Contribution of microscopy for understanding the mechanism of action against trypanosomatids

Transmission electron microscopy (TEM) has proved to be a useful tool to study the ultrastructural alterations and the target organelles of new antitrypanosomatid drugs. Thus, it has been observed that sesquiterpene lactones induce diverse ultrastructural alterations in both T. cruzi and Leishmania spp., such as cytoplasmic vacuolization, appearance of multilamellar structures, condensation of nuclear DNA, and, in some cases, an important accumulation of lipid vacuoles. This accumulation could be related to apoptotic events. Some of the sesquiterpene lactones (e.g., psilostachyin) have also been demonstrated to cause an intense mitochondrial swelling accompanied by a visible kinetoplast deformation as well as the appearance of multivesicular bodies. This mitochondrial swelling could be related to the generation of oxidative stress and associated to alterations in the ergosterol metabolism. The appearance of multilamellar structures and multiple kinetoplasts and flagella induced by the sesquiterpene lactone psilostachyin C indicates that this compound would act at the parasite cell cycle level, in an intermediate stage between kinetoplast segregation and nuclear division. In turn, the diterpene lactone icetexane has proved to induce the external membrane budding on T. cruzi together with an apparent disorganization of the pericellar cytoskeleton. Thus, ultrastructural TEM studies allow elucidating the possible mechanisms and the subsequent identification of molecular targets for the action of natural compounds on trypanosomatids.Fil: Lozano, Esteban Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Spina Zapata, Renata María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Barrera, Patricia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Tonn, Carlos Eugenio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Investigaciones en Tecnología Química. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Investigaciones en Tecnología Química; ArgentinaFil: Sosa Escudero, Miguel Angel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentin

A high-throughput splinkerette-PCR method for the isolation and sequencing of retroviral insertion sites

Insertional mutagens such as viruses and transposons are a useful tool for performing forward genetic screens in mice to discover cancer genes. These screens are most effective when performed using hundreds of mice, however until recently a major limitation to performing screens on this scale has been the cost effective isolation and sequencing of insertion sites. Here we present a method for the high-throughput isolation of insertion sites using a highly efficient splinkerette-PCR method coupled with capillary or 454 sequencing. This protocol includes a description of the procedure for DNA isolation, DNA digestion, linker or splinkerette ligation, primary and secondary PCR amplification, and sequencing. This method, which takes about 1 week to perform, has allowed us to isolate hundreds of thousands of insertion sites from mouse tumours and, unlike other methods, has been specifically optimised for the isolation of insertion sites generated with the murine leukaemia virus (MuLV), and can easily be performed in 96 well plate format for the efficient multiplex isolation of insertion sites

Search for direct pair production of the top squark in all-hadronic final states in proton-proton collisions at s√=8 TeV with the ATLAS detector

The results of a search for direct pair production of the scalar partner to the top quark using an integrated luminosity of 20.1fb−1 of proton–proton collision data at √s = 8 TeV recorded with the ATLAS detector at the LHC are reported. The top squark is assumed to decay via t˜→tχ˜01 or t˜→ bχ˜±1 →bW(∗)χ˜01 , where χ˜01 (χ˜±1 ) denotes the lightest neutralino (chargino) in supersymmetric models. The search targets a fully-hadronic final state in events with four or more jets and large missing transverse momentum. No significant excess over the Standard Model background prediction is observed, and exclusion limits are reported in terms of the top squark and neutralino masses and as a function of the branching fraction of t˜ → tχ˜01 . For a branching fraction of 100%, top squark masses in the range 270–645 GeV are excluded for χ˜01 masses below 30 GeV. For a branching fraction of 50% to either t˜ → tχ˜01 or t˜ → bχ˜±1 , and assuming the χ˜±1 mass to be twice the χ˜01 mass, top squark masses in the range 250–550 GeV are excluded for χ˜01 masses below 60 GeV

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT

Search for R-parity-violating supersymmetry in events with four or more leptons in sqrt(s) =7 TeV pp collisions with the ATLAS detector

A search for new phenomena in final states with four or more leptons (electrons or muons) is presented. The analysis is based on 4.7 fb−1 of $\sqrt{s}=7\;\mathrm{TeV}$ proton-proton collisions delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in two signal regions: one that requires moderate values of missing transverse momentum and another that requires large effective mass. The results are interpreted in a simplified model of R-parity-violating supersymmetry in which a 95% CL exclusion region is set for charged wino masses up to 540 GeV. In an R-parity-violating MSUGRA/CMSSM model, values of m 1/2 up to 820 GeV are excluded for 10 < tan β < 40

Measurement of the cross-section of high transverse momentum vector bosons reconstructed as single jets and studies of jet substructure in pp collisions at √s = 7 TeV with the ATLAS detector

This paper presents a measurement of the cross-section for high transverse momentum W and Z bosons produced in pp collisions and decaying to all-hadronic final states. The data used in the analysis were recorded by the ATLAS detector at the CERN Large Hadron Collider at a centre-of-mass energy of √s = 7 TeV;{\rm Te}{\rm V}$and correspond to an integrated luminosity of$4.6\;{\rm f}{{{\rm b}}^{-1}}$. The measurement is performed by reconstructing the boosted W or Z bosons in single jets. The reconstructed jet mass is used to identify the W and Z bosons, and a jet substructure method based on energy cluster information in the jet centre-of-mass frame is used to suppress the large multi-jet background. The cross-section for events with a hadronically decaying W or Z boson, with transverse momentum${{p}_{{\rm T}}}\gt 320\;{\rm Ge}{\rm V}$and pseudorapidity$|\eta |\lt 1.9$, is measured to be${{\sigma }_{W+Z}}=8.5\pm 1.7$ pb and is compared to next-to-leading-order calculations. The selected events are further used to study jet grooming techniques

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Search for high-mass dilepton resonances in pp collisions at s√=8 TeV with the ATLAS detector

The ATLAS detector at the Large Hadron Collider is used to search for high-mass resonances decaying to dielectron or dimuon final states. Results are presented from an analysis of proton-proton (pp) collisions at a center-of-mass energy of 8 TeV corresponding to an integrated luminosity of 20.3  fb−1 in the dimuon channel. A narrow resonance with Standard Model Z couplings to fermions is excluded at 95% confidence level for masses less than 2.79 TeV in the dielectron channel, 2.53 TeV in the dimuon channel, and 2.90 TeV in the two channels combined. Limits on other model interpretations are also presented, including a grand-unification model based on the E6 gauge group, Z∗ bosons, minimal Z' models, a spin-2 graviton excitation from Randall-Sundrum models, quantum black holes, and a minimal walking technicolor model with a composite Higgs boson

Measurement of long-range pseudorapidity correlations and azimuthal harmonics in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Measurements of two-particle correlation functions and the first five azimuthal harmonics, v1 to v5, are presented, using 28 nb−1 of p+Pb collisions at a nucleon-nucleon center-of-mass energy of √sNN=5.02 TeV measured with the ATLAS detector at the LHC. Significant long-range “ridgelike” correlations are observed for pairs with small relative azimuthal angle (|Δϕ|2π/3) over the transverse momentum range 0.44 GeV. The v2(pT), v3(pT), and v4(pT) are compared to the vn coefficients in Pb+Pb collisions at √sNN=2.76 TeV with similar event multiplicities. Reasonable agreement is observed after accounting for the difference in the average pT of particles produced in the two collision systems

Addendum to ‘measurement of the tt̄ production cross-section using eμ events with b-tagged jets in pp collisions at √s= 7 and 8 TeV with the ATLAS detector’

The ATLAS measurement of the inclusive top quark pair (tt̄) cross-section σtt̄ in proton–proton collisions at √s=8 TeV has been updated using the final 2012 luminosity calibration. The updated cross-section result is: σtt¯=242.9±1.7±5.5±5.1±4.2pb, where the four uncertainties arise from data statistics, experimental and theoretical systematic effects, knowledge of the integrated luminosity and of the LHC beam energy. The result is consistent with theoretical QCD calculations at next-to-next-to-leading order. The measurement of the ratio of tt̄ cross-sections at √s=8 TeV and √s=7 TeV, and the √s=8 TeV fiducial measurement corresponding to the experimental acceptance of the leptons, have also been updated. The most precise measurement of the tt̄ cross-section (σtt̄) in proton–proton collisions at √s=8 TeV from the ATLAS Collaboration was made using events with an opposite-charge electron–muon pair and one or two b-tagged jets [1], and used a preliminary calibration of the integrated luminosity. The luminosity calibration has been finalised since [2] with a total uncertainty of 1.9%, corresponding to a substantial improvement on the previous uncertainty of 2.8%. Since the uncertainty on the integrated luminosity contributed 3.1% of the total 4.3% uncertainty on the σtt¯ measurement reported in [1], a significant improvement in the measurement is possible by using the new luminosity calibration, as documented in this Addendum. The new calibration corresponds to an integrated luminosity of 20.2 fb−¹ for the √s=8 TeV sample, a decrease of 0.2%. The cross-section was recomputed taking into account the effects on both the conversion of the tt¯ event yield to a cross-section, and the background estimates, giving a result of: σtt¯=242.9±1.7±5.5±5.1±4.2pb, where the four uncertainties arise from data statistics, experimental and theoretical systematic effects, knowledge of the integrated luminosity, and of the LHC beam energy, giving a total uncertainty of 8.8 pb (3.6 %). The result is consistent with the theoretical prediction of 252.9−14.5+13.3 pb, calculated at next-to-next-to-leading-order with next-to-next-to-leading-logarithmic soft gluon terms with the top++ 2.0 program [3] as discussed in detail in Ref. [1]. The updated value of the ratio of cross-sections Rtt¯=σtt¯(8 TeV)/σtt¯(7 TeV) is: Rtt¯=1.328±0.024±0.015±0.038±0.001, with uncertainties defined as above, adding in quadrature to a total of 0.047. The largest uncertainty comes from the uncertainties on the integrated luminosities, considered to be uncorrelated between the √s=7 TeV and √s=8 TeV datasets. This result is 2.1σ below the expectation of 1.430±0.013 calculated from top++ 2.0 as discussed in Ref. [1]. The updated fiducial cross-sections, for a tt¯ decay producing an eμ pair within a given fiducial region, are shown in Table 1, updating Table 5 of Ref. [1]. The results are given both for the analysis requirements of pT>25GeV and |η|30GeV and |η|<2.4. They are given separately for the two cases where events with either one or both leptons coming from t→W→τ→ℓ rather than the direct decay t→W→ℓ(ℓ=e or μ) are included, or where the contributions involving τ decays are subtracted. The results shown for the √s=7 TeV data sample are unchanged with respect to those in Ref. [1]. The results for the top quark pole mass and limits on light supersymmetric top squarks presented in Ref. [1] are derived from √s=7 TeV and √s=8 TeV cross-section measurements taken together, and would be only slightly improved by the luminosity update described here