Why children and adults sometimes (but not always) compute implicatures

Noveck (2001) argued that children even as old as 11 do not reliably endorse a scalar interpretation of weak scalar terms (some, might, or) (cf. Braine & Rumain, 1981; Smith, 1980). More recent studies suggest, however, that children's apparent failures may depend on the experimental demands (Papafragou & Musolino, 2003). Although previous studies involved children of different ages as well as different tasks, and are thus not directly comparable, nevertheless a common finding is that children do not seem to derive scalar implicatures to the same extent as adults do. The present article describes a series of experiments that were conducted with Italian speaking subjects (children and adults), focusing mainly on the scalar term some. Our goal was to carefully examine the specific conditions that allow the computation of implicatures by children. In so doing, we demonstrate that children as young as 7 (the youngest age of the children who participated in the Noveck study) are able to compute implicatures in experimental conditions that properly satisfy certain contextual prerequisites for deriving such implicatures. We also present further results that have general consequences for the research methodology employed in this area of study. Our research indicates that certain tasks mask children's understanding of scalar terms, not only including the task used by Noveck, but also tasks that employ certain explicit instructions, such as the training task used by Papafragou & Musolino (2003). Our findings indicate further that, although explicit training apparently improves children's ability to draw implicatures, children nevertheless fail to achieve adult levels of performance for most scalar terms even in such tasks, and that the effects of instruction do not last beyond the training session itself for most children. Another relevant finding of the present study is that some of the manipulations of the experimental context have an effect on all subjects, whereas others produce effects on just a subset of children. Individual differences of this kind may have been concealed in previous research because performance by individual subjects was not reported. Our general conclusions are that even young children (7-year olds) have the prerequisites for deriving scalar implicatures, although these abilities are revealed only when the conversational background is natural

Temozolomide-Acquired Resistance Is Associated with Modulation of the Integrin Repertoire in Glioblastoma, Impact of α5β1 Integrin

Despite extensive treatment, glioblastoma inevitably recurs, leading to an overall survival of around 16 months. Understanding why and how tumours resist to radio/chemotherapies is crucial to overcome this unmet oncological challenge. Primary and acquired resistance to Temozolomide (TMZ), the standard-of-care chemotherapeutic drug, have been the subjects of several studies. This work aimed to evaluate molecular and phenotypic changes occurring during and after TMZ treatment in a glioblastoma cell model, the U87MG. These initially TMZ-sensitive cells acquire long-lasting resistance even after removal of the drug. Transcriptomic analysis revealed that profound changes occurred between parental and resistant cells, particularly at the level of the integrin repertoire. Focusing on α5β1 integrin, which we proposed earlier as a glioblastoma therapeutic target, we demonstrated that its expression was decreased in the presence of TMZ but restored after removal of the drug. In this glioblastoma model of recurrence, α5β1 integrin plays an important role in the proliferation and migration of tumoral cells. We also demonstrated that reactivating p53 by MDM2 inhibitors concomitantly with the inhibition of this integrin in recurrent cells may overcome the TMZ resistance. Our results may explain some integrin-based targeted therapy failure as integrin expressions are highly switchable during the time of treatment. We also propose an alternative way to alter the viability of recurrent glioblastoma cells expressing a high level of α5β1 integrin

The nuclear hormone receptor PPARγ counteracts vascular calcification by inhibiting Wnt5a signalling in vascular smooth muscle cells.

Vascular calcification is a hallmark of advanced atherosclerosis. Here we show that deletion of the nuclear receptor PPARγ in vascular smooth muscle cells of low density lipoprotein receptor (LDLr)-deficient mice fed an atherogenic diet high in cholesterol, accelerates vascular calcification with chondrogenic metaplasia within the lesions. Vascular calcification in the absence of PPARγ requires expression of the transmembrane receptor LDLr-related protein-1 in vascular smooth muscle cells. LDLr-related protein-1 promotes a previously unknown Wnt5a-dependent prochondrogenic pathway. We show that PPARγ protects against vascular calcification by inducing the expression of secreted frizzled-related protein-2, which functions as a Wnt5a antagonist. Targeting this signalling pathway may have clinical implications in the context of common complications of atherosclerosis, including coronary artery calcification and valvular sclerosis