Novel cyclic di-GMP effectors of the YajQ protein family control bacterial virulence

Bis-(3 ',5 ') cyclic di-guanylate (cyclic di-GMP) is a key bacterial second messenger that is implicated in the regulation of many critical processes that include motility, biofilm formation and virulence. Cyclic di-GMP influences diverse functions through interaction with a range of effectors. Our knowledge of these effectors and their different regulatory actions is far from complete, however. Here we have used an affinity pull-down assay using cyclic di-GMP-coupled magnetic beads to identify cyclic di-GMP binding proteins in the plant pathogen Xanthomonas campestris pv. campestris (Xcc). This analysis identified XC_3703, a protein of the YajQ family, as a potential cyclic di-GMP receptor. Isothermal titration calorimetry showed that the purified XC_3703 protein bound cyclic di-GMP with a high affinity (K-d similar to 2 mu M). Mutation of XC_3703 led to reduced virulence of Xcc to plants and alteration in biofilm formation. Yeast two-hybrid and far-western analyses showed that XC_3703 was able to interact with XC_2801, a transcription factor of the LysR family. Mutation of XC_2801 and XC_3703 had partially overlapping effects on the transcriptome of Xcc, and both affected virulence. Electromobility shift assays showed that XC_3703 positively affected the binding of XC_2801 to the promoters of target virulence genes, an effect that was reversed by cyclic di-GMP. Genetic and functional analysis of YajQ family members from the human pathogens Pseudomonas aeruginosa and Stenotrophomonas maltophilia showed that they also specifically bound cyclic di-GMP and contributed to virulence in model systems. The findings thus identify a new class of cyclic di-GMP effector that regulates bacterial virulence

Allergic rhinitis in northern vietnam: increased risk of urban living according to a large population survey

<p>Abstract</p> <p>Background</p> <p>Little is known about prevalence and risk factors of allergic rhinitis and chronic nasal symptoms among adults in Vietnam. We aimed to estimate the prevalence, risk factor patterns and co-morbidities of allergic rhinitis and chronic nasal symptoms in one urban and one rural area in northern Vietnam.</p> <p>Methods</p> <p>A cross-sectional questionnaire survey was conducted from August 2007 to January 2008 in urban Hoankiem and rural Bavi in Hanoi among adults aged 21-70 years. Of 7008 randomly selected subjects, 91.7% participated in Bavi and 70.3% in Hoankiem.</p> <p>Results</p> <p>Allergic rhinitis ever or chronic nasal symptoms were reported by 50.2%. The prevalence of allergic rhinitis ever was considerably higher in Hoankiem compared to Bavi, 29.6% vs 10.0% (p < 0.001). Allergic rhinitis ever and chronic nasal symptoms were both significantly associated with asthma and respiratory symptoms, respectively (p < 0.001). Exposure to gas, dust or fumes at work was significantly associated with allergic rhinitis ever, OR 1.57 (95% CI 1.34 - 1.84), nasal blocking, OR 1.90 (95% CI 1.68 - 2.15) and runny nose, OR 1.32 (95% CI 1.17 - 1.49), while somewhat surprisingly no association with smoking was found. Female sex was a significant risk factor for both nasal blocking and runny nose.</p> <p>Conclusions</p> <p>Allergic rhinitis ever was considerably more common in the urban area. Nasal blocking and runny nose was each reported by about one third of the studied sample with no major urban-rural difference. Further, exposure to air pollution at work was significantly associated with allergic rhinitis ever, nasal blocking and runny nose.</p

Genome, Functional Gene Annotation, and Nuclear Transformation of the Heterokont Oleaginous Alga \u3ci\u3eNannochloropsis oceanica\u3c/i\u3e CCMP1779

Unicellular marine algae have promise for providing sustainable and scalable biofuel feedstocks, although no single species has emerged as a preferred organism. Moreover, adequate molecular and genetic resources prerequisite for the rational engineering of marine algal feedstocks are lacking for most candidate species. Heterokonts of the genus Nannochloropsis naturally have high cellular oil content and are already in use for industrial production of high-value lipid products. First success in applying reverse genetics by targeted gene replacement makes Nannochloropsis oceanica an attractive model to investigate the cell and molecular biology and biochemistry of this fascinating organism group. Here we present the assembly of the 28.7 Mb genome of N. oceanica CCMP1779. RNA sequencing data from nitrogen-replete and nitrogendepleted growth conditions support a total of 11,973 genes, of which in addition to automatic annotation some were manually inspected to predict the biochemical repertoire for this organism. Among others, more than 100 genes putatively related to lipid metabolism, 114 predicted transcription factors, and 109 transcriptional regulators were annotated. Comparison of the N. oceanica CCMP1779 gene repertoire with the recently published N. gaditana genome identified 2,649 genes likely specific to N. oceanica CCMP1779. Many of these N. oceanica–specific genes have putative orthologs in other species or are supported by transcriptional evidence. However, because similarity-based annotations are limited, functions of most of these species-specific genes remain unknown. Aside from the genome sequence and its analysis, protocols for the transformation of N. oceanica CCMP1779 are provided. The availability of genomic and transcriptomic data for Nannochloropsis oceanica CCMP1779, along with efficient transformation protocols, provides a blueprint for future detailed gene functional analysis and genetic engineering of Nannochloropsis species by a growing academic community focused on this genus

A rare missense mutation in CHRNA4 associates with smoking behavior and its consequences

Using Icelandic whole-genome sequence data and an imputation approach we searched for rare sequence variants in CHRNA4 and tested them for association with nicotine dependence. We show that carriers of a rare missense variant (allele frequency = 0.24%) within CHRNA4, encoding an R336C substitution, have greater risk of nicotine addiction than non-carriers as assessed by the Fagerstrom Test for Nicotine Dependence (P= 1.2 × 10−4). The variant also confers risk of several serious smoking-related diseases previously shown to be associated with the D398N substitution in CHRNA5. We observed odds ratios (ORs) of 1.7–2.3 for lung cancer(LC;P= 4.0 × 10−4), chronic obstructive pulmonary disease (COPD;P= 9.3 × 10−4), peripheral artery disease (PAD;P= 0.090) and abdominal aortic aneurysms (AAAs; P= 0.12), and the variant associates strongly with the early-onset forms of LC (OR = 4.49,P= 2.2 × 10−4), COPD (OR = 3.22,P= 2.9 × 10−4), PAD (OR = 3.47,P= 9.2 × 10−3) and AAA (OR = 6.44, P= 6.3 × 10−3). Joint analysis of the four smoking-related diseases reveals significant association (P= 6.8 × 10−5), particularly for early-onset cases (P=2.1 × 10−7). Our results are in agreement with functional studies showing that the human α4β2 isoform of the channel containing R336C has less sensitivity for its agonists than the wild-type form following nicotine incubation

Mouse models to unravel the role of inhaled pollutants on allergic sensitization and airway inflammation

Air pollutant exposure has been linked to a rise in wheezing illnesses. Clinical data highlight that exposure to mainstream tobacco smoke (MS) and environmental tobacco smoke (ETS) as well as exposure to diesel exhaust particles (DEP) could promote allergic sensitization or aggravate symptoms of asthma, suggesting a role for these inhaled pollutants in the pathogenesis of asthma. Mouse models are a valuable tool to study the potential effects of these pollutants in the pathogenesis of asthma, with the opportunity to investigate their impact during processes leading to sensitization, acute inflammation and chronic disease. Mice allow us to perform mechanistic studies and to evaluate the importance of specific cell types in asthma pathogenesis. In this review, the major clinical effects of tobacco smoke and diesel exhaust exposure regarding to asthma development and progression are described. Clinical data are compared with findings from murine models of asthma and inhalable pollutant exposure. Moreover, the potential mechanisms by which both pollutants could aggravate asthma are discussed

Variability of the chronic obstructive pulmonary disease key epidemiological data in Europe: systematic review

<p>Abstract</p> <p>Background</p> <p>Chronic obstructive pulmonary disease (COPD) is predicted to become a major cause of death worldwide. Studies on the variability in the estimates of key epidemiological parameters of COPD may contribute to better assessment of the burden of this disease and to helpful guidance for future research and public policies. In the present study, we examined differences in the main epidemiological characteristics of COPD derived from studies across countries of the European Union, focusing on prevalence, severity, frequency of exacerbations and mortality, as well as on differences between the studies' methods.</p> <p>Methods</p> <p>This systematic review was based on a search for the relevant literature in the Science Citation Index database via the Web of Science and on COPD mortality rates issued from national statistics. Analysis was finally based on 65 articles and Eurostat COPD mortality data for 21 European countries.</p> <p>Results</p> <p>Epidemiological characteristics of COPD varied widely from country to country. For example, prevalence estimates ranged between 2.1% and 26.1%, depending on the country, the age group and the methods used. Likewise, COPD mortality rates ranged from 7.2 to 36.1 per 10⁵inhabitants. The methods used to estimate these epidemiological parameters were highly variable in terms of the definition of COPD, severity scales, methods of investigation and target populations. Nevertheless, to a large extent, several recent international guidelines or research initiatives, such as GOLD, BOLD or PLATINO, have boosted a substantial standardization of methodology in data collection and have resulted in the availability of more comparable epidemiological estimates across countries. On the basis of such standardization, severity estimates as well as prevalence estimates present much less variation across countries. The contribution of these recent guidelines and initiatives is outlined, as are the problems remaining in arriving at more accurate COPD epidemiological estimates across European countries.</p> <p>Conclusions</p> <p>The accuracy of COPD epidemiological parameters is important for guiding decision making with regard to preventive measures, interventions and patient management in various health care systems. Therefore, the recent initiatives for standardizing data collection should be enhanced to result in COPD epidemiological estimates of improved quality. Moreover, establishing international guidelines for reporting research on COPD may also constitute a major contribution.</p