Native CuA Redox Sites are Largely Resilient to pH Variations within Physiological Range

Previous studies on engineered CuA centres have shown that one of the histidine ligands is protonated and dissociated from the metal site at physiological pH values, thus suggesting a role in regulating proton-coupled electron transfer of cytochrome c oxidases in vivo. Here we report that for native CuA such protonation does not take place at physiologically relevant pH values and, furthermore, no significant changes in the spectroscopic and redox properties of the metal site occur at low pH.Fil: Álvarez Paggi, Damián Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de Los Materiales, Medioambiente y Energía; ArgentinaFil: Abriata, Luciano Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Murgida, Daniel Horacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de Los Materiales, Medioambiente y Energía; ArgentinaFil: Vila, Alejandro Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Biología Molecular y Celular de Rosario; Argentin

Identifying pathophysiological bases of disease in COVID-19

COVID-19 is an infectious disease caused by the SARS-CoV-2 virus that can affect lung physiology encompassing a wide spectrum of severities, ranging from asymptomatic and mild symptoms to severe and fatal cases; the latter including massive neutrophil infiltration, stroke and multiple organ failure. Despite many recents findings, a clear mechanistic description underlying symptomatology is lacking. In this article, we thoroughly review the available data involving risk factors, age, gender, comorbidities, symptoms of disease, cellular and molecular mechanisms and the details behind host/pathogen interaction that hints at the existence of different pathophysiological mechanisms of disease. There is clear evidence that, by targeting the angiotensin-converting enzyme II (ACE2) –its natural receptor–, SARS-CoV-2 would mainly affect the reninangiotensin-aldosterone system (RAAS), whose imbalance triggers diverse symptomatology-associated pathological processes. Downstream actors of the RAAS cascade are identified, and their interaction with risk factors and comorbidities are presented, rationalizing why a specific subgroup of individuals that present already lower ACE2 levels is particularly more susceptible to severe forms of disease. Finally, the notion of endotype discovery in the context of COVID-19 is introduced. We hypothesize that COVID-19, and its associated spectrum of severities, is an umbrella term covering different pathophysiological mechanisms (endotypes). This approach should dramatically accelerate our understanding and treatment of disease(s), enabling further discovery of pathophysiological mechanisms and leading to the identification of specific groups of patients that may benefit from personalized treatments.Fil: Goldin, Carla Jimena. Fundación para la Investigación en Infectología Infantil; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Vázquez, Ramiro José. Fondazione Istituto Italiano di Tecnologia; Italia. Early Drug Development Group; FranciaFil: Polack, Fernando Pedro. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Álvarez Paggi, Damián Jorge. Fundación para la Investigación en Infectología Infantil; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

The alkaline transition of cytochrome c revisited: Effects of electrostatic interactions and tyrosine nitration on the reaction dynamics

Here we investigated the effect of electrostatic interactions and of protein tyrosine nitration of mammalian cytochrome c on the dynamics of the so-called alkaline transition, a pH- and redox-triggered conformational change that implies replacement of the axial ligand Met80 by a Lys residue. Using a combination of electrochemical, time-resolved SERR spectroelectrochemical experiments and molecular dynamics simulations we showed that in all cases the reaction can be described in terms of a two steps minimal reaction mechanism consisting of deprotonation of a triggering group followed by ligand exchange. The pK a alk values of the transition are strongly modulated by these perturbations, with a drastic downshift upon nitration and an important upshift upon establishing electrostatic interactions with a negatively charged model surface. The value of pK a alk is determined by the interplay between the acidity of a triggering group and the kinetic constants for the forward and backward ligand exchange processes. Nitration of Tyr74 results in a change of the triggering group from Lys73 in WT Cyt to Tyr74 in the nitrated protein, which dominates the pK a alk downshift towards physiological values. Electrostatic interactions, on the other hand, result in strong acceleration of the backward ligand exchange reaction, which dominates the pK a alk upshift. The different physicochemical conditions found here to influence pK a alk are expected to vary depending on cellular conditions and subcellular localization of the protein, thus determining the existence of alternative conformations of Cyt in vivo.Fil: Oviedo Rouco, Santiago. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; ArgentinaFil: Castro, Maria Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; ArgentinaFil: Álvarez Paggi, Damián Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; ArgentinaFil: Spedalieri, Ana Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; ArgentinaFil: Tortora, Verónica. Universidad de la República; UruguayFil: Tomasina, Florencia. Universidad de la República; UruguayFil: Radi, Rafael. Universidad de la República; UruguayFil: Murgida, Daniel Horacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentin

Manganese porphyrin redox state in endothelial cells: Resonance Raman studies and implications for antioxidant protection towards peroxynitrite

Cationic manganese(III) ortho N-substituted pyridylporphyrins (MnP) act as efficient antioxidants catalyzing superoxide dismutation and accelerating peroxynitrite reduction. Importantly, MnP can reach mitochondria offering protection against reactive species in different animal models of disease. Although an LC-MS/MS-based method for MnP quantitation and subcellular distribution has been reported, a direct method capable of evaluating both the uptake and the redox state of MnP in living cells has not yet been developed. In the present work we applied resonance Raman (RR) spectroscopy to analyze the intracellular accumulation of two potent MnP-based lipophilic SOD mimics, MnTnBuOE-2-PyP5+ and MnTnHex-2-PyP5+ within endothelial cells. RR experiments with isolated mitochondria revealed that the reduction of Mn(III)P was affected by inhibitors of the electron transport chain, supporting the action of MnP as efficient redox active compounds in mitochondria. Indeed, RR spectra confirmed that MnP added in the Mn(III) state can be incorporated into the cells, readily reduced by intracellular components to the Mn(II) state and oxidized by peroxynitrite. To assess the combined impact of reactivity and bioavailability, we studied the kinetics of Mn(III)TnBuOE-2-PyP5+ with peroxynitrite and evaluated the cytoprotective capacity of MnP by exposing the endothelial cells to nitro-oxidative stress induced by peroxynitrite. We observed a preservation of normal mitochondrial function, attenuation of cell damage and prevention of apoptotic cell death. These data introduce a novel application of RR spectroscopy for the direct detection of MnP and their redox states inside living cells, and helps to rationalize their antioxidant capacity in biological systems.Fil: Carballal, Sebastián. Universidad de la República; UruguayFil: Valez, Valeria. Universidad de la República; UruguayFil: Álvarez Paggi, Damián Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Tovmasyan, Artak. University of Duke; Estados UnidosFil: Batinic-Haberle, Ines. University of Duke; Estados UnidosFil: Ferrer-Suetac, Gerardo. Universidad de la República; UruguayFil: Murgida, Daniel Horacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; ArgentinaFil: Radi, Rafael. Universidad de la República; Urugua

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

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 strongly destabilized by P67A but stabilized by P81A. The subsequent global cooperative unfolding corresponding to the main β-sheet core is not affected by the proline mutations. Thus, a clear link exists between the effect of P81 and P67 on the stability of the first transition and oligomerization/aggregation. Interestingly, both P67 and P81 are located far away in space and sequence from the C-terminal helix, indicating a marked global structural dynamics. This provides a mechanism for modulating the oligomerization of NS1 by unfolding of a weak helix that exposes hydrophobic surfaces, linked to the participation of NS1 in multiprotein complexes.Fil: Conci, Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Álvarez Paggi, Damián Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: de Oliveira, Guilherme A. P.. Universidade Federal do Rio de Janeiro; BrasilFil: Pagani, Talita Duarte. Universidade Federal do Rio de Janeiro; BrasilFil: Esperante, Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Borkosky, Silvina Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Aran, Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Alonso, Leonardo Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Mohana Borges, Ronaldo. Universidade Federal do Rio de Janeiro; BrasilFil: de Prat Gay, Gonzalo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentin

Community Mortality due to Respiratory Syncytial Virus in Argentina: Population-based surveillance study

Background. Many deaths in infants from low-middle income countries (LMICs) occur at home or upon arrival to health facilities. Although acute lower respiratory tract illness plays an important role in community mortality, the accuracy of mortality rates due to respiratory syncytial virus (RSV) remains unknown. Methods. An active surveillance study among children aged under 5 years old (U5) was performed in Buenos Aires, Argentina, between January and December 2019, to define the burden and role of RSV in childhood community mortality. Results. A total of 63 families of children U5 participated in the study. Based on a combined approach of tissue sampling, verbal autopsies, and expert’s analysis, RSV infection was found in the causal chain of 11 from 12 cases with positive molecular biology results in respiratory samples. The estimated mortality rate due to RSV among infants was 0.27 deaths/1000 live births. The mean age of RSV-related household deaths was 2.8 months of age (standard deviation [SD] 1.7), and 8/12 were male infants (66.7%). Dying at home from RSV was associated with Streptococcus pneumoniae and/or Moraxella catarrhalis lung coinfection (75%), living in slums and settlement (odds ratio [OR], 17.09; 95% confidence interval [CI], 1.3–219.2), and other underlying comorbidities (OR, 14.87; 95% CI, 1.3–164.6). Conclusions. Infant community mortality rates due to RSV are higher than those reported in industrialized countries and similar to those reported in hospital-based studies in the same catchment population.Fil: Caballero, Mauricio Tomás. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Bianchi, Alejandra Silvina. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Diaz Grigaites, Sebastian. Gobierno de la Provincia de Buenos Aires. Ministerio Publico. Ministerio Publico Fiscal. Instituto de Ciencias Forenses de Lomas de Zamora.; ArgentinaFil: de la Iglesia Niveyro, Paola Ximena. Hospital Italiano; ArgentinaFil: Nuño, Alejandra. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Valle, Sandra. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Afarian, Gabriela. Gobierno de la Provincia de Buenos Aires. Ministerio Publico. Ministerio Publico Fiscal. Instituto de Ciencias Forenses de Lomas de Zamora.; ArgentinaFil: Esperante, Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Ferreti, Adrián. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Jares Baglivo, Sofía. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: De Luca, Julián. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Álvarez Paggi, Damián Jorge. Comisión Nacional de Investigación Científica y Tecnológica; Chile. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Diamanti, Adriana. Gobierno de la Provincia de Buenos Aires. Ministerio Publico. Ministerio Publico Fiscal. Instituto de Ciencias Forenses de Lomas de Zamora.; ArgentinaFil: Bassat, Quique. Universidad de Barcelona; España. Centro de investigação de Saúde de Manhiça; Mozambique. Institució Catalana de Recerca i Estudis Avancats; España. Hospital Sant Joan de Deu Barcelona; España. Consorcio de Investigación Biomédica en Red de Epidemiología y Salud Pública; EspañaFil: Polack, Fernando Pedro. Fundación para la Investigación en Infectología Infantil; Argentin

The discovery BPD (D-BPD) program: Study protocol of a prospective translational multicenter collaborative study to investigate determinants of chronic lung disease in very low birth weight infants

Background: Premature birth is a growing and serious public health problem affecting more than one of every ten infants worldwide. Bronchopulmonary dysplasia (BPD) is the most common neonatal morbidity associated with prematurity and infants with BPD suffer from increased incidence of respiratory infections, asthma, other forms of chronic lung illness, and death (Day and Ryan, Pediatr Res 81: 210-213, 2017; Isayama et la., JAMA Pediatr 171:271-279, 2017). BPD is now understood as a longitudinal disease process influenced by the intrauterine environment during gestation and modulated by gene-environment interactions throughout the neonatal and early childhood periods. Despite of this concept, there remains a paucity of multidisciplinary team-based approaches dedicated to the comprehensive study of this complex disease. Methods: The Discovery BPD (D-BPD) Program involves a cohort of infants < 1,250 g at birth prospectively followed until 6 years of age. The program integrates analysis of detailed clinical data by machine learning, genetic susceptibility and molecular translation studies. Discussion: The current gap in understanding BPD as a complex multi-trait spectrum of different disease endotypes will be addressed by a bedside-to-bench and bench-to-bedside approach in the D-BPD program. The D-BPD will provide enhanced understanding of mechanisms, evolution and consequences of lung diseases in preterm infants. The D-BPD program represents a unique opportunity to combine the expertise of biologists, neonatologists, pulmonologists, geneticists and biostatisticians to examine the disease process from multiple perspectives with a singular goal of improving outcomes of premature infants. Trial registration: Does not apply for this study.Fil: Ofman, Gaston. University of Alabama at Birmingahm; Estados UnidosFil: Caballero, Mauricio Tomás. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Álvarez Paggi, Damián Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Marzec, Jacqui. National Institute of Environmental Health Sciences; Estados UnidosFil: Nowogrodzki, Florencia. No especifíca;Fil: Cho, Hye Youn. National Institute of Environmental Health Sciences; Estados UnidosFil: Sorgetti, Mariana. No especifíca;Fil: Colantonio, Guillermo. No especifíca;Fil: Bianchi, Alejandra. No especifíca;Fil: Prudent, Luis M.. Fundación para la Salud Materno Infantil; ArgentinaFil: Vain, Néstor Eduardo. Fundación para la Salud Materno Infantil; Argentina. Sanatorio de la Trinidad Palermo.; ArgentinaFil: Mariani, Gonzalo Luis. Hospital Italiano; ArgentinaFil: Digregorio, Jorge. Sanatorio de la Trinidad Palermo.; ArgentinaFil: Lopez Turconi, Elba. No especifíca;Fil: Osio, Cristina. Sanatorio "Otamendi y Miroli S. A."; ArgentinaFil: Galletti, Maria Fernanda. Hospital Italiano; ArgentinaFil: Quiros, Mariangeles. Clinica y Maternidad Suizo Argentina; ArgentinaFil: Brum, Andrea. Sanatorio de la Trinidad Palermo.; ArgentinaFil: Lopez Garcia, Santiago. No especifíca;Fil: Garcia, Silvia. Sanatorio "Otamendi y Miroli S. A."; ArgentinaFil: Bell, Douglas. National Institute of Environmental Health Sciences; Estados UnidosFil: Jones, Marcus H.. Pontificia Universidade Católica do Rio Grande do Sul; BrasilFil: Tipple, Trent E.. University of Alabama at Birmingahm; Estados UnidosFil: Kleeberger, Steven R.. National Institute of Environmental Health Sciences; Estados UnidosFil: Polack, Fernando Pedro. University of Alabama at Birmingahm; Estados Unido

Early high-titer plasma therapy to prevent severe Covid-19 in older adults

BACKGROUND: Therapies to interrupt the progression of early coronavirus disease 2019 (Covid-19) remain elusive. Among them, convalescent plasma administered to hospitalized patients has been unsuccessful, perhaps because antibodies should be administered earlier in the course of illness. METHODS We conducted a randomized, double-blind, placebo-controlled trial of convalescent plasma with high IgG titers against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in older adult patients within 72 hours after the onset of mild Covid-19 symptoms. The primary end point was severe respiratory disease, defined as a respiratory rate of 30 breaths per minute or more, an oxygen saturation of less than 93% while the patient was breathing ambient air, or both. The trial was stopped early at 76% of its projected sample size because cases of Covid-19 in the trial region decreased considerably and steady enrollment of trial patients became virtually impossible. RESULTS A total of 160 patients underwent randomization. In the intention-to-treat population, severe respiratory disease developed in 13 of 80 patients (16%) who received convalescent plasma and 25 of 80 patients (31%) who received placebo (relative risk, 0.52; 95% confidence interval [CI], 0.29 to 0.94; P = 0.03), with a relative risk reduction of 48%. A modified intention-to-treat analysis that excluded 6 patients who had a primary end-point event before infusion of convalescent plasma or placebo showed a larger effect size (relative risk, 0.40; 95% CI, 0.20 to 0.81). No solicited adverse events were observed. CONCLUSIONS Early administration of high-titer convalescent plasma against SARS-CoV-2 to mildly ill infected older adults reduced the progression of Covid-19. (Funded by the Bill and Melinda Gates Foundation and the Fundación INFANT Pandemic Fund; Dirección de Sangre y Medicina Transfusional del Ministerio de Salud number, PAEPCC19, Plataforma de Registro Informatizado de Investigaciones en Salud number, 1421, and ClinicalTrials.gov number, NCT04479163.).Fil: Libster, Romina Paula. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Pérez Marc, Gonzalo. Hospital Militar Central, Buenos Aires; ArgentinaFil: Wappner, Diego. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Coviello, Silvina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Bianchi, Alejandra. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Braem, Virginia. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Esteban, Ignacio. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Caballero, Mauricio Tomás. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Wood, Cristian. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Berrueta, Mabel. Hospital Militar Central; ArgentinaFil: Rondan, Aníbal. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Lescano, Gabriela Mariel. Hospital Dr. Carlos Bocalandro; ArgentinaFil: Cruz, Pablo. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Ritou, Yvonne. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Fernández Viña, Valeria Silvina. Hospital Simplemente Evita; ArgentinaFil: Álvarez Paggi, Damián Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Esperante, Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Ferreti, Adrián. Hospital Dr. Carlos Bocalandro; ArgentinaFil: Ofman, Gaston. University of Oklahoma; Estados UnidosFil: Ciganda, Álvaro. Gobierno de la Provincia de Buenos Aires. Hospital Interzonal Especializado de Agudos y Cronicos San Juan de Dios.; ArgentinaFil: Rodriguez, Rocío. Hospital Simplemente Evita; ArgentinaFil: Lantos, Jorge. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Valentini, Ricardo. No especifíca;Fil: Itcovici, Nicolás. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Hintze, Alejandra. No especifíca;Fil: Oyarvide, M. Laura. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Etchegaray, Candela. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Neira, Alejandra. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Name, Ivonne. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Alfonso, Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Swiss Medical Group; ArgentinaFil: López Castelo, Rocío. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; ArgentinaFil: Caruso, Gisela. Hospital Militar Central; ArgentinaFil: Rapelius, Sofía. Hospital Militar Central; ArgentinaFil: Alvez, Fernando. Hospital Militar Central; ArgentinaFil: Etchenique, Federico. Hospital Militar Central; ArgentinaFil: Dimase, Federico. Hospital Militar Central; ArgentinaFil: Alvarez, Darío. Hospital Militar Central; ArgentinaFil: Aranda, Sofía S.. Hospital Militar Central; ArgentinaFil: Sánchez Yanotti, Clara Inés. Hospital Militar Central; ArgentinaFil: De Luca, Julián. Hospital Militar Central; ArgentinaFil: Jares Baglivo, Sofía. Hospital Militar Central; ArgentinaFil: Laudanno, Sofía. Fundación Hematológica Sarmiento; ArgentinaFil: Nowogrodzki, Florencia. Swiss Medical Group; ArgentinaFil: Larrea, Ramiro. Hospital Municipal San Isidro; ArgentinaFil: Silveyra, María. Hospital Militar Central; ArgentinaFil: Leberzstein, Gabriel. No especifíca;Fil: Debonis, Alejandra. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Molinos, Juan. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: González, Miguel. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Perez, Eduardo. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Kreplak, Nicolás. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Pastor Argüello, Susana. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Gibbons, Luz. Hospital Municipal de San Isidro; ArgentinaFil: Althabe, Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Bergel, Eduardo. Sanatorio Sagrado Corazón; ArgentinaFil: Polack, Fernando Pedro. Provincia de Buenos Aires. Ministerio de Salud; Argentin

Toward personalized medicine in bronchiolitis

Nothing essential has changed in the definition of bronchiolitis since itsdescription nearly eighty years ago [1,2]. The syndrome affects infants and youngchildren at different ages, presents with a few overlapping symptoms of varying intensityand other manifestations often associated with specific pathogens (e.g.: fever andpharyngitis in influenza or wheezing with respiratory syncytial virus), and is caused byinfection with one or a combination of half a dozen viruses with different inflammatory,antiviral and/or atopic phenotypes [3]. Conceived as a single entity, a number ofcandidate drugs failed as therapeutics against it in randomized trials [4]. To date,management recommendations for hospitalized patients are based on supportive therapy[2]. Etiologic testing is discouraged [2].Fil: Álvarez Paggi, Damián Jorge. Fundación para la Investigación en Infectología Infantil; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Polack, Fernando Pedro. Fundación para la Investigación en Infectología Infantil; Argentin

The role of protein dynamics and thermal fluctuations in regulating cytochrome c/cytochrome c oxidase electron transfer

In this overview we present recent combined electrochemical, spectroelectrochemical, spectroscopic and computational studies from our group on the electron transfer reactions of cytochrome c and of the primary electron acceptor of cytochrome c oxidase, the CuA site, in biomimetic complexes. Based on these results, we discuss how protein dynamics and thermal fluctuations may impact on protein ET reactions, comment on the possible physiological relevance of these results, and finally propose a regulatory mechanism that may operate in the Cyt/CcO electron transfer reaction in vivo. This article is part of a Special Issue entitled: 18th European Bioenergetic Conference.Fil: Álvarez Paggi, Damián Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; ArgentinaFil: Zitare, Ulises Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; ArgentinaFil: Murgida, Daniel Horacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentin