Proteomic and ionomic profiling reveals significant alterations of protein expression and calcium homeostasis in cystic fibrosis cells

Cystic fibrosis (CF) is an autosomal recessive disorder associated with mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene and defective chloride transport across the epithelial cell membranes. Abnormal epithelial ion transport is the primary cause of persistent airway infections and chronic inflammation in CF patients. In order to gain further insight into the mechanisms of epithelial dysfunctions linked to CFTR mutations, we performed and integrated proteomic and ionomic analysis of human bronchial epithelial IB3-1 cells and compared them with a CFTR-complemented isogenic cell line (C38). Aside from changes that were consistent with known effects related to CFTR mutations, such as differences in glycolytic and gluconeogenic pathways and unfolded protein responses, differential proteomics highlighted significant alteration of protein expression and, in particular, of the 14-3-3 signalling pathway that is known to be involved in cellular calcium (Ca) homeostasis. Of note, restoring chloride efflux by acting on Ca cellular homeostasis has been shown to be a promising therapeutic intervention for CF. Ionomic analysis showed significant changes in the IB3-1 element profile compared with C38 cells and in particular we observed an increase of intracellular Ca that significantly correlates with intracellular zinc (Zn) levels, suggesting a synergistic role of Ca and Zn influx. This finding is particularly intriguing because Zn has been reported to be effective in CF treatment increasing Ca influx. Taken together, our proteomic and ionomic data reveal that CFTR mutation sets in motion endogenous mechanisms counteracting impaired chloride transport mainly acting on epithelial ion transport and increasing intracellular Ca, suggesting potential links between protein expression and this response

Jaws from the deep: biological and ecological insights on the kitefin shark Dalatias licha from the Mediterranean Sea

Due to their late maturation, extreme longevity, low fecundity and slow growth rates, deep-sea Chondrichthyes are extremely vulnerable to human impacts. Moreover, assessing the impact of deep-sea fisheries is difficult, as many species (including sharks) are part of the bycatch and are often discarded at sea, and/or landed under generic commercial-species codes. The lack of this information on fishery data sets and the limited availability of species-specific life history data make challenging the management of deep-sea Chondrichthyes. The kitefin shark Dalatias licha is a cosmopolitan elasmobranch, mainly found on continental and insular shelf-breaks and slopes in warm-temperate and tropical waters. This species is a common by-catch of the deep-sea trawling, considered as “Endangered” by the IUCN Red List for all European waters, Mediterranean Sea included. Here we present the results of a study based on a total of 78 specimens of kitefin shark collected over 3 years in the Ligurian Sea (NW Mediterranean) as by-catch from deep-water fisheries. Total length ranged from 380 to 1164 mm, and individual weight ranged from 198 to 8000 g. Immature and mature individuals showed a sex ratio dominated by males. Adult males were observed throughout the year, while mature females were observed only in spring-summer. These data lead to hypothesise a spatial segregation between genders. The kitefin shark diet was dominated by bony fish (mainly Macrouridae) and other small sharks (e.g., Galeus melastomus and Etmopterus spinax), but their gut included plastic items and parasites. Data reported here underline the rarity, complex ecology and the threat for this shark species and support the urgency of promoting initiatives for their monitoring and conservation

The addition of rituximab to fludarabine improves clinical outcome in untreated patients with ZAP-70-negative chronic lymphocytic leukemia.

Clinical trials of monoclonal antibodies in combination with chemotherapy have reported previously unattained response rates in patients with B-cell chronic lymphocytic leukemia (B-CLL); however, the analysis of ZAP-70 protein and/or CD38 may explain better the discordant outcomes independent of treatment

Digital play and the actualisation of the consumer imagination

In this article, the authors consider emerging consumer practices in digital virtual spaces. Building on constructions of consumer behavior as both a sense-making activity and a resource for the construction of daydreams, as well as anthropological readings of performance, the authors speculate that many performances during digital play are products of consumer fantasy. The authors develop an interpretation of the relationship between the real and the virtual that is better equipped to understand the movement between consumer daydreams and those practices actualized in the material and now also in digital virtual reality. The authors argue that digital virtual performances present opportunities for liminoid transformations through inversions, speculations, and playfulness acted out in aesthetic dramas. To illustrate, the authors consider specific examples of the theatrical productions available to consumers in digital spaces, highlighting the consumer imagination that feeds them, the performances they produce, and the potential for transformation in consumer-players

Challenging notions of gendered game play: teenagers playing `The Sims`

This paper challenges notions of gendered game playing practice implicit in much research into young women\u27s involvement with the computer gaming culture. It draws on a study of Australian teenagers playing The Sims Deluxe as part of an English curriculum unit and insights from feminist media studies to explore relationships between gender and game playing practices. Departing from a reliance on predetermined notions of &ldquo;gender&rdquo;, &ldquo;domestic space&rdquo;, and &ldquo;successful game play&rdquo;, it conceptualizes The Sims as a game in which the boundaries between gender and domestic space are disturbed. It argues that observing students\u27 constructions of gender and domestic space through the act of game play itself provides a more productive insight into the gendered dimensions of game play for educators wishing to work computer games such as The Sims into curriculum development.<br /

Marx’s "Capital"in the Information Age

This article argues that a media and communication studies perspective on reading Marx’s Capital has thus far been missing, but is needed in the age of information capitalism and digital capitalism. Two of the most popular contemporary companions to Marx’s Capital, the ones by David Harvey and Michael Heinrich, present themselves as general guidebooks on how to read Marx, but are actually biased towards particular schools of Marxist thought. A contemporary reading of Marx needs to be mediated with contemporary capitalism’s structures and the political issues of the day. Media, communications and the Internet are important issues for such a reading today. It is time to see Marx not just as a critic of capitalism but also as a critic of capitalist communications

Virtual money, practices and moral orders in Second Life

Virtual monies present a limit case in debates about money's moral and political entanglements between sociologists, anthropologists, and economists. Digitized virtual monies seem ephemeral, almost ideal typical examples of money as a pure medium of exchange. This paper begins with the premise that virtual monies are as value-laden and morally entangled as any other form of money. This assertion is demonstrated by exploring how one type of virtual money, the Linden dollar (L$), and some of its associated practices are bound up with research participants' moral categories and judgments in the virtual world of Second Life (SL). Participants' accounts of virtual money practices are linked to moral attributes, sometimes in stark ‘good’ or ‘bad’ dichotomies, but also in more nuanced terms. These framings reproduce classifications of people and practices along a continuum with virtuousness at one end and maliciousness or harm at the other, passing through various states of possible moral dubiousness. For respondents, these two judgments go together; people are what they do with money. As a result, respondents decide what ‘people like that’ deserve. Evaluating someone's money practices means assessing the person. Participants' accounts of Linden dollar practices overlap with explanations of what SL is and how residents should live there. In SL, money is a form of material culture through which appropriate ways of being in the world are debated and reproduced

The brief international cognitive assessment for multiple sclerosis (BICAMS): Normative values with gender, age and education corrections in the Italian population

Background: BICAMS (Brief International Cognitive Assessment for Multiple Sclerosis) has been recently developed as brief, practical and universal assessment tool for cognitive impairment in MS subjects. It includes the Symbol Digit Modalities Test (SDMT), the California Verbal Learning Test-2 (CVLT2) and the Brief Visuospatial Memory Test-Revised (BVMT-R) . In this study we aimed at gathering regression based normative data for the BICAMS battery in the Italian population.Methods: Healthy subjects were consecutively recruited among patient friends and relatives. Corrections for demographics were calculated using multivariable linear regression models. Test-retest reliability was assessed using the Pearson correlation coefficient.Results: The BICAMS battery was administered to 273 healthy subjects (180 women, mean age 38.9 ± 13.0&nbsp;years, mean education 14.9 ± 3.0&nbsp;years). Test-retest reliability was good for all the tests.Conclusions: The study provided normative data of the BICAMS for the Italian population confirming good test-retest reliability which can facilitate the use of the battery in clinical practice, also for longitudinal patient assessments

Direct CD32 T-cell cytotoxicity: implications for breast cancer prognosis and treatment

The FcγRII (CD32) ligands are IgFc fragments and pentraxins. The existence of additional ligands is unknown. We engineered T cells with human chimeric receptors resulting from the fusion between CD32 extracellular portion and transmembrane CD8α linked toCD28/ζ chain intracellular moiety (CD32-CR). Transduced T cells recognized three breast cancer (BC) and one colon cancer cell line among 15 tested in the absence of targeting antibodies. Sensitive BC cell conjugation with CD32-CR T cells induced CD32 polarization and down-regulation, CD107a release, mutual elimination, and proinflammatory cytokine production unaffected by human IgGs but enhanced by cetuximab. CD32-CR T cells protected immunodeficient mice from subcutaneous growth of MDA-MB-468 BC cells. RNAseq analysis identified a 42 gene fingerprint predicting BC cell sensitivity and favorable outcomes in advanced BC. ICAM1 was a major regulator of CD32-CR T cell–mediated cytotoxicity. CD32-CR T cells may help identify cell surface CD32 ligand(s) and novel prognostically relevant transcriptomic signatures and develop innovative BC treatments