176 research outputs found
Cat. isard, isart, gasc. izar(t), prov. uzart, uzar(n) "cabra montés"
No full textEtimología de estas palabras, que se considera pueden ser de origen ibérico o vasco. El autor cree que estas palabras tienen relación con la vasca "izar" (estrella) que en labortano quiere decir también "centro por donde parte el pelo"Etymology of these words, considered to be of Basque or Iberian origin. The author believes that these words are related with the Basque "izar" (star) that in Basque from Labourd also means "place from which hair stems
Not informed by author
No full textO desenvolvimento social faz parte da maturação de organismos sociais; é crucial para que os indivíduos possam aprender como se comportar num ambiente social complexo e dinâmico. Este ambiente social complexo resulta das relações interindividuais, que são identificadas pela repetição de interações entre os membros de um grupo. A Análise de Redes Sociais (SNA) é uma ferramenta para analisar essa estrutura de forma quantitativa e qualitativa. Embora haja diversos trabalhos com primatas utilizando a SNA, estudos sobre o desenvolvimento social de imaturos são incipientes, principalmente investigações longitudinais de populações selvagens. O macaco-prego-do-peito-amarelo (Sapajus xanthosternos), apresenta longa imaturidade e vive em um ambiente social complexo. Dessa forma, torna-se adequado para este estudo, que teve por objetivo investigar o desenvolvimento da rede social de imaturos de uma população selvagem de e testar a hipótese de que o desenvolvimento social acompanha o processo de independência materna. Com vídeos coletados em campo, analisamos a dinâmica de associação espacial de oito imaturos. A partir desses dados foi construída uma rede egocêntrica para cada imaturo a cada mês de vida, baseadas em matrizes com o índice de associação simples, ao longo dos três primeiros anos de vida dos imaturos. Assim, foi possível analisar as mudanças das propriedades das redes. O desenvolvimento social não acompanhou a maturação física e o desenvolvimento da independência materna, foi mais acelerado e dinâmico, resultando numa infância curta. Os três primeiros meses de vida foram um marco na ontogênese da rede social dos imaturos; houve o maior número de parceiros de associação que visitavam o filhote frequentemente e ao mesmo tempo. A juventude dos imaturos foi um período de maior isolamento, possivelmente em função da confluência da diminuição da tolerância dos adultos e das mudanças no estilo social intrínsecas aos juvenis, em que há um aumento da exploração do ambiente, da ansiedade e de comportamentos de exposição a riscos. Sugerimos que o padrão de desenvolvimento social mais rápido tenha ocorrido em função das características e condições ecológicas a que o grupo estudado está submetido. Os macacos-prego-do-peito-amarelo deste estudo são sujeitos a um alto risco de predação e pressão de caça, com isso pode ocorrer uma pressão para m desenvolvimento social aceleradoThe social development is part of an organism maturation; it is essential for the individual learning of social behaviours and integration in a complex social environment. This complex social environment comprises the interindividual relationships, revealed by the repeated interaction among group members. Social network analysis (SNA) allows for a quantitative as well as qualitative analyses of this social structure.In spite of several primate studies that have employed the SNA, there is a lack of studies on the initial social development, in particular using longitudinal data of wild populations. The yellow breasted capuchin monkey (Sapajus xanthosternos) presents a long period of immaturity, and lives in a complex social environment. Therefore, it is a good modelfor a study aiming at investigating the development of the immature social network in a wild population and testing the hypothesis that the social development follows the acquisition of independency from maternal care. Using a video data base recorded in the field, we analysed the dynamics of association of eighth youngsters. We built an egocentric network for each immature at each month of life based on matrices of simple association index, throughout the first three years of life. We then analysed changes in network measures. The social development did not follow the physical maturation and independency from maternal care; it was faster and more dynamic, resulting in a short infancy. The first three months of life were an ontogenetic mile stone of the social network; there were more association partners that visited then immature often and at the same time. The juvenility was a period of increased social isolation, likely due to the joint effects of decreased tolerance from the adults and intrinsic juvenile social style, that includes more exploration of the habitat, more anxiety and risky behaviours. We suggest that this faster social development reflects the ecological features surrounding the studied social group. The studied yellow breasted capuchin monkeys are submitted to a high risk of predation and hunting pressure what might induce a faster social developmen
Die hepatische Reaktion auf eine Infektion mit Listeria monocytogenes
No full textIn the present study, we investigated the liver specific response upon infection with L. monocytogenes, a model pathogen for Gram-positive infections over a period of 5days. We used whole genome microarray chips to determine the temporal transcriptome at five observation points. Relative mRNA levels were validated for a representative subset of genes by quantitative Real-Time PCR. In the analysis of these data we followed a strict methodology. The quality of microarray data was ensured by several measures, including quality control tools developed and optimized at our institution. The biological effects of differentially expressed genes were investigated and interpretation of these results was followed by confirmatory experiments.In conclusion, this work allows a unique insight into regulatory networks of several biological processes and interconnections following an infection with L. monocytogenes. Based on our results and by integration of known literature, LXR-a and related transcription factors are proposed to be fundamental for the regulation of hepatic and subsequently systemic response to pathogens.In der vorliegenden Studie untersuchten wir die Leber-spezifische Antwort nach Infektion mit L. monocytogenes, ein Gram-positives Modell-Bakterium über einen Zeitraum von 5 Tagen hinweg. Dabei machten wir Gebrauch von whole genome microarrays, mit dessen Hilfe das transiente Transkriptom zu fünf verschiedenen Zeitpunkten bestimmt wurde. Relative mRNA-Veränderungen wurden anhand einer repräsentativen Auswahl von Genen mittels quantitativer Echtzeit-PCR validiert. Die Analyse gewonnener Daten folgte einer strikten Methodologie. Die Qualität der microarray Daten wurde durch bioinformatische Programme, die an unserem Institut enwickelt und optimiert wurden, gesichert. Basierend auf dem Expressionsmuster differenziell regulierter Gene wurden biologische Rückschlüsse gezogen, die in subsequenten Experimenten untersucht und validiert wurden.Zusammenfassend bietet diese Arbeit einen einzigartigen Einblick in regulatorische Netzwerke verschiedenster biologischer Funktionen und Interaktionen nach Infektion mit L. monocytogenes. Basierend auf diesen Resultaten und eingebettet in bekannte Literatur, stellt sich eine herausragende Rolle für LXR und verwandte Transkriptionsfaktoren bei der hepatischen und subsequent auch systemischen Immunantwort dar
Abstract B21: Probing tumor heterogeneity and immune infiltration with Cyclic Immunofluorescence (CycIF), a robust, multiplexed imaging method
No full textAbstract
Tumor microenvironment, defined by surrounding stromal/immune cells as well as blood vessels, plays an important role in disease progression and therapy resistance. Increasing understanding of the heterogeneity in both tumor and its microenvironment will be crucial to development more effective therapies. Recently, several studies employing state-of-the-art single-cell sequencing methods reveal enormous complexity in tumor microenvironment. However, the spatial information and cell-to-cell interaction could not be preserved in these dissociated cells. Immunofluorescence has been widely used in different fields of biological and medical research for decades. The ability to obtain in situ and single-cell information makes this technique particularly important in tumor biology. However, biochemical and optical constraints limit the number of signals that could be captured simultaneously within the same sample. We have developed the CycIF (Cyclic Immunofluorescence), an easy and low-cost method to increase the multiplexity of conventional immunofluorescence. The CycIF method has been first applied in pre-clinical drug discovery, cancer and stem cell biology with adherent cell cultures. In here, we modified the original CycIF method for IHC/IF on FFPE samples, and used that to probe tumor heterogeneity, microenvironment and immune infiltration in various types of tumors. Up to 30 different antigens/markers could be simultaneously detected in different tumor samples, and these makers represent a wide range of biological processes, including the key molecules for lymphocyte surface makers (CD45, CD4, CD8, CD20, CD11c), immune checkpoints (PD-1, PD-L1), stromal/EMT proteins (E-Cadherin, Vimentin), cell cycle regulators (CycD1, PCNA, Ki67, pRB, p21/CIP), signaling proteins (EGFR, pERK, pS6) and apoptosis mediators (p53, Bax, Bcl-2, Survivin). Our study not only provides the first detailed map of tumor and its immune microenvironment, but also illustrates a robust multiplexed imaging platform for probing tumor heterogeneity.
Citation Format: Jia-Ren Lin, Benjamin Izar, Sabrina Hawthorne, Josh Nordberg, Eric Kaldjian, Peter Sorger. Probing tumor heterogeneity and immune infiltration with Cyclic Immunofluorescence (CycIF), a robust, multiplexed imaging method. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2016 Oct 20-23; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2017;5(3 Suppl):Abstract nr B21.</jats:p
How authenticity is signalled in athlete–luxury brand partnerships
No full textThe study investigates how authenticity is signalled in athletes–luxury brand partnerships and its impact on the athlete’s personal brand across different sporting contexts. This paper employs a qualitative multiple case study approach, analyzing 45 Instagram posts from 15 athletes–luxury brand partnerships across seven sports. Posts were examined using a theory-driven authenticity grid comprising four lenses and nine sub-dimensions: athlete antecedents (rarity, stability), authenticity types (true-to-self, true-to-ideal, true-to-fact), cue mechanisms (iconic, indexical), and general authenticity cues (value congruence, clear disclosure). In addition, a content analysis of over 1,000 audience comments was conducted to assess the degree of acceptance of each partnership and specific points where authenticity is contested. The findings of the study contributes to a different perspective on personal branding by having authenticity as the backbone and focusing only on athletes and luxury brands.Este estudo investiga como a autenticidade é sinalizada em parcerias entre atletas e marcas de luxo e qual o seu impacto na marca pessoal do atleta em diferentes contextos esportivos. O trabalho utiliza uma abordagem qualitativa de estudo de casos múltiplos, analisando 45 publicações no Instagram de 15 parcerias entre atletas e marcas de luxo em sete modalidades esportivas. As publicações foram examinadas a partir de uma grade de autenticidade orientada pela teoria, composta por quatro lentes e nove subdimensões: antecedentes do atleta (raridade, estabilidade), tipos de autenticidade (fidelidade a si mesmo, fidelidade ao ideal, fidelidade aos fatos), mecanismos de sinalização (icônicos, indexicais) e sinais gerais de autenticidade (congruência de valores, transparência na divulgação). Além disso, foi realizada uma análise de conteúdo de mais de 1.000 comentários do público para avaliar o grau de aceitação de cada parceria e identificar pontos específicos em que a autenticidade é contestada. Os resultados do estudo contribuem com uma perspectiva distinta sobre personal branding ao ter a autenticidade como eixo central e focar exclusivamente em atletas e marcas de luxo
GILA, a Replacement for the Soft‐Agar Assay that Permits High‐Throughput Drug and Genetic Screens for Cellular Transformation
No full text
Autor[izar-se]: subjetivação e literatura pela obra de Maura Lopes Cançado
No full textO encontro com a escritura de Maura Lopes Cançado é, em grande parte, marcado por uma hiperpersonificação da autora, que produz um ruído despotencializante da experiência literária. Gerado tanto pelas marcas autorreferenciais presentes nos textos, quanto pela especificidade ou excentricidade dos papeis identitários que lhe foram atribuídos em vida: o de mulher vaidosa e imoral, o de louca, o de criminosa, etc. Filtros que se interpõe à leitura e ameaçam verter os textos em meros índices de revelação, apêndice à personagem autoral. Condição presente no ato da leitura e, também no ato da escrita, em que está explicita a ânsia de, ao relatar a si mesma, constituir a si mesma, enquanto sujeito responsivo, reconhecível e aceito socialmente. O conceito de autoria, assim, transborda do território específico da estética até o regime ético da interpelação, revela-se como modo de subjetivação. Mas, quais são os critérios, qual regime de verdade dita as normas para se ser considerado um sujeito? A herança metafísica, instauradora da verdade enquanto presença, privilegia o ser ao devir e excluí como a-significante a pluralidade, tudo o que não se cristaliza em permanência. Nesta ordem do discurso, a univocidade das vozes, diferença, tem de ser superada pela identidade e pela lógica semântica. Fincada nesse solo da autorreferencialidade, a literatura contemporânea pode criar um campo de tensão entre os polos do narcisismo capitalista dominante e da crítica do sujeito da verdade. Afinal, quando o insere na ficção, descredibiliza, por assim dizer, este sujeito coerente, monolítico. Abrindo possíveis vias de escoamento do deserto da consciência. A habilidade fabuladora – tão invisibilizada quanto inerente à linguagem –, funciona intensiva, afetivamente, explicitando o espaço entre as amarras dos discursos, das ordens dos modos de vida. A ficção pode ser ferramenta potente nesse exercício de autor[izar-se]. Escapando tanto da afirmação narcisista, hiperpessoal quanto da afonia do a-pessoal, abrindo, pela impessoalidade, um terreno para que a diferença aconteçaThe encounter with the writing of Maura Lopes Cançado is largely marked by a hyperpersonification of the author, which produces a depotentializing noise from the literary experience. Generated by the self-referential marks present in the texts, as well as by the specificity or eccentricity of the identity roles attributed to them in life: that of vain and immoral woman, that of madwoman, that of criminal, etc. Filters that stand in the way of reading and threaten to turn texts into mere revelation indices, appendix to the author character. A condition present in the act of reading, and also in the act of writing, in which the eagerness to report itself constitutes the self, as a responsive, recognizable and socially accepted subject. The concept of authorship thus overflows from the specific territory of aesthetics to the ethical regime of interpellation, reveals itself as a mode of subjectivation. But what are the criteria, which truth regime dictates the norms for being considered a subject? The metaphysical heritage, establishing truth as a presence, privileges being over becoming and excludes plurality as a signifier, everything that does not permanently crystallize. In this order of discourse, the univocity of voices, difference, has to be overcome by identity and semantic logic. Grounded in this ground of selfreferentiality, contemporary literature can create a field of tension between the poles of dominant capitalist narcissism and the criticism of the subject of truth. After all, when it inserts it in fiction, it discredits, as it were, this coherent, monolithic subject. Opening possible outlets for the desert of consciousness. The fabulous skill - as invisible as inherent in language - it works intensively, affectionately, by explaining the space between the shackles of discourses, of orders of ways of life. Fiction can be a potent tool in this authoring exercise. Escaping both the narcissistic, hyperpersonal statement and the aphonia of the a-personal, opening impersonal ground for difference to take a placeCoordenação de Aperfeiçoamento de Pessoal de Nível Superior – CAPE
Abstract 5561: Single-cell analysis reveals an adaptive, transiently heritable, slowly-dividing, drug-resistant state inhibitable by drug combinations
No full textAbstract
Adaptation and fractional response of tumor cells to targeted inhibitors of oncogenic pathways creates a population of viable tumor cells from which fully resistant clones can ultimately arise. Thus, understanding transient drug adaptation is key for both improving the effectiveness of treatment and delaying/controlling acquired resistance. Despite the wealth of information available about feedback mechanisms associated with adaptive resistance, most of our knowledge in this area comes from studying drug response in bulk tumor cell populations. Furthermore, the phenotypic consequences of drug adaptation have been often studied at a few fixed time-points, when drug-adapted cells exhibit a high population-average activity in multiple pro-growth signaling cascades. It therefore remains unclear how the initial responses to drug relate to subsequent phenotypes such as cell death or adaptation. This is likely a key point for designing novel approaches to overcome fractional drug response in tumor cells and to achieve durable therapy.
We use real-time live-cell imaging, single-cell analysis and molecular profiling to show that exposure of BRAFV600E melanoma cells to RAF/MEK inhibitors elicits a time-variable and heterogeneous response in which some cells die, some arrest and the remainder adapt to drug. Drug-adapted cells up-regulate markers of the neural crest (e.g. NGFR), a melanocyte precursor, and grow slowly. The drug-induced slowly-cycling NFGRHigh state is only transiently stable, reverting to the drug-naïve state within two weeks of drug withdrawal as measured by the restoration of RAF/MEK inhibitor sensitivity, accelerated rate of cell division and reduced expression of NGFR. Transcriptional and biochemical profiling of cell lines and human tumors implicates a role for the c-Jun/ECM/FAK/Src cascade in driving the de-differentiated resistance program. We identify multiple drugs targeting this cascade as well as BET bromodomain inhibitors that block this resistance program in cell lines and in a BRAFV600E melanoma xenograft model and increase sensitivity and maximal effect (Emax) of RAF/MEK inhibitors. Our study reveals directly how drug adaptation happens in individual tumor cells leading to emergence of heterogeneous cell sub-populations with reduced drug-sensitivity that may be targeted by drug combinations.
Citation Format: Mohammad Fallahi-Sichani, Verena Becker, Benjamin Izar, Gregory J. Baker, Jia-Ren Lin, Sarah A. Boswell, Levi A. Garraway, Peter K. Sorger. Single-cell analysis reveals an adaptive, transiently heritable, slowly-dividing, drug-resistant state inhibitable by drug combinations [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 5561. doi:10.1158/1538-7445.AM2017-5561</jats:p
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