Elastic scattering, inelastic excitation, and 1 n pick-up transfer cross sections for 10 B + 120 Sn at energies near the Coulomb barrier

The 10 B + 120 Sn reaction has been systematically studied at laboratory energies around the Coulomb barrier: E LAB = 31.5 , 33.5, 35.0, and 37.5 MeV. Cross sections for the elastic scattering and some reaction processes have been measured: excitation to the 1 + state of 10 B ; excitation to the 2 + and 3 − states of 120 Sn ; and the one-neutron pick-up transfer 120 Sn ( 10 B , 11 B ) 119 Sn . Coupled reaction channel (CRC) calculations have been performed in the context of the double-folding São Paulo potential. The theoretical calculations result in a good overall description of the experimental angular distributions. The effect on the theoretical elastic-scattering angular distributions of couplings to the inelastic and transfer states (through the CRC calculations) and to the continuum states (through continuum-discretized coupled-channels calculations) has been investigated.Instituto Nacional de Ciência e Tecnologia–Física Nuclear e Aplicações (INCT-FNA) 464898/2014-5Ministerio de Economía y Competitividad de España y el Fondo Europeo de Desarrollo Regional (FEDER) FIS2014-51941-P,Junta de Andalucía. FQM-160Programa de investigación e innovación de la Unión Europea Horizonte 2020. 65400

Nitric Oxide Resistance in Leishmania (Viannia) braziliensis Involves Regulation of Glucose Consumption, Glutathione Metabolism and Abundance of Pentose Phosphate Pathway Enzymes

In American Tegumentary Leishmaniasis production of cytokines, reactive oxygen species and nitric oxide (NO) by host macrophages normally lead to parasite death. However, some Leishmania braziliensis strains exhibit natural NO resistance. NO-resistant strains cause more lesions and are frequently more resistant to antimonial treatment than NO-susceptible ones, suggesting that NO-resistant parasites are endowed with specific mechanisms of survival and persistence. To tests this, we analyzed the effect of pro- and antioxidant molecules on the infectivity in vitro of L. braziliensis strains exhibiting polar phenotypes of resistance or susceptibility to NO. In addition, we conducted a comprehensive quantitative mass spectrometry-based proteomics analysis of those parasites. NO-resistant parasites were more infective to peritoneal macrophages, even in the presence of high levels of reactive species. Principal component analysis of protein concentration values clearly differentiated NO-resistant from NO-susceptible parasites, suggesting that there are natural intrinsic differences at molecular level among those strains. Upon NO exposure, NO-resistant parasites rapidly modulated their proteome, increasing their total protein content and glutathione (GSH) metabolism. Furthermore, NO-resistant parasites showed increased glucose analogue uptake, and increased abundance of phosphotransferase and G6PDH after nitrosative challenge, which can contribute to NADPH pool maintenance and fuel the reducing conditions for the recovery of GSH upon NO exposure. Thus, increased glucose consumption and GSH-mediated redox capability may explain the natural resistance of L. braziliensis against NO

In-depth quantitative proteomics uncovers specie-specific metabolic programs in Leishmania (Viannia) species

Author summary Leishmania braziliensis,L.panamensis, andL.guyanensisare responsible for most of the cases of tegumentary leishmaniasis (TL) in the Americas. These species are associated with a variety of clinical manifestations of TL ranging from self-healing localized cutaneous lesions to disseminated and mucocutaneous presentations that may result in severe oropharyngeal mutilation. Here, we report a comprehensive quantitative comparison of the proteome of those species. Assessment of absolute titers of similar to 7000 proteins revealed a very clear differentiation among them. Significant differences in energy metabolism, membrane proteins, transporters, and lipids are contributing for species-specific traits and provide rich substrate for exploring new molecules for diagnosing purposes. Leishmaniaspecies are responsible for a broad spectrum of diseases, denominated Leishmaniasis, affecting over 12 million people worldwide. During the last decade, there have been impressive efforts for sequencing the genome of most of the pathogenicLeishmaniaspp. as well as hundreds of strains, but large-scale proteomics analyses did not follow these achievements and theLeishmaniaproteome remained mostly uncharacterized. Here, we report a comprehensive comparative study of the proteomes of strains representingL.braziliensis,L.panamensisandL.guyanensisspecies. Proteins extracted by SDS-mediated lysis were processed following the multi-enzyme digestion-filter aided sample preparation (FASP) procedure and analysed by high accuracy mass spectrometry. "Total Protein Approach" and "Proteomic Ruler" were applied for absolute quantification of proteins. Principal component analysis demonstrated very high reproducibility among biological replicates and a very clear differentiation of the three species. Our dataset comprises near 7000 proteins, representing the most completeLeishmaniaproteome yet known, and provides a comprehensive quantitative picture of the proteomes of the three species in terms of protein concentration and copy numbers. Analysis of the abundance of proteins from the major energy metabolic processes allow us to highlight remarkably differences among the species and suggest that these parasites depend on distinct energy substrates to obtain ATP. WhereasL.braziliensisrelies the more on glycolysis,L.panamensisandL.guyanensisseem to depend mainly on mitochondrial respiration. These results were confirmed by biochemical assays showing opposite profiles for glucose uptake and O(2)consumption in these species. In addition, we provide quantitative data about different membrane proteins, transporters, and lipids, all of which contribute for significant species-specific differences and provide rich substrate for explore new molecules for diagnosing purposes. Data are available via ProteomeXchange with identifier PXD017696

Is Mitigation Translocation an Effective Strategy for Conserving Common Chuckwallas?

Mitigation translocation remains a popular conservation tool despite ongoing debate regarding its utility for population conservation. To add to the understanding of the effectiveness of mitigation translocation, in 2017 and 2018 we monitored a population of protected common chuckwallas (Sauromalus ater) following translocation away from the area of construction of a new highway near the South Mountains, Phoenix, Arizona, USA. We removed chuckwallas from the construction right-of-way, paint-marked and pit-tagged them, and then released them in a nearby municipal preserve. We deployed very high frequency radio-telemetry transmitters on a sub-sample of 15 translocated adult chuckwallas. We monitored the radio-marked chuckwallas once a day at 1- to 3-day intervals for up to 46 days to document survival, body mass, and post-release movements. The average distance moved following translocation was 359 ± 53 m. Using minimum convex polygons, the average home range size of translocated lizards was 0.9 ± 0.3 ha, which was 18–45 times larger than expected for the species. Following translocations, we surveyed the translocation sites 1 month later and again 1 year later to determine the presence of translocated chuckwallas. Translocated individuals were rarely observed a second time: in 2017, only 11 of 160 translocated chuckwallas were seen again, and in 2018, only 11 of 192 translocated chuckwallas were detected. In the light of low recapture rate, consistent loss of body mass, and large movements of marked lizards, we conclude that survival of translocated chuckwallas was low over a single year. In the future, efficacy of mitigation translocation could be better evaluated by assessing the spatial ecology of both resident and translocated individuals simultaneously using radio-telemetry

A system of three transiting super-Earths in a cool dwarf star

We present the detection of three super-Earths transiting the cool star LP415-17, monitored by K2 mission in its 13th campaign. High resolution spectra obtained with HARPS-N/TNG showed that the star is a mid-late K dwarf. Using spectral synthesis models we infer its effective temperature, surface gravity and metallicity and subse- quently determined from evolutionary models a stellar radius of 0.58 R Sun. The planets have radii of 1.8, 2.6 and 1.9 R Earth and orbital periods of 6.34, 13.85 and 40.72 days. High resolution images discard any significant contamination by an intervening star in the line of sight. The orbit of the furthest planet has radius of 0.18 AU, close to the inner edge of the habitable zone. The system is suitable to improve our understanding of formation and dynamical evolution of super-Earth systems in the rocky - gaseous threshold, their atmospheres, internal structure, composition and interactions with host stars.Comment: Accepted for publication in MNRAS Letter

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

Key Lessons Learned from Moffitt's Molecular Tumor Board: The Clinical Genomics Action Committee Experience

The increasing practicality of genomic sequencing technology has led to its incorporation into routine clinical practice. Successful identification and targeting of driver genomic alterations that provide proliferative and survival advantages to tumor cells have led to approval and ongoing development of several targeted cancer therapies. Within many major cancer centers, molecular tumor boards are constituted to shepherd precision medicine into clinical practice