Strong correlation between the antifungal effect of amphotericin B and its inhibitory action on germ-tube formation in a Candida albicans URA+ strain

The hypothetical capacity of amphotericin B to suppress the formation of germ-tubes, which is the first step of yeast-to-hypha conversion in Candida albicans, has been investigated in the wild-type strain CEY.1 (CAI.4-URA+). Exponential cells exposed to concentrations of amphotericin B below or around the MIC90, exhibited a weak reduction in the percentage of human serum-induced germ-tube formation at 37ºC compared with a non-exposed control. However, the dimorphic transition was drastically suppressed after addition of potentially lethal doses of amphotericin B, which also caused severe cell killing. In contrast, an identical experimental approach carried out with the fungistatic compound 5-fluorocytosine had no significant effect on the level of the germ-tube formation. Together, these results strongly point to a close correlation between the fungicidal action of amphotericin B and its ability to impair morphogenetic conversion in C. albicans. [Int Microbiol 2015; 18(1):25-31]Keywords: Candida albicans · amphotericin B · 5-fluorocytosine · germ-tube · cell killin

Trehalose accumulation induced during the oxidative stress response is independent of TPS1 mRNA levels in Candida albicans

Growing cells of the Candida albicans trehalose- deficient mutant tps1/tps1 were extremely sensitive to severe oxidative stress exposure (H2O2). However, their viability was not affected after saline stress or heatshock treatments, being roughly equivalent to that of the parental strain. In wild-type cells, these adverse conditions induced the intracellular accumulation of trehalose together with activation of trehalose-6P synthase, whereas the endogenous trehalose content and the corresponding biosynthetic activity were barely detectable in the tps1/tps1 mutant. The addition of cycloheximide did not prevent the marked induction of trehalose-6P synthase activity. Furthermore, the presence of H2O2 decreased the level of TPS1 mRNA expression. Hence, the conspicuous trehalose accumulation in response to oxidative stress is not induced by increased transcription of TPS1. Our results are consistent with a specific requirement of trehalose in order to withstand a severe oxidative stress in C. albicans, and suggest that trehalose accumulation observed under these conditions is a complex process that most probably involves post-translational modifications of the trehalose synthase complex

Evaluación de la competencia transversal “Responsabilidad ética, medioambiental y profesional” a través de una e-rúbrica en el laboratorio

[ES] El proceso de convergencia hacia el Espacio Europeo de Enseñanza Superior ha puesto de relieve la importancia del dominio de competencias transversales (CTs) durante la formación universitaria. Dichas competencias confieren al estudiante la capacidad de innovación y de adaptación a los cambios, siendo su adquisición necesaria para la vida profesional. En la Universidad Politécnica de Valencia, se han redactado 13 CTs que aúnan las competencias de la normativa vigente y las de las agencias de acreditación. En nuestro grupo de innovación educativa estudiamos diferentes métodos de enseñanza-aprendizaje y evaluación de las competencias transversales en asignaturas relacionadas con las ciencias de la vida. En concreto, en este trabajo presentamos una propuesta para evaluar la CT “Responsabilidad ética, medioambiental y profesional”. Esta competencia pretende la obtención de conocimientos, habilidades, destrezas y actitudes útiles para interactuar con el entorno, de forma ética, responsable y sostenible, ante uno mismo y los demás. Las asignaturas relacionadas con las ciencias de la vida y, en particular, sus créditos de laboratorio, resultan un marco idóneo para la adquisición de dicha competencia. Nuestra propuesta de evaluación de la misma se basa en una rúbrica que ha de ser cumplimentada por los pares a través de una aplicación telemática.Este trabajo ha sido financiado por un Proyecto de Innovación y Mejora Educativa concedido por el Vicerrectorado de Estudios, Calidad y Acreditación de la Universitat Politècnica de València.Bañuls Polo, M.; López Gresa, MP.; Cebolla Cornejo, J.; Díez Niclós, MJTDJ.; Esteras Gómez, C.; Ferriol Molina, M.; González Martínez, MÁ.... (2015). Evaluación de la competencia transversal “Responsabilidad ética, medioambiental y profesional” a través de una e-rúbrica en el laboratorio. En In-Red 2015 - CONGRESO NACIONAL DE INNOVACIÓN EDUCATIVA Y DE DOCENCIA EN RED. Editorial Universitat Politècnica de València. https://doi.org/10.4995/INRED2015.2015.154

Respuesta al estrés oxidativo (H202) en Candida albicans : función protectora del glutatión y las enzimas antioxidantes / Mª del Pilar González Párraga; directores, Juan Carlos Argüelles y José Antonio Hernández Cortés.

Tesis-Universidad de Murcia.Consulte la tesis en: BCA. GENERAL. ARCHIVO UNIVERSITARIO. T.M. 3245

Trehalose accumulation induced during the oxidative stress response is independent of TPS1 mRNA levels in Candida albicans

5 pages, 2 figures, 2 tables.Growing cells of the Candida albicans trehalose- deficient mutant tps1/tps1 were extremely sensitive to severe oxidative stress exposure (H2O2). However, their viability was not affected after saline stress or heatshock treatments, being roughly equivalent to that of the parental strain. In wild-type cells, these adverse conditions induced the intracellular accumulation of trehalose together with activation of trehalose-6P synthase, whereas the endogenous trehalose content and the corresponding biosynthetic activity were barely detectable in the tps1/tps1 mutant. The addition of cycloheximide did not prevent the marked induction of trehalose-6P synthase activity. Furthermore, the presence of H2O2 decreased the level of TPS1 mRNA expression. Hence, the conspicuous trehalose accumulation in response to oxidative stress is not induced by increased transcription of TPS1. Our results are consistent with a specific requirement of trehalose in order to withstand a severe oxidative stress in C. albicans, and suggest that trehalose accumulation observed under these conditions is a complex process that most probably involves post-translational modifications of the trehalose synthase complex.This work was partially supported by the research project ALI99–1224-C02–02 from CICYT (Spain) and PB/07/FS/02 from Fundación Séneca (Comunidad de Murcia, Spain).Peer reviewe

Aprendizaje innovador de la lecto-escritura como proceso

Experiencia sobre el aprendizaje de la lecto-escritura en las primeras etapas educativas, que consiste en implantar una metodología basada en un enfoque neurolingüístico para este aprendizaje. Los objetivos son: no causar en el alumno desajustes al cambiar de etapa educativa, realizar adaptaciones curriculares más adecuadas a cada alumno, incluidos los que necesitan educación especial, y prevenir el fracaso escolar. También se pretende la globalización con otras áreas de aprendizaje, despertar el interés por el lenguaje escrito y potenciar la creatividad. Las actividades se basan en ejercicios de lectura perceptiva, combinatoria, alfabética y universal. Se evalúa el proceso lecto-escritor de los alumnos, las actividades realizadas en el aula y el grado de consecución de los objetivos programados.Madrid (Comunidad Autónoma). Consejería de Educación y CulturaMadridMadrid (Comunidad Autónoma). Subdirección General de Formación del Profesorado. CRIF Las Acacias; General Ricardos 179 - 28025 Madrid; Tel. + 34915250893ES

Developmental outcome of electroencephalographic findings in SYNGAP1 encephalopathy

SYNGAP1 haploinsufficiency results in a developmental and epileptic encephalopathy (DEE) causing generalized epilepsies accompanied by a spectrum of neurodevelopmental symptoms. Concerning interictal epileptiform discharges (IEDs) in electroencephalograms (EEG), potential biomarkers have been postulated, including changes in background activity, fixation-off sensitivity (FOS) or eye closure sensitivity (ECS). In this study we clinically evaluate a new cohort of 36 SYNGAP1-DEE individuals. Standardized questionnaires were employed to collect clinical, electroencephalographic and genetic data. We investigated electroencephalographic findings, focusing on the cortical distribution of interictal abnormalities and their changes with age. Among the 36 SYNGAP1-DEE cases 18 presented variants in the SYNGAP1 gene that had never been previously reported. The mean age of diagnosis was 8 years and 8 months, ranging from 2 to 17 years, with 55.9% being male. All subjects had global neurodevelopmental/language delay and behavioral abnormalities; 83.3% had moderate to profound intellectual disability (ID), 91.7% displayed autistic traits, 73% experienced sleep disorders and 86.1% suffered from epileptic seizures, mainly eyelid myoclonia with absences (55.3%). A total of 63 VEEGs were revised, observing a worsening of certain EEG findings with increasing age. A disorganized background was observed in all age ranges, yet this was more common among older cases. The main IEDs were bilateral synchronous and asynchronous posterior discharges, accounting for ≥50% in all age ranges. Generalized alterations with maximum amplitude in the anterior region showed as the second most frequent IED (≥15% in all age ranges) and were also more common with increasing age. Finally, diffuse fast activity was much more prevalent in cases with 6 years or older. To the best of our knowledge, this is the first study to analyze EEG features across different age groups, revealing an increase in interictal abnormalities over infancy and adolescence. Our findings suggest that SYNGAP1 haploinsufficiency has complex effects in human brain development, some of which might unravel at different developmental stages. Furthermore, they highlight the potential of baseline EEG to identify candidate biomarkers and the importance of natural history studies to develop specialized therapies and clinical trials

Developmental outcome of electroencephalographic findings in SYNGAP1 encephalopathy

SYNGAP1 haploinsufficiency results in a developmental and epileptic encephalopathy (DEE) causing generalized epilepsies accompanied by a spectrum of neurodevelopmental symptoms. Concerning interictal epileptiform discharges (IEDs) in electroencephalograms (EEG), potential biomarkers have been postulated, including changes in background activity, fixation-off sensitivity (FOS) or eye closure sensitivity (ECS). In this study we clinically evaluate a new cohort of 36 SYNGAP1-DEE individuals. Standardized questionnaires were employed to collect clinical, electroencephalographic and genetic data. We investigated electroencephalographic findings, focusing on the cortical distribution of interictal abnormalities and their changes with age. Among the 36 SYNGAP1-DEE cases 18 presented variants in the SYNGAP1 gene that had never been previously reported. The mean age of diagnosis was 8 years and 8 months, ranging from 2 to 17 years, with 55.9% being male. All subjects had global neurodevelopmental/language delay and behavioral abnormalities; 83.3% had moderate to profound intellectual disability (ID), 91.7% displayed autistic traits, 73% experienced sleep disorders and 86.1% suffered from epileptic seizures, mainly eyelid myoclonia with absences (55.3%). A total of 63 VEEGs were revised, observing a worsening of certain EEG findings with increasing age. A disorganized background was observed in all age ranges, yet this was more common among older cases. The main IEDs were bilateral synchronous and asynchronous posterior discharges, accounting for ≥50% in all age ranges. Generalized alterations with maximum amplitude in the anterior region showed as the second most frequent IED (≥15% in all age ranges) and were also more common with increasing age. Finally, diffuse fast activity was much more prevalent in cases with 6 years or older. To the best of our knowledge, this is the first study to analyze EEG features across different age groups, revealing an increase in interictal abnormalities over infancy and adolescence. Our findings suggest that SYNGAP1 haploinsufficiency has complex effects in human brain development, some of which might unravel at different developmental stages. Furthermore, they highlight the potential of baseline EEG to identify candidate biomarkers and the importance of natural history studies to develop specialized therapies and clinical trials

Table1_Developmental outcome of electroencephalographic findings in SYNGAP1 encephalopathy.xlsx

SYNGAP1 haploinsufficiency results in a developmental and epileptic encephalopathy (DEE) causing generalized epilepsies accompanied by a spectrum of neurodevelopmental symptoms. Concerning interictal epileptiform discharges (IEDs) in electroencephalograms (EEG), potential biomarkers have been postulated, including changes in background activity, fixation-off sensitivity (FOS) or eye closure sensitivity (ECS). In this study we clinically evaluate a new cohort of 36 SYNGAP1-DEE individuals. Standardized questionnaires were employed to collect clinical, electroencephalographic and genetic data. We investigated electroencephalographic findings, focusing on the cortical distribution of interictal abnormalities and their changes with age. Among the 36 SYNGAP1-DEE cases 18 presented variants in the SYNGAP1 gene that had never been previously reported. The mean age of diagnosis was 8 years and 8 months, ranging from 2 to 17 years, with 55.9% being male. All subjects had global neurodevelopmental/language delay and behavioral abnormalities; 83.3% had moderate to profound intellectual disability (ID), 91.7% displayed autistic traits, 73% experienced sleep disorders and 86.1% suffered from epileptic seizures, mainly eyelid myoclonia with absences (55.3%). A total of 63 VEEGs were revised, observing a worsening of certain EEG findings with increasing age. A disorganized background was observed in all age ranges, yet this was more common among older cases. The main IEDs were bilateral synchronous and asynchronous posterior discharges, accounting for ≥50% in all age ranges. Generalized alterations with maximum amplitude in the anterior region showed as the second most frequent IED (≥15% in all age ranges) and were also more common with increasing age. Finally, diffuse fast activity was much more prevalent in cases with 6 years or older. To the best of our knowledge, this is the first study to analyze EEG features across different age groups, revealing an increase in interictal abnormalities over infancy and adolescence. Our findings suggest that SYNGAP1 haploinsufficiency has complex effects in human brain development, some of which might unravel at different developmental stages. Furthermore, they highlight the potential of baseline EEG to identify candidate biomarkers and the importance of natural history studies to develop specialized therapies and clinical trials.</p