Multivariate QTL linkage analysis suggests a QTL for platelet count on chromosome 19q

Platelet count is a highly heritable trait with genetic factors responsible for around 80% of the phenotypic variance. We measured platelet count longitudinally in 327 monozygotic and 418 dizygotic twin pairs at 12, 14 and 16 years of age. We also performed a genome-wide linkage scan of these twins and their families in an attempt to localize QTLs that influenced variation in platelet concentrations. Suggestive linkage was observed on chromosome 19q13.13-19q13.31 at 12 (LOD=2.12, P=0.0009), 14 (LOD=2.23, P=0.0007) and 16 (LOD=1.01, P=0.016) years of age and multivariate analysis of counts at all three ages increased the LOD to 2.59 (P=0.0003). A possible candidate in this region is the gene for glycoprotein VI, a receptor involved in platelet aggregation. Smaller linkage peaks were also seen at 2p, 5p, 5q, 10p and 15q. There was little evidence for linkage to the chromosomal regions containing the genes for thrombopoietin (3q27) and the thrombopoietin receptor (1q34), suggesting that polymorphisms in these genes do not contribute substantially to variation in platelet count between healthy individuals.

Increased platelet-derived microparticles in the coronary circulation of percutaneous transluminal coronary angioplasty patients

Platelet-derived microparticles that are produced during platelet activation are capable of adhesion and aggregation. Endothelial trauma that occurs during percutaneous transluminal coronary angioplasty (PTCA) may support platelet-derived microparticle adhesion and contribute to development of restenosis. We have previously reported an increase in platelet-derived microparticles in peripheral arterial blood with angioplasty. This finding raised concerns regarding the role of platelet-derived microparticles in restenosis, and therefore the aim of this study was to monitor levels in the coronary circulation. The study population consisted of 19 angioplasty patients. Paired coronary artery and sinus samples were obtained following heparinization, following contrast administration, and subsequent to all vessel manipulation. Platelet-derived microparticles were identified with an anti-CD61 (glycoprotein IIIa) fluorescence-conjugated antibody using flow cytometry. There was a significant decrease in arterial platelet-derived microparticles from heparinization to contrast administration (P=0.001), followed by a significant increase to the end of angioplasty (P=0.004). However, there was no significant change throughout the venous samples. These results indicate that the higher level of platelet-derived microparticles after angioplasty in arterial blood remained in the coronary circulation. Interestingly, levels of thrombin-antithrombin complexes did not rise during PTCA. This may have implications for the development of coronary restenosis post-PTCA, although this remains to be determined.

Iron-rich intermetallic phases and their role in casting defect formation in hypoeutectic Al-Si alloys

Iron is the most common and detrimental impurity in aluminum casting alloys and has long been associated with an increase in casting defects. While the negative effects of iron are clear, the mechanism involved is not fully understood. It is generally believed to be associated with the formation of Fe-rich intermetallic phases. Many factors, including alloy composition, melt superheating, Sr modification, cooling, rate, and oxide bifilms, could play a role. In the present investigation, the interactions between iron and each individual element commonly present in aluminum casting alloys, were investigated using a combination of thermal analysis and interrupted quenching tests. The Fe-rich intermetallic phases were characterized using optical microscope, scanning electron microscope, and electron probe microanalysis (EPMA), and the results were compared with the predictions by Thermocalc. It was found that increasing the iron content changes the precipitation sequence of the beta phase, leading to the precipitation of coarse binary beta platelets at a higher temperature. In contrast, manganese, silicon, and strontium appear to suppress the coarse binary beta platelets, and Mn further promotes the formation of a more compact and less harmful a phase. They are therefore expected to reduce the negative effects of the phase. While reported in the literature, no effect of P on the amount of beta platelets was observed. Finally, attempts are made to correlate the Fe-rich intermetallic phases to the formation of casting defects. The role of the beta phase as a nucleation site for eutectic Si and the role of the oxide bifilms and AIP as a heterogeneous substrate of Fe intermetallics are also discussed.

A Genetic Marker to Separate Emiliania Huxleyi (Prymnesiophyceae) Morphotypes

Emiliania huxleyi (Lohm.) Hay and Mohler is a ubiquitous unicellular marine alga surrounded by an elaborate covering of calcite platelets called coccoliths. It is an important primary producer involved in oceanic biogeochemistry and climate regulation. Currently, E. huxleyi is separated into five morphotypes based on morphometric, physiological, biochemical, and immunological differences. However, a genetic marker has yet to be found to characterize these morphotypes. With the use of sequence analysis and denaturing gradient gel electrophoresis, we discovered a genetic marker that correlates significantly with the separation of the most widely recognized A and B morphotypes. Furthermore, we reveal that the A morphotype is composed of a number of distinct genotypes. This marker lies within the 3' untranslated region of a coccolith associated protein mRNA, which is implicated in regulating coccolith calcification. Consequently, we tentatively termed this marker the coccolith morphology motif.

Platelet nitric oxide responsiveness - A novel prognostic marker in acute coronary syndromes

Objectives - Nitric oxide (NO) is critically important in the regulation of vascular tone and the inhibition of platelet aggregation. We have shown previously that patients with acute coronary syndromes (ACS) or stable angina pectoris have impaired platelet responses to NO donors when compared with normal subjects. We tested the hypotheses that platelet hyporesponsiveness to NO is a predictor of (1) cardiovascular readmission and/or death and (2) all-cause mortality in patients with ACS (unstable angina pectoris or non-Q-wave myocardial infarction). Methods and Results - Patients (n = 51) with ACS had evaluation of platelet aggregation within 24 hours of coronary care unit admission using impedance aggregometry. Patients were categorized as having normal (>= 32% inhibition of ADP-induced aggregation with the NO donor sodium nitroprusside; 10 mu mol/L; n = 18) or impaired (>= 32% inhibition of ADP-induced aggregation; n = 33) NO responses. We then compared the incidence of cardiovascular readmission and death during a median of 7 years of follow-up in these 2 groups. Using a Cox proportional hazards model adjusting for age, sex, index event, postdischarge medical treatment, revascularization status, left ventricular systolic dysfunction, concurrent disease states, and cardiac risk factors, impaired NO responsiveness was associated with an increased risk of the combination of cardiovascular readmission and/or death (relative risk, 2.7; 95% CI, 1.03 to 7.10; P = 0.041) and all-cause mortality (relative risk, 6.3; 95% CI, 1.09 to 36.7; P = 0.033). Conclusions - Impaired platelet NO responsiveness is a novel, independent predictor of increased mortality and cardiovascular morbidity in patients with high-risk ACS.

Influence of calcium on the microstructure and properties of an Al-7Si-0.3Mg-xFe alloy

The effect of Ca addition on the microstructure, physical characteristics (density/porosity), and mechanical properties (tensile and impact strength) has been investigated in an Al-7Si-0.3Mg-xFe (x = 0.2, 0.4, and 0.7) alloy. The size of Al-Fe intermetallic platelets (beta-Al5FeSi) increased with increasing Fe content. The addition of Ca modified the eutectic microstructure and also reduced the size of intermetallic Fe-platelets, causing improved elongation and impact strengths. A low level of Ca addition (39 ppm) reduced the porosity of the alloys. The tensile strength was decreased marginally with Ca addition. However, Ca addition improved the ductility of the alloy by 18.3, 16.7, and 44 pet and the impact strength by 44, 48, and 15.8 pct for Fe contents of 0.2, 0.4, and 0.7 pct, respectively.

SNAREing immunity: the role of SNAREs in the immune system

The trafficking of molecules and membranes within cells is a prerequisite for all aspects of cellular immune functions, including the delivery and recycling of cell-surface proteins, secretion of immune mediators, ingestion of pathogens and activation of lymphocytes. SNARE (soluble-N-ethylmaleimide-sensitive-factor accessory-protein receptor)-family members mediate membrane fusion during all steps of trafficking, and function in almost all aspects of innate and adaptive immune responses. Here, we provide an overview of the roles of SNAREs in immune cells, offering insight into one level at which precision and tight regulation are instilled on immune responses.