Reconocimiento de objetos por color en ratones mus musculus cepa C57BL/6J

The aim of the present study was to evaluate the ability of the mice Mus musculus C57BL/6J strain to form and evoke a visual recognition memory of objects that differ only by their color. In order to do this, we use the paradigm of novel objet recognition (NOR), which takes advantage of the innate tendency of mice to explore a novel object longer than a familiar one. The present study is the first to show preliminary results on the ability to form long-term memories of visual recognition by color in this mouse strain. In addition, this work suggests this mouse strain as a model to be used in further research on the study of the formation of recognition memory based on color.El objetivo del presente trabajo fue evaluar la capacidad de los ratones Mus musculus cepa C57BL/6J de formar y evocar una memoria de reconocimiento visual de objetos que difieren exclusivamente por su color. Para ello, empleamos el paradigma de reconocimiento de objeto novedoso (novel objet recognition, NOR), el cual toma ventaja de la tendencia innata de los ratones a explorar más tiempo un objeto novedoso que uno familiar. El presente estudio es el primero en mostrar resultados preliminares acerca de la capacidad de formar memorias de reconocimiento visual por color y de largo término en esta cepa de ratón. Además, este trabajo sugiere a esta cepa de ratón como modelo a utilizar en investigaciones sobre los procesos de formación de memorias de reconocimiento por color

Identifying and Targeting Androgen Receptor-Variant Oncogenic Networks as Exploitable Prostate Cancer Vulnerabilities

Castration-resistant prostate cancer (CRPC) progresses rapidly and is incurable. Constitutively active androgen receptor splice variants, such as AR-V7, represent a well-established mechanism of therapeutic resistance and disease progression. These AR variants lack the carboxy-terminal ligand binding domain, the target of all approved drugs against AR. Consequently, a significant challenge is to identify novel therapeutic strategies that are effective against AR variant-expressing prostate tumors. In this work, we evaluated the possibility of targeting AR-V7 in PC and CRPC through two independent approaches. The first approach consisted of disrupting the interaction between AR-V7 and its coactivators as an exploitable PC vulnerability. Using mutational and biochemical studies, we identified the domain in Vav3 (an established AR coactivator) necessary and sufficient to interact with AR-V7. Expressing this Vav3 domain in CRPC cells in vitro disrupted the interaction of Vav3 (as well as other coactivators) with AR-V7 and the subsequent enhancement of AR-V7 activity. Disrupting these interactions decreased CRPC cell proliferation, increased apoptosis, and decreased migration. Second, as an indirect approach to target cells that depend on AR-V7, we used a multi-pronged, unbiased systems biology analysis to identify downstream AR-V7-regulated hub genes that both drive cancer progression and feed back to enhance AR-V7 activity. Such genes likely encode prognostic markers as well as potential therapeutic targets acting within the AR-V7 network. Our systems biology approach utilized: 1) clinically relevant gene sets upregulated during human PC progression obtained by Weighted Gene-Co-expression Network Analysis (WGCNA); 2) an AR-V7 functional interactome from a high-throughput synthetic genetic array (SGA) screening in the yeast, S. pombe; and 3) genes regulated by AR-V7 in CRPC cells. We identified seven genes that were upregulated in human PC, functionally interacted with AR-V7, and were AR-V7 targets in PC. This gene set, composed of cell cycle and mitosis-regulating genes, comprised a signature that strongly correlated with patient Gleason score and predicted disease-free survival in large independent PC patient cohorts. Individually depleting the expression of these genes decreased ligand-independent AR transcriptional activity concomitant with reduced CRPC cell proliferation. Because CRPC may exhibit “addiction” to AR-V7 activity through dependency on the seven inter-related genes that we identified, pharmacologically targeting proteins encoded by two genes in this gene set led to potent synergistic inhibition of CRPC cell proliferation. This study utilized two different approaches to disrupt AR-V7 oncogenic signaling. First, we demonstrated the potential therapeutic utility of inhibiting constitutively active AR-V signaling by disrupting coactivator binding; second, by utilizing an unbiased and novel gene discovery strategy to identify clinically-relevant AR-V7 interaction networks, forming the basis for both prognostic use and rational, combinatorial therapy for CRPC.</p

Semantic Memory Organization in Children and Young Adults

The study of the organization of semantic memory has become of great interest in the cognitive psychology field and in neuropsychological research. Semantic knowledge considered to be represented by concepts, which can be related taxonomically (when they are hierarchically organized) or thematically (when they are linked by cross-categorical relations). Both relations arise from distinct processes, as evidenced by numerous neuropsychological and behavioral dissociations. Many works have stated that the production of thematic relations outnumbers that of taxonomic relations in children, and that as they grow older a thematic-to-taxonomic shift occurs, while others claim that such a shift does not take place and state that one major problem is that the tasks used in previous studies to assess concept-relations are biased. In our work we performed a feature production task in such a way that subjects could freely associate concepts with their features. Our results, using this non-biased-task, show that the evocation of taxonomic relations was higher in the adult group (formed by thirty 20-to 40-year-olds) compared to the children group (formed by forty-eight 6-to 9-year-olds), but that, nonetheless, thematic relations were still present in the adult group. This suggests, instead of a thematic-to-taxonomic shift in adulthood, the coexistence of both types of relations, which is crucial to research on language structure and conceptual knowledge. Thus, our results contribute to the understanding of semantic knowledge organization and provide valuable groundwork to the development of clinical instruments used in neuropsychological tests to assess language, attention and semantic memory, where precise information of concept-relations is crucial.Fil: Favarotto, Victoria. Universidad Nacional de Mar del Plata. Facultad de Psicología. Centro De Investigación en Procesos Básicos, Metodologías y Educación; ArgentinaFil: García Coni Bosch, Ana Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Mar del Plata. Facultad de Psicología. Centro De Investigación en Procesos Básicos, Metodologías y Educación; ArgentinaFil: Magani, Fiorella. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Vivas, Jorge Ricardo. Universidad Nacional de Mar del Plata. Facultad de Psicología. Centro De Investigación en Procesos Básicos, Metodologías y Educación; Argentin

Abstract 5545: Integrated system-level analyses of androgen receptor variant networks to identify novel prostate cancer-relevant genes

Abstract Unbiased high-throughput approaches provide a global view of the massive genetic and transcriptomic changes that occur in and potentially drive cancer. Such approaches permit the discovery of novel markers and therapeutic targets. Current treatments for advanced prostate cancer (PC) focus on inhibiting the androgen receptor (AR). However, PC inevitably progresses to a stage termed castration-resistant prostate cancer (CRPC), which is incurable. In CRPC, C-terminal truncated, constitutively active AR splice variants (such as AR-V7) play key transcription-regulatory roles resulting in treatment resistance and disease progression. However, designing high-affinity drugs to target the amino terminus of AR and AR variants is a major challenge due to the intrinsic disorganized structure of this region. Thus there is an imperative need to identify novel AR-V7 hub genes in PC that may serve as therapeutic targets. We performed an extensive and highly robust gene expression meta-analysis on PC patient samples. We defined gene modules correlated with disease progression using a powerful systems biology approach termed Weighted Gene-Co-expression Network Analysis (WGCNA). Further, we mapped the AR-V7 interactome for the first time using a novel high-throughput synthetic genetic array screening in yeast, known as Yeast Augmented Network Analysis (YANA). YANA was performed by crossing yeast expressing AR-V7 with a large collection of yeast strains lacking non-essential genes, and identifying those genes that caused a change in yeast growth (fitness). Human orthologs of the identified yeast genes were used to build an AR-V7 functional gene network. Finally, we combined the results from our independent system-level analyses with experimental data to identify hub genes that are upregulated in PC patients, regulated by AR-V7, and also functionally interact with AR-V7. The identified genes not only include select genes previously linked to PC, such as members of the cyclin and topoisomerase families, but also genes that have not been previously linked to AR-V7 activity or PC progression. Moreover, our gene expression signature predicts a higher risk of PC recurrence after primary treatment in patients. In sum, we show here an unbiased and novel gene discovery strategy using bioinformatics in concert with experimental approaches to identify new candidate genes in CRPC that may lead to prognostic markers and future targeted therapies. Citation Format: Fiorella Magani, Eric R. Bray, Ning Zhao, Stephanie Peacock, Kerry L. Burnstein. Integrated system-level analyses of androgen receptor variant networks to identify novel prostate cancer-relevant genes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5545. doi:10.1158/1538-7445.AM2017-5545</jats:p

Reconocimiento de objetos por color en ratones Mus musculus cepa C57BL/6J

The aim of the present study was to evaluate the ability of the mice Mus musculus C57BL/6J strain to form and evoke a visual recognition memory of objects that differ only by their color. In order to do this, we use the paradigm of novel objet recognition (NOR), which takes advantage of the innate tendency of mice to explore a novel object longer than a familiar one. The present study is the first to show preliminary results on the ability to form long-term memories of visual recognition by color in this mouse strain. In addition, this work suggests this mouse strain as a model to be used in further research on the study of the formation of recognition memory based on color.El objetivo del presente trabajo fue evaluar la capacidad de los ratones Mus musculus cepa C57BL/6J de formar y evocar una memoria de reconocimiento visual de objetos que difieren exclusivamente por su color. Para ello, empleamos el paradigma de reconocimiento de objeto novedoso (novel objet recognition, NOR), el cual toma ventaja de la tendencia innata de los ratones a explorar más tiempo un objeto novedoso que uno familiar. El presente estudio es el primero en mostrar resultados preliminares acerca de la capacidad de formar memorias de reconocimiento visual por color y de largo término en esta cepa de ratón. Además, este trabajo sugiere a este ratón como modelo a utilizar en investigaciones ulteriores sobre el estudio de los procesos de formación de memorias de reconocimiento por color en humanos.

Targeting AR Variant-Coactivator Interactions to Exploit Prostate Cancer Vulnerabilities

Castration-resistant prostate cancer (CRPC) progresses rapidly and is incurable. Constitutively active androgen receptor splice variants (AR-Vs) represent a well-established mechanism of therapeutic resistance and disease progression. These variants lack the AR ligand-binding domain and, as such, are not inhibited by androgen deprivation therapy (ADT), which is the standard systemic approach for advanced prostate cancer. Signaling by AR-Vs, including the clinically relevant AR-V7, is augmented by Vav3, an established AR coactivator in CRPC. Using mutational and biochemical studies, we demonstrated that the Vav3 Diffuse B-cell lymphoma homology (DH) domain interacted with the N-terminal region of AR-V7 (and full length AR). Expression of the Vav3 DH domain disrupted Vav3 interaction with and enhancement of AR-V7 activity. The Vav3 DH domain also disrupted AR-V7 interaction with other AR coactivators: Src1 and Vav2, which are overexpressed in PC. This Vav3 domain was used in proof-of-concept studies to evaluate the effects of disrupting the interaction between AR-V7 and its coactivators on CRPC cells. This disruption decreased CRPC cell proliferation and anchorage-independent growth, caused increased apoptosis, decreased migration, and resulted in the acquisition of morphological changes associated with a less aggressive phenotype. While disrupting the interaction between FL-AR and its coactivators decreased N-C terminal interaction, disrupting the interaction of AR-V7 with its coactivators decreased AR-V7 nuclear levels. This study demonstrates the potential therapeutic utility of inhibiting constitutively active AR-V signaling by disrupting coactivator binding. Such an approach is significant, as AR-Vs are emerging as important drivers of CRPC that are particularly recalcitrant to current therapies.

Hydraulic stopper effect as a regulator of inorganic nutrients distribution in Mar Chiquita coastal lagoon (Argentina)

Estuaries are transitional systems that link both land and oceans, with particular dynamics regulated by their own characteristics. The main aim of the present study was the assessment of the effects generated by a strong dry period on the distribution of inorganic nutrients and biological production within Mar Chiquita coastal lagoon, comparing this information with that from periods of precipitation regularly conducted. For this study we selected Mar Chiquita coastal lagoon and analyzed a 20-year data series for concentration and distribution of physical and chemical parameters, in particular salinity, inorganic nutrients (i.e. dissolved inorganic nitrogen, phosphate, silicate) and photosynthetical pigments (i.e. chlorophyll a). We also evaluated the association between these parameters and climate conditions within the region, and found a strong relationship and very quick response to changes. As a result, we report, for the first time in the region, rainfall as a main driver of biogeochemical processes within the estuarine system. The obtained results allowed us to confirm the clear transference processes between land and oceanic systems, and the role of climate as a driver of the corresponding transference processes.Fil: Marcovecchio, Jorge Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto Argentino de Oceanografía. Universidad Nacional del Sur. Instituto Argentino de Oceanografía; Argentina. Academia Nacional de Ciencias Exactas, Físicas y Naturales; Argentina. Universidad Tecnológica Nacional. Facultad Regional Bahía Blanca; Argentina. Universidad FASTA "Santo Tomas de Aquino"; ArgentinaFil: de Marco, Silvia Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Marinas y Costeras; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales; Argentina. Universidad FASTA "Santo Tomas de Aquino"; ArgentinaFil: Magani, Fiorella. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. University of Miami; Estados UnidosFil: Spetter, Carla Vanesa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto Argentino de Oceanografía. Universidad Nacional del Sur. Instituto Argentino de Oceanografía; Argentina. Universidad Nacional del Sur. Departamento de Química; ArgentinaFil: Beltrame, Maria Ornela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata; Argentina. Universidad FASTA "Santo Tomas de Aquino"; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Cionchi, Jose Luis. Universidad FASTA "Santo Tomas de Aquino"; Argentin