The genome sequence of Bacillus anthracis Ames and comparison to closely related bacteria

Bacillus anthracis is an endospore-forming bacterium that causes inhalational anthrax. Key virulence genes are found on plasmids (extra-chromosomal, circular, double-stranded DNA molecules) pXO1 (ref. 2) and pXO2 (ref. 3). To identify additional genes that might contribute to virulence, we analysed the complete sequence of the chromosome of B. anthracis Ames (about 5.23 megabases). We found several chromosomally encoded proteins that may contribute to pathogenicity--including haemolysins, phospholipases and iron acquisition functions--and identified numerous surface proteins that might be important targets for vaccines and drugs. Almost all these putative chromosomal virulence and surface proteins have homologues in Bacillus cereus, highlighting the similarity of B. anthracis to near-neighbours that are not associated with anthrax. By performing a comparative genome hybridization of 19 B. cereus and Bacillus thuringiensis strains against a B. anthracis DNA microarray, we confirmed the general similarity of chromosomal genes among this group of close relatives. However, we found that the gene sequences of pXO1 and pXO2 were more variable between strains, suggesting plasmid mobility in the group. The complete sequence of B. anthracis is a step towards a better understanding of anthrax pathogenesis.     

Mutations in the polyglutamine binding protein 1 gene cause X-linked mental retardation

We found mutations in the gene PQBP1 in 5 of 29 families with nonsyndromic (MRX) and syndromic (MRXS) forms of X-linked mental retardation (XLMR). Clinical features in affected males include mental retardation, microcephaly, short stature, spastic paraplegia and midline defects. PQBP1 has previously been implicated in the pathogenesis of polyglutamine expansion diseases. Our findings link this gene to XLMR and shed more light on the pathogenesis of this common disorder.     

Immobile survival of motoneuron (SMN) protein stored in Cajal bodies can be mobilized by protein interactions

Reduced levels of survival of motoneuron (SMN) protein lead to spinal muscular atrophy, but it is still unknown how SMN protects motoneurons in the spinal cord against degeneration. In the nucleus, SMN is associated with two types of nuclear bodies denoted as gems and Cajal bodies (CBs). The 23 kDa isoform of fibroblast growth factor-2 (FGF-2²³) is a nuclear protein that binds to SMN and destabilizes the SMN-Gemin2 complex. In the present study, we show that FGF-2²³ depletes SMN from CBs without affecting their general structure. FRAP analysis of SMN-EGFP in CBs demonstrated that the majority of SMN in CBs remained mobile and allowed quantification of fast, slow and immobile nuclear SMN populations. The potential for SMN release was confirmed by in vivo photoconversion of SMN-Dendra2, indicating that CBs concentrate immobile SMN that could have a specialized function in CBs. FGF-2²³ accelerated SMN release from CBs, accompanied by a conversion of immobile SMN into a mobile population. Furthermore, FGF-2²³ caused snRNP accumulation in CBs. We propose a model in which Cajal bodies store immobile SMN that can be mobilized by its nuclear interaction partner FGF-2²³, leading to U4 snRNP accumulation in CBs, indicating a role for immobile SMN in tri-snRNP assembly.     

HCN2 channels in local inhibitory interneurons constrain LTP in the hippocampal direct perforant path

Neuronal hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are known to modulate spontaneous activity, resting membrane potential, input resistance, afterpotential, rebound activity, and dendritic integration. To evaluate the role of HCN2 for hippocampal synaptic plasticity, we recorded long-term potentiation (LTP) in the direct perforant path (PP) to CA1 pyramidal cells. LTP was enhanced in mice carrying a global deletion of the channel (HCN2^−/−) but not in a pyramidal neuron-restricted knockout. This precludes an influence of HCN2 located in postsynaptic pyramidal neurons. Additionally, the selective HCN blocker zatebradine reduced the activity of oriens-lacunosum moleculare interneurons in wild-type but not HCN2^−/− mice and decreased the frequency of spontaneous inhibitory currents in postsynaptic CA1 pyramidal cells. Finally, we found amplified LTP in the PP of mice carrying an interneuron-specific deletion of HCN2. We conclude that HCN2 channels in inhibitory interneurons modulate synaptic plasticity in the PP by facilitating the GABAergic output onto pyramidal neurons.     

Data Mining as an Enabler for Customer Data Driven Vehicle Development

对于汽车等面向消费者的行业,数据驱动的产品开发是一项关键的系统工程。数据驱动方法的前提是数据本身,由于现代车辆的联网能力不断提高,使得汽车制造商能够以内部总线信号的形式记录并储存客户数据。由于这些数据并不用于外部,只用于内部通信以保证车辆的安全性和功能性,这给这些数据的应用带来了一定的困难,因此汽车行业的主要问题在于如何利用数据挖掘技术从这些数据中提取客户需求及相关信息。为此,对上述数据应用问题进行了文献调研,并在此基础上开展数据挖掘的模拟研究,以确定现有数据挖掘过程在需求获取领域的适用性;进而提出一种扩展程序,使得数据挖掘技术能够应用于相关客户数据之中,从而加快车辆开发的进程。     

Probability distributions,trading strategies and leverage: an application of Gaussian mixture models

The purpose of this paper is twofold. Firstly, to assess the merit of estimating probability density functions rather than level or classification estimations on a one‐day‐ahead forecasting task of the EUR/USD time series. This is implemented using a Gaussian mixture model neural network, benchmarking the results against standard forecasting models, namely a naïve model, a moving average convergence divergence technical model (MACD), an autoregressive moving average model (ARMA), a logistic regression model (LOGIT) and a multi‐layer perceptron network (MLP). Secondly, to examine the possibilities of improving the trading performance of those models with confirmation filters and leverage. While the benchmark models perform best without confirmation filters and leverage, the Gaussian mixture model outperforms all of the benchmarks when taking advantage of the possibilities offered by a combination of more sophisticated trading strategies and leverage. This might be due to the ability of the Gaussian mixture model to identify successfully trades with a high Sharpe ratio. Copyright © 2004 John Wiley & Sons, Ltd.     

Lack of long-term cortical reorganization after macaque retinal lesions

Several aspects of cortical organization are thought to remain plastic into adulthood, allowing cortical sensorimotor maps to be modified continuously by experience. This dynamic nature of cortical circuitry is important for learning, as well as for repair after injury to the nervous system. Electrophysiology studies suggest that adult macaque primary visual cortex (V1) undergoes large-scale reorganization within a few months after retinal lesioning, but this issue has not been conclusively settled. Here we applied the technique of functional magnetic resonance imaging (fMRI) to detect changes in the cortical topography of macaque area V1 after binocular retinal lesions. fMRI allows non-invasive, in vivo, long-term monitoring of cortical activity with a wide field of view, sampling signals from multiple neurons per unit cortical area. We show that, in contrast with previous studies, adult macaque V1 does not approach normal responsivity during 7.5 months of follow-up after retinal lesions, and its topography does not change. Electrophysiology experiments corroborated the fMRI results. This indicates that adult macaque V1 has limited potential for reorganization in the months following retinal injury.     

Electronic tagging and population structure of Atlantic bluefin tuna

Electronic tags that archive or transmit stored data to satellites have advanced the mapping of habitats used by highly migratory fish in pelagic ecosystems. Here we report on the electronic tagging of 772 Atlantic bluefin tuna in the western Atlantic Ocean in an effort to identify population structure. Reporting electronic tags provided accurate location data that show the extensive migrations of individual fish (n = 330). Geoposition data delineate two populations, one using spawning grounds in the Gulf of Mexico and another from the Mediterranean Sea. Transatlantic movements of western-tagged bluefin tuna reveal site fidelity to known spawning areas in the Mediterranean Sea. Bluefin tuna that occupy western spawning grounds move to central and eastern Atlantic foraging grounds. Our results are consistent with two populations of bluefin tuna with distinct spawning areas that overlap on North Atlantic foraging grounds. Electronic tagging locations, when combined with US pelagic longline observer and logbook catch data, identify hot spots for spawning bluefin tuna in the northern slope waters of the Gulf of Mexico. Restrictions on the time and area where longlining occurs would reduce incidental catch mortalities on western spawning grounds.