Clonal analysis of meningococci during a 26 year period prior to the introduction of meningococcal serogroup C vaccines

Meningococcal disease remains a public health burden in the UK and elsewhere. Invasive Neisseria meningitidis, isolated in Scotland between 1972 and 1998, were characterised retrospectively to examine the serogroup and clonal structure of the circulating population. 2607 isolates causing invasive disease were available for serogroup and MLST analysis whilst 2517 were available for multilocus sequence typing (MLST) analysis only. Serogroup distribution changed from year to year but serogroups B and C were dominant throughout. Serogroup B was dominant throughout the 1970s and early 1980s until serogroup C became dominant during the mid-1980s. The increase in serogroup C was not associated with one particular sequence type (ST) but was associated with a number of STs, including ST-8, ST-11, ST-206 and ST-334. This is in contrast to the increase in serogroup C disease seen in the 1990s that was due to expansion of the ST-11 clonal complex. While there was considerable diversity among the isolates (309 different STs among the 2607 isolates), a large proportion of isolates (59.9%) were associated with only 10 STs. These data highlight meningococcal diversity over time and the need for ongoing surveillance during the introduction of new meningococcal vaccines

A novel role of Drosophila cytochrome P450-4e3 in permethrin insecticide tolerance

The exposure of insects to xenobiotics, such as insecticides, triggers a complex defence response necessary for survival. This response includes the induction of genes that encode key Cytochrome P450 monooxygenase detoxification enzymes. Drosophila melanogaster Malpighian (renal) tubules are critical organs in the detoxification and elimination of these foreign compounds, so the tubule response induced by dietary exposure to the insecticide permethrin was examined. We found that expression of the gene encoding Cytochrome P450-4e3 (Cyp4e3) is significantly up-regulated by Drosophila fed on permethrin and that manipulation of Cyp4e3 levels, specifically in the principal cells of the Malpighian tubules, impacts significantly on the survival of permethrin-fed flies. Both dietary exposure to permethrin and Cyp4e3 knockdown cause a significant elevation of oxidative stress-associated markers in the tubules, including H2O2 and lipid peroxidation byproduct, HNE (4-hydroxynonenal). Thus, Cyp4e3 may play an important role in regulating H2O2 levels in the endoplasmic reticulum (ER) where it resides, and its absence triggers a JAK/STAT and NF-κB-mediated stress response, similar to that observed in cells under ER stress. This work increases our understanding of the molecular mechanisms of insecticide detoxification and provides further evidence of the oxidative stress responses induced by permethrin metabolism

Competitive formation of spiro and ansa derivatives in the reactions of tetrafluorobutane-1,4-diol with hexachlorocyclotriphosphazene: a comparison with butane-1,4-diol

Reaction of hexachlorocyclotriphosphazene, N3P3Cl6 (1), in two stoichiometries (1:1.2 and 1:3) with the sodium derivative of the fluorinated diol, 2,2,3,3-tetrafluorobutane-1,4-diol, (2), in THF solution at room temperature afforded six products, whose structures have been characterized by X-ray crystallography and 1H, 19F and 31P NMR spectroscopy: the mono-spiro compound, N3P3Cl4(OCH2CF2CF2CH2O), (3), its ansa isomer, (4), a di-spiro derivative N3P3Cl2(OCH2CF2CF2CH2O)2, (5), its spiro-ansa (6) and non-gem cis bis-ansa (7) isomers and a tri-spiro compound N3P3(OCH2CF2CF2CH2O)3, (8). The tri-spiro derivative (8) was also formed in the reaction of the ansa compound (4) with diol (2) in a 1:3 ratio in THF at room temperature. The reactions of (1) with step-wise additions of (2) were also investigated at low temperature (-780C) to give the same range of products as at room temperature. The results of all reactions are compared with previous work on the reactions of (1) with butane-1,4-diol/pyridine mixtures and with the reaction of hexafluorocyclotriphosphazene, N3P3F6 (9), with the silyl derivative of the diol (2), (Me3SiOCH2CF2)2, in a 1:0.4 mole ratio in the same solvent, THF

The Monodromy Matrices of the XXZ Model in the Infinite Volume Limit

We consider the XXZ model in the infinite volume limit with spin half quantum space and higher spin auxiliary space. Using perturbation theory arguments, we relate the half infinite transfer matrices of this class of models to certain $U_q(\hat{sl_2})$ intertwiners introduced by Nakayashiki. We construct the monodromy matrices, and show that the one with spin one auxiliary space gives rise to the L operator.Comment: 19 page

Stereoisomerism in pentaerythritol-bridged cyclotriphosphazene tri-spiranes: spiro and ansa 1,3-propanediyldioxy disubstituted derivatives

Four isomeric products were isolated and purified from the reaction of 1,3-propanediol with the tetra-spirane cyclophosphazene-organophosphate compound (1): viz. the di-monospiro (2a), di-monoansa (2b) and two monospiro-monoansa derivatives (2c) and (2d). It is shown by 31P NMR spectroscopy on addition of a chiral solvating agent (CSA) that both the di-monospiro (2a) and di-monoansa (2b) derivatives are racemates, as expected, whereas no splitting of NMR signals occurred on addition of CSA to solutions of (2c) and (2d). It is found by X-ray crystallography that the two monospiro-monoansa spirane derivatives, (2c) and (2d), are meso diastereoisomers, which represent a new case of the stereochemistry of bis di-substituted cyclophosphazene derivatives of (1). It is also observed from the 31P NMR spectrum of the reaction mixture, supported by the yields of pure compounds, that formation of a spiro group is about 4.5 times more likely than that of an ansa moiety under the conditions of the reaction

Association between genotypic diversity and biofilm production in group B Streptococcus

Background: Group B Streptococcus (GBS) is a leading cause of sepsis and meningitis and an important factor in premature and stillbirths. Biofilm production has been suggested to be important for GBS pathogenesis alongside many other elements, including phylogenetic lineage and virulence factors, such as pili and capsule type. A complete understanding of the confluence of these components, however, is lacking. To identify associations between biofilm phenotype, pilus profile and lineage, 293 strains from asymptomatic carriers, invasive disease cases, and bovine mastitis cases, were assessed for biofilm production using an in vitro assay. Results: Multilocus sequence type (ST) profile, pilus island profile, and isolate source were associated with biofilm production. Strains from invasive disease cases and/or belonging to the ST-17 and ST-19 lineages were significantly more likely to form weak biofilms, whereas strains producing strong biofilms were recovered more frequently from individuals with asymptomatic colonization. Conclusions: These data suggest that biofilm production is a lineage-specific trait in GBS and may promote colonization of strains representing lineages other than STs 17 and 19. The findings herein also demonstrate that biofilms must be considered in the treatment of pregnant women, particularly for women with heavy GBS colonization

Structural investigations of phosphorus-nitrogen compounds. 7. Relationships between physical properties, electron densities, reaction mechanisms and hydrogen-bonding motifs of N3P3Cl(6-n)(NHBut)(n) derivatives

A series of compounds of the N3P3Cl(6-n)(NHBut)n family (where n = 0, 1, 2, 4 and 6) are presented and their molecular parameters are related to trends in physical properties, which provides insight into a potential reaction mechanism for nucleophilic substitution. The crystal structures of N3P3Cl5(NHBut) and N3P3Cl2(NHBut)4 have been determined at 120K and those of N3P3Cl6 and N3P3Cl4(NHBut)2 have been re-determined at 120K. These are compared with the known structure of N3P3(NHBut)6 studied at 150K. Trends in molecular parameters (phosphazene ring, P-Cl & P-N(HBut) distances, PCl2 angles and endo- and exo-cyclic phosphazene ring parameters) across the series are observed. Hydrogen-bonding motifs are identified, characterised and compared. Both the molecular and hydrogen bonding parameters are related to the electron distribution in bonds and the derived basicities of the cyclophosphazene series of compounds. These findings provide evidence for a proposed mechanism for nucleophilic substitution at a phosphorus site bearing a PCl(NHBut) moiety

Bilingual lexical selection as a dynamic process:evidence from Arabic-French bilinguals

The nature of the lexical selection process in bilingual spoken word production is one of the pending questions of research on bilingualism. According to one view this competitive process is language-specific, while another holds that it is language-nonspecific (i.e., lexical competition is cross-linguistic). In recent years, research on bilingual language production has seen the rise of a third view that postulates that lexical selection is in fact dynamic and may function as language-specific or nonspecific depending on a number of factors. The aim of the present study was to investigate the lexical selection process among moderately proficient bilinguals whose two languages are typologically distant: Tunisian Arabic and French. The picture-word interference task was used in two experiments where moderately proficient Tunisian Arabic (L1)-French (L2) bilinguals were asked to name pictures in their L2 while ignoring auditory distractors (semantic, phono-translation, phonological, or unrelated) in their L2 (Experiment 1) or their L1 (Experiment 2). Thus, the language context was entirely monolingual in Experiment 1 and bilingual in Experiment 2. In Experiment 1, only a phonological facilitation effect was observed. In Experiment 2, interference was found in the phono-translation, semantic, and phonological conditions. Taken together, these results indicate that cross-language competition occurs among moderately proficient Tunisian Arabic-French bilinguals only in a bilingual context (Experiment 2) as indexed by the phono-translation interference effect observed. Our findings are in line with the recent hypothesis that lexical selection is a dynamic process modulated by factors like language similarity, language proficiency, and the experimental language context