Otherworldly but not the Otherworld: Tolkien’s Adaptation of Medieval Faerie and Fairies into a Sub-creative Elvendom

Through a comparative analysis of Lothlorien and the medieval stories of Lanval and Sir Orfeo, this article attempts to shed some light on how the inherently pessimistic and recursive nature of Tolkien\u27s sub-creation affects his adaptation of medieval Faerie into a sub-creative elvendom born of the creative instincts of the elves. In doing so, the article also questions Tolkien\u27s adherence to parameters of Faerie and characteristics of elves as laid out in OFS

Critical moments? Life transitions and energy biographies

Family and youth research has highlighted the importance of lifecourse transitions, illustrating how they can have a substantial impact on people’s everyday lives and anticipated futures. Given their apparent significance, it is surprising that relatively little attention has been paid to life transitions – particularly unexpected ones – to explore how they can impact upon everyday energy use. This is a central concern of Energy Biographies project. The project’s qualitative longitudinal design makes an original contribution, affording a detailed view of how transitions unfold and their significance for energy demand and environmental action. Central to elucidating these issues is the concept of ‘linked lives’, recognising that people live interdependently. In this paper, we explore the accounts of three participants who experienced one or more life transitions during the course of the project, in order to consider the impacts of these events (both planned and unanticipated) on their everyday energy use and environmental actions as part of their linked lives with others

Engineering the Controlled Assembly of Filamentous Injectisomes in E. coli K-12 for Protein Translocation into Mammalian Cells.

Bacterial pathogens containing type III protein secretion systems (T3SS) assemble large needle-like protein complexes in the bacterial envelope, called injectisomes, for translocation of protein effectors into host cells. The application of these molecular syringes for the injection of proteins into mammalian cells is hindered by their structural and genomic complexity, requiring multiple polypeptides encoded along with effectors in various transcriptional units (TUs) with intricate regulation. In this work, we have rationally designed the controlled expression of the filamentous injectisomes found in enteropathogenic Escherichia coli (EPEC) in the nonpathogenic strain E. coli K-12. All structural components of EPEC injectisomes, encoded in a genomic island called the locus of enterocyte effacement (LEE), were engineered in five TUs (eLEEs) excluding effectors, promoters and transcriptional regulators. These eLEEs were placed under the control of the IPTG-inducible promoter Ptac and integrated into specific chromosomal sites of E. coli K-12 using a marker-less strategy. The resulting strain, named synthetic injector E. coli (SIEC), assembles filamentous injectisomes similar to those in EPEC. SIEC injectisomes form pores in the host plasma membrane and are able to translocate T3-substrate proteins (e.g., translocated intimin receptor, Tir) into the cytoplasm of HeLa cells reproducing the phenotypes of intimate attachment and polymerization of actin-pedestals elicited by EPEC bacteria. Hence, SIEC strain allows the controlled expression of functional filamentous injectisomes for efficient translocation of proteins with T3S-signals into mammalian cells

Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution.

Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF ≥5%) and nine low-frequency or rare (MAF <5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants

Properties of hot and dense matter from relativistic heavy ion collisions

We review the progress achieved in extracting the properties of hot and dense matter from relativistic heavy ion collisions at the relativistic heavy ion collider (RHIC) at Brookhaven National Laboratory and the large hadron collider (LHC) at CERN. We focus on bulk properties of the medium, in particular the evidence for thermalization, aspects of the equation of state, transport properties, as well as fluctuations and correlations. We also discuss the in-medium properties of hadrons with light and heavy quarks, and measurements of dileptons and quarkonia. This review is dedicated to the memory of Gerald E. Brown

Hundreds of variants clustered in genomic loci and biological pathways affect human height

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.

The Justy mutation identifies Gon4-like as a gene that is essential for B lymphopoiesis

A recessive mutation named Justy was found that abolishes B lymphopoiesis but does not impair other major aspects of hematopoiesis. Transplantation experiments showed that homozygosity for Justy prevented hematopoietic progenitors from generating B cells but did not affect the ability of bone marrow stroma to support B lymphopoiesis. In bone marrow from mutant mice, common lymphoid progenitors and pre-pro–B cells appeared normal, but cells at subsequent stages of B lymphopoiesis were dramatically reduced in number. Under culture conditions that promoted B lymphopoiesis, mutant pre-pro–B cells remained alive and began expressing the B cell marker CD19 but failed to proliferate. In contrast, these cells were able to generate myeloid or T/NK precursors. Genetic and molecular analysis demonstrated that Justy is a point mutation within the Gon4-like (Gon4l) gene, which encodes a protein with homology to transcriptional regulators. This mutation was found to disrupt Gon4l pre-mRNA splicing and dramatically reduce expression of wild-type Gon4l RNA and protein. Consistent with a role for Gon4l in transcriptional regulation, the levels of RNA encoding C/EBPα and PU.1 were abnormally high in mutant B cell progenitors. Our findings indicate that the Gon4l protein is required for B lymphopoiesis and may function to regulate gene expression during this process

Can Thermoclines Be a Cue to Prey Distribution for Marine Top Predators? A Case Study with Little Penguins

The use of top predators as bio-platforms is a modern approach to understanding how physical changes in the environment may influence their foraging success. This study examined if the presence of thermoclines could be a reliable signal of resource availability for a marine top predator, the little penguin (Eudyptula minor). We studied weekly foraging activity of 43 breeding individual penguins equipped with accelerometers. These loggers also recorded water temperature, which we used to detect changes in thermal characteristics of their foraging zone over 5 weeks during the penguin’s guard phase. Data showed the thermocline was detected in the first 3 weeks of the study, which coincided with higher foraging efficiency. When a thermocline was not detected in the last two weeks, foraging efficiency decreased as well. We suggest that thermoclines can represent temporary markers of enhanced food availability for this top-predator to which they must optimally adjust their breeding cycle

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy