A genome-wide scan of Ashkenazi Jewish Crohn's disease suggests novel susceptibility loci

Crohn''s disease (CD) is a complex disorder resulting from the interaction of intestinal microbiota with the host immune system in genetically susceptible individuals. The largest meta-analysis of genome-wide association to date identified 71 CD–susceptibility loci in individuals of European ancestry. An important epidemiological feature of CD is that it is 2–4 times more prevalent among individuals of Ashkenazi Jewish (AJ) descent compared to non-Jewish Europeans (NJ). To explore genetic variation associated with CD in AJs, we conducted a genome-wide association study (GWAS) by combining raw genotype data across 10 AJ cohorts consisting of 907 cases and 2,345 controls in the discovery stage, followed up by a replication study in 971 cases and 2,124 controls. We confirmed genome-wide significant associations of 9 known CD loci in AJs and replicated 3 additional loci with strong signal (p<5×10⁻⁶). Novel signals detected among AJs were mapped to chromosomes 5q21.1 (rs7705924, combined p = 2×10⁻⁸; combined odds ratio OR = 1.48), 2p15 (rs6545946, p = 7×10⁻⁹; OR = 1.16), 8q21.11 (rs12677663, p = 2×10⁻⁸; OR = 1.15), 10q26.3 (rs10734105, p = 3×10⁻⁸; OR = 1.27), and 11q12.1 (rs11229030, p = 8×10⁻⁹; OR = 1.15), implicating biologically plausible candidate genes, including RPL7, CPAMD8, PRG2, and PRG3. In all, the 16 replicated and newly discovered loci, in addition to the three coding NOD2 variants, accounted for 11.2% of the total genetic variance for CD risk in the AJ population. This study demonstrates the complementary value of genetic studies in the Ashkenazim.     

A stochastic model for survival of early prostate cancer with adjustments for leadtime, length bias, and over-detection

To compare the survival between screen-detected and clinically detected cancers, we applied a series of non-homogeneous stochastic processes to deal with leadtime, length bias, and over-detection by using full information on detection modes obtained from the Finnish randomized controlled trial for prostate cancer screening. The results show after 9-year follow-up the hazard ratio of prostate cancer death for screen-detected cases against clinically detected cases increased from 0.24 (95% CI: 0.16-0.35) without correction for these biases, to 0.76 after correction for leadtime and length biases, and finally to 1.03 (95% CI: 0.79-1.33) for a further adjustment for over-detection. Adjustment for leadtime and length bias but no over-detection led to a 24% reduction in prostate cancer death as a result of prostate-specific antigen test. The further calibration of over-detection indicates no gain in survival of screen-detected prostate cancers (excluding over-detected case as stayer considered in the mover-stayer model) as compared with the control group in the absence of screening that is considered as the mover. However, whether the model assumption on over-detection is robust should be validated with other data sets and longer follow-up.     

A rare sugar xylitol. Part II: biotechnological production and future applications of xylitol

Xylitol is the first rare sugar that has global markets. It has beneficial health properties and represents an alternative to current conventional sweeteners. Industrially, xylitol is produced by chemical hydrogenation of d-xylose into xylitol. The biotechnological method of producing xylitol by metabolically engineered yeasts, Saccharomyces cerevisiae or Candida, has been studied as an alternative to the chemical method. Due to the industrial scale of production, xylitol serves as an inexpensive starting material for the production of other rare sugars. The second part of this mini-review on xylitol will look more closely at the biotechnological production and future applications of the rare sugar, xylitol.     

Common genetic variants and modification of penetrance of BRCA2-associated breast cancer

The considerable uncertainty regarding cancer risks associated with inherited mutations of BRCA2 is due to unknown factors. To investigate whether common genetic variants modify penetrance for BRCA2 mutation carriers, we undertook a two-staged genome-wide association study in BRCA2 mutation carriers. In stage 1 using the Affymetrix 6.0 platform, 592,163 filtered SNPs genotyped were available on 899 young (<40 years) affected and 804 unaffected carriers of European ancestry. Associations were evaluated using a survival-based score test adjusted for familial correlations and stratified by country of the study and BRCA2*6174delT mutation status. The genomic inflation factor (λ) was 1.011. The stage 1 association analysis revealed multiple variants associated with breast cancer risk: 3 SNPs had p-values<10(-5) and 39 SNPs had p-values<10(-4). These variants included several previously associated with sporadic breast cancer risk and two novel loci on chromosome 20 (rs311499) and chromosome 10 (rs16917302). The chromosome 10 locus was in ZNF365, which contains another variant that has recently been associated with breast cancer in an independent study of unselected cases. In stage 2, the top 85 loci from stage 1 were genotyped in 1,264 cases and 1,222 controls. Hazard ratios (HR) and 95% confidence intervals (CI) for stage 1 and 2 were combined and estimated using a retrospective likelihood approach, stratified by country of residence and the most common mutation, BRCA2*6174delT. The combined per allele HR of the minor allele for the novel loci rs16917302 was 0.75 (95% CI 0.66-0.86, ) and for rs311499 was 0.72 (95% CI 0.61-0.85, ). FGFR2 rs2981575 had the strongest association with breast cancer risk (per allele HR = 1.28, 95% CI 1.18-1.39, ). These results indicate that SNPs that modify BRCA2 penetrance identified by an agnostic approach thus far are limited to variants that also modify risk of sporadic BRCA2 wild-type breast cancer.     

Bloom forming Alexandrium ostenfeldii (Dinophyceae) in shallow waters of the Åland Archipelago,Northern Baltic Sea

In the past years, late summer blooms of the bioluminescent dinoflagellate Alexandrium ostenfeldii have become a recurrent phenomenon in coastal waters of the central and Northern Baltic Sea. This paper reports exceptionally high cell concentrations (10⁵ to 10⁶ cells L^?1) of the species found during bioluminescent blooms in 2003 and 2004 in a shallow embayment of the Åland archipelago at the SW coast of Finland. Clonal cultures were established for morphological, molecular, toxicological and ecophysiological investigations to characterize the Finnish populations and compare them to other global A. ostenfeldii isolates. The Finnish isolates exhibited typical morphological features of A. ostenfeldii such as large size, a prominent ventral pore and an orthogonally bent first apical plate. However, unambiguous differentiation from closely related Alexandrium peruvianum was difficult due to considerable variation of sulcal anterior plate shapes. The Finnish strains were genetically distinct from other isolates of the species, but phylogenetic analyses revealed a close relationship to isolates from southern England and an A. peruvianum morphotype from the Spanish Mediterranean. Together these isolates formed a distinct clade which was separated from a clade containing other Northern European, North American and New Zealand populations. Toxin analyses confirmed the presence of the PSP toxins GTX2, GTX3 and STX in both Finnish isolates with GTX3 being the dominant toxin. Total relative PSP toxin contents were moderate, ranging from approximately 6 to 15 fmol cell^?1 at local salinities of 5 and 10 psu, respectively. Spirolides were not detected. Salinity tolerance experiments showed that the Finnish isolates were well adapted to grow at the low salinities of the Baltic Sea. With a salinity range of approximately 6 to 20–25 psu, Baltic populations are physiologically distinct from their marine relatives. Vigorous production of different cyst types in the cultures suggest that cysts may play a crucial role in the survival and retainment of A. ostenfeldii populations in the Baltic Sea.     

Early succession of bacterial biofilms in paper machines

Formation of biofilms causes severe problems in paper machines, and hence financial costs. It would be preferable to prevent attachment of the primary-colonizing bacteria than to control the growth of secondary communities, which are sheltered by exopolysaccharide slime layers. We have therefore investigated the early succession of paper-machine biofilms by incubating stainless-steel test coupons in the process water-flow lines in two paper machines operating in slightly alkaline conditions in temperatures (45 and 49°C) supporting thermophilic microbes. Microbial succession was profiled using length heterogeneity analysis of PCR-amplified 16S rRNA genes (LH-PCR) and linking the sequence data of the created 16S rRNA gene libraries to the dominant LH-PCR peaks. Although the bacterial fingerprints obtained from the attached surface communities varied slightly in different samples, the biomarker signals of the dominating primary-colonizing bacterial groups remained high over time in each paper machine. Most of the 16S rRNA gene copies in the early biofilms were assigned to the genera Rhodobacter, Tepidimonas, and Cloacibacterium. The dominance of these sequence types decreased in the developing biofilms. Finally, as phylogenetically identical primary-colonizers were detected in the two different paper mills, the machines evidently had similar environmental conditions for bacterial growth and potentially a common source of contamination.     

Effects of a hydropower plant on Coleopteran diversity and abundance in the Udzungwa Mountains, Tanzania

The effects of river flow diversion on biodiversity were assessed using Coleoptera as an indicator group in three habitats of the Kihansi Gorge (Udzungwa Mountains, Tanzania), before and after commissioning of a hydropower plant. Data collected using sweep netting and pitfall traps showed that the effect of diversion of the river flow was site-specific, affecting particularly the spray habitat. Rarefaction analysis of both sweep netting and pitfall samples indicated that the expected richness of Coleoptera declined significantly in all habitats after commissioning of the power plant. Sweep netting and pitfall samples showed that the highest Shannon–Wiener diversity index value before the diversion of the river flow was in the spray zone, but the index value decreased after diversion. Changes in the other two habitats were less prominent. Analysis of variance using diversity index values from five pitfall samples in each habitat type before and after commissioning indicated that there were no statistically significant differences in the diversity index between the two sampling periods or among the three habitat types. Renkonen's similarity index between habitats showed that pitfall samples had higher similarity (87%) than did samples from sweep netting (69%). It is suggested that for mitigation purposes, artificial spray systems, which have been installed in other wetlands of the Kihansi Gorge, also be installed to cover the whole Lower Wetland in which this study was undertaken. In order to maintain overall biodiversity in the Kihansi Gorge, it is suggested that the ecosystem conservation approach be prioritised.     

Effects of electromagnetic field emitted by cellular phones on the EEG during an auditory memory task: a double blind replication study

The effects of electromagnetic fields (EMF) emitted by cellular phones on the event related desynchronization/synchronization (ERD/ERS) of the 4-6, 6-8, 8-10, and 10-12 Hz electroencephalogram (EEG) frequency bands were studied in 24 normal subjects performing an auditory memory task. This study was a systematic replication of our previous work. In the present double blind study, all subjects performed the memory task both with and without exposure to a digital 902 MHz field in a counterbalanced order. We were not able to replicate the findings from our earlier study. All eight of the significant changes in our earlier study were not significant in the present double blind replication. Also, the effect of EMF on the number of incorrect answers in the memory task was inconsistent. We previously reported no significant effect of EMF exposure on the number of incorrect answers in the memory task, but a significant increase in errors was observed in the present study. We conclude that EMF effects on the EEG and on the performance on memory tasks may be variable and not easily replicable for unknown reasons.