Inositol Hexakisphosphate-Induced Autoprocessing of Large Bacterial Protein Toxins

Large bacterial protein toxins autotranslocate functional effector domains to the eukaryotic cell cytosol, resulting in alterations to cellular functions that ultimately benefit the infecting pathogen. Among these toxins, the clostridial glucosylating toxins (CGTs) produced by Gram-positive bacteria and the multifunctional-autoprocessing RTX (MARTX) toxins of Gram-negative bacteria have distinct mechanisms for effector translocation, but a shared mechanism of post-translocation autoprocessing that releases these functional domains from the large holotoxins. These toxins carry an embedded cysteine protease domain (CPD) that is activated for autoprocessing by binding inositol hexakisphosphate (InsP6), a molecule found exclusively in eukaryotic cells. Thus, InsP6-induced autoprocessing represents a unique mechanism for toxin effector delivery specifically within the target cell. This review summarizes recent studies of the structural and molecular events for activation of autoprocessing for both CGT and MARTX toxins, demonstrating both similar and potentially distinct aspects of autoprocessing among the toxins that utilize this method of activation and effector delivery

The Nutrition and Enjoyable Activity for Teen Girls (NEAT girls) randomized controlled trial for adolescent girls from disadvantaged secondary schools: rationale, study protocol, and baseline results

Background: Child and adolescent obesity predisposes individuals to an increased risk of morbidity and mortality from a range of lifestyle diseases. Although there is some evidence to suggest that rates of pediatric obesity have leveled off in recent years, this has not been the case among youth from low socioeconomic backgrounds. The purpose of this paper is to report the rationale, study design and baseline findings of a school-based obesity prevention program for low-active adolescent girls from disadvantaged secondary schools. Methods/Design: The Nutrition and Enjoyable Activity for Teen Girls (NEAT Girls) intervention will be evaluated using a group randomized controlled trial. NEAT Girls is a 12-month multi-component school-based intervention developed in reference to Social Cognitive Theory and includes enhanced school sport sessions, interactive seminars, nutrition workshops, lunch-time physical activity (PA) sessions, PA and nutrition handbooks, parent newsletters, pedometers for self-monitoring and text messaging for social support. The following variables were assessed at baseline and will be completed again at 12- and 24-months: adiposity, objectively measured PA, muscular fitness, time spent in sedentary behaviors, dietary intake, PA and nutrition social-cognitive mediators, physical self-perception and global self-esteem. Statistical analyses will follow intention-to-treat principles and hypothesized mediators of PA and nutrition behavior change will be explored. Discussion: NEAT Girls is an innovative intervention targeting low-active girls using evidence-based behavior change strategies and nutrition and PA messages and has the potential to prevent unhealthy weight gain and reduce the decline in physical activity and poor dietary habits associated with low socio-economic status. Few studies have reported the long-term effects of school-based obesity prevention programs and the current study has the potential to make an important contribution to the field

Synaptic Wnt signaling—a contributor to major psychiatric disorders?

Wnt signaling is a key pathway that helps organize development of the nervous system. It influences cell proliferation, cell fate, and cell migration in the developing nervous system, as well as axon guidance, dendrite development, and synapse formation. Given this wide range of roles, dysregulation of Wnt signaling could have any number of deleterious effects on neural development and thereby contribute in many different ways to the pathogenesis of neurodevelopmental disorders. Some major psychiatric disorders, including schizophrenia, bipolar disorder, and autism spectrum disorders, are coming to be understood as subtle dysregulations of nervous system development, particularly of synapse formation and maintenance. This review will therefore touch on the importance of Wnt signaling to neurodevelopment generally, while focusing on accumulating evidence for a synaptic role of Wnt signaling. These observations will be discussed in the context of current understanding of the neurodevelopmental bases of major psychiatric diseases, spotlighting schizophrenia, bipolar disorder, and autism spectrum disorder. In short, this review will focus on the potential role of synapse formation and maintenance in major psychiatric disorders and summarize evidence that defective Wnt signaling could contribute to their pathogenesis via effects on these late neural differentiation processes

Assimilation of alternative sulfur sources in fungi

Fungi are well known for their metabolic versatility, whether it is the degradation of complex organic substrates or the biosynthesis of intricate secondary metabolites. The vast majority of studies concerning fungal metabolic pathways for sulfur assimilation have focused on conventional sources of sulfur such as inorganic sulfur ions and sulfur-containing biomolecules. Less is known about the metabolic pathways involved in the assimilation of so-called “alternative” sulfur sources such as sulfides, sulfoxides, sulfones, sulfonates, sulfate esters and sulfamates. This review summarizes our current knowledge regarding the structural diversity of sulfur compounds assimilated by fungi as well as the biochemistry and genetics of metabolic pathways involved in this process. Shared sequence homology between bacterial and fungal sulfur assimilation genes have lead to the identification of several candidate genes in fungi while other enzyme activities and pathways so far appear to be specific to the fungal kingdom. Increased knowledge of how fungi catabolize this group of compounds will ultimately contribute to a more complete understanding of sulfur cycling in nature as well as the environmental fate of sulfur-containing xenobiotics

Fetal microchimeric cells in autoimmune thyroid diseases

Autoimmune thyroid diseases (AITD) show a female predominance, with an increased incidence in the years following parturition. Fetal microchimerism has been suggested to play a role in the pathogenesis of AITD. However, only the presence of fetal microchimeric cells in blood and in the thyroid gland of these patients has been proven, but not an actual active role in AITD. Is fetal microchimerism harmful for the thyroid gland by initiating a Graft versus Host reaction (GvHR) or being the target of a Host versus Graft reaction (HvGR)? Is fetal microchimerism beneficial for the thyroid gland by being a part of tissue repair or are fetal cells just innocent bystanders in the process of autoimmunity? This review explores every hypothesis concerning the role of fetal microchimerism in AITD