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.     

Identifying distinct classes of bladder carcinoma using microarrays

Bladder cancer is a common malignant disease characterized by frequent recurrences. The stage of disease at diagnosis and the presence of surrounding carcinoma in situ are important in determining the disease course of an affected individual. Despite considerable effort, no accepted immunohistological or molecular markers have been identified to define clinically relevant subsets of bladder cancer. Here we report the identification of clinically relevant subclasses of bladder carcinoma using expression microarray analysis of 40 well characterized bladder tumors. Hierarchical cluster analysis identified three major stages, Ta, T1 and T2-4, with the Ta tumors further classified into subgroups. We built a 32-gene molecular classifier using a cross-validation approach that was able to classify benign and muscle-invasive tumors with close correlation to pathological staging in an independent test set of 68 tumors. The classifier provided new predictive information on disease progression in Ta tumors compared with conventional staging (P < 0.005). To delineate non-recurring Ta tumors from frequently recurring Ta tumors, we analyzed expression patterns in 31 tumors by applying a supervised learning classification methodology, which classified 75% of the samples correctly (P < 0.006). Furthermore, gene expression profiles characterizing each stage and subtype identified their biological properties, producing new potential targets for therapy.     

Cortex-restricted disruption of NMDAR1 impairs neuronal patterns in the barrel cortex

In the rodent primary somatosensory cortex, the configuration of whiskers and sinus hairs on the snout and of receptor-dense zones on the paws is topographically represented as discrete modules of layer IV granule cells (barrels) and thalamocortical afferent terminals. The role of neural activity, particularly activity mediated by NMDARs (N-methyl-D-aspartate receptors), in patterning of the somatosensory cortex has been a subject of debate. We have generated mice in which deletion of the NMDAR1 (NR1) gene is restricted to excitatory cortical neurons, and here we show that sensory periphery-related patterns develop normally in the brainstem and thalamic somatosensory relay stations of these mice. In the somatosensory cortex, thalamocortical afferents corresponding to large whiskers form patterns and display critical period plasticity, but their patterning is not as distinct as that seen in the cortex of normal mice. Other thalamocortical patterns corresponding to sinus hairs and digits are mostly absent. The cellular aggregates known as barrels and barrel boundaries do not develop even at sites where thalamocortical afferents cluster. Our findings indicate that cortical NMDARs are essential for the aggregation of layer IV cells into barrels and for development of the full complement of thalamocortical patterns.     

Corticosteroidogenesis by isolated human adrenal cells: effect of serotonin and serotonin antagonists.

The direct effect of serotonin and antiserotonin agents on adrenal steroid biosynthesis was studied in isolated adrenal cells derived from patients with Cushing's syndrome. The results indicate that serotonin increases corticosterone production, while the serotonin antagonists cyproheptadine and methysergide depress adrenal steroid - particularly cortisol and aldosterone - biosynthesis.     

GABAergic inhibition of neurons in the ventral tegmental area.

Stimulation of the nucleus accumbens evokes a potent inhibition in neurons of the ventral tegmental area. GABA is likely to act as a transmitter in this descending inhibitory system.     

Constrained Multilevel Latent Class Models for the Analysis of Three-Way Three-Mode Binary Data

Probabilistic feature models (PFMs) can be used to explain binary rater judgements about the associations between two types of elements (e.g., objects and attributes) on the basis of binary latent features. In particular, to explain observed object-attribute associations PFMs assume that respondents classify both objects and attributes with respect to a, usually small, number of binary latent features, and that the observed object-attribute association is derived as a specific mapping of these classifications. Standard PFMs assume that the object-attribute association probability is the same according to all respondents, and that all observations are statistically independent. As both assumptions may be unrealistic, a multilevel latent class extension of PFMs is proposed which allows objects and/or attribute parameters to be different across latent rater classes, and which allows to model dependencies between associations with a common object (attribute) by assuming that the link between features and objects (attributes) is fixed across judgements. Formal relationships with existing multilevel latent class models for binary three-way data are described. As an illustration, the models are used to study rater differences in product perception and to investigate individual differences in the situational determinants of anger-related behavior.     

The carotenoid pigments of the cedar apple rust fungus

Zusammenfassung Die Untersuchung der Carotinoide aus den Äzidien des RostpilzesGymnosporangium juniperi-virginianae Schw. ergab das Vorliegen von 66,5%-Carotin und 33,5%-Carotin (Durchschnittswerte). Diese Werte stimmen mit denjenigen anderer Autoren für Teleuto-Stadium und Pyknidenform überein. Art und Mengenverhältnis der Carotinoide in drei Stadien vonGymnosporangium juniperi-virginianae Schw. (auf verschiedenen Wirtspflanzen) sind daher ungefähr identisch.