A two-component regulatory system playing a critical role in plant pathogens and endosymbionts is present in Brucella abortus and controls cell invasion and virulence

Two mutants showing increased sensitivity to polycations and surfactants were obtained by transposon mutagenesis of virulent Brucella abortus 2308 Nal^r. These mutants showed no obvious in vitro growth defects and produced smooth-type lipopolysaccharides. However, they hardly multiplied or persisted in mouse spleens, displayed reduced invasiveness in macrophages and HeLa cells, lost the ability to inhibit lysosome fusion and were unable to replicate intracellularly. Subsequent DNA analyses identified a two-component regulatory system [ Brucella virulence related (Bvr)] with a regulatory (BvrR) and sensory (BvrS) protein. Cloning of bvrR in the BvrR-deficient mutant restored the resistance to polycations and, in part, the invasiveness and the ability to multiply intracellularly. BvrR and BvrS were highly similar (87–89% and 70–80% respectively) to the regulatory and sensory proteins of the chromosomally encoded Rhizobium meliloti ChvI–ExoS and Agrobacterium tumefaciens ChvI–ChvG systems previously shown to be critical for endosymbiosis and pathogenicity in plants. Divergence among the three sensory proteins was located mostly within a periplasmic domain probably involved in stimulus sensing. As B. abortus , R. meliloti and A. tumefaciens are phylogenetically related, these observations suggest that these systems have a common ancestor that has evolved to sense stimuli in plant and animal microbial environments.     

Genotypic and phenotypic variation of Lewis antigen expression in geographically diverse Helicobacter pylori isolates

Background: Helicobacter pylori are a persistent colonizer of the human gastric mucosa, which can lead to the development of peptic ulcer disease and gastric adenocarcinomas. However, H. pylori can asymptomatically colonize a host for years. One factor that has been hypothesized to contribute to such persistence is the production of Lewis (Le) antigens in the lipopolysaccharide layer of the bacterial outer membrane as a form of molecular mimicry, because humans also express these antigens on their gastric mucosa. Humans and H. pylori both are polymorphic for Le expression, which is driven in H. pylori by variation at the Le synthesis loci. In this report, we sought to characterize Le genotypic and phenotypic variation in geographically diverse H. pylori isolates. Materials and Methods: From patients undergoing endoscopy in 29 countries, we determined Le phenotypes of 78 H. pylori strains and performed genotyping of the galT and β‐(1,3)galT loci in 113 H. pylori strains. Results: Le antigen phenotyping revealed a significant (p < .0001) association between type 1 (Le^a and Le^b) expression and strains of East Asian origin. Genotyping revealed a significant correlation between strain origin and the size of the promoter region upstream of the Le synthesis gene, galT (p < .0001). Conclusion: These results indicate that the heterogeneity of human Le phenotypes is reflected in their H. pylori colonizing strains and suggest new loci that can be studied to assess the variation of Le expression.     

Prevalence survey of schistosomiasis in Mindanao and the Visayas, The Philippines

The first two phases of a national prevalence survey of schistosomiasis in The Philippines were completed in Mindanao in 2005 and the Visayas in the first quarter of 2007. The design was a stratified two-step systematic cluster sampling, with two Kato-Katz thick smears examined from each participant. In Mindanao, a total of 22 provinces spread in six regions were covered by the survey with five barangays (equivalent to a village) per province for a total of 110 barangays. The response rate was 70.9% with a total of 21,390 individuals examined. The province of Maguindanao, a known endemic area for schistosomiasis japonica, failed to take part in the survey. In the Visayas, 10 out of 11 provinces, spread out in three regions, participated in the survey. There were 6321 respondents for an overall participation rate of 32.2%. Mindanao showed a wider coverage of the disease than the Visayas (60% versus 45%). By region, Caraga or Region 13 ranked first in Mindanao and Region 8 in the Visayas. By province, Agusan del Sur is first on the list, followed by Northern Samar and then Eastern Samar. Overall, the prevalence rate among males is higher than that of females suggesting the occupational hazard of farming and fishing among the males. The higher exposure among farmers and fishermen is also borne out by the age distribution of the disease. Prevalence remains consistently high among the adults compared with the younger age groups. The survey also covered other helminth infections that can be detected in a stool survey, notably soil-transmitted helminthes and food-borne trematodes.     

The influence of climate on the distribution of lichens: a case study in a borderline area (Liguria,NW Italy)

The purposes of this article are to quantify the relationship between epiphytic lichen distribution and macroclimatic variables in the study area and to provide a case study for evaluating the predictive role of epiphytic lichens as bioclimatic indicators. The study was carried out in the Liguria region (NW-Italy), a small (5432 km²) borderline area, where phytoclimatic features range from the dry Mediterranean to the Alpine in a few kilometers. Epiphytic lichen diversity was sampled using a standardized protocol [Asta et al (2002) In: Nimis et al (eds) Monitoring with lichens: monitoring lichens. Kluwer, Dordrecht]. Abundance of the species in the sampling sites was related to macroclimatic parameters (yearly average temperature and rainfall) and non-parametric multivariate models were calculated to find significative relationships among predictive and response variables. A total of 59 species showed highly significant relation with macroclimatic parameters. Four groups were selected, by means of a cluster analysis, related to four climatic niches (warm-humid, cold-humid, mesothermic-humid, warm-dry). Distributional pattern of the groups in the survey area showed a good correspondence with the bioclimatic units of Liguria region described by Nimis [(2003) Checklist of the Lichens of Italy 3.0. University of Trieste, Dept of Biology. http://www.dbiodbs.univ.trieste.it. Cited 1 Jun 2006]. A significant subset of epiphytic lichen species in the study area have been proved to be efficient bioclimatic indicator and it is supposed to give good results to monitor climatic changes, in a long-term perspective.     

Ontogeny of Toll-like receptor mediated cytokine responses of human blood mononuclear cells

Newborns and young infants suffer increased infectious morbidity and mortality as compared to older children and adults. Morbidity and mortality due to infection are highest during the first weeks of life, decreasing over several years. Furthermore, most vaccines are not administered around birth, but over the first few years of life. A more complete understanding of the ontogeny of the immune system over the first years of life is thus urgently needed. Here, we applied the most comprehensive analysis focused on the innate immune response following TLR stimulation over the first 2 years of life in the largest such longitudinal cohort studied to-date (35 subjects). We found that innate TLR responses (i) known to support Th17 adaptive immune responses (IL-23, IL-6) peaked around birth and declined over the following 2 years only to increase again by adulthood; (ii) potentially supporting antiviral defense (IFN-α) reached adult level function by 1 year of age; (iii) known to support Th1 type immunity (IL-12p70, IFN-γ) slowly rose from a low at birth but remained far below adult responses even at 2 years of age; (iv) inducing IL-10 production steadily declined from a high around birth to adult levels by 1 or 2 years of age, and; (v) leading to production of TNF-α or IL-1β varied by stimuli. Our data contradict the notion of a linear progression from an 'immature' neonatal to a 'mature' adult pattern, but instead indicate the existence of qualitative and quantitative age-specific changes in innate immune reactivity in response to TLR stimulation.     

Assignment of function to histidines 260 and 298 by engineering the E1 component of the Escherichia coli 2-oxoglutarate dehydrogenase complex; substitutions that lead to acceptance of substrates lacking the 5-carboxyl group

The first component (E1o) of the Escherichia coli 2-oxoglutarate dehydrogenase complex (OGDHc) was engineered to accept substrates lacking the 5-carboxylate group by subjecting H260 and H298 to saturation mutagenesis. Apparently, H260 is required for substrate recognition, but H298 could be replaced with hydrophobic residues of similar molecular volume. To interrogate whether the second component would allow synthesis of acyl-coenzyme A derivatives, hybrid complexes consisting of recombinant components of OGDHc (o) and pyruvate dehydrogenase (p) enzymes were constructed, suggesting that a different component is the "gatekeeper" for specificity for these two multienzyme complexes in bacteria, E1p for pyruvate but E2o for 2-oxoglutarate.     

The Role of Neighbours Selection on Cohesion and Order of Swarms

We introduce a multi-agent model for exploring how selection of neighbours determines some aspects of order and cohesion in swarms. The model algorithm states that every agents'' motion seeks for an optimal distance from the nearest topological neighbour encompassed in a limited attention field. Despite the great simplicity of the implementation, varying the amplitude of the attention landscape, swarms pass from cohesive and regular structures towards fragmented and irregular configurations. Interestingly, this movement rule is an ideal candidate for implementing the selfish herd hypothesis which explains aggregation of alarmed group of social animals.     

HIV-1 Nef induces dendritic cell differentiation: a possible mechanism of uninfected CD4(+) T cell activation

Human immunodeficiency virus (HIV)-1 Nef protein is an essential modulator of AIDS pathogenesis and we have previously demonstrated that rNef enters uninfected human monocytes and induces T cells bystander activation, up-regulating IL-15 production. Since dendritic cells (DCs) play a central role in HIV-1 primary infection we investigated whether rNef affects DCs phenotypic and functional maturation in order to define its role in the immunopathogenesis of AIDS. We found that rNef up-regulates the expression on immature DCs of surface molecules known to be critical for their APC function. These molecules include CD1a, HLA-DR, CD40, CD83, CXCR4, and to a lower extent CD80 and CD86. On the other hand, rNef down-regulates surface expression of HLA-ABC and mannose receptor. The functional consequence of rNef treatment of immature DCs is a decrease in their endocytic and phagocytic activities and an increase in cytokine (IL-1beta, IL-12, IL-15, TNF-alpha) and chemokine (MIP-1alpha, MIP-1beta, IL-8) production as well as in their stimulatory capacity. These results indicate that rNef induces a coordinate series of phenotypic and functional changes promoting DC differentiation and making them more competent APCs. Indeed, Nef induces CD4(+) T cell bystander activation by a novel mechanism involving DCs, thus promoting virus dissemination.