Disturbed brain phospholipid and docosahexaenoic acid metabolism in calcium-independent phospholipase A(2)-VIA (iPLA(2)β)-knockout mice

Calcium-independent phospholipase A(2) group VIA (iPLA(2)β) releases docosahexaenoic acid (DHA) from phospholipids in vitro. Mutations in the iPLA(2)β gene, PLA2G6, are associated with dystonia-parkinsonism and infantile neuroaxonal dystrophy. To understand the role of iPLA(2)β in brain, we applied our in vivo kinetic method using radiolabeled DHA in 4 to 5-month-old wild type (iPLA(2)β(+/+)) and knockout (iPLA(2)β(-/-)) mice, and measured brain DHA kinetics, lipid concentrations, and expression of PLA(2), cyclooxygenase (COX), and lipoxygenase (LOX) enzymes. Compared to iPLA(2)β(+/+) mice, iPLA(2)β(-/-) mice showed decreased rates of incorporation of unesterified DHA from plasma into brain phospholipids, reduced concentrations of several fatty acids (including DHA) esterified in ethanolamine- and serine-glycerophospholipids, and increased lysophospholipid fatty acid concentrations. DHA turnover in brain phospholipids did not differ between genotypes. In iPLA(2)β(-/-) mice, brain levels of iPLA(2)β mRNA, protein, and activity were decreased, as was the iPLA(2)γ (Group VIB PLA(2)) mRNA level, while levels of secretory sPLA(2)-V mRNA, protein, and activity and cytosolic cPLA(2)-IVA mRNA were increased. Levels of COX-1 protein were decreased in brain, while COX-2 protein and mRNA were increased. Levels of 5-, 12-, and 15-LOX proteins did not differ significantly between genotypes. Thus, a genetic iPLA(2)β deficiency in mice is associated with reduced DHA metabolism, profound changes in lipid-metabolizing enzyme expression (demonstrating lack of redundancy) and of phospholipid fatty acid content of brain (particularly of DHA), which may be relevant to neurologic abnormalities in humans with PLA2G6 mutations.     

Gastroprotective activity and mechanism of novel dichlorido-zinc(II)-4-(2-(5-methoxybenzylideneamino)ethyl)piperazin-1-iumphenolate complex on ethanol-induced gastric ulceration

Zinc complexes were reported to have anti-ulcer activity and used as drug for the treatment of gastrointestinal disorders. A novel compound dichlorido-zinc(II)-4-(2-(5-methoxybenzylidene amino)ethyl)piperazin-1-iumphenolate (ZnHMS) was synthesized, characterized and evaluated for its gastroprotective activity against ethanol-induced ulcer in rats. Gross and microscopic lesions, histochemical staining of glycogen storage, biochemical and immunological parameters were taken into consideration. Oral administration of ZnHMS (30 and 60 mg/kg; 14 days) dose-dependently inhibited gastric lesions. It significantly increased the mucus content and total acidity compared to the control group (P<0.01). Serum levels of aspartate (AST), alanine (ALT) transaminases, pro-inflammatory interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and anti-inflammatory interleukin-10 (IL-10) in the rats exposed to ethanol induced ulceration have been altered. ZnHMS considerably enhances (P<0.05) the protection of gastric epithelia by modulating the acute alterations of AST, ALT, IL-6, IL-10, TNF-α and stomach glycogen. Interestingly, ZnHMS did interfere with the natural release of nitric oxide. In addition, acute toxicity study revealed no abnormal sign to the rats treated with ZnHMS (2000 mg/kg). These findings suggest that the gastroprotective activity of ZnHMS might contribute in adjusting the inflammatory cytokine-mediated oxidative damage to the gastric mucosa.     

The very low density lipoprotein receptor is not necessary for maintaining brain polyunsaturated fatty acid concentrations

Polyunsaturated fatty acids (PUFA), especially docosahexaenoic and arachidonic acids, as well as cholesterol are important for neural development and maintaining brain function. However, in contrast to cholesterol, the brain is unable to synthesize the required amounts of these PUFA de novo and requires a constant supply from plasma. Suggested pools of uptake include plasma unesterified PUFA or the uptake of PUFA-containing lipoproteins via lipoprotein receptors into endothelial cells of the blood brain barrier. Our study tested whether the very low density lipoprotein receptor (VLDLr) is necessary for maintaining brain PUFA and cholesterol concentrations. Moreover, since VLDLr knockout (VLDLr^?/?) mice have been reported to have behavioural deficits, this study asked the question whether altered brain PUFA and cholesterol concentrations might be related to these deficits. VLDLr^?/? and wild-type mice had ad libitum access to chow. At 7 weeks of age the mice were sacrificed, and the cortex, cerebellum, hippocampus, and the remainder of the brain were isolated for total fatty acid and cholesterol analyses. There were no differences in total lipid PUFA or cholesterol concentrations in any of the four brain regions between VLDLr^?/? and wild-type mice. These findings demonstrate that the VLDLr is not necessary for maintaining brain PUFA concentrations and suggest that other mechanisms to transport PUFA into the brain must exist.     

金属离子抗性衣藻品系的分离筛选及其鉴定

从乌鲁木齐南山土壤中分离得到62株绿藻,利用印迹法筛选对Cu2＋、Fe3＋、Zn2＋、Co2＋4种金属离子有抗性的藻株。结果发现XJU-3、XJU-28和XJU-36对0.1mmol·L-1 Co2＋有抗性;XJU-28对1mmol·L-1 Zn2＋和Fe3＋有抗性;而XJU-36仅对0.05mmol·L-1 Cu2＋有抗性。利用形态学特征和rDNA转录单元内间隔区（ITS1和TIS2,包括5.8S）序列对3株绿藻进行了分类学鉴定。依据形态特征,初步判断3株绿藻可能属于衣藻属（Chlamydomonas）。利用ITS（包括5.8S）序列构建系统进化树分析,结果表明,XJU-3、XJU-28与Chlamydomonas zebra的关系较近,XJU-36与Chlamydomonas petasua的关系较近。     

Gender Disparities in the Presentation,Management and Outcomes of Acute Coronary Syndrome Patients: Data from the 2nd Gulf Registry of Acute Coronary Events (Gulf RACE-2)

Background

Gender-related differences in mortality of acute coronary syndrome (ACS) have been reported. The extent and causes of these differences in the Middle-East are poorly understood. We studied to what extent difference in outcome, specifically 1-year mortality are attributable to demographic, baseline clinical differences at presentation, and management differences between female and male patients.

Methodology/Principal Findings

Baseline characteristics, treatment patterns, and 1-year mortality of 7390 ACS patients in 65 hospitals in 6 Arabian Gulf countries were evaluated during 2008–2009, as part of the 2nd Gulf Registry of Acute Coronary Events (Gulf RACE-2). Women were older (61.3±11.8 vs. 55.6±12.4; P<0.001), more overweight (BMI: 28.1±6.6 vs. 26.7±5.1; P<0.001), and more likely to have a history of hypertension, hyperlipidemia or diabetes. Fewer women than men received angiotensin-converting enzyme inhibitors (ACE), aspirin, clopidogrel, beta blockers or statins at discharge. They also underwent fewer invasive procedures including angiography (27.0% vs. 34.0%; P<0.001), percutaneous coronary intervention (PCI) (10.5% vs. 15.6%; P<0.001) and reperfusion therapy (6.9% vs. 20.2%; P<0.001) than men. Women were at higher unadjusted risk for in-hospital death (6.8% vs. 4.0%, P<0.001) and heart failure (HF) (18% vs. 11.8%, P<0.001). Both 1-month and 1-year mortality rates were higher in women than men (11% vs. 7.4% and 17.3% vs. 11.4%, respectively, P<0.001). Both baseline and management differences contributed to a worse outcome in women. Together these variables explained almost all mortality disparities.

Conclusions/Significance

Differences between genders in mortality appeared to be largely explained by differences in prognostic variables and management patterns. However, the origin of the latter differences need further study.     

Ecoregion-Based Conservation Planning in the Mediterranean: Dealing with Large-Scale Heterogeneity

Spatial priorities for the conservation of three key Mediterranean habitats, i.e. seagrass Posidonia oceanica meadows, coralligenous formations, and marine caves, were determined through a systematic planning approach. Available information on the distribution of these habitats across the entire Mediterranean Sea was compiled to produce basin-scale distribution maps. Conservation targets for each habitat type were set according to European Union guidelines. Surrogates were used to estimate the spatial variation of opportunity cost for commercial, non-commercial fishing, and aquaculture. Marxan conservation planning software was used to evaluate the comparative utility of two planning scenarios: (a) a whole-basin scenario, referring to selection of priority areas across the whole Mediterranean Sea, and (b) an ecoregional scenario, in which priority areas were selected within eight predefined ecoregions. Although both scenarios required approximately the same total area to be protected in order to achieve conservation targets, the opportunity cost differed between them. The whole-basin scenario yielded a lower opportunity cost, but the Alboran Sea ecoregion was not represented and priority areas were predominantly located in the Ionian, Aegean, and Adriatic Seas. In comparison, the ecoregional scenario resulted in a higher representation of ecoregions and a more even distribution of priority areas, albeit with a higher opportunity cost. We suggest that planning at the ecoregional level ensures better representativeness of the selected conservation features and adequate protection of species, functional, and genetic diversity across the basin. While there are several initiatives that identify priority areas in the Mediterranean Sea, our approach is novel as it combines three issues: (a) it is based on the distribution of habitats and not species, which was rarely the case in previous efforts, (b) it considers spatial variability of cost throughout this socioeconomically heterogeneous basin, and (c) it adopts ecoregions as the most appropriate level for large-scale planning.     

Molecular interactions involved in proton-dependent gating in KcsA potassium channels

The bacterial potassium channel KcsA is gated open by the binding of protons to amino acids on the intracellular side of the channel. We have identified, via channel mutagenesis and x-ray crystallography, two pH-sensing amino acids and a set of nearby residues involved in molecular interactions that influence gating. We found that the minimal mutation of one histidine (H25) and one glutamate (E118) near the cytoplasmic gate completely abolished pH-dependent gating. Mutation of nearby residues either alone or in pairs altered the channel’s response to pH. In addition, mutations of certain pairs of residues dramatically increased the energy barriers between the closed and open states. We proposed a Monod–Wyman–Changeux model for proton binding and pH-dependent gating in KcsA, where H25 is a “strong” sensor displaying a large shift in pK_a between closed and open states, and E118 is a “weak” pH sensor. Modifying model parameters that are involved in either the intrinsic gating equilibrium or the pK_a values of the pH-sensing residues was sufficient to capture the effects of all mutations.     

Anti-pathogenic,antibiofilm, and technological properties of fermented food associated Staphylococcus succinus strain AAS2

Abstract

The present investigation was aimed to determine the anti-pathogenic, antibiofilm, and technological properties of fermented food associated Staphylococcus succinus strain AAS2. The anti-pathogenic attribute of cell-free neutralized supernatant (CFNS) of strain AAS2 was assessed against food-borne and enteric pathogens that revealed promising activity against Staphylococcus aureus and Enterobacter aerogenes with high arbitrary unit of 220.25?±?3.3 and 170.2?±?4.6?AU/mL, respectively. Furthermore, the antibiofilm and time-kill assay of CFNS of strain AAS2 depicted remarkable reduction in biofilm formation of indicator pathogens in a dose-dependent manner. Moreover, time-kill assay data revealed the drastic reduction in the viability (log cfu/mL) of S. aureus and E. aerogenes in the presence of varied minimum inhibitory concentration ranges of CFNS. The distinct technological properties of strain AAS2 were demonstrated using standard methodologies. Reported results estimated moderate level of exopolysaccharide (41.3?±?0.6?mg/L) and lipase production (8.3?±?0.3?mm), followed by remarkable autolytic (30.1?±?1.2–43.1?±?1.3%), catalase (13.82?±?0.3?AU), and nitrate reductase (10.25?±?0.3?mM nitrite/mg dry weight) activities under standard conditions. Most importantly, the strain cleared the specific in vitro safety assessment tests. The described anti-pathogenic and technological traits of strain AAS2 paved the way to utilize it in pharmaceutical as well as food processing industries as starter/adjunct culture.     

乌鲁木齐南部山区地生地衣群落分布格局

为了查明乌鲁木齐南部山区地生地衣群落分布格局,作者选取了24个样点(20 m×20 m),设置了240个50cm×50 cm样方,调查地生地衣的种类及盖度,分析其分布格局及其与环境因子的关系.结果表明,乌鲁木齐南部山区共有地生地衣17种,隶属于2目5科10属.聚类分析和DCA排序将该地区的地生地衣分为4个主要样点组,分...