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

Quiropterofauna Do Cerrado Leste Maranhense, Brasil, Com Ocorrência De Novos Registros. Biota Neotropica

In Brazil, 179 bat species have been recorded to date, representing 68 genera and nine families. Few data are available on the bat fauna of the state of Maranhão, so the present study was based on a survey of the bat fauna of the Inhamum Municipal Environmental Protection Area (APA Inhamum) in the Cerrado savanna of the eastern extreme of the state. This inventory provides new records of bat species for the state of Maranhão and the Cerrado biome. A total of 31 species (four families) were collected, representing 39% of the bat species known to occur in Maranhão and 28.71% of the species described for the Cerrado. The family Phyllostomidae was the most diverse, with 23 species (74.20% of the total), and also the most abundant, with 86.09% of the specimens collected. The Molossidae (four species) was the second most diverse, followed by the Vespertilionidae (three species) and the Emballonuridae (one species). Carollia perspicillata was the most abundant species (28%).The records of Artibeus fimbriatus and Platyrrhinus fusciventris are the first for the Cerrado and were also recorded in Maranhão for the first time. The cumulative species curve did not reach an asymptote. The species Dermanura gnoma, Lasiurus blossevillii, Lasiurus ega, Micronycteris schmidtorum, Molossops temminckii, Platyrrhinus cf. recifinus, Phylloderma stenops and Trachops cirrhosus, were also recorded in Maranhão for the first time demonstrating the value of for mammal inventories and emphasizing the need for further surveys in this poorly-known region. © 2016, Universidade Estadual de Campinas UNICAMP. All Rights Reserved.16

The quadratic spinor Lagrangian is equivalent to the teleparallel theory

The quadratic spinor Lagrangian is shown to be equivalent to the teleparallel / tetrad representation of Einstein's theory. An important consequence is that the energy-momentum density obtained from this quadratic spinor Lagrangian is essentially the same as the ``tensor'' proposed by Moller in 1961.Comment: 10 pages, RevTe

Effect of High-Intensity Interval Training on Body Composition, Cardiorespiratory Fitness, Blood Pressure, and Substrate Utilization During Exercise Among Prehypertensive and Hypertensive Patients With Excessive Adiposity

Indexación: Scopus.Regular exercise training is a recognized lifestyle strategy to lower resting blood pressure (BP), but little is known about substrate metabolism in population with high BP. Thus, the purpose of this study was to investigate the effects of 16-weeks of HIIT on body composition, BP, cardiorespiratory fitness by (Formula presented.) O2max, and substrate utilization during exercise among prehypertensive and hypertensive patients with excessive adiposity. We also aimed to test the potential association between changes in cardiorespiratory fitness, substrate utilization during exercise and BP. Forty-two physically inactive overweight/obese participants participated in 16-weeks of HIIT intervention. The HIIT frequency was three times a week (work ratio 1:2:10, for interval cycling: rest period: repeated times; 80–100% of the maximum heart rate). Groups were distributed based on their baseline BP: HIIT-hypertensive (H-HTN: age 47.7 ± 12.0 years; body mass index [BMI] 30.3 ± 5.5 kg/m2; systolic [SBP]/diastolic BP [DBP] 151.6 ± 10/81.9 ± 4.2 mmHg), HIIT-pre-hypertensive (H-PreHTN: age 37.6 ± 12.0 years; BMI 31.9 ± 5.3 kg/m2; SBP/DBP 134.4 ± 3.2/74.9 ± 7.0 mmHg), and a normotensive control group (H-CG: age 40.7 ± 11.0 years; BMI 29.5 ± 4.2 kg/m2; SBP/DBP 117.0 ± 6.2/72.4 ± 4.1 mmHg). Anthropometry/body composition, BP, and metabolic substrate utilization during exercise (fat [FATox], carbohydrate [CHOox] oxidation, respiratory exchange ratio [RER], and (Formula presented.) O2max), were measured before and after the 16-week HIIT intervention. Adjusted mixed linear models revealed a significant improved in (Formula presented.) O2max were + 3.34 in the H-CG, + 3.63 in the H-PreHTN, and + 5.92 mL⋅kg–1⋅min–1, in the H-HTN group, however, the Time × Group interaction were not significant (p = 0.083). All the exercise types induced similar decreases on SBP (−8.70) in the H-HTN, (−7.14) in the H-CG, and (−5.11) mmHg in the H-PreHTN, as well as DBP levels (−5.43) mmHg in H-CG group (p = 0.032 vs. H-HTN group). At 16-week, no significant correlations were noted for the changes of blood pressure, cardiorespiratory fitness or exercise metabolism substrates outcomes. In conclusion, our results suggest that a 16-week HIIT-intervention improved (Formula presented.) O2max and blood pressure BP, but these changes are independent of substrate utilization during exercise in normotensive and hypertensive participants with excessive adiposity. © Copyright © 2020 Delgado-Floody, Izquierdo, Ramírez-Vélez, Caamaño-Navarrete, Moris, Jerez-Mayorga, Andrade and Álvarez.https://www.frontiersin.org/articles/10.3389/fphys.2020.558910/ful

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

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