Effects of PM10 in human peripheral blood monocytes and J774 macrophages

Background

Asthma is characterized by type 2 T-helper cell (Th2) inflammation, goblet cell hyperplasia, airway hyperreactivity, and airway fibrosis. Monocyte chemoattractant protein-1 (MCP-1 or CCL2) and its receptor, CCR2, have been shown to play important roles in the development of Th2 inflammation. CCR2-deficient mice have been found to have altered inflammatory and physiologic responses in some models of experimental allergic asthma, but the role of CCR2 in contributing to inflammation and airway hyperreactivity appears to vary considerably between models. Furthermore, MCP-1-deficient mice have not previously been studied in models of experimental allergic asthma.

Methods

To test whether MCP-1 and CCR2 are each required for the development of experimental allergic asthma, we applied an Aspergillus antigen-induced model of Th2 cytokine-driven allergic asthma associated with airway fibrosis to mice deficient in either MCP-1 or CCR2. Previous studies with live Aspergillus conidia instilled into the lung revealed that MCP-1 and CCR2 play a role in anti-fungal responses; in contrast, we used a non-viable Aspergillus antigen preparation known to induce a robust eosinophilic inflammatory response.

Results

We found that wild-type C57BL/6 mice developed eosinophilic airway inflammation, goblet cell hyperplasia, airway hyperreactivity, elevations in serum IgE, and airway fibrosis in response to airway challenge with Aspergillus antigen. Surprisingly, mice deficient in either MCP-1 or CCR2 had responses to Aspergillus antigen similar to those seen in wild-type mice, including production of Th2 cytokines.

Conclusion

We conclude that robust Th2-mediated lung pathology can occur even in the complete absence of MCP-1 or CCR2.     

An edit script for taxonomic classifications

Background  

The NCBI taxonomy provides one of the most powerful ways to navigate sequence data bases but currently users are forced to formulate queries according to a single taxonomic classification. Given that there is not universal agreement on the classification of organisms, providing a single classification places constraints on the questions biologists can ask. However, maintaining multiple classifications is burdensome in the face of a constantly growing NCBI classification.     

Multiple subsurface phytoplankton blooms occurring simultaneously in the Skagerrak

The distribution and characteristics of phytoplankton in theSkagerrak in August–September 2000 were analysed in orderto evaluate the importance of subsurface phytoplankton peaksto water column ecology and primary production. In areas affectedby outflow from the Baltic, enhanced chlorophyll concentrationswere found in the warm surface waters (i.e. upper 10–20m). However, for the central Skagerrak, the major part (50–80%)of the chlorophyll in the water column was found below the warmsurface waters. The highest chlorophyll concentrations (up to>18 µg l^-1) in the study area were also found belowthe warm surface waters and up to 95% of total water columnprimary production was recorded below the warm surface waterlayer. Measurements of variable fluorescence (F_v/F_m) indicatedthe greatest potential capacity for electron flow in photosystemII in phytoplankton was located below the warm surface waters.Spectrophotometrically determined pigment ratios suggest thatthe enhanced capacity for photosynthesis in the deeper watersmay be related to greater nutrient availability here than insurface waters. Subsurface chlorophyll distributions seen inrelation to the different water masses identified in the area,as well as community analysis of the phytoplankton present inthe subsurface peaks, indicate the presence of at least threedistinct subsurface phytoplankton blooms in the Skagerrak duringthe study period. Local oxygen saturation maxima recorded immediatelyabove the subsurface peaks provide in situ evidence that thesepeaks are photosynthetically active. This suggests that newproduction is taking place in these peaks, although quantificationof this production is hampered due to a lack of informationconcerning the initial conditions in and lifetime of the subsurfacepeaks. The subsurface phytoplankton peaks were, generally, foundimmediately above an oxygen minimum that covered the entirestudy area. In the relatively cold deep Atlantic water foundbelow the oxygen minimum layer, no or very little chlorophyllwas recorded and oxygen concentrations increased. Thus, it isargued that the respiration of the organic material producedin the upper part of the water column during late summer mayprimarily occur in the intermediate layers of the water column.     

Cytosolic isocitrate dehydrogenase in humans, mice, and voles and phylogenetic analysis of the enzyme family

In this study, we report cDNA sequences of the cytosolic NADP-dependent isocitrate dehydrogenase for humans, mice, and two species of voles (Microtus mexicanus and Microtus ochrogaster). Inferred amino acid sequences from these taxa display a high level of amino acid sequence conservation, comparable to that of myosin beta heavy chain, and share known structural features. A Caenorhabditis elegans enzyme that was previously identified as a protein similar to isocitrate dehydrogenase is most likely the NADP-dependent cytosolic isocitrate dehydrogenase enzyme equivalent, based on amino acid similarity to mammalian enzymes and phylogenetic analysis. We also suggest that NADP-dependent isocitrate dehydrogenases characterized from alfalfa, soybean, and eucalyptus are most likely cytosolic enzymes. The phylogenetic tree of various isocitrate dehydrogenases from eukaryotic sources revealed that independent gene duplications may have given rise to the cytosolic and mitochondrial forms of NADP-dependent isocitrate dehydrogenase in animals and fungi. There appears to be no statistical support for a hypothesis that the mitochondrial and cytosolic forms of the enzyme are orthologous in these groups. A possible scenario of the evolution of NADP-dependent isocitrate dehydrogenases is proposed.      

TBMap: a taxonomic perspective on the phylogenetic database TreeBASE

Background  

TreeBASE is currently the only available large-scale database of published organismal phylogenies. Its utility is hampered by a lack of taxonomic consistency, both within the database, and with names of organisms in external genomic, specimen, and taxonomic databases. The extent to which the phylogenetic knowledge in TreeBASE becomes integrated with these other sources is limited by this lack of consistency.     

A transferable plasticity region in Campylobacter coli allows isolates of an otherwise non‐glycolytic food‐borne pathogen to catabolize glucose

Thermophilic Campylobacter species colonize the intestine of agricultural and domestic animals commensally but cause severe gastroenteritis in humans. In contrast to other enteropathogenic bacteria, Campylobacter has been considered to be non‐glycolytic, a metabolic property originally used for their taxonomic classification. Contrary to this dogma, we demonstrate that several Campylobacter coli strains are able to utilize glucose as a growth substrate. Isotopologue profiling experiments with ¹³C‐labeled glucose suggested that these strains catabolize glucose via the pentose phosphate and Entner‐Doudoroff (ED) pathways and use glucose efficiently for de novo synthesis of amino acids and cell surface carbohydrates. Whole genome sequencing of glycolytic C. coli isolates identified a genomic island located within a ribosomal RNA gene cluster that encodes for all ED pathway enzymes and a glucose permease. We could show in vitro that a non‐glycolytic C. coli strain could acquire glycolytic activity through natural transformation with chromosomal DNA of C. coli and C. jejuni subsp. doylei strains possessing the ED pathway encoding plasticity region. These results reveal for the first time the ability of a Campylobacter species to catabolize glucose and provide new insights into how genetic macrodiversity through intra‐ and interspecies gene transfer expand the metabolic capacity of this food‐borne pathogen.     

Paenibacillus larvae-Directed Bacteriophage HB10c2 and Its Application in American Foulbrood-Affected Honey Bee Larvae

Paenibacillus larvae is the causative agent of American foulbrood (AFB), the most serious honey bee brood bacterial disease. We isolated and characterized P. larvae-directed bacteriophages and developed criteria for safe phage therapy. Whole-genome analysis of a highly lytic virus of the family Siphoviridae (HB10c2) provided a detailed safety profile and uncovered its lysogenic nature and a putative beta-lactamase-like protein. To rate its antagonistic activity against the pathogens targeted and to specify potentially harmful effects on the bee population and the environment, P. larvae genotypes ERIC I to IV, representatives of the bee gut microbiota, and a broad panel of members of the order Bacillales were analyzed for phage HB10c2-induced lysis. Breeding assays with infected bee larvae revealed that the in vitro phage activity observed was not predictive of the real-life scenario and therapeutic efficacy. On the basis of the disclosed P. larvae-bacteriophage coevolution, we discuss the future prospects of AFB phage therapy.