BRAF Modulates Stretch-Induced Intercellular Gap Formation through Localized Actin Reorganization

Mechanical forces acting on cell–cell adhesion modulate the barrier function of endothelial cells. The actively remodeled actin cytoskeleton impinges on cell–cell adhesion to counteract external forces. We applied stress on endothelial monolayers by mechanical stretch to uncover the role of BRAF in the stress-induced response. Control cells responded to external forces by organizing and stabilizing actin cables in the stretched cell junctions. This was accompanied by an increase in intercellular gap formation, which was prevented in BRAF knockdown monolayers. In the absence of BRAF, there was excess stress fiber formation due to the enhanced reorganization of actin fibers. Our findings suggest that stretch-induced intercellular gap formation, leading to a decrease in barrier function of blood vessels, can be reverted by BRAF RNAi. This is important when the endothelium experiences changes in external stresses caused by high blood pressure, leading to edema, or by immune or cancer cells in inflammation or metastasis.     

Prolonged corneal anaesthesia by proxymetacaine hydrochloride detected by a thermal cooling stimulus

Purpose

To assess the duration, depth and recovery time of anaesthesia produced by 0.5% proxymetacaine hydrochloride (proparacaine), using a thermal cooling stimulus.

Methods

Seventeen non-contact lens-wearing subjects were recruited (mean age = 26 ± 3.6 years, range = 23-39; blue iris = 8, brown iris = 9). Central corneal sensitivity was measured in the right eye of each patient to establish a baseline, before 20 μl of either 0.5% proxymetacaine hydrochloride (p) or 0.9% unpreserved saline (s) was instilled under four experimental conditions (right eye-left eye): p-p, p-s, s-p, s-s. Corneal sensitivity was re-measured at 2, 5, 10, 15, 20, 30, 45 and 60 min post-instillation.

Results

The onset of anaesthesia was observed at 2 min (Wilcoxon, p < 0.001), with the maximum anaesthesia occurring at 15 min (Wilcoxon, p < 0.001). Recovery of corneal sensitivity to baseline levels did not occur by 60 min (Wilcoxon, p < 0.001). No difference in onset time, depth of anaesthesia, or recovery time was noted between the blue and brown iris subjects (Mann-Whitney, p > 0.05).

Conclusions

Although the anaesthetic effect of 0.5% proxymetacaine hydrochloride continues for more than 60 min, this finding does not alter current clinical practice. The extended duration, however, is of relevance to studies that use corneal anaesthesia to investigate the role of corneal nerves in the blink mechanism.     

Effect of drying temperature on polyphenolic content and antioxidant activity of apricots

This study was carried out in order to check for the influence of drying parameters on the phenolic compounds and antioxidant activity on two apricot cultivars (Pelese and Cafona) using two sets of air drying temperatures: (1) air temperature at 55 °C; (2) air temperature at 75 °C. Whole fresh and dried fruits were assessed for: phenolics, ascorbic acid, antioxidant activity and redox potential (all parameters were calculated on a dry matter basis). Analysis of data shows that the decrease in chlorogenic and neochlorogenic acid in Cafona cultivar is higher at the lower drying temperature. Catechin showed the same behaviour of hydroxycinnamic acids in both cultivars, while the decrease in the other compounds was significantly more marked in the sample dried at 75 °C. The antioxidant activity increased significantly in Cafona fruits and this increase was confirmed by a diminution of the redox potential.     

燕麦片加工品质评价及其品种相关性研究

拟通过燕麦品种间品质性状的差异来寻求燕麦片加工品质的客观评价方法,并从中筛选出适宜加工燕麦片的优良品种.结果显示,燕麦品种间在粗脂肪、粗纤维、千粒重及β-葡聚糖含量等理化指标上存在较大变异;燕麦片的理化和感官评价指标中以汤汁黏度、口感、色泽等指标对产品整体品质影响最为显著.从燕麦片的营养和食用品质综合考虑,从34个国产燕麦品种中筛选出适宜加工燕麦片的5个优质品种-坝莜1号(河北产)、白燕2号(山西产)、坝莜3号、张莜1号、定莜2号.     

Modeling stimulus‐driven attentional selection in dynamic natural scenes

In this paper we have developed a neuromorphic model of bottom‐up (BU) visual attentional selection. The output of a recently developed neuromorphic multi‐channel retina model has represented the input of our model. As a first step, a saliency map has been calculated for each retinal channel which, next, has been integrated into a master saliency map. Model parameters have been optimized based on human eye movement data measured during viewing dynamic natural scenes. We have tested two different strategies for weighting the channel‐specific saliency maps during integration into a master map. In the first case, channel weights have been kept constant throughout the verification measurements, whereas, in the other case, they have been updated on each frame, according to the specific properties of the visual input. Surprisingly, the constant channel weighting strategies have performed better than the continually updated ones. We have measured the model's accuracy by defining the hit ratio (concurrence) between the first few predicted locations (the most salient locations) and the measured fixation locations. Constant weighting methods have achieved ～74% hit ratio on four predictions. For a comparison, the accidental chance for this case has been less than 20%. This pure BU approach has performed surprisingly well on dynamic natural input. Some practical applications have already been made with task‐dependent simplifications. Copyright © 2008 John Wiley & Sons, Ltd.     

Common Muscle Metabolic Signatures Highlight Arginine and Lysine Metabolism as Potential Therapeutic Targets to Combat Unhealthy Aging

Biological aging research is expected to reveal modifiable molecular mechanisms that can be harnessed to slow or possibly reverse unhealthy trajectories. However, there is first an urgent need to define consensus molecular markers of healthy and unhealthy aging. Established aging hallmarks are all linked to metabolism, and a ‘rewired’ metabolic circuitry has been shown to accelerate or delay biological aging. To identify metabolic signatures distinguishing healthy from unhealthy aging trajectories, we performed nontargeted metabolomics on skeletal muscles from 2-month-old and 21-month-old mice, and after dietary and lifestyle interventions known to impact biological aging. We hypothesized that common metabolic signatures would highlight specific pathways and processes promoting healthy aging, while revealing the molecular underpinnings of unhealthy aging. Here, we report 50 metabolites that commonly distinguished aging trajectories in all cohorts, including 18 commonly reduced under unhealthy aging and 32 increased. We stratified these metabolites according to known relationships with various aging hallmarks and found the greatest associations with oxidative stress and nutrient sensing. Collectively, our data suggest interventions aimed at maintaining skeletal muscle arginine and lysine may be useful therapeutic strategies to minimize biological aging and maintain skeletal muscle health, function, and regenerative capacity in old age.     

Cyclic chronopotentiometry as a detection tool for flowing solution systems

Cyclic chronopotentiometry provides a very simple detection method, which may be particularly useful in capillary electrophoresis (CE) and microseparation systems. It has been shown that for disk microelectrodes it is possible to define safe reduction and oxidation currents that would never lead to the formation of H2 or O2 gas bubbles, even if they are applied for an indefinitely long time period. During end-column CE detection, currents passing through the working microelectrode can be completely controlled by the external electronic circuit and they are not affected by the separation current. Consequently, problems created by the offset potential in CE can be completely eliminated. The detection can be accomplished through a variety of different mechanisms; however, generation of the electrode response as a result of analyte adsorption seems to be most common. The method is applicable to many analytes, which do not have to be electroactive. The analytical signal is obtained by monitoring the change in the average electrode potential (calculated for either a cathodic or an anodic half-cycle) caused by an analyte interacting with the electrode. The analytical signal is proportional to the analyte concentration, within a concentration range extending over approximately 2 orders of magnitude.     

Levels of 12 perfluorinated chemicals in pooled australian serum, collected 2002-2003, in relation to age, gender, and region

Pooled serum samples from 3802 Australian residents were analyzed for four perfluoroalkylsulfonates, seven perfluoroalkylcarboxylates, and perfluorooctanesulfonamide (PFOSA). Serum was collected from men and women of five different age groups and from rural and urban regions in Australia. The highest mean concentration was obtained for perfluorooctane sulfonate (PFOS, 20.8 ng/mL) followed by perfluorooctanoic acid (PFOA, 7.6 ng/mL), perfluorohexane sulfonate (PFHxS, 6.2 ng/mL), perfluorononanoic acid (PFNA, 1.1 ng/mL), and PFOSA (0.71 ng/mL). Additional four PFCs were detected in 5-18% of the samples at concentrations near the detection limits (0.1-0.5 ng/mL). An increase in PFOS concentration with increasing age in both regions and genders was observed. The male pool levels of some of the age groups compared to females were higherfor PFOS, PFOA, and PFHxS. In contrast, PFNA concentrations were higher in the female pools. No substantial difference was found in levels of PFCs between the urban and rural regions. The levels are equal or higher than previously reported serum levels in Europe and Asia but lower compared to the U.S.A. These results suggest that emissions from production in the Northern Hemisphere are of less importance for human exposure.     

Procyanidin effects on adipocyte-related pathologies

Procyanidins, a class of flavonoids, have clear and well-defined beneficial effects against several pathologies including cardiovascular heart disease. Now, studies in vivo are revealing the effects of procyanidins against obesity, where they prevent weight gain and adipose tissue mass increase, and against diabetes and insulin resistance, where they act as antihiperglycemic agents. Several mechanisms may be responsible for these effects. One of these, due to the key role of adipose tissue in the development of obesity and insulin resistance, is their effect on adipocytes. In this review we compile the studies that indicate a protective role for procyanidins in obesity and insulin resistance, focusing on their effects on the adipocyte, where procyanidins modify lipid synthesis, lipid degradation, glucose uptake, and adipose differentiation.     

Laser-induced breakdown spectroscopy of high-pressure bulk aqueous solutions

Laser-induced breakdown spectroscopy (LIBS) is presented for detection of several Group I and II elements (e.g., Na, Ca, Li, and K), as well as Mn and CaOH, in bulk aqueous solution at pressures exceeding 2.76 x 10(7) Pa (276 bar). Preliminary investigations reveal only minor pressure effects on the emission intensity and line width for all elements examined. These effects are found to depend on detector timing and laser pulse energy. The results of these investigations have implications for potential applications of LIBS for in situ multi-elemental detection in deep-ocean environments.