Early-life nutrition interacts with developmental genes to shape the brain and sleep behavior in Drosophila melanogaster.

The mechanisms by which the genotype interacts with nutrition during development to contribute to the variation of complex behaviors and brain morphology of adults are not well understood. Here we use the Drosophila Genetic Reference Panel to identify genes and pathways underlying these interactions in sleep behavior and mushroom body morphology. We show that early-life nutritional restriction effects on sleep behavior and brain morphology depends on the genotype. We mapped genes associated with sleep sensitivity to early-life nutrition, which were enriched for protein-protein interactions responsible for translation, endocytosis regulation, ubiquitination, lipid metabolism, and neural development. By manipulating the expression of candidate genes in the mushroom bodies (MBs) and all neurons, we confirm that genes regulating neural development, translation and insulin signaling contribute to the variable response of sleep and brain morphology to early-life nutrition. We show that the interaction between differential expression of candidate genes with nutritional restriction in early life resides in the MBs or other neurons and that these effects are sex-specific. Natural variations in genes that control the systemic response to nutrition and brain development and function interact with early-life nutrition in different types of neurons to contribute to the variation of brain morphology and adult sleep behavior.

Autocrine/Paracrine Slit-Robo Signaling Controls Optic Lobe Development in Drosophila melanogaster.

Cell segregation mechanisms play essential roles during the development of the central nervous system (CNS) to support its organization into distinct compartments. The Slit protein is a secreted signal, classically considered a paracrine repellent for axonal growth through Robo receptors. However, its function in the compartmentalization of CNS is less explored. In this work, we show that Slit and Robo3 are expressed in the same neuronal population of the Drosophila optic lobe, where they are required for the correct compartmentalization of optic lobe neuropils by the action of an autocrine/paracrine mechanism. We characterize the endocytic route followed by the Slit/Robo3 complex and detected genetic interactions with genes involved in endocytosis and actin dynamics. Thus, we report that the Slit-Robo3 pathway regulates the morphogenesis of the optic lobe through an atypical autocrine/paracrine mechanism in addition to its role in axon guidance, and in association with proteins of the endocytic pathway and small GTPases.

Slit/Robo Signaling Regulates Multiple Stages of the Development of the Drosophila Motion Detection System.

Neurogenesis is achieved through a sequence of steps that include specification and differentiation of progenitors into mature neurons. Frequently, precursors migrate to distinct positions before terminal differentiation. The Slit-Robo pathway, formed by the secreted ligand Slit and its membrane bound receptor Robo, was first discovered as a regulator of axonal growth. However, today, it is accepted that this pathway can regulate different cellular processes even outside the nervous system. Since most of the studies performed in the nervous system have been focused on axonal and dendritic growth, it is less clear how versatile is this signaling pathway in the developing nervous system. Here we describe the participation of the Slit-Robo pathway in the development of motion sensitive neurons of the Drosophila visual system. We show that Slit and Robo receptors are expressed in different stages during the neurogenesis of motion sensitive neurons. Furthermore, we find that Slit and Robo regulate multiple aspects of their development including neuronal precursor migration, cell segregation between neural stem cells and daughter cells and formation of their connectivity pattern. Specifically, loss of function of slit or robo receptors in differentiated motion sensitive neurons impairs dendritic targeting, while knocking down robo receptors in migratory progenitors or neural stem cells leads to structural defects in the adult optic lobe neuropil, caused by migration and cell segregation defects during larval development. Thus, our work reveals the co-option of the Slit-Robo signaling pathway in distinct developmental stages of a neural lineage.

Cell segregation and boundary formation during nervous system development.

The development of multicellular organisms involves three main events: differentiation, growth, and morphogenesis. These processes need to be coordinated for a correct developmental program to work. Mechanisms of cell segregation and the formation of boundaries during development play essential roles in this coordination, allowing the generation and maintenance of distinct regions in an organism. These mechanisms are also at work in the nervous system. The process of regionalization involves first the patterning of the developing organism through gradients and the expression of transcription factors in specific regions. Once different tissues have been induced, segregation mechanisms may operate to avoid cell mixing between different compartments. Three mechanisms have been proposed to achieve segregation: (1) differential affinity, which mainly involves the expression of distinct pools of adhesion molecules such as members of the cadherin superfamily; (2) contact inhibition, which is largely mediated by Eph-ephrin signaling; and (3) cortical tension, which involves the actomyosin cytoskeleton. In many instances, these mechanisms collaborate in cell segregation. In the last three decades, there have been several advances in our understanding of how cell segregation and boundaries participate in the development of the nervous system. Interestingly, as in other aspects of development, the molecular players are remarkably similar between vertebrates and invertebrates. Here we summarize the main concepts of cell segregation and boundary formation, focusing on the nervous system and highlighting the similarities between vertebrate and invertebrate model organisms.

Slit neuronal secretion coordinates optic lobe morphogenesis in Drosophila.

The complexity of the nervous system requires the coordination of multiple cellular processes during development. Among them, we find boundary formation, axon guidance, cell migration and cell segregation. Understanding how different cell populations such as glial cells, developing neurons and neural stem cells contribute to the formation of boundaries and morphogenesis in the nervous system is a critical question in neurobiology. Slit is an evolutionary conserved protein essential for the development of the nervous system. For signaling, Slit has to bind to its cognate receptor Robo, a single-pass transmembrane protein. Although the Slit/Robo signaling pathway is well known for its involvement in axon guidance, it has also been associated to boundary formation in the Drosophila visual system. In the optic lobe, Slit is expressed in glial cells, positioned at the boundaries between developing neuropils, and in neurons of the medulla ganglia. Although it has been assumed that glial cells provide Slit to the system, the contribution of the neuronal expression has not been tested. Here, we show that, contrary to what was previously thought, Slit protein provided by medulla neurons is also required for boundary formation and morphogenesis of the optic lobe. Furthermore, tissue specific rescue using modified versions of Slit demonstrates that this protein acts at long range and does not require processing by extracellular proteases. Our data shed new light on our understanding of the cellular mechanisms involved in Slit function in the fly visual system morphogenesis.

Variabilidad en la medición del índice acetabular / Variability in measurement of acetabular index

Introducción: La Displasia del desarrollo de la cadera (DDC) es un espectro de enfermedades que abarca desde la luxación franca de la cadera hasta la displasia acetabular leve. El screening de detección de DDC se realiza de rutina en nuestro país, mediante una radiografía de pelvis a los 3 meses. El índice acetabular medido en estas radiografías se utiliza para evaluar la cadera displásica, tanto en la presentación inicial como durante el seguimiento posterior. Objetivo: Evaluar la variabilidad tanto intra como inter observador en la medición del índice acetabular, entre profesionales médicos. Material y Métodos: Cuatro evaluadores (un cirujano-ortopédico infantil, un médico general, un pediatra y un radiólogo) realizaron la medición del índice acetabular en 100 radiografías de screening (200 caderas), en tres ocasiones, separadas por un mes cada una (600 mediciones totales). Un observador independiente evaluó la reproductibilidad en la medición. Se utilizó el coeficiente de correlación intraclase para determinar diferencias significativas. Resultados: La variabilidad intra observador fue menor que la interobservador. La variabilidad intra observador fue similar para los diferentes evaluadores, +/- 1,5°. La variabilidad inter observador fue de +/- 3,4°. Conclusiones: Demostramos una alta concordancia entre las mediciones, determinando una alta reproductibilidad del índice acetabular. El índice acetabular es un método seguro para el diagnóstico y seguimiento de displasia acetabular.

Developmental dysplasia of the hip (DDH) is a spectrum of diseases ranging from frank dislocation of the hip to mild acetabular dysplasia. DDH screening for detection is performed routinely in our country using pelvic x-ray at 3 months of age. The radiographic measured acetabular index is used to evaluate the dysplastic hip, at initial presentation and during follow-up. Objective: Evaluation of the intra- and inter-observer variability, among medical professionals, when measuring acetabular index. Methods: Four reviewers (a children orthopedic surgeon, a general practitioner, a pediatrician and a radiologist) performed acetabular index measurement in 100 radiographs (200 hips), on three occasions, separated each by one month (600 total measurements). An independent observer evaluated the measurement reproducibility. The intra-class correlation coefficient to determine significant differences was used. Results: The intra-observer variability was less than the inter-observer variability. The intra-observer variability was similar among the different assessors, +/- 1.5 degrees. The inter-observer variability was +/- 3.4 degrees. Conclusions: A high concordance among measurements was reported, evidencing a high reproducibility of the acetabular index; this index is a reliable method for the diagnosis and follow-up of acetabular dysplasia.

Fracturas de la tuberosidad anterior de la tibia en adolescentes: reporte de 4 casos / Fractures of the tibial anterior tuberosity in adolescents: report of four cases

Avulsion fractures of the anterior tibial tubercle are uncommon, occurring mainly in male sporting adolescents. We report four cases of acute tibial tubercle fractures. The fractures occurred in two patients after falling on their knees, a third patient presented a quadriceps contraction and in the remaining case suffered a direct blow to the knee. Acording to Ogden’s classification the fractures were stage IIA, IIB, IIIA and IIIB. In all cases treatment was open reduction and internal fixation with good results.

Las fracturas por avulsión de la tuberosidad anterior de la tibia son infrecuentes, ocurriendo principalmente en adolescentes varones durante la práctica deportiva. Se presentan cuatro casos de fracturas de la tuberosidad tibial anterior. El mecanismo de la lesión en 2 de los casos correspondió a una caída a nivel asociada a golpe de ambas rodillas, un tercer paciente presentó una contracción excéntrica del cuadriceps y en el caso restante sufrió un golpe directo en la rodilla. Las fracturas corresponden a los tipos IIA, IIB IIIA y IIIB según la clasificación de Ogden. En todos los casos el tratamiento fue reducción abierta y fijación interna con tornillos, con buenos resultados.

Estudio biomecánico de resistencia en fémur porcino y predictibilidad de zona de fractura / Biomechanical study of porcine femur resistance and predictability of fracture zone

During everyday activities, bones are submitted to the action of different strengths. While walking, the femur must support loads up to 3 times the body weight. It is for this that the need of knowing the mechanical behavior of the femur submitted to different loads and the place where the fracture would occur is born. This study analyzes, through experimental testing, the maximum resistance of the porcine femur, mechanically comparable to the human femur, submitted to different strengths, to obtain the location of fracture and compare the results obtained with computational simulation and with information described for human femur.

Durante actividades de la vida diaria, los huesos se ven sometidos a la acción de diferentes fuerzas. En la marcha, el fémur debe soportar cargas de hasta 3 veces el peso corporal. Es por esto que nace la inquietud de conocer el comportamiento mecánico del fémur sometido a distintos tipos de cargas, y el lugar de falla donde se produciría una fractura. Este estudio analiza, mediante ensayo experimental, la resistencia máxima del fémur porcino, mecánicamente comparable al fémur humano, frente a distintas cargas, para obtener así el sitio de fractura y luego comparar los resultados obtenidos con simulación computacional y con datos descritos para el fémur humano.