Segregation analysis of 1,546 prostate cancer families in Finland shows recessive inheritance

Prostate cancer (PCa) is the most frequently diagnosed cancer in men worldwide and is likely to be caused by a number of genes with different modes of inheritance, population frequencies and penetrance. The objective of this study was to assess the familial aggregation of PCa in a sample of 1,546 nuclear families ascertained through an affected father and diagnosed during 1988–1993, from the unique, founder population-based resource of the Finnish Cancer Registry. Segregation analysis was performed for two cohorts of 557 early-onset and 989 late-onset families evaluating residual paternal effects and assuming that age at diagnosis followed a logistic distribution after log-transformation. The results did not support an autosomal dominant inheritance as has been reported in many of the hospital-based prostatectomy series. Instead, it confirmed the existence of hereditary PCa in the Finnish population under a complex model that included a major susceptibility locus with Mendelian recessive inheritance and a significant paternal regressive coefficient that is indicative of a polygenic/multifactorial component. The strengths of our study are the homogenous Finnish population, large epidemiological population-based data, histologically confirmed cancer diagnosis done before the PSA-era in Finland and registry based approach. Our results support the evidence that the inheritance of PCa is controlled by major genes and are in line with the previous linkage studies. Moreover, this is the first time a recessive inheritance is suggested to fit PCa in all data even when divided to early and late-onset cohorts. Sanna Pakkanen and Agnes B Baffoe-Bonnie equally contributed to this work.     

Impairment of proprioception after whiplash injury

Whiplash injury usually occurs in traffic accidents. Persons experienced this injury might have an impairment of proprioception clinically expressed as inability to determine the exact position of their heads. The aim of this study was to examine the loss of proprioception in people who had a whiplash injury. The study included 60 subjects with cervical spine injury, aged 20 to 50 years and 60 healthy volunteers matched by sex and age. The instrument used for cervical spine mobility assessment was the Cervical Measurement System (CMS), which determines the ability of subjects to return their head in the exact position as it was before they turned it 30 degrees left or right. Patients with cervical spine injury showed significant impairment of proprioception in comparison with healthy subjects (P < 0.001). The results support the hypothesis that subject with recent cervical spine injury have incorrect perception of their head position. Therefore, their rehabilitation should include the correction of proprioception and head coordination.     

The distance decay of similarity in ecological communities

Biological similartiy typically decreases with geographical distance. Despite the recent attention to the distance decay relationship, there is no consensus on how the relationship varies across organism groups, geographic gradients and environments. We first conducted a quantitative meta-analysis of 401 distance decay relationships across a wide range of organisms, ecosystems and geographical gradients, and then united the effects of categorical and continuous variables on the rate of distance decay using a general linear model (GLM). As effect sizes we used the similarity at one km distance (initial similarity) and the distance that halves the similarity from its value at one km distance (halving distance). Both the initial similarity and halving distance were significantly affected by variables characterizing the spatial scale, organism properties, study region and ecosystem concerned. The patterns appear robust as the results of meta-analysis and GLM only differed in marginal details. According to GLM with Akaike's information criterion, the most parsimonious models explained 55.3 and 37.6% of variance in initial similarity and halving distance, respectively. Across large scales, similarity was decreasing slightly faster at high latitudes than at low latitudes, while small-scale turnover was higher at low latitudes. We also found significant differences in initial similarity among the realms, with terrestrial systems showing higher small-scale beta diversity. The decrease in community similarity at large scales was higher among organisms that are actively mobile than among passively dispersed organisms. We conclude that regression of similarity against distance unites several ecological phenomena such as dispersal propensity and environmental structuring, and provides an effective approach for gauging the spatial turnover across sites. We also found that the patterns in beta-diversity are highly scale-dependent.     

Haloarchaeal communities in the crystallizers of two adriatic solar salterns

Solar salterns operate only for short dry periods of the year in the north shore of the Adriatic Sea because of its relatively humid and cold Mediterranean climate. In a previous paper, we showed that the NaCl precipitation ponds (crystallizers) of Northern Adriatic Secovlje salterns have different haloarchaeal populations from those typically found in dry and hot climates such as Southern Spain. To check whether there is a common pattern of haloarchaeal diversity in these less extreme conditions, diversity in crystallizers of other Adriatic solar salterns in Ston, Croatia was ascertained by molecular and culture methods. In addition, the cultivation approach was used to further describe haloarchaeal diversity in both salterns. Over the period of two solar salt collection seasons, isolates related to species of the genera Haloferax, Haloarcula, and Haloterrigena were recovered from both salterns. Within the same sampling effort, relatives of the genus Halorubrum and a Natrinema-like isolate were cultivated from Slovenian Secovlje salterns while Halobacterium related isolates were obtained from the Croatian Ston salterns. Concurrent with our previous findings, a library of Croatian saltern crystallizer PCR-amplified 16S rRNA genes was dominated by sequences related to the genus Halorubrum. The microbial community structure was similar in both salterns but diversity indices showed greater values in Slovenian salterns when compared with Croatian salterns.     

New insights into the distribution of alien cyanobacterium Chrysosporum bergii (Nostocales,Cyanobacteria)

Invasive and alien cyanobacteria are considered as a serious threat to aquatic ecosystems due to their ability to produce cyanotoxins and outcompeting native species. Among cyanobacteria, Nostocales is a group with strong competitive advantages including the production of resting cells, ability to fix nitrogen or high affinity to phosphorus. A species Chrysosporum bergii has broadened its original distribution from brackish and seawater habitats of Caspian and Aral Seas to northern regions of Europe. The aim of our study was to expand the knowledge on the distribution of C. bergii, its preferred habitats in the invaded areas and examine whether the biomass of C. bergii is related with biomass of other alien or native cyanobacteria. We examined the phytoplankton community composition and the abiotic factors in randomly selected lakes of western Poland. For the first time, we showed that it occurs widely in lakes of this region. However, it occurred in one third of the investigated lakes and its contribution to total phytoplankton biomass was low. It occurred more frequently in shallow lakes with low conductivity and dissolved phosphorus, yet with higher total phosphorus concentration. The most remarkable finding was a negative relationship of C. bergii biomass with the biomass of native A. gracile, but a positive relationship with an invasive cyanobacterium C. raciborskii. This result suggests that these alien species occur under similar environmental conditions in Polish lakes. Moreover, the morphological features of C. bergii in Poland were similar to those of Anabaena bergii var. limnetica Couté et Preisig from Lithuania and Anabaena bergii from Czech Republic.     

Lipoprotein subclass metabolism in nonalcoholic steatohepatitis

Nonalcoholic steatohepatitis (NASH) is associated with increased synthesis of triglycerides and cholesterol coupled with increased VLDL synthesis in the liver. In addition, increased cholesterol content in the liver associates with NASH. Here we study the association of lipoprotein subclass metabolism with NASH. To this aim, liver biopsies from 116 morbidly obese individuals [age 47.3 ± 8.7 (mean ± SD) years, BMI 45.1 ± 6.1 kg/m², 39 men and 77 women] were used for histological assessment. Proton NMR spectroscopy was used to measure lipid concentrations of 14 lipoprotein subclasses in native serum samples at baseline and after obesity surgery. We observed that total lipid concentration of VLDL and LDL subclasses, but not HDL subclasses, associated with NASH [false discovery rate (FDR) < 0.1]. More specifically, total lipid and cholesterol concentration of VLDL and LDL subclasses associated with inflammation, fibrosis, and cell injury (FDR < 0.1), independent of steatosis. Cholesterol concentration of all VLDL subclasses also correlated with total and free cholesterol content in the liver. All NASH-related changes in lipoprotein subclasses were reversed by obesity surgery. High total lipid and cholesterol concentration of serum VLDL and LDL subclasses are linked to cholesterol accumulation in the liver and to liver cell injury in NASH.     

Hc-daf-2 encodes an insulin-like receptor kinase in the barber’s pole worm, Haemonchus contortus, and restores partial dauer regulation

Infective L3s (iL3s) of parasitic nematodes share common behavioural, morphological and developmental characteristics with the developmentally arrested (dauer) larvae of the free-living nematode Caenorhabditis elegans. It is proposed that similar molecular mechanisms regulate entry into or exit from the dauer stage in C. elegans, and the transition from free-living to parasitic forms of parasitic nematodes. In C. elegans, one of the key factors regulating the dauer transition is the insulin-like receptor (designated Ce-DAF-2) encoded by the gene Ce-daf-2. However, nothing is known about DAF-2 homologues in most parasitic nematodes. Here, using a PCR-based approach, we identified and characterised a gene (Hc-daf-2) and its inferred product (Hc-DAF-2) in Haemonchus contortus (a socioeconomically important parasitic nematode of ruminants). The sequence of Hc-DAF-2 displays significant sequence homology to insulin receptors (IR) in both vertebrates and invertebrates, and contains conserved structural domains. A sequence encoding an important proteolytic motif (RKRR) identified in the predicted peptide sequence of Hc-DAF-2 is consistent with that of the human IR, suggesting that it is involved in the formation of the IR complex. The Hc-daf-2 gene was transcribed in all life stages of H. contortus, with a significant up-regulation in the iL3 compared with other stages. To compare patterns of expression between Hc-daf-2 and Ce-daf-2, reporter constructs fusing the Ce-daf-2 or Hc-daf-2 promoter to sequence encoding GFP were microinjected into the N2 strain of C. elegans, and transgenic lines were established and examined. Both genes showed similar patterns of expression in amphidial (head) neurons, which relate to sensation and signal transduction. Further study by heterologous genetic complementation in a daf-2-deficient strain of C. elegans (CB1370) showed partial rescue of function by Hc-daf-2. Taken together, these findings provide a first insight into the roles of Hc-daf-2/Hc-DAF-2 in the biology and development of H. contortus, particularly in the transition to parasitism.     

Novel Loci for metabolic networks and multi-tissue expression studies reveal genes for atherosclerosis

Association testing of multiple correlated phenotypes offers better power than univariate analysis of single traits. We analyzed 6,600 individuals from two population-based cohorts with both genome-wide SNP data and serum metabolomic profiles. From the observed correlation structure of 130 metabolites measured by nuclear magnetic resonance, we identified 11 metabolic networks and performed a multivariate genome-wide association analysis. We identified 34 genomic loci at genome-wide significance, of which 7 are novel. In comparison to univariate tests, multivariate association analysis identified nearly twice as many significant associations in total. Multi-tissue gene expression studies identified variants in our top loci, SERPINA1 and AQP9, as eQTLs and showed that SERPINA1 and AQP9 expression in human blood was associated with metabolites from their corresponding metabolic networks. Finally, liver expression of AQP9 was associated with atherosclerotic lesion area in mice, and in human arterial tissue both SERPINA1 and AQP9 were shown to be upregulated (6.3-fold and 4.6-fold, respectively) in atherosclerotic plaques. Our study illustrates the power of multi-phenotype GWAS and highlights candidate genes for atherosclerosis.     

Transmembrane collagen XVII is a novel component of the glomerular filtration barrier

The kidney filtration barrier consists of the capillary endothelium, the glomerular basement membrane and the slit diaphragm localized between foot processes of neighbouring podocytes. We report that collagen XVII, a transmembrane molecule known to be required for epithelial adhesion, is expressed in podocytes of normal human and mouse kidneys and in endothelial cells of the glomerular filtration barrier. Immunoelectron microscopy has revealed that collagen XVII is localized in foot processes of podocytes and in the glomerular basement membrane. Its role in kidney has been analysed in knockout mice, which survive to birth but have high neonatal mortality and skin blistering and structural abnormalities in their glomeruli. Morphometric analysis has shown increases in glomerular volume fraction and surface densities of knockout kidneys, indicating an increased glomerular amount in the cortex. Collagen XVII deficiency causes effacement of podocyte foot processes; however, major slit diaphragm disruptions have not been detected. The glomerular basement membrane is split in areas in which glomerular and endothelial basement membranes meet. Differences in the expression of collagen IV, integrins α3 or β1, laminin α5 and nephrin have not been observed in mutant mice compared with controls. We propose that collagen XVII has a function in the attachment of podocyte foot processes to the glomerular basement membrane. It probably contributes to podocyte maturation and might have a role in glomerular filtration.