The alpha-to-beta conformational transition of Alzheimer's Abeta-(1-42) peptide in aqueous media is reversible: a step by step conformational analysis suggests the location of beta conformation seeding

Current views of the role of beta-amyloid (Abeta) peptide fibrils range from regarding them as the cause of Alzheimer's pathology to having a protective function. In the last few years, it has also been suggested that soluble oligomers might be the most important toxic species. In all cases, the study of the conformational properties of Abeta peptides in soluble form constitutes a basic approach to the design of molecules with "antiamyloid" activity. We have experimentally investigated the conformational path that can lead the Abeta-(1-42) peptide from the native state, which is represented by an alpha helix embedded in the membrane, to the final state in the amyloid fibrils, which is characterized by beta-sheet structures. The conformational steps were monitored by using CD and NMR spectroscopy in media of varying polarities. This was achieved by changing the composition of water and hexafluoroisopropanol (HFIP). In the presence of HFIP, beta conformations can be observed in solutions that have very high water content (up to 99 % water; v/v). These can be turned back to alpha helices simply by adding the appropriate amount of HFIP. The transition of Abeta-(1-42) from alpha to beta conformations occurs when the amount of water is higher than 80 % (v/v). The NMR structure solved in HFIP/H2O with high water content showed that, on going from very apolar to polar environments, the long N-terminal helix is essentially retained, whereas the shorter C-terminal helix is lost. The complete conformational path was investigated in detail with the aid of molecular-dynamics simulations in explicit solvent, which led to the localization of residues that might seed beta conformations. The structures obtained might help to find regions that are more affected by environmental conditions in vivo. This could in turn aid the design of molecules able to inhibit fibril deposition or revert oligomerization processes.     

Synthesis and in vitro properties of dexamethasone 21-sulfate sodium as a colon-specific prodrug of dexamethasone

We synthesized dexamethasone 21-sulfate sodium (DS) as a colon-specific prodrug of dexamethasone and investigated its properties. Introduction of a sulfate group to dexamethasone lowered the apparent partition coefficient from 52.5 to 0.27 in 1-octanol/pH 6.8 phosphate buffer at 37°C. DS was stable on incubation with buffer solutions of varied pH or with the upper intestinal contents of rats at 37°C for 24 h. On incubation with the cecal contents, DS was hydrolyzed by producing dexamethasone over 80% of the dose at 10 h. When DS was incubated with the cecal contents collected from trinitrobenzenesulfonic acid (TNBS)-induced colitic rats, the degree of prodrug hydrolysis and production of dexamethasone amounted to 70% of healthy rats. In comparison with prednisolone, hydrocortisone, and cortisone, dexamethasone was stable against bioinactivation by the cecal contents, a desirable property for the development of a colon-specific prodrug. These results demonstrated that DS might be delivered specifically to the colon as an intact form to produce dexamethasone in high yield, suggesting DS as a potential colon-specific prodrug of dexamethasone.     

Calf respiratory disease and pen microenvironments in naturally ventilated calf barns in winter

Relationships between air quality, a variety of environmental risk factors, and calf respiratory health were studied in 13 naturally ventilated calf barns during winter. A minimum of 12 preweaned calves were randomly selected and scored for the presence of respiratory disease in each barn. An air sampling device was used to determine airborne bacteria colony-forming units per cubic meter (cfu/m³) of air in calf pens and central alleys within the barns. Airborne bacteria samples were collected on sheep blood agar (BAP) and eosin methylene blue (EMB) agar plates. Temperature and relative humidity were recorded in each calf pen, the barn alley, and outside the barn. Samples of bedding were collected in each pen and DM was measured. Pen bedding type and a calf nesting score (degree to which the calves could nestle into the bedding) was assigned to each barn. Calf numbers, barn and pen dimensions, ridge, eave, and curtain openings, and exterior wind speed and direction were determined and used to estimate building ventilation rates. Factors that were significantly associated with a reduced prevalence of respiratory disease were reduced pen bacterial counts (log₁₀ cfu/m³) on BAP, presence of a solid barrier between each calf pen, and increased ability to nest. Individual calf pen bacterial counts were significantly different from barn alley bacterial counts on both BAP and EMB. Significant factors associated with reduced calf pen bacterial counts on BAP were increasing pen area, increasing number of open planes of the calf pen, decreasing pen temperature, and wood-particle bedding. Significant factors associated with reduced alley bacterial counts on BAP were increased ventilation changes per hour, increased barn volume per kilogram of calf, reduced pen bacterial counts, and barn type.     

金纳米颗粒在疾病诊断和食品检测领域的研究进展

纳米科技的发展使纳米在各个领域得到了广泛的应用。由于金纳米颗粒具有较高的摩尔吸光系数和特殊的光学、电学、磁学性质,因此它在化学、生物传感、疾病诊断和食品检测等领域的应用取得了突出进展。综述了最近几年金纳米颗粒在疾病诊断和食品检测领域的最新研究进展,特别介绍了国家纳米科学中心近期的研究结果,他们重点研发了可控功能化纳米材料的合成和应用,构建了便携式、高灵敏度的生物化学分析方法系列,为HIV和阿尔茨海默等重大疾病的诊断提供了新方法。讨论了金纳米颗粒具有的优势及存在的问题,并对其未来的发展进行了展望。     

MMSE as a predictor of on-road driving performance in community dwelling older drivers

Screening tools such as the MMSE have been used extensively in driving research studies to determine mild cognitive impairment or dementia. While some studies have shown the MMSE to correlate with driving performance, few studies have shown the predictive validity of the MMSE in determining on-road performance. In a sample of 168 community dwelling older adults, including 20 with Parkinson's disease (PD), the primary objective was to determine the validity of the MMSE to predict pass/fail outcomes of an on-road driving test using receiver operating characteristics curves. The area under the curve (AUC), an index of discriminability, for the total sample was .654, 95% CI = 0.536–0.772, p = .009. Meanwhile, the AUC for the PD group was 0.791, 95% CI = 0.587–0.996, p = .036. The total sample showed statistically significant yet poor predictive validity. However, the PD group showed statistically significant and good predictive validity of the MMSE to predict pass/fail outcomes on the road test, but caution is warranted as the confidence intervals are wide (due to small sample) and the positive and negative predictive values are less than desirable due to the associated error. The findings show that using the current cut-off point of ≤24 on the MMSE is not adequately sensitive to predict on-road performance in both community dwelling older drivers and in drivers with PD. This study offers strong evidence to support the current best practice of not using the MMSE in isolation to predict on-road performance.     

Characterization of water-soluble conjugates of polyacrylic acid and antigenic peptide of FMDV by size exclusion chromatography with quadruple detection

Intermolecular complex by electrostatic interaction and specifically coupled conjugates between polyacrylic acid (PAA) and a synthetic peptide representing 170-188 sequence from the GH loop of VP1 protein of foot-and-mouth disease virus (FMDV) were investigated as an intermolecular model system due to their importance in biotechnology and immunology. In this study, polyacrylic acid (PAA) with a synthetic peptide representing 170-188 sequence from the GH loop of VP1 protein of foot-and-mouth disease virus at a wide range of mixing ratios of components (C_Peptide/C_PAA 0.1, 0.25, 0.5, 0.75 and 1.0, respectively) were characterized by size-exclusion high performance liquid chromatography with on-line refractive index, UV, light scattering and viscometer detectors. The results revealed that two molecules are both negatively charged as a result of repulsive forces preventing complex formation at neutral pH. Therefore, these molecules bound covalently to each other by using water-soluble carbodiimide when pH levels are higher than the pI of the peptide. High performance liquid chromatography analysis showed that the amount of protein-polymer complex increased and free peptide amount decreased with the increase in molar ratio of the peptide. Also, this paper presents that number of the bound peptide molecules with one PAA molecule was expressed by a Langmuir-type equation as a function of the amount of excess synthetic peptide existing free in the solution.     

Left atrial volume index as a predictor of ventricle repolarization abnormalities in adult dialyzed patients

This study was performed to investigate the relationship between left atrium (LA) volume index (LAVI) and left ventricle electrical activity presumably repolarization in end‐stage renal disease patients. Study group was consisted of 120 dialyzed patients divided into two subgroups: 57 (age 50.7 ± 7.1) were on continuous ambulatory peritoneal dialysis (CAPD) and 73 (age 51.6 ± 7.6) were hemodialyzed (HD). All patients were undergoing three‐dimensional vectorcardiographic (VCG) monitoring to assess parameters concerning T vector: QRS‐T angle, Tel, and Taz. Standard echocardiography was performed to assess: LA_max, LA_short, LA_long. LAVI was calculated due to formula: LAVI = (π/6X [LA_max × LA_short × LA_long])/m². LAVI in HD as well as in CAPD patients was significantly higher compared with controls (respectively: 36.29 ± 10.92; 36.41 ± 11.06; 20.64 ± 6.77 mL/m²). The calculated cutoff value of LAVI was 36.32 mL/m². In HD patients, the strong correlations between LAVI and QRS‐T angle and Tel were determined (respectively: r = 0.407, P < 0.001 and r = 0.359, P = 0.006). Similarly in CAPD group were significant associations between LAVI and QRS‐T angle and Tel (respectively: r = 0.423, P < 0.001 and r = 0.374, P = 0.004). The QRS‐T angle, Tel and Taz are independently and markedly associated with LAVI in both HD and CAPD patients. LAVI and VCG indices are higher in both HD and CAPD patients. Correlation between QRS‐T angle and LAVI may reflect unfavorable influence on the electrical activity of the heart in dialyzed patients with left ventricle diastolic dysfunction. LAVI cutoff value is useful biomarker for stratification of ventricle repolarization disturbances in those patients.     

基于胶囊SE-Inception的茄科病害识别方法研究

针对番茄和茄子2类茄科蔬菜的病害,基于SE-Inception和胶囊网络构建了一个具有抗噪性的茄科病害识别网络,称为胶囊SE-Inception.该网络主要分为特征提取和胶囊网络2部分.其特征提取部分采用了批处理归一化层(BN)加速网络收敛;利用SE-Inception结构和多尺度特征提取模块来提高模型的精度.胶囊网络...     

冶金矿山职业病危害因素控制研究的必要性探讨

根据目前我国职业病危害的现状,结合冶金矿山主要职业病危害因素及其防治情况,参考国家相关政策与社会发展趋势,论述了开展冶金矿山职业病危害因素控制研究的必要性,并提出了相关的研究方向。