The juxtamembrane region of the cadherin cytoplasmic tail supports lateral clustering, adhesive strengthening, and interaction with p129(ctn)

Cadherin cell-cell adhesion molecules form membrane-spanning molecular complexes that couple homophilic binding by the cadherin ectodomain to the actin cytoskeleton. A fundamental issue in cadherin biology is how this complex converts the weak intrinsic binding activity of the ectodomain into strong adhesion. Recently we demonstrated that cellular cadherins cluster in a ligand-dependent fashion when cells attached to substrata coated with the adhesive ectodomain of Xenopus C-cadherin (CEC1-5). Moreover, forced clustering of the ectodomain alone significantly strengthened adhesiveness (Yap, A.S., W.M. Brieher, M. Pruschy, and B.M. Gumbiner. Curr. Biol. 7:308-315). In this study we sought to identify the determinants of the cadherin cytoplasmic tail responsible for clustering activity. A deletion mutant of C-cadherin (CT669) that retained the juxtamembrane 94-amino acid region of the cytoplasmic tail, but not the beta-catenin-binding domain, clustered upon attachment to substrata coated with CEC1-5. Like wild-type C-cadherin, this clustering was Ligand dependent. In contrast, mutant molecules lacking either the complete cytoplasmic tail or just the juxtamembrane region did not cluster. The juxtamembrane region was itself sufficient to induce clustering when fused to a heterologous membrane-anchored protein, albeit in a ligand-independent fashion. The CT669 cadherin mutant also displayed significant adhesive activity when tested in laminar flow detachment assays and aggregation assays. Purification of proteins binding to the juxtamembrane region revealed that the major associated protein is p120(ctn). These findings identify the juxtamembrane region of the cadherin cytoplasmic tail as a functionally active region supporting cadherin clustering and adhesive strength and raise the possibility that p120(ctn) is involved in clustering and cell adhesion

Combined treatment modality for intracranial germinomas: results of a multicentre SFOP experience

Conventional therapy for intracranial germinomas is craniospinal irradiation. In 1990, the Société Française d'Oncologie Pédiatrique initiated a study combining chemotherapy (alternating courses of etoposide–carboplatin and etoposide–ifosfamide for a recommended total of four courses) with 40 Gy local irradiation for patients with localized germinomas. Metastatic patients were allocated to receive low-dose craniospinal radiotherapy. Fifty-seven patients were enrolled between 1990 and 1996. Forty-seven had biopsy-proven germinoma. Biopsy was not performed in ten patients (four had diagnostic tumour markers and in six the neurosurgeon felt biopsy was contraindicated). Fifty-one patients had localized disease, and six leptomeningeal dissemination. Seven patients had bifocal tumour. All but one patient received at least four courses of chemotherapy. Toxicity was mainly haematological. Patients with diabetus insipidus (n = 25) commonly developed electrolyte disturbances during chemotherapy. No patient developed tumour progression during chemotherapy. Fifty patients received local radiotherapy with a median dose of 40 Gy to the initial tumour volume. Six metastatic patients, and one patient with localized disease who stopped chemotherapy due to severe toxicity, received craniospinal radiotherapy. The median follow-up for the group was 42 months. Four patients relapsed 9, 10, 38 and 57 months after diagnosis. Three achieved second complete remission following salvage treatment with chemotherapy alone or chemo-radiotherapy. The estimated 3-year survival probability is 98% (CI: 86.6–99.7%) and the estimated 3-year event-free survival is 96.4% (CI: 86.2–99.1%). This study shows that excellent survival rates can be achieved by combining chemotherapy and local radiotherapy in patients with non-metastatic intracranial germinomas. © 1999 Cancer Research Campaig

Naturally Occurring Food Toxins

Although many foods contain toxins as a naturally-occurring constituent or, are formed as the result of handling or processing, the incidence of adverse reactions to food is relatively low. The low incidence of adverse effects is the result of some pragmatic solutions by the US Food and Drug Administration (FDA) and other regulatory agencies through the creative use of specifications, action levels, tolerances, warning labels and prohibitions. Manufacturers have also played a role by setting limits on certain substances and developing mitigation procedures for process-induced toxins. Regardless of measures taken by regulators and food producers to protect consumers from natural food toxins, consumption of small levels of these materials is unavoidable. Although the risk for toxicity due to consumption of food toxins is fairly low, there is always the possibility of toxicity due to contamination, overconsumption, allergy or an unpredictable idiosyncratic response. The purpose of this review is to provide a toxicological and regulatory overview of some of the toxins present in some commonly consumed foods, and where possible, discuss the steps that have been taken to reduce consumer exposure, many of which are possible because of the unique process of food regulation in the United States

Not all flavor expertise is equal : The language of wine and coffee experts

People in Western cultures are poor at naming smells and flavors. However, for wine and coffee experts, describing smells and flavors is part of their daily routine. So are experts better than lay people at conveying smells and flavors in language? If smells and flavors are more easily linguistically expressed by experts, or more "codable", then experts should be better than novices at describing smells and flavors. If experts are indeed better, we can also ask how general this advantage is: do experts show higher codability only for smells and flavors they are expert in (i.e., wine experts for wine and coffee experts for coffee) or is their linguistic dexterity more general? To address these questions, wine experts, coffee experts, and novices were asked to describe the smell and flavor of wines, coffees, everyday odors, and basic tastes. The resulting descriptions were compared on a number of measures. We found expertise endows a modest advantage in smell and flavor naming. Wine experts showed more consistency in how they described wine smells and flavors than coffee experts, and novices; but coffee experts were not more consistent for coffee descriptions. Neither expert group was any more accurate at identifying everyday smells or tastes. Interestingly, both wine and coffee experts tended to use more source-based terms (e.g., vanilla) in descriptions of their own area of expertise whereas novices tended to use more evaluative terms (e.g., nice). However, the overall linguistic strategies for both groups were en par. To conclude, experts only have a limited, domain-specific advantage when communicating about smells and flavors. The ability to communicate about smells and flavors is a matter not only of perceptual training, but specific linguistic training too

The noise-lovers: cultures of speech and sound in second-century Rome

This chapter provides an examination of an ideal of the ‘deliberate speaker’, who aims to reflect time, thought, and study in his speech. In the Roman Empire, words became a vital tool for creating and defending in-groups, and orators and authors in both Latin and Greek alleged, by contrast, that their enemies produced babbling noise rather than articulate speech. In this chapter, the ideal of the deliberate speaker is explored through the works of two very different contemporaries: the African-born Roman orator Fronto and the Syrian Christian apologist Tatian. Despite moving in very different circles, Fronto and Tatian both express their identity and authority through an expertise in words, in strikingly similar ways. The chapter ends with a call for scholars of the Roman Empire to create categories of analysis that move across different cultural and linguistic groups. If we do not, we risk merely replicating the parochialism and insularity of our sources.Accepted manuscrip

Linguistic Anthropology

Abstract This chapter reviews the development of linguistic anthropology as it relates to sociolinguistics, including some particulars of the concept of fieldwork and ethnography, as well as some of the changes in the nature of field sites that have occurred over the last few decades. It also looks at some of the new strands of empirical work and theorizing that have emerged as a result of these changes. The chapter ends with some thoughts on how socially oriented linguistics of all sorts might productively work together toward meshing the concerns of quantitative sociolinguistics in the population-wide, emergent patterns of language use that characterize a community of speakers with the historical, discursive, and ideological understandings of on-the-ground speaking events, which remain the core concern of linguistic anthropology.</jats:p