Foundational guiding principles for a flourishing Earth System

In this perspectives article, we maintain that the current local to global sustainable development predicaments we face are the result of humanity's impact on the Earth System (ES)—that is to say, on the very systemic fabric of the ES (i.e., its functioning and configuration), combined with an insufficiently coherent application of sustainable development policy to address and resolve this systemic problem. In response to what is an urgent crisis, we propose four foundational guiding principles, which we contend provide an overarching framing that, if implemented, would offer an approach to steer global sustainable development policy in a manner that would be to the benefit of the ES and the securing of a flourishing future for all. Our principles are applicable at the levels from a local business ecosystem, national-regional networks, to global policy

The varieties of vitality: A cross-cultural lexical analysis

Vitality has been underappreciated and underexplored by academia at large. This oversight is potentially explained by the Western-centric nature of most fields, with vitality having been comparatively neglected in the West relative to elsewhere. One explanation for this lacuna is that vitality is not easily pigeonholed within the ontological categories dominant in the West, such as mind and body. This paper therefore aims to learn from cultures that have cultivated a greater understanding of vitality, doing so by engaging with relevant ‘untranslatable’ words (i.e., those without exact equivalent in English), thus enriching our conceptual map of this topic. Over 200 relevant terms were located and analyzed using an adapted form of grounded theory. Three themes were identified, each with four subthemes: spirit (life force, channels, soul, and transcendence); energy (fortitude, channeling, willpower, and recharging); and heart (desire, passion, affection, and satisfaction). The paper thus refines our understanding of this important topic and provides a foundation for future research.

Beyond a single story: The heterogeneity of human flourishing in 22 countries

Contemporary cross-cultural research on flourishing and development has been limited by a focus on Western populations and typically Western priorities, and by attention to only a few indicators of flourishing, such as life satisfaction, life expectancy, or GDP per capita. This paper highlights some significant challenges for robust cross-national and cross-cultural research on the domains and drivers of flourishing. Using data from the recently proposed Global Comparison Framework and the Gallup World Poll, we explore the within- and between-country heterogeneity of flourishing and its determinants across the 22 countries which are the subject of the Global Flourishing Study. Sources of heterogeneity considered include potential tradeoffs among domains of flourishing; the effects of cultural differences on the conceptualization and actualization of flourishing; and the cultural specificity of core analytical concepts, including “life evaluation” and “nation.

GARFIELD classifies disease-relevant genomic features through integration of functional annotations with association signals.

Loci discovered by genome-wide association studies predominantly map outside protein-coding genes. The interpretation of the functional consequences of non-coding variants can be greatly enhanced by catalogs of regulatory genomic regions in cell lines and primary tissues. However, robust and readily applicable methods are still lacking by which to systematically evaluate the contribution of these regions to genetic variation implicated in diseases or quantitative traits. Here we propose a novel approach that leverages genome-wide association studies' findings with regulatory or functional annotations to classify features relevant to a phenotype of interest. Within our framework, we account for major sources of confounding not offered by current methods. We further assess enrichment of genome-wide association studies for 19 traits within Encyclopedia of DNA Elements- and Roadmap-derived regulatory regions. We characterize unique enrichment patterns for traits and annotations driving novel biological insights. The method is implemented in standalone software and an R package, to facilitate its application by the research community

High-throughput analysis of candidate imprinted genes and allele-specific gene expression in the human term placenta.

BACKGROUND: Imprinted genes show expression from one parental allele only and are important for development and behaviour. This extreme mode of allelic imbalance has been described for approximately 56 human genes. Imprinting status is often disrupted in cancer and dysmorphic syndromes. More subtle variation of gene expression, that is not parent-of-origin specific, termed 'allele-specific gene expression' (ASE) is more common and may give rise to milder phenotypic differences. Using two allele-specific high-throughput technologies alongside bioinformatics predictions, normal term human placenta was screened to find new imprinted genes and to ascertain the extent of ASE in this tissue. RESULTS: Twenty-three family trios of placental cDNA, placental genomic DNA (gDNA) and gDNA from both parents were tested for 130 candidate genes with the Sequenom MassArray system. Six genes were found differentially expressed but none imprinted. The Illumina ASE BeadArray platform was then used to test 1536 SNPs in 932 genes. The array was enriched for the human orthologues of 124 mouse candidate genes from bioinformatics predictions and 10 human candidate imprinted genes from EST database mining. After quality control pruning, a total of 261 informative SNPs (214 genes) remained for analysis. Imprinting with maternal expression was demonstrated for the lymphocyte imprinted gene ZNF331 in human placenta. Two potential differentially methylated regions (DMRs) were found in the vicinity of ZNF331. None of the bioinformatically predicted candidates tested showed imprinting except for a skewed allelic expression in a parent-specific manner observed for PHACTR2, a neighbour of the imprinted PLAGL1 gene. ASE was detected for two or more individuals in 39 candidate genes (18%). CONCLUSIONS: Both Sequenom and Illumina assays were sensitive enough to study imprinting and strong allelic bias. Previous bioinformatics approaches were not predictive of new imprinted genes in the human term placenta. ZNF331 is imprinted in human term placenta and might be a new ubiquitously imprinted gene, part of a primate-specific locus. Demonstration of partial imprinting of PHACTR2 calls for re-evaluation of the allelic pattern of expression for the PHACTR2-PLAGL1 locus. ASE was common in human term placenta.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Intergenerational Communication – an interdisciplinary mapping review of research between 1996 and 2017

Concerns have been raised regarding the limited opportunities for intergenerational communication both outside and within the family. This “mapping review” draws together empirical literature in the topic published since 1996. Three hundred and twenty-four published studies met inclusion criteria, based on abstract review. The contents of each study were subjected to thematic analysis and nine broad themes emerged. These were (1) Dynamics of relationships, (2) Health & Well-being, (3) Learning & Literacy, (4) Attitudes, (5) Culture, (6) Digital, (7) Space, (8) Professional Development, and (9) Gender & Sexual Orientation. Studies commonly intersected disciplinary research areas. There was a marked rise across three key academic journals since 2007. An emergent finding was that a third of the studies relate to programs addressing intergenerational interventions, but many of these were primarily descriptive and failed to specify a primary outcome. Review implications and future research directions are discussed

The telomerase-recruitment domain of the telomere binding protein Cdc13 is regulated by Mec1p/Tel1p-dependent phosphorylation

The DNA damage-responsive protein kinases ATM and ATR phosphorylate SQ/TQ motifs that lie in clusters in most of their in vivo targets. Budding yeast Cdc13p contains two clusters of SQ/TQ motifs, suggesting that it might be a target of Mec1p/Tel1p (yeast ATR/ATM). Here we demonstrated that the telomerase recruitment domain of Cdc13p is phosphorylated by Mec1p and Tel1p. Gel analysis showed that Cdc13p contains a Mec1/Tel1-dependent post-translational modification. Using an immunoprecipitate (IP)-kinase assay, we showed that Mec1p phosphorylates Cdc13p on serine 225, 249, 255 and 306, and Tel1p phosphorylates Cdc13p on serine 225, 249 and 255 in vitro. Phenotypic analysis in vivo revealed that the mutations in the Cdc13p SQ motifs phosphorylated by Mec1p and Tel1p caused multiple telomere and growth defects. In addition, normal telomere length and growth could be restored by expressing a Cdc13–Est1p hybrid protein. These results demonstrate the telomerase recruitment domain of Cdc13p as an important new telomere-specific target of Mec1p/Tel1p

'Behavioural System Dynamics': a very tentative and slightly sceptical map of the territory

In this piece, I consider the paper by Stouten et al. (2017) in terms of behavioural science. I first consider what, in broad terms, a ‘behavioural turn’ might offer System Dynamics (SD) and then explore in more detail the scope of the territory within which a behavioural approach to SD might be useful

Active HHV-6 Infection of Cerebellar Purkinje Cells in Mood Disorders

Early-life infections and associated neuroinflammation is incriminated in the pathogenesis of various mood disorders. Infection with human roseoloviruses, HHV-6A and HHV-6B, allows viral latency in the central nervous system and other tissues, which can later be activated causing cognitive and behavioral disturbances. Hence, this study was designed to evaluate possible association of HHV-6A and HHV-6B activation with three different groups of psychiatric patients. DNA qPCR, immunofluorescence and FISH studies were carried out in post-mortem posterior cerebellum from 50 cases each of bipolar disorder (BPD), schizophrenia, 15 major depressive disorder (MDD) and 50 appropriate control samples obtained from two well-known brain collections (Stanley Medical Research Institute). HHV-6A and HHV-6B late proteins (indicating active infection) and viral DNA were detected more frequently (p < 0.001 for each virus) in human cerebellum in MDD and BPD relative to controls. These roseolovirus proteins and DNA were found less frequently in schizophrenia cases. Active HHV-6A and HHV-6B infection in cerebellar Purkinje cells were detected frequently in BPD and MDD cases. Furthermore, we found a significant association of HHV-6A infection with reduced Purkinje cell size, suggesting virus-mediated abnormal Purkinje cell function in these disorders. Finally, gene expression analysis of cerebellar tissue revealed changes in pathways reflecting an inflammatory response possibly to HHV-6A infection. Our results provide molecular evidence to support a role for active HHV-6A and HHV-6B infection in BPD and MDD