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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.

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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.

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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.

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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.

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INTRODUCTION: Diaphyseal fractures of the forearm comprise 6%-10% of all fractures in children. The treatment depends on the age and type of displacement, and conservative and surgical management with fixation of intramedullary nails, among other techniques, is valid. The aim is to show the radiological and functional outcomes, and complications of intramedullary fixation with Kirschner nails in children. MATERIALS AND METHODS: A retrospective descriptive case series of patients treated with intramedullary fixation of forearm fractures. The radiological and functional results, and complications are correlated. RESULTS: Of the 117 patients operated, 59 met the inclusion criteria. The average age was 10 years. Eighty-four point seven percent were males and the left side was the most affected (62.7%). In 88.1% both bones were fractured and 11 cases had open fractures. An open reduction was performed in 72.8% of the cases, the main indications for this being instability, failed reduction and refracture. There were 52 excellent outcomes, 2 good, and 4 regular and 1 bad. There were 13.5% minor complications. DISCUSSION: This study shows that intramedullary fixation with Kirschner nails in radius and ulna diaphysis fractures in children is a safe, low-cost procedure and offers adequate short and medium term functional outcomes, with a low prevalence of serious complications with only 6 cases of non-consolidation and refracture. Larger preoperative angulations in the anteroposterior and lateral planes, and lateral postoperative angulations, could be considered predictors of less satisfactory functional results.

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It has been described that febrile seizures during infancy increase risk of subsequent non-febrile seizures during the adulthood. However, latency period between febrile seizure and the onset of the first spontaneous seizure has not been evaluated. The present study was designed to investigate the susceptibility to subsequent seizures in immature rats that had experienced early-life hyperthermic seizures and before they achieved the adult age. The results were compared with those induced by hyperthermia alone. Pentylenetetrazol (PTZ) was applied 24h or 20 days after hyperthermic seizures or hyperthermia were induced in 10-day-old rats by a regulated stream of moderately heated air. One day after hyperthermic seizures or hyperthermia, animals demonstrated enhanced latency to the PTZ-induced myoclonic (88% and 53%, respectively), clonic (60% and 60%, respectively) and tonic seizures (233% and 659%, respectively). The incidence of myoclonic and clonic seizures was similar to that in control group (100%). However, hyperthermic seizures reduced (50%) the incidence of tonic seizures. Twenty days after hyperthermic seizures there was an augmented latency to tonic seizures (123%) and reduced incidence for all the PTZ-induced seizures (71% myoclonic; 71% clonic seizures; 57% tonic seizures) when compared with control group (100%). In contrast, hyperthermia enhanced only the latency to myoclonic (133%) and clonic seizures (659%). Our data indicate that hyperthermic seizures or hyperthermia induces a protective effect against PTZ-induced seizures during a latency period. A possible involvement of gamma-aminobutyric acid (GABA) system is discussed.

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The susceptibility of larvae, prepupae, and pupae of the grass looper Mocis latipes (Guenée) to the entomopathogenic nematode Heterorhabditis bacteriophora (Poinar) NC strain was evaluated under laboratory conditions. Concentrations of 0, 5, 10, 20, 40, 60, and 120 nematodes per larva, applied in 1 ml of sterile-distilled water, were bioassayed, applying them to groups of 20 individuals of each instar, prepupa or pupa. Mortality was recorded daily for 5 d. All instars and the prepupal stage were the most susceptible to H. bacteriophora. Mortality ranged from 22.5 to 100%. Prepupae had 97.5-100% mortality starting at 10 nematodes per prepupa. Pupal mortality ranged from 27.5 to 41.3% as nematode concentration was increased. H. bacteriophora presented LC50 values that ranged between 5.26 and 37.66 nematodes per larva and LT50 values that ranged between 1.5 and 4.3 d. Results of this study suggest that H. bacteriophora has potential as a biocontrol agent against M. latipes.

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OBJECTIVE: To investigate if the changes in the activity of the tryptophan-5-hydroxylase and in brain serotonin synthesis provoked by diabetes mellitus persist or return to normal in the diabetic rats submitted to treatment with insulin. METHODS: Diabetes induced by the administration of streptozotocin in rats and their treatment with insulin was the paradigm used. At days 7, 14 and 21 of evolution, the brain serotonergic biosynthetic activity was evaluated. RESULTS: The diabetic rats showed a significant decrease of body weight. Also, they showed a low concentration of I-tryptophan, as well as a diminution in the activity of the key enzyme tryptophan-5-hydroxylase and its product serotonin in the cerebral cortex and brainstem. Interestingly, the activity of the enzyme was higher in the brainstem from day 14, accompanied with an elevation of the neurotransmitter. The diabetic rats submitted to treatment with insulin showed a complete physical recovery and a return to normal of plasma and brain I-tryptophan. The activity of the enzyme not only normalized but was elevated and with an increase of serotonin in the brainstem and cerebral cortex. CONCLUSION: The present findings confirm that diabetes mellitus produced a chronic anabolic deficit and a decrease in some brain regions of serotonin synthesis. Also, demonstrate that the diabetic rats under specific treatment with insulin had a complete physical recovery and a return to normal of the serotonin precursor in the blood and brain. However, the activity of the limiting enzyme TrpOH case was elevated with an increase of the neurotransmitter in all regions studied. Since the diabetic animal, insulin treated, does recover metabolically, the mechanism of activation of the serotonin biosynthetic path in the brain may not be dependent on the decreased availability of its precursor the free plasma I-tryptophan. Instead, it might be due to a change in the kinetics of tryptophan-5-hydroxylase, since its activity remains significantly increased in spite of plasma and brain normalization of its substrate. Altogether these changes in the biosynthesis of an important brain neurotransmitter may be of relevance in the pathophysiology of the psychoneurological complications in diabetic patients.

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OBJECTIVE: Evaluate if the rats with diabetes mellitus insulin-dependent have a minor activity of the serotonergic biosynthetic pathway through the decrease of the free fraction of L-tryptophan in plasma. METHODS: Diabetes mellitus was induced in rats, and the brain serotonergic biosynthetic activity was evaluated at 7, 14, and 21 days after streptozotocin administration. RESULTS: The diabetic animals showed a general decrease in body weight. In plasma they had a decrease in the free fraction of L-tryptophan. Also, in the brain they show low levels of the amino acid, as well as decrease of the activity of the limiting enzyme tryptophan-5-hydroxylase and its product serotonin. Interestingly, the activity of the enzyme was higher in the brainstem from day 14, accompanied with an elevation of the neurotransmitter. CONCLUSIONS: The results confirm that diabetes mellitus insulin-depend induce chronic undernourishment. The low levels of L-tryptophan in blood of the diabetic animals suggest a minor transport of the amino acid to the brain and a decrease in serotonin synthesis, in cerebral cortex and hypothalamus. Besides, during the evolution of the disease, the activity of tryptophan hydroxylase was elevated, independently of L-tryptophan concentration in the brainstem of diabetic animals, suggesting a different response according to the brain region and possibly a different functional change, accompanied by an increase in the synthesis of the neurotransmitter.

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