Human Frataxin Folds Via an Intermediate State. Role of the C-Terminal Region

The aim of this study is to investigate the folding reaction of human frataxin, whose deficiency causes the neurodegenerative disease Friedreich’s Ataxia (FRDA). The characterization of different conformational states would provide knowledge about how frataxin can be stabilized without altering its functionality. Wild-type human frataxin and a set of mutants, including two highly destabilized FRDA-associated variants were studied by urea-induced folding/unfolding in a rapid mixing device and followed by circular dichroism. The analysis clearly indicates the existence of an intermediate state (I) in the folding route with significant secondary structure content but relatively low compactness, compared with the native ensemble. However, at high NaCl concentrations I-state gains substantial compaction, and the unfolding barrier is strongly affected, revealing the importance of electrostatics in the folding mechanism. The role of the C-terminal region (CTR), the key determinant of frataxin stability, was also studied. Simulations consistently with experiments revealed that this stretch is essentially unstructured, in the most compact transition state ensemble (TSE2). The complete truncation of the CTR drastically destabilizes the native state without altering TSE2. Results presented here shed light on the folding mechanism of frataxin, opening the possibility of mutating it to generate hyperstable variants without altering their folding kinetics.Fil: Faraj, Santiago Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Gonzalez-Lebrero, Rodolfo Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Roman, Ernesto Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Santos, Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentin

Disseminação de Campylobacter entre cães vadios e de estimação

The natural distribution of thermotolerant Campylobacter sp. in dogs (150 stray animals and 64 pets) was studied. Campylobacters were more frequently isolated (pFoi estudada a distribuição natural de espécies termotolerantes de Campylobacter em 159 cães vadios e em 64 cães de companhia em confinamento permanente. Espécies de Campylobacter foram isoladas mais freqüentemente (

Proton helicity structure function g_1^p from a holographic Pomeron

We present a detailed analysis of the polarized and the unpolarized deep inelastic scattering structure functions of the proton, g_1^p and F_2^p respectively, in the context of a holographic dual description based on type IIB superstring theory. We compare this description with experimental data and Quantum Chromodynamics estimates computed at leading, next-to-leading and next-to-next-to-leading order in perturbation. We confront the predictions of a holographic dual model and those of perturbative QCD for g_1^p at the kinematics that will be probed by the forthcoming Electron-Ion Collider. We find that the extrapolation of g_1^p to very small values the Bjorken variable computed with a Holographic Pomeron model based on actual data at higher momentum fractions is always positive and differs significantly with standard projections based on perturbative QCD.Comment: 34 pages, 3 figure

Diferenciación social, jerarquías y comparatismo: apuntes para una reflexión teórica en perspectiva antropológica

Este trabajo tiene por objetivo esbozar una reflexión teórica en torno a un campo de problemas construido alrededor de la diferenciación social, las estructuras jerárquicas y la perspectiva comparativa. Para ello haremos referencias a la perspectiva teórica y la estrategia comparatista esbozadas en dos obras centrales de la tradición clásica de la antropología: Sistemas políticos de la Alta Birmania de Edmund Leach y Homo Hierarchicus. Ensayo sobre el sistema de castas10 (en adelante H.h.) de Louis Dumont.Fil: Iuliano, Rodolfo Martin. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Humanidades y Ciencias de la Educación; Argentina. Universidad Nacional de San Martín; Argentin