Variant alleles of the CYP1B1 gene are associated with colorectal cancer susceptibility

<p>Abstract</p> <p>Background</p> <p>CYP1B1 is a P450 enzyme which is involved in the activation of pro-carcinogens to carcinogens as well as sex hormone metabolism. Because differences in the activity of the enzyme have been correlated with variant alleles of single nucleotide polymorphisms (SNPs), it represents an attractive candidate gene for studies into colorectal cancer susceptibility.</p> <p>Methods</p> <p>We genotyped 597 cancer patients and 597controls for three CYP1B1 SNPs, which have previously been shown to be associated with altered enzymatic activity. Using the three SNPs, eight different haplotypes were constructed. The haplotype frequencies were estimated in cases and controls and then compared. The odds ratio for each tumour type, associated with each haplotype was estimated, with reference to the most common haplotype observed in the controls.</p> <p>Results</p> <p>The three SNPs rs10012, rs1056827 and rs1056836 alone did not provide any significant evidence of association with colorectal cancer risk. Haplotypes of rs1056827 and rs10012 or rs1056827 and rs1056836 revealed an association with colorectal cancer which was significantly stronger in the homozygous carriers. One haplotype was under represented in the colorectal cancer patient group compared to the control population suggesting a protective effect.</p> <p>Conclusion</p> <p>Genetic variants within the CYP1B1 that are associated with altered function appear to influence susceptibility to a colorectal cancer in Poland. Three haplotypes were associated with altered cancer risk; one conferred protection and two were associated with an increased risk of disease. These observations should be confirmed in other populations.</p

A novel application of motion analysis for detecting stress responses in embryos at different stages of development.

Motion analysis is one of the tools available to biologists to extract biologically relevant information from image datasets and has been applied to a diverse range of organisms. The application of motion analysis during early development presents a challenge, as embryos often exhibit complex, subtle and diverse movement patterns. A method of motion analysis able to holistically quantify complex embryonic movements could be a powerful tool for fields such as toxicology and developmental biology to investigate whole organism stress responses. Here we assessed whether motion analysis could be used to distinguish the effects of stressors on three early developmental stages of each of three species: (i) the zebrafish Danio rerio (stages 19 h, 21.5 h and 33 h exposed to 1.5% ethanol and a salinity of 5); (ii) the African clawed toad Xenopus laevis (stages 24, 32 and 34 exposed to a salinity of 20); and iii) the pond snail Radix balthica (stages E3, E4, E6, E9 and E11 exposed to salinities of 5, 10 and 15). Image sequences were analysed using Sparse Optic Flow and the resultant frame-to-frame motion parameters were analysed using Discrete Fourier Transform to quantify the distribution of energy at different frequencies. This spectral frequency dataset was then used to construct a Bray-Curtis similarity matrix and differences in movement patterns between embryos in this matrix were tested for using ANOSIM

Tumour necrosis factor gene polymorphism: a predictive factor for the development of post-transplant lymphoproliferative disease

Epstein–Barr virus-positive post-transplant lymphoproliferative disease (PTLD) is a potentially lethal complication of iatrogenic immunosupression after transplantation. Predicting the development of PTLD allowing early and effective intervention is therefore of importance. Polymorphisms within cytokine genes are implicated in susceptibility to, and progression of, disease however the published data are often conflicting. We undertook investigation of polymorphic alleles within cytokine genes in PTLD and non-PTLD transplant cohorts to determine risk factors for disease. &lt;br/&gt; Methods: SSP-PCR was used to analyse single nucleotide polymorphism within tumour necrosis factor (TNF)-α, interleukin- 1, -6, -10 and lymphotoxin-α genes. The TNF-α levels were measured by standard enzyme-linked immuno-absorbant assay. &lt;br/&gt; Results: We show an association between variant alleles within the TNF-α promoter (−1031C (&lt;i&gt;P&lt;/i&gt;=0.005)); −863A (&lt;i&gt;P&lt;/i&gt;=0.0001) and TNF receptor I promoter regions (−201T (&lt;i&gt;P&lt;/i&gt;=0.02)); −1135C (&lt;i&gt;P&lt;/i&gt;=0.03) with the development of PTLD. We also show an association with TNF-α promoter haplotypes with haplotype-3 significantly increased (&lt;i&gt;P&lt;/i&gt;=0.0001) and haplotype-1 decreased (P=0.02) in PTLD patients compared to transplant controls. Furthermore, we show a significant increase (&lt;i&gt;P&lt;/i&gt;=0.02) in the level of TNF-α in PTLD patient plasma (range 0–97.97 pg ml&lt;sup&gt;−1&lt;/sup&gt;) compared to transplant controls (0–8.147 pg ml&lt;sup&gt;−1&lt;/sup&gt;), with the highest levels found in individuals carrying the variant alleles. &lt;br/&gt; Conclusion: We suggest that genetic variation within TNF-α loci and the level of plasma cytokine could be used as a predictive risk factor for the development of PTLD

Mapping recent information behavior research: an analysis of co-authorship and cocitation networks

There has been an increase in research published on information behavior in recent years, and this has been accompanied by an increase in its diversity and interaction with other fields, particularly information retrieval (HR). The aims of this study are to determine which researchers have contributed to producing the current body of knowledge on this subject, and to describe its intellectual basis. A bibliometric and network analysis was applied to authorship and co-authorship as well as citation and co-citation. According to these analyses, there is a small number of authors who can be considered to be the most productive and who publish regularly, and a large number of transient ones. Other findings reveal a marked predominance of theoretical works, some examples of qualitative methodology that originate in other areas of social science, and a high incidence of research focused on the user interaction with information retrieval systems and the information behavior of doctors

Team Dynamics Theory: Nomological network among cohesion, team mental models, coordination, and collective efficacy

I put forth a theoretical framework, namely Team Dynamics Theory (TDT), to address the need for a parsimonious yet integrated, explanatory and systemic view of team dynamics. In TDT, I integrate team processes and outputs and explain their relationships within a systemic view of team dynamics. Specifically, I propose a generative nomological network linking cohesion, team mental models, coordination, collective efficacy, and team outcomes. From this nomological conceptualization, I illustrate how myriad alternative models can be derived to account for variance in different working teams, each comprised of unique members, and embedded in singular contexts. I outline TDT’s applied implications for team development, the enhancement of team functioning, and the profiling of team resilience. I conclude by discussing how TDT’s ontological and nomological propositions can be tested through various theoretical inquiries, methodological approaches, and intervention-based studies