Platelet PECAM-1 inhibits thrombus formation in vivo

Platelet endothelial cell adhesion molecule-1 (PECAM-1) is a cell surface glycoprotein receptor expressed on a range of blood cells, including platelets, and on vascular endothelial cells. PECAM-1 possesses adhesive and signaling properties, the latter being mediated by immunoreceptor tyrosine-based inhibitory motifs present on the cytoplasmic tail of the protein. Recent studies in vitro have demonstrated that PECAM-1 signaling inhibits the aggregation of platelets. In the present study we have used PECAM-1-deficient mice and radiation chimeras to investigate the function of this receptor in the regulation of thrombus formation. Using intravital microscopy and laser-induced injury to cremaster muscle arterioles, we show that thrombi formed in PECAM-1-deficient mice were larger, formed more rapidly than in control mice, and were more stable. Larger thrombi were also formed in control mice that received transplants of PECAM-1-deficient bone marrow, in comparison to mice that received control transplants. A ferric chloride model of thrombosis was used to investigate thrombus formation in carotid arteries. In PECAM-1-deficient mice the time to 75% vessel occlusion was significantly shorter than in control mice. These data provide evidence for the involvement of platelet PECAM-1 in the negative regulation of thrombus formation.

The effects of web logs and the semantic web on autonomous web agents

Search engines exploit the Web's hyperlink structure to help infer information content. The new phenomenon of personal Web logs, or 'blogs', encourage more extensive annotation of Web content. If their resulting link structures bias the Web crawling applications that search engines depend upon, there are implications for another form of annotation rapidly on the rise, the Semantic Web. We conducted a Web crawl of 160 000 pages in which the link structure of the Web is compared with that of several thousand blogs. Results show that the two link structures are significantly different. We analyse the differences and infer the likely effect upon the performance of existing and future Web agents. The Semantic Web offers new opportunities to navigate the Web, but Web agents should be designed to take advantage of the emerging link structures, or their effectiveness will diminish.

Search adaptations and the challenges of the web

Search has become a hot topic in Internet computing, with rival search engines battling to become the de facto Web portal, harnessing search algorithms to wade through information on a scale undreamed of by early information retrieval (IR) pioneers. This article examines how search has matured from its roots in specialized IR systems to become a key foundation of the Web. The authors describe new challenges posed by the Web's scale, and show how search is changing the nature of the Web as much as the Web has changed the nature of search

Effects of food structure and ingredient interactions on antioxidant capacity

Foods are complex biological materials, and the lipids within the food are susceptible to lipid oxidation, which is retarded by antioxidants. The precise structure and composition of the food may affect the antioxidant activity quite strongly in some cases. Solubility of the antioxidant in the phases present is one of the main parameters that affects the variation in antioxidant activity with phase composition of food. Polar antioxidants are more effective in oils, whereas non-polar antioxidants are more effective in oil-in-water emulsions. Antioxidant activity has been reported in a range of different media, including oils, emulsions, liposomes, microemulsions, fish and meat muscles, and the antioxidant activity may vary from one medium to another. Synergy between antioxidants may also vary from one medium to another. Interactions with metals and with proteins affect antioxidant activity and these interactions are also dependent on the phases present.

Antioxidant activity of selected phenols and herbs used in diets for medical conditions.

The antioxidant capacity of some herbs used in dietology practice was determined by the DPPH free radical method, which was calibrated with ascorbic acid. Partially hydrophilic phenolic compounds are the most active compounds in plants, and therefore water was used as the extraction agent. Besides antioxidant capacity, the content of total phenolic compounds was also measured and a strong correlation between these two variables was found. The extracts of lemon balm (Melissa officinalis L.), peppermint (Mentha x piperita L.), oregano (Origanum vulgare L.), Greek oregano (Origanum heracleoticum L.), sage (Salvia officinalis L.) and winter savory (Satureja montana L.) showed very significant activity. It was comparable with the activity of green tea in the case of oregano and peppermint. Lower activity was observed in the case of rosemary (Rosmarinus officinalis L.), marjoram (Majorana hortensis), hyssop (Hyssopus officinalis L.), sweet basil (Ocimum basilicum), and lovage (Levisticum officinale Koch.). The inhibitory activity of the herb extracts was monitored also during the autooxidation of lard. Very high antioxidant capacity was observed mainly in sage samples, but also in marjoram and Greek oregano. The extracts of peppermint, oregano, rosemary, winter savory, lemon balm and hyssop showed middle activity comparable to that of alpha-tocopherol. The antioxidant capacity of sweet basil and lovage was insignificant.

Platelet endothelial cell adhesion molecule-1 regulates collagen-stimulated platelet function by modulating the association of phosphatidylinositol 3-kinase with Grb-2-associated binding protein-1 and linker for activation of T cells

Background: Platelet activation by collagen depends on signals transduced by the glycoprotein (GP)VI–Fc receptor (FcR)-chain collagen receptor complex, which involves recruitment of phosphatidylinositol 3-kinase (PI3K) to phosphorylated tyrosines in the linker for activation of T cells (LAT). An interaction between the p85 regulatory subunit of PI3K and the scaffolding molecule Grb-2-associated binding protein-1 (Gab1), which is regulated by binding of the Src homology 2 domain-containing protein tyrosine phosphatase-2 (SHP-2) to Gab1, has been shown in other cell types to sustain PI3K activity to elicit cellular responses. Platelet endothelial cell adhesion molecule-1 (PECAM-1) functions as a negative regulator of platelet reactivity and thrombosis, at least in part by inhibiting GPVI–FcR-chain signaling via recruitment of SHP-2 to phosphorylated immunoreceptor tyrosine-based inhibitory motifs in PECAM-1. Objective: To investigate the possibility that PECAM-1 regulates the formation of the Gab1–p85 signaling complexes, and the potential effect of such interactions on GPVI-mediated platelet activation in platelets. Methods: The ability of PECAM-1 signaling to modulate the LAT signalosome was investigated with immunoblotting assays on human platelets and knockout mouse platelets. Results: PECAM-1-associated SHP-2 in collagen-stimulated platelets binds to p85, which results in diminished levels of association with both Gab1 and LAT and reduced collagen-stimulated PI3K signaling. We therefore propose that PECAM-1-mediated inhibition of GPVI-dependent platelet responses result, at least in part, from recruitment of SHP-2–p85 complexes to tyrosine-phosphorylated PECAM-1, which diminishes the association of PI3K with activatory signaling molecules, such as Gab1 and LAT.

Multimodel climate and variability of the stratosphere

The stratospheric climate and variability from simulations of sixteen chemistry‐climate models is evaluated. On average the polar night jet is well reproduced though its variability is less well reproduced with a large spread between models. Polar temperature biases are less than 5 K except in the Southern Hemisphere (SH) lower stratosphere in spring. The accumulated area of low temperatures responsible for polar stratospheric cloud formation is accurately reproduced for the Antarctic but underestimated for the Arctic. The shape and position of the polar vortex is well simulated, as is the tropical upwelling in the lower stratosphere. There is a wide model spread in the frequency of major sudden stratospheric warnings (SSWs), late biases in the breakup of the SH vortex, and a weak annual cycle in the zonal wind in the tropical upper stratosphere. Quantitatively, “metrics” indicate a wide spread in model performance for most diagnostics with systematic biases in many, and poorer performance in the SH than in the Northern Hemisphere (NH). Correlations were found in the SH between errors in the final warming, polar temperatures, the leading mode of variability, and jet strength, and in the NH between errors in polar temperatures, frequency of major SSWs, and jet strength. Models with a stronger QBO have stronger tropical upwelling and a colder NH vortex. Both the qualitative and quantitative analysis indicate a number of common and long‐standing model problems, particularly related to the simulation of the SH and stratospheric variability.

Preliminary observations on the presence of sustained tendon strain and eccentric contractions of the wrist extensors during a common manual task: implications for lateral epicondylitis

Lateral epicondylitis (LE) is hypothesized to occur as a result of repetitive, strenuous and abnormal postural activities of the elbow and wrist. There is still a lack of understanding of how wrist and forearm positions contribute to this condition during common manual tasks. In this study the wrist kinematics and the wrist extensors’ musculotendon patterns were investigated during a manual task believed to elicit LE symptoms in susceptible subjects. A 42-year-old right-handed male, with no history of LE, performed a repetitive movement involving pushing and turning a spring-loaded mechanism. Motion capture data were acquired for the upper limb and an inverse kinematic and dynamic analysis was subsequently carried out. Results illustrated the presence of eccentric contractions sustained by the extensor carpi radialis longus (ECRL), together with an almost constant level of tendon strain of both extensor carpi radialis brevis (ECRB) and extensor digitorum communis lateral (EDCL) branch. It is believed that these factors may partly contribute to the onset of LE as they are both responsible for the creation of microtears at the tendons’ origins. The methodology of this study can be used to explore muscle actions during movements that might cause or exacerbate LE.

Sustained monitoring of the Southern Ocean at Drake Passage: past achievements and future priorities

Drake Passage is the narrowest constriction of the Antarctic Circumpolar Current (ACC) in the Southern Ocean, with implications for global ocean circulation and climate. We review the long-term sustained monitoring programmes that have been conducted at Drake Passage, dating back to the early part of the twentieth century. Attention is drawn to numerous breakthroughs that have been made from these programmes, including (a) the first determinations of the complex ACC structure and early quantifications of its transport; (b) realization that the ACC transport is remarkably steady over interannual and longer periods, and a growing understanding of the processes responsible for this; (c) recognition of the role of coupled climate modes in dictating the horizontal transport, and the role of anthropogenic processes in this; (d) understanding of mechanisms driving changes in both the upper and lower limbs of the Southern Ocean overturning circulation, and their impacts. It is argued that monitoring of this passage remains a high priority for oceanographic and climate research, but that strategic improvements could be made concerning how this is conducted. In particular, long-term programmes should concentrate on delivering quantifications of key variables of direct relevance to large-scale environmental issues: in this context, the time-varying overturning circulation is, if anything, even more compelling a target than the ACC flow. Further, there is a need for better international resource-sharing, and improved spatio-temporal coordination of the measurements. If achieved, the improvements in understanding of important climatic issues deriving from Drake Passage monitoring can be sustained into the future.