The Peptide Network between Tetanus Toxin and Human Proteins Associated with Epilepsy

Sequence matching analyses show that Clostridium tetani neurotoxin shares numerous pentapeptides (68, including multiple occurrences) with 42 human proteins that, when altered, have been associated with epilepsy. Such a peptide sharing is higher than expected, nonstochastic, and involves tetanus toxin-derived epitopes that have been validated as immunopositive in the human host. Of note, an unexpected high level of peptide matching is found in mitogen-activated protein kinase 10 (MK10), a protein selectively expressed in hippocampal areas. On the whole, the data indicate a potential for cross-reactivity between the neurotoxin and specific epilepsy-associated proteins and may help evaluate the potential risk for epilepsy following immune responses induced by tetanus infection. Moreover, this study may contribute to clarifying the etiopathogenesis of the different types of epilepsy

Neolatin group on headache - the spoken languages of men and the international transmission of scientific knowledge.

This initiative stems from previous projects[1] designed to benefit a category of people who live a particular linguistic ‘‘disadvantage’’: the immigrants. Even more so, those immigrants who suffer from Chronic Headache and its comorbidities (physical/psychological disorders)

Which is the best algorithm for evaluating a patient’s candidate to sleeve with suspected reflux or hiatal hernia: is manometry or reflux assessment always necessary

Laparoscopic sleeve gastrectomy (SG) has reached wide popularity during the last 15 years, owing to limited morbidity and mortality rates, very successful weight loss results, and impact on comorbidities. However, the postoperative development or worsening of gastroesophageal reflux disease (GERD) is one of the most important drawbacks of this surgical procedure. To date, there is great heterogeneity concerning the definition of GERD, the indication for SG in patients with GERD, and the standardization of pre and postoperative diagnostic pathways. In patients with severe obesity, a strictly symptom-based diagnosis of GERD is unreliable. In fact, a high rate of silent GERD (s-GERD, asymptomatic patients despite objective evidence of GERD) has been reported. Moreover, patients with preoperative s-GERD have a significantly higher risk of experiencing GERD symptoms after SG. For these reasons, the reflux burden and the competence of the anti-reflux barrier should be carefully assessed during the preoperative work-up of patients undergoing SG. Ambulatory pH monitoring (APM) and high-resolution manometry (HRM) are useful diagnostic tools that could provide valuable evidence in the guidance of surgical strategy. In this review, we evaluate the current literature concerning the use of APM and HRM in the diagnostic pathway before SG, as well as their predictive value for the evolution of GERD in the postoperative course. Moreover, we propose a diagnostic algorithm for preoperative GERD assessment, which includes validated symptom questionnaires, upper gastrointestinal endoscopy, APM, and HRM

Density Functional Theory for the Photoionization Dynamics of Uracil

Photoionization dynamics of the RNA base Uracil is studied in the framework of Density Functional Theory (DFT). The photoionization calculations take advantage of a newly developed parallel version of a multicentric approach to the calculation of the electronic continuum spectrum which uses a set of B-spline radial basis functions and a Kohn-Sham density functional hamiltonian. Both valence and core ionizations are considered. Scattering resonances in selected single-particle ionization channels are classified by the symmetry of the resonant state and the peak energy position in the photoelectron kinetic energy scale; the present results highlight once more the site specificity of core ionization processes. We further suggest that the resonant structures previously characterized in low-energy electron collision experiments are partly shifted below threshold by the photoionization processes. A critical evaluation of the theoretical results providing a guide for future experimental work on similar biosystems

Hyperglycemia and angiotensin II cooperate to enhance collagen I deposition by cardiac fibroblasts through a ROS-STAT3-dependent mechanism

AbstractCardiac fibroblasts significantly contribute to diabetes-induced structural and functional changes in the myocardium. The objective of the present study was to determine the effects of high glucose (alone or supplemented with angiotensin II) in the activation of the JAK2/STAT3 pathway and its involvement in collagen I production by cardiac fibroblasts. We observed that the diabetic environment 1) enhanced tyrosine phosphorylation of JAK2 and STAT3; 2) induced nuclear localization of tyrosine phosphorylated STAT3 through a reactive oxygen species-mediated mechanism, with angiotensin II stimulation further enhancing STAT3 nuclear accumulation; and 3) stimulated collagen I production. The effects were inhibited by depletion of reactive oxygen species or silencing of STAT3 in high glucose alone or supplemented with exogenous angiotensin II. Combined, our data demonstrate that increased collagen I deposition in the setting of high glucose occurred through a reactive oxygen species- and STAT3-dependent mechanism. Our results reveal a novel role for STAT3 as a key signaling molecule of collagen I production in cardiac fibroblasts exposed to a diabetic environment

Cardioplegia and angiotensin II receptor antagonists modulate signal transducers and activators of transcription activation in neonatal rat myocytes.

A crescente necessidade de informação para a tomada de decisões dos gestores do setor do transporte urbano de passageiros obriga a desenvolver sistemas para o cálculo, análise e controle de custos que permitam conhecer de forma acurada os mecanismos de formação dos seus preços internos. Nesse contexto, a medida do rendimento adquire um interesse especial quando é comparada a parâmetros e padrões significativos, que permitam aplicar técnicas de benchmarking para melhorar a gestão econômica do serviço. Com esses fins, entende-se que a geração de medidas representativas de padrões coletivos de comportamento constitui-se em uma ferramenta útil para orientar a ação de gestores e administradores públicos. E, como conseqüência, nós apresentamos à Asociación de Empresas de Transporte Urbano Colectivo (ATUC), na Espanha, um projeto para a criação de um Observatório de Custos que possa constituir-se em um importante ponto de referência para as empresas de transporte urbano de passageiros. Palavras-chave: Custos. Financiamento. Transporte urbano de passageiros. * Trabalho apresentado no XIII Congresso Brasileiro de Custos, realizado em Belo Horizonte – MG, no período de 30 de outubro a 01 de novembro 2006.The possibility of providing more complete and detailed data about passenger transport enterprises management justifies the development of analysis and cost control systems that provide precise and rigorous knowledge about internal price formation mechanisms. In this framework, measurement of performance is especially relevant when compared with some other significant reference parameters that allow the use of benchmarking in order to improve the economic management of the service. To this end, we consider it especially useful for the ATUC (Asociación de Empresas de Transporte Urbano Colectivo, i.e., the Association of Collective Urban Transport Companies) to provide a service that establishes measures which represent actual behaviour patterns, that enhances the knowledge of the reality of the sector and that generates a spirit of self-improvement in their associates. We presented a project to ATUC proposing the establishment of a Costs Observatory that can become a significant reference point for passenger transport companies. Key words: Costs. Funding. Urban Passenger Transport.Las crecientes necesidades de información para la gestión y la toma de decisiones de los agentes que operan en el sector del transporte urbano de pasajeros, obliga a desarrollar sistemas para el cálculo, análisis y control de costes que permitan un conocimiento riguroso de los mecanismos de formación de sus precios internos. En dicho marco, la medida del rendimiento adquiere especial interés cuando entra en comparación con parámetros y estándares significativos, que permitan aplicar técnicas de benchmarking para mejorar la gestión económica del servicio. A tales efectos, entendemos que la generación de medidas representativas de patrones colectivos de comportamiento, constituye una herramienta de gran utilidad para orientar la acción de gestores y administradores públicos. Y, en consecuencia, en España, y en el seno de la Asociación de Empresas de Transporte Urbano Colectivo (ATUC), estamos desarrollando un proyecto para la creación de un Observatorio de Costes que pueda constituirse en significativo punto de referencia para las empresas de transporte urbano de viajeros. Palabras clave: Costes. Financiación.Transporte urbano de viajeros

Cardioplegia and angiotensin II receptor antagonists modulate signal transducers and activators of transcription activation in neonatal rat myocytes.

Previous investigations have shown that the signal transducers and activators of transcription (STATs) signaling pathway play an important role in the modulation of apoptosis after ischemia and reperfusion. The mechanism for this enhanced cardioprotection is unknown, but we believe that alterations STATs may play a role. To investigate this hypothesis, we examined the effects of angiotension II type 1 (AT1) and angiotension II type 2 (AT2) receptor antagonist added to cardioplegia on the downstream response of different STATs, connected with proinflammatory pathways (STAT2, STAT5) and prohypertrophic and antiapoptotic pathways (STAT3). Isolated, nonworking hearts (n = 3 per group) from neonatal rats were perfused aerobically (4°C) for 20 min in the Langendorff mode with the modified St. Thomas' Hospital no. 2 (MSTH2) cardioplegic solution (Group 1), the MSTH2 cardioplegic solution + AT1 receptor antagonist (Group 2), and MSTH2 cardioplegic solution + AT2 receptor antagonist (Group 3). Thus, myocytes were isolated by enzymatic digestion, and STAT2, STAT3, and STAT5 were investigated in Western blot studies. Times to arrest after cardioplegia were 8-12 s for all groups. Total cardioplegia delivery volume was about 300 mL for the 20 min. Perfusion with the MSTH2 cardioplegic solution supplemented with AT1 receptor antagonist (Group 2) induced a significant reduction in STAT2 and STAT5 tyrosine phosphorylation (-58 and -63%, respectively, vs. Group 1, P < 0.05). Conversely, STAT2 and STAT5 activation were unaffected by perfusion with the MSTH2 cardioplegic solution supplemented with AT2 receptor antagonist (Group 3). The decreased activation of STAT2 and STAT5 observed in Group 2 was accompanied by reduction of interleukin-1β (-57% in Group 2 vs. Group 1, P < 0.05). There were no significant differences in STAT3 phosphorylation among all groups. Only the addition of AT1 receptor antagonist to MSTH2 cardioplegia significantly decreases the inflammatory response of the neonatal rat cardiomyocytes without affecting antiapoptotic influence provided by tyrosine phosphorylation of STAT3. AT1 receptor antagonist added to cardioplegia represents an additional modality for enhancing myocardial protection during cardiac surgery and could contribute to optimize the ischemia tolerance of the pediatric heart

Quality versus efficiency in document scoring with learning-to-rank models

Learning-to-Rank (LtR) techniques leverage machine learning algorithms and large amounts of training data to induce high-quality ranking functions. Given a set of docu- ments and a user query, these functions are able to precisely predict a score for each of the documents, in turn exploited to effectively rank them. Although the scoring efficiency of LtR models is critical in several applications – e.g., it directly impacts on response time and throughput of Web query processing – it has received relatively little attention so far. The goal of this work is to experimentally investigate the scoring efficiency of LtR models along with their ranking quality. Specifically, we show that machine-learned ranking mod- els exhibit a quality versus efficiency trade-off. For example, each family of LtR algorithms has tuning parameters that can influence both effectiveness and efficiency, where higher ranking quality is generally obtained with more complex and expensive models. Moreover, LtR algorithms that learn complex models, such as those based on forests of regression trees, are generally more expensive and more effective than other algorithms that induce simpler models like linear combination of features. We extensively analyze the quality versus efficiency trade-off of a wide spectrum of state- of-the-art LtR, and we propose a sound methodology to devise the most effective ranker given a time budget. To guarantee reproducibility, we used publicly available datasets and we contribute an open source C++ framework providing optimized, multi-threaded imple- mentations of the most effective tree-based learners: Gradient Boosted Regression Trees (GBRT), Lambda-Mart (λ-MART), and the first public-domain implementation of Oblivious Lambda-Mart (λ-MART), an algorithm that induces forests of oblivious regression trees. We investigate how the different training parameters impact on the quality versus effi- ciency trade-off, and provide a thorough comparison of several algorithms in the quality- cost space. The experiments conducted show that there is not an overall best algorithm, but the optimal choice depends on the time budget