Mitochondrial gene order is not conserved in arthropods: prostriate and metastriate tick mitochondrial genomes

The entire mitochondrial genome was sequenced in a prostriate tick, Ixodes hexagonus, and a metastriate tick, Rhipicephalus sanguineus. Both genomes encode 22 tRNAs, 13 proteins, and two ribosomal RNAs. Prostriate ticks are basal members of Ixodidae and have the same gene order as Limulus polyphemus. In contrast, in R. sanguineus, a block of genes encoding NADH dehydrogenase subunit 1 (ND1), tRNA(Leu)(UUR), tRNA(Leu)(CUN), 16S rDNA, tRNA(Val), 12S rDNA, the control region, and the tRNA(Ile) and tRNA(Gln) have translocated to a position between the tRNA(Glu) and tRNA(Phe) genes. The tRNA(Cys) gene has translocated between the control region and the tRNA(Met) gene, and the tRNA(Leu)(CUN) gene has translocated between the tRNA(Ser)(UCN) gene and the control region. Furthermore, the control region is duplicated, and both copies undergo concerted evolution. Primers that flank these rearrangements confirm that this gene order is conserved in all metastriate ticks examined. Correspondence analysis of amino acid and codon use in the two ticks and in nine other arthropod mitochondrial genomes indicate a strong bias in R. sanguineus towards amino acids encoded by AT-rich codons.      

Nucleotide polymorphism at the alcohol dehydrogenase locus of pocket gophers, genus Geomys

Using the strictly neutral model as a null hypothesis, we tested for deviations from expected levels of nucleotide polymorphism at the alcohol dehydrogenase locus (Adh-1) within and among four species of pocket gophers (Geomys bursarius major, G. knoxjonesi, G. texensis llanensis, and G. attwateri). The complete protein-encoding region was examined, and 10 unique alleles, representing both electromorphic and cryptic alleles, were used to test hypotheses (e.g., the neutral model) concerning the maintenance of genetic variation. Nineteen variable sites were identified among the 10 alleles examined, including 9 segregating sites occurring in synonymous positions and 10 that were nonsynonymous. Several statistical methods, including those that test for within-species variation as well as those that examine variation within and among species, failed to reject the null hypothesis that variation (both within and between species of Geomys) at the Adh locus is consistent with the neutral theory. However, there was significant heterogeneity in the ratio of polymorphism to divergence across the gene, with polymorphisms clustered in the first half of the coding region and fixed differences clustered in the second half of the gene. Two alternative hypotheses are discussed as possible explanations for this heterogeneity: an old balanced polymorphism in the first half of the gene or a recent selective sweep in the second half of the gene.      

Characterization of GP21 and GP12: Two Potential Probiotic Bacteria Isolated from the Gastrointestinal Tract of Atlantic Cod

This study evaluated the probiotic potential of GP21 (Pseudomonas sp.) and GP12 (Psychrobacter sp.), two bacteria isolated from the intestinal tract of a cold-water fish, Atlantic cod. The antagonistic activity of the two intestinal bacteria against two fish pathogens (Vibrio anguillarum and Aeromonas salmonicida subsp. salmonicida) was studied under different physical conditions. Further, their resistance to physiological barriers and their ability to form biofilms were examined. In addition, a test was conducted to confirm that the isolates were not pathogenic to the host fish. The two bacteria exhibited differences in their antagonism to the pathogens. Both were active against V. anguillarum at mildly acidic conditions over a 5-day period. The activity of GP21 against A. salmonicida was greater at pH 7–8. The maximum antagonistic activity was observed at a temperature of 15°C and at a salt concentration of 15 ppt for both the isolates. They did not produce acids, could release siderophores and tolerated both the acidic environment and the bile salts. Their ability to form biofilms was high around 15°C and when iron was supplemented in the medium at 5 μmol l^?1. There was no mortality of fish during the pathogenicity experiment, confirming the safety of both isolates for further applications. Considering the favorable characteristics identified here, it could be concluded that GP21 and GP12 isolated from the gastrointestinal tract of Atlantic cod are potential probiotic candidates.     

Salivary gland NK cells are phenotypically and functionally unique

Natural killer (NK) cells and CD8(+) T cells play vital roles in containing and eliminating systemic cytomegalovirus (CMV). However, CMV has a tropism for the salivary gland acinar epithelial cells and persists in this organ for several weeks after primary infection. Here we characterize a distinct NK cell population that resides in the salivary gland, uncommon to any described to date, expressing both mature and immature NK cell markers. Using RORγt reporter mice and nude mice, we also show that the salivary gland NK cells are not lymphoid tissue inducer NK-like cells and are not thymic derived. During the course of murine cytomegalovirus (MCMV) infection, we found that salivary gland NK cells detect the infection and acquire activation markers, but have limited capacity to produce IFN-γ and degranulate. Salivary gland NK cell effector functions are not regulated by iNKT or T(reg) cells, which are mostly absent in the salivary gland. Additionally, we demonstrate that peripheral NK cells are not recruited to this organ even after the systemic infection has been controlled. Altogether, these results indicate that viral persistence and latency in the salivary glands may be due in part to the presence of unfit NK cells and the lack of recruitment of peripheral NK cells.     

GAB2 alleles modify Alzheimer's risk in APOE epsilon4 carriers

The apolipoprotein E (APOE) epsilon4 allele is the best established genetic risk factor for late-onset Alzheimer's disease (LOAD). We conducted genome-wide surveys of 502,627 single-nucleotide polymorphisms (SNPs) to characterize and confirm other LOAD susceptibility genes. In epsilon4 carriers from neuropathologically verified discovery, neuropathologically verified replication, and clinically characterized replication cohorts of 1411 cases and controls, LOAD was associated with six SNPs from the GRB-associated binding protein 2 (GAB2) gene and a common haplotype encompassing the entire GAB2 gene. SNP rs2373115 (p = 9 x 10(-11)) was associated with an odds ratio of 4.06 (confidence interval 2.81-14.69), which interacts with APOE epsilon4 to further modify risk. GAB2 was overexpressed in pathologically vulnerable neurons; the Gab2 protein was detected in neurons, tangle-bearing neurons, and dystrophic neuritis; and interference with GAB2 gene expression increased tau phosphorylation. Our findings suggest that GAB2 modifies LOAD risk in APOE epsilon4 carriers and influences Alzheimer's neuropathology.     

Hypoxia recruits intrapulmonary arteriovenous pathways in intact rats but not isolated rat lungs

Intrapulmonary arteriovenous anastomoses (IPAVS) directly connect the arterial and venous circulations in the lung, bypassing the capillary network. Here, we used solid, latex microspheres and isolated rat lung and intact, spontaneously breathing rat models to test the hypothesis that IPAVS are recruited by alveolar hypoxia. We found that hypoxia recruits IPAVS in the intact rat, but not the isolated lung. IPAVS are at least 70 μm in the rat and, interestingly, appear to be recruited when the mixed venous Po(2) falls below 22 mmHg. These data provide evidence that large-diameter, direct arteriovenous connections exist in the lung and are recruitable by hypoxia in the intact animal.     

Evolution of Synthyris sect. Dissecta (Plantaginaceae) on sky islands in the Northern Rocky Mountains

We examined the phylogeography of Synthyris sect. Dissecta (Plantaginaceae), which is restricted to the Olympic (S. lanuginosa) and Northern Rocky Mountains (S. dissecta and S. canbyi), to infer effects of sky islands and modes of speciation. Sequences of cpDNA trnT-trnL and psbA-trnH intergenic spacers resolved 22 haplotypes among 185 individuals sampled from 16 populations of the three species. Gene flow in the ancestral lineage and random capture of haplotypes in species lineages of sect. Dissecta have resulted in haplotype clades that are not exclusive to species. Nested clade analysis (NCA) indicates that allopatric fragmentation separated Olympic and Northern Rocky Mountain populations, giving rise to the Olympic endemic S. lanuginosa, which is characterized by unique haplotypes consistent with long temporal isolation. Low haplotype and nucleotide diversity in S. canbyi are consistent with newly founded populations experiencing a bottleneck. Furthermore, we infer S. canbyi evolved as a peripheral isolate of S. dissecta. NCA indicated limited migration in S. dissecta with possible isolation by distance. Both isolation on interglacial sky islands and valley glaciers during at least the last glaciation limited gene flow among populations of S. dissecta in different ranges of the Northern Rocky Mountains.     

NK Cell–Like Behavior of Vα14i NK T Cells during MCMV Infection

Immunity to the murine cytomegalovirus (MCMV) is critically dependent on the innate response for initial containment of viral replication, resolution of active infection, and proper induction of the adaptive phase of the anti-viral response. In contrast to NK cells, the Vα14 invariant natural killer T cell response to MCMV has not been examined. We found that Vα14i NK T cells become activated and produce significant levels of IFN-γ, but do not proliferate or produce IL-4 following MCMV infection. In vivo treatment with an anti-CD1d mAb and adoptive transfer of Vα14i NK T cells into MCMV-infected CD1d^−/− mice demonstrate that CD1d is dispensable for Vα14i NK T cell activation. In contrast, both IFN-α/β and IL-12 are required for optimal activation. Vα14i NK T cell–derived IFN-γ is partially dependent on IFN-α/β but highly dependent on IL-12. Vα14i NK T cells contribute to the immune response to MCMV and amplify NK cell–derived IFN-γ. Importantly, mortality is increased in CD1d^−/− mice in response to high dose MCMV infection when compared to heterozygote littermate controls. Collectively, these findings illustrate the plasticity of Vα14i NK T cells that act as effector T cells during bacterial infection, but have NK cell–like behavior during the innate immune response to MCMV infection.