1,331 research outputs found
Tobacco smoking is associated with DNA methylation of diabetes susceptibility genes.
AIMS/HYPOTHESIS: Tobacco smoking, a risk factor for diabetes, is an established modifier of DNA methylation. We hypothesised that tobacco smoking modifies DNA methylation of genes previously identified for diabetes. METHODS: We annotated CpG sites available on the Illumina Human Methylation 450K array to diabetes genes previously identified by genome-wide association studies (GWAS), and investigated them for an association with smoking by comparing current to never smokers. The discovery study consisted of 630 individuals (Bonferroni-corrected p = 1.4 × 10(-5)), and we sought replication in an independent sample of 674 individuals. The replicated sites were tested for association with nearby genetic variants and gene expression and fasting glucose and insulin levels. RESULTS: We annotated 3,620 CpG sites to the genes identified in the GWAS on type 2 diabetes. Comparing current smokers to never smokers, we found 12 differentially methylated CpG sites, of which five replicated: cg23161492 within ANPEP (p = 1.3 × 10(-12)); cg26963277 (p = 1.2 × 10(-9)), cg01744331 (p = 8.0 × 10(-6)) and cg16556677 (p = 1.2 × 10(-5)) within KCNQ1 and cg03450842 (p = 3.1 × 10(-8)) within ZMIZ1. The effect of smoking on DNA methylation at the replicated CpG sites attenuated after smoking cessation. Increased DNA methylation at cg23161492 was associated with decreased gene expression levels of ANPEP (p = 8.9 × 10(-5)). rs231356-T, which was associated with hypomethylation of cg26963277 (KCNQ1), was associated with a higher odds of diabetes (OR 1.06, p = 1.3 × 10(-5)). Additionally, hypomethylation of cg26963277 was associated with lower fasting insulin levels (p = 0.04). CONCLUSIONS/INTERPRETATION: Tobacco smoking is associated with differential DNA methylation of the diabetes risk genes ANPEP, KCNQ1 and ZMIZ1. Our study highlights potential biological mechanisms connecting tobacco smoking to excess risk of type 2 diabetes
Holographic GB gravity in arbitrary dimensions
We study the properties of the holographic CFT dual to Gauss-Bonnet gravity
in general dimensions. We establish the AdS/CFT dictionary and in
particular relate the couplings of the gravitational theory to the universal
couplings arising in correlators of the stress tensor of the dual CFT. This
allows us to examine constraints on the gravitational couplings by demanding
consistency of the CFT. In particular, one can demand positive energy fluxes in
scattering processes or the causal propagation of fluctuations. We also examine
the holographic hydrodynamics, commenting on the shear viscosity as well as the
relaxation time. The latter allows us to consider causality constraints arising
from the second-order truncated theory of hydrodynamics.Comment: 48 pages, 9 figures. v2: New discussion on free fields in subsection
3.3 and new appendix B on conformal tensor fields. Added comments on the
relation between the central charge appearing in the two-point function and
the "central charge" characterizing the entropy density in the discussion.
References adde
HFE gene mutations increase the risk of coronary heart disease in women
The purpose of the present study is to examine HFE gene mutations in relation to newly diagnosed (incident) coronary heart disease (CHD). In a population-based follow-up study of 7,983 individuals aged 55 years and older, we compared the risk of incident CHD between HFE carriers and non-carriers, overall and stratified by sex and smoking status. HFE mutations were significantly associated with an increased risk of incident CHD in women but not in men (hazard ratio [HR] for women = 1.7, 95% confidence interval [CI] 1.2–2.4 versus HR for men = 0.9, 95% CI 0.7–1.2). This increased CHD risk associated with HFE mutations in women was statistically significant in never smokers (HR = 1.8, 95% CI 1.1–2.8) and current smokers (HR = 3.1, 95% CI 1.4–7.1), but not in former smokers (HR = 1.3, 95% CI 0.7–2.4). HFE mutations are associated with increased risk of incident CHD in women
Holographic studies of quasi-topological gravity
Quasi-topological gravity is a new gravitational theory including
curvature-cubed interactions and for which exact black hole solutions were
constructed. In a holographic framework, classical quasi-topological gravity
can be thought to be dual to the large limit of some non-supersymmetric
but conformal gauge theory. We establish various elements of the AdS/CFT
dictionary for this duality. This allows us to infer physical constraints on
the couplings in the gravitational theory. Further we use holography to
investigate hydrodynamic aspects of the dual gauge theory. In particular, we
find that the minimum value of the shear-viscosity-to-entropy-density ratio for
this model is .Comment: 45 pages, 6 figures. v2: References adde
Long term time variability of cosmic rays and possible relevance to the development of life on Earth
An analysis is made of the manner in which the cosmic ray intensity at Earth
has varied over its existence and its possible relevance to both the origin and
the evolution of life. Much of the analysis relates to the 'high energy' cosmic
rays () and their variability due to the changing
proximity of the solar system to supernova remnants which are generally
believed to be responsible for most cosmic rays up to PeV energies. It is
pointed out that, on a statistical basis, there will have been considerable
variations in the likely 100 My between the Earth's biosphere reaching
reasonable stability and the onset of very elementary life. Interestingly,
there is the increasingly strong possibility that PeV cosmic rays are
responsible for the initiation of terrestrial lightning strokes and the
possibility arises of considerable increases in the frequency of lightnings and
thereby the formation of some of the complex molecules which are the 'building
blocks of life'. Attention is also given to the well known generation of the
oxides of nitrogen by lightning strokes which are poisonous to animal life but
helpful to plant growth; here, too, the violent swings of cosmic ray
intensities may have had relevance to evolutionary changes. A particular
variant of the cosmic ray acceleration model, put forward by us, predicts an
increase in lightning rate in the past and this has been sought in Korean
historical records. Finally, the time dependence of the overall cosmic ray
intensity, which manifests itself mainly at sub-10 GeV energies, has been
examined. The relevance of cosmic rays to the 'global electrical circuit'
points to the importance of this concept.Comment: 18 pages, 5 figures, accepted by 'Surveys in Geophysics
Recurrent and Founder Mutations in the Netherlands: the Long-QT Syndrome
Background and objective The long-QT syndrome (LQTS) is associated with premature sudden cardiac deaths affecting whole families and is caused by mutations in genes encoding for cardiac proteins. When the same mutation is found in different families (recurrent mutations), this may imply either a common ancestor (founder) or multiple de novo mutations. We aimed to review recurrent mutations in patients with LQTS. Methods By use of our databases, we investigated the number of mutations that were found recurrently (at least three times) in LQT type 1-3 patients in the Netherlands. We studied familial links in the apparently unrelated probands, and we visualised the geographical distribution of these probands. Our results were compared with published literature of founder effects in LQTS outside the Netherlands. Results We counted 14 recurrent LQT mutations in the Netherlands. There are 326 identified carriers of one of these mutations. For three of these mutations, familial links were found between apparently unrelated probands. Conclusion Whereas true LQT founder mutations are described elsewhere in the world, we cannot yet demonstrate a real founder effect of these recurrent mutations in the Netherlands. Further studies on the prevalence of these mutations are indicated, and haplotype-sharing of the mutation carriers is pertinent to provide more evidence for founder mutation-based LQTS pathology in our countr
Holographic c-theorems in arbitrary dimensions
We re-examine holographic versions of the c-theorem and entanglement entropy
in the context of higher curvature gravity and the AdS/CFT correspondence. We
select the gravity theories by tuning the gravitational couplings to eliminate
non-unitary operators in the boundary theory and demonstrate that all of these
theories obey a holographic c-theorem. In cases where the dual CFT is
even-dimensional, we show that the quantity that flows is the central charge
associated with the A-type trace anomaly. Here, unlike in conventional
holographic constructions with Einstein gravity, we are able to distinguish
this quantity from other central charges or the leading coefficient in the
entropy density of a thermal bath. In general, we are also able to identify
this quantity with the coefficient of a universal contribution to the
entanglement entropy in a particular construction. Our results suggest that
these coefficients appearing in entanglement entropy play the role of central
charges in odd-dimensional CFT's. We conjecture a new c-theorem on the space of
odd-dimensional field theories, which extends Cardy's proposal for even
dimensions. Beyond holography, we were able to show that for any
even-dimensional CFT, the universal coefficient appearing the entanglement
entropy which we calculate is precisely the A-type central charge.Comment: 62 pages, 4 figures, few typo's correcte
From External Evaluation, to School Self-evaluation, to Peer Review
Most modern systems of school education around the world now have highly developed evaluation processes. Following quickly in the wake of external evaluation policies have followed calls for schools to develop their own capacities for self-review. An OECD report (2013) describes a number of ways in which developing school evaluation capacity should be a priority for school improvement. Among the report’s suggestions are promoting peer learning among schools (pp. 469–470). This chapter describes the research on external evaluation, internal evaluation and the relationship between these two. It then moves on to define and describes peer review and chart its growth. The accountability dimension of peer review is also explored. Finally the existing evidence on peer review is presented from the vocational and schools sectors to show key findings so far, and key conditions for effective peer review are described
Alcohol breaks down interhemispheric inhibition in females but not in males: Alcohol and frontal connectivity
- …