Cell cycle-dependent phosphorylation of Theileria annulata schizont surface proteins

The invasion of Theileria sporozoites into bovine leukocytes is rapidly followed by the destruction of the surrounding host cell membrane, allowing the parasite to establish its niche within the host cell cytoplasm. Theileria infection induces host cell transformation, characterised by increased host cell proliferation and invasiveness, and the activation of anti-apoptotic genes. This process is strictly dependent on the presence of a viable parasite. Several host cell kinases, including PI3-K, JNK, CK2 and Src-family kinases, are constitutively activated in Theileria-infected cells and contribute to the transformed phenotype. Although a number of host cell molecules, including IkB kinase and polo-like kinase 1 (Plk1), are recruited to the schizont surface, very little is known about the schizont molecules involved in host-parasite interactions. In this study we used immunofluorescence to detect phosphorylated threonine (p-Thr), serine (p-Ser) and threonine-proline (p-Thr-Pro) epitopes on the schizont during host cell cycle progression, revealing extensive schizont phosphorylation during host cell interphase. Furthermore, we established a quick protocol to isolate schizonts from infected macrophages following synchronisation in S-phase or mitosis, and used mass spectrometry to detect phosphorylated schizont proteins. In total, 65 phosphorylated Theileria proteins were detected, 15 of which are potentially secreted or expressed on the surface of the schizont and thus may be targets for host cell kinases. In particular, we describe the cell cycle-dependent phosphorylation of two T. annulata surface proteins, TaSP and p104, both of which are highly phosphorylated during host cell S-phase. TaSP and p104 are involved in mediating interactions between the parasite and the host cell cytoskeleton, which is crucial for the persistence of the parasite within the dividing host cell and the maintenance of the transformed state

Systematic review and meta-analysis of the pharmacokinetics of benznidazole in the treatment of Chagas disease

Chagas disease is a neglected parasitic illness affecting approximately 8 million people, predominantly in Latin America. Benznidazole is the drug of choice for treatment, although its availability has been limited. A paucity of knowledge of the pharmacokinetic properties of this drug has contributed to its limited availability in several jurisdictions. The objective of this study was to conduct a systematic literature review and a Bayesian meta-analysis of pharmacokinetic studies to improve estimates of the basic pharmacokinetic properties of benznidazole. A systematic search of the Embase, Medline, LILACS, and SciELO (Scientific Electronic Library Online) databases was conducted. Eligible studies reported patient-level data from single-100-mg-dose pharmacokinetic evaluations of benznidazole in adults or otherwise provided data relevant to the estimation of pharmacokinetic parameters which could be derived from such studies. A Bayesian hierarchical model was used for analysis. Secondary data (i.e., data from studies that did not include patient-level, single-100-mg-dose data) were used for the generation of empirical priors for the Bayesian analysis. The systematic search identified nine studies for inclusion. Nine pharmacokinetic parameters were estimated, including the area under the concentration-time curve (AUC), the maximum concentration of drug in plasma (Cmax), the time to Cmax, the elimination rate constant (kel), the absorption rate constant (Ka), the absorption and elimination half-lives, the apparent oral clearance, and the apparent oral volume of distribution. The results showed consistency across studies. AUC and Cmax were 51.31 mg · h/liter (95% credible interval [CrI], 45.01, 60.28 mg · h/liter) and 2.19 mg/liter (95% CrI, 2.06, 2.33 mg/liter), respectively. Ka and kel were 1.16 h-1 (95% CrI, 0.59, 1.76 h-1) and 0.052 h-1 (95% CrI, 0.045, 0.059 h-1), respectively, with the corresponding absorption and elimination half-lives being 0.60 h (95% CrI, 0.38, 1.11 h) and 13.27 h (95% CrI, 11.79, 15.42 h), respectively. The oral clearance and volume of distribution were 2.04 liters/h (95% CrI, 1.77, 2.32 liters/h) and 39.19 liters (95% CrI, 36.58, 42.17 liters), respectively. A Bayesian meta-analysis was used to improve the estimates of the standard pharmacokinetic parameters of benznidazole. These data can inform clinicians and policy makers as access to this drug increases.Fil: Wiens, Matthew O.. University of British Columbia; CanadáFil: Kanters, Steve. Precision Global Health;Fil: Mills, Edward. Mc Master University; CanadáFil: Peregrina Lucano, Alejandro A.. Universidad de Guadalajara; MéxicoFil: Gold, Silvia. Fundación Mundo Sano; ArgentinaFil: Ayers, Dieter. Precision Global Health;Fil: Ferrero, Luis. Fundación Mundo Sano; ArgentinaFil: Krolewiecki, Alejandro Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental. Universidad Nacional de Salta. Facultad de Ciencias de la Salud. Instituto de Patología Experimental; Argentin

A Comparison of Solar Wind and Estimated Solar System Xenon Abundances: A Test for Solid/ Gas Fractionation in the Solar Nebula

Significant fractionation of dust/gas from the original interstellar cloud during the formation of the solar system is a distinct possibility. Identification of such an effect would provide important clues to nebular processes. Fractionation of volatiles is not constrained by CI abundances and only for the most abundant ones by photospheric observations. The solar Xe elemental abundance is determined here via solar wind measurements from lunar ilmenites and normalized to Si by spacecraft data. The results are compared with estimated abundances assuming no fractionation, which are relatively well constrained for Xe by s-process calculations, odd-mass abundance interpolations, and odd-even abundance systematics. When corrected for solar wind/photospheric fractionation, the ^(130)Xe abundance given by surface layer oxidation of ilmenite from soil 71501, exposed within the last - 200 m.y., is 0.24 ± 0.09 normalized to Si = 10^6. This is indistinguishable from the estimates made assuming no solid/gas fractionation. A similar result was obtained for Kr by Wiens et al (1991). Results from breccia 79035 ilmenite, exposed at least ~1 Gy ago, indicate that the solar wind Xe flux may have been significantly higher relative to other noble gases, perhaps due to more efficient Xe ionization. If this is true, fluxes of C and S, which have similar first ionization potentials to Xe, should also be higher in the ancient solar wind from the same time period, though such variations have not been observed

Characterisation of Float Rocks at Ireson Hill, Gale Crater

Float rocks discovered by surface missions on Mars have given unique insights into the sedimentary, diagenetic and igneous processes that have operated throughout the planets history. In addition, Gale sedimentary rocks, both float and in situ, record a combination of source compositions and diagenetic overprints. We examine a group of float rocks that were identified by the Mars Science Laboratory missions Curiosity rover at the Ireson Hill site, circa. sol 1600 using ChemCam LIBS, APXS and images from the MastCam, Mars Hand Lens Imager (MAHLI) and ChemCam Remote Micro-Imager (RMI) cameras. Geochemical data provided by the APXS and ChemCam instruments allow us to compare the compositions of these rocks to known rock types from Gale crater, as well as elsewhere on Mars. Ireson Hill is a 15 m long butte in the Murray formation with a dark cap-ping unit with chemical and stratigraphic consistency with the Stimson formation. A total of 6 float rocks have been studied on the butte

First Gale Western Butte Capping-Unit Compositions, and Relationships to Earlier Units Along Curiosity's Traverse

The Curiosity rover has been traversing through the clay-bearing unit (Glen Torridon; GT), approaching Greenheugh pediment, a large, fan-shaped surface surrounding the mouth of Gediz Vallis on the lower slope of Mt. Sharp. The pediment unconformably overlies the underlying bedrock, and is hence younger than units of the Mt. Sharp group. Orbital imaging of the pediment has shown it to have a slightly lower albedo and higher thermal inertia than neighboring units, to be relatively retentive of craters (e.g., erosion resistant), and to exhibit curved bedforms suggestive of lithified eolian bedforms. No diagnostic spectral signature has been observed from orbit. Recent rover positions allowed remote imaging of the contact between Greenheugh pediment and the eroded Murray formation strata below it, showing that the pediment capping material is cross-bedded and relatively thin (1-3 m), and suggesting that the pediment may have been much larger at one time. As Curiosity approached the edge of the pediment, the team investigated two buttes named Central and Western. The latter butte contains dark capping material that initially looked similar to the pediment cap, but close inspection revealed important physical differences. Here we report on compositions from ChemCam of two float rocks that appear to have rolled down from the capping unit, and on potential relation-ships to other targets along the traverse of the rover

Apatites in Gale Crater

ChemCam is an active remote sensing instrument suite that has operated successfully on MSL since landing Aug. 6th, 2012. It uses laser pulses to remove dust and to analyze rocks up to 7 m away. Laser-induced breakdown spectroscopy (LIBS) obtains emission spectra of materials ablated from the samples in electronically excited states. The intensities of the emission lines scale with the abundances of the related element. ChemCam is sensitive to most major rock-forming elements as well as to a set of minor and trace elements such as F, Cl, Li, P, Sr, Ba, and Rb. The measured chemical composition can then be used to infer the mineralogical composition of the ablated material. Here, we report a summary of inferred apatite detections along the MSL traverse at Gale Crater. We present the geologic settings of these findings and derive some interpretations about the formation conditions of apatite in time and space

Applications of Abundance Data and Requirements for Cosmochemical Modeling

Understanding the evolution of the universe from Big Bang to its present state requires an understanding of the evolution of the abundances of the elements and isotopes in galaxies, stars, the interstellar medium, the Sun and the heliosphere, planets and meteorites. Processes that change the state of the universe include Big Bang nucleosynthesis, star formation and stellar nucleosynthesis, galactic chemical evolution, propagation of cosmic rays, spallation, ionization and particle transport of interstellar material, formation of the solar system, solar wind emission and its fractionation (FIP/FIT effect), mixing processes in stellar interiors, condensation of material and subsequent geochemical fractionation. Here, we attempt to compile some major issues in cosmochemistry that can be addressed with a better knowledge of the respective element or isotope abundances. Present and future missions such as Genesis, Stardust, Interstellar Pathfinder, and Interstellar Probe, improvements of remote sensing instrumentation and experiments on extraterrestrial material such as meteorites, presolar grains, and lunar or returned planetary or cometary samples will result in an improved database of elemental and isotopic abundances. This includes the primordial abundances of D, ^3He, ^4He, and ^7Li, abundances of the heavier elements in stars and galaxies, the composition of the interstellar medium, solar wind and comets as well as the (highly) volatile elements in the solar system such as helium, nitrogen, oxygen or xenon