Host Genes Related to Paneth Cells and Xenobiotic Metabolism Are Associated with Shifts in Human Ileum-Associated Microbial Composition

The aim of this study was to integrate human clinical, genotype, mRNA microarray and 16 S rRNA sequence data collected on 84 subjects with ileal Crohn’s disease, ulcerative colitis or control patients without inflammatory bowel diseases in order to interrogate how host-microbial interactions are perturbed in inflammatory bowel diseases (IBD). Ex-vivo ileal mucosal biopsies were collected from the disease unaffected proximal margin of the ileum resected from patients who were undergoing initial intestinal surgery. Both RNA and DNA were extracted from the mucosal biopsy samples. Patients were genotyped for the three major NOD2 variants (Leufs1007, R702W, and G908R) and the ATG16L1T300A variant. Whole human genome mRNA expression profiles were generated using Agilent microarrays. Microbial composition profiles were determined by 454 pyrosequencing of the V3–V5 hypervariable region of the bacterial 16 S rRNA gene. The results of permutation based multivariate analysis of variance and covariance (MANCOVA) support the hypothesis that host mucosal Paneth cell and xenobiotic metabolism genes play an important role in host microbial interactions

Genetic Association Study Identifies HSPB7 as a Risk Gene for Idiopathic Dilated Cardiomyopathy

Dilated cardiomyopathy (DCM) is a structural heart disease with strong genetic background. Monogenic forms of DCM are observed in families with mutations located mostly in genes encoding structural and sarcomeric proteins. However, strong evidence suggests that genetic factors also affect the susceptibility to idiopathic DCM. To identify risk alleles for non-familial forms of DCM, we carried out a case-control association study, genotyping 664 DCM cases and 1,874 population-based healthy controls from Germany using a 50K human cardiovascular disease bead chip covering more than 2,000 genes pre-selected for cardiovascular relevance. After quality control, 30,920 single nucleotide polymorphisms (SNP) were tested for association with the disease by logistic regression adjusted for gender, and results were genomic-control corrected. The analysis revealed a significant association between a SNP in HSPB7 gene (rs1739843, minor allele frequency 39%) and idiopathic DCM (p = 1.06×10−6, OR = 0.67 [95% CI 0.57–0.79] for the minor allele T). Three more SNPs showed p < 2.21×10−5. De novo genotyping of these four SNPs was done in three independent case-control studies of idiopathic DCM. Association between SNP rs1739843 and DCM was significant in all replication samples: Germany (n = 564, n = 981 controls, p = 2.07×10−3, OR = 0.79 [95% CI 0.67–0.92]), France 1 (n = 433 cases, n = 395 controls, p = 3.73×10−3, OR = 0.74 [95% CI 0.60–0.91]), and France 2 (n = 249 cases, n = 380 controls, p = 2.26×10−4, OR = 0.63 [95% CI 0.50–0.81]). The combined analysis of all four studies including a total of n = 1,910 cases and n = 3,630 controls showed highly significant evidence for association between rs1739843 and idiopathic DCM (p = 5.28×10−13, OR = 0.72 [95% CI 0.65–0.78]). None of the other three SNPs showed significant results in the replication stage

Exploiting Fast-Variables to Understand Population Dynamics and Evolution

We describe a continuous-time modelling framework for biological population dynamics that accounts for demographic noise. In the spirit of the methodology used by statistical physicists, transitions between the states of the system are caused by individual events while the dynamics are described in terms of the time-evolution of a probability density function. In general, the application of the diffusion approximation still leaves a description that is quite complex. However, in many biological applications one or more of the processes happen slowly relative to the system's other processes, and the dynamics can be approximated as occurring within a slow low-dimensional subspace. We review these time-scale separation arguments and analyse the more simple stochastic dynamics that result in a number of cases. We stress that it is important to retain the demographic noise derived in this way, and emphasise this point by showing that it can alter the direction of selection compared to the prediction made from an analysis of the corresponding deterministic model.Comment: 33 pages, 9 figure

Representations of 'race' in British science and culture during the eighteenth century

A dominant narrative of change is fundamental to how recent historiography has accounted for the apparent emergence of 'racial' theories in the late eighteenth century. This model argues that non-Europeans were largely evaluated and differentiated by their relative cultural qualities during the early-modern period, rather than through 'racialised' bodily features such as skin colour. With the evolution of Enlightenment sciences, these cultural varieties were supposedly eroded by categorical, scientifically validated differences between Europeans and non-Europeans. Thus modern ideas of 'racial' hierarchy are seen to originate from the 1770s onwards. This thesis re-evaluates the British contribution to 'racial science' during the eighteenth century, examining sources in a more comprehensive and intertextual manner than has so far been achieved. Juxtaposing the post-1770s anatomy, natural history and philosophy with texts from the late seventeenth century onwards, this thesis argues that there are profound representational continuities throughout this period which challenge the above shift. Common belief in specific categories of human variety, established through repeated attention to particular bodily features, is seen to be prevalent in travel literature throughout the period. Here it is maintained that the tendency towards a basic comparative anatomy in earlier texts is tantamount to a 'racial science' in itself. Four distinct representational motifs are studied herein, which are seen to operate in texts throughout the eighteenth century. Stereotypes of animality were used to convey a sense of inferior distinctiveness upon 'savage' peoples: an idea which becomes apparent in both travelogues and later anatomical works. Disproportional depictions of sensory capacity are part of this representation, whilst the use of animalised metaphor in discussions of 'interracial' breeding shows an awareness of 'racial' divides from at least the 1690s. Also explored are the connections between 'racial science' and scientific theories of sex and gender, which offer a similar challenge to the dominant historical narrative.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Representations of 'race' in British science and culture during the eighteenth century

A dominant narrative of change is fundamental to how recent historiography has accounted for the apparent emergence of 'racial' theories in the late eighteenth century. This model argues that non-Europeans were largely evaluated and differentiated by their relative cultural qualities during the early-modern period, rather than through 'racialised' bodily features such as skin colour. With the evolution of Enlightenment sciences, these cultural varieties were supposedly eroded by categorical, scientifically validated differences between Europeans and non-Europeans. Thus modern ideas of 'racial' hierarchy are seen to originate from the 1770s onwards. This thesis re-evaluates the British contribution to 'racial science' during the eighteenth century, examining sources in a more comprehensive and intertextual manner than has so far been achieved. Juxtaposing the post-1770s anatomy, natural history and philosophy with texts from the late seventeenth century onwards, this thesis argues that there are profound representational continuities throughout this period which challenge the above shift. Common belief in specific categories of human variety, established through repeated attention to particular bodily features, is seen to be prevalent in travel literature throughout the period. Here it is maintained that the tendency towards a basic comparative anatomy in earlier texts is tantamount to a 'racial science' in itself. Four distinct representational motifs are studied herein, which are seen to operate in texts throughout the eighteenth century. Stereotypes of animality were used to convey a sense of inferior distinctiveness upon 'savage' peoples: an idea which becomes apparent in both travelogues and later anatomical works. Disproportional depictions of sensory capacity are part of this representation, whilst the use of animalised metaphor in discussions of 'interracial' breeding shows an awareness of 'racial' divides from at least the 1690s. Also explored are the connections between 'racial science' and scientific theories of sex and gender, which offer a similar challenge to the dominant historical narrative.EThOS - Electronic Theses Online ServiceGBUnited Kingdo