Discovery of 6-Amino-2-{[(1S)-1-methylbutyl]oxy}-9-[5-(1-piperidinyl)pentyl]-7,9-dihydro-8H-purin-8-one (GSK2245035), a Highly Potent and Selective Intranasal Toll-Like Receptor 7 Agonist for the Treatment of Asthma.

Induction of IFNα in the upper airways via activation of TLR7 represents a novel immunomodulatory approach to the treatment of allergic asthma. Exploration of 8-oxoadenine derivatives bearing saturated oxygen or nitrogen heterocycles in the N-9 substituent has revealed a remarkable selective enhancement in IFNα inducing potency in the nitrogen series. Further potency enhancement was achieved with the novel (S)-pentyloxy substitution at C-2 leading to the selection of GSK2245035 (32) as an intranasal development candidate.

Gram-negative bacteria associated with brewery yeasts: reclassification of Obesumbacterium proteus biogroup 2 as Shimwellia pseudoproteus gen. nov., sp. nov., and transfer of Escherichia blattae to Shimwellia blattae comb. nov.

Phylogenetic analyses of type and reference strains of Obesumbacterium proteus biogroups 1 and 2 plus a novel isolate of biogroup 2 were carried out based on 16S rRNA gene sequences and partial sequences of four protein-coding genes (fusA, leuS, pyrG and rpoB). Both approaches revealed that O. proteus biogroup 1 strains were closely related to Hafnia alvei.

Inhaled house dust mite induces pulmonary T helper 2 cytokine production.

Background: Inhaled house dust mite (HDM) results in T-helper (TH) 2 type pathology in unsensitized mice, in conjunction with airway hyperreactivity and airway remodelling. However, the pulmonary cytokine and chemokine profile has not been reported.

Methods: We have performed a time course analysis of the characteristic molecular mediators and cellular influx in the bronchoalveolar lavage (BAL) and lung in order to define the pulmonary inflammatory response to inhaled HDM extract.

Composition of peats used in the preparation of malt for scotch whisky productioninfluence of geographical source and extraction depth.

Peat is burned during malt kilning to provide flavor compounds in Scotch malt whisky. The aim of this work was to establish whether peats from different locations in Scotland are chemically distinct and could impart different flavors. Peat samples from four locations (Islay, Orkney, St.

Evolution of pathogenicity in the Bacillus cereus group.

The Bacillus cereus group of bacteria comprises soil-dwelling saprophytes but on occasion these bacteria can cause a wide range of diseases in humans, including food poisoning, systemic infections and highly lethal forms of anthrax. While anthrax is almost invariably caused by strains from a single evolutionary lineage, Bacillus anthracis, variation in the virulence properties of strains from other lineages has not been fully addressed. Using multi-locus sequence data from 667 strains, we reconstructed the evolutionary history of the B.

A Bacillus thuringiensis strain producing a polyglutamate capsule resembling that of Bacillus anthracis.

Bacillus thuringiensis serovar Monterrey strain BGSC 4AJ1 produced a microscopically visible capsule that reacted with a fluorescent antibody specific for the poly-gamma-d-glutamic acid (PGA) capsule of Bacillus anthracis. PGA capsule biosynthesis genes with 75%, 81%, 72%, 65% and 63% similarity, respectively, to those of the B. anthracis capBCADE cluster were present on a plasmid (pAJ1-1).

Sneathiella chinensis gen. nov., sp. nov., a novel marine alphaproteobacterium isolated from coastal sediment in Qingdao, China.

The taxonomic position of strain LMG 23452(T), which was isolated from coastal sediment from an aquaculture site near Qingdao, China, in 2000, was determined. Strain LMG 23452(T) comprised Gram-negative, non-spore-forming, motile rods and was found to be a halotolerant, aerobic, chemoheterotroph that produces catalase and oxidase. Comparative 16S rRNA gene sequence analysis revealed that strain LMG 23452(T) shared approximately 89 % sequence similarity with members of the genera Devosia, Hyphomonas, Ensifer and Chelatococcus, which belong to two different orders within the Alphaproteobacteria.

Multilocus sequence typing reveals that Bacillus cereus strains isolated from clinical infections have distinct phylogenetic origins.

Eight strains of Bacillus cereus isolated from bacteremia and soft tissue infections were assigned to seven sequence types (STs) by multilocus sequence typing (MLST). Two strains from different locations had identical STs. The concatenated sequences of the seven STs were aligned with 65 concatenated sequences from reference STs and a neighbor-joining tree was constructed.

Lactobacillus suntoryeus sp. nov., isolated from malt whisky distilleries.

Eight strains of Lactobacillus with identical partial 16S rRNA gene sequences and similar randomly amplified polymorphic DNA patterns were isolated from fermentation samples from Japanese and Scottish malt whisky distilleries. Phylogenetic analysis of almost complete 16S rRNA gene sequences from three representative strains (two from Japan, one from Scotland) placed them in the genus Lactobacillus as members of the Lactobacillus acidophilus group. Lactobacillus helveticus and Lactobacillus gallinarum were the most closely related species, with 16S rRNA gene similarities of 99.

Population structure and evolution of the Bacillus cereus group.

Representative strains of the Bacillus cereus group of bacteria, including Bacillus anthracis (11 isolates), B. cereus (38 isolates), Bacillus mycoides (1 isolate), Bacillus thuringiensis (53 isolates from 17 serovars), and Bacillus weihenstephanensis (2 isolates) were assigned to 59 sequence types (STs) derived from the nucleotide sequences of seven alleles, glpF, gmk, ilvD, pta, pur, pycA, and tpi. Comparisons of the maximum likelihood (ML) tree of the concatenated sequences with individual gene trees showed more congruence than expected by chance, indicating a generally clonal structure to the population.

Identification of anthrax toxin genes in a Bacillus cereus associated with an illness resembling inhalation anthrax.

Bacillus anthracis is the etiologic agent of anthrax, an acute fatal disease among mammals. It was thought to differ from Bacillus cereus, an opportunistic pathogen and cause of food poisoning, by the presence of plasmids pXO1 and pXO2, which encode the lethal toxin complex and the poly-gamma-d-glutamic acid capsule, respectively. This work describes a non-B.

Asperger's disorder: a review of its diagnosis and treatment.

Asperger's disorder is a pervasive developmental disorder that shares similar features of social impairment disorder, restricted interests, and repetitive behaviors with autistic disorder. Although both Asperger's disorder and autistic disorder persist into adulthood, autistic disorder is usually apparent before the age of 3, while Asperger's disorder usually manifests itself at preschool age. Asperger's disorder in the majority of cases is not associated with delay in language development and there is an increased likelihood to seek social interactions and to engage in activities and friendship with others.

Taxonomic characterization and plant colonizing abilities of some bacteria related to Bacillus amyloliquefaciens and Bacillus subtilis.

The phylogenetic relationships of 17 Bacillus strains isolated from plants and soil were determined from partial sequences of genes encoding 16S rRNA, gyraseA (gyrA) and the cheA histidine kinase. Five strains were closely related to Bacillus subtilis subsp. subtilis, three strains were more closely related to B.

Ultrastructural and behavioural changes precede amyloid deposition in a transgenic model of Alzheimer's disease.

We describe the thorough characterisation of a new transgenic mouse line overexpressing the 695-amino acid isoform of human amyloid precursor protein harbouring the Swedish double familial Alzheimer's disease mutation. This line, referred to as TAS10, exhibits neuropathological features and cognitive deficits that are closely correlated to the accumulation of Abeta in their brain and that are reminiscent of those observed in AD. Data on the TAS10 line are presented at five time points: 2, 6, 12, 18 and 24 months in a longitudinal study.

Molecular typing of Bacillus thuringiensis serovars by RAPD-PCR.

One hundred and twenty-six strains of Bacillus thuringiensis representing 57 serovars were allocated to 58 genomic types using random amplified polymorphic DNA (RAPD)-PCR patterns. Serovars darmstadiensis, israelensis, kenyae, kumamotoensis, kurstaki, morrisoni, pakistani, sotto, thuringiensis and tolworthi each encompassed identical or closely related strains. Despite this genomic homogeneity, most of these serovars also included at least one variant strain.

Pulsed field gel electrophoresis of chromosomal DNA reveals a clonal population structure to Bacillus thuringiensis that relates in general to crystal protein gene content.

Seventy strains of Bacillus thuringiensis representing 21 serovars were allocated to 38 genomic groups using pulsed field gel electrophoresis (PFGE) of restriction enzyme-digested DNA. There was a broad correlation between PFGE type and serotype for serovars darmstadiensis, israelensis, kenyae, kumamotoensis, kurstaki, sotto, thuringiensis, and tolworthi, although some serovars included atypical strains. Serovars canadensis and entomocidus were heterogeneous.

Bacillus endophyticus sp. nov., isolated from the inner tissues of cotton plants (Gossypium sp.).

Four strains of aerobic, endospore-forming bacteria were isolated from the inner tissues of healthy cotton plants (Gossypium sp., Dushanbe, Tajikistan). The organisms had identical randomly amplified polymorphic DNA patterns that distinguished them from other bacilli that are commonly isolated from plant tissues, e.

Evolution of the lactic acid bacterial community during malt whisky fermentation: a polyphasic study.

The development of the lactic acid bacterial community in a commercial malt whisky fermentation occurred in three broad phases. Initially, bacteria were inhibited by strong yeast growth. Fluorescence microscopy and environmental scanning electron microscopy revealed, in this early stage, both cocci and rods that were at least partly derived from the wort and yeast but also stemmed from the distillery plant.

Characterization of lactobacilli from Scotch malt whisky distilleries and description of Lactobacillus ferintoshensis sp. nov., a new species isolated from malt whisky fermentations.

Sixty-four strains of Lactobacillus were isolated from fermentation samples from 23 malt whisky distilleries located in the major whisky producing regions of Scotland. The strains were assigned to 26 ribotype patterns. Strains of some ribotype patterns were widely distributed and recovered from distilleries throughout Scotland, while strains representing other ribotypes were particular to a specific region or even a certain distillery.

Regulation of polyglutamic acid synthesis by glutamate in Bacillus licheniformis and Bacillus subtilis.

The synthesis of polyglutamic acid (PGA) was repressed by exogenous glutamate in strains of Bacillus licheniformis but not in strains of Bacillus subtilis, indicating a clear difference in the regulation of synthesis of capsular slime in these two species. Although extracellular gamma-glutamyltranspeptidase (GGT) activity was always present in PGA-producing cultures of B. licheniformis under various growth conditions, there was no correlation between the quantity of PGA and enzyme activity.

Bacillus siralis sp. nov., a novel species from silage with a higher order structural attribute in the 16S rRNA genes.

A novel bacterial strain (171544T) was recently isolated from silage and was classified in the genus Bacillus by 16S rDNA sequence analysis. Additional silage samples have been investigated in the present study and four organisms resembling strain 171544T were isolated. Phenotypic and genotypic characterization of these bacteria showed that they constitute a new species of the genus Bacillus.

Decarboxylation of substituted cinnamic acids by lactic acid bacteria isolated during malt whisky fermentation.

Seven strains of Lactobacillus isolated from malt whisky fermentations and representing Lactobacillus brevis, L. crispatus, L. fermentum, L.

Construction of chromosomal integrants of Bacillus sphaericus 2362 by conjugation with Escherichia coli.

IncP-based plasmids conjugated between Escherichia coli and mosquitocidal strains of Bacillus sphaericus at frequencies of 10(-7) to 10(-9) per recipient. Plasmid transfer was most efficient when a restriction-deficient strain of B. sphaericus 2362 (serotype 5a5b) was used as recipient and was least efficient with recipients from serotypes 1a and 2a2b.