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.

Tumor Imaging with 99mTc-Labeled FC-5.01 Monoclonal Antibody Using a Single Step Labeling Method

Abstract: A lyophilized one-step kit of Mab FC-5.01, reactive with human breast cancer and malignant melanomas, was formulated. A direct method based on the reduction of protein disulphide bridges using 2-mercaptoethanol was used with methylene diphosphonate as the transchelating ligand. The labeled species were analyzed by ITLC thin layer chromatography and high performance liquid chromatography. Labeling efficiency was greater than 90%. Immunoreactivity was assessed on IIB-BR-G cells. 99mTc-labeled Mab FC-5.01 biodistribution and tumor imaging were performed in nude mice bearing IIB-BR-G breast cancer xenografts. At 24 hs accumulation of 99mTc increased in tumor and decreased in blood and most organs in agreement with results of an in vitro cysteine challenge assay. Quality control tests demonstrated that the kit was stable for up to 120 days. Animal studies demonstrated good and specific in vivo tumor targeting.

The molecular link between auxin and ROS-Mediated polar root hair growth

Abstract: Root hair polar growth is endogenously controlled by auxin and sustained by oscillating levels of reactive oxygen species (ROS). These cells extend several hundred-fold their original size toward signals important for plant survival. Although their final cell size is of fundamental importance, the molecular mechanisms that control it remain largely unknown. Here, we show that ROS production is controlled by the transcription factors RSL4, which in turn is transcriptionally regulated by auxin through several Auxin Responsive Factors (ARFs). In this manner, auxin controls ROS-mediated polar growth by activating RSL4, which then upregulates the expression of genes encoding NADPH oxidases (also known as RBOHs, RESPIRATORY BURST OXIDASE HOMOLOG proteins) and Class-III Peroxidases (PER), which catalyse ROS production. Chemical or genetic interference with the ROS balance or peroxidase activity affect root hair final cell size. Overall, our findings establish a molecular link between auxin regulated ARFs-RSL4 and ROS-mediated polar root hair growth. Significance Statement Tip-growing root hairs are excellent model systems to decipher the molecular mechanism underlying reactive oxygen species (ROS)-mediated cell elongation. Root hairs are able to expand in response to external signals, increasing several hundred-fold their original size, which is important for survival of the plant. Although their final cell size is of fundamental importance, the molecular mechanisms that control it remain largely unknown. In this study, we propose a molecular mechanism that links the auxin-Auxin Response Factors (ARFs) module to activation of RSL4, which directly targets genes encoding ROS-producing enzymes, such as NADPH oxidases (or RBOHs) and secreted type-III peroxidases (PERs). Activation of these genes impacts apoplastic ROS homeostasis, thereby stimulating root hair cell elongation.

Conformational Isomerization Involving Conserved Proline Residues Modulates Oligomerization of the NS1 Interferon Response Inhibitor from the Syncytial Respiratory Virus.

Abstract: Interferon response suppression by the respiratory syncytial virus relies on two unique nonstructural proteins, NS1 and NS2, that interact with cellular partners through high-order complexes. We hypothesized that two conserved proline residues, P81 and P67, participate in the conformational change leading to oligomerization. We found that the molecular dynamics of NS1 show a highly mobile C-terminal helix, which becomes rigid upon in silico replacement of P81. A soluble oligomerization pathway into regular spherical structures at low ionic strengths competes with an aggregation pathway at high ionic strengths with an increase in temperature. P81A requires higher temperatures to oligomerize and has a small positive effect on aggregation, while P67A is largely prone to aggregation. Chemical denaturation shows a first transition, involving a high fluorescence and ellipticity change corresponding to both a conformational change and substantial effects on the environment of its single tryptophan, that is stron...

Synaptogenesis in the adult CNS—Hippocampus

Abstract: The adult dentate gyrus generates granule cells that make thousands of new synapses in the preexisting circuitry. Synapses from GABAergic and glutamatergic neurons along the somatodendritic compartments of new cells develop at variable rates. GABAergic inputs are formed early but develop at slow speed, while glutamatergic inputs display late onset and rapid maturation. This asynchrony defines discrete functional stages with differential capacity for signal integration in new neurons. Glutamatergic excitation reaches sufficient strength to trigger spiking, while inhibitory GABA responses are still weak and immature, resulting in hyperactive cells with facilitated activity-dependent modification of excitatory synapses. The late maturation of GABAergic connections reduces excitability and defines the end of neuronal development. At the output level, synaptogenesis also displays distinct kinetics depending on the nature of the target neurons (principal cells or interneurons) and the region (hilus or CA3). All of these phenomena are modulated by activity, behavior, and the physiological status of the brain.