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Institution

Fundación Instituto Leloir

FacilityBuenos 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.


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Journal ArticleDOI
TL;DR: In this article, the authors report the emergency development and application of a robust serologic test to evaluate acute and convalescent antibody responses to SARS-CoV-2 in Argentina.
Abstract: We report the emergency development and application of a robust serologic test to evaluate acute and convalescent antibody responses to SARS-CoV-2 in Argentina. The assays, COVIDAR IgG and IgM, which were produced and provided for free to health authorities, private and public health institutions and nursing homes, use a combination of a trimer stabilized spike protein and the receptor binding domain (RBD) in a single enzyme-linked immunosorbent assay (ELISA) plate. Over half million tests have already been distributed to detect and quantify antibodies for multiple purposes, including assessment of immune responses in hospitalized patients and large seroprevalence studies in neighborhoods, slums and health care workers, which resulted in a powerful tool for asymptomatic detection and policy making in the country. Analysis of antibody levels and longitudinal studies of symptomatic and asymptomatic SARS-CoV-2 infections in over one thousand patient samples provided insightful information about IgM and IgG seroconversion time and kinetics, and IgM waning profiles. At least 35% of patients showed seroconversion within 7 days, and 95% within 45 days of symptoms onset, with simultaneous or close sequential IgM and IgG detection. Longitudinal studies of asymptomatic cases showed a wide range of antibody responses with median levels below those observed in symptomatic patients. Regarding convalescent plasma applications, a protocol was standardized for the assessment of end point IgG antibody titers with COVIDAR with more than 500 plasma donors. The protocol showed a positive correlation with neutralizing antibody titers, and was used for clinical trials and therapies across the country. Using this protocol, about 80% of convalescent donor plasmas were potentially suitable for therapies. Here, we demonstrate the importance of providing a robust and specific serologic assay for generating new information about antibody kinetics in infected individuals and mitigation policies to cope with pandemic needs.

56 citations

Journal ArticleDOI
TL;DR: The results show that a lack of UGGT activity alters plant vegetative development and impairs the response to several abiotic and biotic stresses, and uncover an unexpected role of U GGT in the incorporation of UDP-Glucose into the ER lumen in Arabidopsis thaliana.
Abstract: UDP-glucose: glycoprotein glucosyltransferase (UGGT) is a key player in the quality control mechanism (ER-QC) that newly synthesized glycoproteins undergo in the ER. It has been shown that the UGGT Arabidopsis orthologue is involved in ER-QC; however, its role in plant physiology remains unclear. Here, we show that two mutant alleles in the At1g71220 locus have none or reduced UGGT activity. In wild type plants, the AtUGGT transcript levels increased upon activation of the unfolded protein response (UPR). Interestingly, mutants in AtUGGT exhibited an endogenous up–regulation of genes that are UPR targets. In addition, mutants in AtUGGT showed a 30 % reduction in the incorporation of UDP-Glucose into the ER suggesting that this enzyme drives the uptake of this substrate for the CNX/CRT cycle. Plants deficient in UGGT exhibited a delayed growth rate of the primary root and rosette as well as an alteration in the number of leaves. These mutants are more sensitive to pathogen attack as well as heat, salt, and UPR-inducing stressors. Additionally, the plants showed impairment in the establishment of systemic acquired resistance (SAR). These results show that a lack of UGGT activity alters plant vegetative development and impairs the response to several abiotic and biotic stresses. Moreover, our results uncover an unexpected role of UGGT in the incorporation of UDP-Glucose into the ER lumen in Arabidopsis thaliana.

56 citations

Journal ArticleDOI
TL;DR: The data suggest a role of hippocampal TGF-β1 and early-life neuroinflammation in the development of the behavioral alterations observed in autism spectrum disorders, and show a central role in the programming and modulation of social interaction, repetitive behavior and depression-related behavior.
Abstract: TGF-β1 is an anti-inflammatory cytokine that is augmented in the brain of autistic patients and that can affect brain development. In this work, we studied the effects of overexpressing TGF-β1 in the dentate gyrus of adult or young mice on behavior. TGF-β1 overexpression during postnatal development led to a long-term decrease in social interaction and to long-term increases in self-grooming and depression-related behaviors. Our analysis shows that these behavioral changes correlate with the long-term downregulation of TGF-β1 and IL-6 expression in the dentate gyrus, as well as to decreases in the mRNA levels of the synaptic protein neuroligin 3 and in the number of Reelin-positive neurons in the dentate gyrus. In contrast, chronic expression of TGF-β1 during adulthood led to transient opposite effects on these behaviors. These results show a central role of hippocampal TGF-β1 in the programming and modulation of social interaction, repetitive behavior and depression-related behavior. Finally, our data suggest a role of hippocampal TGF-β1 and early-life neuroinflammation in the development of the behavioral alterations observed in autism spectrum disorders.

56 citations

Journal ArticleDOI
TL;DR: Twenty-two CD38-specific nanobody families were identified using phage display technology from immunized llamas to represent highly specific tools for modulating the enzymatic activity of CD38 and for diagnostic monitoringCD38-expressing tumors.
Abstract: The cell surface ecto-enzyme CD38 is a promising target antigen for the treatment of hematological malignancies, as illustrated by the recent approval of daratumumab for the treatment of multiple myeloma. Our aim was to evaluate the potential of CD38-specific nanobodies as novel diagnostics for hematological malignancies. We successfully identified 22 CD38-specific nanobody families using phage display technology from immunized llamas. Crossblockade analyses and in-tandem epitope binning revealed that the nanobodies recognize three different non-overlapping epitopes, with four nanobody families binding complementary to daratumumab. Three nanobody families inhibit the enzymatic activity of CD38 in vitro, while two others were found to act as enhancers. In vivo, fluorochrome-conjugated CD38 nanobodies efficiently reach CD38 expressing tumors in a rodent model within 2 hours after intravenous injection, thereby allowing for convenient same day in vivo tumor imaging. These nanobodies represent highly specific tools for modulating the enzymatic activity of CD38 and for diagnostic monitoring CD38-expressing tumors.

56 citations

Journal ArticleDOI
TL;DR: It is shown that subtle structural changes within the circadian network are responsible for behavioral arrhythmicity, and disrupted PDF signaling by slo dysfunction directly affects the structure of the underlying circuit.
Abstract: Substantial progress has been made in elucidating the molecular processes that impart a temporal control to physiology and behavior in most eukaryotes. In Drosophila, dorsal and ventral neuronal networks act in concert to convey rhythmicity. Recently, the hierarchical organization among the different circadian clusters has been addressed, but how molecular oscillations translate into rhythmic behavior remains unclear. The small ventral lateral neurons can synchronize certain dorsal oscillators likely through the release of pigment dispersing factor (PDF), a neuropeptide central to the control of rhythmic rest-activity cycles. In the present study, we have taken advantage of flies exhibiting a distinctive arrhythmic phenotype due to mutation of the potassium channel slowpoke (slo) to examine the relevance of specific neuronal populations involved in the circadian control of behavior. We show that altered neuronal function associated with the null mutation specifically impaired PDF accumulation in the dorsal protocerebrum and, in turn, desynchronized molecular oscillations in the dorsal clusters. However, molecular oscillations in the small ventral lateral neurons are properly running in the null mutant, indicating that slo is acting downstream of these core pacemaker cells, most likely in the output pathway. Surprisingly, disrupted PDF signaling by slo dysfunction directly affects the structure of the underlying circuit. Our observations demonstrate that subtle structural changes within the circadian network are responsible for behavioral arrhythmicity.

56 citations


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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
202210
2021107
202099
201986
201865
201781