Rab proteins and Rab-associated proteins: major actors in the mechanism of protein-trafficking disorders

Ras-associated binding (Rab) proteins and Rab-associated proteins are key regulators of vesicle transport, which is essential for the delivery of proteins to specific intracellular locations. More than 60 human Rab proteins have been identified, and their function has been shown to depend on their interaction with different Rab-associated proteins regulating Rab activation, post-translational modification and intracellular localization. The number of known inherited disorders of vesicle trafficking due to Rab cycle defects has increased substantially during the past decade. This review describes the important role played by Rab proteins in a number of rare monogenic diseases as well as common multifactorial human ones. Although the clinical phenotype in these monogenic inherited diseases is highly variable and dependent on the type of tissue in which the defective Rab or its associated protein is expressed, frequent features are hypopigmentation (Griscelli syndrome), eye defects (Choroideremia, Warburg Micro syndrome and Martsolf syndrome), disturbed immune function (Griscelli syndrome and Charcot–Marie–Tooth disease) and neurological dysfunction (X-linked non-specific mental retardation, Charcot–Marie–Tooth disease, Warburg Micro syndrome and Martsolf syndrome). There is also evidence that alterations in Rab function play an important role in the progression of multifactorial human diseases, such as infectious diseases and type 2 diabetes. Rab proteins must not only be bound to GTP, but they need also to be ‘prenylated’—i.e. bound to the cell membranes by isoprenes, which are intermediaries in the synthesis of cholesterol (e.g. geranyl geranyl or farnesyl compounds). This means that isoprenylation can be influenced by drugs such as statins, which inhibit isoprenylation, or biphosphonates, which inhibit that farnesyl pyrophosphate synthase necessary for Rab GTPase activity. Conclusion: Although protein-trafficking disorders are clinically heterogeneous and represented in almost every subspeciality of pediatrics, the identification of common pathogenic mechanisms may provide a better diagnosis and management of patients with still unknown Rab cycle defects and stimulate the development of therapeutic agents

The paradoxical role of meritocratic selection in the perpetuation of social inequalities at school

The school system is intended to offer all students the same opportunities, but most international surveys reveal an overall lower achievement for students from disadvantaged groups compared with more advantaged students. Recent experimental research in social psychology has demonstrated that schools as institutions contribute with their implicit cultural norms and structure to the production of inequalities. This chapter examines the role that a structural feature of school, namely meritocratic selection, plays in this reproduction of inequalities at school. First, we describe how meritocracy in the educational system can hold paradoxical effects by masking the virtuous/vicious cycles of opportunities created by educational institutions. Second, we present recent research suggesting that selection practices relying on a meritocratic principle—more than other practices—can lead to biased academic decisions hindering disadvantaged students. We propose that inequalities in school might not just result from isolated failures in an otherwise functional meritocratic system, but rather that merit-based selection itself contributes to the perpetuation of inequalities at school

Deregulation of Rab and Rab Effector Genes in Bladder Cancer

Growing evidence indicates that Rab GTPases, key regulators of intracellular transport in eukaryotic cells, play an important role in cancer. We analysed the deregulation at the transcriptional level of the genes encoding Rab proteins and Rab-interacting proteins in bladder cancer pathogenesis, distinguishing between the two main progression pathways so far identified in bladder cancer: the Ta pathway characterized by a high frequency of FGFR3 mutation and the carcinoma in situ pathway where no or infrequent FGFR3 mutations have been identified. A systematic literature search identified 61 genes encoding Rab proteins and 223 genes encoding Rab-interacting proteins. Transcriptomic data were obtained for normal urothelium samples and for two independent bladder cancer data sets corresponding to 152 and 75 tumors. Gene deregulation was analysed with the SAM (significant analysis of microarray) test or the binomial test. Overall, 30 genes were down-regulated, and 13 were up-regulated in the tumor samples. Five of these deregulated genes (LEPRE1, MICAL2, RAB23, STXBP1, SYTL1) were specifically deregulated in FGFR3-non-mutated muscle-invasive tumors. No gene encoding a Rab or Rab-interacting protein was found to be specifically deregulated in FGFR3-mutated tumors. Cluster analysis showed that the RAB27 gene cluster (comprising the genes encoding RAB27 and its interacting partners) was deregulated and that this deregulation was associated with both pathways of bladder cancer pathogenesis. Finally, we found that the expression of KIF20A and ZWINT was associated with that of proliferation markers and that the expression of MLPH, MYO5B, RAB11A, RAB11FIP1, RAB20 and SYTL2 was associated with that of urothelial cell differentiation markers. This systematic analysis of Rab and Rab effector gene deregulation in bladder cancer, taking relevant tumor subgroups into account, provides insight into the possible roles of Rab proteins and their effectors in bladder cancer pathogenesis. This approach is applicable to other group of genes and types of cancer

Is ``what has been cared for'' necessarily good? Further evidence for the negative impact of cosmetics use on impression formation

International audienceThe effects of cosmetics on impression formation were tested with students from either psychology or business and aesthetic schools. They were presented photographs of young and older female targets wearing or not wearing facial makeup and rated them for both physical attractiveness and a number of personality traits. In contrast with Graham and Jouhar's (1981) idea of a positive cosmetic stereotype, makeup had a negative impact on impression formation, especially for the young targets. More consistent with these authors' perspective, this impact was not mediated by attribution of physical attractiveness (PA), suggesting the existence of a separate cosmetic stereotype (relative to the PA stereotype). The influence of makeup was also stronger on the psychology undergraduates than on the other participants, suggesting that the way cosmetic users are perceived also depends on perceivers' group membership

La menace du stéréotype : une interaction entre situation et identité

This article proposes a critical review of the literature on stereotype threat. First, we present the pioneering studies of Steele and Aronson (1995). We discuss the originality of their approach and review the research that has established the generality of the stereotype threat phenomenon. Then, we examine the conditions necessary for this phenomenon, its scope, and the mediators thought to explain how stereotypes can undermine performance. We present the research that has focused on the means to reduce the detrimental effects of stereotype threat on performance. Finally, we discuss the relevance of this phenomenon for understanding the well-known academic underachievement of low status groups