Multivariate proteomic profiling identifies novel accessory proteins of coated vesicles.

Despite recent advances in mass spectrometry, proteomic characterization of transport vesicles remains challenging. Here, we describe a multivariate proteomics approach to analyzing clathrin-coated vesicles (CCVs) from HeLa cells. siRNA knockdown of coat components and different fractionation protocols were used to obtain modified coated vesicle-enriched fractions, which were compared by stable isotope labeling of amino acids in cell culture (SILAC)-based quantitative mass spectrometry. 10 datasets were combined through principal component analysis into a "profiling" cluster analysis. Overall, 136 CCV-associated proteins were predicted, including 36 new proteins. The method identified >93% of established CCV coat proteins and assigned >91% correctly to intracellular or endocytic CCVs. Furthermore, the profiling analysis extends to less well characterized types of coated vesicles, and we identify and characterize the first AP-4 accessory protein, which we have named tepsin. Finally, our data explain how sequestration of TACC3 in cytosolic clathrin cages causes the severe mitotic defects observed in auxilin-depleted cells. The profiling approach can be adapted to address related cell and systems biological questions

Iconic dishes, culture and identity: the Christmas pudding and its hundred years’ journey in the USA, Australia, New Zealand and India

Asserting that recipes are textual evidences reflecting the society that produced them, this article explores the evolution of the recipes of the iconic Christmas pudding in the United States, Australia, New Zealand and India between the mid-nineteenth and the mid-twentieth centuries. Combining a micro-analysis of the recipes and the cookbook that provided them with contemporary testimonies, the article observes the dynamics revealed by the preparation and consumption of the pudding in these different societies. The findings demonstrate the relevance of national iconic dishes to the study of notions of home, migration and colonization, as well as the development of a new society and identity. They reveal how the preservation, transformation and even rejection of a traditional dish can be representative of the complex and sometimes conflicting relationships between colonists, migrants or new citizens and the places they live in

GA4GH: International policies and standards for data sharing across genomic research and healthcare.

The Global Alliance for Genomics and Health (GA4GH) aims to accelerate biomedical advances by enabling the responsible sharing of clinical and genomic data through both harmonized data aggregation and federated approaches. The decreasing cost of genomic sequencing (along with other genome-wide molecular assays) and increasing evidence of its clinical utility will soon drive the generation of sequence data from tens of millions of humans, with increasing levels of diversity. In this perspective, we present the GA4GH strategies for addressing the major challenges of this data revolution. We describe the GA4GH organization, which is fueled by the development efforts of eight Work Streams and informed by the needs of 24 Driver Projects and other key stakeholders. We present the GA4GH suite of secure, interoperable technical standards and policy frameworks and review the current status of standards, their relevance to key domains of research and clinical care, and future plans of GA4GH. Broad international participation in building, adopting, and deploying GA4GH standards and frameworks will catalyze an unprecedented effort in data sharing that will be critical to advancing genomic medicine and ensuring that all populations can access its benefits

Fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin with gemtuzumab ozogamicin improves event-free survival in younger patients with newly diagnosed aml and overall survival in patients with npm1 and flt3 mutations

Purpose To determine the optimal induction chemotherapy regimen for younger adults with newly diagnosed AML without known adverse risk cytogenetics. Patients and Methods One thousand thirty-three patients were randomly assigned to intensified (fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin [FLAG-Ida]) or standard (daunorubicin and Ara-C [DA]) induction chemotherapy, with one or two doses of gemtuzumab ozogamicin (GO). The primary end point was overall survival (OS). Results There was no difference in remission rate after two courses between FLAG-Ida + GO and DA + GO (complete remission [CR] + CR with incomplete hematologic recovery 93% v 91%) or in day 60 mortality (4.3% v 4.6%). There was no difference in OS (66% v 63%; P = .41); however, the risk of relapse was lower with FLAG-Ida + GO (24% v 41%; P < .001) and 3-year event-free survival was higher (57% v 45%; P < .001). In patients with an NPM1 mutation (30%), 3-year OS was significantly higher with FLAG-Ida + GO (82% v 64%; P = .005). NPM1 measurable residual disease (MRD) clearance was also greater, with 88% versus 77% becoming MRD-negative in peripheral blood after cycle 2 (P = .02). Three-year OS was also higher in patients with a FLT3 mutation (64% v 54%; P = .047). Fewer transplants were performed in patients receiving FLAG-Ida + GO (238 v 278; P = .02). There was no difference in outcome according to the number of GO doses, although NPM1 MRD clearance was higher with two doses in the DA arm. Patients with core binding factor AML treated with DA and one dose of GO had a 3-year OS of 96% with no survival benefit from FLAG-Ida + GO. Conclusion Overall, FLAG-Ida + GO significantly reduced relapse without improving OS. However, exploratory analyses show that patients with NPM1 and FLT3 mutations had substantial improvements in OS. By contrast, in patients with core binding factor AML, outcomes were excellent with DA + GO with no FLAG-Ida benefit

Writing About Cannibal Diets And Consuming Black Africans In France During The First Half Of The Twentieth Century

This article examines the meaning of references to cannibalism in French descriptions of black African cuisine in the first half of the twentieth century. Because of the intimacy of eating and the perceived importance of diet in defining racial boundaries, exotic dining and gastronomic writing about the colonised Other were fraught with tension about the possible crossing of boundaries. When African cuisine was discussed in cooking magazines, by gastronomes, and in the context of the 1931 Colonial Exposition, references to cannibalism guarded these borders. The discourse surrounding African food and African chefs at the exposition also used eating as a metaphor for the cannibalistic nature of French imperialism in Africa. The physical and metaphoric consumption of the colonised African Other was featured dramatically in the French dessert tete de negre, which presented a representation of an African head for French consumption, ritualising and taming the violent incorporation of African bodies into the French empire

Curiosité Gastronomique Et Cuisine Exotique Dans L\u27entre-deux-guerres Une Histoire De Goût Et De Dégoût

À partir de 1890, plusieurs revues de recettes de cuisine commencèrent à évoquer les habitudes culinaires des peuples colonisés. Les articles et recettes naviguèrent sans cesse entre deux pôles. Le plus puissant consistait à susciter une forme de dégoût chez le lecteur, fondant ainsi un sentiment d’altérité et de supériorité vis-à-vis de populations présentées comme primitives car mangeant du chien, des insectes ou des aliments avariés. Mais parallèlement, il existait un exotisme acceptable, non transgressif, lié à la consommation de fruits tropicaux ou de plats au curry, qui trouvèrent alors leur place dans la cuisine bourgeoise de l’entre-deux-guerres

Selling Rice To Wheat Eaters: The Colonial Lobby And The Promotion Of Pain de Riz During And After The First World War

This article examines the efforts to promote pain de riz (rice-flour bread) in France during and after the First World War. This effort marked the beginning of the campaign toincrease French consumption of Indochinese rice, a campaign that began during the First World War and intensified throughout the 1920s and 1930s. In the face of cultural resistance to rice in France, the Indochina lobby first encouraged the use of rice flour in French bread. The centrality of bread to the French diet and to French national identity seriously complicated the introduction of rice flour. This study expands our understanding of the complex meaning of the whiteness of French bread and the cultural significance of bread\u27s key ingredient: flour. All stages of bread production were heavily regulated in France, and the story of pain de riz reveals how closely various business interests in Indochina and France coordinated with government officials to influence legislation concerning bread\u27s content. In addition, it demonstrates how the production of scientific knowledge in colonial Indochina developed in ways that supported the political and economic interests of the colonial lobby. In incorporating rice flour into French bread, the colonial lobby attempted to include Indochina economically and culturally within Greater France. Their ultimate failure reveals some of the limits of the colonial lobby\u27s attempts to integrate the colonies into French national identity