107 research outputs found

    Longueur et fonction des SMS : étude comparative chez les filles et les garcž ons de 13 à 18 ans

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    International audienceObjective. – The use of SMS messaging has grown rapidly over the past decade. Up until now, most Frenchlanguage studies have focused on one predominant SMS characteristic: spelling. The goal of this paper is to extend previous research topics so as to include new dependant variables such as message length and message functions.Method. – A corpus of 1131 SMSes produced in a natural environment by teenage French speakers was analysed. This group was made up of teenage girls and boys between the ages of 13 and 18 who reported frequent usage of SMS messaging over an extended period of time. Did these SMS exchanges confirm stereotypes regarding gender differences? That is, did girls produce longer messages than boys? Did girls send more messages with a relational function than with an informational function, while boys did just the opposite?Results. – The results led to a mitigation of these stereotypes. Girls did produce longer messages than boys. However, this only occurred when the girls were 15–16 years of age and had a long-standing and frequent practice of SMS usage. Regarding functions, girls’ messages more often had a relational function than an informational one, but again, only in girls who were 15–16 years of age and had been SMSing frequently for a long period of time. In boys, it took until 17–18 years of age for the same result to appear. More than a gender difference, these results emphasized a discrepancy in the developmental curves of girls and boys, girls being more precocious than boys

    Antitumour activity of a potent MEK inhibitor RDEA119/BAY 869766 combined with rapamycin in human orthotopic primary pancreatic cancer xenografts

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    <p>Abstract</p> <p>Background</p> <p>Combining MEK inhibitors with other signalling pathway inhibitors or conventional cytotoxic drugs represents a promising new strategy against cancer. RDEA119/BAY 869766 is a highly potent and selective MEK1/2 inhibitor undergoing phase I human clinical trials. The effects of RDEA119/BAY 869766 as a single agent and in combination with rapamycin were studied in 3 early passage primary pancreatic cancer xenografts, OCIP19, 21, and 23, grown orthotopically.</p> <p>Methods</p> <p>Anti-cancer effects were determined in separate groups following chronic drug exposure. Effects on cell cycle and downstream signalling were examined by flow cytometry and western blot, respectively. Plasma RDEA119 concentrations were measured to monitor the drug accumulation <it>in vivo</it>.</p> <p>Results</p> <p>RDEA119/BAY 869766 alone or in combination with rapamycin showed significant growth inhibition in all the 3 models, with a significant decrease in the percentage of cells in S-phase, accompanied by a large decrease in bromodeoxyuridine labelling and cell cycle arrest predominantly in G1. The S6 ribosomal protein was inhibited to a greater extent with combination treatment in all the three models. Blood plasma pharmacokinetic analyses indicated that RDEA119 levels achieved <it>in vivo </it>are similar to those that produce target inhibition and cell cycle arrest <it>in vitro</it>.</p> <p>Conclusions</p> <p>Agents targeting the ERK and mTOR pathway have anticancer activity in primary xenografts, and these results support testing this combination in pancreatic cancer patients.</p

    Role of LKB1 in lung cancer development

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    Three phenotypically related genetic syndromes and their lesions (LKB1, PTEN, and TSC1/2) are identified as frequently altered in lung cancer. LKB1, a kinase inactivated in 30% of lung cancers, is discussed in this review. Loss of LKB1 regulation often coincident with KRAS activation allows for unchecked growth and the metabolic capacity to accommodate the proliferation

    Re-cycling paradigms: cell cycle regulation in adult hippocampal neurogenesis and implications for depression

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    Since adult neurogenesis became a widely accepted phenomenon, much effort has been put in trying to understand the mechanisms involved in its regulation. In addition, the pathophysiology of several neuropsychiatric disorders, such as depression, has been associated with imbalances in adult hippocampal neurogenesis. These imbalances may ultimately reflect alterations at the cell cycle level, as a common mechanism through which intrinsic and extrinsic stimuli interact with the neurogenic niche properties. Thus, the comprehension of these regulatory mechanisms has become of major importance to disclose novel therapeutic targets. In this review, we first present a comprehensive view on the cell cycle components and mechanisms that were identified in the context of the homeostatic adult hippocampal neurogenic niche. Then, we focus on recent work regarding the cell cycle changes and signaling pathways that are responsible for the neurogenesis imbalances observed in neuropathological conditions, with a particular emphasis on depression

    Type I interferon/IRF7 axis instigates chemotherapy-induced immunological dormancy in breast cancer

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    Neoadjuvant and adjuvant chemotherapies provide survival benefits to breast cancer patients, in particular in estrogen receptor negative (ER-) cancers, by reducing rates of recurrences. It is assumed that the benefits of (neo)adjuvant chemotherapy are due to the killing of disseminated, residual cancer cells, however, there is no formal evidence for it. Here, we provide experimental evidence that ER- breast cancer cells that survived high-dose Doxorubicin and Methotrexate based chemotherapies elicit a state of immunological dormancy. Hallmark of this dormant phenotype is the sustained activation of the IRF7/IFN-beta/IFNAR axis subsisting beyond chemotherapy treatment. Upregulation of IRF7 in treated cancer cells promoted resistance to chemotherapy, reduced cell growth and induced switching of the response from a myeloid derived suppressor cell-dominated immune response to a CD4(+)/CD8(+) T cell-dependent anti-tumor response. IRF7 silencing in tumor cells or systemic blocking of IFNAR reversed the state of dormancy, while spontaneous escape from dormancy was associated with loss of IFN-beta production. Presence of IFN-beta in the circulation of ER- breast cancer patients treated with neoadjuvant Epirubicin chemotherapy correlated with a significantly longer distant metastasis-free survival. These findings establish chemotherapy-induced immunological dormancy in ER- breast cancer as a novel concept for (neo)adjuvant chemotherapy activity, and implicate sustained activation of the IRF7/IFN-beta/IFNAR pathway in this effect. Further, IFN-beta emerges as a potential predictive biomarker and therapeutic molecule to improve outcome of ER- breast cancer patients treated with (neo)adjuvant chemotherapy.Peer reviewe

    Polysome Profiling of mAb Producing CHO Cell Lines Links Translational Control of Cell Proliferation and Recombinant mRNA Loading onto Ribosomes with Global and Recombinant Protein Synthesis

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    mRNA translation is a key process determining growth, proliferation and duration of a Chinese hamster ovary (CHO) cell culture and influences recombinant protein synthesis rate. During bioprocessing, CHO cells can experience stresses leading to reprogramming of translation and decreased global protein synthesis. Here we apply polysome profiling to determine reprogramming and translational capabilities in host and recombinant monoclonal antibody-producing (mAb) CHO cell lines during batch culture. Recombinant cell lines with the fastest cell specific growth rates were those with the highest global translational efficiency. However, total ribosomal capacity, determined from polysome profiles, did not relate to the fastest growing or highest producing mAb cell line, suggesting it is the ability to utilise available machinery that determines protein synthetic capacity. Cell lines with higher cell specific productivities tended to have elevated recombinant heavy chain transcript copy numbers, localised to the translationally active heavy polysomes. The highest titre cell line was that which sustained recombinant protein synthesis and maintained high recombinant transcript copy numbers in polysomes. Investigation of specific endogenous transcripts revealed a number that maintained or reprogrammed into heavy polysomes, identifying targets for potential cell engineering or those with 5? untranslated regions that might be utilised to enhance recombinant transcript translation

    GTnum CREM ELN #ELN – Monographie de terrain : CM1 – CSP mixtes– Zone rurale – Occitanie - Groupes thĂ©matiques numĂ©riques de la Direction du numĂ©rique pour l'Ă©ducation (MinistĂšre de l'Éducation nationale et de la jeunesse) 2020-2022

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    Productions des groupes thĂ©matiques numĂ©riques (Direction du numĂ©rique pour l’éducation du MinistĂšre de l’Education nationale et de la jeunesse)Cette monographie de terrain est rĂ©digĂ©e dans le cadre du GTnum « Enfances et LittĂ©raties NumĂ©riques », menĂ© par le CREM, UniversitĂ© de Lorraine, et EPSYLON, UniversitĂ© de Montpellier, ainsi que les laboratoires CCLE, ESO et IMS. Elle rend compte des donnĂ©es recueillies sur un temps long au sein d’un Ă©tablissement scolaire, et d’une classe oĂč ont Ă©tĂ© observĂ©s et interrogĂ©s les usages numĂ©riques dĂ©veloppĂ©s dans l’acte d’enseignement-apprentissage, ainsi que les compĂ©tences numĂ©riques en lien, et la prise en compte des pratiques numĂ©riques enfantines au sein de la pratique de classe.Ce travail s’inscrit dans le cadre du GTnum CREM ELN, Enfances et LittĂ©raties NumĂ©riques, dans la thĂ©matique « NumĂ©rique et Ă©ducation : pour une prise en compte des disparitĂ©s sociales et territoriales » des GTnum 2020/2022 soutenus par la Direction du numĂ©rique pour l’éducation (DNE)
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