Evaluation of low density array technology for quantitative parallel measurement of multiple genes in human tissue

BACKGROUND: Low density arrays (LDAs) have recently been introduced as a novel approach to gene expression profiling. Based on real time quantitative RT-PCR (QRT-PCR), these arrays enable a more focused and sensitive approach to the study of gene expression than gene chips, while offering higher throughput than more established approaches to QRT-PCR. We have now evaluated LDAs as a means of determining the expression of multiple genes simultaneously in human tissues and cells. RESULTS: Comparisons between LDAs reveal low variability, with correlation coefficients close to 1. By performing 2-fold and 10-fold serial dilutions of cDNA samples in the LDAs we determined a clear linear relationship between the gene expression data points over 5 orders of magnitude. We also showed that it is possible to use LDAs to accurately and quantitatively detect 2-fold changes in target copy number as well as measuring genes that are expressed with low and high copy numbers in the range of 1 × 10(2 )– 1 × 10(6 )copies. Furthermore, the data generated by the LDA from a cell based pharmacological study were comparable to data generated by conventional QRT-PCR. CONCLUSION: LDAs represent a valuable new approach for sensitive and quantitative gene expression profiling

OPTIMA: A prospective randomized trial to validate the predictive utility and cost-effectiveness of gene expression test-directed chemotherapy decisions in early breast cancer

Background: Multi-parameter gene expression assays (MPAs) are widely used to estimate individual patient residual risk in hormone-sensitive HER2-negative node-negative early breast cancer, allowing patients with low risk to safely avoid chemotherapy. Evidence for MPA use in node-positive breast cancer is limited. OPTIMA (Optimal Personalised Treatment of early breast cancer usIng Multi-parameter Analysis) aims to validate MPA’s as predictors of chemotherapy sensitivity in a largely node-positive breast cancer population

REVEILLE8 and PSEUDO-REPONSE REGULATOR5 Form a Negative Feedback Loop within the Arabidopsis Circadian Clock

Circadian rhythms provide organisms with an adaptive advantage, allowing them to regulate physiological and developmental events so that they occur at the most appropriate time of day. In plants, as in other eukaryotes, multiple transcriptional feedback loops are central to clock function. In one such feedback loop, the Myb-like transcription factors CCA1 and LHY directly repress expression of the pseudoresponse regulator TOC1 by binding to an evening element (EE) in the TOC1 promoter. Another key regulatory circuit involves CCA1 and LHY and the TOC1 homologs PRR5, PRR7, and PRR9. Purification of EE–binding proteins from plant extracts followed by mass spectrometry led to the identification of RVE8, a homolog of CCA1 and LHY. Similar to these well-known clock genes, expression of RVE8 is circadian-regulated with a dawn phase of expression, and RVE8 binds specifically to the EE. However, whereas cca1 and lhy mutants have short period phenotypes and overexpression of either gene causes arrhythmia, rve8 mutants have long-period and RVE8-OX plants have short-period phenotypes. Light input to the clock is normal in rve8, but temperature compensation (a hallmark of circadian rhythms) is perturbed. RVE8 binds to the promoters of both TOC1 and PRR5 in the subjective afternoon, but surprisingly only PRR5 expression is perturbed by overexpression of RVE8. Together, our data indicate that RVE8 promotes expression of a subset of EE–containing clock genes towards the end of the subjective day and forms a negative feedback loop with PRR5. Thus RVE8 and its homologs CCA1 and LHY function close to the circadian oscillator but act via distinct molecular mechanisms

A global-scale screening of non-native aquatic organisms to identify potentially invasive species under current and future climate conditions

The threat posed by invasive non-native species worldwide requires a global approach to identify which introduced species are likely to pose an elevated risk of impact to native species and ecosystems. To inform policy, stakeholders and management decisions on global threats to aquatic ecosystems, 195 assessors representing 120 risk assessment areas across all six inhabited continents screened 819 non-native species from 15 groups of aquatic organisms (freshwater, brackish, marine plants and animals) using the Aquatic Species Invasiveness Screening Kit. This multi-lingual decision-support tool for the risk screening of aquatic organisms provides assessors with risk scores for a species under current and future climate change conditions that, following a statistically based calibration, permits the accurate classification of species into high-, medium-and low-risk categories under current and predicted climate conditions. The 1730 screenings undertaken encompassed wide geographical areas (regions, political entities, parts thereof, water bodies, river basins, lake drainage basins, and marine regions), which permitted thresholds to be identified for almost all aquatic organismal groups screened as well as for tropical, temperate and continental climate classes, and for tropical and temperate marine ecoregions. In total, 33 species were identified as posing a 'very high risk' of being or becoming invasive, and the scores of several of these species under current climate increased under future climate conditions, primarily due to their wide thermal tolerances. The risk thresholds determined for taxonomic groups and climate zones provide a basis against which area-specific or climate-based calibrated thresholds may be interpreted. In turn, the risk rankings help decision-makers identify which species require an immediate 'rapid' management action (e.g. eradication, control) to avoid or mitigate adverse impacts, which require a full risk assessment, and which are to be restricted or banned with regard to importation and/or sale as ornamental or aquarium/fishery enhancement. Decision support tools AS-ISK Hazard identification Non-native species Risk analysis Climate changepublishedVersio

A global-scale screening of non-native aquatic organisms to identify potentially invasive species under current and future climate conditions

The threat posed by invasive non-native species worldwide requires a global approach to identify which introduced species are likely to pose an elevated risk of impact to native species and ecosystems. To inform policy, stakeholders and management decisions on global threats to aquatic ecosystems, 195 assessors representing 120 risk assessment areas across all six inhabited continents screened 819 non-native species from 15 groups of aquatic organisms (freshwater, brackish, marine plants and animals) using the Aquatic Species Invasiveness Screening Kit. This multi-lingual decision-support tool for the risk screening of aquatic organisms provides assessors with risk scores for a species under current and future climate change conditions that, following a statistically based calibration, permits the accurate classification of species into high-, medium- and low-risk categories under current and predicted climate conditions. The 1730 screenings undertaken encompassed wide geographical areas (regions, political entities, parts thereof, water bodies, river basins, lake drainage basins, and marine regions), which permitted thresholds to be identified for almost all aquatic organismal groups screened as well as for tropical, temperate and continental climate classes, and for tropical and temperate marine ecoregions. In total, 33 species were identified as posing a ‘very high risk’ of being or becoming invasive, and the scores of several of these species under current climate increased under future climate conditions, primarily due to their wide thermal tolerances. The risk thresholds determined for taxonomic groups and climate zones provide a basis against which area-specific or climate-based calibrated thresholds may be interpreted. In turn, the risk rankings help decision-makers identify which species require an immediate ‘rapid’ management action (e.g. eradication, control) to avoid or mitigate adverse impacts, which require a full risk assessment, and which are to be restricted or banned with regard to importation and/or sale as ornamental or aquarium/fishery enhancement.publishedVersio

ENIGMA-anxiety working group : Rationale for and organization of large-scale neuroimaging studies of anxiety disorders

Altres ajuts: Anxiety Disorders Research Network European College of Neuropsychopharmacology; Claude Leon Postdoctoral Fellowship; Deutsche Forschungsgemeinschaft (DFG, German Research Foundation, 44541416-TRR58); EU7th Frame Work Marie Curie Actions International Staff Exchange Scheme grant 'European and South African Research Network in Anxiety Disorders' (EUSARNAD); Geestkracht programme of the Netherlands Organization for Health Research and Development (ZonMw, 10-000-1002); Intramural Research Training Award (IRTA) program within the National Institute of Mental Health under the Intramural Research Program (NIMH-IRP, MH002781); National Institute of Mental Health under the Intramural Research Program (NIMH-IRP, ZIA-MH-002782); SA Medical Research Council; U.S. National Institutes of Health grants (P01 AG026572, P01 AG055367, P41 EB015922, R01 AG060610, R56 AG058854, RF1 AG051710, U54 EB020403).Anxiety disorders are highly prevalent and disabling but seem particularly tractable to investigation with translational neuroscience methodologies. Neuroimaging has informed our understanding of the neurobiology of anxiety disorders, but research has been limited by small sample sizes and low statistical power, as well as heterogenous imaging methodology. The ENIGMA-Anxiety Working Group has brought together researchers from around the world, in a harmonized and coordinated effort to address these challenges and generate more robust and reproducible findings. This paper elaborates on the concepts and methods informing the work of the working group to date, and describes the initial approach of the four subgroups studying generalized anxiety disorder, panic disorder, social anxiety disorder, and specific phobia. At present, the ENIGMA-Anxiety database contains information about more than 100 unique samples, from 16 countries and 59 institutes. Future directions include examining additional imaging modalities, integrating imaging and genetic data, and collaborating with other ENIGMA working groups. The ENIGMA consortium creates synergy at the intersection of global mental health and clinical neuroscience, and the ENIGMA-Anxiety Working Group extends the promise of this approach to neuroimaging research on anxiety disorders

Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults

Background Underweight and obesity are associated with adverse health outcomes throughout the life course. We estimated the individual and combined prevalence of underweight or thinness and obesity, and their changes, from 1990 to 2022 for adults and school-aged children and adolescents in 200 countries and territories. Methods We used data from 3663 population-based studies with 222 million participants that measured height and weight in representative samples of the general population. We used a Bayesian hierarchical model to estimate trends in the prevalence of different BMI categories, separately for adults (age ≥20 years) and school-aged children and adolescents (age 5–19 years), from 1990 to 2022 for 200 countries and territories. For adults, we report the individual and combined prevalence of underweight (BMI <18·5 kg/m2) and obesity (BMI ≥30 kg/m2). For schoolaged children and adolescents, we report thinness (BMI <2 SD below the median of the WHO growth reference) and obesity (BMI >2 SD above the median). Findings From 1990 to 2022, the combined prevalence of underweight and obesity in adults decreased in 11 countries (6%) for women and 17 (9%) for men with a posterior probability of at least 0·80 that the observed changes were true decreases. The combined prevalence increased in 162 countries (81%) for women and 140 countries (70%) for men with a posterior probability of at least 0·80. In 2022, the combined prevalence of underweight and obesity was highest in island nations in the Caribbean and Polynesia and Micronesia, and countries in the Middle East and north Africa. Obesity prevalence was higher than underweight with posterior probability of at least 0·80 in 177 countries (89%) for women and 145 (73%) for men in 2022, whereas the converse was true in 16 countries (8%) for women, and 39 (20%) for men. From 1990 to 2022, the combined prevalence of thinness and obesity decreased among girls in five countries (3%) and among boys in 15 countries (8%) with a posterior probability of at least 0·80, and increased among girls in 140 countries (70%) and boys in 137 countries (69%) with a posterior probability of at least 0·80. The countries with highest combined prevalence of thinness and obesity in school-aged children and adolescents in 2022 were in Polynesia and Micronesia and the Caribbean for both sexes, and Chile and Qatar for boys. Combined prevalence was also high in some countries in south Asia, such as India and Pakistan, where thinness remained prevalent despite having declined. In 2022, obesity in school-aged children and adolescents was more prevalent than thinness with a posterior probability of at least 0·80 among girls in 133 countries (67%) and boys in 125 countries (63%), whereas the converse was true in 35 countries (18%) and 42 countries (21%), respectively. In almost all countries for both adults and school-aged children and adolescents, the increases in double burden were driven by increases in obesity, and decreases in double burden by declining underweight or thinness. Interpretation The combined burden of underweight and obesity has increased in most countries, driven by an increase in obesity, while underweight and thinness remain prevalent in south Asia and parts of Africa. A healthy nutrition transition that enhances access to nutritious foods is needed to address the remaining burden of underweight while curbing and reversing the increase in obesit