Large-scale heterospecific segregation distortion in Populus revealed by a dense genetic map

Abstract We report the most complete genetic map to have been constructed for the genus Populus

A quantum McKay correspondence for fractional 2p-branes on LG orbifolds

We study fractional 2p-branes and their intersection numbers in non-compact orbifolds as well the continuation of these objects in Kahler moduli space to coherent sheaves in the corresponding smooth non-compact Calabi-Yau manifolds. We show that the restriction of these objects to compact Calabi-Yau hypersurfaces gives the new fractional branes in LG orbifolds constructed by Ashok et. al. in hep-th/0401135. We thus demonstrate the equivalence of the B-type branes corresponding to linear boundary conditions in LG orbifolds, originally constructed in hep-th/9907131, to a subset of those constructed in LG orbifolds using boundary fermions and matrix factorization of the world-sheet superpotential. The relationship between the coherent sheaves corresponding to the fractional two-branes leads to a generalization of the McKay correspondence that we call the quantum McKay correspondence due to a close parallel with the construction of branes on non-supersymmetric orbifolds. We also provide evidence that the boundary states associated to these branes in a conformal field theory description corresponds to a sub-class of the boundary states associated to the permutation branes in the Gepner model associated with the LG orbifold.Comment: LaTeX2e, 1+39 pages, 3 figures (v2) refs added, typos and report no. correcte

Regulatory feedback cycle of the insulin-degrading enzyme and the amyloid precursor protein intracellular domain: Implications for Alzheimer's disease

One of the major pathological hallmarks of Alzheimer´s disease (AD) is an accumulation of amyloid-β (Aβ) in brain tissue leading to formation of toxic oligomers and senile plaques. Under physiological conditions, a tightly balanced equilibrium between Aβ-production and -degradation is necessary to prevent pathological Aβ-accumulation. Here, we investigate the molecular mechanism how insulin-degrading enzyme (IDE), one of the major Aβ-degrading enzymes, is regulated and how amyloid precursor protein (APP) processing and Aβ-degradation is linked in a regulatory cycle to achieve this balance. In absence of Aβ-production caused by APP or Presenilin deficiency, IDE-mediated Aβ-degradation was decreased, accompanied by a decreased IDE activity, protein level, and expression. Similar results were obtained in cells only expressing a truncated APP, lacking the APP intracellular domain (AICD) suggesting that AICD promotes IDE expression. In return, APP overexpression mediated an increased IDE expression, comparable results were obtained with cells overexpressing C50, a truncated APP representing AICD. Beside these genetic approaches, also AICD peptide incubation and pharmacological inhibition of the γ-secretase preventing AICD production regulated IDE expression and promoter activity. By utilizing CRISPR/Cas9 APP and Presenilin knockout SH-SY5Y cells results were confirmed in a second cell line in addition to mouse embryonic fibroblasts. In vivo, IDE expression was decreased in mouse brains devoid of APP or AICD, which was in line with a significant correlation of APP expression level and IDE expression in human postmortem AD brains. Our results show a tight link between Aβ-production and Aβ-degradation forming a regulatory cycle in which AICD promotes Aβ-degradation via IDE and IDE itself limits its own production by degrading AICD

The cost of changing physical activity behaviour: Evidence from a "physical activity pathway" in the primary care setting

Copyright @ 2011 Boehler et al.BACKGROUND: The ‘Physical Activity Care Pathway’ (a Pilot for the ‘Let’s Get Moving’ policy) is a systematic approach to integrating physical activity promotion into the primary care setting. It combines several methods reported to support behavioural change, including brief interventions, motivational interviewing, goal setting, providing written resources, and follow-up support. This paper compares costs falling on the UK National Health Service (NHS) of implementing the care pathway using two different recruitment strategies and provides initial insights into the cost of changing physical activity behaviour. METHODS: A combination of a time driven variant of activity based costing, audit data through EMIS and a survey of practice managers provided patient-level cost data for 411 screened individuals. Self reported physical activity data of 70 people completing the care pathway at three month was compared with baseline using a regression based ‘difference in differences’ approach. Deterministic and probabilistic sensitivity analyses in combination with hypothesis testing were used to judge how robust findings are to key assumptions and to assess the uncertainty around estimates of the cost of changing physical activity behaviour. RESULTS: It cost £53 (SD 7.8) per patient completing the PACP in opportunistic centres and £191 (SD 39) at disease register sites. The completer rate was higher in disease register centres (27.3% vs. 16.2%) and the difference in differences in time spent on physical activity was 81.32 (SE 17.16) minutes/week in patients completing the PACP; so that the incremental cost of converting one sedentary adult to an ‘active state’ of 150 minutes of moderate intensity physical activity per week amounts to £ 886.50 in disease register practices, compared to opportunistic screening. CONCLUSIONS: Disease register screening is more costly than opportunistic patient recruitment. However, additional costs come with a higher completion rate and better outcomes in terms of behavioural change in patients completing the care pathway. Further research is needed to rigorously evaluate intervention efficiency and to assess the link between behavioural change and changes in quality adjusted life years (QALYs).This article is available through the Brunel Open Access Publishing Fund

Numerical properties of isotrivial fibrations

In this paper we investigate the numerical properties of relatively minimal isotrivial fibrations \varphi \colon X \lr C, where $X$ is a smooth, projective surface and $C$ is a curve. In particular we prove that, if $g(C) \geq 1$ and $X$ is neither ruled nor isomorphic to a quasi-bundle, then K_X^2 \leq 8 \chi(\mO_X)-2; this inequality is sharp and if equality holds then $X$ is a minimal surface of general type whose canonical model has precisely two ordinary double points as singularities. Under the further assumption that $K_X$ is ample, we obtain K_X^2 \leq 8 \chi(\mO_X)-5 and the inequality is also sharp. This improves previous results of Serrano and Tan.Comment: 30 pages. Final version, to appear in Geometriae Dedicat

Cathepsin D SNP associated with increased risk of variant Creutzfeldt-Jakob disease

<p>Abstract</p> <p>Background</p> <p>Variant Creutzfeldt-Jakob disease (vCJD) originally resulted from the consumption of foodstuffs contaminated by bovine spongiform encephalopathy (BSE) material, with 163 confirmed cases in the UK to date. Many thousands are likely to have been exposed to dietary infection and so it is important (for surveillance, epidemic modelling, public health and understanding pathogenesis) to identify genetic factors that may affect individual susceptibility to infection. This study looked at a polymorphism in the cathepsin D gene (refSNP ID: rs17571) previously examined in Alzheimer's disease (AD).</p> <p>Methods</p> <p>Blood samples taken from 110 vCJD patients were tested for the C-T base change, and genotype data were compared with published frequencies for a control population using multiple logistic regression.</p> <p>Results</p> <p>There was a significant excess of the cathepsin D polymorphism TT genotype in the vCJD cohort compared to controls. The TT genotype was found to have a 9.75 fold increase in risk of vCJD compared to the CT genotype and a 10.92 fold increase compared to the CC genotype.</p> <p>Conclusion</p> <p>This mutation event has been observed to alter the protease activity of the cathepsin D protein and has been linked to an increase in amyloid beta plaque formation in AD. vCJD neuropathology is characterised by the presence of amyloid plaques, formed from the prion protein, and therefore alterations in the amyloid processing activity of cathepsin D may affect the neuropathogenesis of this disease.</p

U.S. Billion-ton Update: Biomass Supply for a Bioenergy and Bioproducts Industry

The Report, Biomass as Feedstock for a Bioenergy and Bioproducts Industry: The Technical Feasibility of a Billion-Ton Annual Supply (generally referred to as the Billion-Ton Study or 2005 BTS), was an estimate of “potential” biomass within the contiguous United States based on numerous assumptions about current and future inventory and production capacity, availability, and technology. In the 2005 BTS, a strategic analysis was undertaken to determine if U.S. agriculture and forest resources have the capability to potentially produce at least one billion dry tons of biomass annually, in a sustainable manner—enough to displace approximately 30% of the country’s present petroleum consumption. To ensure reasonable confidence in the study results, an effort was made to use relatively conservative assumptions. However, for both agriculture and forestry, the resource potential was not restricted by price. That is, all identified biomass was potentially available, even though some potential feedstock would more than likely be too expensive to actually be economically available. In addition to updating the 2005 study, this report attempts to address a number of its shortcoming

Tropospheric O 3 moderates responses of temperate hardwood forests to elevated CO 2 : a synthesis of molecular to ecosystem results from the Aspen FACE project

1.   The impacts of elevated atmospheric CO 2 and/or O 3 have been examined over 4 years using an open-air exposure system in an aggrading northern temperate forest containing two different functional groups (the indeterminate, pioneer, O 3 -sensitive species Trembling Aspen, Populus tremuloides and Paper Birch, Betula papyrifera , and the determinate, late successional, O 3 -tolerant species Sugar Maple, Acer saccharum ). 2.   The responses to these interacting greenhouse gases have been remarkably consistent in pure Aspen stands and in mixed Aspen/Birch and Aspen/Maple stands, from leaf to ecosystem level, for O 3 -tolerant as well as O 3 -sensitive genotypes and across various trophic levels. These two gases act in opposing ways, and even at low concentrations (1·5 × ambient, with ambient averaging 34–36 nL L −1 during the summer daylight hours), O 3 offsets or moderates the responses induced by elevated CO 2 . 3.   After 3 years of exposure to 560 µmol mol −1 CO 2 , the above-ground volume of Aspen stands was 40% above those grown at ambient CO 2 , and there was no indication of a diminishing growth trend. In contrast, O 3 at 1·5 × ambient completely offset the growth enhancement by CO 2 , both for O 3 -sensitive and O 3 -tolerant clones. Implications of this finding for carbon sequestration, plantations to reduce excess CO 2 , and global models of forest productivity and climate change are presented.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72125/1/j.1365-2435.2003.00733.x.pd