Identification of bacteria infecting Ixodes ricinus ticks by 16S rDNA amplification and denaturing gradient gel electrophoresis

Ticks harbor a complex microbial population, which they acquire while feeding on a variety of mammalians and birds. Zoonotic diseases transferred by ticks are an increasing problem and have become a burden to the community. 16S rDNA amplification and denaturing gradient gel electrophoresis (DGGE) enables detection of the broad spectrum of bacteria that settles in the ticks. Profiling the complete microbial population in ticks may provide a better understanding of the ticks' potential to harbor and disperse pathogens. Separation of pathogenic species by DGGE is based on variation in %GC content within the 16S rDNA genetic region. Sequencing of these fragments allows identification of bacterial species. Present study identified some well-known tick-infecting bacteria, such as members of genus Borrelia, Rickettsiales, and Pseudomonas, but also less described tick-infecting bacteria such as Rhodococcus erythropolis, Spiroplasma spp., and an endosymbiont of the microarthropod Folsomia candida. This is the first report of Segniliparus rugosus-infected Ixodes ricinus ticks. Also, it is the first report of several of these pathogens in the Norwegian tick population.     

A genome-wide association study identifies novel loci associated with circulating IGF-I and IGFBP-3

Insulin-like growth factor-I (IGF-I) and insulin-like growth factor-binding protein-3 (IGFBP-3) are involved in cell replication, proliferation, differentiation, protein synthesis, carbohydrate homeostasis and bone metabolism. Circulating IGF-I and IGFBP-3 concentrations predict anthropometric traits and risk of cancer and cardiovascular disease. In a genome-wide association study of 10 280 middle-aged and older men and women from four community-based cohort studies, we confirmed a known association of single nucleotide polymorphisms in the IGFBP3 gene region on chromosome 7p12.3 with IGFBP-3 concentrations using a significance threshold of P < 5 × 10(-8) (P = 3.3 × 10(-101)). Furthermore, the same IGFBP3 gene locus (e.g. rs11977526) that was associated with IGFBP-3 concentrations was also associated with the opposite direction of effect, with IGF-I concentration after adjustment for IGFBP-3 concentration (P = 1.9 × 10(-26)). A novel and independent locus on chromosome 7p12.3 (rs700752) had genome-wide significant associations with higher IGFBP-3 (P = 4.4 × 10(-21)) and higher IGF-I (P = 4.9 × 10(-9)) concentrations; when the two measurements were adjusted for one another, the IGF-I association was attenuated but the IGFBP-3 association was not. Two additional loci demonstrated genome-wide significant associations with IGFBP-3 concentration (rs1065656, chromosome 16p13.3, P = 1.2 × 10(-11), IGFALS, a confirmatory finding; and rs4234798, chromosome 4p16.1, P = 4.5 × 10(-10), SORCS2, a novel finding). Together, the four genome-wide significant loci explained 6.5% of the population variation in IGFBP-3 concentration. Furthermore, we observed a borderline statistically significant association between IGF-I concentration and FOXO3 (rs2153960, chromosome 6q21, P = 5.1 × 10(-7)), a locus associated with longevity. These genetic loci deserve further investigation to elucidate the biological basis for the observed associations and clarify their possible role in IGF-mediated regulation of cell growth and metabolism.     

Treatment of sleep apnoea using a mandibular advancement splint - an open prospective study

Obstructive sleep apnoea (OSA) may cause considerable disturbances, including the development of health problems. This study was performed in order to evaluate the results of treating OAS with a mandibular advancement splint (MAS), and to evaluate the effects of this treatment. This was a prospective open longitudinal study. Ninety patients were randomly selected and included in the study. All 90 patients received an MAS. Forty-eight patients concluded the study, whereas 27 dropped-out and 15 were excluded. The sleep pattern was monitored at home with portable equipment. There was a clear tendency towards a reduction in the apnoea/hypopnea index (AHI) and the oxygen desaturation index (ODI) between the two investigations. Furthermore, there was a tendency towards reduced sleep apnoea; ratings on the Epworth sleepiness scale were lower, indicating a reduction in daytime sleepiness. Treatment with MAS in our study reduced sleep apnoea and snoring, and lowered the values of the Epworth sleepiness scale, indicating a reduction in daytime sleepiness in the majority of the patients. Lifestyle factors are not believed to have affected the results.     

Genetic associations with lipoprotein subfractions provide information on their biological nature

Adverse levels of lipoproteins are highly heritable and constitute risk factors for cardiovascular outcomes. Hitherto, genome-wide association studies revealed 95 lipid-associated loci. However, due to the small effect sizes of these associations large sample numbers (>100 000 samples) were needed. Here we show that analyzing more refined lipid phenotypes, namely lipoprotein subfractions, can increase the number of significantly associated loci compared with bulk high-density lipoprotein and low-density lipoprotein analysis in a study with identical sample numbers. Moreover, lipoprotein subfractions provide novel insight into the human lipid metabolism. We measured 15 lipoprotein subfractions (L1-L15) in 1791 samples using (1)H-NMR (nuclear magnetic resonance) spectroscopy. Using cluster analyses, we quantified inter-relationships among lipoprotein subfractions. Additionally, we analyzed associations with subfractions at known lipid loci. We identified five distinct groups of subfractions: one (L1) was only marginally captured by serum lipids and therefore extends our knowledge of lipoprotein biochemistry. During a lipid-tolerance test, L1 lost its special position. In the association analysis, we found that eight loci (LIPC, CETP, PLTP, FADS1-2-3, SORT1, GCKR, APOB, APOA1) were associated with the subfractions, whereas only four loci (CETP, SORT1, GCKR, APOA1) were associated with serum lipids. For LIPC, we observed a 10-fold increase in the variance explained by our regression models. In conclusion, NMR-based fine mapping of lipoprotein subfractions provides novel information on their biological nature and strengthens the associations with genetic loci. Future clinical studies are now needed to investigate their biomedical relevance.