DISC1 conditioned GWAS for psychosis proneness in a large Finnish birth cohort

Background

Genetic evidence implicates the DISC1 gene in the etiology of a number of mental illnesses. Previously, we have reported association between DISC1 and measures of psychosis proneness, the Revised Social Anhedonia Scale (RSAS) and Revised Physical Anhedonia Scale (RPAS), in the Northern Finland Birth Cohort 1966 (NFBC66). As part of the studies of this Finnish birth cohort genome-wide association analysis has recently been performed.

Methodology

In the present study, we re-analyzed the genome-wide association data with regard to these two measures of psychosis proneness, conditioning on our previous DISC1 observation. From the original NFBC66 sample (N = 12 058), 4 561 individuals provided phenotype and genotype data. No markers were significant at the genome-wide level. However, several genes with biological relevance to mental illnesses were highlighted through loci displaying suggestive evidence for association (≥3 SNP with P<10E-4). These included the protein coding genes, CXCL3, KIAA1128, LCT, MED13L, TMCO7, TTN, and the micro RNA MIR620.

Conclusions

By conditioning a previous genome-wide association study on DISC1, we have been able to identify eight genes as associating to psychosis proneness. Further, these molecules predominantly link to the DISC1 pathway, strengthening the evidence for the role of this gene network in the etiology of mental illness. The use of quantitative measures of psychosis proneness in a large population cohort will make these findings, once verified; more generalized to a broad selection of disorders related to psychoses and psychosis proneness.     

Plant species richness belowground: higher richness and new patterns revealed by next-generation sequencing

Variation in plant species richness has been described using only aboveground vegetation. The species richness of roots and rhizomes has never been compared with aboveground richness in natural plant communities. We made direct comparisons of grassland plant richness in identical volumes (0.1 × 0.1 × 0.1 m) above and below the soil surface, using conventional species identification to measure aboveground richness and 454 sequencing of the chloroplast trnL(UAA) intron to measure belowground richness. We described above- and belowground richness at multiple spatial scales (from a neighbourhood scale of centimetres to a community scale of hundreds of metres), and related variation in richness to soil fertility. Tests using reference material indicated that 454 sequencing captured patterns of species composition and abundance with acceptable accuracy. At neighbourhood scales, belowground richness was up to two times greater than aboveground richness. The relationship between above- and belowground richness was significantly different from linear: beyond a certain level of belowground richness, aboveground richness did not increase further. Belowground richness also exceeded that of aboveground at the community scale, indicating that some species are temporarily dormant and absent aboveground. Similar to other grassland studies, aboveground richness declined with increasing soil fertility; in contrast, the number of species found only belowground increased significantly with fertility. These results indicate that conventional aboveground studies of plant richness may overlook many coexisting species, and that belowground richness becomes relatively more important in conditions where aboveground richness decreases. Measuring plant belowground richness can considerably alter perceptions of biodiversity and its responses to natural and anthropogenic factors.     

Calpains promote α2β1 integrin turnover in nonrecycling integrin pathway

Collagen receptor integrins recycle between the plasma membrane and endosomes and facilitate formation and turnover of focal adhesions. In contrast, clustering of α2β1 integrin with antibodies or the human pathogen echovirus 1 (EV1) causes redistribution of α2 integrin to perinuclear multivesicular bodies, α2-MVBs. We show here that the internalized clustered α2 integrin remains in α2-MVBs and is not recycled back to the plasma membrane. Instead, receptor clustering and internalization lead to an accelerated down-regulation of α2β1 integrin compared to the slow turnover of unclustered α2 integrin. EV1 infection or integrin degradation is not associated with proteasomal or autophagosomal processes and shows no significant association with lysosomal pathway. In contrast, degradation is dependent on calpains, such that it is blocked by calpain inhibitors. We show that active calpain is present in α2-MVBs, internalized clustered α2β1 integrin coprecipitates with calpain-1, and calpain enzymes can degrade α2β1 integrin. In conclusion, we identified a novel virus- and clustering-specific pathway that diverts α2β1 integrin from its normal endo/exocytic traffic to a nonrecycling, calpain-dependent degradative endosomal route.     

Loss of Anti-Viral Immunity by Infection with a Virus Encoding a Cross-Reactive Pathogenic Epitope

T cell cross-reactivity between different strains of the same virus, between different members of the same virus group, and even between unrelated viruses is a common occurrence. We questioned here how an intervening infection with a virus containing a sub-dominant cross-reactive T cell epitope would affect protective immunity to a previously encountered virus. Pichinde virus (PV) and lymphocytic choriomeningitis virus (LCMV) encode subdominant cross-reactive NP_205–212 CD8 T cell epitopes sharing 6 of 8 amino acids, differing only in the MHC anchoring regions. These pMHC epitopes induce cross-reactive but non-identical T cell receptor (TCR) repertoires, and structural studies showed that the differing anchoring amino acids altered the conformation of the MHC landscape presented to the TCR. PV-immune mice receiving an intervening infection with wild type but not NP205-mutant LCMV developed severe immunopathology in the form of acute fatty necrosis on re-challenge with PV, and this pathology could be predicted by the ratio of NP205-specific to the normally immunodominant PV NP_38–45 -specific T cells. Thus, cross-reactive epitopes can exert pathogenic properties that compromise protective immunity by impairing more protective T cell responses.     

The roles of elevation and local environmental factors as drivers of diatom diversity in subarctic streams

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Diagenetic fate of bioapatite in linguliform brachiopods: multiple apatite phases in shells of Cambrian lingulate brachiopod Ungula ingrica (Eichwald)

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Environmental factors and ground disturbance affecting the composition of species and functional traits of ground layer lichens on grey dunes and dune heaths of Estonia

A unique, species‐rich and endangered lichen biota can be found on European coastal and inland sand dunes. However, it is increasingly affected by natural succession as well as by anthropogenic disturbances. We studied lichen diversity on the grey dunes and dune heaths of coastal and inland regions of Estonia. A total of 28 study plots were investigated; in each 0.1 ha study plot general environmental variables and anthropogenic disturbances were described and all epigeic lichen species were identified. We found 66 lichenized fungus (lichen) species, including several rare and ten red‐listed lichens. Multivariate analysis (DCA, CCA) was performed to examine gradients in species composition and to relate variation in species data to environmental factors. In addition, we used redundancy analysis (RDA) to relate variation in species’ trait composition to environmental factors. Species composition on grey dunes differed significantly from that on dune heaths. The characteristic species for grey dunes are, besides several Cladonia species, foliose lichens, e.g. Hypogymnia physodes, Parmelia sulcata and Peltigera spp. Also species’ traits composition was different for either habitat, indicating that sorediate lichens, foliose lichens, lichens with cyanobacterium as the main photobiont, and sparsely branched Cladonia species dominate on grey dunes, while esorediate, green‐algal, crustose and richly branched fruticose lichens are common on dune heaths. Soil pH was the most essential environmental variable for determining both species composition and species’ traits composition. The composition of lichen species was also significantly influenced by forest closeness, soil Mg content and cover of bare sand; the effect of ground disturbances was low compared to the effect of these environmental factors. To protect and conserve the species‐rich lichen biota, it is necessary to protect the dune habitats from building activity, to avoid overtrampling in recreation areas and to regularly remove shrubs and trees.     

Adverse Effects of Plant Food Supplements Self-Reported by Consumers in the PlantLIBRA Survey Involving Six European Countries

Background

The use of food supplements containing botanicals is increasing in European markets. Although intended to maintain the health status, several cases of adverse effects to Plant Food Supplements (PFS) have been described.

Objectives

To describe the self-reported adverse effects collected during the European PlantLIBRA PFS Consumer Survey 2011–2012, with a critical evaluation of the plausibility of the symptomatology reported using data from the literature and from the PlantLIBRA Poisons Centers'' survey.

Subjects/Setting

From the total sample of 2359 consumers involved in the consumers'' survey, 82 subjects reported adverse effects due to a total of 87 PFS.

Results

Cases were self-reported, therefore causality was not classified on the basis of clinical evidence, but by using the frequency/strength of adverse effects described in scientific papers: 52 out of 87 cases were defined as possible (59.8%) and 4 as probable (4.6%). Considering the most frequently cited botanicals, eight cases were due to Valeriana officinalis (garden valerian); seven to Camellia sinensis (tea); six to Ginkgo biloba (Maidenhair tree) and Paullinia cupana (guarana). Most adverse events related to the gastrointestinal tract, nervous and cardiovascular systems.

Conclusions

Comparing the data from this study with those published in scientific papers and obtained by the PlantLIBRA Poisons Centers'' survey, some important conclusions can be drawn: severe adverse effects to PFS are quite rare, although mild or moderate adverse symptoms can be present. Data reported in this paper can help health professionals (and in particular family doctors) to become aware of possible new problems associated with the increasing use of food supplements containing botanicals.     

Polyamine levels in buds and twigs of Tilia cordata from dormancy onset to bud break

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