Presence in a plant of a compound similar to the dolichyl diphosphate oligosaccharide of animal tissue

originalFil: Staneloni, Roberto Julio. Instituto de Investigaciones Bioquímicas Fundación Campomar; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Tolmasky, Marcelo E.. Instituto de Investigaciones Bioquímicas Fundación Campomar; ArgentinaFil: Petriella, Claudio. Instituto de Investigaciones Bioquímicas Fundación Campomar; ArgentinaFil: Ugalde, Rodolfo. Instituto de Investigaciones Bioquímicas Fundación Campomar; ArgentinaFil: Leloir, Luis Federico. Instituto de Investigaciones Bioquímicas Fundación Campomar; Argentinablanco y negro1 ejemplarLFL-PI-O-ART. Artículos científicosUnidad documental simpleAR-HYL-201

Late Miocene mammalian burrows in the Camacho Formation of Uruguay reveal a complex community of ecosystem engineers

We report fossil mammal burrows from backshore beach facies in the Camacho Formation of southern Uruguay, of Late Miocene (Huayquerian SALMA) age. The presence of desiccation cracks and rhizoliths indicate the occurrence of relatively extended periods of subaerial exposure and the incipient development of vegetation. The analysis of the burrows' spatial extent, size, and structure reveals the existence of exceptionally well-preserved and intercrossing tunnel systems. We show the existence of different size classes of burrows, which indicate that at least four different taxa were responsible for their construction. Considering the inferred body masses of the trace makers obtained from allometric relationships and the body masses of taxa recovered for the Camacho Formation, the burrows may have been produced by a combination of the following mammals: one of several rodents, notoungulates, cingulates, folivorans, and a carnivoran. The fossil association represents an exceptional case of a community of ecosystem engineers in the Late Miocene of southeastern South America.ANII: POS_NAC_2014_1_10237

Glucocerebrosidase is imported into mitochondria and preserves complex I integrity and energy metabolism

Mutations in GBA1, the gene encoding the lysosomal enzyme β-glucocerebrosidase (GCase), which cause Gaucher's disease, are the most frequent genetic risk factor for Parkinson's disease (PD). Here, we employ global proteomic and single-cell genomic approaches in stable cell lines as well as induced pluripotent stem cell (iPSC)-derived neurons and midbrain organoids to dissect the mechanisms underlying GCase-related neurodegeneration. We demonstrate that GCase can be imported from the cytosol into the mitochondria via recognition of internal mitochondrial targeting sequence-like signals. In mitochondria, GCase promotes the maintenance of mitochondrial complex I (CI) integrity and function. Furthermore, GCase interacts with the mitochondrial quality control proteins HSP60 and LONP1. Disease-associated mutations impair CI stability and function and enhance the interaction with the mitochondrial quality control machinery. These findings reveal a mitochondrial role of GCase and suggest that defective CI activity and energy metabolism may drive the pathogenesis of GCase-linked neurodegeneration

Reaction Rates Uncertainties and the Production of F19 in AGB Stars

We present nucleosynthesis calculations and the resulting 19F stellar yields for a large set of models with different masses and metallicity. We find that the production of fluorine depends on the temperature of the convective pulses, the amount of primary 12C mixed into the envelope by third dredge up and the extent of the partial mixing zone. Then we perform a detailed analysis of the reaction rates involved in the production of 19F and the effects of their uncertainties. We find that the major uncertainties are associated with the 14C(alpha,gamma)18O and the 19F(alpha,p)22Ne reaction rates. For these two reactions we present new estimates of the rates and their uncertainties. The importance of the partial mixing zone is reduced when using our estimate for the 14C(alpha,gamma)18O rate. Taking into account both the uncertainties related to the partial mixing zone and those related to nuclear reactions, the highest values of 19F enhancements observed in AGB stars are not matched by the models. This is a problem that will have to be revised by providing a better understanding of the formation and nucleosynthesis in the partial mixing zone, also in relation to reducing the uncertainties of the 14C(alpha,gamma)18O reaction rate. At the same time the possible effect of Cool Bottom Processing at the base of the convective envelope should be included in the computation of AGB nucleosynthesis. This process could in principle help matching the highest 19F abundances observed by decreasing the C/O ratio at the surface of the star, while leaving the 19F abundance unchanged.Comment: 40 pages, 8 figures, accepted for publication on the Astrophysical Journa

Desde el pacífico a la foresta tropical: redes de interacción social en el desierto de atacama durante el pleistoceno final

The social groups that initially inhabited the hyper arid core of the Atacama Desert of northern Chile during the late Pleistocene integrated a wide range of local, regional and supra regional goods and ideas for their social reproduction as suggested by the archaeological evidence contained in several open camps in Pampa del Tamarugal (PdT). Local resources for maintaining their every-day life, included stone raw material, wood, plant and animal fibers, game, and fresh water acquired within a radius of ∼30 km (ca. 1-2 days journey). At a regional scale, some goods were introduced from the Pacific coast (60-80 km to the west, ca. 3-4 days journey), including elongated rounded cobbles used as hammer stones in lithic production, and shells, especially from non-edible species of mollusks. From the Andes (ranging 80-150 km to the east, ca. 5-8 days of journey), they obtained camelid fiber, obsidian and a high-quality chalcedony, in addition to sharing knowledge on projectile point designs (Patapatane and Tuina type forms). Pieces of wood of a tropical forest tree species (Ceiba spp.) from the east Andean lowlands (600 km away, ca. 30 days of journey) were also brought to the PdT. While local goods were procured by the circulation of people within the PdT, the small number of foreign items would have been acquired through some sort of exchange networks that integrated dispersed local communities throughout several ecosystems. These networks may have been a key factor behind the success exhibited by these early huntergatherers in the hyper arid ecosystems of the Atacama Desert at the end of the Pleistocene. Different lines of archaeological evidence including open camps, workshop-quarries, lithic artifacts, archaeofaunal remains, plant and animal fibers and textiles, archaeobotanical remains, and paleoecological data show that people of the PdT managed a wide range of cultural items from the Pacific coast, the Andean highland and the tropical forest, that were integrated with resources gathered locally within the socio-cultural systems established by the end of the Pleistocene. These results are interpreted as material expressions of multi-scalar networking for resource management and other social material and immaterial requirements, which in other words, means that these people were actively connected to regional (coastal and highland), and supra-regional (trans-Andean) exchange networks from and out of the PdT.Los grupos sociales que inicialmente habitaban el núcleo hiperárido del Desierto de Atacama en el norte de Chile durante el Pleistoceno tardío integraron una amplia gama de bienes e ideas, locales, regionales y supra regionales, para su reproducción social, como lo sugieren las evidencias arqueológicas materiales recuperadas en varios campamentos al aire libre en Pampa del Tamarugal (PdT). Los recursos locales para mantener su vida diaria, incluían materias primas líticas, fibras de plantas y animales, presas de caza y agua dulce adquiridos en un radio de ̴30 km (ca. 1-2 días de viaje). A escala regional, se introdujeron algunos elementos desde la costa del Pacífico (60-80 km hacia el oeste, ca. 3 a 4 días de viaje), incluidos rodados redondeados alargados, utilizados como percutores en la producción lítica y conchas, especialmente de especies no comestibles de moluscos. Desde los Andes (80-150 km al este, ca. 5-8 días de viaje), obtuvieron fibra de camélido, obsidiana y una calcedonia de alta calidad, además de compartir conocimientos sobre diseños de puntas de proyectil (tipo Patapatane y Tuina). También se llevaron a la PdT trozos de madera de una especie de árbol de los bosques tropicales (Ceiba spp.) de las tierras bajas al este de los Andes (600 km de distancia, ca. 30 días de viaje). Mientras que los bienes locales fueron adquiridos por la circulación de personas dentro de la PdT, el pequeño número de artículos foráneos se adquirieron a través de redes de intercambio que integraron comunidades locales dispersas en varios ecosistemas; lo que debió ser un factor clave detrás del éxito demostrado por estos primeros cazadores-recolectores en los ecosistemas hiperáridos del Desierto de Atacama hacia el final del Pleistoceno. Diferentes líneas de evidencia arqueológica que incluyen campamentos al aire libre, talleres, canteras, artefactos líticos, restos arqueofaunales, fibras y textiles de plantas y animales, restos arqueobotánicos y datos paleoecológicos, muestran que la gente de la PdT manejaron una amplia gama de elementos culturales desde la costa del Pacífico, el altiplano andino y el bosque tropical, que se integraron a los recursos recolectados localmente dentro de los sistemas socioculturales establecidos al final del Pleistoceno. Estos resultados se interpretan como una expresión material de una red de múltiples escalas para la gestión de recursos y otros requisitos sociales e inmateriales, lo que en otras palabras, significaría que estos grupos sociales estaban conectados activamente con redes de interacción regionales (costa y tierras altas) y supra-regionales (transandinas) desde y hacia la PdT.Fil: Santoro, Calógero M.. Universidad de Tarapaca.; ChileFil: Gayo, Eugenia M.. Centro de Ciencia del Clima y la Resiliencia; Chile. Universidad de Concepción; ChileFil: Capriles Flores, Jose Mariano. State University of Pennsylvania; Estados UnidosFil: Rivadeneira Valenzuela, Marcelo Michel. Comisión Nacional de Investigación Científica y Tecnológica. Centro de Investigación Regional. Centro de Estudios en Zonas Áridas; Chile. Universidad Católica del Norte; Chile. Universidad de La Serena; ChileFil: Herrera, Katherine A.. Universite Paris Ouest Nanterre la Defense; Francia. Universidad de Tarapaca.; ChileFil: Mandakovic, Valentina. No especifíca;Fil: Rallo, Mónica. No especifíca;Fil: Rech, Jason A.. University of Miami; Estados UnidosFil: Cases, Bárbara. Universidad de Tarapaca.; ChileFil: Briones, Luis. Museo Municipalidad de Pica; ChileFil: Olguín, Laura. Universidad Católica del Norte, San Pedro de Atacama; ChileFil: Valenzuela, Daniela. Universidad de Tarapaca.; ChileFil: Borrero, Luis Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Saavedra 15. Instituto Multidisciplinario de Historia y Ciencias Humanas; ArgentinaFil: Ugalde, Paula C.. University of Arizona; Estados Unidos. Universidad de Tarapaca.; ChileFil: Rothhammer, Francisco. Universidad de Tarapaca.; ChileFil: Latorre, Claudio. Pontificia Universidad Católica de Chile; Chile. Instituto de Ecología y Biodiversidad; ChileFil: Szpak, Paul. Trent University; Canad

Dopamine receptor D3 expression is altered in CD4(+) T-cells from parkinson's disease patients and its pharmacologic inhibition attenuates the motor impairment in a mouse model

Neuroinflammation constitutes a fundamental process involved in Parkinson's disease (PD). Microglial cells play a central role in the outcome of neuroinflammation and consequent neurodegeneration of dopaminergic neurons in the substantia nigra. Current evidence indicates that CD4(+) T-cells infiltrate the brain in PD, where they play a critical role determining the functional phenotype of microglia, thus regulating the progression of the disease. We previously demonstrated that mice bearing dopamine receptor D3 (DRD3)-deficient CD4(+) T-cells are completely refractory to neuroinflammation and consequent neurodegeneration induced by the administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In this study we aimed to determine whether DRD3-signalling is altered in peripheral blood CD4(+) T-cells obtained from PD patients in comparison to healthy controls (HC). Furthermore, we evaluated the therapeutic potential of targeting DRD3 confined to CD4(+) T-cells by inducing the pharmacologic antagonism or the transcriptional inhibition of DRD3-signalling in a mouse model of PD induced by the chronic administration of MPTP and probenecid (MPTPp). In vitro analyses performed in human cells showed that the frequency of peripheral blood Th1 and Th17 cells, two phenotypes favoured by DRD3-signalling, were significantly increased in PD patients. Moreover, native CD4(+) T-cells obtained from PD patients displayed a significant higher Th1 -biased differentiation in comparison with those naive CD4(+) T-cells obtained from HC. Nevertheless, DRD3 expression was selectively reduced in CD4(+) T-cells obtained from PD patients. The results obtained from in vivo experiments performed in mice show that the transference of CD4(+) T-cells treated ex vivo with the DRD3-selective antagonist PG01037 into MPTPp-mice resulted in a significant reduction of motor impairment, although without significant effect in neurodegeneration. Conversely, the transference CD4(+) T-cells transduced ex vivo with retroviral pArtículos codifying for an shRNA for DRD3 into MPTPp-mice had no effects neither in motor impairment nor in neurodegeneration. Notably, the systemic antagonism of DRD3 significantly reduced both motor impairment and neurodegeneration in MPTPp mice. Our findings show a selective alteration of DRD3-signalling in CD4(+) T-cells from PD patients and indicate that the selective DRD3-antagonism in this subset of lymphocytes exerts a therapeutic effect in parkinsonian animals dampening motor impairment

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio