Platelets in aging and cancer—“double-edged sword”

Platelets control hemostasis and play a key role in inflammation and immunity. However, platelet function may change during aging, and a role for these versatile cells in many age-related pathological processes is emerging. In addition to a well-known role in cardiovascular disease, platelet activity is now thought to contribute to cancer cell metastasis and tumor-associated venous thromboembolism (VTE) development. Worldwide, the great majority of all patients with cardiovascular disease and some with cancer receive anti-platelet therapy to reduce the risk of thrombosis. However, not only do thrombotic diseases remain a leading cause of morbidity and mortality, cancer, especially metastasis, is still the second cause of death worldwide. Understanding how platelets change during aging and how they may contribute to aging-related diseases such as cancer may contribute to steps taken along the road towards a “healthy aging” strategy. Here, we review the changes that occur in platelets during aging, and investigate how these versatile blood components contribute to cancer progression

Ohm's Law for Plasma in General Relativity and Cowling's Theorem

The general-relativistic Ohm's law for a two-component plasma which includes the gravitomagnetic force terms even in the case of quasi-neutrality has been derived. The equations that describe the electromagnetic processes in a plasma surrounding a neutron star are obtained by using the general relativistic form of Maxwell equations in a geometry of slow rotating gravitational object. In addition to the general-relativistic effect first discussed by Khanna \& Camenzind (1996) we predict a mechanism of the generation of azimuthal current under the general relativistic effect of dragging of inertial frames on radial current in a plasma around neutron star. The azimuthal current being proportional to the angular velocity $\omega$ of the dragging of inertial frames can give valuable contribution on the evolution of the stellar magnetic field if $\omega$ exceeds $2.7\times 10^{17} (n/\sigma) \textrm{s}^{-1}$ ($n$ is the number density of the charged particles, $\sigma$ is the conductivity of plasma). Thus in general relativity a rotating neutron star, embedded in plasma, can in principle generate axial-symmetric magnetic fields even in axisymmetry. However, classical Cowling's antidynamo theorem, according to which a stationary axial-symmetric magnetic field can not be sustained against ohmic diffusion, has to be hold in the general-relativistic case for the typical plasma being responsible for the rotating neutron star.Comment: Accepted for publication in Astrophysics & Space Scienc

The role of phospho-tyrosine signaling in platelet biology and hemostasis

Platelets are small enucleated cell fragments specialized in the control of hemostasis, but also playing a role in angiogenesis, inflammation and immunity. This plasticity demands a broad range of physiological processes. Platelet functions are mediated through a variety of receptors, the concerted action of which must be tightly regulated, in order to allow specific and timely responses to different stimuli. Protein phosphorylation is one of the main key regulatory mechanisms by which extracellular signals are conveyed. Despite the importance of platelets in health and disease, the molecular pathways underlying the activation of these cells are still under investigation. Here, we review current literature on signaling platelet biology and in particular emphasize the newly emerging role of phosphatases in these processes

Targeting Tyrosine Phosphatases by 3-Bromopyruvate Overcomes Hyperactivation of Platelets from Gastrointestinal Cancer Patients

Venous thromboembolism (VTE) is one of the most common causes of cancer related mortality. It has been speculated that hypercoagulation in cancer patients is triggered by direct or indirect contact of platelets with tumor cells, however the underlying molecular mechanisms involved are currently unknown. Unraveling these mechanisms may provide potential avenues for preventing platelet-tumor cell aggregation. Here, we investigated the role of protein tyrosine phosphatases in the functionality of platelets in both healthy individuals and patients with gastrointestinal cancer, and determined their use as a target to inhibit platelet hyperactivity. This is the first study to demonstrate that platelet agonists selectively activate low molecular weight protein tyrosine phosphatase (LMWPTP) and PTP1B, resulting in activation of Src, a tyrosine kinase known to contribute to several platelet functions. Furthermore, we demonstrate that these phosphatases are a target for 3-bromopyruvate (3-BP), a lactic acid analog currently investigated for its use in the treatment of various metabolic tumors. Our data indicate that 3-BP reduces Src activity, platelet aggregation, expression of platelet activation makers and platelet-tumor cell interaction. Thus,

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results

Jet size dependence of single jet suppression in lead-lead collisions at sqrt(s(NN)) = 2.76 TeV with the ATLAS detector at the LHC

Measurements of inclusive jet suppression in heavy ion collisions at the LHC provide direct sensitivity to the physics of jet quenching. In a sample of lead-lead collisions at sqrt(s) = 2.76 TeV corresponding to an integrated luminosity of approximately 7 inverse microbarns, ATLAS has measured jets with a calorimeter over the pseudorapidity interval |eta| < 2.1 and over the transverse momentum range 38 < pT < 210 GeV. Jets were reconstructed using the anti-kt algorithm with values for the distance parameter that determines the nominal jet radius of R = 0.2, 0.3, 0.4 and 0.5. The centrality dependence of the jet yield is characterized by the jet "central-to-peripheral ratio," Rcp. Jet production is found to be suppressed by approximately a factor of two in the 10% most central collisions relative to peripheral collisions. Rcp varies smoothly with centrality as characterized by the number of participating nucleons. The observed suppression is only weakly dependent on jet radius and transverse momentum. These results provide the first direct measurement of inclusive jet suppression in heavy ion collisions and complement previous measurements of dijet transverse energy imbalance at the LHC.Comment: 15 pages plus author list (30 pages total), 8 figures, 2 tables, submitted to Physics Letters B. All figures including auxiliary figures are available at http://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/HION-2011-02

Building The Sugarcane Genome For Biotechnology And Identifying Evolutionary Trends

Background: Sugarcane is the source of sugar in all tropical and subtropical countries and is becoming increasingly important for bio-based fuels. However, its large (10 Gb), polyploid, complex genome has hindered genome based breeding efforts. Here we release the largest and most diverse set of sugarcane genome sequences to date, as part of an on-going initiative to provide a sugarcane genomic information resource, with the ultimate goal of producing a gold standard genome.Results: Three hundred and seventeen chiefly euchromatic BACs were sequenced. A reference set of one thousand four hundred manually-annotated protein-coding genes was generated. A small RNA collection and a RNA-seq library were used to explore expression patterns and the sRNA landscape. In the sucrose and starch metabolism pathway, 16 non-redundant enzyme-encoding genes were identified. 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