129 research outputs found

    Issues of Cost & Access in Canada’s Early Childhood Education System: Lessons for the Civil Justice System

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    In recent years in Canada, there has been growing appreciation that early childhood education (ECE) is a basic foundation for building a successful education system, competitive global economy, and a well functioning democracy. A policy of publicly funding ECE programming is, in other words, seen as a smart investment in the future. This new appreciation of ECE is evident from the fact that ECE is now integrated into our school system and early childhood educators are recognized as trained professionals, not mere childcare workers. ECE policies in Ontario are now a model of evidence-based decision-making. Early learning initiatives such as full-day kindergartens and seamless days are based on new innovative research on child development that shows the long term benefits of skills such as early literacy and self-regulation for young children. ECE is also an effective compensatory vehicle for children from disadvantaged socio-economic backgrounds

    Phylogenetic analysis of Croatian orf viruses isolated from sheep and goats

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    <p>Abstract</p> <p>Background</p> <p>The <it>Orf virus </it>(ORFV) is the prototype of the parapoxvirus genus and it primarily causes contagious ecthyma in goats, sheep, and other ruminants worldwide. In this paper, we described the sequence and phylogenetic analysis of the B2L gene of ORFV from two natural outbreaks: i) in autochthonous Croatian Cres-breed sheep and ii) on small family goat farm.</p> <p>Results</p> <p>Sequence and phylogenetic analyses of the ORFV B2L gene showed that the Cro-Cres-12446/09 and Cro-Goat-11727/10 were not clustered together. Cro-Cres-12446/09 shared the highest similarity with ORFV NZ2 from New Zealand, and Ena from Japan; Cro-Goat-11727/10 was closest to the HuB from China and Taiping and Hoping from Taiwan.</p> <p>Conclusion</p> <p>Distinct ORFV strains are circulating in Croatia. Although ORFV infections are found ubiquitously wherever sheep and goats are farmed in Croatia, this is the first information on genetic relatedness of any Croatian ORFV with other isolates around the world.</p

    ERRα promotes breast cancer cell dissemination to bone by increasing RANK expression in primary breast tumors

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    Bone is the most common metastatic site for breast cancer. Estrogen-related-receptor alpha (ERRα) has been implicated in cancer cell invasiveness. Here, we established that ERRα promotes spontaneous metastatic dissemination of breast cancer cells from primary mammary tumors to the skeleton. We carried out cohort studies, pharmacological inhibition, gain-of-function analyses in vivo and cellular and molecular studies in vitro to identify new biomarkers in breast cancer metastases. Meta-analysis of human primary breast tumors revealed that high ERRα expression levels were associated with bone but not lung metastases. ERRα expression was also detected in circulating tumor cells from metastatic breast cancer patients. ERRα overexpression in murine 4T1 breast cancer cells promoted spontaneous bone micro-metastases formation when tumor cells were inoculated orthotopically, whereas lung metastases occurred irrespective of ERRα expression level. In vivo, Rank was identified as a target for ERRα. That was confirmed in vitro in Rankl stimulated tumor cell invasion, in mTOR/pS6K phosphorylation, by transactivation assay, ChIP and bioinformatics analyses. Moreover, pharmacological inhibition of ERRα reduced primary tumor growth, bone micro-metastases formation and Rank expression in vitro and in vivo. Transcriptomic studies and meta-analysis confirmed a positive association between metastases and ERRα/RANK in breast cancer patients and also revealed a positive correlation between ERRα and BRCA1mut carriers. Taken together, our results reveal a novel ERRα/RANK axis by which ERRα in primary breast cancer promotes early dissemination of cancer cells to bone. These findings suggest that ERRα may be a useful therapeutic target to prevent bone metastases

    The Phylogenetics and Ecology of the Orthopoxviruses Endemic to North America

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    The data presented herein support the North American orthopoxviruses (NA OPXV) in a sister relationship to all other currently described Orthopoxvirus (OPXV) species. This phylogenetic analysis reaffirms the identification of the NA OPXV as close relatives of “Old World” (Eurasian and African) OPXV and presents high support for deeper nodes within the Chordopoxvirinae family. The natural reservoir host(s) for many of the described OPXV species remains unknown although a clear virus-host association exists between the genus OPXV and several mammalian taxa. The hypothesized host associations and the deep divergence of the OPXV/NA OPXV clades depicted in this study may reflect the divergence patterns of the mammalian faunas of the Old and New World and reflect a more ancient presence of OPXV on what are now the American continents. Genes from the central region of the poxvirus genome are generally more conserved than genes from either end of the linear genome due to functional constraints imposed on viral replication abilities. The relatively slower evolution of these genes may more accurately reflect the deeper history among the poxvirus group, allowing for robust placement of the NA OPXV within Chordopoxvirinae. Sequence data for nine genes were compiled from three NA OPXV strains plus an additional 50 genomes collected from Genbank. The current, gene sequence based phylogenetic analysis reaffirms the identification of the NA OPXV as the nearest relatives of “Old World” OPXV and presents high support for deeper nodes within the Chordopoxvirinae family. Additionally, the substantial genetic distances that separate the currently described NA OPXV species indicate that it is likely that many more undescribed OPXV/NA OPXV species may be circulating among wild animals in North America

    Complete Genome Viral Phylogenies Suggests the Concerted Evolution of Regulatory Cores and Accessory Satellites

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    We consider the concerted evolution of viral genomes in four families of DNA viruses. Given the high rate of horizontal gene transfer among viruses and their hosts, it is an open question as to how representative particular genes are of the evolutionary history of the complete genome. To address the concerted evolution of viral genes, we compared genomic evolution across four distinct, extant viral families. For all four viral families we constructed DNA-dependent DNA polymerase-based (DdDp) phylogenies and in addition, whole genome sequence, as quantitative descriptions of inter-genome relationships. We found that the history of the polymerase gene was highly predictive of the history of the genome as a whole, which we explain in terms of repeated, co-divergence events of the core DdDp gene accompanied by a number of satellite, accessory genetic loci. We also found that the rate of gene gain in baculovirus and poxviruses proceeds significantly more quickly than the rate of gene loss and that there is convergent acquisition of satellite functions promoting contextual adaptation when distinct viral families infect related hosts. The congruence of the genome and polymerase trees suggests that a large set of viral genes, including polymerase, derive from a phylogenetically conserved core of genes of host origin, secondarily reinforced by gene acquisition from common hosts or co-infecting viruses within the host. A single viral genome can be thought of as a mutualistic network, with the core genes acting as an effective host and the satellite genes as effective symbionts. Larger virus genomes show a greater departure from linkage equilibrium between core and satellites functions

    Middle Neolithic farming of open-air sites in SE France: new insights from archaeobotanical investigations of three wells found at Les Bagnoles (L'Isle-sur-la-Sorgue, Dépt. Vaucluse, France)

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    Previous reviews of Middle Neolithic agricultural practice (4400–3500 cal bc) in southern France have highlighted a change in crop assemblages after 4000 cal bc, with a reduction of naked wheat and an increase of emmer and partly of einkorn. The recent investigation of three wells from the site of Les Bagnoles (4250–3800 cal bc) in the periphery of the southern Rhône valley yielded an unprecedented amount of waterlogged uncharred and charred plant macro remains that offer new insights into crop diversity and its changes over time. The results from the wells at Les Bagnoles were compared with other dated sunken features from open-air sites (in contrast to caves and rock shelters), with the aim of identifying patterns sug-gesting changes in the crop spectra between the early (MN1) and late (MN2) Middle Neolithic phases from taphonomically comparable contexts. The results from Les Bagnoles demonstrate that oil crops and pulses are underrepresented in dry sites and that they were a significant part of Middle Neolithic agriculture. They also indicate an increase in the representation of einkorn (instead of emmer) during MN2 that is also visible in other open-air sites. The comparison of the archaeobotani-cal results with silo storage capacity values as a proxy for average production capacity per household leads us to propose a possible drop in naked wheat productivity and opens new questions in factors affecting crop choice at the beginning of the 4th millennium cal bc
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