Institution
Fundación Instituto Leloir
Facility•Buenos Aires, Argentina•
About: Fundación Instituto Leloir is a facility organization based out in Buenos Aires, Argentina. It is known for research contribution in the topics: Dentate gyrus & Neurogenesis. The organization has 702 authors who have published 1052 publications receiving 39299 citations.
Topics: Dentate gyrus, Neurogenesis, RNA, Arabidopsis, Population
Papers published on a yearly basis
Papers
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TL;DR: In this article, a repurposed drug, carvedilol, was used to increase the accumulation of immature autophagosomes characterized by lower acidity and hydrolytic properties.
Abstract: T. cruzi, the causal agent of Chagas disease, is a parasite able to infect different types of host cells and to persist chronically in the tissues of human and animal hosts. These qualities and the lack of an effective treatment for the chronic stage of the disease have contributed to the durability and the spread of the disease around the world. There is an urgent necessity to find new therapies for Chagas disease. Drug repurposing is a promising and cost-saving strategy for finding new drugs for different illnesses. In this work we describe the effect of carvedilol on T. cruzi. This compound, selected by virtual screening, increased the accumulation of immature autophagosomes characterized by lower acidity and hydrolytic properties. As a consequence of this action, the survival of trypomastigotes and the replication of epimastigotes and amastigotes were impaired, resulting in a significant reduction of infection and parasite load. Furthermore, carvedilol reduced the whole-body parasite burden peak in infected mice. In summary, in this work we present a repurposed drug with a significant in vitro and in vivo activity against T. cruzi. These data in addition to other pharmacological properties make carvedilol an attractive lead for Chagas disease treatment.
5 citations
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TL;DR: The root hair cell walls contain polysaccharides and hydroxyproline-rich glycoproteins (HRGPs) including extensins (EXTs), which are secreted into the apoplastic space and are thought to trigger either cell wall loosening mediated by oxygen radical species, or polymerization of cell wall components including the Tyr-mediated assembly of an EXT network.
Abstract: Root hair cells acts at the root surface as important sensors of soil conditions. Root hairs are able to expand several hundred times their original size in a couple of hours to reach and uptake water-soluble nutrients. This fast and oscillating growth requires a continuous remodelling of the cell wall to allow for the root hair to expand in a tightly controlled manner. Root hair cell walls contain polysaccharides and hydroxyproline-rich glycoproteins (HRGPs) including extensins (EXTs). Class-III peroxidases (PRXs) are secreted into the apoplastic space and are thought to trigger either cell wall loosening mediated by oxygen radical species, or polymerization of cell wall components including the Tyr-mediated assembly of an EXT network (EXT-PRXs). The precise role of each of these EXT-PRXs remains to be discovered. By using genetic, biochemical and modeling approaches we have identified and characterized three root hair specific EXT-PRXs, PRX01, PRX44, and PRX73. The triple mutant prx01,44,73 as well as the overexpressors for PRX44 and PRX73 showed opposite effect on root hair growth, peroxidase activity, ROS-production, cell wall thickness, and Tyr-crosslinks in EXTs. These results suggest a key role of these three EXT-PRXs in the control of root hair growth linked to cell wall properties during polar cell expansion. Finally, modeling and docking calculations have suggested these three EXT-PRXs might be able to interact with non-O-glycosylated sections of EXT peptides that reduced Tyr-to-Tyr intra-chain distances in EXT aggregates and might enhance Tyr-crosslinks.
5 citations
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TL;DR: A model in which the occurrence of cysteine-rich positions is dictated by topological constrains is proposed, providing an explanation to why a degenerate pattern of cySteines can be achieved in a family of homologs.
Abstract: Redox regulation in biology is largely operated by cysteine chemistry in response to a variety of cell environmental and intracellular stimuli. The high chemical reactivity of cysteines determines their conservation in functional roles, but their presence can also result in harmful oxidation limiting their general use by proteins. Papillomaviruses constitute a unique system for studying protein sequence evolution since there are hundreds of anciently evolved stable genomes. E7, the viral transforming factor, is a dimeric, cysteine-rich oncoprotein that shows both conserved structural and variable regulatory cysteines constituting an excellent model for uncovering the mechanism that drives the acquisition of redox-sensitive groups. By analyzing over 300 E7 sequences, we found that although noncanonical cysteines show no obvious sequence conservation pattern, they are nonrandomly distributed based on topological constrains. Regulatory residues are strictly excluded from six positions stabilizing the hydrophobic core while they are enriched in key positions located at the dimerization interface or around the Zn+2 ion. Oxidation of regulatory cysteines is linked to dimer dissociation, acting as a reversible redox-sensing mechanism that triggers a conformational switch. Based on comparative sequence analysis, molecular dynamics simulations and biophysical analysis, we propose a model in which the occurrence of cysteine-rich positions is dictated by topological constrains, providing an explanation to why a degenerate pattern of cysteines can be achieved in a family of homologs. Thus, topological principles should enable the possibility to identify hidden regulatory cysteines that are not accurately detected using sequence based methodology.
5 citations
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TL;DR: Focusing on data obtained from Parkinson's disease patients, it is shown that iPSC‐derived neurons possess morphological and functional characteristics of this disease and a case is built for the use of this technology to study PD and other neuropathologies while disease is in progress.
5 citations
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TL;DR: The pathogenic bacterium Brucella abortus codes for a multi-domain dimeric cytoplasmic histidine kinase called LOV-HK, which is a key blue light-activated virulence factor in this microorganism and is activated by light and crystallized under a controlled illumination environment.
Abstract: The pathogenic bacterium Brucella abortus codes for a multi-domain dimeric cytoplasmic histidine kinase called LOV-HK, which is a key blue light-activated virulence factor in this microorganism. The structural basis of the light activation mechanism of this protein remains unclear. In this work, full-length LOV-HK was cloned, expressed and purified. The protein was activated by light and crystallized under a controlled illumination environment. The merge of 14 individual native data sets collected on a single crystal resulted in a complete X-ray diffraction data set to a resolution of 3.70 A with over 2 million reflections. Crystals belong to space group P212121, with unit-cell parameters a = 95.96, b = 105.30, c = 164.49 A with a dimer in the asymmetric unit. Molecular replacement with Phaser using the individual domains as search models allowed for the reconstruction of almost the whole protein. Very recently, improved LOV-HK crystals led to a 3.25-A resolution dataset. Refinement and model building is underway. This crystal model will represent one of the very few examples of a multi-domain histidine kinase with known structure.
5 citations
Authors
Showing all 707 results
Name | H-index | Papers | Citations |
---|---|---|---|
Jorge J. Casal | 61 | 182 | 10814 |
Silvia N.J. Moreno | 61 | 225 | 10585 |
Won Sang Park | 58 | 227 | 10501 |
Su Young Kim | 51 | 198 | 8829 |
Marcelo J. Yanovsky | 44 | 93 | 7949 |
Mario D. Galigniana | 40 | 99 | 5257 |
Eduardo M. Castaño | 40 | 89 | 7125 |
Andrea V. Gamarnik | 38 | 82 | 5896 |
Osvaldo L. Podhajcer | 35 | 122 | 4996 |
Alejandro F. Schinder | 34 | 64 | 10256 |
Juliana Idoyaga | 32 | 63 | 5326 |
Fernando Alberto Goldbaum | 32 | 103 | 3385 |
Fernando Juan Pitossi | 31 | 65 | 4489 |
Kevin Gaston | 29 | 78 | 2725 |
Jong Woo Lee | 29 | 77 | 3453 |