Granito Los Chilenos: Una nueva unidad granítica jurásica en Cerro Colorado, Sierras Australes de Buenos Aires. Implicancias tectónicas

Los Chilenos granite: a new Jurassic granite unit in Cerro Colorado, Sierras Australes de Buenos Aires. Tectonic implication. The Sierras Australes of Buenos Aires are located in the south-west corner of the Province about 100 km west of Bahia Blanca. On the south-west flank of these hills, younger Palaeozoic sedimentary formations overlie poorly exposed granitic and volcanic basement rocks. Granitic Cerro Colorado outcrops, located 16 km strike to the south of the town of San Martin de Tours, and near Lago Los Chilenos, have been included in this broadly interpreted "basement" in many previous geological studies. This contribution is mainly based on detailed structural mapping of the cerro Colorado area, and systematic sampling of granitic and sedimentary rocks for petrographical, microtectonic and Rb/Sr isotopic age analysis. In contrast to previous studies, two Phanerozoic granitic units have been recognised and mapped in the cerro Colorado area of Sierras Australes. The older one, the Cerro Colorado Granite (CC), is composed of foliated and sheared anisotropic granitic rocks with a Rb/Sr isochron age of 381±9 Ma (ir= 0.7035). The younger one, Los Chilenos Granite (LCh), consists of isotropic granophiric microgranite with a Rb/Sr isochron age of 140 ± 14 Ma (ir= 0.7126). This granite has intrusive contacts with both, the folded quartzite of the Mascota Formation and Cerro Colorado Granite (CC).The older tectomagmatic event (CC) is correlated with the compressive Chañica Orogeny, which was associated in the Sierras Australes region, with the eruption of La Mascota - La Hermita rhyolites (360±21 Ma) and the unconformity between Lolén Formation (Middle Devonian) and Sauce Grande Formation (Carboniferous).The younger intrusive event of Los Chilenos Granite (LCh) is considered to be associated with an extensional tectonic regime during the Late Jurassic initial rifting of the Atlantic Ocean. © 1999 Asociación Geológica Argentina.Fil:Massabie, A.C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Rossello, E.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Linares, E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Párica, C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina

Monoaryl derivatives as transthyretin fibril formation inhibitors: Design, synthesis, biological evaluation and structural analysis

Transthyretin (TTR) is a ß-sheet-rich homotetrameric protein that transports thyroxine (T4) and retinol both in plasma and in cerebrospinal fluid. TTR also interacts with amyloid-β, playing a protective role in Alzheimer's disease. Dissociation of the native transthyretin (TTR) tetramer is widely accepted as the critical step in TTR amyloids fibrillogenesis, and is responsible for extracellular deposition of amyloid fibrils. Small molecules, able to bind in T4 binding sites and stabilize the TTR tetramer, are interesting tools to treat and prevent systemic ATTR amyloidosis. We report here the synthesis, in vitro evaluation and three-dimensional crystallographic analyses of new monoaryl-derivatives in complex with TTR. Of the derivatives reported here, the best inhibitor of TTR fibrillogenesis, 1d, exhibits an activity similar to diflunisal

Antioxidant quercetin 3-O-glycosylated plant flavonols contribute to Transthyretin stabilization

Plants are rich in secondary metabolites, which are often useful as a relevant source of nutraceuticals. Quercetin (QUE) is a flavonol aglycone able to bind Transthyretin (TTR), a plasma protein that under pathological conditions can lose its native structure leading to fibrils formation and amyloid diseases onset. Here, the dual nature of five quercetin 3-O-glycosylated flavonol derivatives, isolated from different plant species, such as possible binders of TTR and antioxidants, was investigated. The crystal structure of 3-O-β-D-galactopyranoside in complex with TTR was solved, suggesting that not only quercetin but also its metabolites can contribute to stabilizing the TTR tetramer

Activation of carbonic anhydrases from human brain by amino alcohol oxime ethers: towards human carbonic anhydrase VII selective activators

The synthesis and carbonic anhydrase (CA; EC 4.2.1.1) activating effects of a series of oxime ether-based amino alcohols towards four human (h) CA isoforms expressed in human brain, hCA I, II, IV and VII, are described. Most investigated amino alcohol derivatives induced a consistent activation of the tested CAs, with KAs spanning from a low micromolar to a medium nanomolar range. Specifically, hCA II and VII, putative main CA targets when central nervous system (CNS) diseases are concerned, were most efficiently activated by these oxime ether derivatives. Furthermore, a multitude of selective hCA VII activators were identified. As hCA VII is one of the key isoforms involved in brain metabolism and other brain functions, the identified potent and selective hCA VII activators may be considered of interest for investigations of various therapeutic applications or as lead compounds in search of even more potent and selective CA activators

The metalloproteinase ADAM10 requires its activity to sustain surface expression

The metalloproteinase ADAM10 critically contributes to development, inflammation, and cancer and can be controlled by endogenous or synthetic inhibitors. Here, we demonstrate for the first time that loss of proteolytic activity of ADAM10 by either inhibition or loss of function mutations induces removal of the protease from the cell surface and the whole cell. This process is temperature dependent, restricted to mature ADAM10, and associated with an increased internalization, lysosomal degradation, and release of mature ADAM10 in extracellular vesicles. Recovery from this depletion requires de novo synthesis. Functionally, this is reflected by loss and recovery of ADAM10 substrate shedding. Finally, ADAM10 inhibition in mice reduces systemic ADAM10 levels in different tissues. Thus, ADAM10 activity is critically required for its surface expression in vitro and in vivo. These findings are crucial for development of therapeutic ADAM10 inhibition strategies and may showcase a novel, physiologically relevant mechanism of protease removal due to activity loss

Identification of a Novel p53 Modulator Endowed with Antitumoural and Antibacterial Activity through a Scaffold Repurposing Approach

Intracellular pathogens, such as Chlamydia trachomatis, have been recently shown to induce degradation of p53 during infection, thus impairing the protective response of the host cells. Therefore, p53 reactivation by disruption of the p53-MDM2 complex could reduce infection and restore pro-apoptotic effect of p53. Here, we report the identification of a novel MDM2 inhibitor with potential antitumoural and antibacterial activity able to reactivate p53. A virtual screening was performed on an in-house chemical library, previously synthesised for other targets, and led to the identification of a hit compound with a benzo[a]dihydrocarbazole structure, RM37. This compound induced p53 up-regulation in U343MG glioblastoma cells by blocking MDM2-p53 interaction and reduced tumour cell growth. NMR studies confirmed its ability to dissociate the MDM2-p53 complex. Notably, RM37 reduced Chlamydia infection in HeLa cells in a concentration-dependent manner and ameliorated the inflammatory status associated with infection

Value, but high costs in post-deposition data Curation

© The Author(s) 2016. Published by Oxford University Press. Discoverability of sequence data in primary data archives is proportional to the richness of contextual information associated with the data. Here, we describe an exercise in the improvement of contextual information surrounding sample records associated with metagenomics sequence reads available in the European Nucleotide Archive. We outline the annotation process and summarize findings of this effort aimed at increasing usability of publicly available environmental data. Furthermore, we emphasize the benefits of such an exercise and detail its costs. We conclude that such a third party annotation approach is expensive and has value as an element of curation, but should form only part of a more sustainable submitter-driven approach

Value, but high costs in post-deposition data curation

Discoverability of sequence data in primary data archives is proportional to the richness of contextual information associated with the data. Here, we describe an exercise in the improvement of contextual information surrounding sample records associated with metagenomics sequence reads available in the European Nucleotide Archive. We outline the annotation process and summarize findings of this effort aimed at increasing usability of publicly available environmental data. Furthermore, we emphasize the benefits of such an exercise and detail its costs. We conclude that such a third party annotation approach is expensive and has value as an element of curation, but should form only part of a more sustainable submitter-driven approach

Accelerating surveillance and research of antimicrobial resistance - an online repository for sharing of antimicrobial susceptibility data associated with whole-genome sequences

Antimicrobial resistance (AMR) is an emerging threat to modern medicine. Improved diagnostics and surveillance of resistant bacteria require the development of next-generation analysis tools and collabor