Activated αIIbβ3 on platelets mediates flow-dependent NETosis via SLC44A2.

Platelet-neutrophil interactions are important for innate immunity, but also contribute to the pathogenesis of deep vein thrombosis, myocardial infarction and stroke. Here we report that, under flow, von Willebrand factor/glycoprotein Ibα-dependent platelet 'priming' induces integrin αIIbβ3 activation that, in turn, mediates neutrophil and T-cell binding. Binding of platelet αIIbβ3 to SLC44A2 on neutrophils leads to mechanosensitive-dependent production of highly prothrombotic neutrophil extracellular traps. A polymorphism in SLC44A2 (rs2288904-A) present in 22% of the population causes an R154Q substitution in an extracellular loop of SLC44A2 that is protective against venous thrombosis results in severely impaired binding to both activated αIIbβ3 and VWF-primed platelets. This was confirmed using neutrophils homozygous for the SLC44A2 R154Q polymorphism. Taken together, these data reveal a previously unreported mode of platelet-neutrophil crosstalk, mechanosensitive NET production, and provide mechanistic insight into the protective effect of the SLC44A2 rs2288904-A polymorphism in venous thrombosis

The rational synthesis and catalytic testing of heterogeneous multimetallic nanoparticles for the hydrogenation of CO2

It has been documented for over a century that metal surfaces can act as catalysts for many different reactions, such as the Fe-based catalyst used in the Haber-Bosch ammonia synthesis. For many decades, metal nanoparticles, defined as particles less than 100 nm in diameter, have become widely used as catalysts for many industrially important reactions, including hydrogenations, dehydrogenations, oxidations, reductions, and more. The nanoscopic size of a metallic nanoparticle results in extremely high surface area to volume ratios, which in turn results in a large number of catalytic sites per quantity of material used. Since catalyst design focuses on the highest activity and selectivity towards the desired product using the least material possible, metal nanoparticles have become an attractive choice. Multimetallic nanoparticles, which include more than one metal, have become increasingly popular over the past two decades. Synergistic effects between metals have been reported by many research teams. A wide array of publications have indicated a superior catalytic activity and selectivity towards the desired product when adding a second, or even a third metal, to a nanoparticle catalyst, when compared to monometallic catalysts. When designing a multimetallic nanoparticle catalyst for application in an industrial reaction, there are many factors to consider. Particle size, shape, morphology, structure, and molar ratio between metals are all highly important. Small alterations to even one of these factors can have a dramatic impact on catalytic performance. Many traditional synthesis methods still commonly used today, such as wet and incipient wetness impregnation, are crude processes that afford poor control over these factors. This is especially an issue in the design of multimetallic nanoparticles, which are more complex than monometallic nanoparticles. A highly rational synthetic procedure known as Strong Electrostatic Adsorption (SEA), developed by John Regalbuto, has been investigated in the synthesis of supported multimetallic Pd-containing nanoparticles as catalysts for the hydrogenation of CO2 to methanol. Methanol is a highly important industrial chemical – 53 million tonnes were consumed in 2011 alone – and this process is important for CO2 capture. The SEA method involves altering the pH of the solution to induce a charge on the supporting material, maximising electrostatic interaction between the supporting material and the metal precursors to yield small nanoparticles around 1 nm in diameter

Social deficits, stereotypy and early emergence of repetitive behavior in the C58/J inbred mouse strain

Mouse lines with behavioral phenotypes relevant to symptoms in neurodevelopmental disorders may provide models to test hypotheses about disease etiology and to evaluate potential treatments. The present studies were designed to confirm and expand earlier work on the intriguing behavioral profile of the C58/J inbred strain, including low social approach and aberrant repetitive movements. Additional tests were selected to reflect aspects of autism, a severe neurodevelopmental disorder characterized by emergence of symptoms early in life, higher prevalence in males, social deficits and abnormal repetitive behavior. Mice from the C57BL/6J inbred strain, which has a similar genetic lineage and physical appearance to C58/J, served as a comparison group. Our results revealed that C58/J mice display elevated activity levels by postnatal day 6, which persist into adulthood. Despite normal olfactory ability, young adult male C58/J mice showed deficits in social approach in the three-chambered choice assay and failed to demonstrate social transmission of food preference. In contrast, female C58/J mice performed similarly to female C57BL/6J mice in both social tests. C58/J mice of both sexes demonstrated abnormal repetitive behaviors, displaying excessive jumping and back flipping in both social and non-social situations. These stereotypies were clearly evident in C58/J pups by postnatal days 20–21, and were also observed in C58/J dams during a test for maternal behavior. Overall, the strain profile for C58/J, including spontaneously developing motor stereotypies emerging early in the developmental trajectory, and social deficits primarily in males, models multiple components of the autism phenotype

Clifford-Jacobs Forging Company v. Capital Engineering & (and) Manufacturing Co.: The Continuing Problem within U.C.C. Section 2-207, 16 J. Marshall L. Rev. 589 (1983)

status: accepte

Measuring and understanding the differences between urban and rural areas

Understanding the factors that make a location more rural or urban is an important task for planners and policymakers. Traditional individual characteristics of rurality sometimes hide the more complex social as well as physical dynamics of a locality. This paper builds on early work which applied factor analysis to construct a single index of rurality. An approach is developed with a combined metric encompassing multiple measures. These are capable individually of defining rurality but together they deliver greater insight on more complex patterns and help to redefine the simple notion of rurality. The paper then utilises a novel graphical method, the constellation graph, providing a diagnostic and visual framework to aid planners when assessing the spatial dimensions of a locality

Quantitative analysis of water distribution in human articular cartilage using terahertz time-domain spectroscopy

The water distribution in human osteoarthritic articular cartilage has been quantitatively characterized using terahertz time-domain spectroscopy (THz TDS). We measured the refractive index and absorption coefficient of cartilage tissue in the THz frequency range. Based on our measurements, the estimated water content was observed to decrease with increasing depth cartilage tissue, showing good agreement with a previous report based on destructive biochemical methods