Progesterone effects on the oligodendrocyte linage: all roads lead to the progesterone receptor

A new role has emerged for progesterone after discovering its potent actions away from reproduction in both the central and the peripheral nervous system. The aim of the present report is to discuss progesterone’s mechanisms of action involved in myelination, remyelination and neuroinflammation. The pivotal role of the classic progesterone receptor is described and evidence is compiled about progesterone’s direct effects on oligodendrocyte linage and its indirect effects on oligodendrocyte precursor cell differentiation by decreasing the neuroinflammatory environment.Fil: Jure, Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: de Nicola, Alejandro Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; ArgentinaFil: Labombarda, Maria Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentin

Small obstacle in a large polar flock

We show that arbitrarily large polar flocks are susceptible to the presence of a single small obstacle. In a wide region of parameter space, the obstacle triggers counterpropagating dense bands leading to reversals of the flow. In very large systems, these bands interact, yielding a never-ending chaotic dynamics that constitutes a new disordered phase of the system. While most of these results were obtained using simulations of aligning self-propelled particles, we find similar phenomena at the continuous level, not when considering the basic Toner-Tu hydrodynamic theory, but in simulations of truncations of the relevant Boltzmann equation

Efecto de la fecha de siembra para grupos de madurez de soja sembrado en localidades de la Provincia de Córdoba durante las campañas del 2005 al 2017

Trabajo Final Integrador (Área de Consolidación Métodos Cuantitativos para la Investigación Agropecuaria) -- UNC- Facultad de Ciencias Agropecuarias, 2017La soja (Glycine Max (L) Merr.) es una especie cuyos granos (ricos en proteína y con contenido medio de aceite) y subproductos (aceite y harina), poseen alta demanda mundial y buenos precios. En Argentina y en la provincia de Córdoba, es una de las principales producciones agrícolas; por ello es de interés reconocer variedades que logren los mejores rendimientos. El ambiente, el grupo de madurez (GM) y la fecha de siembra (FS), son factores que inciden en la producción. El objetivo de este estudio fue evaluar rendimientos de 12 campañas de soja (2005 a 2017) de la provincia de Córdoba, para determinar el periodo de siembra más conveniente para los GM más utilizados (III, IV, V y VI). El análisis se realizó a nivel de 4 departamentos ubicados alrededor del Departamento Capital y en cada uno de ellos, por GM, se compararon los rendimientos obtenidos según distintas decenas mensuales de siembra que abarcaban desde setiembre a enero. Se ajustó un modelo con efectos fijos de FS y efecto aleatorio de localidad y campaña dentro de localidad; las medias se compararon mediante la prueba DGC. En general: con los genotipos del GM V se obtuvieron iguales rendimientos en todo el rango de siembras (tempranas, óptimas y tardías); para los GM III y VI las FS más favorables para la producción dependieron de los departamentos y para el GM IV el rango de FS con mejores respuestas correspondió a las fechas consideradas óptimas (octubre a comienzos de diciembre).Soybean (Glycine Max (L) Merr.) is a species whose grains (rich in protein and with an medium oil content) and by-products (oil and flour), have high global demand and good prices. In Argentina and in the province of Córdoba, it is one of the main agricultural productions; therefore it is of interest to recognize varieties with the best yields. The environment, the maturity group (GM) and the sowing date (FS) are factors that affect production. The objective of this study was to evaluate yields of 12 soybean harvests (2005 to 2017) from the province of Córdoba, to determine the most suitable sowing period for the most used GM (III, IV, V and VI). The analysis was carried out at the level of 4 departments located around the Capital Department; for each department, by GM, the obtained yields were compared according to different monthly sowing tens that covered from September to January. A model with fixed effects for FS and random effects for locality and harvest within locality, was adjusted. The means were compared by the DGC test. In general: with GM V genotypes, equals yields were obtained in the whole range of sowings (early, optimal and late), for GM III and GM VI the most favorable FS depended on the departments; finaly, the FS range with the best answers for GM IV, corresponded to optimal dates (October to the beginning of December)

Efecto de la fecha de siembra para grupos de madurez de soja sembrado en localidades de la Provincia de Córdoba durante las campañas del 2005 al 2017

Trabajo Final Integrador (Área de Consolidación Métodos Cuantitativos para la Investigación Agropecuaria) -- UNC- Facultad de Ciencias Agropecuarias, 2017La soja (Glycine Max (L) Merr.) es una especie cuyos granos (ricos en proteína y con contenido medio de aceite) y subproductos (aceite y harina), poseen alta demanda mundial y buenos precios. En Argentina y en la provincia de Córdoba, es una de las principales producciones agrícolas; por ello es de interés reconocer variedades que logren los mejores rendimientos. El ambiente, el grupo de madurez (GM) y la fecha de siembra (FS), son factores que inciden en la producción. El objetivo de este estudio fue evaluar rendimientos de 12 campañas de soja (2005 a 2017) de la provincia de Córdoba, para determinar el periodo de siembra más conveniente para los GM más utilizados (III, IV, V y VI). El análisis se realizó a nivel de 4 departamentos ubicados alrededor del Departamento Capital y en cada uno de ellos, por GM, se compararon los rendimientos obtenidos según distintas decenas mensuales de siembra que abarcaban desde setiembre a enero. Se ajustó un modelo con efectos fijos de FS y efecto aleatorio de localidad y campaña dentro de localidad; las medias se compararon mediante la prueba DGC. En general: con los genotipos del GM V se obtuvieron iguales rendimientos en todo el rango de siembras (tempranas, óptimas y tardías); para los GM III y VI las FS más favorables para la producción dependieron de los departamentos y para el GM IV el rango de FS con mejores respuestas correspondió a las fechas consideradas óptimas (octubre a comienzos de diciembre).Soybean (Glycine Max (L) Merr.) is a species whose grains (rich in protein and with an medium oil content) and by-products (oil and flour), have high global demand and good prices. In Argentina and in the province of Córdoba, it is one of the main agricultural productions; therefore it is of interest to recognize varieties with the best yields. The environment, the maturity group (GM) and the sowing date (FS) are factors that affect production. The objective of this study was to evaluate yields of 12 soybean harvests (2005 to 2017) from the province of Córdoba, to determine the most suitable sowing period for the most used GM (III, IV, V and VI). The analysis was carried out at the level of 4 departments located around the Capital Department; for each department, by GM, the obtained yields were compared according to different monthly sowing tens that covered from September to January. A model with fixed effects for FS and random effects for locality and harvest within locality, was adjusted. The means were compared by the DGC test. In general: with GM V genotypes, equals yields were obtained in the whole range of sowings (early, optimal and late), for GM III and GM VI the most favorable FS depended on the departments; finaly, the FS range with the best answers for GM IV, corresponded to optimal dates (October to the beginning of December)

First-in-human phase I/IIa trial to evaluate the safety and initial clinical activity of DuoBody®-PD-L1×4–1BB (GEN1046) in patients with advanced solid tumors

Agonistic 4-1BB monoclonal antibodies were preclinically validated as promising cancer immunotherapies, both as monotherapy and as potentiators of the activity of PD-(L) 1–blocking agents. However, toxicity and a narrow therapeutic window have hampered their clinical development. DuoBodyPD-L1×4-1BB, a first-in-class, bispecific, next-generation checkpoint immunotherapy, was designed to overcome these limitations by activating T cells through conditional 4-1BB costimulation, while simultaneously blocking the PD-L1 axis. We present preliminary data from the ongoing, first-in-human, open-label, phase I/IIa trial of DuoBody-PD-L1×4-1BB in advanced solid tumors (NCT03917381)

Prevalence of Fabry Disease in Young Patients with Stroke in Argentina.

Background: Fabry disease (FD) is an underdiagnosed cause of stroke in youngadults, but the frequency of this association is largely unknown. We estimatedthe prevalence of FD in a nationwide cohort of young adults who had stroke andtransient ischemic attack (TIA) in Argentina. Methods: This was a prospective, multicenterstudy of stroke and FD in young adults (18-55 years) conducted in Argentinabetween 2011 and 2015. Patients were enrolled if they had had a TIA or an ischemicor hemorrhagic stroke within the previous 180 days. FD was diagnosed bymeasuring α-galactosidase A activity (males) and through genetic studies (females).Results: We enrolled 311 patients (54% men, mean age: 41 years). Ischemic eventsoccurred in 89% of patients (80% infarcts, 9% TIA) and hemorrhagic strokes in11%. One female (.3% of the total group, 1% of the cryptogenic ischemic strokes)had the pathogenic mutation c.888G>A/p.Met296Ile /Exon 6 on the GAL gene.Her only other manifestation of FD was angiokeratoma. Eighteen females hadnonpathogenic intronic variations: c.-10C>T, c.-12G>A, or both. Two patients hadthe nonpathogenic mutation D313Y, while a third had the likely benign mutationS126G. Conclusions: FD was identified in 1 patient (.3%) in this first LatinAmerican study. The patient presented with a late-onset oligo-symptomatic formof the disease. A large number of nonpathogenic mutations were present in ourcohort, and it is essential that they not be mistaken for pathogenic mutations to avoid unnecessary enzyme replacement treatment.Fil: Reisin, Ricardo C.. Hospital Británico de Buenos Aires; ArgentinaFil: Mazziotti, Julieta. Hospital Británico de Buenos Aires; ArgentinaFil: León Cejas, Luciana. Hospital Británico de Buenos Aires; ArgentinaFil: Zinnerman, Alberto. Hospital Posadas; ArgentinaFil: Bonardo, Pablo. Hospital Británico de Buenos Aires; ArgentinaFil: Fernandez Pardal, M.. Hospital Británico de Buenos Aires; ArgentinaFil: Martinez, A.. Hospital Posadas; ArgentinaFil: Riccio, Patricia. Fundación Favaloro; ArgentinaFil: Ameriso, Sebastián. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Bendersky, Eduardo. INAREPS; ArgentinaFil: Nofal, Pedro. Sanatorio Parque Tucumán; ArgentinaFil: Cairola, Patricia. CEMIC; ArgentinaFil: Jure, Lorena. Sanatorio Parque Rosario; ArgentinaFil: Sotelo, Andrea. Sanatorio Adventista del Plata; ArgentinaFil: Rozenfeld, Paula Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; ArgentinaFil: Ceci, Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; ArgentinaFil: Casas Parera, Ignacio Faustino. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaFil: Sánchez Luceros, Analía Gabriela. Academia de Medicina; Argentin

Cancer immunotherapy with immunomodulatory anti-CD137 and anti-PD-1 monoclonal antibodies requires Batf3-dependent dendritic cells

Weak and ineffective antitumor cytotoxic T lymphocyte (CTL) responses can be rescued by immunomodulatory mAbs targeting PD-1 or CD137. Using Batf3−/− mice, which are defective for cross-presentation of cell-associated antigens, we show that BATF3-dependent dendritic cells (DC) are essential for the response to therapy with anti-CD137 or anti–PD-1 mAbs. Batf3−/− mice failed to prime an endogenous CTL-mediated immune response toward tumor-associated antigens, including neoantigens. As a result, the immunomodulatory mAbs could not amplify any therapeutically functional immune response in these mice. Moreover, administration of systemic sFLT3L and local poly-ICLC enhanced DC-mediated cross-priming and synergized with anti–CD137- and anti–PD-1–mediated immunostimulation in tumor therapy against B16-ovalbumin–derived melanomas, whereas this function was lost in Batf3−/− mice. These experiments show that cross-priming of tumor antigens by FLT3L- and BATF3-dependent DCs is crucial to the efficacy of immunostimulatory mAbs and represents a very attractive point of intervention to enhance their clinical antitumor effects

The Agrodiversity Experiment: three years of data from a multisite study in intensively managed grasslands

Intensively managed grasslands are globally prominent ecosystems. We investigated whether experimental increases in plant diversity in intensively managed grassland communities can increase their resource use efficiency. This work consisted of a coordinated, continental-scale 33-site experiment. The core design was 30 plots, representing 15 grassland communities at two seeding densities. The 15 communities were comprised of four monocultures (two grasses and two legumes) and 11 four-species mixtures that varied in the relative abundance of the four species at sowing. There were 1028 plots in the core experiment, with another 572 plots sown for additional treatments. Sites agreed a protocol and employed the same experimental methods with certain plot management factors, such as seeding rates and number of cuts, determined by local practice. The four species used at a site depended on geographical location, but the species were chosen according to four functional traits: a fast-establishing grass, a slow-establishing persistent grass, a fast-establishing legume, and a slow-establishing persistent legume. As the objective was to maximize yield for intensive grassland production, the species chosen were all high-yielding agronomic species. The data set contains species-specific biomass measurements (yield per species and of weeds) for all harvests for up to four years at 33 sites. Samples of harvested vegetation were also analyzed for forage quality at 26 sites. Analyses showed that the yield of the mixtures exceeded that of the average monoculture in >97% of comparisons. Mixture biomass also exceeded that of the best monoculture (transgressive overyielding) at about 60% of sites. There was also a positive relationship between the diversity of the communities and aboveground biomass that was consistent across sites and persisted for three years. Weed invasion in mixtures was very much less than that in monocultures. These data should be of interest to ecologists studying relationships between diversity and ecosystem function and to agronomists interested in sustainable intensification. The large spatial scale of the sites provides opportunity for analyses across spatial (and temporal) scales. The database can also complement existing databases and meta-analyses on biodiversity–ecosystem function relationships in natural communities by focusing on those same relationships within intensively managed agricultural grasslands

Prevalence of Fabry Disease in Young Patients with Stroke in Argentina

Background Fabry disease (FD) is an underdiagnosed cause of stroke in young adults, but the frequency of this association is largely unknown. We estimated the prevalence of FD in a nationwide cohort of young adults who had stroke and transient ischemic attack (TIA) in Argentina. Methods This was a prospective, multicenter study of stroke and FD in young adults (18-55 years) conducted in Argentina between 2011 and 2015. Patients were enrolled if they had had a TIA or an ischemic or hemorrhagic stroke within the previous 180 days. FD was diagnosed by measuring α-galactosidase A activity (males) and through genetic studies (females). Results We enrolled 311 patients (54% men, mean age: 41 years). Ischemic events occurred in 89% of patients (80% infarcts, 9% TIA) and hemorrhagic strokes in 11%. One female (.3% of the total group, 1% of the cryptogenic ischemic strokes) had the pathogenic mutation c.888G>A/p.Met296Ile /Exon 6 on the GAL gene. Her only other manifestation of FD was angiokeratoma. Eighteen females had nonpathogenic intronic variations: c.-10C>T, c.-12G>A, or both. Two patients had the nonpathogenic mutation D313Y, while a third had the likely benign mutation S126G. Conclusions FD was identified in 1 patient (.3%) in this first Latin American study. The patient presented with a late-onset oligo-symptomatic form of the disease. A large number of nonpathogenic mutations were present in our cohort, and it is essential that they not be mistaken for pathogenic mutations to avoid unnecessary enzyme replacement treatment.Instituto de Estudios Inmunológicos y Fisiopatológico

Weed suppression greatly increased by plant diversity in intensively managed grasslands: A continental-scale experiment

Publisher's version (útgefin grein)Grassland diversity can support sustainable intensification of grassland production through increased yields, reduced inputs and limited weed invasion. We report the effects of diversity on weed suppression from 3 years of a 31-site continental-scale field experiment. At each site, 15 grassland communities comprising four monocultures and 11 four-species mixtures based on a wide range of species' proportions were sown at two densities and managed by cutting. Forage species were selected according to two crossed functional traits, “method of nitrogen acquisition” and “pattern of temporal development”. Across sites, years and sown densities, annual weed biomass in mixtures and monocultures was 0.5 and 2.0 t DM ha−1 (7% and 33% of total biomass respectively). Over 95% of mixtures had weed biomass lower than the average of monocultures, and in two-thirds of cases, lower than in the most suppressive monoculture (transgressive suppression). Suppression was significantly transgressive for 58% of site-years. Transgressive suppression by mixtures was maintained across years, independent of site productivity. Based on models, average weed biomass in mixture over the whole experiment was 52% less (95% confidence interval: 30%–75%) than in the most suppressive monoculture. Transgressive suppression of weed biomass was significant at each year across all mixtures and for each mixture. Weed biomass was consistently low across all mixtures and years and was in some cases significantly but not largely different from that in the equiproportional mixture. The average variability (standard deviation) of annual weed biomass within a site was much lower for mixtures (0.42) than for monocultures (1.77). Synthesis and applications. Weed invasion can be diminished through a combination of forage species selected for complementarity and persistence traits in systems designed to reduce reliance on fertiliser nitrogen. In this study, effects of diversity on weed suppression were consistently strong across mixtures varying widely in species' proportions and over time. The level of weed biomass did not vary greatly across mixtures varying widely in proportions of sown species. These diversity benefits in intensively managed grasslands are relevant for the sustainable intensification of agriculture and, importantly, are achievable through practical farm-scale actions.We thank the many colleagues who have assisted this work. We thank M. Coll for her early contribution. Co-ordination of this project was supported by the EU Commission through COST Action 852 ‘Quality legume-based forage systems for contrasting environments’. M.T.S., R.L. and A.R. were supported by the Spanish Ministry of the Economy and Competitiveness through projects CARBOAGROPAS (CGL2006-13555- C03- 01/ BOS) and BIOGEI (CGL2013-49142- C2- 1- R) and the Ministry of the Environment through OPS (209/PC08/3-08.2). L.K. was supported by an award from Science Foundation Ireland (09/RFP/EOB2546). A.L., J.A.F., J.C. and M.S. were partly supported by the EU FP7 project ‘AnimalChange’ under grant agreement no. 266018.Peer Reviewe