416 research outputs found

    Assessing the competitiveness of Matera and the Basilicata Region (Italy) ahead of the 2019 European Capital of Culture

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    Cities/regions are increasingly using events to aid social/economic development. The European Capital of Culture promotes urban management and economic production using culture to drive social legacies, job creation and civic repositioning. This paper aims to understand how Matera and Basilicata’s residents perceive destination competitiveness ahead of the 2019 European Capital of Culture. This paper adapts the Integrated Model of Destination Competitiveness and suggests a new determinant to understand resident perceptions. This paper contributes a new determinant to consider in competitiveness research: social conditions to improve local wellbeing. Two hundred respondents identify strengths/weaknesses of each competitiveness determinant. The results presented in this study display sample mean values and standard deviations for each indicator, as well as Wilcoxon test statistic (z). Competitive indicators are those showing means above 4.0. Descriptive and inferential analyses using SPSS 17 show strengths/weaknesses comparing Matera (city) and Basilicata (region) with similarities and differences outlined to consider both urban and regional perspectives and differences. For the data analysis, Wilcoxon paired signed rank test displays differences in the competitiveness factors between Matera and Basilicata. Wilcoxon (a nonparametric alternative to paired sample t-test) was performed since the data distribution was left skewed and Kolmogorov–Smirnov statistic indicates violation of normality assumption. Results show the majority of inherited, created and supporting resources are competitive, as well as image and social conditions; however, management and organisation needs improvement. It is essential that European Capital of Culture hosts have long-term competitive strategies in place to strengthen urban and regional capacity when delivering diverse cultural programmes, at present, and into the future. This study offers insight before the 2019 European Capital of Culture to inform planners and policymakers ahead of the event and offers consideration and discussion of social impacts and the need to gain such insight in competitiveness research going forward

    Establishment of dsDNA-dsDNA interactions by the condensin complex

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    Condensin is a structural maintenance of chromosomes (SMC) complex family member thought to build mitotic chromosomes by DNA loop extrusion. However, condensin variants unable to extrude loops, yet proficient in chromosome formation, were recently described. Here, we explore how condensin might alternatively build chromosomes. Using bulk biochemical and single-molecule experiments with purified fission yeast condensin, we observe that individual condensins sequentially and topologically entrap two double-stranded DNAs (dsDNAs). Condensin loading transitions through a state requiring DNA bending, as proposed for the related cohesin complex. While cohesin then favors the capture of a second single-stranded DNA (ssDNA), second dsDNA capture emerges as a defining feature of condensin. We provide complementary in vivo evidence for DNA-DNA capture in the form of condensin-dependent chromatin contacts within, as well as between, chromosomes. Our results support a “diffusion capture” model in which condensin acts in mitotic chromosome formation by sequential dsDNA-dsDNA capture

    Scaling of the buckling transition of ridges in thin sheets

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    When a thin elastic sheet crumples, the elastic energy condenses into a network of folding lines and point vertices. These folds and vertices have elastic energy densities much greater than the surrounding areas, and most of the work required to crumple the sheet is consumed in breaking the folding lines or ``ridges''. To understand crumpling it is then necessary to understand the strength of ridges. In this work, we consider the buckling of a single ridge under the action of inward forcing applied at its ends. We demonstrate a simple scaling relation for the response of the ridge to the force prior to buckling. We also show that the buckling instability depends only on the ratio of strain along the ridge to curvature across it. Numerically, we find for a wide range of boundary conditions that ridges buckle when our forcing has increased their elastic energy by 20% over their resting state value. We also observe a correlation between neighbor interactions and the location of initial buckling. Analytic arguments and numerical simulations are employed to prove these results. Implications for the strength of ridges as structural elements are discussed.Comment: 42 pages, latex, doctoral dissertation, to be submitted to Phys Rev

    Chronic high fat feeding restricts islet mRNA translation initiation independently of ER stress via DNA damage and p53 activation

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    Under conditions of high fat diet (HFD) consumption, glucose dyshomeostasis develops when β-cells are unable to adapt to peripheral insulin demands. Few studies have interrogated the molecular mechanisms of β-cell dysfunction at the level of mRNA translation under such conditions. We sought to address this issue through polyribosome profile analysis of islets from mice fed 16-weeks of 42% HFD. HFD-islet analysis revealed clear trends toward global reductions in mRNA translation with a significant reduction in the polyribosome/monoribosome ratio for Pdx1 mRNA. Transcriptional and translational analyses revealed endoplasmic reticulum stress was not the etiology of our findings. HFD-islets demonstrated evidence of oxidative stress and DNA damage, as well as activation of p53. Experiments in MIN-6 β-cells revealed that treatment with doxorubicin to directly induce DNA damage mimicked our observed effects in islets. Islets from animals treated with pioglitazone concurrently with HFD demonstrated a reversal of effects observed from HFD alone. Finally, HFD-islets demonstrated reduced expression of multiple ribosome biogenesis genes and the key translation initiation factor eIF4E. We propose a heretofore unappreciated effect of chronic HFD on β-cells, wherein continued DNA damage owing to persistent oxidative stress results in p53 activation and a resultant inhibition of mRNA translation

    Annotation of two large contiguous regions from the Haemonchus contortus genome using RNA-seq and comparative analysis with Caenorhabditis elegans

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    The genomes of numerous parasitic nematodes are currently being sequenced, but their complexity and size, together with high levels of intra-specific sequence variation and a lack of reference genomes, makes their assembly and annotation a challenging task. Haemonchus contortus is an economically significant parasite of livestock that is widely used for basic research as well as for vaccine development and drug discovery. It is one of many medically and economically important parasites within the strongylid nematode group. This group of parasites has the closest phylogenetic relationship with the model organism Caenorhabditis elegans, making comparative analysis a potentially powerful tool for genome annotation and functional studies. To investigate this hypothesis, we sequenced two contiguous fragments from the H. contortus genome and undertook detailed annotation and comparative analysis with C. elegans. The adult H. contortus transcriptome was sequenced using an Illumina platform and RNA-seq was used to annotate a 409 kb overlapping BAC tiling path relating to the X chromosome and a 181 kb BAC insert relating to chromosome I. In total, 40 genes and 12 putative transposable elements were identified. 97.5% of the annotated genes had detectable homologues in C. elegans of which 60% had putative orthologues, significantly higher than previous analyses based on EST analysis. Gene density appears to be less in H. contortus than in C. elegans, with annotated H. contortus genes being an average of two-to-three times larger than their putative C. elegans orthologues due to a greater intron number and size. Synteny appears high but gene order is generally poorly conserved, although areas of conserved microsynteny are apparent. C. elegans operons appear to be partially conserved in H. contortus. Our findings suggest that a combination of RNA-seq and comparative analysis with C. elegans is a powerful approach for the annotation and analysis of strongylid nematode genomes

    DOC2B: A Novel Syntaxin-4 Binding Protein Mediating Insulin-Regulated GLUT4 Vesicle Fusion in Adipocytes

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    OBJECTIVE— Insulin stimulates glucose uptake in skeletal muscle and adipose tissues primarily by stimulating the translocation of vesicles containing a facilitative glucose transporter, GLUT4, from intracellular compartments to the plasma membrane. The formation of stable soluble N-ethyl-maleimide–sensitive fusion protein [NSF] attachment protein receptor (SNARE) complexes between vesicle-associated membrane protein-2 (VAMP-2) and syntaxin-4 initiates GLUT4 vesicle docking and fusion processes. Additional factors such as munc18c and tomosyn were reported to be negative regulators of the SNARE complex assembly involved in GLUT4 vesicle fusion. However, despite numerous investigations, the positive regulators have not been adequately clarified

    Identification of the sex-determining factor in the liverwort Marchantia polymorpha reveals unique evolution of sex chromosomes in a haploid system

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    半数体生物の性染色体上の性決定遺伝子を解明 --コケがもつ現生生物最古の起源の性染色体--. 京都大学プレスリリース. 2021-11-08.Sex determination is a central process for sexual reproduction and is often regulated by a sex determinant encoded on a sex chromosome. Rules that govern the evolution of sex chromosomes via specialization and degeneration following the evolution of a sex determinant have been well studied in diploid organisms. However, distinct predictions apply to sex chromosomes in organisms where sex is determined in the haploid phase of the life cycle: both sex chromosomes, female U and male V, are expected to maintain their gene functions, even though both are non-recombining. This is in contrast to the X-Y (or Z-W) asymmetry and Y (W) chromosome degeneration in XY (ZW) systems of diploids. Here, we provide evidence that sex chromosomes diverged early during the evolution of haploid liverworts and identify the sex determinant on the Marchantia polymorpha U chromosome. This gene, Feminizer, encodes a member of the plant-specific BASIC PENTACYSTEINE transcription factor family. It triggers female differentiation via regulation of the autosomal sex-determining locus of FEMALE GAMETOPHYTE MYB and SUPPRESSOR OF FEMINIZATION. Phylogenetic analyses of Feminizer and other sex chromosome genes indicate dimorphic sex chromosomes had already been established 430 mya in the ancestral liverwort. Feminizer also plays a role in reproductive induction that is shared with its gametolog on the V chromosome, suggesting an ancestral function, distinct from sex determination, was retained by the gametologs. This implies ancestral functions can be preserved after the acquisition of a sex determination mechanism during the evolution of a dominant haploid sex chromosome system
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