958 research outputs found

    Summary report on excavations at Tell Khaiber, an administrative centre of the Sealand period, 2013-2017

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    Excavations at Tell Khaiber by the Ur Region Archaeological Project have revealed a substantial building (hereafter the Public Building) dating to the mid-second millennium BC. The results are significant for several reasons: they shed light on Babylonian provincial administration; they reveal a previously unknown type of fortified monumental building; and they produced a provenanced, dated archive of the little-understood Sealand Dynasty. Here we give a summary of the main results, including the architecture and the material culture. There are also comments on the historical background, and a discussion of the form and function of the Public Building

    RNA-seq transcriptional profiling of peripheral blood leukocytes from cattle infected with Mycobacterium bovis

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    Bovine tuberculosis, caused by infection with Mycobacterium bovis, is a major endemic disease affecting cattle populations worldwide, despite the implementation of stringent surveillance and control programs in many countries. The development of high-throughput functional genomics technologies, including gene expression microarrays and RNA-sequencing (RNA-seq), has enabled detailed analysis of the host transcriptome to M. bovis infection, particularly at the macrophage and peripheral blood level. In the present study, we have analyzed the peripheral blood leukocyte (PBL) transcriptome of eight natural M. bovis-infected and eight age- and sex-matched non-infected control Holstein-Friesian animals using RNA-seq. In addition, we compared gene expression profiles generated using RNA-seq with those previously generated using the high-density Affymetrix(®) GeneChip(®) Bovine Genome Array platform from the same PBL-extracted RNA. A total of 3,250 differentially expressed (DE) annotated genes were detected in the M. bovis-infected samples relative to the controls (adjusted P-value ≤0.05), with the number of genes displaying decreased relative expression (1,671) exceeding those with increased relative expression (1,579). Ingenuity(®) Systems Pathway Analysis (IPA) of all DE genes revealed enrichment for genes with immune function. Notably, transcriptional suppression was observed among several of the top-ranking canonical pathways including Leukocyte Extravasation Signaling. Comparative platform analysis demonstrated that RNA-seq detected a larger number of annotated DE genes (3,250) relative to the microarray (1,398), of which 917 genes were common to both technologies and displayed the same direction of expression. Finally, we show that RNA-seq had an increased dynamic range compared to the microarray for estimating differential gene expression

    Whole-transcriptome, high-throughput RNA sequence analysis of the bovine macrophage response to Mycobacterium bovis infection in vitro

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    BACKGROUND: Mycobacterium bovis, the causative agent of bovine tuberculosis, is an intracellular pathogen that can persist inside host macrophages during infection via a diverse range of mechanisms that subvert the host immune response. In the current study, we have analysed and compared the transcriptomes of M. bovis-infected monocyte-derived macrophages (MDM) purified from six Holstein-Friesian females with the transcriptomes of non-infected control MDM from the same animals over a 24 h period using strand-specific RNA sequencing (RNA-seq). In addition, we compare gene expression profiles generated using RNA-seq with those previously generated by us using the high-density Affymetrix® GeneChip® Bovine Genome Array platform from the same MDM-extracted RNA. RESULTS: A mean of 7.2 million reads from each MDM sample mapped uniquely and unambiguously to single Bos taurus reference genome locations. Analysis of these mapped reads showed 2,584 genes (1,392 upregulated; 1,192 downregulated) and 757 putative natural antisense transcripts (558 upregulated; 119 downregulated) that were differentially expressed based on sense and antisense strand data, respectively (adjusted P-value ≤ 0.05). Of the differentially expressed genes, 694 were common to both the sense and antisense data sets, with the direction of expression (i.e. up- or downregulation) positively correlated for 693 genes and negatively correlated for the remaining gene. Gene ontology analysis of the differentially expressed genes revealed an enrichment of immune, apoptotic and cell signalling genes. Notably, the number of differentially expressed genes identified from RNA-seq sense strand analysis was greater than the number of differentially expressed genes detected from microarray analysis (2,584 genes versus 2,015 genes). Furthermore, our data reveal a greater dynamic range in the detection and quantification of gene transcripts for RNA-seq compared to microarray technology. CONCLUSIONS: This study highlights the value of RNA-seq in identifying novel immunomodulatory mechanisms that underlie host-mycobacterial pathogen interactions during infection, including possible complex post-transcriptional regulation of host gene expression involving antisense RNA

    Did they report it to stop it? A realist evaluation of the effect of an advertising campaign on victims’ willingness to report unwanted sexual behaviour

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    Tackling unwanted sexual behaviour (USB) on public transport is a concern for transit authorities across the world. However, high rates of underreporting mean a lack of reliable information about USB, presenting a key barrier to prevention. This paper presents a realist evaluation of an initiative called ‘Report It To Stop It’ (RITSI) implemented in London, UK, to tackle underreporting. RITSI aimed to encourage victims to report details of USB incidents to police and transit authorities through media campaigns. Results show that the initiative did increase reporting of USB and, that this increase was not due to a rise in the prevalence of USB. Crucially, there was no evidence of any increase in passengers’ fear of crime during the campaign activity. However, the impacts of this campaign were more pronounced in earlier waves, and on certain modes of transport. These findings demonstrate the importance of the context in motivating reporting behaviour change

    Celebrate teaching and learning: A SoTL symposium at the University of the Pacific

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    This paper presents a faculty-driven teaching and learning celebration that fostered institutional cultural change. The symposium showcased exemplar instructional methods at an institution, whose mission is to to provide a superior, student-centered learning experience integrating liberal arts and professional education. The symposium was a grass-roots effort that attracted seventy-two faculty members from various disciplines to attend the four day symposium sessions to share, discuss, and learn about the best practices used by their colleagues. The overall evaluation and response to the symposium exceeded the expectations of the organizers. The paper contributes to both the scholarship of teaching and learning and institutional cultural change literature by providing an overview of the program, reflections on the endeavor, and four successful presentations that helped to foster an interdisciplinary community of practice committed to sustainable pedagogies

    Neuronal differentiation by TAp73 is mediated by microRNA-34a regulation of synaptic protein targets

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    The p53-family member TAp73 is a transcription factor that plays a key role in many biological processes. Here, we show that p73 drives the expression of microRNA (miR)-34a, but not miR-34b and -c, by acting on specific binding sites on the miR-34a promoter. Expression of miR-34a is modulated in parallel with that of TAp73 during in vitro differentiation of neuroblastoma cells and cortical neurons. Retinoid-driven neuroblastoma differentiation is inhibited by knockdown of either p73 or miR-34a. Transcript expression of miR-34a is significantly reduced in vivo both in the cortex and hippocampus of p73−/− mice; miR-34a and TAp73 expression also increase during postnatal development of the brain and cerebellum when synaptogenesis occurs. Accordingly, overexpression or silencing of miR-34a inversely modulates expression of synaptic targets, including synaptotagmin-1 and syntaxin-1A. Notably, the axis TAp73/miR-34a/synaptotagmin-1 is conserved in brains from Alzheimer's patients. These data reinforce a role for TAp73 in neuronal development
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