Identification and characterization of PlAlix, the Alix homologue from the Mediterranean sea urchin Paracentrotus lividus.

The sea urchin provides a relatively simple and tractable system for analyzing the early stages of embryo development. Here, we use the sea urchin species, Paracentrotus lividus, to investigate the role of Alix in key stages of embryogenesis, namely the egg fertilization and the first cleavage division. Alix is a multifunctional protein involved in different cellular processes including endocytic membrane trafficking, filamentous (F)-actin remodeling, and cytokinesis. Alix homologues have been identified in different metazoans; in these organisms, Alix is involved in oogenesis and in determination/differentiation events during embryo development. Herein, we describe the identification of the sea urchin homologue of Alix, PlAlix. The deduced amino acid sequence shows that Alix is highly conserved in sea urchins. Accordingly, we detect the PlAlix protein cross-reacting with monoclonal Alix antibodies in extracts from P. lividus, at different developmental stages. Focusing on the role of PlAlix during early embryogenesis we found that PlAlix is a maternal protein that is expressed at increasingly higher levels from fertilization to the 2-cell stage embryo. In sea urchin eggs, PlAlix localizes throughout the cytoplasm with a punctuated pattern and, soon after fertilization, accumulates in larger puncta in the cytosol, and in microvilli-like protrusions. Together our data show that PlAlix is structurally conserved from sea urchin to mammals and may open new lines of inquiry into the role of Alix during the early stages of embryo development

Improving the vibration suppression capabilities of a magneto-rheological damper using hybrid active and semi-active control

This paper presents a new hybrid active & semi-active control method for vibration suppression in flexible structures. The method uses a combination of a semi-active device and an active control actuator situated elsewhere in the structure to suppress vibrations. The key novelty is to use the hybrid controller to enable the magneto-rheological damper to achieve a performance as close to a fully active device as possible. This is achieved by ensuring that the active actuator can assist the magneto-rheological damper in the regions where energy is required. In addition, the hybrid active & semi-active controller is designed to minimize the switching of the semi-active controller. The control framework used is the immersion and invariance control technique in combination with sliding mode control. A two degree-of-freedom system with lightly damped resonances is used as an example system. Both numerical and experimental results are generated for this system, and then compared as part of a validation study. The experimental system uses hardware-in-the-loop to simulate the effect of both the degrees-of-freedom. The results show that the concept is viable both numerically and experimentally, and improved vibration suppression results can be obtained for the magneto-rheological damper that approach the performance of an active device

Dysregulated Expression of Glycolipids in Tumor Cells: From Negative Modulator of Anti-tumor Immunity to Promising Targets for Developing Therapeutic Agents

Glycolipids are complex molecules consisting of a ceramide lipid moiety linked to a glycan chain of variable length and structure. Among these are found the gangliosides, which are sialylated glycolipids ubiquitously distributed on the outer layer of vertebrate plasma membranes. Changes in the expression of certain species of gangliosides have been described to occur during cell proliferation, differentiation and ontogenesis. However, the aberrant and elevated expression of gangliosides has been also observed in different types of cancer cells, thereby promoting tumor survival. Moreover, gangliosides are actively released from the membrane of tumor cells, having a strong impact on impairing anti-tumor immunity. Beyond the undesirable effects of gangliosides in cancer cells, a substantial number of cancer immunotherapies have been developed in recent years that have used gangliosides as the main target. This has resulted in successful immune cell- or antibody-responses against glycolipids, with promising results having been obtained in clinical trials. In this review, we provide a general overview on the metabolism of glycolipids, both in normal and tumor cells, as well as examining glycolipid-mediated immune modulation and the main successes achieved in immunotherapies using gangliosides as molecular targets

Leukodystrophies: a proposed classification system based on pathological changes and pathogenetic mechanisms

Leukodystrophies are genetically determined disorders characterized by the selective involvement of the central nervous system white matter. Onset may be at any age, from prenatal life to senescence. Many leukodystrophies are degenerative in nature, but some only impair white matter function. The clinical course is mostly progressive, but may also be static or even improving with time. Progressive leukodystrophies are often fatal, and no curative treatment is known. The last decade has witnessed a tremendous increase in the number of defined leukodystrophies also owing to a diagnostic approach combining magnetic resonance imaging pattern recognition and next generation sequencing. Knowledge on white matter physiology and pathology has also dramatically built up. This led to the recognition that only few leukodystrophies are due to mutations in myelin- or oligodendrocyte-specific genes, and many are rather caused by defects in other white matter structural components, including astrocytes, microglia, axons and blood vessels. We here propose a novel classification of leukodystrophies that takes into account the primary involvement of any white matter component. Categories in this classification are the myelin disorders due to a primary defect in oligodendrocytes or myelin (hypomyelinating and demyelinating leukodystrophies, leukodystrophies with myelin vacuolization); astrocytopathies; leuko-axonopathies; microgliopathies; and leuko-vasculopathies. Following this classification, we illustrate the neuropathology and disease mechanisms of some leukodystrophies taken as example for each category. Some leukodystrophies fall into more than one category. Given the complex molecular and cellular interplay underlying white matter pathology, recognition of the cellular pathology behind a disease becomes crucial in addressing possible treatment strategies

Hijxs de familias homoparentales y diversidad sexual en la educación inicial

El presente trabajo aborda, por tanto, la temática de hijxs de familias homoparentales y su inserción en el Nivel Inicial del sistema educativo argentino.\n Según los resultados obtenidos del último Censo Nacional de 2010, se declaran 24.228 hogares con parejas del mismo sexo en todo el país, de las cuales 5079 tiene hijxs a su cargo. La cantidad de niñxs escolarizadxs que conviven bajo estas organizaciones familiares asciende a 7600. En este proceso de cambio histórico, social y cultural, el rol de los jardines de infantes y las escuelas, además de innegable e indiscutible, es fundamental.\n Dentro del ámbito educativo, lxs maestrxs jardinerxs y docentes cuentan con una herramienta clave de inclusión, formación y transmisión de conocimiento de las nuevas familias, norma que está en vigencia cuando “Lulú” asiste al jardín: el Programa Nacional de Educación Sexual Integral, ley N°26.150. Esta normativa y el grado de implementación de sus contenidos respecto de las nuevas estructuras familiares actuales, son un eje pertinente que atraviesa toda la investigación.\n La comprensión del tema engloba las experiencias de las familias, la visión de los agentes del sistema educativo y la mirada de educadores sexuales y psicólogxs especializados en Género y Sexualidad.Fil: D’Azzo, Gala Nerea. Universidad de Buenos Aires. Facultad de Ciencias Sociales. Buenos Aires, Argentin