Loss of active neurogenesis in the adult shark retina

Neurogenesis is the process by which progenitor cells generate new neurons. As development progresses neurogenesis becomes restricted to discrete neurogenic niches, where it persists during postnatal life. The retina of teleost fishes is thought to proliferate and produce new cells throughout life. Whether this capacity may be an ancestral characteristic of gnathostome vertebrates is completely unknown. Cartilaginous fishes occupy a key phylogenetic position to infer ancestral states fixed prior to the gnathostome radiation. Previous work from our group revealed that the juvenile retina of the catshark Scyliorhinus canicula, a cartilaginous fish, shows active proliferation and neurogenesis. Here, we compared the morphology and proliferative status of the retina in catshark juveniles and adults. Histological and immunohistochemical analyses revealed an important reduction in the size of the peripheral retina (where progenitor cells are mainly located), a decrease in the thickness of the inner nuclear layer (INL), an increase in the thickness of the inner plexiform layer and a decrease in the cell density in the INL and in the ganglion cell layer in adults. Contrary to what has been reported in teleost fish, mitotic activity in the catshark retina was virtually absent after sexual maturation. Based on these results, we carried out RNA-Sequencing (RNA-Seq) analyses comparing the retinal transcriptome of juveniles and adults, which revealed a statistically significant decrease in the expression of many genes involved in cell proliferation and neurogenesis in adult catsharks. Our RNA-Seq data provides an excellent resource to identify new signaling pathways controlling neurogenesis in the vertebrate retinaFunded by the Ministerio de Economía Industria y Competitividad (to EC; grant number BFU-2017-89861-P) and Xunta de Galicia Predoctoral Fellowship (to IH-N; grant number ED 481 A 2018 216). Both grants were partially financed by the European Social FundS

Hybridizing Feature Selection and Feature Learning Approaches in QSAR Modeling for Drug Discovery

Quantitative structure–activity relationship modeling using machine learning techniques constitutes a complex computational problem, where the identification of the most informative molecular descriptors for predicting a specific target property plays a critical role. Two main general approaches can be used for this modeling procedure: feature selection and feature learning. In this paper, a performance comparative study of two state-of-art methods related to these two approaches is carried out. In particular, regression and classification models for three different issues are inferred using both methods under different experimental scenarios: two drug-like properties, such as blood-brain-barrier and human intestinal absorption, and enantiomeric excess, as a measurement of purity used for chiral substances. Beyond the contrastive analysis of feature selection and feature learning methods as competitive approaches, the hybridization of these strategies is also evaluated based on previous results obtained in material sciences. From the experimental results, it can be concluded that there is not a clear winner between both approaches because the performance depends on the characteristics of the compound databases used for modeling. Nevertheless, in several cases, it was observed that the accuracy of the models can be improved by combining both approaches when the molecular descriptor sets provided by feature selection and feature learning contain complementary information.Fil: Ponzoni, Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias e Ingeniería de la Computación. Universidad Nacional del Sur. Departamento de Ciencias e Ingeniería de la Computación. Instituto de Ciencias e Ingeniería de la Computación; ArgentinaFil: Sebastián Pérez, Víctor. Consejo Superior de Investigaciones Científicas. Centro de Investigaciones Biológicas; EspañaFil: Requena Triguero, Carlos. Consejo Superior de Investigaciones Científicas. Centro de Investigaciones Biológicas; EspañaFil: Roca, Carlos. Consejo Superior de Investigaciones Científicas. Centro de Investigaciones Biológicas; EspañaFil: Martínez, María Jimena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias e Ingeniería de la Computación. Universidad Nacional del Sur. Departamento de Ciencias e Ingeniería de la Computación. Instituto de Ciencias e Ingeniería de la Computación; ArgentinaFil: Cravero, Fiorella. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; ArgentinaFil: Diaz, Monica Fatima. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; ArgentinaFil: Páez, Juan A.. Consejo Superior de Investigaciones Científicas. Instituto de Química Médica; EspañaFil: Gómez Arrayás, Ramón. Universidad Autónoma de Madrid; EspañaFil: Adrio, Javier. Universidad Autónoma de Madrid; España. Institute for Advanced Research in Chemical Sciences; EspañaFil: Campillo, Nuria E.. Consejo Superior de Investigaciones Científicas. Centro de Investigaciones Biológicas; Españ

Pth4, an ancient parathyroid hormone lost in eutherian mammals, reveals a new brain-to-bone signaling pathway

Regulation of bone development, growth, and remodeling traditionally has been thought to depend on endocrine and autocrine/paracrine modulators. Recently, however, brain-derived signals have emerged as key regulators of bone metabolism, although their mechanisms of action have been poorly understood. We reveal the existence of an ancient parathyroid hormone (Pth)4 in zebrafish that was secondarily lost in the eutherian mammals' lineage, including humans, and that is specifically expressed in neurons of the hypothalamus and appears to be a central neural regulator of bone development and mineral homeostasis. Transgenic fish lines enabled mapping of axonal projections leading from the hypothalamus to the brainstem and spinal cord. Targeted laser ablation demonstrated an essential role for of pth4-expressing neurons in larval bone mineralization. Moreover, we show that Runx2 is a direct regulator of pth4 expression and that Pth4 can activate cAMP signaling mediated by Pth receptors. Finally, gain-of-function experiments show that Pth4 can alter calcium/phosphorus levels and affect expression of genes involved in phosphate homeostasis. Based on our discovery and characterization of Pth4, we propose a model for evolution of bone homeostasis in the context of the vertebrate transition from an aquatic to a terrestrial lifestyle.Spanish Economy and Competitiveness Ministry Project [ALG2011-23581, AGL2014-52473R]; Portuguese Foundation for Science and Technology [PTDC/BIA-ANM/4225/2012-phos-fate]; U. S. National Institutes of Health/Office of the Director Grant [R01OD011116, R01 RR020833]; Generalitat de Catalunya [SGR2014-290]; Spanish Economy and Competitiveness Ministry [BFU2010-14875]; Science and Innovation Ministry [AGL2010-22247-C03-01]; Campus do Mar Ph.D. grant; Xunta de Galicia (Santiago, Spain) [AGL2014-52473R]info:eu-repo/semantics/publishedVersio

Geologia dos granitóides Sanga do Areal, intrusivos no complexo Arroio dos Ratos na região de Quitéria, RS

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Petrologia de granitóides intrusivos no complexo gnaíssico Arroio dos Ratos na região de Butiá, RS : projeto de iniciação científica

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Petrologia de granitóides intrusivos no complexo gnaíssico Arroio dos Ratos na região de Butiá, RS : projeto de iniciação científica

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