Existence of homoclinic connections in continuous piecewise linear systems

Altres ajuts: Conserjería de Educación y Ciencia de la Junta de Andalucía (TIC-0130, EXC/2005/FQM-872, P08-FQM-03770)Altres ajuts: Universitat de les Illes Balears grant UIB2005/6 and by CAIB grand number CEH-064864Numerical methods are often used to put in evidence the existence of global connections in differential systems. The principal reason is that the corresponding analytical proofs are usually very complicated. In this work we give an analytical proof of the existence of a pair of homoclinic connections in a continuous piecewise linear system, which can be considered to be a version of the widely studied Michelson system. Although the computations developed in this proof are specific to the system, the techniques can be extended to other piecewise linear systems

NOTES ON INSECT PESTS OF SOURSOP (GUANABANA), ANNONA MURICATA L., AND THEIR NATURAL ENEMIES IN PUERTO RICO

NOTES ON INSECT PESTS OF SOURSOP (GUANABANA), ANNONA MURICATA L., AND THEIR NATURAL ENEMIES IN PUERTO RIC

Site-to-site interdomain communication may mediate different loss-of-function mechanisms in a cancer-associated NQO1 polymorphism

Disease associated genetic variations often cause intracellular enzyme inactivation, dysregulation and instability. However, allosteric communication of mutational effects to distant functional sites leading to loss-of-function remains poorly understood. We characterize here interdomain site-to-site communication by which a common cancer-associated single nucleotide polymorphism (c.C609T/p.P187S) reduces the activity and stability in vivo of NAD(P)H:quinone oxidoreductase 1 (NQO1). NQO1 is a FAD-dependent, two-domain multifunctional stress protein acting as a Phase II enzyme, activating cancer pro-drugs and stabilizing p53 and p73a oncosuppressors. We show that p.P187S causes structural and dynamic changes communicated to functional sites far from the mutated site, affecting the FAD binding site located at the N-terminal domain (NTD) and accelerating proteasomal degradation through dynamic effects on the C-terminal domain (CTD). Structural protein:protein interaction studies reveal that the cancer-associated polymorphism does not abolish the interaction with p73a, indicating that oncosuppressor destabilization largely mirrors the low intracellular stability of p.P187S. In conclusion, we show how a single disease associated amino acid change may allosterically perturb several functional sites in an oligomeric and multidomain protein. These results have important implications for the understanding of loss-of-function genetic diseases and the identification of novel structural hot spots as targets for pharmacological intervention

Switching from natalizumab to fingolimod: an observational study

Background – Multiple sclerosis patients who discontinue using natalizumab are at risk of a rebound in disease activity. However, the optimal alternative therapy is not currently known. Aims of the study – We report on clinical and MRI data and patient safety in a group of relapsing–remitting multiple sclerosis patients who tested seropositive for the JC virus and who have switched from natalizumab to fingolimod because of concerns regarding PML risks. Methods – The test for JC virus antibodies was performed in 18 relapsing–remitting multiple sclerosis patients who were being treated with natalizumab for more than 1 year. Eight seropositive patients switched to fingolimod while the seronegative patients continued with natalizumab. Results – After switching to fingolimod, five of eight patients (63%) experienced clinical relapses, and MRI activity was detected in six of eight patients (75%). Neither clinical relapses nor MRI activity was observed in the patients who continued with natalizumab. No serious adverse effects were detected. Conclusions – Natalizumab is an effective treatment for relapsing–remitting multiple sclerosis, but its discontinuation continues to be a complex problem. All of the therapies tried thus far, including fingolimod, have been unable to control the reactivation of the disease. Further studies addressing alternative therapies after natalizumab discontinuation are necessary

Reversible periodic orbits in a class of 3D continuous piecewise linear systems of differential equations

Agraïments: This work was partially supported by the Consejería de Educación y Ciencia de la Junta de Andalucía (TIC-0130, P08-FQM-03770). The second author is supported by Ministerio de Educaci'on, grant AP2008-02486

Online teaching tasks in the subjects biology and Spanish as a foreign language

hay consenso en admitir que uno de los rasgos distintivos que la sociedad demanda a la universidad del siglo XXI es la innovación educativa. de esta problemática surge el concepto “universidad innovadora”, caracterizada por la integración de las Tecnologías de la Información y la Comunicación (TIC) en todos sus procesos formativos. Esta problemática ha provocado un aumento en la presencia de las tendencias actuales de la integración de las TIC en la educación superior, que ha devenido en foco de interés para la investigación educativa. El trabajo que se presenta se centra en las experiencias de sus autoras en el desarrollo de clases en línea, de idioma español con fines específicos (aprendizaje en línea) y con utilización de dispositivos móviles (aprendizaje móvil) en del Curso Preparatorio (CP) de la facultad de Español para no hispanohablantes (fEnhI), de la Universidad de La habanaThere is consensus in admitting that one of the distinctive features that society demands of the 21st century university is educational innovation. from this problem arises the concept of "innovative university", characterized by the integration of Information and Communication Technologies (ICT) in all its training processes. This problem has caused an increase in the presence of current trends in the integration of ICT in higher education, which has become a focus of interest for educational research. The article that is presented focuses on the experiences of its authors in the development of online classes, of Spanish language for specific purposes (online learning) and with the use of mobile devices (mobile learning) in the Preparatory Course (CP) of the faculty of Spanish for non-Spanish Speakers (fEnhI), of the University of Havan

Enhanced vulnerability of human proteins towards disease-associated inactivation through divergent evolution

Human proteins are vulnerable towards disease-associated single amino acid replacements affecting protein stability and function. Interestingly, a few studies have shown that consensus amino acids from mammals or vertebrates can enhance protein stability when incorporated into human proteins. Here, we investigate yet unexplored relationships between the high vulnerability of human proteins towards disease-associated inactivation and recent evolutionary site-specific divergence of stabilizing amino acids. Using phylogenetic, structural and experimental analyses, we show that divergence from the consensus amino acids at several sites during mammalian evolution has caused local protein destabilization in two human proteins linked to disease: cancer-associated NQO1 and alanine: glyoxylate aminotransferase, mutated in primary hyperoxaluria type I. We demonstrate that a single consensus mutation (H80R) acts as a disease suppressor on the most common cancer-associated polymorphism in NQO1 (P187S). The H80R mutation reactivates P187S by enhancing FAD binding affinity through local and dynamic stabilization of its binding site. Furthermore, we show how a second suppressor mutation (E247Q) cooperates with H80R in protecting the P187S polymorphism towards inactivation through long-range allosteric communication within the structural ensemble of the protein. Our results support that recent divergence of consensus amino acids may have occurred with neutral effects on many functional and regulatory traits of wild-type human proteins. However, divergence at certain sites may have increased the propensity of some human proteins towards inactivation due to disease-associated mutations and polymorphisms. Consensus mutations also emerge as a potential strategy to identify structural hot-spots in proteins as targets for pharmacological rescue in loss-of-function genetic diseases.Spanish Ministry of Economy and Competitiveness, MINECO (BIO 2015 66426-R to JMSR, CTQ 2015-64445-R to JLN, ‘Factoría Española de Cristalización’, Consolider-Ingenio 2010 to JAG and SAF2015-69796 to ES), Junta de Andalucia (P11-CTS-07187 to ALP) and FEDER fun

Características clínicas y urodinámicas de las mujeres con detrusor hipoactivo

Objective: To describe the clinical and urodynamic features of the hypoactive detrusor (DU) in women. Methods: Cross sectional comparative study between two groups of women with lower tract urinary symptoms. Group 1 were patients with Pdet Qmax 30 or with the bladder emptying efficiency (BVE) criteria, and Group 2 were patients without DU. Central tendency measures and proportions were used to report results and parametric tests were performed to compare groups. Results: 155 patients were included, 44 with DU (Group 1) and 111 without DU (Group 2); mean age was 60,8 ± 16,3 and 55,7 ± 13,4 respectively (p=0,0468). Nocturia (p=0,0061) and micturition effort (p=0,000) were the only variables identified in the bivariate analysis who achieved statistical significance. Mean Watts factor (WF) was 3,2 ± 1,0 y 6,0 ± 2,2 in Group 1 and 2, respectively (p=0,000), while mean projected isovolumetric pressure 1 (PIP1) was 28,0 ± 7,5 and 45,9 ± 11,2, respectively (p=0,000). The multivariate analysis identified age above 60 years, nocturia and micturition effort associated with DU. Conclusion: Urodynamic parameters such as PIP1, BCI, BE and WF showed significant difference in the bivariate analysis, WF<5 and BCI <80 are best predictors of DU.Objetivo: Determinar las características clínicas y urodinámicas en mujeres con detrusor hipoactivo (DU). Material y métodos: Estudio de serie de casos de corte transversal, retrospectivo, comparativo, entre 2 grupos de pacientes femeninos con síntomas del tracto urinario inferior (STUI). Grupo 1: pacientes con DU según criterios urodinámicos, presión del del detrusor en el flujo máximo de 30 cm H20 (PdetQmax30) o eficiencia del vaciado de la vejiga (BVE) y grupo 2: pacientes sin DU. Se utilizaron medidas de tendencia central y proporciones para la descripción de los datos y pruebas paramétricas para la comparación entre grupos. Resultados: Ciento cincuenta y cinco pacientes fueron incluidos, 44 con DU (grupo 1) y 111 sin DU (grupo 2), con una media de edad de 60,8 ± 16,3 y 55,7 ± 13,4 respectivamente (p=0,0468). La nicturia (p=0,0061) y el esfuerzo miccional (p=0,000) fueron las únicas variables clínicas que presentaron una diferencia significativa en el análisis bivariado. La media de watts factor (WF) fue 3,2 ± 1,0 y 6,0 ± 2,2 en el grupo 1 y 2 respectivamente (p=0,000), mientras que el promedio de la presión isovolumétrica proyectada 1 (PIP1) fue de 28,0 ± 7,5 y 45,9 ± 11,2 respectivamente (p=0,000).En el análisis multivariado, la edad > 60 años, la nicturia, el esfuerzo miccional, tuvieron asociación significativa con DU. Conclusión: Las variables urodinámicas como PIP1, índice de contracción vesical (BCI), BVE y WF mostraron una diferencia significativa en el análisis bivariado, siendo el WF <5 y BCI <80 las que mejor identifican la presencia de DU en mujeres