Polymorphisms in the xenobiotic transporter Multidrug Resistance 1 (MDR1) and interaction with meat intake in relation to risk of colorectal cancer in a Danish prospective case-cohort study

<p>Abstract</p> <p>Background</p> <p>The xenobiotic transporters, Multidrug Resistance 1 <it>(MDR1/ABCB1) </it>and Breast Cancer Resistance Protein <it>(BCRP/ABCG2) </it>may restrict intestinal absorption of various carcinogens, including heterocyclic amines (HCA) and polycyclic aromatic hydrocarbons (PAH). Cyclooxygenase-2 (COX-2) derived prostaglandins promote gastrointestinal carcinogenesis, affecting angiogenesis, apoptosis, and invasiveness.</p> <p>The aim of this study was to investigate if polymorphisms in these genes were associated with risk of colorectal cancer (CRC), and to investigate possible interactions with lifestyle factors such as smoking, meat consumption, and NSAID use.</p> <p>Methods</p> <p>The following polymorphisms were analyzed; a synonymous <it>MDR1 </it>C3435T (rs1045642) in exon26, G-rs3789243-A in intron3, the functional <it>BCRP </it>C421A (rs2231142), the two <it>COX-2 </it>A-1195G (rs689466) and G-765C (rs20417) in the promoter region, and the <it>COX-2 </it>T8473C (rs5275) polymorphisms in the 3'-untranslated region. The polymorphisms were assessed together with lifestyle factors in a nested case-cohort study of 359 cases and a random cohort sample of 765 participants from the Danish prospective Diet, Cancer and Health study.</p> <p>Results</p> <p>Carriers of the variant allele of <it>MDR1 </it>intron 3 polymorphism were at 1.52-fold higher risk of CRC than homozygous wild type allele carriers (Incidence rate ratio (IRR) = 1.52, 95% Confidence Interval (CI): 1.12-2.06). Carriers of the variant allele of <it>MDR1 </it>C3435T exon 26 had a lower risk of CRC than homozygous C-allele carriers (IRR = 0.71 (CI:0.50-1.00)). There was interaction between these <it>MDR1 </it>polymorphisms and intake of red and processed meat in relation to CRC risk. Homozygous <it>MDR1 </it>C3435T C-allele carriers were at 8% increased risk pr 25 gram meat per day (CI: 1.00-1.16) whereas variant allele carriers were not at increased risk (p for interaction = 0.02). <it>COX-2 </it>and <it>BCRP </it>polymorphisms were not associated with CRC risk. There was interaction between NSAID use and <it>MDR1 </it>C3435T and COX-2 T8473C (p-values for interaction 0.001 and 0.04, respectively).</p> <p>Conclusion</p> <p>Two polymorphisms in <it>MDR1 </it>were associated with CRC risk and there was interaction between these polymorphisms and meat intake in relation to CRC risk. Our results suggest that <it>MDR1 </it>polymorphisms affect the relationship between meat and CRC risk.</p

Modeling Habitat Associations for the Common Loon (\u3cem\u3eGavia immer\u3c/em\u3e) at Multiple Scales in Northeastern North America

Common Loon (Gavia immer) is considered an emblematic and ecologically important example of aquatic-dependent wildlife in North America. The northern breeding range of Common Loon has contracted over the last century as a result of habitat degradation from human disturbance and lakeshore development. We focused on the state of New Hampshire, USA, where a long-term monitoring program conducted by the Loon Preservation Committee has been collecting biological data on Common Loon since 1976. The Common Loon population in New Hampshire is distributed throughout the state across a wide range of lake-specific habitats, water quality conditions, and levels of human disturbance. We used a multiscale approach to evaluate the association of Common Loon and breeding habitat within three natural physiographic ecoregions of New Hampshire. These multiple scales reflect Common Loon-specific extents such as territories, home ranges, and lake-landscape influences. We developed ecoregional multiscale models and compared them to single-scale models to evaluate model performance in distinguishing Common Loon breeding habitat. Based on information-theoretic criteria, there is empirical support for both multiscale and single-scale models across all three ecoregions, warranting a model-averaging approach. Our results suggest that the Common Loon responds to both ecological and anthropogenic factors at multiple scales when selecting breeding sites. These multiscale models can be used to identify and prioritize the conservation of preferred nesting habitat for Common Loon populations

Polymorphisms in NF-kappa B, PXR, LXR, PPAR gamma and risk of inflammatory bowel disease

AIM: To investigate the contribution of polymorphisms in nuclear receptors to risk of inflammatory bowel disease (IBD). METHODS: Genotypes of nuclear factor (NF)-kappa B (NFKB1) NF kappa B -94ins/del (rs28362491); peroxisome proliferator-activated receptor (PPAR)-gamma (PPAR gamma) PPAR gamma Pro12Ala (rs 1801282) and C1431T (rs 3856806); pregnane X receptor (PXR) (NR1I2) PXR A-24381C (rs1523127), C8055T (2276707), and A7635G (rs 6785049); and liver X receptor (LXR) (NR1H2) LXR T-rs1405655-C and T-rs2695121-C were assessed in a Danish case-control study of 327 Crohn's disease patients, 495 ulcerative colitis (UC) patients, and 779 healthy controls. Odds ratio (OR) and 95% CI were estimated by logistic regression models. RESULTS: The PXR A7635G variant, the PPAR gamma Pro12Ala and LXR T-rs2695121-C homozygous variant genotypes were associated with risk of UC (OR: 1.31, 95% CI: 1.03-1.66, P = 0.03, OR: 2.30, 95% CI: 1.04-5.08, P = 0.04, and OR: 1.41, 95% CI: 1.00-1.98, P = 0.05, respectively) compared to the corresponding homozygous wild-type genotypes. Among never smokers, PXR A7635G and the LXR T-rs1405655-C and T-rs2695121-C variant genotypes were associated with risk of IBD (OR: 1.41, 95% CI: 1.05-1.91, P = 0.02, OR: 1.63, 95% CI: 1.21-2.20, P = 0.001, and OR: 2.02, 95% CI: 1.36-2.99, P = 0.0005, respectively) compared to the respective homozygous variant genotypes. PXR A7635G (rs6785049) variant genotype was associated with a higher risk of UC diagnosis before the age of 40 years and with a higher risk of extensive disease (OR: 1.34, 95% CI: 1.03-1.75 and OR: 2.49, 95% CI: 1.24-5.03, respectively). CONCLUSION: Common PXR and LXR polymorphisms may contribute to risk of IBD, especially among never smokers. (C) 2011 Baishideng. All rights reserved

Cognitive and affective reassurance and patient outcomes in primary care:a systematic review

In the context of uncertainty about aetiology and prognosis, good clinical practice commonly recommends both affective (creating rapport, showing empathy) and cognitive reassurance (providing explanations and education) to increase self-management in groups with nonspecific pain conditions. The specific impact of each of these components in reference to patients' outcomes has not been studied. This review aimed to systematically evaluate the evidence from prospective cohorts in primary care that measured patient-practitioner interactions with reference to patient outcomes. We carried out a systematic literature search and appraisal of study methodology. We extracted measures of affective and cognitive reassurance in consultations and their associations with consultation exit and follow-up measures of patients' outcomes. We identified 16 studies from 16,059 abstracts. Eight studies were judged to be high in methodological quality. Pooling could not be achieved as a result of heterogeneity of samples and measures. Affective reassurance showed inconsistent findings with consultation exit outcomes. In 3 high-methodology studies, an association was found between affective reassurance and higher symptom burden and less improvement at follow-up. Cognitive reassurance was associated with higher satisfaction and enablement and reduced concerns directly after the consultations in 8 studies; with improvement in symptoms at follow-up in 7 studies; and with reduced health care utilization in 3 studies. Despite limitations, there is support for the notion that cognitive reassurance is more beneficial than affective reassurance. We present a tentative model based on these findings and propose priorities for future research. © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved

Explicit processing of verbal and spatial features during letter-location binding modulates oscillatory activity of a fronto-parietal network.

The present study investigated the binding of verbal and spatial features in immediate memory. In a recent study, we demonstrated incidental and asymmetrical letter-location binding effects when participants attended to letter features (but not when they attended to location features) that were associated with greater oscillatory activity over prefrontal and posterior regions during the retention period. We were interested to investigate whether the patterns of brain activity associated with the incidental binding of letters and locations observed when only the verbal feature is attended differ from those reflecting the binding resulting from the controlled/explicit processing of both verbal and spatial features. To achieve this, neural activity was recorded using magnetoencephalography (MEG) while participants performed two working memory tasks. Both tasks were identical in terms of their perceptual characteristics and only differed with respect to the task instructions. One of the tasks required participants to process both letters and locations. In the other, participants were instructed to memorize only the letters, regardless of their location. Time–frequency representation of MEG data based on the wavelet transform of the signals was calculated on a single trial basis during the maintenance period of both tasks. Critically, despite equivalent behavioural binding effects in both tasks, single and dual feature encoding relied on different neuroanatomical and neural oscillatory correlates. We propose that enhanced activation of an anterior–posterior dorsal network observed in the task requiring the processing of both features reflects the necessity for allocating greater resources to intentionally process verbal and spatial features in this task

Multiple origins, one evolutionary trajectory: gradual evolution characterizes distinct lineages of allotetraploid "Brachypodium"

The “genomic shock” hypothesis posits that unusual challenges to genome integrity such as whole genome duplication may induce chaotic genome restructuring. Decades of research on polyploid genomes have revealed that this is often, but not always the case. While some polyploids show major chromosomal rearrangements and derepression of transposable elements in the immediate aftermath of whole genome duplication, others do not. Nonetheless, all polyploids show gradual diploidization over evolutionary time. To evaluate these hypotheses, we produced a chromosome-scale reference genome for the natural allotetraploid grass Brachypodium hybridum, accession “Bhyb26.” We compared 2 independently derived accessions of B. hybridum and their deeply diverged diploid progenitor species Brachypodium stacei and Brachypodium distachyon. The 2 B. hybridum lineages provide a natural timecourse in genome evolution because one formed 1.4 million years ago, and the other formed 140 thousand years ago. The genome of the older lineage reveals signs of gradual post-whole genome duplication genome evolution including minor gene loss and genome rearrangement that are missing from the younger lineage. In neither B. hybridum lineage do we find signs of homeologous recombination or pronounced transposable element activation, though we find evidence supporting steady post-whole genome duplication transposable element activity in the older lineage. Gene loss in the older lineage was slightly biased toward 1 subgenome, but genome dominance was not observed at the transcriptomic level. We propose that relaxed selection, rather than an abrupt genomic shock, drives evolutionary novelty in B. hybridum, and that the progenitor species’ similarity in transposable element load may account for the subtlety of the observed genome dominance

Concert recording 2019-03-26

[Track 1]. Amarilli mia bella / Guilio Caccini -- [Track 2]. Les Berceaux / Gabriel Fauré -- [Tracks 3-4]. O del mio dolce ardor / Christoph Willibald von Gluck -- [Track 5]. Song of the blackbird / Roger Quilter -- [Track 6]. Per Piera bell\u27idol mio / Vincenzo Bellini -- [Track 7]. Beau soir / Claude Debussy -- [Track 8]. Heart, we will forget him / Aaron Copland -- [Track 9]. Lascia ch\u27io pianga / George Frideric Handel -- [Track 10]. E amore un ladroncello from Cosí fan tutte / Wolfgang Amadeus Mozart -- [Track 11]. Tell me oh blue blue sky / Vittorio Giannini -- [Track 12]. O del mio amoto ben / Stefano Donuady -- [Track 13]. The roadside fire / Ralph Vaughan Williams -- [Track 14]. A blackbird singing / Michael Head -- [Track 15]. Saper Vorreste from Un ballo in maschera / Giuseppe Verdi -- [Track 16]. Mit Würd und Hoheit angetan from Die Schöpfung / Joseph Haydn -- [Track 17]. The one way / Charles Ives -- [Track 18]. From Sechs Lieder, op. 13. Ich stand in dunklen Träumen Liebeszauber Ich hab\u27 in Deinem Auge / Clara Schumann -- [Track 19]. From Though love be a day. Thy fingers make early flowers All the white horses are in bed / Gwenyth Walker -- [Track 20]. Der Rattenfänger / Hugo Wolf -- [Track 21]. Fin Ch\u27han dal vano from Don Giovanni / W.A. Mozart -- [Track 22]. From Brenntano Lieder. Ich wollte ein Straüßlein binden Saüsle, liebe Myrte / Richard Strauss

Strategic argumentation: A game theoretical investigation

Argumentation is modelled as a game where the payoffs are measured in terms of the probability that the claimed conclusion is, or is not, defeasibly provable, given a history of arguments that have actually been exchanged, and given the probability of the factual premises. The probability of a conclusion is calculated using a standard variant of Defeasible Logic, in combination with standard probability calculus. It is a new element of the present approach that the exchange of arguments is analysed with game theoretical tools, yielding a prescriptive and to some extent even predictive account of the actual course of play. A brief comparison with existing argument-based dialogue approaches confirms that such a prescriptive account of the actual argumentation has been almost lacking in the approaches proposed so far