Inhibitor recurrence after immune tolerance induction: a multicenter retrospective cohort study

Immune tolerance induction (ITI) in patients with congenital hemophilia A is successful in up to 70%. Although there is growing understanding of predictors of response to ITI, the probability and predictors of inhibitor recurrence following successful ITI are not well understood

Zinc-Regulated DNA Binding of the Yeast Zap1 Zinc-Responsive Activator

The Zap1 transcription factor of Saccharomyces cerevisiae plays a central role in zinc homeostasis by controlling the expression of genes involved in zinc metabolism. Zap1 is active in zinc-limited cells and repressed in replete cells. At the transcriptional level, Zap1 controls its own expression via positive autoregulation. In addition, Zap1's two activation domains are regulated independently of each other by zinc binding directly to those regions and repressing activation function. In this report, we show that Zap1 DNA binding is also inhibited by zinc. DMS footprinting showed that Zap1 target gene promoter occupancy is regulated with or without transcriptional autoregulation. These results were confirmed using chromatin immunoprecipitation. Zinc regulation of DNA binding activity mapped to the DNA binding domain indicating other parts of Zap1 are unnecessary for this control. Overexpression of Zap1 overrode DNA binding regulation and resulted in constitutive promoter occupancy. Under these conditions of constitutive binding, both the zinc dose response of Zap1 activity and cellular zinc accumulation were altered suggesting the importance of DNA binding control to zinc homeostasis. Thus, our results indicated that zinc regulates Zap1 activity post-translationally via three independent mechanisms, all of which contribute to the overall zinc responsiveness of Zap1

An intrinsically disordered proteins community for ELIXIR.

Intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs) are now recognised as major determinants in cellular regulation. This white paper presents a roadmap for future e-infrastructure developments in the field of IDP research within the ELIXIR framework. The goal of these developments is to drive the creation of high-quality tools and resources to support the identification, analysis and functional characterisation of IDPs. The roadmap is the result of a workshop titled "An intrinsically disordered protein user community proposal for ELIXIR" held at the University of Padua. The workshop, and further consultation with the members of the wider IDP community, identified the key priority areas for the roadmap including the development of standards for data annotation, storage and dissemination; integration of IDP data into the ELIXIR Core Data Resources; and the creation of benchmarking criteria for IDP-related software. Here, we discuss these areas of priority, how they can be implemented in cooperation with the ELIXIR platforms, and their connections to existing ELIXIR Communities and international consortia. The article provides a preliminary blueprint for an IDP Community in ELIXIR and is an appeal to identify and involve new stakeholders

Adolescent deviation and age

Traditional theories of delinquency causation generally fail to consider delinquency in the context of norms and age-role transitions peculiar to adolescence. Hence, in this study, an age-based theory of delinquency causation is developed, which assumes the importance of norms and roles specific to adolescence. This theory draws upon the assumption that socialization is recurrent, in contrast to the premises regarding socialization which underlie traditional theories of adolescent deviance. The recurrent model of socialization and that assumed by traditional theorists are discussed, and their implications for the causes of delinquent behavior are examined. Some effort is made to show that the recurrent model of socialization suggests an anomie of age as the basis for delinquent acts. It is suggested that this age-based anomie stems from conditions of normlessness associated with certain role transitions in adolescence and the pacing of these transitions. Further, it is suggested that certain groups are especially prone to an anomic age transition. The role transitions most likely to be subject to such anomic conditions and the adolescent subgroups most prone to experience anomie as a result of the pacing of their age-role transitions are identified .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45260/1/10964_2005_Article_BF01537174.pd