Coexistence of Wolbachia with Buchnera aphidicola and a secondary symbiont in the aphid Cinara cedri.

Intracellular symbiosis is very common in the insect world. For the aphid Cinara cedri, we have identified by electron microscopy three symbiotic bacteria that can be characterized by their different sizes, morphologies, and electrodensities. PCR amplification and sequencing of the 16S ribosomal DNA (rDNA) genes showed that, in addition to harboring Buchnera aphidicola, the primary endosymbiont of aphids, C. cedri harbors a secondary symbiont (S symbiont) that was previously found to be associated with aphids (PASS, or R type) and an alpha-proteobacterium that belongs to the Wolbachia genus. Using in situ hybridization with specific bacterial probes designed for symbiont 16S rDNA sequences, we have shown that Wolbachia was represented by only a few minute bacteria surrounding the S symbionts. Moreover, the observed B. aphidicola and the S symbionts had similar sizes and were housed in separate specific bacterial cells, the bacteriocytes. Interestingly, in contrast to the case for all aphids examined thus far, the S symbionts were shown to occupy a similarly sized or even larger bacteriocyte space than B. aphidicola. These findings, along with the facts that C. cedri harbors the B. aphidicola strain with the smallest bacterial genome and that the S symbionts infect all Cinara spp. analyzed so far, suggest the possibility of bacterial replacement in these species

Momento Económico (13)

En este número Temas de hoy, El desprendimiento de las paraestatales, 21 México: La coyuntura del susector paraestatal, Ramón Martínez Escamilla, 3/ Imperialismo y petróleo: una evocación de la leyenda de Transilvania, Isaac Palacios Solano, 6/ El mercado petrolero mundial y las perspectivas de recuperación de la economía mexicana, Raúl Gonzlllez Soriano, 9/ Presupuesto del D.F. para 1985: 6% menos que en 1984, Alejandro Méndez Rodriguez, 11/ El impacto de la política urbana del régimen actual en los sectores populares, Bernardo Navano y Jum Manuel Ramírez S., 1

Incorporando dispositivos de radio definida por software en la materia de Comunicaciones Digitales: del grupo piloto a la gran clase

La innovación educativa es un proceso que se extiende más allá de un curso académico. En su desarrollo se distinguen las etapas de planificación, implementación, evaluación y realimentación, para identificar aspectos susceptibles de mejora. En esta contribución presentamos el trabajo desarrollado en los dos últimos cursos en la asignatura Teoría de la Comunicación (materia de Comunicaciones Digitales), Grado en Ingeniería Telemática, de la Universitat de València. Concretamente, se incorporan dispositivos de radio definida por software en los laboratorios como herramienta para conseguir unas prácticas más realistas. El artículo describe el proceso de adaptación de una sesión de laboratorio, que inicialmente fue desarrollada por un grupo piloto reducido en el curso 2018-2019, para un grupo experimental de laboratorio en el curso 2019-2020. Para evaluar el impacto de la innovación se cuantifica la implicación del alumnado, comparando los resultados del grupo experimental con respecto a dos grupos de control que han continuado con las sesiones simuladas estándar. Los resultados indican que el impacto ha sido positivo en la capacidad de los estudiantes para afrontar nuevos retos y en su percepción de la relevancia de las actividades que realizan, aunque esta mejora no se refleje en su capacidad de centrarse en ellas.Educational innovation is a process that extends beyond an academic year. In its development, the stages of planning, implementation, evaluation and feedback are distinguished in order to identify aspects that could be improved. In this contribution, we present the work developed over the last two years in the subject Communication Theory (Digital Communications), Degree in Telematic Engineering, from the University of Valencia. Specifically, software defined radio devices have been incorporated in the laboratories as a tool to bring students closer to more realistic practices. The paper describes the adaptation process of a laboratory session, which was initially developed by a small pilot group in the academic year 2018-2019, for an experimental laboratory group in the academic year 2019-2020. In order to evaluate the impact of the innovation, the involvement of the students is quantified, comparing the results of the experimental group with two control groups that have continued with the standard simulated sessions. The results indicate that the impact has been positive on the students’ ability to face new challenges and on their perception of the relevance of the activities they carry out, although this improvement is not reflected in their ability to focus on the

Normalization of sphingomyelin levels by 2-hydroxyoleic acid induces autophagic cell death of SF767 cancer cells

The very high mortality rate of gliomas reflects the unmet therapeutic need associated with this type of brain tumor. We have discovered that the plasma membrane fulfills a critical role in the propagation of tumorigenic signals, whereby changes in membrane lipid content can either activate or silence relevant pathways. We have designed a synthetic fatty acid, 2-hydroxyoleic acid (2OHOA), that specifically activates sphingomyelin synthase (SGMS), thereby modifying the lipid content of cancer cell membranes and restoring lipid levels to those found in normal cells. In reverting, the structure of the membrane by activating SGMS, 2OHOA inhibits the RAS-MAPK pathway, which in turn fails to activate the CCND (Cyclin D)-CDK4/CDK6 and PI3K-AKT1 pathways. The overall result in SF767 cancer cells, a line that is resistant to apoptosis, is the sequential induction of cell cycle arrest, cell differentiation and autophagy. Such effects are not observed in normal cells (MRC-5) and thus, this specific activation of programmed cell death infers greater efficacy and lower toxicity to 2OHOA than that associated with temozolomide (TMZ), the reference drug for the treatment of glioma

2-Hydroxyoleate, a nontoxic membrane binding anticancer drug, induces glioma cell differentiation and autophagy

Despite recent advances in the development of new cancer therapies, the treatment options for glioma remain limited, and the survival rate of patients has changed little over the past three decades. Here, we show that 2-hydroxyoleic acid (2OHOA) induces differentiation and autophagy of human glioma cells. Compared to the current reference drug for this condition, temozolomide (TMZ), 2OHOA combated glioma more efficiently and, unlike TMZ, tumor relapse was not observed following 2OHOA treatment. The novel mechanism of action of 2OHOA is associated with important changes in membrane-lipid composition, primarily a recovery of sphingomyelin (SM) levels, which is markedly low in glioma cells before treatment. Parallel to membrane-lipid regulation, treatment with 2OHOA induced a dramatic translocation of Ras from the membrane to the cytoplasm, which inhibited the MAP kinase pathway, reduced activity of the PI3K/Akt pathway, and downregulated Cyclin D-CDK4/6 proteins followed by hypophosphorylation of the retinoblastoma protein (RB). These regulatory effects were associated with induction of glioma cell differentiation into mature glial cells followed by autophagic cell death. Given its high efficacy, low toxicity, ease of oral administration, and good distribution to the brain, 2OHOA constitutes a new and potentially valuable therapeutic tool for glioma patients

Evaluación del impacto del uso de dispositivos de radio definida por software como herramienta docente en la materia de comunicaciones digitales

La innovación educativa es un proceso que se extiende más allá de un año académico. En su desarrollo se distinguen las etapas de planificación, implementación, evaluación y retroalimentación para identificar los aspectos susceptibles de mejora. En esta contribución, presentamos un procedimiento para evaluar el impacto del uso de dispositivos de radio definidos por software en los laboratorios de comunicaciones digitales. Este procedimiento evalúa el compromiso de los estudiantes, además se implementan sesiones de laboratorio más realistas que se acercan a los sistemas de comunicaciones actuales y se alejan de las prácticas de simulación estándar. Se cuantifica el compromiso de los estudiantes, comparando los resultados de un grupo experimental con dos grupos de control que han continuado con las sesiones simuladas estándar. Los resultados indican que el impacto ha sido positivo en la capacidad de los alumnos para afrontar nuevos retos y en su percepción de la relevancia de las actividades que realizan, aunque esta mejora no se refleja en su capacidad de concentración.UV-SFPIE PID19-1097673Educational innovation is a process that extends beyond an academic year. In its development, the stages of planning, implementation, evaluation and feedback are distinguished in order to identify aspects that could be improved. In this contribution, we present a procedure for evaluating the impact of the use of software-defined radio devices in digital communications laboratories. This procedure evaluates the students' engagement, following more realistic laboratory sessions that are closer to current communications systems and far from standard simulation practices. The engagement of the students is quantified, comparing the results of an experimental group with two control groups that have continued with the standard simulated sessions. The results indicate that the impact has been positive on the students' ability to face new challenges and on their perception of the relevance of the activities they carry out, although this improvement is not reflected in their ability to focus on them

Protein misfolding and clearance in the pathogenesis of a new infantile onset ataxia caused by mutations in PRDX3

17 páginas, 8 figurasPeroxiredoxin 3 (PRDX3) encodes a mitochondrial antioxidant protein, which is essential for the control of reactive oxygen species homeostasis. So far, PRDX3 mutations are involved in mild-to-moderate progressive juvenile onset cerebellar ataxia. We aimed to unravel the molecular bases underlying the disease in an infant suffering from cerebellar ataxia that started at 19 months old and presented severe cerebellar atrophy and peripheral neuropathy early in the course of disease. By whole exome sequencing, we identified a novel homozygous mutation, PRDX3 p.D163E, which impaired the mitochondrial ROS defense system. In mouse primary cortical neurons, the exogenous expression of PRDX3 p.D163E was reduced and triggered alterations in neurite morphology and in mitochondria. Mitochondrial computational parameters showed that p.D163E led to serious mitochondrial alterations. In transfected HeLa cells expressing the mutation, mitochondria accumulation was detected by correlative light electron microscopy. Mitochondrial morphology showed severe changes, including extremely damaged outer and inner membranes with a notable cristae disorganization. Moreover, spherical structures compatible with lipid droplets were identified, which can be associated with a generalized response to stress and can be involved in the removal of unfolded proteins. In the patient's fibroblasts, PRDX3 expression was nearly absent. The biochemical analysis suggested that the mutation p.D163E would result in an unstable structure tending to form aggregates that trigger unfolded protein responses via mitochondria and endoplasmic reticulum. Altogether, our findings broaden the clinical spectrum of the recently described PRDX3-associated neurodegeneration and provide new insight into the pathological mechanisms underlying this new form of cerebellar ataxia.The Instituto de Salud Carlos III (ISCIII)—Subdirección General de Evaluación y Fomento de la Investigación within the framework of the National R + D + I Plan cofunded with European Regional Development Funds (ERDF) (grants PI18/00147 and PI21/00103 to C.E.); the Spanish Ministry of Economy and Competitiveness (grant SAF2017-89020-R to P.F.); the Fundació La Marató TV3 (grants 20143130 and 20143131 to B.P.-D. and C.E.) and the Generalitat Valenciana (grant PROMETEO/2018/135 to C.E.). Part of the equipment employed in this work was funded by Generalitat Valenciana and co-financed with ERDF (OP ERDF of Comunitat Valenciana 2014-2020). P.F. and A.R.-P. are supported by the Spanish Ministry of Science and Innovation (grants RyC-2014-16410 to P.F. and PRE2018-083562 to A.R.-P.).Peer reviewe

Clinical guide of the Spanish Society of Nephrology on the prevention and treatment of peritoneal infection in peritoneal dialysis

[Resumen] Las infecciones peritoneales siguen constituyendo una complicación muy relevante de la diálisis peritoneal, por su incidencia todavía elevada y por sus importantes consecuencias clínicas, en términos de mortalidad, fracaso de la técnica y costes para el sistema sanitario. Las prácticas de prevención y tratamiento de esta complicación muestran una notable heterogeneidad derivada, entre otros factores, de la complejidad del problema y de la escasez de evidencia clínica que permitan responder de manera clara a muchas de las dudas planteadas. El propósito de este documento es proporcionar una revisión completa y actualizada de los métodos de diagnóstico, prevención y tratamiento de estas infecciones. El documento se ha elaborado tomando como referencia de partida la guía más reciente de la Sociedad Internacional de Diálisis Peritoneal (2016). Mientras que para el capítulo diagnóstico se ha adoptado una estructura más narrativa, el análisis de las medidas de prevención y tratamiento ha seguido una metodología sistemática (Grading of Recommendations, Assessment, Development and Evaluation [GRADE]), que especifica el nivel de evidencia y la fuerza de las sugerencias y recomendaciones propuestas, y facilita actualizaciones futuras de la guía. La gran extensión y numerosas recomendaciones o sugerencias emanadas de la revisión ponen de manifiesto la complejidad y gran número de facetas a tener en cuenta para un adecuado abordaje de esta importante complicación de la diálisis peritoneal.[Abstract] Peritoneal infections still represent a most feared complication of chronic peritoneal dialysis, due to their high incidence and relevant clinical consequences, including direct mortality, technique failure and a significant burden for the health system. The practices for prevention and treatment of this complication show a remarkable heterogeneity emerging, among other factors, from the complexity of the problem and from a paucity of quality evidence which could permit to respond clearly to many of the raised questions. The purpose of this document is to provide a complete and updated review of the main methods of diagnosis, prevention and treatment of these infections. The document has been elaborated taking as a reference the most recent guidelines of the International Society of Peritoneal Dialysis (2016). The diagnostic considerations are presented in a narrative style while, for prevention and therapy, we have used a systematic methodology (Grading of Recommendations, Assessment, Development and Evaluation [GRADE]), which specifies the level of evidence and the strength of the proposed suggestions and recommendations and facilitates future updates of the document. The length of the document and the many suggestions and recommendations coming out of the review underline the large number and the complexity of the factors to be taken into consideration for an adequate approach to this complication of peritoneal dialysis

Neddylation orchestrates the complex transcriptional and posttranscriptional program that drives Schwann cell myelination

Myelination is essential for neuronal function and health. In peripheral nerves, >100 causative mutations have been identified that cause Charcot-Marie-Tooth disease, a disorder that can affect myelin sheaths. Among these, a number of mutations are related to essential targets of the posttranslational modification neddylation, although how these lead to myelin defects is unclear. Here, we demonstrate that inhibiting neddylation leads to a notable absence of peripheral myelin and axonal loss both in developing and regenerating mouse nerves. Our data indicate that neddylation exerts a global influence on the complex transcriptional and posttranscriptional program by simultaneously regulating the expression and function of multiple essential myelination signals, including the master transcription factor EGR2 and the negative regulators c-Jun and Sox2, and inducing global secondary changes in downstream pathways, including the mTOR and YAP/TAZ signaling pathways. This places neddylation as a critical regulator of myelination and delineates the potential pathogenic mechanisms involved in CMT mutations related to neddylation

Neddylation orchestrates the complex transcriptional and posttranscriptional program that drives Schwann cell myelination

Myelination is essential for neuronal function and health. In peripheral nerves, >100 causative mutations have been identified that cause Charcot-Marie-Tooth disease, a disorder that can affect myelin sheaths. Among these, a number of mutations are related to essential targets of the posttranslational modification neddylation, although how these lead to myelin defects is unclear. Here, we demonstrate that inhibiting neddylation leads to a notable absence of peripheral myelin and axonal loss both in developing and regenerating mouse nerves. Our data indicate that neddylation exerts a global influence on the complex transcriptional and posttranscriptional program by simultaneously regulating the expression and function of multiple essential myelination signals, including the master transcription factor EGR2 and the negative regulators c-Jun and Sox2, and inducing global secondary changes in downstream pathways, including the mTOR and YAP/TAZ signaling pathways. This places neddylation as a critical regulator of myelination and delineates the potential pathogenic mechanisms involved in CMT mutations related to neddylation