Profile of common prostate cancer risk variants in an unscreened Romanian population

To find sequence variants affecting prostate cancer (PCA) susceptibility in an unscreened Romanian population we use a genome‐wide association study (GWAS). The study population included 990 unrelated pathologically confirmed PCA cases and 1034 male controls. DNA was genotyped using Illumina SNP arrays, and 24.295.558 variants were imputed using the 1000 Genomes data set. An association test was performed between the imputed markers and PCA. A systematic literature review for variants associated with PCA risk identified 115 unique variants that were tested in the Romanian sample set. Thirty of the previously reported SNPs replicated (P‐value < 0.05), with the strongest associations observed at: 8q24.21, 11q13.3, 6q25.3, 5p15.33, 22q13.2, 17q12 and 3q13.2. The replicated variants showing the most significant association in Romania are rs1016343 at 8q24.21 (P = 2.2 × 10^?4), rs7929962 at 11q13.3 (P = 2.7 × 10^?4) and rs9364554 at 6q25.2 (P = 4.7 × 10^?4). None of the variants tested in the Romanian GWAS reached genome‐wide significance (P‐value <5 × 10^?8) but 807 markers had P‐values <1 × 10^?4. Here, we report the results of the first GWAS of PCA performed in a Romanian population. Our study provides evidence that a substantial fraction of previously validated PCA variants associate with risk in this unscreened Romanian population.     

X-ray crystal structure of Vibrio alkaline phosphatase with the non-competitive inhibitor cyclohexylamine

BackgroundPara-nitrophenyl phosphate, the common substrate for alkaline phosphatase (AP), is available as a cyclohexylamine salt. Here, we report that cyclohexylamine is a non-competitive inhibitor of APs.MethodsCyclohexylamine inhibited four different APs. Co-crystallization with the cold-active Vibrio AP (VAP) was performed and the structure solved.ResultsInhibition of VAP fitted a non-competitive kinetic model (K_m unchanged, V_max reduced) with IC₅₀ 45.3 mM at the pH optimum 9.8, not sensitive to 0.5 M NaCl, and IC₅₀ 27.9 mM at pH 8.0, where the addition of 0.5 M NaCl altered the inhibition to the level observed at pH 9.8. APs from E. coli and calf intestines were less sensitive to cyclohexylamine, whereas an Antarctic bacterial AP was similar to VAP in this respect. X-ray crystallography at 2.3 Å showed two binding sites, one in the active site channel and another at the surface close to dimer interface. Antarctic bacterial AP and VAP have Trp274 in common in their active-sites, that takes part in binding cyclohexylamine. VAP variants W274A, W274K, and W274H gave IC₅₀ values of 179 mM, 188 mM and 187 mM, respectively, at pH 9.8.ConclusionsThe binding of cyclohexylamine in locations at the dimeric interface and/or in the active site of APs may delay product release or reduce the rate of catalytic step(s) involving conformational changes and intersubunit communications.General significanceCyclohexylamine is a common chemical in industries and used as a counterion in substrates for alkaline phosphatase, a clinically important and common enzyme in the biosphere.     

Nature and prevalence of combinations of mental disorders and their association with excess mortality in a population‐based cohort study

The nature and prevalence of combinations of mental disorders and their associations with premature mortality have never been reported in a comprehensive way. We describe the most common combinations of mental disorders and estimate excess mortality associated with these combinations. We designed a population‐based cohort study including all 7,505,576 persons living in Denmark at some point between January 1, 1995 and December 31, 2016. Information on mental disorders and mortality was obtained from national registers. A total of 546,090 individuals (10.5%) living in Denmark on January 1, 1995 were diagnosed with at least one mental disorder during the 22‐year follow‐up period. The overall crude rate of diagnosis of mental disorders was 9.28 (95% CI: 9.26‐9.30) per 1,000 person‐years. The rate of diagnosis of additional mental disorders was 70.01 (95% CI: 69.80‐70.26) per 1,000 person‐years for individuals with one disorder already diagnosed. At the end of follow‐up, two out of five individuals with mental disorders were diagnosed with two or more disorder types. The most prevalent were neurotic/stress‐related/somatoform disorders (ICD‐10 F40‐F48) and mood disorders (ICD‐10 F30‐F39), which – alone or in combination with other disorders – were present in 64.8% of individuals diagnosed with any mental disorder. Mortality rates were higher for people with mental disorders compared to those without mental disorders. The highest mortality rate ratio was 5.97 (95% CI: 5.52‐6.45) for the combination of schizophrenia (ICD‐10 F20‐F29), neurotic/stress‐related/somatoform disorders and substance use disorders (ICD‐10 F10‐F19). Any combination of mental disorders was associated with a shorter life expectancy compared to the general Danish population, with differences in remaining life expectancy ranging from 5.06 years (95% CI: 5.01‐5.11) to 17.46 years (95% CI: 16.86‐18.03). The largest excess mortality was observed for combinations that included substance use disorders. This study reports novel estimates related to the “force of comorbidity” and provides new insights into the contribution of substance use disorders to premature mortality in those with comorbid mental disorders.     

Invertebrate biodiversity in cold groundwater fissures in Iceland

Iceland has an abundance of fissures that are parallel to the Mid‐Atlantic Ridge where bedrock cracks as a result of continental rifting. Some fissures penetrate the aquifer and expose the groundwater within the bedrock, becoming springs. As such, groundwater fissures have uniform and constant physical and chemical environment but they can differ greatly in morphology. In addition, there is often great variation in depth within fissures and substrate types contrast between vertical rock wall and more heterogenous horizontal bottom. The variation in morphological environment may create dissimilar habitats with unique characteristics and/or influence distribution of resources. Our objective was to study macrozoobenthos communities in cold groundwater fissures in Iceland in relation to physical habitat by comparing invertebrate diversity and density both between fissures with different morphological characteristics as well as between substrate types and depths within fissures. Samples were collected in two fissures in SW Iceland, Silfra and Flosagjá. Assemblages were similar between fissures except for higher densities of cladocerans in Flosagjá fissure. Within fissures, there was significant difference in Shannon diversity between substrate types in Flosagjá, and ostracods were found in significantly higher densities on the bottom. The distribution of all other taxa groups was homogenous in both fissures regardless of depth gradient and substrate. Invertebrates were found to be living within and around a biofilm that covered the entire substrate. These biofilm mats are made from Cyanobacteria and benthic diatoms, which are successful under low light conditions and may minimize any effect of the heterogeneous habitat creating a uniform and suitable microhabitat for invertebrates regardless of depth and substrate type.     

The effect of insect herbivory on seed production of Lupinus nootkatensis,an introduced species in Iceland

1. Lupinus nootkatensis is an exotic plant species that has been used for large‐scale sowing all around Iceland for land reclamation of eroded surfaces protected from livestock grazing.
2. Until the early 1990s, L. nootkatensis was free from any significant arthropod herbivory in Iceland, whereas, after 1991, many outbreaks of native insect species, primarily Ceramica pisi and Eupithecia satyrata, have been recorded. These outbreaks have caused repeated total defoliation of extensive areas of L. nootkatensis, although the effects on its development are mostly unknown.
3. We studied the effect of: (i) reduced herbivory; (ii) increased herbivory; and (iii) simulated increased herbivory, compared with (iv) unmanipulated herbivory, on defoliation and seed production of L. nootkatensis in a 3‐year field study within two sites at contrasting ages and successional stages.
4. The results obtained showed that: (i) seed production across all treatments was negatively related to defoliation; (ii) reduced herbivory had a positive effect on the number of flowering stems and seed yield; and (iii) these effects depended on age and/or the successional stage because they were only significant in the older L. nootkatensis site.
5. These findings indicate that arthropod herbivory may affect the invasiveness of L. nootkatensis in Iceland by reducing the seed production and the spatial distribution rate of late successional lupin communities.

     

Seasonal variation in the invertebrate community and diet of a top fish predator in a thermally stable spring

Hydrobiologia - Many life-history events in aquatic invertebrates are triggered by seasonal changes in water temperature, but other ecological factors may be important as well. To rule out the...     

Network-Based Interpretation of Genomic Variation Data

Advances in sequencing technologies are allowing genome-wide association studies at an ever-growing scale. The interpretation of these studies requires dealing with statistical and combinatorial challenges, owing to the multi-factorial nature of human diseases and the huge space of genomic markers that are being monitored. Recently, it was proposed that using protein–protein interaction network information could help in tackling these challenges by restricting attention to markers or combinations of markers that map to close proteins in the network. In this review, we survey techniques for integrating genomic variation data with network information to improve our understanding of complex diseases and reveal meaningful associations.     

The effect of the pine woolly aphid (Pineus pini) on survival,growth and natural selection in Scots pine (Pinus sylvestris) in Iceland

1. Scots pine Pinus sylvestris was originally introduced to Iceland in the beginning of the 20th Century. Extensive plantings started in the late 1940s and, in total, 2–3 million Scots pine seedlings were planted, mainly originating from two counties in northern Norway. Part of this plant material was imported as seedlings.
2. Pine woolly aphid Pineus pini was introduced to Iceland before 1940, most likely on imported seedlings in 1937.
3. High mortality of Scots pine, concurrent with high infestation of the pine woolly aphid, was observed in Iceland during the late 1950s and 1960s and planting was discontinued.
4. Provenance trials with Scots pine were established in Iceland in 2004–2006. They consisted of 15 provenances from Norway, four from Finland, four from Scotland, one from Russia, one from the Austrian Alps and three first generation Scots pine provenances from Iceland, collected from survivors of the epidemic in the 1950s and 1960s. In total, there were 28 provenances.
5. The Icelandic provenances had significantly lower P. pini infestation than all the provenances of non‐Icelandic origin, which indicates that natural selection in Scots pine in Iceland has occurred in favour of individuals less susceptible to P. pini.