Inclusivos los queremos: homoparentalidades en jardines de infantes de la Ciudad Autónoma de Buenos Aires y el conurbano bonaerense

El trabajo se propone describir y analizar la experiencia educativa de familias homoparentales en jardines de infantes de la Ciudad Autónoma de Buenos Aires y las localidades del conurbano bonaerense Ituzaingó, Ramos Mejía y San Fernando, considerando las dificultades pedagógicas y presupuestarias en la implementación de las leyes de educación sexual a nivel nacional y local. Con el propósito de conocer y visibilizar las vivencias que están teniendo al interior de las instituciones y las relaciones que establecen con la comunidad escolar, la investigación reúne testimonios de adultos integrantes de las organizaciones familiares, sistematizados en los ejes Criterios de elección de la institución educativa, Entrevistas de admisión, Visibilidad dentro de la escuela, y Relación con los maestros y compañeros. En las conclusiones, se arriba a la existencia de vínculos actuales entre diversidad familiar y educación religiosa, se identifica la persistencia del silencio en el ámbito educativo como herramienta de transmisión y se observa una invisibilización de hechos discriminantes hacia el interior de las instituciones escolares.Facultad de Periodismo y Comunicación Socia

Inclusivos los queremos: homoparentalidades en jardines de infantes de la Ciudad Autónoma de Buenos Aires y el conurbano bonaerense

El trabajo se propone describir y analizar la experiencia educativa de familias homoparentales en jardines de infantes de la Ciudad Autónoma de Buenos Aires y las localidades del conurbano bonaerense Ituzaingó, Ramos Mejía y San Fernando, considerando las dificultades pedagógicas y presupuestarias en la implementación de las leyes de educación sexual a nivel nacional y local. Con el propósito de conocer y visibilizar las vivencias que están teniendo al interior de las instituciones y las relaciones que establecen con la comunidad escolar, la investigación reúne testimonios de adultos integrantes de las organizaciones familiares, sistematizados en los ejes Criterios de elección de la institución educativa, Entrevistas de admisión, Visibilidad dentro de la escuela, y Relación con los maestros y compañeros. En las conclusiones, se arriba a la existencia de vínculos actuales entre diversidad familiar y educación religiosa, se identifica la persistencia del silencio en el ámbito educativo como herramienta de transmisión y se observa una invisibilización de hechos discriminantes hacia el interior de las instituciones escolares.Facultad de Periodismo y Comunicación Socia

Inclusivos los queremos: homoparentalidades en jardines de infantes de la Ciudad Autónoma de Buenos Aires y el conurbano bonaerense

El trabajo se propone describir y analizar la experiencia educativa de familias homoparentales en jardines de infantes de la Ciudad Autónoma de Buenos Aires y  las localidades del conurbano bonaerense Ituzaingó, Ramos Mejía y San Fernando, considerando las dificultades pedagógicas y presupuestarias en la implementación de las leyes de educación sexual a nivel nacional y local.Con el propósito de conocer y visibilizar las vivencias que están teniendo al interior de las instituciones y las relaciones que establecen con la comunidad escolar, la investigación reúne testimonios de adultos integrantes de las organizaciones familiares, sistematizados en los ejes Criterios de elección de la institución educativa, Entrevistas de admisión, Visibilidad dentro de la escuela, y Relación con los maestros y compañeros.En las conclusiones, se arriba a la existencia de vínculos actuales entre diversidad familiar y educación religiosa, se identifica la persistencia del silencio en el ámbito educativo como herramienta de transmisión y se observa una invisibilización de hechos discriminantes hacia el interior de las instituciones escolares

In silico identification of new putative pathogenic variants in the NEU1 sialidase gene affecting enzyme function and subcellular localization

The NEU1 gene is the first identified member of the human sialidases, glycohydrolitic enzymes that remove the terminal sialic acid from oligosaccharide chains. Mutations in NEU1 gene are causative of sialidosis (MIM 256550), a severe lysosomal storage disorder showing autosomal recessive mode of inheritance. Sialidosis has been classified into two subtypes: sialidosis type I, a normomorphic, late-onset form, and sialidosis type II, a more severe neonatal or early-onset form. A total of 50 causative mutations are reported in HGMD database, most of which are missense variants. To further characterize the NEU1 gene and identify new functionally relevant protein isoforms, we decided to study its genetic variability in the human population using the data generated by two large sequencing projects: the 1000 Genomes Project (1000G) and the NHLBI GO Exome Sequencing Project (ESP). Together these two datasets comprise a cohort of 7595 sequenced individuals, making it possible to identify rare variants and dissect population specific ones. By integrating this approach with biochemical and cellular studies, we were able to identify new rare missense and frameshift alleles in NEU1 gene. Among the 9 candidate variants tested, only two resulted in significantly lower levels of sialidase activity (pC and c.700G>A. These two mutations give rise to the amino acid substitutions p.V217A and p.D234N, respectively. NEU1 variants including either of these two amino acid changes have 44% and 25% residual sialidase activity when compared to the wild-type enzyme, reduced protein levels and altered subcellular localization. Thus they may represent new, putative pathological mutations resulting in sialidosis type I. The in silico approach used in this study has enabled the identification of previously unknown NEU1 functional alleles that are widespread in the population and could be tested in future functional studies

Neuraminidase 1 Is a Negative Regulator of Lysosomal Exocytosis

SummaryLysosomal exocytosis is a Ca2+-regulated mechanism that involves proteins responsible for cytoskeletal attachment and fusion of lysosomes with the plasma membrane. However, whether luminal lysosomal enzymes contribute to this process remains unknown. Here we show that neuraminidase NEU1 negatively regulates lysosomal exocytosis in hematopoietic cells by processing the sialic acids on the lysosomal membrane protein LAMP-1. In macrophages from NEU1-deficient mice, a model of the disease sialidosis, and in patients' fibroblasts, oversialylated LAMP-1 enhances lysosomal exocytosis. Silencing of LAMP-1 reverts this phenotype by interfering with the docking of lysosomes at the plasma membrane. In neu1−/− mice the excessive exocytosis of serine proteases in the bone niche leads to inactivation of extracellular serpins, premature degradation of VCAM-1, and loss of bone marrow retention. Our findings uncover an unexpected mechanism influencing lysosomal exocytosis and argue that exacerbations of this process form the basis for certain genetic diseases

Ozz-E3 Ubiquitin Ligase Targets Sarcomeric Embryonic Myosin Heavy Chain during Muscle Development

Muscle contractile proteins are expressed as a series of developmental isoforms that are in constant dynamic remodeling during embryogenesis, but how obsolete molecules are recognized and removed is not known. Ozz is a developmentally regulated protein that functions as the adaptor component of a RING-type ubiquitin ligase complex specific to striated muscle. Ozz−/− mutants exhibit defects in myofibrillogenesis and myofiber differentiation. Here we show that Ozz targets the rod portion of embryonic myosin heavy chain and preferentially recognizes the sarcomeric rather than the soluble pool of myosin. We present evidence that Ozz binding to the embryonic myosin isoform within sarcomeric thick filaments marks it for ubiquitination and proteolytic degradation, allowing its replacement with neonatal or adult isoforms. This unique function positions Ozz within a system that facilitates sarcomeric myosin remodeling during muscle maturation and regeneration. Our findings identify Ozz-E3 as the ubiquitin ligase complex that interacts with and regulates myosin within its fully assembled cytoskeletal structure

Alix protein is substrate of Ozz-E3 ligase and modulates actin remodeling in skeletal muscle

Alix/AIP1 is a multifunctional adaptor protein that participates in basic cellular processes, including membrane trafficking and actin cytoskeleton assembly, by binding selectively to a variety of partner proteins. However, the mechanisms regulating Alix turnover, subcellular distribution, and function in muscle cells are unknown. We now report that Alix is expressed in skeletal muscle throughout myogenic differentiation. In myotubes, a specific pool of Alix colocalizes with Ozz, the substrate-binding component of the muscle-specific ubiquitin ligase complex Ozz-E3. We found that interaction of the two endogenous proteins in the differentiated muscle fibers changes Alix conformation and promotes its ubiquitination. This in turn regulates the levels of the protein in specific subcompartments, in particular the one containing the actin polymerization factor cortactin. In Ozz(−/−) myotubes, the levels of filamentous (F)-actin is perturbed, and Alix accumulates in large puncta positive for cortactin. In line with this observation, we show that the knockdown of Alix expression in C2C12 muscle cells affects the amount and distribution of F-actin, which consequently leads to changes in cell morphology, impaired formation of sarcolemmal protrusions, and defective cell motility. These findings suggest that the Ozz-E3 ligase regulates Alix at sites where the actin cytoskeleton undergoes remodeling

Information-theoretic approach to the study of control systems

We propose an information-theoretic framework for analyzing control systems based on the close relationship of controllers to communication channels. A communication channel takes an input state and transforms it into an output state. A controller, similarly, takes the initial state of a system to be controlled and transforms it into a target state. In this sense, a controller can be thought of as an actuation channel that acts on inputs to produce desired outputs. In this transformation process, two different control strategies can be adopted: (i) the controller applies an actuation dynamics that is independent of the state of the system to be controlled (open-loop control); or (ii) the controller enacts an actuation dynamics that is based on some information about the state of the controlled system (closed-loop control). Using this communication channel model of control, we provide necessary and sufficient conditions for a system to be perfectly controllable and perfectly observable in terms of information and entropy. In addition, we derive a quantitative trade-off between the amount of information gathered by a closed-loop controller and its relative performance advantage over an open-loop controller in stabilizing a system. This work supplements earlier results [H. Touchette, S. Lloyd, Phys. Rev. Lett. 84, 1156 (2000)] by providing new derivations of the advantage afforded by closed-loop control and by proposing an information-based optimality criterion for control systems. New applications of this approach pertaining to proportional controllers, and the control of chaotic maps are also presented.Comment: 18 pages, 7 eps figure

AAV-Mediated Gene Delivery in Adult GM1-Gangliosidosis Mice Corrects Lysosomal Storage in CNS and Improves Survival

Background: GM1-gangliosidosis is a glycosphingolipid (GSL) lysosomal storage disease caused by a genetic deficiency of acid β-galactosidase (βgal), which results in the accumulation of GM1-ganglioside and its asialo-form (GA1) primarily in the CNS. Age of onset ranges from infancy to adulthood, and excessive ganglioside accumulation produces progressive neurodegeneration and psychomotor retardation in humans. Currently, there are no effective therapies for the treatment of GM1-gangliosidosis. Methodology/Principal Findings: In this study we examined the effect of thalamic infusion of AAV2/1-βgal vector in adult GM1 mice on enzyme distribution, activity, and GSL content in the CNS, motor behavior, and survival. Six to eight week-old GM1 mice received bilateral injections of AAV vector in the thalamus, or thalamus and deep cerebellar nuclei (DCN) with pre-determined endpoints at 1 and 4 months post-injection, and the humane endpoint, or 52 weeks of age. Enzyme activity was elevated throughout the CNS of AAV-treated GM1 mice and GSL storage nearly normalized in most structures analyzed, except in the spinal cord which showed ∼50% reduction compared to age-matched untreated GM1 mice spinal cord. Survival was significantly longer in AAV-treated GM1 mice (52 wks) than in untreated mice. However the motor performance of AAV-treated GM1 mice declined over time at a rate similar to that observed in untreated GM1 mice. Conclusions/Significance: Our studies show that the AAV-modified thalamus can be used as a ‘built-in’ central node network for widespread distribution of lysosomal enzymes in the mouse cerebrum. In addition, this study indicates that thalamic delivery of AAV vectors should be combined with additional targets to supply the cerebellum and spinal cord with therapeutic levels of enzyme necessary to achieve complete correction of the neurological phenotype in GM1 mice