Fundación Instituto Leloir

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.

Deciphering New Players in the Neurogenic Adult Hippocampal Niche.

Abstract: In the mammalian adult hippocampus, new neurons are continuously generated throughout life in the subgranular zone of the dentate gyrus. Increasing evidence point out the contribution of adult-born hippocampal granule cells (GCs) to cognitive processes such as learning and memory, indicating the relevance of understanding the molecular mechanisms that control the development of these new neurons in the preexisting hippocampal circuits. Cell proliferation and functional integration of adult-born GCs is a process highly regulated by different intrinsic and extrinsic factors. In this review, we discuss recent advances related with cellular components and extrinsic signals of the hippocampal neurogenic niche that support and modulate neurogenesis under physiological conditions.

Characterization of a double-CRD-mutated Gal-8 recombinant protein that retains co-stimulatory activity on antigen-specific T-cell response.

Abstract: Galectins (Gals) constitute a family of mammalian lectins with affinity for β-galactosides, characterized by the presence of conserved CRDs (carbohydrate-recognition domains). We have found previously that Gal-8, from the tandem-repeat group with two linked CRDs, exerts two separate actions on CD4 + T-cells: antigen-independent proliferation and, at lower concentration, antigen-specific co-stimulation. Whereas proliferation can be ascribed to the pro-inflammatory role of Gal-8, the co-stimulatory activity of borderline T-cell-specific responses allows the proposal of Gal-8 as an adjuvant in vaccination. To study the relevance of glycan–lectin interaction to these T-cell activities, we generated a double-mutated protein (Gal-8mut) by replacing canonical arginine residues on each CRD, so as to abolish sugar-binding capacity. As expected, Gal-8mut was unable to bind to lactosyl-Sepharose, confirming that lactose recognition was precluded; however, preservation of lectin activity was still evident since Gal-8mut displayed haemoagglutinatory effects and binding capacity to the T-cell surface. To search for glycan affinity, a glycan microarray analysis was conducted which revealed that Gal-8mut lost most low- and intermediate-, but retained high-, affinity interactions, mainly to polylactosamines and blood group antigens. These findings were supported further by molecular modelling. Regarding biological activity, Gal-8mut was unable to induce T-cell proliferation, but efficiently co-stimulated antigen-specific responses, both in vitro and in vivo. Therefore Gal-8mut represents a useful tool to dissect the specificities of lectin–glycan interactions underlying distinctive Gal-8 activities on T-cell biology. Moreover, given its distinguishing properties, Gal-8mut could be used to enhance borderline immune responses without the non-specific pro-inflammatory activity or other potential adverse effects.

A genetic toolkit for the analysis of metabolic changes in Drosophila provides new insights into metabolic responses to stress and malignant transformation.

Abstract: Regulation of the energetic metabolism occurs fundamentally at the cellular level, so analytical strategies must aim to attain single cell resolution to fully embrace its inherent complexity. We have developed methods to utilize a toolset of metabolic FRET sensors for assessing lactate, pyruvate and 2-oxoglutarate levels of Drosophila tissues in vivo by imaging techniques. We show here how the energetic metabolism is altered by hypoxia: While some larval tissues respond to low oxygen levels by executing a metabolic switch towards lactic fermentation, the fat body and salivary glands do not alter their energetic metabolism. Analysis of tumor metabolism revealed that depending on the genetic background, some tumors undergo a lactogenic switch typical of the Warburg effect, while other tumors do not. This toolset allows for developmental and physiologic studies in genetically manipulated Drosophila individuals in vivo.

Cortical and meningeal pathology in progressive multiple sclerosis: a new therapeutic target?

Abstract: Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease that involves an intricate interaction between the central nervous system and the immune system. Nevertheless, its etiology is still unknown. MS exhibits different clinical courses: recurrent episodes with remission periods ('relapsing-remitting') that can evolve to a 'secondary progressive' form or persistent progression from the onset of the disease ('primary progressive'). The discovery of an effective treatment and cure has been hampered due to the pathological and clinical heterogeneity of the disease. Historically, MS has been considered as a disease exclusively of white matter. However, patients with progressive forms of MS present with cortical lesions associated with meningeal inflammation along with physical and cognitive disabilities. The pathogenesis of the cortical lesions has not yet been fully described. Animal models that represent both the cortical and meningeal pathologies will be critical in addressing MS pathogenesis as well as the design of specific treatments. In this review, we will address the state-of-the-art diagnostic and therapeutic alternatives and the development of strategies to discover new therapeutic approaches, especially for the progressive forms.