expected from other measurements, possibly because the diffusion coefficients of larger DNA molecules are somewhat dependent on the ionic strength of the solution.     

Trophic state and nutrient limitation in Lake Baringo,Kenya

The trophic state of Lake Baringo and factors that could be limiting the development of algal biomass in it were investigated during one wet/dry hydrological cycle in 2014–2015. Water samples were analysed for dissolved inorganic nutrients, including , and , total phosphorus and Chlorophyll a. Light attenuation was estimated using Secchi depth. The trophic state was determined using Carlson trophic state indices (CTSI). Deviations in CTSI, nutrient ratios and ambient nutrient concentrations were used to identify factors limiting phytoplankton growth. The mean values measured for Secchi depth, nitrate, total phosphorus and Chlorophyll a showed significant seasonal variation (p < 0.05). Based on the Carlson trophic state index, the results show that Lake Baringo is eutrophic. However, the lake is also experiencing phosphorus limitation and poor light penetration, because of high turbidity, which is more pronounced during the wet season.     

Whole Grain Rye Intake,Reflected by a Biomarker,Is Associated with Favorable Blood Lipid Outcomes in Subjects with the Metabolic Syndrome – A Randomized Study

Background and Aim

Few studies have explored the possible plasma cholesterol lowering effects of rye consumption. The aim of this secondary analysis in the SYSDIET study was to investigate the association between plasma alkylresorcinols (AR), a biomarker for whole grain wheat and rye intake, and blood lipid concentrations in a population with metabolic syndrome. Furthermore, we analyzed the associations between the AR C17∶0/C21∶0 ratio, a suggested marker of the relative intake of whole grain/bran rye, and blood lipid concentrations.

Methods

Participants were 30–65 years of age, with body mass index (BMI) 27–40 kg/m² and had metabolic syndrome. Individuals were recruited through six centers in the Nordic countries and randomized either to a healthy Nordic diet (ND, n = 93), rich in whole grain rye and wheat, as well as berries, fruits and vegetables, rapeseed oil, three fish meals per week and low-fat dairy products, or a control diet (n = 65) for 18/24 weeks. Associations between total plasma AR concentration and C17∶0/C21∶0 homologue ratio and blood lipids were investigated in pooled (ND + control group) regression analyses at 18/24 weeks adjusted for baseline value for the dependent variable, age, BMI and statin use.

Results

When adjusted for confounders, total plasma AR at 18/24 weeks was not significantly associated with blood lipids but the AR ratio C17∶0/C21∶0 was inversely associated with LDL cholesterol concentrations (B (95% CI): −0.41 (−0.80 to −0.02)), log LDL/HDL cholesterol ratio (−0.20 (−0.37 to −0.03)), log non-HDL cholesterol (−0.20 (−0.37 to −0.03)), log apolipoprotein B (−0.12 (−0.24 to 0.00)) and log triglyceride concentrations (−0.35 (−0.59 to −0.12)).

Discussion

Increased proportion of whole grain rye, reflected by a biomarker, in the diet is associated with favorable blood lipid outcomes, a relationship that should be further investigated.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00992641","term_id":"NCT00992641"}}NCT00992641     

The crystal structure of a human PP2A phosphatase activator reveals a novel fold and highly conserved cleft implicated in protein-protein interactions

Protein phosphatase 2A (PP2A) is a heterotrimeric Ser/Thr phosphatase that is involved in regulating a plethora of signaling pathways in the cell, making its regulation a critical part of the well being of the cell. For example, three of the non-catalytic PP2A subunits have been linked to carcinogenic events. Therefore, the molecular basis for the complicated protein-protein interaction pattern of PP2A and its regulators is of special interest. The PP2A phosphatase activator (PTPA) protein is highly conserved from humans to yeast. It is an activator of PP2A and has been shown to be essential for a fully functional PP2A, but its mechanism of activation is still not well defined. We have solved the crystal structure of human PTPA to 1.6A. It reveals a two-domain protein with a novel fold comprised of 13 alpha-helices. We have identified a highly conserved cleft as a potential region for interaction with peptide segments of other proteins. Binding studies with ATP and its analogs are not consistent with ATP being a cofactor/substrate for PTPA as had previously been proposed. The structure of PTPA can serve as a basis for structure-function studies directed at elucidating its mechanism as an activator of PP2A.