147 research outputs found

    The Uneasiest State: Art, Culture, and Society in New Deal Louisiana, 1933-1943. (Volumes I and II).

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    During the Great Depression artists working in programs funded by the federal government roamed the nation wielding brushes, jotting notes, and pointing cameras in an attempt to define and characterize American society. Never before and not since has this country conducted so intensive a survey of itself, or one so controversial. Federal patronage of the arts occurred during an anxious period of political and cultural turmoil, a turmoil inherent in the story of the Arts Projects themselves. The very structure, organization, composition, execution, and objectives of the arts agencies mirror the tensions of the age. The artists\u27 selection or avoidance of subjects, even the manner by which the fruits of their labors were disseminated among the American people, reflects the turbulence of the 1930s. Nowhere is this more evident than in Huey Long\u27s Louisiana, where the government art program recorded some of its greatest achievements and most bitter disappointments. This dissertation is an interdisciplinary analysis of four federal programs in Louisiana, a state then undergoing rapid political and social transformation. Each of the projects, individually and collectively, not only provides a valuable glimpse into the character of American society in crisis, but also addresses many of the enduring questions of this Republic

    Functional complementarity between the HMG1-like yeast mitochondrial histone HM and the bacterial histone-like protein HU

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    The mitochondrial histone HM is the major DNA-binding protein in mitochondria and is necessary for maintenance of the mitochondrial genome in the yeast Saccharomyces cerevisiae during growth on fermentable sugars. HM and the Escherichia coli histone-like protein HU have similar activities in vitro, including DNA supercoiling, but share no sequence similarity. We show that HU can functionally complement the respiration deficiency associated with yeast strains lacking HM. Conversely, phenotypes of E. coli cells lacking HU protein, including nucleoid loss and a filamentous cell morphology, were alleviated by expression of HM in these cells. The HU protein of bacteria and the HM protein of mitochondria are therefore functionally complementary in vivo. Functional similarities among HM, HU, and the nuclear HMG1 proteins are implicated and discussed

    Essential role of the HMG domain in the function of yeast mitochondrial histone HM: functional complementation of HM by the nuclear nonhistone protein NHP6A.

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    The yeast mitochondrial histone protein HM is required for maintenance of the mitochondrial genome, and disruption of the gene encoding HM (H1M1/ABF2) results in formation of a respiration-deficient petite mutant phenotype. HM contains two homologous regions, which share sequence similarity with the eukaryotic nuclear nonhistone protein, HMG-1. Experiments with various deletion mutants of HM show that a single HMG domain of HM is functional and can restore respiration competency to cells that lack HM protein (him1 mutant cells). The gene encoding the putative yeast nuclear HMG-1 homolog, the NHP6A protein, can functionally complement the him1 mutation.The yeast mitochondrial histone protein HM is required for maintenance of the mitochondrial genome, and disruption of the gene encoding HM (H1M1/ABF2) results in formation of a respiration-deficient petite mutant phenotype. HM contains two homologous regions, which share sequence similarity with the eukaryotic nuclear nonhistone protein, HMG-1. Experiments with various deletion mutants of HM show that a single HMG domain of HM is functional and can restore respiration competency to cells that lack HM protein (him1 mutant cells). The gene encoding the putative yeast nuclear HMG-1 homolog, the NHP6A protein, can functionally complement the him1 mutation

    PlantSimLab - a modeling and simulation web tool for plant biologists.

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    BACKGROUND: At the molecular level, nonlinear networks of heterogeneous molecules control many biological processes, so that systems biology provides a valuable approach in this field, building on the integration of experimental biology with mathematical modeling. One of the biggest challenges to making this integration a reality is that many life scientists do not possess the mathematical expertise needed to build and manipulate mathematical models well enough to use them as tools for hypothesis generation. Available modeling software packages often assume some modeling expertise. There is a need for software tools that are easy to use and intuitive for experimentalists. RESULTS: This paper introduces PlantSimLab, a web-based application developed to allow plant biologists to construct dynamic mathematical models of molecular networks, interrogate them in a manner similar to what is done in the laboratory, and use them as a tool for biological hypothesis generation. It is designed to be used by experimentalists, without direct assistance from mathematical modelers. CONCLUSIONS: Mathematical modeling techniques are a useful tool for analyzing complex biological systems, and there is a need for accessible, efficient analysis tools within the biological community. PlantSimLab enables users to build, validate, and use intuitive qualitative dynamic computer models, with a graphical user interface that does not require mathematical modeling expertise. It makes analysis of complex models accessible to a larger community, as it is platform-independent and does not require extensive mathematical expertise

    E-Cadherin Is Required for Centrosome and Spindle Orientation in Drosophila Male Germline Stem Cells

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    Many adult stem cells reside in a special microenvironment known as the niche, where they receive essential signals that specify stem cell identity. Cell-cell adhesion mediated by cadherin and integrin plays a crucial role in maintaining stem cells within the niche. In Drosophila melanogaster, male germline stem cells (GSCs) are attached to niche component cells (i.e., the hub) via adherens junctions. The GSC centrosomes and spindle are oriented toward the hub-GSC junction, where E-cadherin-based adherens junctions are highly concentrated. For this reason, adherens junctions are thought to provide a polarity cue for GSCs to enable proper orientation of centrosomes and spindles, a critical step toward asymmetric stem cell division. However, understanding the role of E-cadherin in GSC polarity has been challenging, since GSCs carrying E-cadherin mutations are not maintained in the niche. Here, we tested whether E-cadherin is required for GSC polarity by expressing a dominant-negative form of E-cadherin. We found that E-cadherin is indeed required for polarizing GSCs toward the hub cells, an effect that may be mediated by Apc2. We also demonstrated that E-cadherin is required for the GSC centrosome orientation checkpoint, which prevents mitosis when centrosomes are not correctly oriented. We propose that E-cadherin orchestrates multiple aspects of stem cell behavior, including polarization of stem cells toward the stem cell-niche interface and adhesion of stem cells to the niche supporting cells

    miRMaid: a unified programming interface for microRNA data resources

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    <p>Abstract</p> <p>Background</p> <p>MicroRNAs (miRNAs) are endogenous small RNAs that play a key role in post-transcriptional regulation of gene expression in animals and plants. The number of known miRNAs has increased rapidly over the years. The current release (version 14.0) of miRBase, the central online repository for miRNA annotation, comprises over 10.000 miRNA precursors from 115 different species. Furthermore, a large number of decentralized online resources are now available, each contributing with important miRNA annotation and information.</p> <p>Results</p> <p>We have developed a software framework, designated here as miRMaid, with the goal of integrating miRNA data resources in a uniform web service interface that can be accessed and queried by researchers and, most importantly, by computers. miRMaid is built around data from miRBase and is designed to follow the official miRBase data releases. It exposes miRBase data as inter-connected web services. Third-party miRNA data resources can be modularly integrated as miRMaid plugins or they can loosely couple with miRMaid as individual entities in the World Wide Web. miRMaid is available as a public web service but is also easily installed as a local application. The software framework is freely available under the LGPL open source license for academic and commercial use.</p> <p>Conclusion</p> <p>miRMaid is an intuitive and modular software platform designed to unify miRBase and independent miRNA data resources. It enables miRNA researchers to computationally address complex questions involving the multitude of miRNA data resources. Furthermore, miRMaid constitutes a basic framework for further programming in which microRNA-interested bioinformaticians can readily develop their own tools and data sources.</p

    Genetic Interaction of Centrosomin and Bazooka in Apical Domain Regulation in Drosophila Photoreceptor

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    Cell polarity genes including Crumbs (Crb) and Par complexes are essential for controlling photoreceptor morphogenesis. Among the Crb and Par complexes, Bazooka (Baz, Par-3 homolog) acts as a nodal component for other cell polarity proteins. Therefore, finding other genes interacting with Baz will help us to understand the cell polarity genes' role in photoreceptor morphogenesis. mutation on developing eyes to determine its role in photoreceptor morphogenesis. We found that Cnn is dispensable for retinal differentiation in eye imaginal discs during the larval stage. However, photoreceptors deficient in Cnn display dramatic morphogenesis defects including the mislocalization of Crumbs (Crb) and Bazooka (Baz) during mid-stage pupal eye development, suggesting that Cnn is specifically required for photoreceptor morphogenesis during pupal eye development. This role of Cnn in apical domain modulation was further supported by Cnn's gain-of-function phenotype. Cnn overexpression in photoreceptors caused the expansion of the apical Crb membrane domain, Baz and adherens junctions (AJs). photoreceptor

    The Characterisation of Three Types of Genes that Overlie Copy Number Variable Regions

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    Background: Due to the increased accuracy of Copy Number Variable region (CNV) break point mapping, it is now possible to say with a reasonable degree of confidence whether a gene (i) falls entirely within a CNV; (ii) overlaps the CNV or (iii) actually contains the CNV. We classify these as type I, II and III CNV genes respectively. Principal Findings: Here we show that although type I genes vary in copy number along with the CNV, most of these type I genes have the same expression levels as wild type copy numbers of the gene. These genes must, therefore, be under homeostatic dosage compensation control. Looking into possible mechanisms for the regulation of gene expression we found that type I genes have a significant paucity of genes regulated by miRNAs and are not significantly enriched for monoallelically expressed genes. Type III genes, on the other hand, have a significant excess of genes regulated by miRNAs and are enriched for genes that are monoallelically expressed. Significance: Many diseases and genomic disorders are associated with CNVs so a better understanding of the different ways genes are associated with normal CNVs will help focus on candidate genes in genome wide association studies

    Identification of microRNA-mRNA modules using microarray data

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    <p>Abstract</p> <p>Background</p> <p>MicroRNAs (miRNAs) are post-transcriptional regulators of mRNA expression and are involved in numerous cellular processes. Consequently, miRNAs are an important component of gene regulatory networks and an improved understanding of miRNAs will further our knowledge of these networks. There is a many-to-many relationship between miRNAs and mRNAs because a single miRNA targets multiple mRNAs and a single mRNA is targeted by multiple miRNAs. However, most of the current methods for the identification of regulatory miRNAs and their target mRNAs ignore this biological observation and focus on miRNA-mRNA pairs.</p> <p>Results</p> <p>We propose a two-step method for the identification of many-to-many relationships between miRNAs and mRNAs. In the first step, we obtain miRNA and mRNA clusters using a combination of miRNA-target mRNA prediction algorithms and microarray expression data. In the second step, we determine the associations between miRNA clusters and mRNA clusters based on changes in miRNA and mRNA expression profiles. We consider the miRNA-mRNA clusters with statistically significant associations to be potentially regulatory and, therefore, of biological interest.</p> <p>Conclusions</p> <p>Our method reduces the interactions between several hundred miRNAs and several thousand mRNAs to a few miRNA-mRNA groups, thereby facilitating a more meaningful biological analysis and a more targeted experimental validation.</p

    Correlation of microRNA levels during hypoxia with predicted target mRNAs through genome-wide microarray analysis

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    <p>Abstract</p> <p>Background</p> <p>Low levels of oxygen in tissues, seen in situations such as chronic lung disease, necrotic tumors, and high altitude exposures, initiate a signaling pathway that results in active transcription of genes possessing a hypoxia response element (HRE). The aim of this study was to investigate whether a change in miRNA expression following hypoxia could account for changes in the cellular transcriptome based on currently available miRNA target prediction tools.</p> <p>Methods</p> <p>To identify changes induced by hypoxia, we conducted mRNA- and miRNA-array-based experiments in HT29 cells, and performed comparative analysis of the resulting data sets based on multiple target prediction algorithms. To date, few studies have investigated an environmental perturbation for effects on genome-wide miRNA levels, or their consequent influence on mRNA output.</p> <p>Results</p> <p>Comparison of miRNAs with predicted mRNA targets indicated a lower level of concordance than expected. We did, however, find preliminary evidence of combinatorial regulation of mRNA expression by miRNA.</p> <p>Conclusion</p> <p>Target prediction programs and expression profiling techniques do not yet adequately represent the complexity of miRNA-mediated gene repression, and new methods may be required to better elucidate these pathways. Our data suggest the physiologic impact of miRNAs on cellular transcription results from a multifaceted network of miRNA and mRNA relationships, working together in an interconnected system and in context of hundreds of RNA species. The methods described here for comparative analysis of cellular miRNA and mRNA will be useful for understanding genome wide regulatory responsiveness and refining miRNA predictive algorithms.</p
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