71 research outputs found
Zebrafish and medaka : model organisms for a comparative developmental approach of brain asymmetry
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Genetics: A Common Origin for Neuronal Asymmetries?
SummaryA new study reveals an unexpected genetic link between two distinct types of neuronal asymmetries in the nematode Caenorhabditis elegans. This finding suggests a common origin of genetically determined asymmetries and raises intriguing questions about their evolution
Heterochrony and Morphological Variation of Epithalamic Asymmetry
© 2016 Wiley Periodicals, Inc. Heterochrony is one proposed mechanism to explain how morphological variation and novelty arise during evolution. To experimentally approach heterochrony in a comprehensive manner, we must consider all three aspects of developmental time (sequence, timing, duration). This task is only possible in developmental models that allow the acquisition of high-quality temporal data in the context of normalized developmental time. Here we propose that epithalamic asymmetry of teleosts is one such model. Comparative studies among related teleost species have revealed heterochronic shifts in the timing of ontogenic events leading to the development of epithalamic asymmetry. Such temporal changes involve neural structures critical for tissue–tissue interactions underlying the generation of asymmetry and are concurrent with the appearance of morphological differences in the pattern of asymmetry between species. Based on these findings, we hypothesize that interspecie
Estudio comparado del desarrollo de asimetría cerebral en el epitálamo de pez cebra (Danio rerio) y pez medaka (Oryzias latipes)
Memoria para optar al título de BioquímicaLas asimetrías cerebrales en el eje izquierda-derecha de vertebrados poseen componentes altamente conservados y son un punto importante de estudio para la biología del desarrollo. Entre estas asimetrías, las más estudiadas se encuentran en el epitálamo, una región ubicada en el diencéfalo dorsal de vertebrados cuyas conspicuas asimetrías poseen un importante factor hereditario y de lateralidad. En esta región, se encuentra la presencia de un par de núcleos habenulares (Hb, órgano par), además se encuentra el complejo pineal formado por el órgano pineal (órgano impar) en la línea media y por el órgano parapineal (Opp) que se encuentra a la izquierda y proyecta axones eferentes hacia la habénula ipsilateral.
En este trabajo se realizó un estudio comparado entre dos especies de teleósteos, pez cebra (D. rerio) y pez medaka (O. latipes), para intentar dilucidar como se generan las características conservadas y especie-específicas durante la ontogenia del epitálamo.
Estudios realizados en nuestro laboratorio demostraron que estos teleósteos poseen variaciones morfotopológicas especie-específicas en la región del epitálamo (heterotopías) y, luego de normalizar los tiempos de desarrollo en ambas especies, se comprobó que también existen variaciones en la temporalidad del desarrollo (heterocronías). La heterocronía más significativa es que las proyecciones Opp de pez medaka se desarrollan antes que en pez cebra. Debido a lo anterior, se puede hipotetizar que las diferencias topológicas observadas entre ambas especies podrían tener relación con la temporalidad de desarrollo de los componentes que forman el circuito Opp-Hb. En este contexto, el momento en que ocurre la interacción entre el Opp y la Hb podría ser un factor importante para definir la citoarquitectura final del circuito. Lo anterior se respalda en el hecho de que en pez cebra las células habenulares tienen distinta temporalidad de proliferación en cada núcleo, lo que genera subnúcleos habenulares lateral y medial, de distintos tamaños. Este rasgo asimétrico sería dependiente de la presencia del órgano parapineal, ya que a cada subnúcleo se han asociado marcadores moleculares cuya expresión suele ser asimétrica, pero ésta se pierde cuando el Opp es ablacionado. Por otra parte, la neurogénesis habenular, posee asimetría izquierda en su inicio, la cual se conserva incluso luego de ablacionar el Opp, lo que la define como un rasgo asimétrico independiente de la presencia del Opp. Luego, si suponemos que estas interacciones son conservadas también en el modelo de pez medaka, las eventuales variaciones heterocrónicas pueden estudiarse para comprender como podrían generarse las diferencias topológicas entre ambos teleósteos. Por lo tanto, el objetivo de este trabajo fue dilucidar si estas características se encuentran conservadas y observar de qué manera podría influir el adelantamiento de las proyecciones del Opp.
Se esperaba que la neurogénesis habenular de pez medaka inicie de manera asimétrica en el mismo momento de desarrollo que pez cebra. Por otro lado, se esperaba que la proliferación celular, al ser un evento dependiente del Opp, se inicie antes debido al adelantamiento de la ontogenia del Opp. Para estudiar lo anterior se utilizó el marcador pan neuronal HuC, para identificar neuronas diferenciadas y se usaron marcadores moleculares que en pez cebra se asocian al dominio de los subnúcleos habenulares.
Los resultados de nuestro estudio demostraron nueva evidencia de heterotopía y heterocronía entre pez cebra y medaka, se descartó la hipótesis planteada, pues la neurogénesis habenular en pez medaka está adelantada pero continúa siendo asimétrica en su inicio, lo que podría indicar que en esta especie sí existe una relación entre el Opp y la neurogénesis habenular. Por otro lado, con el gen nptx2a, ortólogo de narp de pez cebra, se encontró un arreglo topológico diferente a la asimetría izquierda esperada con narp, pues el marcador de pez medaka es más simétrico y se limita a una región más pequeña en ambas habénulas, asemejándose más a una topología propia a la descrita en la habénula derecha de pez cebra.
Nuestros estudios respaldan la idea de que las interacciones entre el Opp y la HbI parecen ser más complejas de lo que los estudios en pez cebra revelan. Nuestros resultados sugieren interacciones más tempranas y probablemente bidireccional entre la habénula izquierda y el órgano parapinealBrain asymmetries along the left-right axis show highly conserved components across vertebrates. Among these asymmetries the most studied is found in the epithalamus, a region located in the dorsal diencephalon. Epithalamic asymmetries are conspicuous and genetically controlled, and are characterised by the presence of left-right differences in morphology and gene expression of the bilaterally paired habenular nuclei and by the left-sided asymmetric position and connectivity to the left habenula (Hb) of the unpaired parapineal organ (PpO), an accesory component of the pineal complex. In this work we performed a comparative study between two species of teleosts, zebrafish (D. rerio) and medaka (O. latipes), to elucidate how the conserved and species-specific features of epithalamic asymmetries are generated during the ontogeny of the epithalamus. Previous studies of our laboratory showed that these teleosts show both topological and temporal variations in the development of epithalamic asymmetries, known as heterotopies and heterochronies, respectively. Among the latter, the most significant difference is observed in the timing of connectivity of the parapineal organ to the left Hb, which in medaka fish begins earlier than in zebrafish.
Due to the above, we hypothesised that the topological differences observed between both species could be related to the temporality of development of the components that make up the parapineal-habenula circuit. In this context, the time in which the interaction between the parapineal organ and the habenula occurs could be an important factor in defining the final cytoarchitecture of the circuit. This idea is supported by the fact that in zebrafish the habenular cells have different temporality of proliferation in the left and right nuclei, which generates size differences in the lateral and medial habenular subnuclei on both sides. This asymmetric trait appears to depend on the presence of the parapineal organ, since the asymmetric expression of the molecular markers that have been associated to each habenular sub-nuclei is lost when the parapineal organ is physically removed during development. In contrast, the onset of habenular neurogenesis is asymmetric even after ablating the PpO, which defines a type of asymmetry that is independent of the parapineal organ. Based on the above and if we assume that these types of asymmetries are also conserved in medaka, the heterochronic variations can be studied as a possible factor that explains how the topological differences of epithalamic asymmetry between both teleosts are generated. Therefore, the aim of this work was to have a first mechanistic approach to this question and investigate the timing and organisation of habenular neurogenesis in medaka and relate this to the pattern observed in zebrafish and the advancement of parapineal projections in both species. Habenular neurogenesis of medaka was expected to start asymmetrically at the same time as in zebrafish while cell proliferation, being an event dependent of the parapineal organ, it was expected to start earlier due to overtaking of parapineal projections in this species. The pan-neuronal marker HuC was used to identify differentiated neurons and molecular subnuclei.
The results of this study provided new evidence of heterotopic and heterochronic shifts between zebrafish and medaka that appear to rule out our hypothesis. The onset of habenular neurogenesis in medaka was asymmetric as in zebrafish but appeared at an earlier stage. This observation suggest that in contrast to zebrafish, the onset of asymmetric habenular neurogenesis in medaka has some type of dependency on the parapineal organ. This possibility can be assesed in the future by performing parapineal ablation in medaka. On the other hand, using the medaka nptx2a gene, an ortholog of zebrafish narp, we observed a different topological arrangement with a more restricted and fairly symmetric habenular expression, in contrast to the broad and pronounced left-sided asymmetric expression observed in zebrafish. This expression pattern resembles the topology described in the right habenula of zebrafish. In summary, our studies support the idea that interactions between the parapineal organ and the left Hb are more complex than the studies of zebrafish suggest. These interactions appear to have an earlier onset and show a bi-directional natureFONDECYT; CONICYT; FONDAP; Iniciativa Científica Milenio, ICM P-09-015-
De divulgar a compartir: análisis preliminar de la campaña de difusión del “Decálogo de la Investigación” de ANIP
En octubre de 2020, la Asociación Nacional de Investigadores de Postgrado [ANIP] de Chile publicó en su sitio web[1] un breve informe que detalla los resultados de un estudio exploratorio sobre las condiciones laborales que son prioritarias para los investigadores y las investigadoras en Chile (ANIP, 2020). A pesar de tener un alcance más bien limitado, este informe es especialmente interesante para todas y todos quienes participamos en actividades de investigación. En efecto, es el primero -y, hasta hoy, sigue siendo el único instrumento- que aborda la precarización laboral en este campo de manera más o menos sistemática en el país.En octubre de 2020, la Asociación Nacional de Investigadores de Postgrado (ANIP) publicó un informe que sintetiza las condiciones laborales prioritarias para los investigadores y las investigadoras del país. En este artículo llevamos a cabo un análisis preliminar de la campaña de divulgación de este documento, que consistió en el envío de un boletín masivo a los socios y las socias, y las publicaciones en las redes oficiales de la organización (Twitter, Facebook, Instagram y YouTube). Los resultados sugirieron que la campaña tuvo éxito en términos del diseño y la implementación, aunque pudimos identificar ciertos puntos de mejora. En cualquier caso, los resultados nos obligaron a reflexionar sobre qué significa que una campaña de divulgación tenga éxito. Por esto, elaboramos una propuesta conceptual, anclada al constructivismo de orientación histórico-cultural, que nos sirvió para clarificar hasta qué punto la campaña fue exitosa y en qué sentido, a la vez, pudo haber fracasado. Finalmente, reflexionamos sobre cómo esta propuesta conceptual nos ayuda a complejizar y mejorar el análisis de las campañas de divulgación en el futuro
Il Signore Risorto – la Gioia del Vangelo (GV 20, 20b)
The author analyses exegetically J 20, 19–20 where the disciples were filled with joy when they saw Risen Jesus. Starting from the analysis of the literary context and the motives related to the disciples’ joy, the author stresses church-centered role of the Risen Lord (kyrios). He points out a number of references to the appearances of Risen Christ in Luke 24, which seem to have many points in common with the Johannine tradition. He particularly focuses on the very moment of appearance when Jesus in a symbolic gesture shows his hands and side to the disciples. The hands and side are the symbols of tender love of the Good Shepherd and inexhaustible source of the Holy Spirit. Moreover, he presents the contrast between the experience of fear, confusion and scattering (before the Resurrection) and the experience of joy, confidence and unity which was rediscovered around the Risen Jesus.L’articolo presenta un’analisi esegetica di Gv 20, 19–20, dove gli apostoli si rallegrarono al vedere Gesù risorto. Si esamina il contesto letterario, i motivi inerenti alla gioia dei discepoli e il ruolo ecclesiocentrico del Signore Risorto (kyrios). Non mancano riferimenti al racconto delle apparizioni in Lc 24, che sembra molto vicino alla tradizione giovannea. Un’attenzione particolare viene data al momento dell’apparizione, quando Gesù, eseguendo un gesto simbolico, mostra ai discepoli le mani e il costato, entrambi i simboli della amorevole cura del Buon Pastore e dell’inesauribile fonte dello Spirito Santo. Inoltre, viene messo in risalto il contrasto tra lo stato di paura, smarrimento e dispersione (prima dell’apparizione del Risorto) e lo stato di gioia, fiducia e ritrovata unità attorno a Gesù Risorto
Development of phenotypic indexes for the description of morphological injury in breast cancer cell mitochondria.
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Development of phenotypic indexes for the description of morphological injury in breast cancer cell mitochondria.
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Sub-category:
Tumor/Cell Biology
Category:
Tumor Biology
Meeting:
2009 ASCO Annual Meeting
Session Type and Session Title:
This abstract will not be presented at the 2009 ASCO Annual Meeting but has been published in conjunction with the meeting.
Abstract No:
e22055
Citation:
J Clin Oncol 27, 2009 (suppl; abstr e22055)
Author(s):
L. Putignani, S. Raffa, R. Pescosolido, F. Signore, D. Menichella, R. Boldrini, M. Torrisi, P. Grammatico; Bambino Gesù, Rome, Italy; S. Andrea Hospital, Rome, Italy; S. Camillo-Forlanini Hospital, Rome, Italy; Bambino Gesù Hospital, Rome, Italy; S. Andrea Hospital, University Sapienza, Rome, Italy
Abstract Disclosures
Faculty and Discussant Disclosures
Annual Meeting Planning Committee Disclosures
2009 Annual Meeting Proceedings Part I Errata
Abstract:
Background: Mitochondriopathy has been recently rekindled as new cancer theory. We report on structural damage of breast-infiltrating ductal carcinoma (IDC) mitochondria characterised by reduced expression levels of the oxidative phosphorylation system (OXPHOS). Methods: Mitochondria from HMC-1 (human mammary carcinoma) and HMEC (human mammary epithelial cell) cultures, traced by Mitotracker, were assayed for OXPHOS expression levels using cryo-immunoelectron microscopy (CIEM) quantitative labelling and fluorescence immunolabelling on unfractionated HMC-1 and HEMC cells. Convolution degeneration was established by transmission electron microscopy (TEM). Twenty different cell sections for both HMC-1 and HEMC cells, including 65 and 72 mitochondria, respectively, were randomly recorded and quantitatively analyzed for the percentage of area occupied by intact cristae to provide a grading of mitochondrial damage (cristae loss index). Results: Depressed expression levels were detected for all HMC-1 OXPHOS complexes by CIEM. Normalized labelling density (HEMC/HMC-1), expressed as colloidal gold particles/mitochondrial area (ρ) provided the following values: 1.77 for the NADH-ubiquinone oxidoreductase complex I NDUFS3; 1.86 for the succinate- dehydrogenase complex II SDH-B protein; 1.63 for the ubiquinol cytochrome c reductase complex III UQCRC2; 4.88 and 1.58 for the cytochrome-oxidase complex IV (CO) subunit I and IV, respectively; 2.70 for the ATP-synthase complex V F1β protein. Fluorescence immunolabelling confirmed CIEM quantitative data. MitoTracker's co-staining showed altered membrane potential and permeability. Injury grading was categorised assigning three levels of morphological damage: i) severe, ii) moderate, iii) slight, corresponding to 0 % (6.2 % and 1.4 % for HMC-1 and HMEC, respectively), 1-50 % (21.5 % and 2.8 % for HMC-1 and HMEC, respectively) and 51-75 % (44.6 % and 15.3 % for HMC-1 and HMEC, respectively) of area occupied by intact cristae (p<0.0001, χ2 Test). The entire HMC-1 mitochondrial damage resulted 3.7 times higher than that observed for HMEC cells (72.3HMC-1 %/19.5HMEC %). Conclusions: New phenotypic harm indexes for IDC cell mitochondria might provide new hallmarks in breast cancer cell biology
Morphogens during embryonic development of vertebrates Morfógenos durante el desarrollo embrionario de vertebrados
During embryonic development, cells in many tissues differ according to the positional information that is set by the concentration of morphogen gradients. These are signaling molecules that are secreted in a restricted region of a tissue and diffuse away from their source forming a concentration gradient. Morphogens generally act at different development stages in an organism and cause different reactions in cells depending on their history of differentiation. The best known example of morphogens are members of growth factor beta (TGF-beta), Hedgehog(Hh), and Wnt families or microRNAs
Nodal signalling and asymmetry of the nervous system
The role of Nodal signalling in nervous system asymmetry is still poorly understood. Here, we review and discuss how asymmetric Nodal signalling controls the ontogeny of nervous system asymmetry using a comparative developmental perspective. A detailed analysis of asymmetry in ascidians and fishes reveals a critical context-dependency of Nodal function and emphasizes that bilaterally paired and midline-unpaired structures/organs behave as different entities. We propose a conceptual framework to dissect the developmental function of Nodal as asymmetry inducer and laterality modulator in the nervous system, which can be used to study other types of body and visceral organ asymmetries. Using insights from developmental biology, we also present novel evolutionary hypotheses on how Nodal led the evolution of directional asymmetry in the brain, with a particular focus on the epithalamus. We intend this paper to provide a synthesis on how Nodal signalling controls left-right asymmetry of the nervous systemChilean National Commission for Scientific and Technological Research
FONDECYT 1161274
FONDAP 15150012
ACT1402
Chilean Millennium Science Initiative
P09-015-
Il Presbitero e le Signore: Studio sulla personificazione delle Comunità in 2Gv
In 2 Jn, the Elder refers to two Sisters. Taken as a whole, the text suggests that these feminine individuals are a literary figuration of believing communities known to the sender. Recently, the way in which the Johannine author expresses himself has been explained with the rhetorical device of the fictio personae. Adopting this explanation as a starting point, the article is organized in three parts plus a conclusion. In the first part, a brief definition of the rhetorical device of personification is sketched out. Instead, in the second part, two other New Testament examples of personification (Gal 4,21-31; Ap 17–22) are further examined. Then in the third part an investigation is conducted which clarifies what the function of the personification of the two Sisters could be within the Letter, better defining the strategies used to make it work. In conclusion, we look at the methodological gains of this particular personification and the benefits regarding content in the relationship between the Elder and the two Johannine communities.In 2Gv, il Presbitero fa riferimento a due Sorelle. L’insieme del testo lascia intendere che questi individui femminili siano una figurazione letteraria di comunità di credenti, note al mittente. Di recente, questa modalità di esprimersi da parte dell’autore giovanneo è stata spiegata con il dispositivo retorico della fictio personae. Assumendo questa spiegazione come dato di partenza, l’articolo è organizzato in tre parti più una conclusione. Nella prima parte, viene tratteggiata una breve definizione del dispositivo retorico della personificazione. Nella seconda, invece, è offerto un approfondimento su altri due esempi neotestamentari di personificazione (Gal 4,21-31; Ap 17–22). Nella terza parte, poi, viene svolta un’indagine che chiarisca quale sia la funzione della personificazione delle due Signore all’interno della Lettera e che definisca meglio le strategie attuate per il suo funzionamento. Nella conclusione, si raccolgono alcuni guadagni di metodo, in merito a questa particolare personificazione, e altri di contenuto, riguardo al rapporto tra il Presbitero e le due comunità giovannee
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