Swiprosin-1 modulates actin dynamics by regulating the F-actin accessibility to cofilin

Membrane protrusions, like lamellipodia, and cell movement are dependent on actin dynamics, which are regulated by a variety of actin-binding proteins acting cooperatively to reorganize actin filaments. Here, we provide evidence that Swiprosin-1, a newly identified actin-binding protein, modulates lamellipodial dynamics by regulating the accessibility of F-actin to cofilin. Overexpression of Swiprosin-1 increased lamellipodia formation in B16F10 melanoma cells, whereas knockdown of Swiprosin-1 inhibited EGF-induced lamellipodia formation, and led to a loss of actin stress fibers at the leading edges of cells but not in the cell cortex. Swiprosin-1 strongly facilitated the formation of entangled or clustered F-actin, which remodeled the structural organization of actin filaments making them inaccessible to cofilin. EGF-induced phosphorylation of Swiprosin-1 at Ser183, a phosphorylation site newly identified using mass spectrometry, effectively inhibited clustering of actin filaments and permitted cofilin access to F-actin, resulting in actin depolymerization. Cells overexpressing a Swiprosin-1 phosphorylation-mimicking mutant or a phosphorylation-deficient mutant exhibited irregular membrane dynamics during the protrusion and retraction cycles of lamellipodia. Taken together, these findings suggest that dynamic exchange of Swiprosin-1 phosphorylation and dephosphorylation is a novel mechanism that regulates actin dynamics by modulating the pattern of cofilin activity at the leading edges of cells.     

Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expression

Hepcidin is a key regulator of systemic iron homeostasis. Hepcidin deficiency induces iron overload, whereas hepcidin excess induces anemia. Mutations in the gene encoding hemojuvelin (HFE2, also known as HJV) cause severe iron overload and correlate with low hepcidin levels, suggesting that hemojuvelin positively regulates hepcidin expression. Hemojuvelin is a member of the repulsive guidance molecule (RGM) family, which also includes the bone morphogenetic protein (BMP) coreceptors RGMA and DRAGON (RGMB). Here, we report that hemojuvelin is a BMP coreceptor and that hemojuvelin mutants associated with hemochromatosis have impaired BMP signaling ability. Furthermore, BMP upregulates hepatocyte hepcidin expression, a process enhanced by hemojuvelin and blunted in Hfe2-/- hepatocytes. Our data suggest a mechanism by which HFE2 mutations cause hemochromatosis: hemojuvelin dysfunction decreases BMP signaling, thereby lowering hepcidin expression.     

A simple interspike interval analyzer for study of neuronal spike trains

Summary A simple, low cost interspike interval analyzer for the analysis of trains of nerve impulses is described. The analyzer is built with readily available integrated circuits and has been used to analyze spike trains in the lateral vestibular nucleus of cats.Acknowledgment. This research is supported in part by Higher Degrees and Research Grant No. 158/363 to J.C.H. from the University of Hong Kong.     

Host cell reactivation capacity of different strains ofE. coli B resistant or sensitive to ozone

Summary Host cell reactivation capacity for ozonated or irradiated phage was determined for different strains ofE. coli either more sensitive or resistant to ozone than the wild type strain. The results suggest that theozr gene product could be involved in the same repair pathway for ozone-induced lesions on DNA as thepolA gene. The possible involment of a specific endonuclease for these lesions is also considered.This research was sponsored by the National Sciences and Engineering Research Council of Canada. P.L.H. acknowledges a postgraduate scholarship from the NSERC of Canada.     

Mutagenecity in the mal regions ofEscherichia coli

Résumé L'efficacité de la nitrosoguanidine (MNG) dans différents milieux de culture et tampons a été étudiée. Les résultats obtenus montrent qu'avec le temps, la fraction de cellules survivant au traitement diminue progressivement alors que la fréquence de mutation augmente dans tous les milieux. L'activité de cet agent atteint un maximum dans le milieu DM-glucose tandis que dans le tampon TM elle est à son plus bas niveau.     

Function and regulation of Dyrk1A: towards understanding Down syndrome

Down syndrome (DS) is associated with a variety of symptoms, such as incapacitating mental retardation and neurodegeneration (i.e., Alzheimer’s disease), that prevent patients from leading fully independent lives. These phenotypes are a direct consequence of the overexpression of chromosome 21 genes, which are present in duplicate due to non-disjunction of chromosome 21. Accumulating data suggest that the chromosome 21 gene product, dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A (Dyrk1A), participates in the pathogenic mechanisms underlying the mental and other physical symptoms of DS. In this review, we summarize the evidence supporting a role for Dyrk1A in DS, especially DS pathogenesis. Recently, several natural and synthetic compounds have been identified as Dyrk1A inhibitors. Understanding the function and regulation of Dyrk1A may lead to the development of novel therapeutic agents aimed at treating DS.     

Key factors for efficiently implementing customized e-learning system in the service industry

In recent years,e-learning system has been adopted as a training tool in many firms,as it can help employees to complete training in a short time and at a low cost.Within this context,since 2003 the Industrial Development Bureau(IDB) of the Ministry of Economic Affairs(MOEA) in Taiwan sponsored more than 50 enterprises each year to help them implement customized e-learning systems. Past research on e-learning mostly focused on one criterion and adopted regression approach,such as examining the relationsh...