Seasonal changes in patterns of gene expression in avian song control brain regions.

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Photoperiod and hormonal cues drive dramatic seasonal changes in structure and function of the avian song control system. Little is known, however, about the patterns of gene expression associated with seasonal changes. Here we address this issue by altering the hormonal and photoperiodic conditions in seasonally-breeding Gambel's white-crowned sparrows and extracting RNA from the telencephalic song control nuclei HVC and RA across multiple time points that capture different stages of growth and regression. We chose HVC and RA because while both nuclei change in volume across seasons, the cellular mechanisms underlying these changes differ. We thus hypothesized that different genes would be expressed between HVC and RA. We tested this by using the extracted RNA to perform a cDNA microarray hybridization developed by the SoNG initiative. We then validated these results using qRT-PCR. We found that 363 genes varied by more than 1.5 fold (>log(2) 0.585) in expression in HVC and/or RA. Supporting our hypothesis, only 59 of these 363 genes were found to vary in both nuclei, while 132 gene expression changes were HVC specific and 172 were RA specific. We then assigned many of these genes to functional categories relevant to the different mechanisms underlying seasonal change in HVC and RA, including neurogenesis, apoptosis, cell growth, dendrite arborization and axonal growth, angiogenesis, endocrinology, growth factors, and electrophysiology. This revealed categorical differences in the kinds of genes regulated in HVC and RA. These results show that different molecular programs underlie seasonal changes in HVC and RA, and that gene expression is time specific across different reproductive conditions. Our results provide insights into the complex molecular pathways that underlie adult neural plasticity

Analysis of the potential of cancer cell lines to release tissue factor-containing microvesicles: correlation with tissue factor and PAR2 expression

BackgroundDespite the association of cancer-derived circulating tissue factor (TF)-containing microvesicles and hypercoagulable state, correlations with the incidence of thrombosis remain unclear.MethodsIn this study the upregulation of TF release upon activation of various cancer cell lines, and the correlation with TF and PAR2 expression and/or activity was examined. Microvesicle release was induced by PAR2 activation in seventeen cell lines and released microvesicle density, microvesicle-associated TF activity, and phoshpatidylserine-mediated activity were measured. The time-course for TF release was monitored over 90 min in each cell line. In addition, TF mRNA expression, cellular TF protein and cell-surface TF activities were quantified. Moreover, the relative expression of PAR2 mRNA and cellular protein were analysed. Any correlations between the above parameters were examined by determining the Pearson’s correlation coefficients.ResultsTF release as microvesicles peaked between 30–60 min post-activation in the majority of cell lines tested. The magnitude of the maximal TF release positively correlated with TF mRNA (c = 0.717; p

Serum uric acid concentrations in meat eaters, fish eaters, vegetarians and vegans: a cross-sectional analysis in the EPIC-Oxford cohort

Introduction Circulating concentrations of uric acid may be affected by dietary components such as meat, fish and dairy products, but only a few studies have compared uric acid concentrations among individuals who exclude some or all of these foods from their diet. The aim of this study was to investigate differences in serum uric acid concentrations between meat eaters, fish eaters, vegetarians and vegans. Subjects and Methods A sample of 670 men and 1,023 women (424 meat eaters, 425 fish eaters, 422 vegetarians and 422 vegans, matched on age and sex) from the European Prospective Investigation into Cancer and Nutrition Oxford cohort were included in this cross-sectional analysis. Diet was assessed using a semi-quantitative food frequency questionnaire and serum concentrations of uric acid were measured. Mean concentrations of uric acid by diet group were calculated after adjusting for age, body mass index, calcium and alcohol intake. Results In both men and women, serum uric acid concentrations differed significantly by diet group (p<0.0001 and p = 0.01, respectively). The differences between diet groups were most pronounced in men; vegans had the highest concentration (340, 95% confidence interval 329–351 µmol/l), followed by meat eaters (315, 306–324 µmol/l), fish eaters (309, 300–318 µmol/l) and vegetarians (303, 294–312 µmol/l). In women, serum uric acid concentrations were slightly higher in vegans (241, 234–247 µmol/l) than in meat eaters (237, 231–242 µmol/l) and lower in vegetarians (230, 224–236 µmol/l) and fish eaters (227, 221–233 µmol/l). Conclusion Individuals consuming a vegan diet had the highest serum concentrations of uric acid compared to meat eaters, fish eaters and vegetarians, especially in men. Vegetarians and individuals who eat fish but not meat had the lowest concentrations of serum uric acid

KLF2 mutation is the most frequent somatic change in splenic marginal zone lymphoma and identifies a subset with distinct genotype.

To characterise the genetics of splenic marginal zone lymphoma (SMZL), we performed whole exome sequencing of 16 cases and identified novel recurrent inactivating mutations in Kruppel-like factor 2 (KLF2), a gene whose deficiency was previously shown to cause splenic marginal zone hyperplasia in mice. KLF2 mutation was found in 40 (42%) of 96 SMZLs, but rarely in other B-cell lymphomas. The majority of KLF2 mutations were frameshift indels or nonsense changes, with missense mutations clustered in the C-terminal zinc finger domains. Functional assays showed that these mutations inactivated the ability of KLF2 to suppress NF-κB activation by TLR, BCR, BAFFR and TNFR signalling. Further extensive investigations revealed common and distinct genetic changes between SMZL with and without KLF2 mutation. IGHV1-2 rearrangement and 7q deletion were primarily seen in SMZL with KLF2 mutation, while MYD88 and TP53 mutations were nearly exclusively found in those without KLF2 mutation. NOTCH2, TRAF3, TNFAIP3 and CARD11 mutations were observed in SMZL both with and without KLF2 mutation. Taken together, KLF2 mutation is the most common genetic change in SMZL and identifies a subset with a distinct genotype characterised by multi-genetic changes. These different genetic changes may deregulate various signalling pathways and generate cooperative oncogenic properties, thereby contributing to lymphomagenesis.The research was supported by grants from Leukaemia & Lymphoma Research, U.K., Addenbrooke’s Charitable Trust. SM is a PhD student supported by MRC and Department of Pathology, University of Cambridge. LEI is a PhD student supported by the Pathological Society of UK & Ireland. NB is a fellow of the European Hematology Association and was supported by a starter grant from the Academy of Medical Sciences

Red wine and components flavonoids inhibit UGT2B17 in vitro

Background The metabolism and excretion of the anabolic steroid testosterone occurs by glucuronidation to the conjugate testosterone glucuronide which is then excreted in urine. Alterations in UGT glucuronidation enzyme activity could alter the rate of testosterone excretion and thus its bioavailability. The aim of this study is to investigate if red wine, a common dietary substance, has an inhibitory effect on UGT2B17. Methods Testosterone glucuronidation was assayed using human UGT2B17 supersomes with quantification of unglucuronidated testosterone over time using HPLC with DAD detection. The selected red wine was analysed using HPLC and the inhibitory effects of the wine and phenolic components were tested independently in a screening assay. Further analyses were conducted for the strongest inhibitors at physiologically relevant concentrations. Control experiments were conducted to determine the effects of the ethanol on UGT2B17. Results Over the concentration range of 2 to 8% the red wine sample inhibited the glucuronidation of testosterone by up to 70% over 2 hours. The ethanol content had no significant effect. Three red wine phenolics, identified by HLPC analyses, also inhibited the enzyme by varying amounts in the order of quercetin (72%), caffeic acid (22%) and gallic acid (9%); using a ratio of phenolic:testosterone of 1:2.5. In contrast p-coumaric acid and chlorogenic acid had no effect on the UGT2B17. The most active phenolic was selected for a detailed study at physiologically relevant concentrations, and quercetin maintained inhibitory activity of 20% at 2 M despite a ten-fold excess of testosterone. Conclusion This study reports that in an in vitro supersome-based assay, the key steroid-metabolising enzyme UGT2B17 is inhibited by a number of phenolic dietary substances and therefore may reduce the rate of testosterone glucuronidation in vivo. These results highlight the potential interactions of a number of common dietary compounds on testosterone metabolism. Considering the variety of foodstuffs that contain flavonoids, it is feasible that diet can elevate levels of circulating testosterone through reduction in urinary excretion. These results warrant further investigation and extension to a human trial to delineate the healt

The puzzle of non-party actors in party democracy: Independents in Ireland

It is an accepted truth that parties are the central political actors in all liberal democracies. This dominance of parties is often considered the logical outcome of rational politicians’ attempts to maximize their utility in terms of votes and policy influence. However, the last twenty years have seen a number of significant Independent (i.e. non-party) actors emerge in more than a few political systems. From an actor-centred point of view, party affiliation can, depending on the particular environment, be rather a liability than an advantage, which has significant implications for the role of non-party actors in face of weakening party democracies. To demonstrate this point, we deliver an account of the rise of Independents in the Irish political system, opposed to the dominant scholarly perspective that tends to consider Independents as an idiosyncrasy. We show that the choice of organizational independence over party affiliation represents a reaction to incentives inherent in the electoral, parliamentary and governmental stages that can disfavour party as the most efficient vehicle for individual goal attainment. This becomes evident when avoiding the misleading comparison between parties as collective bodies with that of Independents as individuals, instead focussing on the respective strategic positions of the individual MPs

The South, the suburbs, and the Vatican too: explaining partisan change among Catholics

This paper explains changes in partisanship among Catholics in the last quarter of the 20th Century using a theory of partisan change centered on the contexts in which Catholics lived. Catholics were part of the post-New Deal Democratic coalition, but they have become a swing demographic group. We argue that these changes in partisanship are best explained by changes in elite messages that are filtered through an individual’s social network. Those Catholics who lived or moved into the increasingly Republican suburbs and South were the Catholics who were most likely to adopt a non-Democratic partisan identity. Changes in context better explain Catholic partisanship than party abortion policy post Roe v. Wade or ideological sorting. We demonstrate evidence in support of our argument using the ANES cumulative file from 1972 through 2000

Extreme variations of pCO2 and pH in a macrophyte meadow of the Baltic Sea in summer: evidence of the effect of photosynthesis and local upwelling

The impact of ocean acidification on benthic habitats is a major preoccupation of the scientific community. However, the natural variability of pCO2 and pH in those habitats remains understudied, especially in temperate areas. In this study we investigated temporal variations of the carbonate system in nearshore macrophyte meadows of the western Baltic Sea. These are key benthic ecosystems, providing spawning and nursery areas as well as food to numerous commercially important species. In situ pCO2, pH (total scale), salinity and PAR irradiance were measured with a continuous recording sensor package dropped in a shallow macrophyte meadow (Eckernförde bay, western Baltic Sea) during three different weeks in July (pCO2 and PAR only), August and September 2011.The mean (± SD) pCO2 in July was 383±117 µatm. The mean (± SD) pCO2 and pHtot in August were 239±20 µatm and 8.22±0.1, respectively. The mean (± SD) pCO2 and pHtot in September were 1082±711 µatm and 7.83±0.40, respectively. Daily variations of pCO2 due to photosynthesis and respiration (difference between daily maximum and minimum) were of the same order of magnitude: 281±88 µatm, 219±89 μatm and 1488±574 µatm in July, August and September respectively. The observed variations of pCO2 were explained through a statistical model considering wind direction and speed together with PAR irradiance. At a time scale of days to weeks, local upwelling of elevated pCO2 water masses with offshore winds drives the variation. Within days, primary production is responsible. The results demonstrate the high variability of the carbonate system in nearshore macrophyte meadows depending on meteorology and biological activities. We highlight the need to incorporate these variations in future pCO2 scenarios and experimental designs for nearshore habitats

Body mass index and circulating oestrone sulphate in women treated with adjuvant letrozole

Background: Obesity is an independent adverse prognostic factor in early breast cancer patients, but it is still controversial whether obesity may affect adjuvant endocrine therapy efficacy. The aim of our study (ancillary to the two clinical trials Gruppo Italiano Mammella (GIM)4 and GIM5) was to investigate whether the circulating oestrogen levels during treatment with the aromatase inhibitor letrozole are related to body mass index (BMI) in postmenopausal women with breast cancer. Methods: Plasma concentration of oestrone sulphate (ES) was evaluated by radioimmunoassay in 370 patients. Plasma samples were obtained after at least 6 weeks of letrozole therapy (steady-state time). Patients were divided into four groups according to BMI. Differences among the geometric means (by ANOVA and ANCOVA) and correlation (by Spearman's rho) between the ES levels and BMI were assessed. Results: Picomolar geometric mean values (95% confidence interval, n=patients) of circulating ES during letrozole were 58.6 (51.0-67.2, n=150) when BMI was <25.0 kg m-2; 65.6 (57.8-74.6, n=154) when 25.0-29.9 kg m-2; 59.3 (47.1-74.6, n=50) when 30.0-34.9 kg m -2; and 43.3 (23.0-81.7, n=16) when 6535.0 kg m-2. No statistically significant difference in terms of ES levels among groups and no correlation with BMI were observed. Conclusions: Body mass index does not seem to affect circulating oestrogen levels in letrozole-treated patient