Gender moderates the relationship between empathy and aggressiveness in sport: The mediating role of anger

This research investigated whether gender moderates, and anger mediates, the relationship between empathy (i.e., perspective taking and empathic concern) and aggressiveness in sport. In Study 1, perspective taking and empathic concern were negatively associated with aggressiveness, and this effect was stronger in women compared to men. In Study 2, perspective taking was a negative predictor of aggressiveness and antisocial behavior in sport, and anger mediated these relationships in women, but not in men. Our findings suggest that empathy and emotion-based strategies targeted at reducing aggressiveness in sport need to be tailored for males and females

Statistical and visual differentiation of subcellular imaging

<p>Abstract</p> <p>Background</p> <p>Automated microscopy technologies have led to a rapid growth in imaging data on a scale comparable to that of the genomic revolution. High throughput screens are now being performed to determine the localisation of all of proteins in a proteome. Closer to the bench, large image sets of proteins in treated and untreated cells are being captured on a daily basis to determine function and interactions. Hence there is a need for new methodologies and protocols to test for difference in subcellular imaging both to remove bias and enable throughput. Here we introduce a novel method of statistical testing, and supporting software, to give a rigorous test for difference in imaging. We also outline the key questions and steps in establishing an analysis pipeline.</p> <p>Results</p> <p>The methodology is tested on a high throughput set of images of 10 subcellular localisations, and it is shown that the localisations may be distinguished to a statistically significant degree with as few as 12 images of each. Further, subtle changes in a protein's distribution between nocodazole treated and control experiments are shown to be detectable. The effect of outlier images is also examined and it is shown that while the significance of the test may be reduced by outliers this may be compensated for by utilising more images. Finally, the test is compared to previous work and shown to be more sensitive in detecting difference. The methodology has been implemented within the iCluster system for visualising and clustering bio-image sets.</p> <p>Conclusion</p> <p>The aim here is to establish a methodology and protocol for testing for difference in subcellular imaging, and to provide tools to do so. While iCluster is applicable to moderate (<1000) size image sets, the statistical test is simple to implement and will readily be adapted to high throughput pipelines to provide more sensitive discrimination of difference.</p

Application of quantitative proteomics to discover biomarkers for tick resistance in cattle

Introduction: Breeding for tick resistance is a sustainable alternative to control cattle ticks due to widespread resistance to acaricidal drugs and the lack of a protective vaccine. The most accurate method used to characterise the phenotype for tick resistance in field studies is the standard tick count, but this is labour-intensive and can be hazardous to the operator. Efficient genetic selection requires reliable phenotyping or biomarker(s) for accurately identifying tick-resistant cattle. Although breed-specific genes associated with tick resistance have been identified, the mechanisms behind tick resistance have not yet been fully characterised. Methods: This study applied quantitative proteomics to examine the differential abundance of serum and skin proteins using samples from naïve tick-resistant and -susceptible Brangus cattle at two-time points following tick exposure. The proteins were digested into peptides, followed by identification and quantification using sequential window acquisition of all theoretical fragment ion mass spectrometry. Results: Resistant naïve cattle had a suite of proteins associated with immune response, blood coagulation and wound healing that were significantly (adjusted P &lt; 10- 5) more abundant compared with susceptible naïve cattle. These proteins included complement factors (C3, C4, C4a), alpha-1-acid glycoprotein (AGP), beta-2-glycoprotein-1, keratins (KRT1 &amp; KRT3) and fibrinogens (alpha &amp; beta). The mass spectrometry findings were validated by identifying differences in the relative abundance of selected serum proteins with ELISA. The proteins showing a significantly different abundance in resistant cattle following early and prolonged tick exposures (compared to resistant naïve) were associated with immune response, blood coagulation, homeostasis, and wound healing. In contrast, susceptible cattle developed some of these responses only after prolonged tick exposure. Discussion: Resistant cattle were able to transmigrate immune-response related proteins towards the tick bite sites, which may prevent tick feeding. Significantly differentially abundant proteins identified in this research in resistant naïve cattle may provide a rapid and efficient protective response to tick infestation. Physical barrier (skin integrity and wound healing) mechanisms and systemic immune responses were key contributors to resistance. Immune response-related proteins such as C4, C4a, AGP and CGN1 (naïve samples), CD14, GC and AGP (post-infestation) should be further investigated as potential biomarkers for tick resistance

The influence of tumor size and environment on gene expression in commonly used human tumor lines

BACKGROUND: The expression profiles of solid tumor models in rodents have been only minimally studied despite their extensive use to develop anticancer agents. We have applied RNA expression profiling using Affymetrix U95A GeneChips to address fundamental biological questions about human tumor lines. METHODS: To determine whether gene expression changed significantly as a tumor increased in size, we analyzed samples from two human colon carcinoma lines (Colo205 and HCT-116) at three different sizes (200 mg, 500 mg and 1000 mg). To investigate whether gene expression was influenced by the strain of mouse, tumor samples isolated from C.B-17 SCID and Nu/Nu mice were also compared. Finally, the gene expression differences between tissue culture and in vivo samples were investigated by comparing profiles from lines grown in both environments. RESULTS: Multidimensional scaling and analysis of variance demonstrated that the tumor lines were dramatically different from each other and that gene expression remained constant as the tumors increased in size. Statistical analysis revealed that 63 genes were differentially expressed due to the strain of mouse the tumor was grown in but the function of the encoded proteins did not link to any distinct biological pathways. Hierarchical clustering of tissue culture and xenograft samples demonstrated that for each individual tumor line, the in vivo and in vitro profiles were more similar to each other than any other profile. We identified 36 genes with a pattern of high expression in xenograft samples that encoded proteins involved in extracellular matrix, cell surface receptors and transcription factors. An additional 17 genes were identified with a pattern of high expression in tissue culture samples and encoded proteins involved in cell division, cell cycle and RNA production. CONCLUSIONS: The environment a tumor line is grown in can have a significant effect on gene expression but tumor size has little or no effect for subcutaneously grown solid tumors. Furthermore, an individual tumor line has an RNA expression pattern that clearly defines it from other lines even when grown in different environments. This could be used as a quality control tool for preclinical oncology studies

Inositol 1,4,5-Trisphosphate Signalling Regulates the Avoidance Response to Nose Touch in Caenorhabditis elegans

When Caenorhabditis elegans encounters an unfavourable stimulus at its anterior, it responds by initiating an avoidance response, namely reversal of locomotion. The amphid neurons, ASHL and ASHR, are polymodal in function, with roles in the avoidance responses to high osmolarity, nose touch, and both volatile and non-volatile repellents. The mechanisms that underlie the ability of the ASH neurons to respond to such a wide range of stimuli are still unclear. We demonstrate that the inositol 1,4,5-trisphosphate receptor (IP3R), encoded by itr-1, functions in the reversal responses to nose touch and benzaldehyde, but not in other known ASH-mediated responses. We show that phospholipase Cβ (EGL-8) and phospholipase Cγ (PLC-3), which catalyse the production of IP3, both function upstream of ITR-1 in the response to nose touch. We use neuron-specific gene rescue and neuron-specific disruption of protein function to show that the site of ITR-1 function is the ASH neurons. By rescuing plc-3 and egl-8 in a neuron-specific manner, we show that both are acting in ASH. Imaging of nose touch–induced Ca2+ transients in ASH confirms these conclusions. In contrast, the response to benzaldehyde is independent of PLC function. Thus, we have identified distinct roles for the IP3R in two specific responses mediated by ASH

Refinement of the associations between risk of colorectal cancer and polymorphisms on chromosomes 1q41 and 12q13.13

In genome-wide association studies (GWASs) of colorectal cancer, we have identified two genomic regions in which pairs of tagging-single nucleotide polymorphisms (tagSNPs) are associated with disease; these comprise chromosomes 1q41 (rs6691170, rs6687758) and 12q13.13 (rs7163702, rs11169552). We investigated these regions further, aiming to determine whether they contain more than one independent association signal and/or to identify the SNPs most strongly associated with disease. Genotyping of additional sample sets at the original tagSNPs showed that, for both regions, the two tagSNPs were unlikely to identify a single haplotype on which the functional variation lay. Conversely, one of the pair of SNPs did not fully capture the association signal in each region. We therefore undertook more detailed analyses, using imputation, logistic regression, genealogical analysis using the GENECLUSTER program and haplotype analysis. In the 1q41 region, the SNP rs11118883 emerged as a strong candidate based on all these analyses, sufficient to account for the signals at both rs6691170 and rs6687758. rs11118883 lies within a region with strong evidence of transcriptional regulatory activity and has been associated with expression of PDGFRB mRNA. For 12q13.13, a complex situation was found: SNP rs7972465 showed stronger association than either rs11169552 or rs7136702, and GENECLUSTER found no good evidence for a two-SNP model. However, logistic regression and haplotype analyses supported a two-SNP model, in which a signal at the SNP rs706793 was added to that at rs11169552. Post-GWAS fine-mapping studies are challenging, but the use of multiple tools can assist in identifying candidate functional variants in at least some cases

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Identification and Visualization of CD8+ T Cell Mediated IFN-γ Signaling in Target Cells during an Antiviral Immune Response in the Brain

CD8+ T cells infiltrate the brain during an anti-viral immune response. Within the brain CD8+ T cells recognize cells expressing target antigens, become activated, and secrete IFNγ. However, there are no methods to recognize individual cells that respond to IFNγ. Using a model that studies the effects of the systemic anti-adenoviral immune response upon brain cells infected with an adenoviral vector in mice, we describe a method that identifies individual cells that respond to IFNγ. To identify individual mouse brain cells that respond to IFNγ we constructed a series of adenoviral vectors that contain a transcriptional response element that is selectively activated by IFNγ signaling, the gamma-activated site (GAS) promoter element; the GAS element drives expression of a transgene, Cre recombinase (Ad-GAS-Cre). Upon binding of IFNγ to its receptor, the intracellular signaling cascade activates the GAS promoter, which drives expression of the transgene Cre recombinase. We demonstrate that upon activation of a systemic immune response against adenovirus, CD8+ T cells infiltrate the brain, interact with target cells, and cause an increase in the number of cells expressing Cre recombinase. This method can be used to identify, study, and eventually determine the long term fate of infected brain cells that are specifically targeted by IFNγ. The significance of this method is that it will allow to characterize the networks in the brain that respond to the specific secretion of IFNγ by anti-viral CD8+ T cells that infiltrate the brain. This will allow novel insights into the cellular and molecular responses underlying brain immune responses

Mutation burden and other molecular markers of prognosis in colorectal cancer treated with curative intent: results from the QUASAR 2 clinical trial and an Australian community-based series

Background Several relatively large studies have assessed molecular indicators of colorectal cancer (CRC) prognosis, but most analyses have been restricted to a handful of markers. Methods In stage II/III CRCs from the QUASAR2 clinical trial and from an Australian community-based series, we assessed gene panels for somatic driver mutations and overall mutation burden. We determined molecular pathways of tumorigenesis, and analysed associations with treatment response and prognosis. Findings In QUASAR2 (N=511), TP53, KRAS, BRAF and GNAS mutations were independently associated with shorter relapse-free survival, whereas total somatic mutation burden was associated with longer survival, even after excluding mismatch repair-deficient (MSI+) and POLE-mutant tumours. We successfully validated these associations in the Australian sample set (N=296). In an extended analysis of 1,752 QUASAR2 and Australian CRCs for which KRAS, BRAF and MSI status was available, we found that KRAS and BRAF mutations were specifically associated with poor prognosis in MSI- cancers. This association was not present in MSI+ cancers, and MSI+ tumours with KRAS or BRAF mutation actually had better prognosis than MSI- cancers that were wildtype for KRAS or BRAF. New rare molecular pathways were also uncovered: mutations in the genes NF1 and NRAS from the MAP kinase pathway co-occurred, mutations in TP53 and ATM appeared to be alternative ways of inactivating the DNA damage response pathway. Interpretation A multi-gene panel has identified two previously unreported prognostic associations in CRC involving both TP53 mutation and total mutation burden, and confirmed associations with KRAS and BRAF. We conclude that even a modest-sized gene panel can provide important information for use in clinical practice and out-perform MSI-based models.</p