Primer encuentro de docentes de Fisiología y Física Biológica: una experiencia nueva en nuestro país

Bajo la consigna de que la Universidad debe ser creadora de conocimiento y no sólo simple transmisora, surgió la inquietud desde la Sociedad Argentina de Fisiología (SAFIS) de buscar un espacio de encuentro, entre los docentes de Fisiología del país y los investigadores involucrados en el área. Surgió así el Primer Encuentro Nacional de Docentes de Fisiología, realizado en Noviembre de 2010, en el marco del Congreso Anual de SAFIS.Facultad de Ciencias Médica

La enseñanza de la Fisiología en la Argentina

Objetivo: Realizar un diagnóstico de la enseñanza de la Fisiología en las cátedras de las facultades o escuelas de salud de la Argentina: analizar el cuerpo docente y las actividades de cada cátedra.Facultad de Ciencias Médica

The two-loop four-fermion scattering amplitude in QED

We present the analytic evaluation of the two-loop corrections to the amplitude for the scattering of four fermions in Quantum Electrodynamics, $f^- + f^+ + F^- + F^+ \to 0$, with $f$ and $F$ representing a massless and a massive lepton, respectively. Dimensional regularization is employed to evaluate the loop integrals. Ultraviolet divergences are removed by renormalizing the coupling constant in the ${\overline{\text{MS}}}$-scheme, and the lepton mass as well as the external fields in the on-shell scheme. The analytic result for the renormalized amplitude is expressed as Laurent series around $d=4$ space-time dimensions, and contains Generalized Polylogarithms with up to weight four. The structure of the residual infrared divergences of the virtual amplitude is in agreement with the prediction of the Soft Collinear Effective Theory. Our analytic results are an essential ingredient for the computation of the scattering cross section for massive fermion-pair production in massless fermion-pair annihilation, i.e. $f^- f^+ \to F^- F^+$, and crossing related processes such as the elastic scattering $f F \to f F$, with up to Next-to-Next to Leading Order accuracy.Comment: 5 pages, 2 figures, 1 table + supplemental materia

La enseñanza de la Fisiología en la Argentina

Objetivo: Realizar un diagnóstico de la enseñanza de la Fisiología en las cátedras de las facultades o escuelas de salud de la Argentina: analizar el cuerpo docente y las actividades de cada cátedra.Facultad de Ciencias Médica

Two-Loop Four-Fermion Scattering Amplitude in QED

We present the first fully analytic evaluation of the transition amplitude for the scattering of a massless into a massive pair of fermions at the two-loop level in quantum electrodynamics. Our result is an essential ingredient for the determination of the electromagnetic coupling within scattering reactions, beyond the currently known accuracy, which has a crucial impact on the evaluation of the anomalous magnetic moment of the muon. It will allow, in particular, for a precise determination of the leading hadronic contribution to the (g−2)μ in the MUonE experiment at CERN, and therefore can be used to shed light on the current discrepancy between the standard model prediction and the experimental measurement for this important physical observable

La enseñanza de la Fisiología en la Argentina

Objetivo: Realizar un diagnóstico de la enseñanza de la Fisiología en las cátedras de las facultades o escuelas de salud de la Argentina: analizar el cuerpo docente y las actividades de cada cátedra.Facultad de Ciencias Médica

La proteína quinasa dependiente de Ca2+ y calmodulina (CaMKII): ¿es proarritmogénica en reperfusión?

La reperfusión del miocardio isquémico lo hace más propenso a la aparición de arritmias. Experimentos previos de nuestro laboratorio mostraron que al inicio de la reperfusión (R), momento en el que se detecta el mayor número de arritmias, aumenta la fosforilación dependiente de CaMKII del residuo PT17 de fosfolamban (PLN) (Vittone, 2002). El objetivo de este trabajo, fue evaluar la posibilidad de que la activación de CaMKII al inicio de la reperfusión sea un mecanismo proarritmogénico.Facultad de Ciencias Médica

RNAseq Analyses Identify Tumor Necrosis Factor-Mediated Inflammation as a Major Abnormality in ALS Spinal Cord

ALS is a rapidly progressive, devastating neurodegenerative illness of adults that produces disabling weakness and spasticity arising from death of lower and upper motor neurons. No meaningful therapies exist to slow ALS progression, and molecular insights into pathogenesis and progression are sorely needed. In that context, we used high-depth, next generation RNA sequencing (RNAseq, Illumina) to define gene network abnormalities in RNA samples depleted of rRNA and isolated from cervical spinal cord sections of 7 ALS and 8 CTL samples. We aligned \u3e50 million 2X150 bp paired-end sequences/sample to the hg19 human genome and applied three different algorithms (Cuffdiff2, DEseq2, EdgeR) for identification of differentially expressed genes (DEG’s). Ingenuity Pathways Analysis (IPA) and Weighted Gene Co-expression Network Analysis (WGCNA) identified inflammatory processes as significantly elevated in our ALS samples, with tumor necrosis factor (TNF) found to be a major pathway regulator (IPA) and TNFα-induced protein 2 (TNFAIP2) as a major network “hub” gene (WGCNA). Using the oPOSSUM algorithm, we analyzed transcription factors (TF) controlling expression of the nine DEG/hub genes in the ALS samples and identified TF’s involved in inflammation (NFkB, REL, NFkB1) and macrophage function (NR1H2::RXRA heterodimer). Transient expression in human iPSC-derived motor neurons of TNFAIP2 (also a DEG identified by all three algorithms) reduced cell viability and induced caspase 3/7 activation. Using high-density RNAseq, multiple algorithms for DEG identification, and an unsupervised gene co-expression network approach, we identified significant elevation of inflammatory processes in ALS spinal cord with TNF as a major regulatory molecule. Overexpression of the DEG TNFAIP2 in human motor neurons, the population most vulnerable to die in ALS, increased cell death and caspase 3/7 activation. We propose that therapies targeted to reduce inflammatory TNFα signaling may be helpful in ALS patients

Chasing cardiac physiology and pathology down the CaMKII cascade

Calcium dynamics is central in cardiac physiology, as the key event leading to the excitation-contraction coupling (ECC) and relaxation processes. The primary function of Ca2+ in the heart is the control of mechanical activity developed by the myofibril contractile apparatus. This key role of Ca2+ signaling explains the subtle and critical control of important events of ECC and relaxation, such as Ca2+ influx and SR Ca2+ release and uptake. The multifunctional Ca21-calmodulin-dependent protein kinase II (CaMKII) is a signaling molecule that regulates a diverse array of proteins involved not only in ECC and relaxation but also in cell death, transcriptional activation of hypertrophy, inflammation, and arrhythmias. CaMKII activity is triggered by an increase in intracellular Ca2+ levels. This activity can be sustained, creating molecular memory after the decline in Ca2+ concentration, by autophosphorylation of the enzyme, as well as by oxidation, glycosylation, and nitrosylation at different sites of the regulatory domain of the kinase. CaMKII activity is enhanced in several cardiac diseases, altering the signaling pathways by which CaMKII regulates the different fundamental proteins involved in functional and transcriptional cardiac processes. Dysregulation of these pathways constitutes a central mechanism of various cardiac disease phenomena, like apoptosis and necrosis during ischemia/reperfusion injury, digitalis exposure, post-acidosis and heart failure arrhythmias, or cardiac hypertrophy. Here we summarize significant aspects of the molecular physiology of CaMKII and provide a conceptual framework for understanding the role of the CaMKII cascade on Ca2+ regulation and dysregulation in cardiac health and disease.Centro de Investigaciones Cardiovasculare

Adherent Monomer-Misfolded SOD1

Background: Multiple cellular functions are compromised in amyotrophic lateral sclerosis (ALS). In familial ALS (FALS) with Cu/Zn superoxide dismutase (SOD1) mutations, the mechanisms by which the mutation in SOD1 leads to such a wide range of abnormalities remains elusive. Methodology/Principal Findings: To investigate underlying cellular conditions caused by the SOD1 mutation, we explored mutant SOD1-interacting proteins in the spinal cord of symptomatic transgenic mice expressing a mutant SOD1, SOD1 Leu126delTT with a FLAG sequence (DF mice). This gene product is structurally unable to form a functional homodimer. Tissues were obtained from both DF mice and disease-free mice expressing wild-type with FLAG SOD1 (WF mice). Both FLAG-tagged SOD1 and cross-linking proteins were enriched and subjected to a shotgun proteomic analysis. We identified 34 proteins (or protein subunits) in DF preparations, while in WF preparations, interactions were detected with only 4 proteins. Conclusions/Significance: These results indicate that disease-causing mutant SOD1 likely leads to inadequate proteinprotein interactions. This could be an early and crucial process in the pathogenesis of FALS