Unveiling the kinomes of leishmania infantum and L. braziliensis empowers the discovery of new kinase targets and antileishmanial compounds

Leishmaniasis is a neglected tropical disease caused by parasites of the genus Leishmania (NTD) endemic in 98 countries. Although some drugs are available, current treatments deal with issues such as toxicity, low efficacy, and emergence of resistance. Therefore, there is an urgent need to identify new targets for the development of new antileishmanial drugs. Protein kinases (PKs), which play an essential role in many biological processes, have become potential drug targets for many parasitic diseases. A refined bioinformatics pipeline was applied in order to define and compare the kinomes of L. infantum and L. braziliensis, species that cause cutaneous and visceral manifestations of leishmaniasis in the Americas, the latter being potentially fatal if untreated. Respectively, 224 and 221 PKs were identified in L. infantum and L. braziliensis overall. Almost all unclassified eukaryotic PKs were assigned to six of nine major kinase groups and, consequently, most have been classified into family and subfamily. Furthermore, revealing the kinomes for both Leishmania species allowed for the prioritization of potential drug targets that could be explored for discovering new drugs against leishmaniasis. Finally, we used a drug repurposing approach and prioritized seven approved drugs and investigational compounds to be experimentally tested against Leishmania. Trametinib and NMS-1286937 inhibited the growth of L. infantum and L. braziliensis promastigotes and amastigotes and therefore might be good candidates for the drug repurposing pipeline17352361FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE GOIÁS - FAPE

Current status of turbulent dynamo theory: From large-scale to small-scale dynamos

Several recent advances in turbulent dynamo theory are reviewed. High resolution simulations of small-scale and large-scale dynamo action in periodic domains are compared with each other and contrasted with similar results at low magnetic Prandtl numbers. It is argued that all the different cases show similarities at intermediate length scales. On the other hand, in the presence of helicity of the turbulence, power develops on large scales, which is not present in non-helical small-scale turbulent dynamos. At small length scales, differences occur in connection with the dissipation cutoff scales associated with the respective value of the magnetic Prandtl number. These differences are found to be independent of whether or not there is large-scale dynamo action. However, large-scale dynamos in homogeneous systems are shown to suffer from resistive slow-down even at intermediate length scales. The results from simulations are connected to mean field theory and its applications. Recent work on helicity fluxes to alleviate large-scale dynamo quenching, shear dynamos, nonlocal effects and magnetic structures from strong density stratification are highlighted. Several insights which arise from analytic considerations of small-scale dynamos are discussed.Comment: 36 pages, 11 figures, Spa. Sci. Rev., submitted to the special issue "Magnetism in the Universe" (ed. A. Balogh

On the verge of Umdeutung in Minnesota: Van Vleck and the correspondence principle (Part One)

In October 1924, the Physical Review, a relatively minor journal at the time, published a remarkable two-part paper by John H. Van Vleck, working in virtual isolation at the University of Minnesota. Van Vleck combined advanced techniques of classical mechanics with Bohr's correspondence principle and Einstein's quantum theory of radiation to find quantum analogues of classical expressions for the emission, absorption, and dispersion of radiation. For modern readers Van Vleck's paper is much easier to follow than the famous paper by Kramers and Heisenberg on dispersion theory, which covers similar terrain and is widely credited to have led directly to Heisenberg's "Umdeutung" paper. This makes Van Vleck's paper extremely valuable for the reconstruction of the genesis of matrix mechanics. It also makes it tempting to ask why Van Vleck did not take the next step and develop matrix mechanics himself.Comment: 82 page

Identification of GPI anchor attachment signals by a Kohonen self-organizing map

Immunogenetics and cellular immunology of bacterial infectious disease

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