Divergent pro-inflammatory profile of human dendritic cells in response to commensal and pathogenic bacteria associated with the airway microbiota

Recent studies using culture-independent methods have characterized the human airway microbiota and report microbial communities distinct from other body sites. Changes in these airway bacterial communities appear to be associated with inflammatory lung disease, yet the pro-inflammatory properties of individual bacterial species are unknown. In this study, we compared the immune stimulatory capacity on human monocyte-derived dendritic cells (DCs) of selected airway commensal and pathogenic bacteria predominantly associated with lungs of asthma or COPD patients (pathogenic Haemophillus spp. and Moraxella spp.), healthy lungs (commensal Prevotella spp.) or both (commensal Veillonella spp. and Actinomyces spp.). All bacteria were found to induce activation of DCs as demonstrated by similar induction of CD83, CD40 and CD86 surface expression. However, asthma and COPD-associated pathogenic bacteria provoked a 3-5 fold higher production of IL-23, IL-12p70 and IL-10 cytokines compared to the commensal bacteria. Based on the differential cytokine production profiles, the studied airway bacteria could be segregated into three groups (Haemophilus spp. and Moraxella spp. vs. Prevotella spp. and Veillonella spp. vs. Actinomyces spp.) reflecting their pro-inflammatory effects on DCs. Co-culture experiments found that Prevotella spp. were able to reduce Haemophillus influenzae-induced IL-12p70 in DCs, whereas no effect was observed on IL-23 and IL-10 production. This study demonstrates intrinsic differences in DC stimulating properties of bacteria associated with the airway microbiota.     

Biased predation could promote convergence yet maintain diversity within Müllerian mimicry rings of Oreina leaf beetles

Müllerian mimicry is a classic example of adaptation, yet Müller's original theory does not account for the diversity often observed in mimicry rings. Here, we aimed to assess how well classical Müllerian mimicry can account for the colour polymorphism found in chemically defended Oreina leaf beetles by using field data and laboratory assays of predator behaviour. We also evaluated the hypothesis that thermoregulation can explain diversity between Oreina mimicry rings. We found that frequencies of each colour morph were positively correlated among species, a critical prediction of Müllerian mimicry. Predators learned to associate colour with chemical defences. Learned avoidance of the green morph of one species protected green morphs of another species. Avoidance of blue morphs was completely generalized to green morphs, but surprisingly, avoidance of green morphs was less generalized to blue morphs. This asymmetrical generalization should favour green morphs: indeed, green morphs persist in blue communities, whereas blue morphs are entirely excluded from green communities. We did not find a correlation between elevation and coloration, rejecting thermoregulation as an explanation for diversity between mimicry rings. Biased predation could explain within‐community diversity in warning coloration, providing a solution to a long‐standing puzzle. We propose testable hypotheses for why asymmetric generalization occurs, and how predators maintain the predominance of blue morphs in a community, despite asymmetric generalization.     

Inhibition of proliferation and induction of differentiation of osteoblastic cells by a novel 1,25-dihydroxyvitamin D3 analog with an extensively modified side chain (CB1093)

1,25-Dihydroxyvitamin D₃ (1,25D) is involved in the regulation of proliferation and differentiation of a variety of cell types including cancer cells. In recent years, numerous new vitamin D₃ analogs have been developed in order to obtain favorable therapeutic properties. The effects of a new 20-epi analog, CB1093 (20-epi-22-ethoxy-23-yne-24a,26a,27a-trihomo-1α,25(OH)₂D₃), on the proliferation and differentiation of human MG-63 osteosarcoma cell line were compared here with those of the parent compound 1,25D. Proliferation of the MG-63 cells was inhibited similarly by 22%, 50% and 59% after treatment with 0.1 μM 1,25D or CB1093 for 48 h, 96 h, and 144 h, respectively. In transfection experiments, the compounds were equipotent in stimulating reporter gene activity under the control of human osteocalcin gene promoter. In cell culture experiments, however, CB1093 was more potent than 1,25D at low concentrations and more effective for a longer period of time in activating the osteocalcin gene expression at mRNA and protein levels. Also, a 6-h pretreatment and subsequent culture for up to 120 h without 1,25D or CB1093 yielded higher osteocalcin mRNA and protein levels with analog-treated cells than with 1,25D-treated cells. The electrophoretic mobility shift assay (EMSA) revealed stronger VDR-VDRE binding with analog-treated MG-63 cells than with 1,25D-treated cells. The differences in the DNA binding of 1,25D-bound vs. analog-bound VDR, however, largely disappeared when the binding reactions were performed with recombinant hVDR and hRXRβ proteins. These results demonstrate that the new analog CB1093 was equally or even more effective than 1,25D in regulating all human osteosarcoma cell functions ranging from growth inhibition to marker gene expression and that the differences in effectivity most probably resulted from interactions of the hVDR:hRXRβ-complex with additional nuclear proteins. J. Cell. Biochem. 70:414–424, 1998. © 1998 Wiley-Liss, Inc.     

Excitation energy trapping in photosystem I complexes depleted in Lhca1 and Lhca4

We report a time-resolved fluorescence spectroscopy characterization of photosystem I (PSI) particles prepared from Arabidopsis lines with knock-out mutations against the peripheral antenna proteins of Lhca1 or Lhca4. The first mutant retains Lhca2 and Lhca3 while the second retains one other light-harvesting protein of photosystem I (Lhca) protein, probably Lhca5. The results indicate that Lhca2/3 and Lhca1/4 each provides about equally effective energy transfer routes to the PSI core complex, and that Lhca5 provides a less effective energy transfer route. We suggest that the specific location of each Lhca protein within the PSI-LHCI supercomplex is more important than the presence of so-called red chlorophylls in the Lhca proteins.     

A new monitoring PAM fluorometer (<Emphasis Type="Italic">MONI-PAM</Emphasis>) to study the short- and long-term acclimation of photosystem II in field conditions

We present and evaluate the performance of a new field monitoring PAM fluorometer (MONI-PAM) which is intended for short- and long-term monitoring of the acclimation of photosystem II (PSII). The instrument measures chlorophyll fluorescence, photosynthetic photon flux density (PPFD), and temperature in the field, and monitors exactly the same leaf area over prolonged periods of time, facilitating the estimation of both rapidly reversible and sustained non-photochemical quenching (NPQ). The MONI-PAM performance is evaluated in the lab and under natural conditions in a Scots pine canopy during spring recovery of photosynthesis. The instrument provides a new tool to study in detail the acclimation of PSII to the environment under natural field conditions.     

Hepatic Oxidative Stress,Genotoxicity and Vascular Dysfunction in Lean or Obese Zucker Rats

Metabolic syndrome is associated with increased risk of cardiovascular disease, which could be related to oxidative stress. Here, we investigated the associations between hepatic oxidative stress and vascular function in pressurized mesenteric arteries from lean and obese Zucker rats at 14, 24 and 37 weeks of age. Obese Zucker rats had more hepatic fat accumulation than their lean counterparts. Nevertheless, the obese rats had unaltered age-related level of hepatic oxidatively damaged DNA in terms of formamidopyrimidine DNA glycosylase (FPG) or human oxoguanine DNA glycosylase (hOGG1) sensitive sites as measured by the comet assay. There were decreasing levels of oxidatively damaged DNA with age in the liver of lean rats, which occurred concurrently with increased expression of Ogg1. The 37 week old lean rats also had higher expression level of Hmox1 and elevated levels of DNA strand breaks in the liver. Still, both strain of rats had increased protein level of HMOX-1 in the liver at 37 weeks. The external and lumen diameters of mesenteric arteries increased with age in obese Zucker rats with no change in media cross-sectional area, indicating outward re-modelling without hypertrophy of the vascular wall. There was increased maximal response to acetylcholine-mediated endothelium-dependent vasodilatation in both strains of rats. Collectively, the results indicate that obese Zucker rats only displayed a modest mesenteric vascular dysfunction, with no increase in hepatic oxidative stress-generated DNA damage despite substantial hepatic steatosis.     

Association of Genetic Variants at 3q22 with Nephropathy in Patients with Type 1 Diabetes Mellitus

Diabetic nephropathy (DN) is the primary cause of morbidity and mortality in patients with type 1 diabetes mellitus (T1DM) and affects about 30% of these patients. We have previously localized a DN locus on chromosome 3q with suggestive linkage in Finnish individuals. Linkage to this region has also been reported earlier by several other groups. To fine map this locus, we conducted a multistage case-control association study in T1DM patients, comprising 1822 cases with nephropathy and 1874 T1DM patients free of nephropathy, from Finland, Iceland, and the British Isles. At the screening stage, we genotyped 3072 tag SNPs, spanning a 28 Mb region, in 234 patients and 215 controls from Finland. SNPs that met the significance threshold of p < 0.01 at this stage were followed up by a series of sample sets. A genetic variant, rs1866813, in the noncoding region at 3q22 was associated with increased risk of DN (overall p = 7.07 × 10⁻⁶, combined odds ratio [OR] of the allele = 1.33). The estimated genotypic ORs of this variant in all Finnish samples suggested a codominant effect, resulting in significant association, with a p value of 4.7 × 10⁻⁵ (OR = 1.38; 95% confidence interval = 1.18–1.62). Additionally, an 11 kb segment flanked by rs62408925 and rs1866813, two strongly correlated variants (r² = 0.95), contains three elements highly conserved across multiple species. Independent replication will clarify the role of the associated variants at 3q22 in influencing the risk of DN.     

Densities of microtime rodents along a pollution gradient from a copper-nickel smelter

Population densities of microtine rodents were studied along an air pollution gradient in the Kola Peninsula, Russia, by long-term and short-term trapping. The study area is affected by high sulphur dioxide and heavy metal emissions from the Severonikel copper-nickel smelter in Monchegorsk. The density of Clethrionomys rufocanus, the most abundant vole species in the area, was lowest close to the smelter and increased with distance up to the farthest, less polluted trapping sites. Clethrionomys glareolus, C. rutilus and Lemmus lemmus were absent from the most severely damaged area and were also scarce at the moderately polluted area 28 km south of the smelter. Although the population of C. glareolus has previously been cyclic at the moderately polluted area, we were unable to demonstrate any regular cycle. The most likely explanation for the low number of microtine rodents in the damaged and moderately polluted areas in a decrease in the quantity of important food plants: epiphytic lichens for C. glareolus and possibly C. rutilus, mosses for L. lemmus and seed plants, especially Vaccinium myrtillus, for C. rufocanus. Close to the smelter, direct toxic effects of heavy metals may also reduce population densities. The results show that pollutants may change the relative proportions of microtine species.     

Spatio-temporal patterns of habitat use in voles and shrews modified by density, season and predators

1.?Although the intrinsic habitat preferences of a species can be considered to be fixed, the realized habitat use depends on the prevailing abiotic and biotic conditions. Often the core habitats are occupied by dense and stable populations, while marginal habitats become occupied only at times of high density. In a community of interacting species, habitat uses of different species become inter-related, for example an increased density of a strong competitor forcing a weaker competitor to use more marginal habitats. 2.?We studied the spatio-temporal distribution patterns of three common small mammal species, the bank vole Myodes glareolus; the field vole Microtus agrestis; and the common shrew Sorex araneus, in a 4-year trapping study carried out on six large islands, each containing a mixture of three main habitat types (forest, field and clear-cut). We experimentally released least weasels (Mustela n. nivalis) to some of the islands to see how the focal species respond to increased predation pressure. 3.?Both vole species were largely restricted to their core habitats (bank voles to forests and field voles to fields) at times of low population density. With increasing density, the relative habitat use of both species increased in the clear-cut areas. The common shrew was a generalist in its habitat use at all population densities. 4.?The release of the weasels changed the habitat use of all study species. 5.?The vole species showed a stronger aggregated pattern than the common shrew, especially at low population density. The vole aggregations remained in the same localities between seasons, except in the case of bank voles after the weasels were released. 6.?Bank voles and field voles avoided each other at high density. 7.?We conclude that intrinsically differential habitat requirements and flexibility to modify habitat use facilitate the coexistence of the two competing vole species in mosaic landscapes consisting of boreal forests and open habitats.