Integrating personality research and animal contest theory: aggressiveness in the green swordtail <i>Xiphophorus helleri</i>

&lt;p&gt;Aggression occurs when individuals compete over limiting resources. While theoretical studies have long placed a strong emphasis on context-specificity of aggression, there is increasing recognition that consistent behavioural differences exist among individuals, and that aggressiveness may be an important component of individual personality. Though empirical studies tend to focus on one aspect or the other, we suggest there is merit in modelling both within-and among-individual variation in agonistic behaviour simultaneously. Here, we demonstrate how this can be achieved using multivariate linear mixed effect models. Using data from repeated mirror trials and dyadic interactions of male green swordtails, &lt;i&gt;Xiphophorus helleri&lt;/i&gt;, we show repeatable components of (co)variation in a suite of agonistic behaviour that is broadly consistent with a major axis of variation in aggressiveness. We also show that observed focal behaviour is dependent on opponent effects, which can themselves be repeatable but were more generally found to be context specific. In particular, our models show that within-individual variation in agonistic behaviour is explained, at least in part, by the relative size of a live opponent as predicted by contest theory. Finally, we suggest several additional applications of the multivariate models demonstrated here. These include testing the recently queried functional equivalence of alternative experimental approaches, (e. g., mirror trials, dyadic interaction tests) for assaying individual aggressiveness.&lt;/p&gt

Predicting cell types and genetic variations contributing to disease by combining GWAS and epigenetic data

Genome-wide association studies (GWASs) identify single nucleotide polymorphisms (SNPs) that are enriched in individuals suffering from a given disease. Most disease-associated SNPs fall into non-coding regions, so that it is not straightforward to infer phenotype or function; moreover, many SNPs are in tight genetic linkage, so that a SNP identified as associated with a particular disease may not itself be causal, but rather signify the presence of a linked SNP that is functionally relevant to disease pathogenesis. Here, we present an analysis method that takes advantage of the recent rapid accumulation of epigenomics data to address these problems for some SNPs. Using asthma as a prototypic example; we show that non-coding disease-associated SNPs are enriched in genomic regions that function as regulators of transcription, such as enhancers and promoters. Identifying enhancers based on the presence of the histone modification marks such as H3K4me1 in different cell types, we show that the location of enhancers is highly cell-type specific. We use these findings to predict which SNPs are likely to be directly contributing to disease based on their presence in regulatory regions, and in which cell types their effect is expected to be detectable. Moreover, we can also predict which cell types contribute to a disease based on overlap of the disease-associated SNPs with the locations of enhancers present in a given cell type. Finally, we suggest that it will be possible to re-analyze GWAS studies with much higher power by limiting the SNPs considered to those in coding or regulatory regions of cell types relevant to a given disease

Epithelioid sarcoma with muscle metastasis detected by positron emission tomography

<p>Abstract</p> <p>Background</p> <p>Epithelioid sarcoma is an uncommon high-grade sarcoma, mostly involving the extremities.</p> <p>Case presentation</p> <p>A 33-year-old man was referred to our institute with a diagnosis of Volkmann's contracture with the symptom of flexion contracture of the fingers associated with swelling in his left forearm. Magnetic resonance imaging (MRI) showed abnormal signal intensity, comprising iso-signal intensity on T1- and high-signal intensity on T2-weighted images surrounding the flexor tendons in the forearm. Diagnosis of epithelioid sarcoma was made by open biopsy, and amputation at the upper arm was then undertaken. [¹⁸F]-2-fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) detected multiple lesions with an increased uptake in the right neck, the bilateral upper arms and the right thigh, as well as in the left axillary lymph nodes, with maximum standardized uptake value (SUVmax) ranging from 2.0 to 5.5 g/ml. Magnetic resonance imaging confirmed that there was a lesion within the right thigh muscle which was suggestive of metastasis, even though the lesion was occult clinically.</p> <p>Conclusion</p> <p>Increased uptake on FDG-PET might be representative of epithelioid sarcoma, and for this reason FDG-PET may be useful for detecting metastasis. Muscle metastasis is not well documented in epithelioid sarcoma. Accordingly, the frequency of muscle metastasis, including occult metastasis, needs to be further analyzed.</p

Routes for breaching and protecting genetic privacy

We are entering the era of ubiquitous genetic information for research, clinical care, and personal curiosity. Sharing these datasets is vital for rapid progress in understanding the genetic basis of human diseases. However, one growing concern is the ability to protect the genetic privacy of the data originators. Here, we technically map threats to genetic privacy and discuss potential mitigation strategies for privacy-preserving dissemination of genetic data.Comment: Draft for comment

The Parkinson's Disease Mendelian Randomization Research Portal

Background Mendelian randomization is a method for exploring observational associations to find evidence of causality. Objective To apply Mendelian randomization between risk factors/phenotypic traits (exposures) and PD in a large, unbiased manner, and to create a public resource for research. Methods We used two‐sample Mendelian randomization in which the summary statistics relating to single‐nucleotide polymorphisms from 5,839 genome‐wide association studies of exposures were used to assess causal relationships with PD. We selected the highest‐quality exposure genome‐wide association studies for this report (n = 401). For the disease outcome, summary statistics from the largest published PD genome‐wide association studies were used. For each exposure, the causal effect on PD was assessed using the inverse variance weighted method, followed by a range of sensitivity analyses. We used a false discovery rate of 5% from the inverse variance weighted analysis to prioritize exposures of interest. Results We observed evidence for causal associations between 12 exposures and risk of PD. Of these, nine were effects related to increasing adiposity and decreasing risk of PD. The remaining top three exposures that affected PD risk were tea drinking, time spent watching television, and forced vital capacity, but these may have been biased and were less convincing. Other exposures at nominal statistical significance included inverse effects of smoking and alcohol. Conclusions We present a new platform which offers Mendelian randomization analyses for a total of 5,839 genome‐wide association studies versus the largest PD genome‐wide association studies available (https://pdgenetics.shinyapps.io/MRportal/). Alongside, we report further evidence to support a causal role for adiposity on lowering the risk of P

Genetic contributions to stability and change in intelligence from childhood to old age

Understanding the determinants of healthy mental ageing is a priority for society today1,2. So far, we know that intelligence differences show high stability from childhood to old age3,4 and there are estimates of the genetic contribution to intelligence at different ages5,6. However, attempts to discover whether genetic causes contribute to differences in cognitive ageing have been relatively uninformative7–10. Here we provide an estimate of the genetic and environmental contributions to stability and change in intelligence across most of the human lifetime. We used genome-wide single nucleotide polymorphism (SNP) data from 1,940 unrelated individuals whose intelligence was measured in childhood (age 11 years) and again in old age (age 65, 70 or 79 years)11,12. We use a statistical method that allows genetic (co)variance to be estimated from SNP data on unrelated individuals13–17. We estimate that causal genetic variants in linkage disequilibrium with common SNPs account for 0.24 of the variation in cognitive ability change from childhood to old age. Using bivariate analysis, we estimate a genetic correlation between intelligence at age 11 years and in old age of 0.62. These estimates, derived from rarely available data on lifetime cognitive measures, warrant the search for genetic causes of cognitive stability and change

Bonobo personality traits are heritable and associated with vasopressin receptor gene 1a variation

Despite being closely related, bonobos and chimpanzees show remarkable behavioral differences, the proximate origins of which remain unknown. This study examined the link between behavioral variation and variation in the vasopressin 1a receptor gene (Avpr1a) in bonobos. Chimpanzees are polymorphic for a ~360 bp deletion (DupB), which includes a microsatellite (RS3) in the 5′ promoter region of Avpr1a. In chimpanzees, the DupB deletion has been linked to lower sociability, lower social sensitivity, and higher anxiety. Chimpanzees and bonobos differ on these traits, leading some to believe that the absence of the DupB deletion in bonobos may be partly responsible for these differences, and to the prediction that similar associations between Avpr1a genotypes and personality traits should be present in bonobos. We identified bonobo personality dimensions using behavioral measures (Sociability(B), Boldness(B), Openness(B), Activity(B)) and trait ratings (Assertiveness(R), Conscientiousness(R), Openness(R), Agreeableness(R), Attentiveness(R), Extraversion(R)). In the present study we found that all 10 dimensions have nonzero heritabilities, indicating there is a genetic basis to personality, and that bonobos homozygous for shorter RS3 alleles were lower in Attentiveness(R) and higher in Openness(B). These results suggest that variations in Avpr1a genotypes explain both within and between species differences in personality traits of bonobos and chimpanzees

Common SNPs explain some of the variation in the personality dimensions of neuroticism and extraversion

The personality traits of neuroticism and extraversion are predictive of a number of social and behavioural outcomes and psychiatric disorders. Twin and family studies have reported moderate heritability estimates for both traits. Few associations have been reported between genetic variants and neuroticism/extraversion, but hardly any have been replicated. Moreover, the ones that have been replicated explain only a small proportion of the heritability (<∼2%). Using genome-wide single-nucleotide polymorphism (SNP) data from ∼12 000 unrelated individuals we estimated the proportion of phenotypic variance explained by variants in linkage disequilibrium with common SNPs as 0.06 (s.e.=0.03) for neuroticism and 0.12 (s.e.=0.03) for extraversion. In an additional series of analyses in a family-based sample, we show that while for both traits ∼45% of the phenotypic variance can be explained by pedigree data (that is, expected genetic similarity) one third of this can be explained by SNP data (that is, realized genetic similarity). A part of the so-called ‘missing heritability' has now been accounted for, but some of the reported heritability is still unexplained. Possible explanations for the remaining missing heritability are that: (i) rare variants that are not captured by common SNPs on current genotype platforms make a major contribution; and/ or (ii) the estimates of narrow sense heritability from twin and family studies are biased upwards, for example, by not properly accounting for nonadditive genetic factors and/or (common) environmental factors

A PKC-Dependent Recruitment of MMP-2 Controls Semaphorin-3A Growth-Promoting Effect in Cortical Dendrites

There is increasing evidence for a crucial role of proteases and metalloproteinases during axon growth and guidance. In this context, we recently described a functional link between the chemoattractive Sema3C and Matrix metalloproteinase 3 (MMP3). Here, we provide data demonstrating the involvement of MMP-2 to trigger the growth-promoting effect of Sema3A in cortical dendrites. The in situ analysis of MMP-2 expression and activity is consistent with a functional growth assay demonstrating in vitro that the pharmacological inhibition of MMP-2 reduces the growth of cortical dendrites in response to Sema3A. Hence, our results suggest that the selective recruitment and activation of MMP-2 in response to Sema3A requires a PKC alpha dependent mechanism. Altogether, we provide a second set of data supporting MMPs as effectors of the growth-promoting effects of semaphorins, and we identify the potential signalling pathway involved

Methanethiol-dependent dimethylsulfide production in soil environments

Dimethylsulfide (DMS) is an environmentally important trace gas with roles in sulfur cycling, signalling to higher organisms and in atmospheric chemistry. DMS is believed to be predominantly produced in marine environments via microbial degradation of the osmolyte dimethylsulfoniopropionate (DMSP). However, significant amounts of DMS are also generated from terrestrial environments, for example, peat bogs can emit ~6 μmol DMS m−2 per day, likely via the methylation of methanethiol (MeSH). A methyltransferase enzyme termed ‘MddA’, which catalyses the methylation of MeSH, generating DMS, in a wide range of bacteria and some cyanobacteria, may mediate this process, as the mddA gene is abundant in terrestrial metagenomes. This is the first study investigating the functionality of MeSH-dependent DMS production (Mdd) in a wide range of aerobic environments. All soils and marine sediment samples tested produced DMS when incubated with MeSH. Cultivation-dependent and cultivation-independent methods were used to assess microbial community changes in response to MeSH addition in a grassland soil where 35.9% of the bacteria were predicted to contain mddA. Bacteria of the genus Methylotenera were enriched in the presence of MeSH. Furthermore, many novel Mdd+ bacterial strains were isolated. Despite the abundance of mddA in the grassland soil, the Mdd pathway may not be a significant source of DMS in this environment as MeSH addition was required to detect DMS at only very low conversion rates