p130Cas is an essential transducer element in ErbB2 transformation

The ErbB2 oncogene is often overexpressed in breast tumors and associated with poor clinical outcome. p130Cas represents a nodal scaffold protein regulating cell survival, migration, and proliferation in normal and pathological cells. The functional role of p130Cas in ErbB2-dependent breast tumorigenesis was assessed by its silencing in breast cancer cells derived from mouse mammary tumors overexpressing ErbB2 (N202-1A cells), and by its reexpression in ErbB2-transformed p130Cas-null mouse embryonic fibroblasts. We demonstrate that p130Cas is necessary for ErbB2-dependent foci formation, anchorage-independent growth, and in vivo growth of orthotopic N202-1A tumors. Moreover, intranipple injection of p130Cas-stabilized siRNAs in the mammary gland of Balbc-NeuT mice decreases the growth of spontaneous tumors. In ErbB2-transformed cells, p130Cas is a crucial component of a functional molecular complex consisting of ErbB2, c-Src, and Fak. In human mammary cells, MCF10A.B2, the concomitant activation of ErbB2, and p130Cas overexpression sustain and strengthen signaling, leading to Rac1 activation and MMP9 secretion, thus providing invasive properties. Consistently, p130Cas drives N202-1A cell in vivo lung metastases colonization. These results demonstrate that p130Cas is an essential transducer in ErbB2 transformation and highlight its potential use as a novel therapeutic target in ErbB2 positive human breast cancers.-Cabodi, S., Tinnirello, A., Bisaro, B., Tornillo, G., Camacho-Leal, M. P., Forni, G., Cojoca, R., Iezzi, M., Amici, A., Montani, M., Eva, A., Di Stefano, P., Muthuswamy, S. K., Tarone, G., Turco, E., Defilippi, P. p130Cas is an essential transducer element in ErbB2 transformation

Cardiac overexpression of melusin protects from dilated cardiomyopathy due to long-standing pressure overload.

We have previously shown that genetic ablation of melusin, a muscle specific beta 1 integrin interacting protein, accelerates left ventricle (LV) dilation and heart failure in response to pressure overload. Here we show that melusin expression was increased during compensated cardiac hypertrophy in mice subjected to 1 week pressure overload, but returned to basal levels in LV that have undergone dilation after 12 weeks of pressure overload. To better understand the role of melusin in cardiac remodeling, we overexpressed melusin in heart of transgenic mice. Echocardiography analysis indicated that melusin over-expression induced a mild cardiac hypertrophy in basal conditions (30% increase in interventricular septum thickness) with no obvious structural and functional alterations. After prolonged pressure overload (12 weeks), melusin overexpressing hearts underwent further hypertrophy retaining concentric LV remodeling and full contractile function, whereas wild-type LV showed pronounced chamber dilation with an impaired contractility. Analysis of signaling pathways indicated that melusin overexpression induced increased basal phosphorylation of GSK3beta and ERK1/2. Moreover, AKT, GSK3beta and ERK1/2 were hyper-phosphorylated on pressure overload in melusin overexpressing compared with wild-type mice. In addition, after 12 weeks of pressure overload LV of melusin overexpressing mice showed a very low level of cardiomyocyte apoptosis and stromal tissue deposition, as well as increased capillary density compared with wild-type. These results demonstrate that melusin overexpression allows prolonged concentric compensatory hypertrophy and protects against the transition toward cardiac dilation and failure in response to long-standing pressure overload

Difference in outcome between curative intent vs marginal excision as a first treatment in dogs with oral malignant melanoma and the impact of adjuvant CSPG4-DNA electrovaccination: A retrospective study on 155 cases

Canine oral malignant melanoma is locally invasive and highly metastatic. At present, the best option for local control is en bloc excision followed by radiation if excision margins are incomplete. Adjuvantly, the role of chemotherapy is dubious while immunotherapy appears encouraging. This retrospective study evaluated 155 dogs with oral malignant melanomas (24 stage I, 54 stage II, 66 stage III and 11 stage IV) managed in a single institution. The aim was to evaluate the differences in median survival time (MST) and disease‐free interval (DFI) between dogs which, at presentation, were treated surgically with a curative intent (group 1) vs those marginally excised only (group 2). MST in group 1 was longer than in group 2 (594 vs 458 days), but no significant difference was found (P = .57); a statistical difference was, however, found for DFI (232 vs 183 days, P = .008). In the subpopulation of vaccinated dogs, the impact of adjuvant anti‐CSPG4 DNA electrovaccination was then evaluated (curative intent, group 3, vs marginal, group 4); a significant difference for both MST (1333 vs 470 days, respectively, P = .03) and DFI (324 vs 184 days, respectively, P = .008) was found. Progressive disease was significantly more common in dogs undergoing marginal excision than curative intent excision for both the overall population (P = .03) and the vaccinated dogs (P = .02). This study pointed out that, after staging, wide excision together with adjuvant immunotherapy was an effective approach for canine oral malignant melanoma

Language and anxiety: an ethnographic study of international postgraduate students

This paper presents some findings from an ethnographic study of international postgraduate students at a university in the South of England, which involved interviews and participant observation over a twelve-month academic year. One of the major themes that emerged from this research was students’ anxiety over their level of English language. Although all students entered their course with a minimum level of IELTS 6, the majority felt disadvantaged by particularly poor spoken English, and suffered feelings of anxiety, shame and inferiority. Low self-confidence meant that they felt ill-equipped to engage in class discussion and in social interaction which used English as the medium of communication. A common reaction to stress caused by language problems was to retreat into monoethnic communication with students from the same country, further inhibiting progress in language. Whilst some linguistic progress was made by nearly all students during the academic sojourn, the anxiety suffered by students in the initial stage must not be underestimated, and appropriate support systems must be put in place to alleviate their distress

Mobile Augmented Reality and Language-Related Episodes

Applications of locative media (e.g., place‐based mobile augmented reality [AR]) are used in various educational content areas and have been shown to provide learners with valuable opportunities for investigation‐based learning, location‐situated social and collaborative interaction, and embodied experience of place (Squire, 2009; Thorne & Hellermann, 2017; Zheng et al., 2018). Mobile locative media applications’ value for language learning, however, remains underinvestigated. To address this lacuna, this study employed the widely used construct of language‐related episodes (LREs; Swain & Lapkin, 1998) as a unit of analysis to investigate language learning through participation in a mobile AR game. Analysis of videorecorded interactions of four mixed‐proficiency groups of game players (two English language learners [ELLs] and one expert speaker of English [ESE] per group) indicates that LREs in this environment were focused on lexical items relevant to the AR tasks and physical locations. Informed by sociocultural theory and conversation analysis, the microgenesis of learners’ understanding and subsequent use of certain lexical items are indicated in the findings. This understanding of new lexical items was frequently facilitated by ESEs’ assistance and the surrounding physical environment. A strong goal orientation by both ESEs and ELLs was visible, providing implications for task‐based language teaching approaches