Pablo Coss - Academia.edu (original) (raw)

Papers by Pablo Coss

Biophysical Journal, 2015

Physica B-Condensed Matter, 2006

ABSTRACT In the present work, we study the magnetic properties and critical behavior of simple cu... more ABSTRACT In the present work, we study the magnetic properties and critical behavior of simple cubic ferromagnetic thin films. We simulate L×L×d films with semifree boundary conditions on the basis of the Monte Carlo method and the Ising model with nearest neighbor interactions. A Metropolis dynamics was implemented to carry out the energy minimization process. For different film thickness, in the nanometer range, we compute the temperature dependence of the magnetization, the magnetic susceptibility and the fourth order Binder's cumulant. Bulk and surface contributions of these quantities are computed in a differentiated fashion. Additionally, according to finite size scaling theory, we estimate the critical exponents for the correlation length, magnetic susceptibility, and magnetization. Results reveal a strong dependence of critical temperature and critical exponents on the film thickness. The obtained critical exponents are finally compared to those reported in literature for thin films.

PLoS Biology, 2013

Ser/thr phosphatases dephosphorylate their targets with high specificity, yet the structural and ... more Ser/thr phosphatases dephosphorylate their targets with high specificity, yet the structural and sequence determinants of phosphosite recognition are poorly understood. Calcineurin (CN) is a conserved Ca 2+ /calmodulin-dependent ser/thr phosphatase and the target of immunosuppressants, FK506 and cyclosporin A (CSA). To investigate CN substrate recognition we used X-ray crystallography, biochemistry, modeling, and in vivo experiments to study A238L, a viral protein inhibitor of CN. We show that A238L competitively inhibits CN by occupying a critical substrate recognition site, while leaving the catalytic center fully accessible. Critically, the 1.7 Å structure of the A238L-CN complex reveals how CN recognizes residues in A238L that are analogous to a substrate motif, ''LxVP.'' The structure enabled modeling of a peptide substrate bound to CN, which predicts substrate interactions beyond the catalytic center. Finally, this study establishes that ''LxVP'' sequences and immunosuppressants bind to the identical site on CN. Thus, FK506, CSA, and A238L all prevent ''LxVP''-mediated substrate recognition by CN, highlighting the importance of this interaction for substrate dephosphorylation. Collectively, this work presents the first integrated structural model for substrate selection and dephosphorylation by CN and lays the groundwork for structure-based development of new CN inhibitors.

Physical Chemistry Chemical Physics, 2011

FEBS Letters, 2011

The first 17 amino acids of Huntingtin protein (N17) play a crucial role in the protein's aggrega... more The first 17 amino acids of Huntingtin protein (N17) play a crucial role in the protein's aggregation. Here we predict its free energy landscape in aqueous solution by using bias exchange metadynamics. All our findings are consistent with experimental data. N17 populates four main kinetic basins, which interconvert on the microsecond timescale. The most populated basin (about 75%) is a random coil, with an extended flat exposed hydrophobic surface. This might create a hydrophobic seed promoting Huntingtin aggregation. The other main populated basins contain helical conformations, which could facilitate N17 binding on its cellular targets.

European Journal of Pharmacology, 1981

The effects of chagasic sera, containing an antibody (EVI antibody) which reacts with the plasma ... more The effects of chagasic sera, containing an antibody (EVI antibody) which reacts with the plasma membrane of working myocardial cells, on 'toxic' and 'non-toxic' actions of ouabain upon isolated self beating or paced rat atria suspended in different media, were explored. Although ouabain produced a dose-dependent positive inotropic influence on atria suspended in Krebs-Ringer-bicarbonate (KRB) and in KRB plus normal human serum (KRB + NHS) it did not elicit any significant positive inotropic effect on atria beating in KRB plus EVI positive human chagasic serum (EVI(+)S). Additionally, in EVI(+)S dose-response curves of classical signs of digitalis cardiac toxicity shifted to the left. The threshold concentration of ouabain required to elicit the onset of 'toxic' effects was higher in control preparations (kept in KRB or KRB + NHS) than in EVI(+)S exposed preparations. (-)-Propranolol attenuated the overall toxic action of ouabain in EVI(+)S and facilitated its positive inotropic influence. In control media, the ~-adrenoceptor blocker failed to modify either the 'non-toxic' or the 'toxic' effect of ouabain. On the other hand, with control atria, subthreshold exogenous norepinephrine inhibited the positive inotropism of ouabain. The data suggest that an adrenergic mechanism is involved in the action of ouabain on cardiac tissue immersed in an EVI(+)S-containing solution. The foregoing results may explain the severe 'toxic' effects observed with cardioactive glycosides when they are used in patients with Chagas' heart disease, even at low doses. Adrenergic mechanisms Chagasic sera Ouabain Atria

It is currently believed that the atlas of existing protein structures is faithfully represented ... more It is currently believed that the atlas of existing protein structures is faithfully represented in the Protein Data Bank. However, whether this atlas covers the full universe of all possible protein structures is still a highly debated issue. By using a sophisticated numerical approach, we performed an exhaustive exploration of the conformational space of a 60 amino acid polypeptide chain described with an accurate all-atom interaction potential. We generated a database of around 30,000 compact folds with at least 30% of secondary structure corresponding to local minima of the potential energy. This ensemble plausibly represents the universe of protein folds of similar length; indeed, all the known folds are represented in the set with good accuracy. However, we discover that the known folds form a rather small subset, which cannot be reproduced by choosing random structures in the database. Rather, natural and possible folds differ by the contact order, on average significantly smaller in the former. This suggests the presence of an evolutionary bias, possibly related to kinetic accessibility, towards structures with shorter loops between contacting residues. Beside their conceptual relevance, the new structures open a range of practical applications such as the development of accurate structure prediction strategies, the optimization of force fields, and the identification and design of novel folds

ABSTRACT In this work we study the hysteretic behavior of a bilayer formed by a ferromagnetic lay... more ABSTRACT In this work we study the hysteretic behavior of a bilayer formed by a ferromagnetic layer and an antiferromagnetic one, both of them having cubic simple structure. Along the interface between both subsystems, two different exchange integrals were used to represent the interaction between each one of the sublattices of the antiferro-layer with the ferro-film. This was carried out following the Lederman-Ramírez-Kiwi�s model. A Metropolis dynamics and a classical Heisenberg Hamil-tonian with first neighbors interactions plus a magnetocrystalline anisotropy term were used. Semifree boundary conditions were also implemented. We have found the conditions for which the exchange bias phenomenology takes place when cool-ing the bilayer to a temperature below Néel temperature. The variation of the exchange field and the coercive force as func-tion of temperature is alse reported. Our results are finally compared with the experimental reports found in the literature. En este trabajo estudiamos el comportamiento histéretico de una bicapa formada por una capa ferromagnética y otra antife-rromagnética, ambas con estructura cúbica simple. En la interface entre los dos subsistemas, se utilizaron dos integrales de intercambio diferentes para representar la interacción entre cada una de las subredes de la capa antiferro con la película fe-rro. Esto se hizo siguiendo el modelo de Lederman-Ramírez-Kiwi. Se utilizó una dinámica de Metropolis, un Hamiltoniano de Heisenberg clásico con interacciones a primeros vecinos, un término de anisotropía magnetocristalina y se implementa-ron condiciones de frontera semilibres. Se encontraron las condiciones para las cuales tiene lugar el fenómeno de despla-zamiento de los ciclos de histéresis (Exchange Bias) al enfriar la bicapa a una temperatura por debajo de la temperatura de Néel. También se reporta la variación del campo de intercambio y del campo coercitivo en función de la temperatura. Nuestros resultados se comparan finalmente con reportes experimentales encontrados en la literatura.

Clinical and experimental immunology, 1982

Abstract It was previously shown that fresh sera from chagasic patients that contained antibodies... more Abstract It was previously shown that fresh sera from chagasic patients that contained antibodies reacting with the plasma membrane of striated muscle and endothelial cells (EVI (+) serum) could act in co-operation with complement as a partial beta-agonist increasing ...

Virchows Archiv. A, Pathological anatomy and histology, Jan 7, 1975

In six lethal cases of Argentine Haemorrhagic Fever (AHF) a disease caused by Junin virus, kidney... more In six lethal cases of Argentine Haemorrhagic Fever (AHF) a disease caused by Junin virus, kidney samples were studied by means of immunofluorescent and electron microscopic techniques.--The ultrastructural studies showed that the distal and collecting tubes presented a large number of virus like intracytoplasmic particles. Those particles were present in the lumen of the endoplasmic reticulum cisternae and showed two distinct morphological aspects. Some of them were of high electron density and contained a few granules. The others were larger in size, electron lucid, and contained a variable number of ribosome like granules. Both types of particles originated from the endoplasmic reticulum wall by a process of budding. The presence of these particles was coincident with a severe cell damage which lead to necrosis and desquamation; and with large quantities of Junin virus antigen as demonstrated by immunofluorescence.--On the basis of these observations it is assumed that in AHF the...

International Journal of Immunopharmacology, 1986

It has been previously shown that sera from chagasic patients have an antibody specific for/3 adr... more It has been previously shown that sera from chagasic patients have an antibody specific for/3 adrenoceptors, independently of other tissue-reactive antibodies as the EVI (endocardium, blood vessels, interstitium) system, and it is highly specific to other heart diseases. In this paper we demonstrate that the IgG present in chagasic sera was able to bind to/3 adrenoceptors of the heart and also to interact with the membrane bound adenylate cyclase complex, inducing stimulation of enzymatic activity. Moreover, this antibody stimulated contractile activity of guinea pig myocardium, that could be blocked by a specific/3 adrenoceptor antagonist. Chagasic lgG inhibited the binding of (-)-(3H)dyhidroalprenolol to a/3-adrenergic receptor of purified guinea pig myocardial membranes behaving as noncompetitive inhibitor. This IgG also exerted a non-competitive inhibition upon the mechanical effect of exogenous norepinephrine.

Memórias do Instituto Oswaldo Cruz, 1995

Twenty young male Cebus apella monkeys were infected with CA1 Trypanosoma cruzi strain and reinfe... more Twenty young male Cebus apella monkeys were infected with CA1 Trypanosoma cruzi strain and reinfected with CA1 or Tulahuen T. cruzi strains, with different doses and parasite source. Subpatent parasitemia was usually demonstrated in acute and chronic phases. Patent parasitemia was evident in one monkey in the acute phase and in four of them in the chronic phase after re-inoculations with high doses of CA1 strain. Serological conversion was observed in all monkeys; titers were low, regardless of the methods used to investigate anti-T. cruzi specific antibodies. Higher titers were induced only when re-inoculations were performed with the virulent Tulahuén strain or high doses of CA1 strain. Clinical, electrocardiographic and ajmaline test evaluations did not reveal changes between infected and control monkeys. Histopathologically, cardiac lesions were always characterized by focal or multifocal mononuclear infiltrates and/or isolated fibrosis, as seen during the acute and chronic phases; neither amastigote nests nor active inflammation and fibrogenic processes characteristic of human acute and chronic myocarditis respectively, were observed. These morphological aspects more closely resemble those found in the &amp;amp;amp;quot;indeterminate phase&amp;amp;amp;quot; and contrast with the more diffuse and progressive pattern of the human chagasic chronic myocarditis. All monkeys survived and no mortality was observed.

Journal of Medical Virology, 1986

Experimental infection with the XJ‐Clone 3 strain of Junín virus in laboratory bred Akodon molina... more Experimental infection with the XJ‐Clone 3 strain of Junín virus in laboratory bred Akodon molinae, a cricetid rodent inhabiting the borders of endemic Argentine hemorrhagic fever areas, was studied.Suckling animals inoculated intracerebrally proved sensitive and became chronically infected. Sixty percent of the rodents showed neurologic involvement, with mortality reaching 60%.Virus was recovered from the brain at 7, 15, 21, 37, and 57 days postinfection (pi). By immunofluorescence (IF), viral antigens were observed up to 182 days pi in cells of the central nervous system (CNS). Concurrently, immunoglobulin deposits were detected in infected CNS cells from 21 up to 182 days pi. These deposits increased with the progression of the immune response as measured by IF antibodies. The detection of immune complexes in brain cells of apparently healthy animals suggests that neither viral replication nor the development of a humoral immune response are necessary requisites for neurovirulenc...

Computer Physics Communications, 2013

ABSTRACT In protein structure prediction it is of crucial importance, especially at the refinemen... more ABSTRACT In protein structure prediction it is of crucial importance, especially at the refinement stage, to score efficiently large sets of models by selecting the ones that are closest to the native state. We here present a new computational tool, BACHSCORE, that allows its users to rank different structural models of the same protein according to their quality, evaluated by using the BACH++ (Bayesian Analysis Conformation Hunt) scoring function. The original BACH statistical potential was already shown to discriminate with very good reliability the protein native state in large sets of misfolded models of the same protein. BACH++ features a novel upgrade in the solvation potential of the scoring function, now computed by adapting the LCPO (Linear Combination of Pairwise Orbitals) algorithm. This change further enhances the already good performance of the scoring function. BACHSCORE can be accessed directly through the web server: bachserver.pd.infn.it.

Biochemical Pharmacology, 1986

It has been shown that sera from chagasic patients contain an antibody which binds to /3adrenocep... more It has been shown that sera from chagasic patients contain an antibody which binds to /3adrenoceptors of myocardium and modulates their activity. Chagasic IgG triggered a marked stimulation of myocardial contractility with an increase in intramyocardial cyclic AMP and inhibition of (Na* + K*)-ATPase activity. Both the mechanical and enzymatic effects of the IgG could be prevented by /3adrenoceptor blockade or after the absorption of chagasic IgG with turkey red blood cells. In contrast, guinea pig red blood cells were unable to remove the ~reactivity of chagasic IgG. These findings suggest that the IgG from chagasic patients increases myocardial contractility by behaving as a/3-agonist. This effect is likely related to stimulation of the adenylate cyclase coupled to the cardiac/3-adrenoceptor.

Archives of Histology and Cytology, 1998