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.

Clinical and Genetic Spectrum of Stargardt Disease in Argentinean Patients

Abstract: Purpose: To describe the clinical and molecular spectrum of Stargardt disease (STGD) in a cohort of Argentinean patients Methods: This retrospective study included 132 subjects comprising 95 probands clinically diagnosed with STGD and relatives from 16 of them. Targeted next-generation sequencing of the coding and splicing regions of ABCA4 and other phenocopying genes (ELOVL4, PROM1, and CNGB3) was performed in 97 STGD patients. Results: We found two or more disease-causing variants in the ABCA4 gene in 69/95 (73%) probands, a single ABCA4 variant in 9/95 (9.5%) probands, and no ABCA4 variants in 17/95 (18%) probands. The final analysis identified 173 variants in ABCA4. Seventy-nine ABCA4 variants were unique, of which nine were novel. No significant findings were seen in the other evaluated genes. Conclusion: This study describes the phenotypic and genetic features of STGD1 in an Argentinean cohort. The mutations p.(Gly1961Glu) and p.(Arg1129Leu) were the most frequent, representing almost 20% of the mutated alleles. We also expanded the ABCA4 mutational spectrum with nine novel disease-causing variants, of which eight might be associated with South American natives.

The structure of the extended E2 DNA-binding domain of the bovine papillomavirus-1.

Abstract: Bovine papillomavirus proteins were extensively studied as a prototype for the human papillomavirus. Here, the crystal structure of the extended E2 DNA-binding domain of the dominant transcription regulator from the bovine papillomavirus strain 1 is described in the space group P31 21. We found two protein functional dimers packed in the asymmetric unit. This new protein arrangement inside the crystal led to the reduction of the mobility of a previously unobserved loop directly involved in the protein-DNA interaction, which was then modeled for the first time.

Luis Federico Leloir, or how to do good science in a hostile environment

Abstract: EARLY YEARS: TRAINING IN MEDICINE AND BIOCHEMISTRY Luis Federico Leloir was born in one of Paris’ most upscale neighborhoods (81, Avenue Victor Hugo, a few blocks away from the Arc de Triomphe) on September 6, 1906. According to his own account, his ancestors immigrated to Argentina during the colonial period, coming mostly from southwestern France (Oloron-Sainte Marie, in the Béarn region) and northeastern Spain (Basque Country). Argentine land at the time was inexpensive because of the constant threat of attacks by natives, so the newly arrived went on to buy extensive farms. In time, these would become the lands where the early pioneers would grow the grain and raise cattle that would bring the country wealth and prosperity. Such circumstances allowed Leloir an early dedication to research. At that time, it was very difficult (if not impossible) to get a full time position in Argentina. The reasons for his family moving to Paris are quite sad: Leloir’s father was terminally ill, and the Leloirs were in France in search for a cure. Unfortunately, Leloir Sr. passed away before his son was born. His mother brought him back to Buenos Aires 2 years later and sent him to private schools before he finally enrolled in the School of Medicine of the University of Buenos Aires (UBA). Leloir eventually got his M.D. degree in 1932 and practiced medicine at the university’s Hospital. It was not long before he approached the head of the School of Medicine’s Institute of Physiology, Bernardo Houssay, to start working on his doctoral thesis. Houssay had achieved significant results studying the role of the hypophysis gland in sugar metabolism—results that would earn him the Nobel Prize in Physiology or Medicine in 1947, together with Carl Ferdinand and Gerty Theresa Cori. Leloir and Houssay became friends, a relationship that would last until the latter’s death in 1971. Leloir’s thesis (Adrenal Glands and Carbohydrates) got the Thesis of the Year Award in 1934. Taking notice of his own shortcomings in sciences considered ‘‘harder’’ than Medicine, Leloir went on to take several doctorate-level Chemistry courses at UBA’s School of Sciences. Although he never completed the Ph.D. program for Chemistry, Houssay and other colleagues encouraged him to get further training. Leloir would soon move to Cambridge University (U.K.) to deepen his studies in Biochemistry with Sir Frederick Gowland Hopkins, 1929 Nobel Prize for Physiology or Medicine.

The C-terminal extension of chloroplast 2-Cys peroxiredoxin is critical for interaction with ATP.

Abstract: 2-Cys peroxiredoxins (2-Cys Prxs) are ubiquitous enzymes that have been implicated in peroxide-mediated signaling of markedly different processes, such as cancer and photosynthesis. A highly conserved C-terminal extension of eukaryotic homologues modulates both the overoxidation of cysteines and the formation of oligomers. Here, we reveal that the plant counterpart regulates the self-polymerization of 2-Cys Prx triggered by ATP and Mg2+. This feature is of particular importance under oxidative stress because the interaction of ATP with 2-Cys Prx rapidly integrates nonredox chemistry of signaling pathways into a network hub governed by multiple redox transformations at cysteine residues.

Auxin–Environment Integration in Growth Responses to Forage for Resources

Abstract: Plant fitness depends on the adequate morphological adjustment to the prevailing conditions of the environment. Therefore, plants sense environmental cues through their life cycle, including the presence of full darkness, light, or shade, the range of ambient temperatures, the direction of light and gravity vectors, and the presence of water and mineral nutrients (such as nitrate and phosphate) in the soil. The environmental information impinges on different aspects of the auxin system such as auxin synthesis, degradation, transport, perception, and downstream transcriptional regulation to modulate organ growth. Although a single environmental cue can affect several of these points, the relative impacts differ significantly among the various growth processes and cues. While stability in the generation of precise auxin gradients serves to guide the basic developmental pattern, dynamic changes in the auxin system fine-tune body shape to optimize the capture of environmental resources.