Maternal Rnf12/RLIM is required for imprinted X-chromosome inactivation in mice

Two forms of X-chromosome inactivation (XCI) ensure the selective silencing of female sex chromosomes during mouse embryogenesis. Imprinted XCI begins with the detection of Xist RNA expression on the paternal X?chromosome (Xp) at about the four-cell stage of embryonic development. In the embryonic tissues of the inner cell mass, a random form of XCI occurs in blastocysts that inactivates either Xp or the maternal X?chromosome (Xm). Both forms of XCI require the non-coding Xist RNA that coats the inactive X?chromosome from which it is expressed. Xist has crucial functions in the silencing of X-linked genes, including Rnf12 (refs 3, 4) encoding the ubiquitin ligase RLIM (RING finger LIM-domain-interacting protein). Here we show, by targeting a conditional knockout of Rnf12 to oocytes where RLIM accumulates to high levels, that the maternal transmission of the mutant X?chromosome (Δm) leads to lethality in female embryos as a result of defective imprinted XCI. We provide evidence that in Δm female embryos the initial formation of Xist clouds and Xp silencing are inhibited. In contrast, embryonic stem cells lacking RLIM are able to form Xist clouds and silence at least some X-linked genes during random XCI. These results assign crucial functions to the maternal deposit of Rnf12/RLIM for the initiation of imprinted XCI.     

Cell transformation by the superoxide-generating oxidase Mox1.

Reactive oxygen species (ROS) generated in some non-phagocytic cells are implicated in mitogenic signalling and cancer. Many cancer cells show increased production of ROS, and normal cells exposed to hydrogen peroxide or superoxide show increased proliferation and express growth-related genes. ROS are generated in response to growth factors, and may affect cell growth, for example in vascular smooth-muscle cells. Increased ROS in Ras-transformed fibroblasts correlates with increased mitogenic rate. Here we describe the cloning of mox1, which encodes a homologue of the catalytic subunit of the superoxide-generating NADPH oxidase of phagocytes, gp91phox. mox1 messenger RNA is expressed in colon, prostate, uterus and vascular smooth muscle, but not in peripheral blood leukocytes. In smooth-muscle cells, platelet-derived growth factor induces mox1 mRNA production, while antisense mox1 mRNA decreases superoxide generation and serum-stimulated growth. Overexpression of mox1 in NIH3T3 cells increases superoxide generation and cell growth. Cells expressing mox1 have a transformed appearance, show anchorage-independent growth and produce tumours in athymic mice. These data link ROS production by Mox1 to growth control in non-phagocytic cells.     

Forecasting for the generation of trading signals in financial markets

In this paper we show that optimal trading results can be achieved if we can forecast a key summary statistic of future prices. Consider the following optimization problem. Let the return r_i (over time i=1, 2, ..., n) for the ith day be given and the investor has to make investment decision d_i on the ith day with d_i=1 representing a ‘long' position and d_i=0 a ‘neutral' position. The investment return is given by r=Σⁿ_i=1r_id_i−cΣⁿ⁺¹_i=1∣d_i−d_i−1∣, where c is the transaction cost. The mathematical programming problem of choosing d₁, ..., d_n to maximize r under a given transaction cost c is shown to have an analytic solution, which is a function of a key summary statistic called the largest change before reversal. The largest change before reversal is recommended to be used as an output in a neural network for the generation of trading signals. When neural network forecasting is applied to a dataset of Hang Seng Index Futures Contract traded in Hong Kong, it is shown that forecasting the largest change before reversal outperforms the k‐step‐ahead forecast in achieving higher trading profits. Copyright © 2000 John Wiley & Sons, Ltd.     

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.     

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...     

最小学习机

针对极端学习机(ELM)不能用于多层前向神经网络学习的问题,通过揭示单层前向神经网络(SLFN)的ELM与岭回归以及中心化的岭回归之间的关系,提出了SLFN的最小学习机.通过证明核化的中心化岭回归与核化的PCA之间的关系.提出以无限可微的核函数为激励函数的多层前向神经网络(MLFN)的最小学习机LLM.SLFN/MLFN的最小学习机能够保持ELM的上述优势.