451 research outputs found
The GTPase-activating protein Rap1GAP: A new player to modulate Ret signaling
No full textFil: Paratcha, Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Ledda, Maria Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina. Karolinska Huddinge Hospital. Karolinska Institutet; Sueci
Mechanisms regulating dendritic arbor patterning
No full textThe nervous system is populated by diverse types of neurons, each of which has dendritic trees with strikingly different morphologies. These neuron-specific morphologies determine how dendritic trees integrate thousands of synaptic inputs to generate different firing properties. To ensure proper neuronal function and connectivity, it is necessary that dendrite patterns are precisely controlled and coordinated with synaptic activity. Here, we summarize the molecular and cellular mechanisms that regulate the formation of cell type-specific dendrite patterns during development. We focus on different aspects of vertebrate dendrite patterning that are particularly important in determining the neuronal function; such as the shape, branching, orientation and size of the arbors as well as the development of dendritic spine protrusions that receive excitatory inputs and compartmentalize postsynaptic responses. Additionally, we briefly comment on the implications of aberrant dendritic morphology for nervous system disease.Fil: Ledda, Maria Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Paratcha, Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentin
Assembly of neuronal connectivity by neurotrophic factors and leucine-rich repeat proteins
No full textProper function of the nervous system critically relies on sophisticated neuronal networks interconnected in a highly specific pattern. The architecture of these connections arises from sequential developmental steps such as axonal growth and guidance, dendrite development, target determination, synapse formation and plasticity. Leucine-rich repeat (LRR) transmembrane proteins have been involved in cell-type specific signaling pathways that underlie these developmental processes. The members of this superfamily of proteins execute their functions acting as trans-synaptic cell adhesion molecules involved in target specificity and synapse formation or working in cis as cell-intrinsic modulators of neurotrophic factor receptor trafficking and signaling. In this review, we will focus on novel physiological mechanisms through which LRR proteins regulate neurotrophic factor receptor signaling, highlighting the importance of these modulatory events for proper axonal extension and guidance, tissue innervation and dendrite morphogenesis. Additionally, we discuss few examples linking this set of LRR proteins to neurodevelopmental and psychiatric disorders.Fil: Ledda, Maria Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Paratcha, Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentin
Deciphering New Players in the Neurogenic Adult Hippocampal Niche
No full textIn the mammalian adult hippocampus, new neurons are continuously generated throughout life in the subgranular zone of the dentate gyrus. Increasing evidence point out the contribution of adult-born hippocampal granule cells (GCs) to cognitive processes such as learning and memory, indicating the relevance of understanding the molecular mechanisms that control the development of these new neurons in the preexisting hippocampal circuits. Cell proliferation and functional integration of adult-born GCs is a process highly regulated by different intrinsic and extrinsic factors. In this review, we discuss recent advances related with cellular components and extrinsic signals of the hippocampal neurogenic niche that support and modulate neurogenesis under physiological conditions.Fil: Bonafina, Antonela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Paratcha, Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Ledda, Maria Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentin
New insights into the control of neurotrophic growth factor receptor signaling: Implications for nervous system development and repair
No full textNeurotrophic growth factors control neuronal development by activating specific receptor tyrosine kinase positive signaling pathways, such as Ras-MAPK and PI3K-Akt cascades. Once activated, neurotrophic factor receptors also trigger a cascade of molecular events, named negative receptor signaling, that restricts the intensity of the positive signals and modulates cellular behavior. Thus, to avoid signaling errors that ultimately could lead to aberrant neuronal physiology and disease, negative signaling mechanisms have evolved to ensure that suitable thresholds of neuronal stimulation are achieved and maintained during right periods of time. Recent findings have revealed that neurotrophic factor receptor signaling is tightly modulated through the coordinated action of many different protein regulators that limit or potentiate signal propagation in spatially and temporally controlled manners, acting at specific points after receptor engagement. In this review, we discuss progress in this field, highlighting the importance of these modulators in axonal growth, guidance, neural connectivity, and nervous system regeneration.Fil: Alsina, Fernando Cruz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia ; ArgentinaFil: Ledda, Maria Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia ; ArgentinaFil: Paratcha, Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia ; Argentin
GDNF/GFRα1 Complex Abrogates Self-Renewing Activity of Cortical Neural Precursors Inducing Their Differentiation
No full textThe balance between factors leading to proliferation and differentiation of cortical neural precursors (CNPs) determines the correct cortical development. In this work, we show that GDNF and its receptor GFRα1 are expressed in the neocortex during the period of cortical neurogenesis. We show that the GDNF/GFRα1 complex inhibits the self-renewal capacity of mouse CNP cells induced by fibroblast growth factor 2 (FGF2), promoting neuronal differentiation. While GDNF leads to decreased proliferation of cultured cortical precursor cells, ablation of GFRα1 in glutamatergic cortical precursors enhances its proliferation. We show that GDNF treatment of CNPs promoted morphological differentiation even in the presence of the self-renewal-promoting factor, FGF2. Analysis of GFRα1-deficient mice shows an increase in the number of cycling cells during cortical development and a reduction in dendrite development of cortical GFRα1-expressing neurons. Together, these results indicate that GDNF/GFRα1 signaling plays an essential role in regulating the proliferative condition and the differentiation of cortical progenitors. In this article, Ledda and colleagues show that GDNF acting through its receptor GFRα1 plays a critical role in the maturation of cortical progenitors by counteracting FGF2 self-renewal activity on neural stem cells and promoting neuronal differentiation.Fil: Bonafina, Antonela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Fontanet, Paula Aldana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Paratcha, Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Ledda, Maria Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentin
RET-independent signaling by GDNF ligands and GFRα receptors
No full textThe discovery in the late 1990s of the partnership between the RET receptor tyrosine kinase and the GFRα family of GPI-anchored co-receptors as mediators of the effects of GDNF family ligands galvanized the field of neurotrophic factors, firmly establishing a new molecular framework besides the ubiquitous neurotrophins. Soon after, however, it was realized that many neurons and brain areas expressed GFRα receptors without expressing RET. These observations led to the formulation of two new concepts in GDNF family signaling, namely, the non-cell-autonomous functions of GFRα molecules, so-called trans signaling, as well as cell-autonomous functions mediated by signaling receptors distinct from RET, which became known as RET-independent signaling. To date, the best studied RET-independent signaling pathway for GDNF family ligands involves the neural cell adhesion molecule NCAM and its association with GFRα co-receptors. Among the many functions attributed to this signaling system are neuronal migration, neurite outgrowth, dendrite branching, spine formation, and synaptogenesis. This review summarizes our current understanding of this and other mechanisms of RET-independent signaling by GDNF family ligands and GFRα receptors, as well as their physiological importance.Fil: Ibáñez, Carlos F.. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Paratcha, Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Ledda, Maria Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentin
Caminhos de Úrsula, de Maria Firmina dos Reis
No full textDissertação (mestrado) — Universidade de Brasília, Instituto de Letras, Departamento de Teoria Literária e Literaturas, Programa de Pós-Graduação em Literatura, 2024.O objetivo desta pesquisa é investigar a trajetória do romance Úrsula, da escritora e intelectual
Maria Firmina dos Reis, evidenciando sua importância para os estudos sobre sua vida e obras e
para o início dos caminhos da literatura afro-brasileira, como uma escrita que inaugura no país
o romance de autoria de mulheres negras e que delineia novas perspectivas no texto literário.
Inicia-se, a partir de Úrsula, a insurgência de um corpus de romances de autoras negras
brasileiras, por meio do qual se pensa a pessoa negra por representações mais complexas
(Miranda, 2020). Desse modo, nesta dissertação, pensa-se o romance de Maria Firmina dos Reis
em perspectiva com a intelectualidade da autora presente na obra, sobretudo a partir de Mirian
Santos (2018), bell hooks (1995), Conceição Evaristo (2020) e Fernanda Miranda (2022). Além
disso, disserta-se sobre o silenciamento diante da escritora e os caminhos de Úrsula a partir de
1970, considerando as novas edições do romance e as pesquisas acadêmicas brasileiras. Essas
pesquisas, como exposto nesta dissertação, foram essenciais para a formação dos discursos
sobre a autora e também para a sua divulgação. Úrsula, assim, é a porta de entrada para que,
tardiamente, porém relevantemente, Maria Firmina dos Reis e suas obras sejam inseridas na
história literária brasileira.The objective of this research is to investigate the trajectory of the novel Ursula by Maria
Firmina dos Reis, highlighting its importance for studies on the life and works of the writer and
for the beginning of the paths of afro-brazilian literature, as a text that inaugurates in the country
the novel authored by black women and that delineates new perspectives in the literary text.
Starting from Ursula, the insurgency of a corpus of novels by black brazilian authors begins,
through which the black character is thought by more complex representations (Miranda, 2020).
Therefore, this research thinks the novel of Maria Firmina dos Reis in perspective with the
intellectual of the author present in the work, especially from Mirian Santos (2018), bell hooks
(1995), Conceição Evaristo (2020) and Fernanda Miranda (2022). In addition, it discusses the
silence before the writer and the paths of Ursula from 1970, considering the new editions of the
novel and the brazilian academic research. These researches, as exposed in this dissertation,
were essential for the formation of discourses about the author and also for its dissemination.
Ursula is the gateway for Maria Firmina dos Reis and her works to be inserted in brazilian
literature history.Instituto de Letras (IL)Departamento de Teoria Literária e Literaturas (IL TEL)Programa de Pós-Graduação em Literatur
Avaliação da ação citotóxica de cardenolídeos em células tumorais
No full textTese (doutorado) - Universidade Federal de Santa Catarina, Centro de Ciências da Saúde, Programa de Pós-Graduação em Farmácia, Florianópolis, 2015.Os cardenolídeos, tais como digoxina e oubaína, são conhecidos por sua eficácia no tratamento da insuficiência cardíaca congestiva e como fármacos antiarrítmicos. Recentemente, foram detectadas novas atividades farmacológicas para esses "antigos" fármacos. Tendo em vista o crescente interesse na pesquisa e desenvolvimento desta classe de compostos como potenciais quimioterápicos, frente a diversas linhagens celulares tumorais, o presente trabalho de tese objetivou avaliar os efeitos citotóxicos em células tumorais de três cardenolídeos (glucoevatromonosídeo, digitoxigenina monodigitoxosídeo e convalotoxina), previamente selecionados pela sua potente ação citotóxica. Inicialmente, eles foram avaliados em linhagens celulares tumorais de diferentes origens e todos demonstraram uma potente ação, em concentrações nanomolares, em todas as linhagens testadas, especialmente nas células de tumor de pulmão (A549). Essa linhagem tumoral foi então selecionada para a continuação dos experimentos para detectar o tipo de morte celular causada por esses três cardenolídeos. O glucoevatromonosídeo (GEV), composto mais promissor, também foi investigado em células U937 (linfoma histiolítico). Todos os três causaram bloqueio da fase G2/M, enquanto que a convalotoxina (CON) aumentou o número de células em subG0 do ciclo celular. O GEV foi capaz de inibir a expressão de importantes proteínas relacionadas ao ciclo celular, como ciclina B1 e p53 em A549. Ainda, esse composto causou bloqueio em subG0 em células U937, demonstrando um efeito dependente do tipo celular. O efeito de morte celular causado pelo GEV também foi tipo celular dependente, já que foi observada morte celular pela ação de caspases nas células U937 e independente da ação das caspases em células A549. A digitoxigenina monodigitoxosídeo não apresentou efeito significativo de morte celular em células A549. A CON aumentou o número de núcleos picnóticos e células Anexina-V positivas, configurando morte celular apoptótica. Alem disso, os três compostos foram capazes de inibir a migração e invasão celulares, em células A549, bem como de reduzir a expressão das proteínas: MMP2, MMP9 e FAK (proteína de adesão focal), que são essenciais no processo de metástase. Além disso, o GEV foi capaz de inibir a expressão de importantes cinases, geralmente super expressas em células tumorais. O conjunto desses dados sugere que estes compostos, especialmente o GEV, podem ser considerados candidatos promissores para o desenvolvimento de uma forma farmacêutica a ser usada no tratamento do câncer de pulmão.Abstract : Cardenolídeos such as ouabain and digoxin are known for their efficacy in treating congestive heart failure as antiarrhythmic drugs. Recently, new pharmacological activities have been found (antiviral and antitumor) to these "old" drugs. Given the growing interest in research and development of this group of compounds, as potential chemotherapeutic agents, this work aimed to evaluate the cytotoxic effects on tumor cells of three cardenolides (glucoevatromonoside, digitoxigenin monodigitoxoside and convallatoxin) previously selected for its potent cytotoxic action. Initially, they were screened in tumor cell lines of different origins and all of them showed potent action at nanomolar concentrations in all cell lines tested, particularly in lung tumor cells (A549). This cell line was then selected for further investigation to detect the kind of cell death caused by these three cardenolides. Glucoevatromonoside (GEV) was the most promising compound, and also investigated in U937 cells (histiocytic lymphoma). All these compounds block G2/M phase, whereas the convallatoxin increased the number of cells in subG0 phase. GEV was able to inhibit the expression of important proteins related to cell cycle, such as Cyclin B1 and p53. Beyond that, this compound caused cell cycle blockage in subG0 phase in U937 cells, demonstrating dependent cell type effect. The effect of cell death caused by GEV was also cell type dependent. In U937 cells, GEV showed a caspase dependent cell death while it is independent of caspase in A549 cells. Digitoxigenin monodigitoxoside did not show a significant percentage of cell death in A549 cells. Convallatoxin increased the number of pyknotic nuclei and Annexin-V positive cells, setting apoptotic cell death in A549 cells. Furthermore, the three compounds are capable of inhibiting cell migration and invasion in A549 cells as well as to reduce the expression of some proteins as MMP2, MMP9 and FAK (focal adhesion protein), which are essential in the process of metastasis. Moreover, GEV was able to inhibit the expression of important kinases, usually over expressed in tumor cells.. Taken together, these data suggest that these compounds, especially GEV can be considered promising candidates for the development of a pharmaceutical form to be used in the treatment of lung cancer
The GDNF-GFRα1 complex promotes the development of hippocampal dendritic arbors and spines via NCAM
No full textThe formation of synaptic connections during nervous system development requires the precise control of dendrite growth and synapse formation. Although glial cell line-derived neurotrophic factor (GDNF) and its receptor GFRα1 are expressed in the forebrain, the role of this system in the hippocampus remains unclear. Here, we investigated the consequences of GFRα1 deficiency for the development of hippocampal connections. Analysis of conditional Gfra1 knockout mice shows a reduction in dendritic length and complexity, as well as a decrease in postsynaptic density specializations and in the synaptic localization of postsynaptic proteins in hippocampal neurons. Gain- and loss-of-function assays demonstrate that the GDNF-GFRα1 complex promotes dendritic growth and postsynaptic differentiation in cultured hippocampal neurons. Finally, in vitro assays revealed that GDNF-GFRα1- induced dendrite growth and spine formation are mediated by NCAM signaling. Taken together, our results indicate that the GDNF-GFRα1 complex is essential for proper hippocampal circuit development.Fil: Irala, Dolores. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Bonafina, Antonela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Fontanet, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Alsina, Fernando Cruz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Paratcha, Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Ledda, Maria Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentin
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