Magnetic resonance imaging in the diagnosis of white matter signal abnormalities.

Background White matter abnormalities (WMAs) pose a diagnostic challenge when trying to establish etiologic diagnoses. During childhood and adult years, genetic disorders, metabolic disorders and acquired conditions are included in differential diagnoses. To assist clinicians and radiologists, a structured algorithm using cranial magnetic resonance imaging (MRI) has been recommended to aid in establishing working diagnoses that facilitate appropriate biochemical and genetic investigations. This retrospective pilot study investigated the validity and diagnostic utility of this algorithm when applied to white matter signal abnormalities (WMSAs) reported on imaging studies of patients seen in our clinics. Methods The MRI algorithm was applied to 31 patients selected from patients attending the neurometabolic/neurogenetic/metabolic/neurology clinics at a tertiary care hospital. These patients varied in age from 5 months to 79 years old, and were reported to have WMSAs on cranial MRI scans. Twenty-one patients had confirmed WMA diagnoses and 10 patients had non-specific WMA diagnoses (etiology unknown). Two radiologists, blinded to confirmed diagnoses, used clinical abstracts and the WMSAs present on patient MRI scans to classify possible WMA diagnoses utilizing the algorithm. Results The MRI algorithm displayed a sensitivity of 100%, a specificity of 30.0% and a positive predicted value of 74.1%. Cohen\u27s kappa statistic for inter-radiologist agreement was 0.733, suggesting good agreement between radiologists. Conclusions Although a high diagnostic utility was not observed, results suggest that this MRI algorithm has promise as a clinical tool for clinicians and radiologists. We discuss the benefits and limitations of this approach

Soil surface temperatures reveal moderation of the urban heat island effect by trees and shrubs

Urban areas are major contributors to air pollution and climate change, causing impacts on human health that are amplified by the microclimatological effects of buildings and grey infrastructure through the urban heat island (UHI) effect. Urban greenspaces may be important in reducing surface temperature extremes, but their effects have not been investigated at a city-wide scale. Across a midsized UK city we buried temperature loggers at the surface of greenspace soils at 100 sites, stratified by proximity to city centre, vegetation cover and land-use. Mean daily soil surface temperature over 11 months increased by 0.6 °C over the 5 km from the city outskirts to the centre. Trees and shrubs in non-domestic greenspace reduced mean maximum daily soil surface temperatures in the summer by 5.7 °C compared to herbaceous vegetation, but tended to maintain slightly higher temperatures in winter. Trees in domestic gardens, which tend to be smaller, were less effective at reducing summer soil surface temperatures. Our findings reveal that the UHI effects soil temperatures at a city-wide scale, and that in their moderating urban soil surface temperature extremes, trees and shrubs may help to reduce the adverse impacts of urbanization on microclimate, soil processes and human health

Genetic Background Can Result in a Marked or Minimal Effect of Gene Knockout (GPR55 and CB2 Receptor) in Experimental Autoimmune Encephalomyelitis Models of Multiple Sclerosis

PMCID: PMC379391

The Snail repressor recruits EZH2 to specific genomic sites through the enrollment of the lncRNA HOTAIR in epithelial-to-mesenchymal transition

The transcription factor Snail is a master regulator of cellular identity and epithelial-to-mesenchymal transition (EMT) directly repressing a broad repertoire of epithelial genes. How chromatin modifiers instrumental to its activity are recruited to Snail-specific binding sites is unclear. Here we report that the long non-coding RNA (lncRNA) HOTAIR (for HOX Transcript Antisense Intergenic RNA) mediates a physical interaction between Snail and enhancer of zeste homolog 2 (EZH2), an enzymatic subunit of the polycomb-repressive complex 2 and the main writer of chromatin-repressive marks. The Snail-repressive activity, here monitored on genes with a pivotal function in epithelial and hepatic morphogenesis, differentiation and cell-type identity, depends on the formation of a tripartite Snail/HOTAIR/EZH2 complex. These results demonstrate an lncRNA-mediated mechanism by which a transcriptional factor conveys a general chromatin modifier to specific genes, thereby allowing the execution of hepatocyte transdifferentiation; moreover, they highlight HOTAIR as a crucial player in the Snail-mediated EMT.Oncogene advance online publication, 25 July 2016; doi:10.1038/onc.2016.260

Annelid phylogeny and the status of Sipuncula and Echiura

BACKGROUND: Annelida comprises an ancient and ecologically important animal phylum with over 16,500 described species and members are the dominant macrofauna of the deep sea. Traditionally, two major groups are distinguished: Clitellata (including earthworms, leeches) and "Polychaeta" (mostly marine worms). Recent analyses of molecular data suggest that Annelida may include other taxa once considered separate phyla (i.e., Echiura, and Sipuncula) and that Clitellata are derived annelids, thus rendering "Polychaeta" paraphyletic; however, this contradicts classification schemes of annelids developed from recent analyses of morphological characters. Given that deep-level evolutionary relationships of Annelida are poorly understood, we have analyzed comprehensive datasets based on nuclear and mitochondrial genes, and have applied rigorous testing of alternative hypotheses so that we can move towards the robust reconstruction of annelid history needed to interpret animal body plan evolution. RESULTS: Sipuncula, Echiura, Siboglinidae, and Clitellata are all nested within polychaete annelids according to phylogenetic analyses of three nuclear genes (18S rRNA, 28S rRNA, EF1α; 4552 nucleotide positions analyzed) for 81 taxa, and 11 nuclear and mitochondrial genes for 10 taxa (additional: 12S rRNA, 16S rRNA, ATP8, COX1-3, CYTB, NAD6; 11,454 nucleotide positions analyzed). For the first time, these findings are substantiated using approximately unbiased tests and non-scaled bootstrap probability tests that compare alternative hypotheses. For echiurans, the polychaete group Capitellidae is corroborated as the sister taxon; while the exact placement of Sipuncula within Annelida is still uncertain, our analyses suggest an affiliation with terebellimorphs. Siboglinids are in a clade with other sabellimorphs, and clitellates fall within a polychaete clade with aeolosomatids as their possible sister group. None of our analyses support the major polychaete clades reflected in the current classification scheme of annelids, and hypothesis testing significantly rejects monophyly of Scolecida, Palpata, Canalipalpata, and Aciculata. CONCLUSION: Using multiple genes and explicit hypothesis testing, we show that Echiura, Siboglinidae, and Clitellata are derived annelids with polychaete sister taxa, and that Sipuncula should be included within annelids. The traditional composition of Annelida greatly underestimates the morphological diversity of this group, and inclusion of Sipuncula and Echiura implies that patterns of segmentation within annelids have been evolutionarily labile. Relationships within Annelida based on our analyses of multiple genes challenge the current classification scheme, and some alternative hypotheses are provided

Mind your step: the effects of mobile phone use on gaze behavior in stair climbing

Stair walking is a hazardous activity and a common cause of fatal and non-fatal falls. Previous studies have assessed the role of eye movements in stair walking by asking people to repeatedly go up and down stairs in quiet and controlled conditions, while the role of peripheral vision was examined by giving participants specific fixation instructions or working memory tasks. We here extend this research to stair walking in a natural environment with other people present on the stairs and a now common secondary task: Using one's mobile phone. Results show that using the mobile phone strongly draws one's attention away from the stairs, but that the distribution of gaze locations away from the phone is little influenced by using one's phone. Phone use also increased the time needed to walk the stairs, but handrail use remained low. These results indicate that limited foveal vision suffices for adequate stair walking in normal environments, but that mobile phone use has a strong influence on attention, which may pose problems when unexpected obstacles are encountered

Identification of novel associations and localization of signals in idiopathic inflammatory myopathies using genome-wide imputation

Objective: The idiopathic inflammatory myopathies (IIMs) are heterogeneous diseases thought to be initiated by immune activation in genetically predisposed individuals. We imputed variants from the ImmunoChip array using a large reference panel to fine-map associations and identify novel associations in IIM. Methods: We analyzed 2,565 Caucasian IIM patient samples collected through the Myositis Genetics Consortium (MYOGEN) and 10,260 ethnically matched control samples. We imputed 1,648,116 variants from the ImmunoChip array using the Haplotype Reference Consortium panel and conducted association analysis on IIM and clinical and serologic subgroups. Results: The HLA locus was consistently the most significantly associated region. Four non-HLA regions reached genome-wide significance, SDK2 and LINC00924 (both novel) and STAT4 in the whole IIM cohort, with evidence of independent variants in STAT4, and NAB1 in the polymyositis (PM) subgroup. We also found suggestive evidence of association with loci previously associated with other autoimmune rheumatic diseases (TEC and LTBR). We identified more significant associations than those previously reported in IIM for STAT4 and DGKQ in the total cohort, for NAB1 and FAM167A-BLK loci in PM, and for CCR5 in inclusion body myositis. We found enrichment of variants among DNase I hypersensitivity sites and histone marks associated with active transcription within blood cells. Conclusion: We found novel and strong associations in IIM and PM and localized signals to single genes and immune cell types

Exploration, Explanation, and Parent–Child Interaction in Museums

Young children develop causal knowledge through everyday family conversations and activities. Children's museums are an informative setting for studying the social context of causal learning because family members engage together in everyday scientific thinking as they play in museums. In this multisite collaborative project, we investigate children's developing causal thinking in the context of family interaction at museum exhibits. We focus on explaining and exploring as two fundamental collaborative processes in parent–child interaction, investigating how families explain and explore in open-ended collaboration at gear exhibits in three children's museums in Providence, RI, San Jose, CA, and Austin, TX. Our main research questions examined (a) how open-ended family exploration and explanation relate to one another to form a dynamic for children's learning; (b) how that dynamic differs for families using different interaction styles, and relates to contextual factors such as families' science background, and (c) how that dynamic predicts children's independent causal thinking when given more structured tasks. We summarize findings on exploring, explaining, and parent–child interaction (PCI) styles. We then present findings on how these measures related to one another, and finally how that dynamic predicts children's causal thinking. In studying children's exploring we described two types of behaviors of importance for causal thinking: (a) Systematic Exploration: Connecting gears to form a gear machine followed by spinning the gear machine. (b) Resolute Behavior: Problem-solving behaviors, in which children attempted to connect or spin a particular set of gears, hit an obstacle, and then persisted to succeed (as opposed to moving on to another behavior). Older children engaged in both behaviors more than younger children, and the proportion of these behaviors were correlated with one another. Parents and children talked to each other while interacting with the exhibits. We coded causal language, as well as other types of utterances. Parents' causal language predicted children's causal language, independent of age. The proportion of parents' causal language also predicted the proportion of children's systematic exploration. Resolute behavior on the part of children did not correlate with parents' causal language, but did correlate with children's own talk about actions and the exhibit. We next considered who set goals for the play in a more holistic measure of parent–child interaction style, identifying dyads as parent-directed, child-directed, or jointly-directed in their interaction with one another. Children in different parent–child interaction styles engaged in different amounts of systematic exploration and had parents who engaged in different amounts of causal language. Resolute behavior and the language related to children engaging in such troubleshooting, seemed more consistent across the three parent–child interaction styles. Using general linear mixed modeling, we considered relations within sequences of action and talk. We found that the timing of parents' causal language was crucial to whether children engaged in systematic exploration. Parents' causal talk was a predictor of children's systematic exploration only if it occurred prior to the act of spinning the gears (while children were building gear machines). We did not observe an effect of causal language when it occurred concurrently with or after children's spinning. Similarly, children's talk about their actions and the exhibit predicted their resolute behavior, but only when the talk occurred while the child was encountering the problem. No effects were found for models where the talk happened concurrently or after resolving the problem. Finally, we considered how explaining and exploring related to children's causal thinking. We analyzed measures of children's causal thinking about gears and a free play measure with a novel set of gears. Principal component analysis revealed a latent factor of causal thinking in these measures. Structural equation modeling examined how parents' background in science related to children's systematic exploration, parents' causal language, and parent–child interaction style, and then how those factors predicted children's causal thinking. In a full model, with children's age and gender included, children's systematic exploration related to children's causal thinking. Overall, these data demonstrate that children's systematic exploration and parents' causal explanation are best studied in relation to one another, because both contributed to children's learning while playing at a museum exhibit. Children engaged in systematic exploration, which supported their causal thinking. Parents' causal talk supported children's exploration when it was presented at certain times during the interaction. In contrast, children's persistence in problem solving was less sensitive to parents' talk or interaction style, and more related to children's own language, which may act as a form of self-explanation. We discuss the findings in light of ongoing approaches to promote the benefit of parent–child interaction during play for children's learning and problem solving. We also examine the implications of these findings for formal and informal learning settings, and for theoretical integration of constructivist and sociocultural approaches in the study of children's causal thinking.National Science Foundation under Grants 1420259, 1420241, and 1420548

Histological heterogeneity in a large clinical cohort of juvenile idiopathic inflammatory myopathy: analysis by myositis autoantibody and pathological features

AIM: Juvenile idiopathic inflammatory myopathies (IIM) have been recently reclassified into clinico-serological subgroups. Myopathological correlates of the subgroups are incompletely understood. METHODS: We studied muscle biopsies from 101 children with clinically and serologically-defined juvenile IIM from the UK JDM Cohort and Biomarker Study by applying the international JDM score tool, myopathological review, and C5b-9 complement analysis. RESULTS: Autoantibody data were available for 90/101 cases with 18/90 cases positive for anti-TIF1γ, 15/90 anti-NXP2, 11/90 anti-MDA5, 5/90 anti-Mi2, and 6/90 anti-PmScl. JDM biopsy severity scores were consistently low in the anti-MDA5 group, high in the anti-Mi2 group, and widely distributed in the other groups. Biopsies were classified histologically as perifascicular atrophy (22/101), macrophage-rich necrosis (6/101), scattered necrosis (2/101), clustered necrosis (2/101), inflammatory fibre invasion (2/101), chronic myopathic change (1/101), diffuse endomysial macrophage infiltrates (40/101), and minimal change (24/101). MDA5 cases segregated with the minimal change group and showed no capillary C5b-9-deposition. The Mi2 group displayed high severity scores and a tendency towards sarcolemmal complement deposition. NXP2 and TIF1γ groups showed a variety of pathologies with a high proportion of diffuse endomysial macrophage infiltrates and a high proportion of capillary C5b-9 deposition. CONCLUSION: We have shown that juvenile idiopathic inflammatory myopathies have a spectrum of histopathological phenotypes and show distinct complement attack complex deposition patterns. Both correlate in some cases with the serological subtypes. Most cases do not show typical histological features associated with dermatomyositis (e.g. perifascicular atrophy). In contrast, more than half show relatively mild histopathological changes. This article is protected by copyright. All rights reserved