RNA-seq based transcriptomic map reveals new insights into mouse salivary gland development and maturation

Heatmap depicting the hierarchical clustering of the 45 genes that are conserved between the mouse adult salivary gland gene signature and the RNA-seq data obtained from the Human Protein Atlas. The values reported represent Z-scores of the conserved genes in their respective datasets. (PDF 737 kb

An Active Role of the ΔN Isoform of p63 in Regulating Basal Keratin Genes K5 and K14 and Directing Epidermal Cell Fate

BACKGROUND: One major defining characteristic of the basal keratinocytes of the stratified epithelium is the expression of the keratin genes K5 and K14. The temporal and spatial expression of these two genes is usually tightly and coordinately regulated at the transcriptional level. This ensures the obligate pairing of K5 and K14 proteins to generate an intermediate filament (IF) network that is essential for the structure and function of the proliferative keratinocytes. Our previous studies have shown that the basal-keratinocyte restricted transcription factor p63 is a direct regulator of K14 gene. METHODOLOGY/PRINCIPAL FINDINGS: Here we provide evidence that p63, specifically the DeltaN isoform also regulates the expression of the K5 gene by binding to a conserved enhancer within the 5' upstream region. By using specific antibodies against DeltaNp63, we show a concordance in the expression between basal keratins and DeltaNp63 proteins but not the TAp63 isoforms during early embryonic skin development. We demonstrate, that contrary to a previous report, transgenic mice expressing DeltaNp63 in lung epithelium exhibit squamous metaplasia with de novo induction of K5 and K14 as well as transdifferentiation to the epidermal cell lineage. Interestingly, the in vivo epidermal inductive properties of DeltaNp63 do not require the C-terminal SAM domain. Finally, we show that DeltaNp63 alone can restore the expression of the basal keratins and reinitiate the failed epidermal differentiation program in the skin of p63 null animals. SIGNIFICANCE: DeltaNp63 is a critical mediator of keratinocyte stratification program and directly regulates the basal keratin genes

A global analysis of the complex landscape of isoforms and regulatory networks of p63 in human cells and tissues

Expression database. Column A contains the names of the 1099 TFs in humans. Columns B–BC provide the expression of the TFs in FPKM (fragments per kilobase of transcript per million), as calculated by Analysis Pipeline 1, across the 40 cell-types (52 experiments). (CSV 553 kb

Genome-wide search identifies Ccnd2 as a direct transcriptional target of Elf5 in mouse mammary gland

<p>Abstract</p> <p>Background</p> <p>The ETS transcription factor Elf5 (also known as ESE-2) is highly expressed in the mammary gland and plays an important role in its development and differentiation. Indeed studies in mice have illustrated an essential role for Elf5 in directing alveologenesis during pregnancy. Although the molecular mechanisms that underlie the developmental block in Elf5 null mammary glands are beginning to be unraveled, this investigation has been hampered by limited information about the identity of Elf5-target genes. To address this shortcoming, in this study we have performed ChIP-cloning experiments to identify the specific genomic segments that are occupied by Elf5 in pregnant mouse mammary glands.</p> <p>Results</p> <p>Sequencing and genomic localization of <it>cis</it>-regulatory regions bound by Elf5 <it>in vivo </it>has identified several potential target genes covering broad functional categories. A subset of these target genes demonstrates higher expression levels in Elf5-null mammary glands suggesting a repressive functional role for this transcription factor. Here we focus on one putative target of Elf5, the <it>Ccnd2 </it>gene that appeared in our screen. We identify a novel Elf5-binding segment upstream of the <it>Ccnd2 </it>gene and demonstrate that Elf5 can transcriptionally repress Ccnd2 by directly binding to the proximal promoter region. Finally, using Elf5-null mammary epithelial cells and mammary glands, we show that loss of Elf5 <it>in vivo </it>leads to up regulation of Ccnd2 and an altered expression pattern in luminal cells.</p> <p>Conclusions</p> <p>Identification of Elf5-targets is an essential first step in elucidating the transcriptional landscape that is shaped by this important regulator. Our studies offer new toolbox in examining the biological role of Elf5 in mammary gland development and differentiation.</p

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Discutindo a educação ambiental no cotidiano escolar: desenvolvimento de projetos na escola formação inicial e continuada de professores

A presente pesquisa buscou discutir como a Educação Ambiental (EA) vem sendo trabalhada, no Ensino Fundamental e como os docentes desta escola compreendem e vem inserindo a EA no cotidiano escolar., em uma escola estadual do município de Tangará da Serra/MT, Brasil. Para tanto, realizou-se entrevistas com os professores que fazem parte de um projeto interdisciplinar de EA na escola pesquisada. Verificou-se que o projeto da escola não vem conseguindo alcançar os objetivos propostos por: desconhecimento do mesmo, pelos professores; formação deficiente dos professores, não entendimento da EA como processo de ensino-aprendizagem, falta de recursos didáticos, planejamento inadequado das atividades. A partir dessa constatação, procurou-se debater a impossibilidade de tratar do tema fora do trabalho interdisciplinar, bem como, e principalmente, a importância de um estudo mais aprofundado de EA, vinculando teoria e prática, tanto na formação docente, como em projetos escolares, a fim de fugir do tradicional vínculo “EA e ecologia, lixo e horta”.Facultad de Humanidades y Ciencias de la Educació