Promoting Fundamental movement skill development and physical activity in early childhood settings : a cluster randomized controlled trial

The aim of this study was to assess the feasibility, acceptability and potential efficacy of a physical activity program for preschool children. A 20-week, 2-arm parallel cluster randomized controlled pilot trial was conducted. The intervention comprised structured activities for children and professional development for staff. The control group participated in usual care activities, which included designated inside and outside playtime. Primary outcomes were movement skill development and objectively measured physical activity. At follow-up, compared with children in the control group, children in the intervention group showed greater improvements in movement skill proficiency, with this improvement statically significant for overall movement skill development (adjust diff. = 2.08, 95% CI 0.76, 3.40; Cohen&rsquo;s d = 0.47) and significantly greater increases in objectively measured physical activity (counts per minute) during the preschool day (adjust diff. = 110.5, 95% CI 33.6, 187.3; Cohen&rsquo;s d = 0.46). This study demonstrates that a physical activity program implemented by staff within a preschool setting is feasible, acceptable and potentially efficacious.<br /

Ferrets exclusively synthesize Neu5Ac and express naturally humanized influenza A virus receptors

Mammals express the sialic acids ​N-acetylneuraminic acid (​Neu5Ac) and ​N-glycolylneuraminic acid (​Neu5Gc) on cell surfaces, where they act as receptors for pathogens, including influenza A virus (IAV). ​Neu5Gc is synthesized from ​Neu5Ac by the enzyme cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMAH). In humans, this enzyme is inactive and only ​Neu5Ac is produced. Ferrets are susceptible to human-adapted IAV strains and have been the dominant animal model for IAV studies. Here we show that ferrets, like humans, do not synthesize ​Neu5Gc. Genomic analysis reveals an ancient, nine-exon deletion in the ferret CMAH gene that is shared by the Pinnipedia and Musteloidia members of the Carnivora. Interactions between two human strains of IAV with the sialyllactose receptor (sialic acid—α2,6Gal) confirm that the type of terminal sialic acid contributes significantly to IAV receptor specificity. Our results indicate that exclusive expression of ​Neu5Ac contributes to the susceptibility of ferrets to human-adapted IAV strains

Cardiac expression of the cystic fibrosis transmembrane conductance regulator involves novel Exon 1 usage to produce a unique amino-terminal protein

Cystic fibrosis is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which encodes a chloride channel present in many cells. In cardiomyocytes, we report that multiple exon 1 usage and alternative splicing produces four CFTR transcripts, with different 5'-untranslated regions, CFTRTRAD-139, CFTR-1C/-1A, CFTR-1C, and CFTR-1B. CFTR transcripts containing the novel upstream exons (exons -1C, -1B, and -1A) represent more than 90% of cardiac expressed CFTR mRNA. Regulation of cardiac CFTR expression, in response to developmental and pathological stimuli, is exclusively due to the modulation of CFTR-1C and CFTR-1C/-1A expression. Upstream open reading frames have been identified in the 5'-untranslated regions of all CFTR transcripts that, in conjunction with adjacent stem-loop structures, modulate the efficiency of translation initiation at the AUG codon of the main CFTR coding region in CFTRTRAD-139 and CFTR-1C/-1A transcripts. Exon(-1A), only present in CFTR-1C/-1A transcripts, encodes an AUG codon that is in-frame with the main CFTR open reading frame, the efficient translation of which produces a novel CFTR protein isoform with a curtailed amino terminus. As the expression of this CFTR transcript parallels the spatial and temporal distribution of the cAMP-activated whole-cell current density in normal and diseased hearts, we suggest that CFTR-1C/-1A provides the molecular basis for the cardiac cAMP-activated chloride channel. Our findings provide further insight into the complex nature of in vivo CFTR expression, to which multiple mRNA transcripts, protein isoforms, and post-transcriptional regulatory mechanisms are now added

Informative tools for characterizing individual differences in learning: Latent class, latent profile, and latent transition analysis

This article gives an introduction to latent class, latent profile, and latent transition models for researchers interested in investigating individual differences in learning and development. The models allow analyzing how the observed heterogeneity in a group (e.g., individual differences in conceptual knowledge) can be traced back to underlying homogeneous subgroups (e.g., learners differing systematically in their developmental phases). The estimated parameters include a characteristic response pattern for each subgroup, and, in the case of longitudinal data, the probabilities of transitioning from one subgroup to another over time. This article describes the steps involved in using the models, gives practical examples, and discusses limitations and extensions. Overall, the models help to characterize heterogeneous learner populations, multidimensional learning outcomes, non-linear learning pathways, and changing relations between learning processes. The application of these models can therefore make a substantial contribution to our understanding of learning and individual differences.</p

Die Weltwirtschaft im Wandel: Symposium 1975

Seit einigen Jahren verstärkt sich der Eindruck, daß die Weltwirtschaft in einem raschen Wandel begriffen ist. Die Entwicklungsländer fordern eine neue Weltwirtschaftsordnung. Auf die weltweite Hochkonjunktur ist eine scharfe und recht lange anhaltende Rezession gefolgt; aber noch immer dominieren inflationäre Tendenzen. Den Konjunktureinbruch überlagert hat die Vervielfachung des Ölpreises Ende 1973. Sie wurde von vielen Beobachtern als Beginn einer Phase mit zunehmendem Rohstoffmangel und nie gekannten Ungleichgewichten in den Zahlungsbilanzen gedeutet. Von den vielfach geäußerten Befürchtungen haben sich manche als übertrieben erwiesen; denn viele Schwierigkeiten konnte der Markt viel besser als erwartet und ziemlich geräuschlos bewältigen. Gleichwohl erscheint es geraten, die alten und die neuen Probleme der Weltwirtschaft ständig zu beobachten. Vom 23. -27. Juni, traf sich in Kiel eine Gruppe unabhängiger Ökonomen aus Japan, Nordamerika und der Europäischen Gemeinschaft in der Absicht, die Situation der Weltwirtschaft zu analysieren und Vorschläge für wirtschaftspolitische Maßnahmen auf nationaler und internationaler Ebene auszuarbeiten. Das Institut für Weltwirtschaft war Gastgeber. Das Kieler Symposium ist ein Glied in einer Reihe trilateraler Konferenzen über weltwirtschaftliche Fragen, die von der Brookings Institution in Washington, dem Japan Economic Research Center in Tokio und dem Institut für Weltwirtschaft gemeinsam veranstaltet werden. Die Ergebnisse werden jeweils in englischer, japanischer und deutscher Sprache veröffentlicht; frühere Berichte in der deutschen Fassung sind als Kieler Diskussionsbeiträge Nr. 31 "Welthandel und Strukturanpassung in den Industrieländern" und Nr. 36 "Weltrohstoffversorgung: Konflikt oder Kooperation?" erschienen

Die Weltwirtschaft im Wandel: Symposium 1975

Seit einigen Jahren verstärkt sich der Eindruck, daß die Weltwirtschaft in einem raschen Wandel begriffen ist. Die Entwicklungsländer fordern eine neue Weltwirtschaftsordnung. Auf die weltweite Hochkonjunktur ist eine scharfe und recht lange anhaltende Rezession gefolgt; aber noch immer dominieren inflationäre Tendenzen. Den Konjunktureinbruch überlagert hat die Vervielfachung des Ölpreises Ende 1973. Sie wurde von vielen Beobachtern als Beginn einer Phase mit zunehmendem Rohstoffmangel und nie gekannten Ungleichgewichten in den Zahlungsbilanzen gedeutet. Von den vielfach geäußerten Befürchtungen haben sich manche als übertrieben erwiesen; denn viele Schwierigkeiten konnte der Markt viel besser als erwartet und ziemlich geräuschlos bewältigen. Gleichwohl erscheint es geraten, die alten und die neuen Probleme der Weltwirtschaft ständig zu beobachten. Vom 23. -27. Juni, traf sich in Kiel eine Gruppe unabhängiger Ökonomen aus Japan, Nordamerika und der Europäischen Gemeinschaft in der Absicht, die Situation der Weltwirtschaft zu analysieren und Vorschläge für wirtschaftspolitische Maßnahmen auf nationaler und internationaler Ebene auszuarbeiten. Das Institut für Weltwirtschaft war Gastgeber. Das Kieler Symposium ist ein Glied in einer Reihe trilateraler Konferenzen über weltwirtschaftliche Fragen, die von der Brookings Institution in Washington, dem Japan Economic Research Center in Tokio und dem Institut für Weltwirtschaft gemeinsam veranstaltet werden. Die Ergebnisse werden jeweils in englischer, japanischer und deutscher Sprache veröffentlicht; frühere Berichte in der deutschen Fassung sind als Kieler Diskussionsbeiträge Nr. 31 "Welthandel und Strukturanpassung in den Industrieländern" und Nr. 36 "Weltrohstoffversorgung: Konflikt oder Kooperation?" erschienen. --

The inwardly rectifying K+ channel KIR7.1 controls uterine excitability throughout pregnancy

Abnormal uterine activity in pregnancy causes a range of important clinical disorders, including preterm birth, dysfunctional labour and post-partum haemorrhage. Uterine contractile patterns are controlled by the generation of complex electrical signals at the myometrial smooth muscle plasma membrane. To identify novel targets to treat conditions associated with uterine dysfunction, we undertook a genome-wide screen of potassium channels that are enriched in myometrial smooth muscle. Computational modelling identified Kir7.1 as potentially important in regulating uterine excitability during pregnancy. We demonstrate Kir7.1 current hyper-polarizes uterine myocytes and promotes quiescence during gestation. Labour is associated with a decline, but not loss, of Kir7.1 expression. Knockdown of Kir7.1 by lentiviral expression of miRNA was sufficient to increase uterine contractile force and duration significantly. Conversely, overexpression of Kir7.1 inhibited uterine contractility. Finally, we demonstrate that the Kir7.1 inhibitor VU590 as well as novel derivative compounds induces profound, long-lasting contractions in mouse and human myometrium; the activity of these inhibitors exceeds that of other uterotonic drugs. We conclude Kir7.1 regulates the transition from quiescence to contractions in the pregnant uterus and may be a target for therapies to control uterine contractility

In vitro and in vivo MMP gene expression localisation by In Situ-RT-PCR in cell culture and paraffin embedded human breast cancer cell line xenografts

BACKGROUND: Members of the matrix metalloproteinase (MMP) family of proteases are required for the degradation of the basement membrane and extracellular matrix in both normal and pathological conditions. In vitro, MT1-MMP (MMP-14, membrane type-1-MMP) expression is higher in more invasive human breast cancer (HBC) cell lines, whilst in vivo its expression has been associated with the stroma surrounding breast tumours. MMP-1 (interstitial collagenase) has been associated with MDA-MB-231 invasion in vitro, while MMP-3 (stromelysin-1) has been localised around invasive cells of breast tumours in vivo. As MMPs are not stored intracellularly, the ability to localise their expression to their cells of origin is difficult. METHODS: We utilised the unique in situ-reverse transcription-polymerase chain reaction (IS-RT-PCR) methodology to localise the in vitro and in vivo gene expression of MT1-MMP, MMP-1 and MMP-3 in human breast cancer. In vitro, MMP induction was examined in the MDA-MB-231 and MCF-7 HBC cell lines following exposure to Concanavalin A (Con A). In vivo, we examined their expression in archival paraffin embedded xenografts derived from a range of HBC cell lines of varied invasive and metastatic potential. Mouse xenografts are heterogenous, containing neoplastic human parenchyma with mouse stroma and vasculature and provide a reproducible in vivo model system correlated to the human disease state. RESULTS: In vitro, exposure to Con A increased MT1-MMP gene expression in MDA-MB-231 cells and decreased MT1-MMP gene expression in MCF-7 cells. MMP-1 and MMP-3 gene expression remained unchanged in both cell lines. In vivo, stromal cells recruited into each xenograft demonstrated differences in localised levels of MMP gene expression. Specifically, MDA-MB-231, MDA-MB-435 and Hs578T HBC cell lines are able to influence MMP gene expression in the surrounding stroma. CONCLUSION: We have demonstrated the applicability and sensitivity of IS-RT-PCR for the examination of MMP gene expression both in vitro and in vivo. Induction of MMP gene expression in both the epithelial tumour cells and surrounding stromal cells is associated with increased metastatic potential. Our data demonstrate the contribution of the stroma to epithelial MMP gene expression, and highlight the complexity of the role of MMPs in the stromal-epithelial interactions within breast carcinoma

Patterns of Positive Selection and Neutral Evolution in the Protein-Coding Genes of Tetraodon and Takifugu

Recent genome-wide analyses have revealed patterns of positive selection acting on protein-coding genes in humans and mammals. To assess whether the conclusions drawn from these analyses are valid for other vertebrates and to identify mammalian specificities, I have investigated the selective pressure acting on protein-coding genes of the puffer fishes Tetraodon and Takifugu. My results indicate that the strength of purifying selection in puffer fishes is similar to previous reports for murids but stronger in hominids, which have a smaller population size. Gene ontology analyses show that more than half of the biological processes targeted by positive selection in mammals are also targeted in puffer fishes, highlighting general patterns for vertebrates. Biological processes enriched with positively selected genes that are shared between mammals and fishes include immune and defense responses, signal transduction, regulation of transcription and several of their descendent terms. Mammalian-specific processes displaying an excess of positively selected genes are related to sensory perception and neurological processes. The comparative analyses also revealed that, for both mammals and fishes, genes encoding extracellular proteins are preferentially targeted by positive selection, indicating that adaptive evolution occurs more often in the extra-cellular environment rather than inside the cell. Moreover, I present here the first genome-wide characterization of neutrally-evolving regions of protein-coding genes. This analysis revealed an unexpectedly high proportion of genes containing both positively selected motifs and neutrally-evolving regions, uncovering a strong link between neutral evolution and positive selection. I speculate that neutrally-evolving regions are a major source of novelties screened by natural selection