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A catalog of genetic loci associated with kidney function from analyses of a million individuals
(2019)
Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
Introducing the CTA concept
(2013)
The Cherenkov Telescope Array (CTA) is a new observatory for very high-energy (VHE) gamma rays. CTA has ambitions science goals, for which it is necessary to achieve full-sky coverage, to improve the sensitivity by about an order of magnitude, to span about four decades of energy, from a few tens of GeV to above 100 TeV with enhanced angular and energy resolutions over existing VHE gamma-ray observatories. An international collaboration has formed with more than 1000 members from 27 countries in Europe, Asia, Africa and North and South America. In 2010 the CTA Consortium completed a Design Study and started a three-year Preparatory Phase which leads to production readiness of CTA in 2014. In this paper we introduce the science goals and the concept of CTA, and provide an overview of the project.
Electric-Field-Induced Order-Order Transition from Hexagonally Perforated Lamellae to Lamellae
(2015)
Block copolymers form a variety of microphase morphologies due to their ability to phase separate. The hexagonally perforated lamellar (HPL) morphology represents an unusually long-lived, nonequilibrium transient structure between lamellar and cylindrical phases. We present a detailed study of a concentrated, HPL-forming poly(styrene-b-isoprene) diblock copolymer solution in toluene in the presence of an electric field. We will show that this phase is readily aligned by a moderate electric field and provide experimental evidence for an electric-field-induced order order transition toward the lamellar phase under sufficiently strong fields. This process is shown to be fully reversible as lamellar perforations reconnect immediately upon secession of the external stimulus, recovering highly aligned perforated lamellae.
Context: Recent evidence suggests that gene X environment interactions could explain the inconsistent findings of association studies relating the dopamine transporter (DAT1) gene with attention-deficit/hyperactivity disorder (ADHD). 1bjective: To examine whether psychosocial adversity moderated the effect of genetic variation in DAT1 on ADHD symptoms in. adolescents from a high-risk community sample. Design: Prospective cohort study. Setting: Data were taken from the Mannheim Study of Children at Risk, an ongoing longitudinal study of the long-term outcomes of early risk factors followed up from birth on. Participants: Three hundred five adolescents (146 boys, 159 girls) participated in a follow-up assessment at age 15 years. Main Outcome Measures: Measures of ADHD symptoms according to DSM-IV were obtained using standardized structural interviews with adolescents and their parents. Psychosocial adversity was determined according to an "enriched" family adversity index as proposed by Rutter and Quinton. DNA was genotyped for the common DAT1 40-base pair (bp) variable number of tandem repeats (VNTR) polymorphism in the 3' untranslated region; 3 previously described single nucleotide polymorphisms in exon 15, intron 9, and exon 9; and a novel 30-bp VNTR polymorphism in intron 8. Results: Adolescents homozygous for the 10-repeat allele of the 40-bp VNTR polymorphism who grew up in greater psychosocial adversity exhibited significantly more inattention and hyperactivity-impulsivity than adolescents with other genotypes or who lived in less adverse family conditions (significant interaction, P=.013-017). This gene X environment interaction was also observed in individuals homozygous for the 6-repeat allele of the 30-bp VNTR polymorphism and the haplotype comprising both markers. Conclusions: These findings provide initial evidence that environmental risks as described by the Rutter Family Adversity Index moderate the impact of the DAT1 gene on ADHD symptoms, suggesting a DAT1 effect only in those individuals exposed to psychosocial adversity.
I. Introduction
II. Current challenges to the United Nations Human Rights Programme
III. The Secretary General’s Reform report “In larger Freedom” andits impact for the human rights programme
IV. The High Commissioner’s Plan of Action of May 2005
V. Negotiations on the establishment of the Human Rights Counciland first Council activities
VI. Reform of the treaty body system and debates over the creationof a unified standing treaty body
Inhalt: - Kurzzusammenfassung - I. Introduction - II. Current challenges to the United Nations Human Rights Programme - III. The Secretary General’s Reform report “In larger Freedom” and its impact for the human rights programme - IV. The High Commissioner’s Plan of Action of May 2005 - V. Negotiations on the establishment of the Human Rights Council and first Council activities - VI. Reform of the treaty body system and debates over the creation of a unified standing treaty body
Das Heft dokumentiert die siebte Konferenz des Forschungskreises Vereinte Nationen, die am 23. und 24. Juni 2006 an der Universität Potsdam stattfand. Unter dem Titel „Ein Jahr nach dem UN-Weltgipfel 2005 – Eine Bilanz der Reformbemühungen “ widmete sich die Konferenz wichtigen strukturellen Fragen und nahm einzelne Tätigkeitsfelder der Weltorganisation in den Blick. Die aus unterschiedlichen Disziplinen und aus Wissenschaft und Praxis kommenden Referentinnen und Referenten ziehen in den Referaten eine kritische Bilanz und untersuchen, was den Erklärungen des feierlichen Weltgipfels vom September 2005 an konkreten Reformschritten gefolgt ist. In für die „Potsdamer UNO-Konferenzen“ typischer Weise wird allen Interessierten die Möglichkeit gegeben, wichtige Aspekte der aktuellen Diskussion kennenzulernen, welche vor allem die Reform der UN-Hauptorgane, Reformen im Entwicklungssystem der Vereinten Nationen und im Bereich der Überwachung von Menschenrechtsverträgen betreffen sowie Fragen der Friedenssicherung und die Beteiligung von Zivilgesellschaft und Parlamentariern. Außerdem würdigt die Broschüre schweizerische Reforminitiativen in den UN und dokumentiert die aktuelle Diskussion über die deutschsprachige UN-Forschung.
The contemporary state of functional traits and species richness in plant communities depends on legacy effects of past disturbances. Whether temporal responses of community properties to current environmental changes are altered by such legacies is, however, unknown. We expect global environmental changes to interact with land-use legacies given different community trajectories initiated by prior management, and subsequent responses to altered resources and conditions. We tested this expectation for species richness and functional traits using 1814 survey-resurvey plot pairs of understorey communities from 40 European temperate forest datasets, syntheses of management transitions since the year 1800, and a trait database. We also examined how plant community indicators of resources and conditions changed in response to management legacies and environmental change. Community trajectories were clearly influenced by interactions between management legacies from over 200 years ago and environmental change. Importantly, higher rates of nitrogen deposition led to increased species richness and plant height in forests managed less intensively in 1800 (i.e., high forests), and to decreases in forests with a more intensive historical management in 1800 (i.e., coppiced forests). There was evidence that these declines in community variables in formerly coppiced forests were ameliorated by increased rates of temperature change between surveys. Responses were generally apparent regardless of sites’ contemporary management classifications, although sometimes the management transition itself, rather than historic or contemporary management types, better explained understorey responses. Main effects of environmental change were rare, although higher rates of precipitation change increased plant height, accompanied by increases in fertility indicator values. Analysis of indicator values suggested the importance of directly characterising resources and conditions to better understand legacy and environmental change effects. Accounting for legacies of past disturbance can reconcile contradictory literature results and appears crucial to anticipating future responses to global environmental change.
Understorey plant communities play a key role in the functioning of forest ecosystems. Under favourable environmental conditions, competitive understorey species may develop high abundances and influence important ecosystem processes such as tree regeneration. Thus, understanding and predicting the response of competitive understorey species as a function of changing environmental conditions is important for forest managers. In the absence of sufficient temporal data to quantify actual vegetation changes, space-for-time (SFT) substitution is often used, i.e. studies that use environmental gradients across space to infer vegetation responses to environmental change over time. Here we assess the validity of such SFT approaches and analysed 36 resurvey studies from ancient forests with low levels of recent disturbances across temperate Europe to assess how six competitive understorey plant species respond to gradients of overstorey cover, soil conditions, atmospheric N deposition and climatic conditions over space and time. The combination of historical and contemporary surveys allows (i) to test if observed contemporary patterns across space are consistent at the time of the historical survey, and, crucially, (ii) to assess whether changes in abundance over time given recorded environmental change match expectations from patterns recorded along environmental gradients in space. We found consistent spatial relationships at the two periods: local variation in soil variables and overstorey cover were the best predictors of individual species’ cover while interregional variation in coarse-scale variables, i.e. N deposition and climate, was less important. However, we found that our SFT approach could not accurately explain the large variation in abundance changes over time. We thus recommend to be cautious when using SFT substitution to infer species responses to temporal changes.
