225 research outputs found
Spatial patterns of CTCF sites define the anatomy of TADs and their boundaries
No full textBackground: Topologically associating domains (TADs) are genomic regions of self-interaction. Additionally, it is known that TAD boundaries are enriched in CTCF binding sites. In turn, CTCF sites are known to be asymmetric, whereby the convergent configuration of a pair of CTCF sites leads to the formation of a chromatin loop in vivo. However, to date, it has been unclear how to reconcile TAD structure with CTCF-based chromatin loops. Results: We approach this problem by analysing CTCF binding site strengths and classifying clusters of CTCF sites along the genome on the basis of their relative orientation. Analysis of CTCF site orientation classes as a function of their spatial distribution along the human genome reveals that convergent CTCF site clusters are depleted while divergent CTCF clusters are enriched in the 5- to 100-kb range. We then analyse the distribution of CTCF binding sites as a function of TAD boundary conservation across seven primary human blood cell types. This reveals divergent CTCF site enrichment at TAD boundaries. Furthermore, convergent arrays of CTCF sites separate the left and right sections of TADs that harbour internal CTCF sites, resulting in unequal TAD 'halves'. Conclusions: The orientation-based CTCF binding site cluster classification that we present reconciles TAD boundaries and CTCF site clusters in a mechanistically elegant fashion. This model suggests that the emergent structure of nuclear chromatin in the form of TADs relies on the obligate alternation of divergent and convergent CTCF site clusters that occur at different length scales along the genome. Graphical abstract: [Figure not available: see fulltext.]
Supplemental_Material – Supplemental material for Psychometric evaluation of the shortened version of the Functional Difficulties Questionnaire to assess thoracic physical function
No full textSupplemental material, Supplemental_Material for Psychometric evaluation of the shortened version of the Functional Difficulties Questionnaire to assess thoracic physical function by Mohd Ali Katijjahbe, Linda Denehy, Catherine L Granger, Alistair Royse, Colin Royse, Sarah Logie, Tamica Sturgess, Nur Ayub Md Ali, Margaret McManus, Clarke-Errey Sandy and Doa El-Ansary in Clinical Rehabilitation</p
Point Mutation
No full textThis book concerns the signatures left behind in chromosomes by the forces that drive DNA code evolution in the form of DNA nucleotide substitutions. Since the genetic code predetermines the molecular basis of life, it could have been about any aspect of biology. As it happens, it is largely about recent adaptation of pathogens and their human host. Nine chapters are medically oriented, two are bioinformatics-oriented and one is technological, describing the state of the art in synthetic point mutagenesis. What stands out in this book is the increasing rate at which DNA data has been amassed in the course of the past decade and how knowledge in this vibrant research field is currently being translated in the medical world
1967: The Birth of "The Death of the Author"
No full textAbstract: Roland Barthes’s “The Death of the Author” is a foundational text for scholars who are addressing questions of authorship and textual ownership in English studies and its neighboring disciplines. Barthes’s essay is typically presented without significant attention to the circumstances and context surrounding its initial English publication in 1967 (not in 1968, as is often stated). This project works to better understand that context, and thereby to better understand Barthes’s argument. Although it has often been claimed that Barthes’s essay has a “revolutionary spirit,” this spirit is not directly political in nature. Rather, it is grounded in an artistic revolution that was producing sophisticated multimedia well before digital tools made multimedia commonplace.Logie, John. (2013). 1967: The Birth of "The Death of the Author". Retrieved from the University Digital Conservancy, https://hdl.handle.net/11299/148870
Apicomplexa and Histone Variants: What’s New?
No full textPlasmodium spp. and Toxoplasma gondii present a conserved nucleosome composition based on canonical H3 and variants, H4, canonical H2A and variants, and H2B. One-off, the phylum has also a variant H2B, named H2B.Z, which was shown to form a double variant nucleosome H2A.Z/H2B.Z. These histones also present conserved and unique post-translational modifications (PTMs). Histone variants have shown particular genomic localization and PTMs along euchromatin and heterochromatin, including telomere-associated sequences (TAS), suggesting fine-grained chromatin structure modulation. Several other nonhistone proteins present remarkable participation in controlling chromatin state, especially at TAS. Based on that, we discuss the role of epigenetics (PTMs and histone variants) in Plasmodium and Toxoplasma gene expression, replication, and DNA repair. We also discuss TAS structures and chromatin composition and its impact on antigenic variant expression in Plasmodium.Fil: Vanagas, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); ArgentinaFil: Contreras, Susana Marisol. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); ArgentinaFil: Ángel, Sergio Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); Argentin
Chromatin and Epigenetics
No full textGenomics has gathered broad public attention since Lamarck put forward his top-down hypothesis of 'motivated change' in 1809 in his famous book "Philosophie Zoologique" and even more so since Darwin published his famous bottom-up theory of natural selection in "The Origin of Species" in 1859. The public awareness culminated in the much anticipated race to decipher the sequence of the human genome in 2002. Over all those years, it has become apparent that genomic DNA is compacted into chromatin with a dedicated 3D higher-order organization and dynamics, and that on each structural level epigenetic modifications exist. The book "Chromatin and Epigenetics" addresses current issues in the fields of epigenetics and chromatin ranging from more theoretical overviews in the first four chapters to much more detailed methodologies and insights into diagnostics and treatments in the following chapters. The chapters illustrate in their depth and breadth that genetic information is stored on all structural and dynamical levels within the nucleus with corresponding modifications of functional relevance. Thus, only an integrative systems approach allows to understand, treat, and manipulate the holistic interplay of genotype and phenotype creating functional genomes. The book chapters therefore contribute to this general perspective, not only opening opportunities for a true universal view on genetic information but also being key for a general understanding of genomes, their function, as well as life and evolution in general
Chromatin and Epigenetics
No full textGenomics has gathered broad public attention since Lamarck put forward his top-down hypothesis of 'motivated change' in 1809 in his famous book "Philosophie Zoologique" and even more so since Darwin published his famous bottom-up theory of natural selection in "The Origin of Species" in 1859. The public awareness culminated in the much anticipated race to decipher the sequence of the human genome in 2002. Over all those years, it has become apparent that genomic DNA is compacted into chromatin with a dedicated 3D higher-order organization and dynamics, and that on each structural level epigenetic modifications exist. The book "Chromatin and Epigenetics" addresses current issues in the fields of epigenetics and chromatin ranging from more theoretical overviews in the first four chapters to much more detailed methodologies and insights into diagnostics and treatments in the following chapters. The chapters illustrate in their depth and breadth that genetic information is stored on all structural and dynamical levels within the nucleus with corresponding modifications of functional relevance. Thus, only an integrative systems approach allows to understand, treat, and manipulate the holistic interplay of genotype and phenotype creating functional genomes. The book chapters therefore contribute to this general perspective, not only opening opportunities for a true universal view on genetic information but also being key for a general understanding of genomes, their function, as well as life and evolution in general
December 1972
No full textEditor: Glenn Weare, Secretary: Colleen Simms, Business Manager: Ron Herbert, Layout: Daniel A. Sheehy and Judith Burnett, Literary: Raelene Stanley and Julene Cook, Photography: David Crabtree and Robert Logie, Sales Manager: Harvey Carlsen, Sales Committee: Colin Clarke, Gail Harrison, Lee Dunstan, Elizabeth Cook, Robert Bolst, Janice Harders, and Anna Kaczmarek. Printed by Signs Publishing Company, Warburton, Victoria, Australiahttps://research.avondale.edu.au/jacaranda/1007/thumbnail.jp
Extensive epigenomic integration of the glucocorticoid response in primary human monocytes and in vitro derived macrophages
No full textGlucocorticoid receptor is a transcription factor that is ubiquitously expressed. Glucocorticoids are circadian steroids that regulate a wide range of bodily functions, including immunity. Here we report that synthetic glucocorticoids affect 1035 mRNAs in isolated healthy human blood monocytes but only 165 in the respective six day-old monocyte-derived macrophages. The majority of the glucocorticoid response in monocytes concerns genes that are dynamic upon monocyte to macrophage differentiation, whereby macrophage-like mRNA levels are often reached in monocytes within four hours of treatment. Concomitantly, over 5000 chromosomal H3K27ac regions undergo remodelling, of which 60% involve increased H3K27ac signal. We find that chromosomal glucocorticoid receptor binding sites correlate with positive but not with negative local epigenomic effects. To investigate further we assigned our data to topologically associating domains (TADs). This shows that about 10% of macrophage TADs harbour at least one GR binding site and that half of all the glucocorticoid-induced H3K27ac regions are confined to these TADs. Our analyses are therefore consistent with the notion that TADs naturally accommodate information from sets of distal glucocorticoid response elements
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