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Sample records for intrinsic nucleosome occupancy

  1. G+C content dominates intrinsic nucleosome occupancy

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    Hughes Timothy R

    2009-12-01

    Full Text Available Abstract Background The relative preference of nucleosomes to form on individual DNA sequences plays a major role in genome packaging. A wide variety of DNA sequence features are believed to influence nucleosome formation, including periodic dinucleotide signals, poly-A stretches and other short motifs, and sequence properties that influence DNA structure, including base content. It was recently shown by Kaplan et al. that a probabilistic model using composition of all 5-mers within a nucleosome-sized tiling window accurately predicts intrinsic nucleosome occupancy across an entire genome in vitro. However, the model is complicated, and it is not clear which specific DNA sequence properties are most important for intrinsic nucleosome-forming preferences. Results We find that a simple linear combination of only 14 simple DNA sequence attributes (G+C content, two transformations of dinucleotide composition, and the frequency of eleven 4-bp sequences explains nucleosome occupancy in vitro and in vivo in a manner comparable to the Kaplan model. G+C content and frequency of AAAA are the most important features. G+C content is dominant, alone explaining ~50% of the variation in nucleosome occupancy in vitro. Conclusions Our findings provide a dramatically simplified means to predict and understand intrinsic nucleosome occupancy. G+C content may dominate because it both reduces frequency of poly-A-like stretches and correlates with many other DNA structural characteristics. Since G+C content is enriched or depleted at many types of features in diverse eukaryotic genomes, our results suggest that variation in nucleotide composition may have a widespread and direct influence on chromatin structure.

  2. Exploring the Link between Nucleosome Occupancy and DNA Methylation

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    Cecilia Lövkvist

    2018-01-01

    Full Text Available Near promoters, both nucleosomes and CpG sites form characteristic spatial patterns. Previously, nucleosome depleted regions were observed upstream of transcription start sites and nucleosome occupancy was reported to correlate both with CpG density and the level of CpG methylation. Several studies imply a causal link where CpG methylation might induce nucleosome formation, whereas others argue the opposite, i.e., that nucleosome occupancy might influence CpG methylation. Correlations are indeed evident between nucleosomes, CpG density and CpG methylation—at least near promoter sites. It is however less established whether there is an immediate causal relation between nucleosome occupancy and the presence of CpG sites—or if nucleosome occupancy could be influenced by other factors. In this work, we test for such causality in human genomes by analyzing the three quantities both near and away from promoter sites. For data from the human genome we compare promoter regions with given CpG densities with genomic regions without promoters but of similar CpG densities. We find the observed correlation between nucleosome occupancy and CpG density, respectively CpG methylation, to be specific to promoter regions. In other regions along the genome nucleosome occupancy is statistically independent of the positioning of CpGs or their methylation levels. Anti-correlation between CpG density and methylation level is however similarly strong in both regions. On promoters, nucleosome occupancy is more strongly affected by the level of gene expression than CpG density or CpG methylation—calling into question any direct causal relation between nucleosome occupancy and CpG organization. Rather, our results suggest that for organisms with cytosine methylation nucleosome occupancy might be primarily linked to gene expression, with no strong impact on methylation.

  3. Multiple distinct stimuli increase measured nucleosome occupancy around human promoters.

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    Chuong D Pham

    Full Text Available Nucleosomes can block access to transcription factors. Thus the precise localization of nucleosomes relative to transcription start sites and other factor binding sites is expected to be a critical component of transcriptional regulation. Recently developed microarray approaches have allowed the rapid mapping of nucleosome positions over hundreds of kilobases (kb of human genomic DNA, although these approaches have not yet been widely used to measure chromatin changes associated with changes in transcription. Here, we use custom tiling microarrays to reveal changes in nucleosome positions and abundance that occur when hormone-bound glucocorticoid receptor (GR binds to sites near target gene promoters in human osteosarcoma cells. The most striking change is an increase in measured nucleosome occupancy at sites spanning ∼1 kb upstream and downstream of transcription start sites, which occurs one hour after addition of hormone, but is lost at 4 hours. Unexpectedly, this increase was seen both on GR-regulated and GR-non-regulated genes. In addition, the human SWI/SNF chromatin remodeling factor (a GR co-activator was found to be important for increased occupancy upon hormone treatment and also for low nucleosome occupancy without hormone. Most surprisingly, similar increases in nucleosome occupancy were also seen on both regulated and non-regulated promoters during differentiation of human myeloid leukemia cells and upon activation of human CD4+ T-cells. These results indicate that dramatic changes in chromatin structure over ∼2 kb of human promoters may occur genomewide and in response to a variety of stimuli, and suggest novel models for transcriptional regulation.

  4. Links between DNA methylation and nucleosome occupancy in the human genome.

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    Collings, Clayton K; Anderson, John N

    2017-01-01

    DNA methylation is an epigenetic modification that is enriched in heterochromatin but depleted at active promoters and enhancers. However, the debate on whether or not DNA methylation is a reliable indicator of high nucleosome occupancy has not been settled. For example, the methylation levels of DNA flanking CTCF sites are higher in linker DNA than in nucleosomal DNA, while other studies have shown that the nucleosome core is the preferred site of methylation. In this study, we make progress toward understanding these conflicting phenomena by implementing a bioinformatics approach that combines MNase-seq and NOMe-seq data and by comprehensively profiling DNA methylation and nucleosome occupancy throughout the human genome. The results demonstrated that increasing methylated CpG density is correlated with nucleosome occupancy in the total genome and within nearly all subgenomic regions. Features with elevated methylated CpG density such as exons, SINE-Alu sequences, H3K36-trimethylated peaks, and methylated CpG islands are among the highest nucleosome occupied elements in the genome, while some of the lowest occupancies are displayed by unmethylated CpG islands and unmethylated transcription factor binding sites. Additionally, outside of CpG islands, the density of CpGs within nucleosomes was shown to be important for the nucleosomal location of DNA methylation with low CpG frequencies favoring linker methylation and high CpG frequencies favoring core particle methylation. Prominent exceptions to the correlations between methylated CpG density and nucleosome occupancy include CpG islands marked by H3K27me3 and CpG-poor heterochromatin marked by H3K9me3, and these modifications, along with DNA methylation, distinguish the major silencing mechanisms of the human epigenome. Thus, the relationship between DNA methylation and nucleosome occupancy is influenced by the density of methylated CpG dinucleotides and by other epigenomic components in chromatin.

  5. Stimulation of the Drosophila immune system alters genome-wide nucleosome occupancy

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    Yingxue Ren

    2015-03-01

    Full Text Available In eukaryotes, nucleosomes participate in all DNA-templated events by regulating access to the underlying DNA sequence. However, nucleosome dynamics during a genome response have not been well characterized [1,2]. We stimulated Drosophila S2 cells with heat-killed Gram-negative bacteria Salmonella typhimurium, and mapped genome-wide nucleosome occupancy at high temporal resolution by MNase-seq using Illumina HiSeq 2500. We show widespread nucleosome occupancy change in S2 cells during the immune response, with the significant nucleosomal loss occurring at 4 h after stimulation. Data have been deposited to the Gene Expression Omnibus (GEO database repository with the dataset identifier GSE64507.

  6. Differential Nucleosome Occupancies across Oct4-Sox2 Binding Sites in Murine Embryonic Stem Cells.

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    Amy Sebeson

    Full Text Available The binding sequence for any transcription factor can be found millions of times within a genome, yet only a small fraction of these sequences encode functional transcription factor binding sites. One of the reasons for this dichotomy is that many other factors, such as nucleosomes, compete for binding. To study how the competition between nucleosomes and transcription factors helps determine a functional transcription factor site from a predicted transcription factor site, we compared experimentally-generated in vitro nucleosome occupancy with in vivo nucleosome occupancy and transcription factor binding in murine embryonic stem cells. Using a solution hybridization enrichment technique, we generated a high-resolution nucleosome map from targeted regions of the genome containing predicted sites and functional sites of Oct4/Sox2 regulation. We found that at Pax6 and Nes, which are bivalently poised in stem cells, functional Oct4 and Sox2 sites show high amounts of in vivo nucleosome displacement compared to in vitro. Oct4 and Sox2, which are active, show no significant displacement of in vivo nucleosomes at functional sites, similar to nonfunctional Oct4/Sox2 binding. This study highlights a complex interplay between Oct4 and Sox2 transcription factors and nucleosomes among different target genes, which may result in distinct patterns of stem cell gene regulation.

  7. Increasing Nucleosome Occupancy Is Correlated with an Increasing Mutation Rate so Long as DNA Repair Machinery Is Intact.

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    Yazdi, Puya G; Pedersen, Brian A; Taylor, Jared F; Khattab, Omar S; Chen, Yu-Han; Chen, Yumay; Jacobsen, Steven E; Wang, Ping H

    2015-01-01

    Deciphering the multitude of epigenomic and genomic factors that influence the mutation rate is an area of great interest in modern biology. Recently, chromatin has been shown to play a part in this process. To elucidate this relationship further, we integrated our own ultra-deep sequenced human nucleosomal DNA data set with a host of published human genomic and cancer genomic data sets. Our results revealed, that differences in nucleosome occupancy are associated with changes in base-specific mutation rates. Increasing nucleosome occupancy is associated with an increasing transition to transversion ratio and an increased germline mutation rate within the human genome. Additionally, cancer single nucleotide variants and microindels are enriched within nucleosomes and both the coding and non-coding cancer mutation rate increases with increasing nucleosome occupancy. There is an enrichment of cancer indels at the theoretical start (74 bp) and end (115 bp) of linker DNA between two nucleosomes. We then hypothesized that increasing nucleosome occupancy decreases access to DNA by DNA repair machinery and could account for the increasing mutation rate. Such a relationship should not exist in DNA repair knockouts, and we thus repeated our analysis in DNA repair machinery knockouts to test our hypothesis. Indeed, our results revealed no correlation between increasing nucleosome occupancy and increasing mutation rate in DNA repair knockouts. Our findings emphasize the linkage of the genome and epigenome through the nucleosome whose properties can affect genome evolution and genetic aberrations such as cancer.

  8. Weakly positioned nucleosomes enhance the transcriptional competency of chromatin.

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    Yaakov Belch

    2010-09-01

    Full Text Available Transcription is affected by nucleosomal resistance against polymerase passage. In turn, nucleosomal resistance is determined by DNA sequence, histone chaperones and remodeling enzymes. The contributions of these factors are widely debated: one recent title claims "… DNA-encoded nucleosome organization…" while another title states that "histone-DNA interactions are not the major determinant of nucleosome positions." These opposing conclusions were drawn from similar experiments analyzed by idealized methods. We attempt to resolve this controversy to reveal nucleosomal competency for transcription.To this end, we analyzed 26 in vivo, nonlinked, and in vitro genome-wide nucleosome maps/replicates by new, rigorous methods. Individual H2A nucleosomes are reconstituted inaccurately by transcription, chaperones and remodeling enzymes. At gene centers, weakly positioned nucleosome arrays facilitate rapid histone eviction and remodeling, easing polymerase passage. Fuzzy positioning is not due to artefacts. At the regional level, transcriptional competency is strongly influenced by intrinsic histone-DNA affinities. This is confirmed by reproducing the high in vivo occupancy of translated regions and the low occupancy of intergenic regions in reconstitutions from purified DNA and histones. Regional level occupancy patterns are protected from invading histones by nucleosome excluding sequences and barrier nucleosomes at gene boundaries and within genes.Dense arrays of weakly positioned nucleosomes appear to be necessary for transcription. Weak positioning at exons facilitates temporary remodeling, polymerase passage and hence the competency for transcription. At regional levels, the DNA sequence plays a major role in determining these features but positions of individual nucleosomes are typically modified by transcription, chaperones and enzymes. This competency is reduced at intergenic regions by sequence features, barrier nucleosomes, and proteins

  9. Nucleosomes shape DNA polymorphism and divergence.

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    Sasha A Langley

    2014-07-01

    Full Text Available An estimated 80% of genomic DNA in eukaryotes is packaged as nucleosomes, which, together with the remaining interstitial linker regions, generate higher order chromatin structures [1]. Nucleosome sequences isolated from diverse organisms exhibit ∼10 bp periodic variations in AA, TT and GC dinucleotide frequencies. These sequence elements generate intrinsically curved DNA and help establish the histone-DNA interface. We investigated an important unanswered question concerning the interplay between chromatin organization and genome evolution: do the DNA sequence preferences inherent to the highly conserved histone core exert detectable natural selection on genomic divergence and polymorphism? To address this hypothesis, we isolated nucleosomal DNA sequences from Drosophila melanogaster embryos and examined the underlying genomic variation within and between species. We found that divergence along the D. melanogaster lineage is periodic across nucleosome regions with base changes following preferred nucleotides, providing new evidence for systematic evolutionary forces in the generation and maintenance of nucleosome-associated dinucleotide periodicities. Further, Single Nucleotide Polymorphism (SNP frequency spectra show striking periodicities across nucleosomal regions, paralleling divergence patterns. Preferred alleles occur at higher frequencies in natural populations, consistent with a central role for natural selection. These patterns are stronger for nucleosomes in introns than in intergenic regions, suggesting selection is stronger in transcribed regions where nucleosomes undergo more displacement, remodeling and functional modification. In addition, we observe a large-scale (∼180 bp periodic enrichment of AA/TT dinucleotides associated with nucleosome occupancy, while GC dinucleotide frequency peaks in linker regions. Divergence and polymorphism data also support a role for natural selection in the generation and maintenance of these

  10. Changes in Nucleosome Occupancy Associated with Metabolic Alterations in Aged Mammalian Liver

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    Irina M. Bochkis

    2014-11-01

    Full Text Available Aging is accompanied by physiological impairments, which, in insulin-responsive tissues, including the liver, predispose individuals to metabolic disease. However, the molecular mechanisms underlying these changes remain largely unknown. Here, we analyze genome-wide profiles of RNA and chromatin organization in the liver of young (3 months and old (21 months mice. Transcriptional changes suggest that derepression of the nuclear receptors PPARα, PPARγ, and LXRα in aged mouse liver leads to activation of targets regulating lipid synthesis and storage, whereas age-dependent changes in nucleosome occupancy are associated with binding sites for both known regulators (forkhead factors and nuclear receptors and candidates associated with nuclear lamina (Hdac3 and Srf implicated to govern metabolic function of aging liver. Winged-helix transcription factor Foxa2 and nuclear receptor corepressor Hdac3 exhibit a reciprocal binding pattern at PPARα targets contributing to gene expression changes that lead to steatosis in aged liver.

  11. Statistical physics of nucleosome positioning and chromatin structure

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    Morozov, Alexandre

    2012-02-01

    Genomic DNA is packaged into chromatin in eukaryotic cells. The fundamental building block of chromatin is the nucleosome, a 147 bp-long DNA molecule wrapped around the surface of a histone octamer. Arrays of nucleosomes are positioned along DNA according to their sequence preferences and folded into higher-order chromatin fibers whose structure is poorly understood. We have developed a framework for predicting sequence-specific histone-DNA interactions and the effective two-body potential responsible for ordering nucleosomes into regular higher-order structures. Our approach is based on the analogy between nucleosomal arrays and a one-dimensional fluid of finite-size particles with nearest-neighbor interactions. We derive simple rules which allow us to predict nucleosome occupancy solely from the dinucleotide content of the underlying DNA sequences.Dinucleotide content determines the degree of stiffness of the DNA polymer and thus defines its ability to bend into the nucleosomal superhelix. As expected, the nucleosome positioning rules are universal for chromatin assembled in vitro on genomic DNA from baker's yeast and from the nematode worm C.elegans, where nucleosome placement follows intrinsic sequence preferences and steric exclusion. However, the positioning rules inferred from in vivo C.elegans chromatin are affected by global nucleosome depletion from chromosome arms relative to central domains, likely caused by the attachment of the chromosome arms to the nuclear membrane. Furthermore, intrinsic nucleosome positioning rules are overwritten in transcribed regions, indicating that chromatin organization is actively managed by the transcriptional and splicing machinery.

  12. The size of the nucleosome

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    Bohr, Jakob; Olsen, Kasper

    2011-01-01

    The structural origin of the size of the 11 nm nucleosomal disc is addressed. On the nanometer length-scale the organization of DNA as chromatin in the chromosomes involves a coiling of DNA around the histone core of the nucleosome. We suggest that the size of the nucleosome core particle......-pairs of the linker-DNA is included the estimate of the size of an ideal nucleosome is in close agreement with the experimental numbers. Interestingly, the size of the nucleosome is shown to be a consequence of intrinsic properties of the DNA double helix....

  13. Nucleosome Organization in Human Embryonic Stem Cells.

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    Puya G Yazdi

    Full Text Available The fundamental repeating unit of eukaryotic chromatin is the nucleosome. Besides being involved in packaging DNA, nucleosome organization plays an important role in transcriptional regulation and cellular identity. Currently, there is much debate about the major determinants of the nucleosome architecture of a genome and its significance with little being known about its role in stem cells. To address these questions, we performed ultra-deep sequencing of nucleosomal DNA in two human embryonic stem cell lines and integrated our data with numerous epigenomic maps. Our analyses have revealed that the genome is a determinant of nucleosome organization with transcriptionally inactive regions characterized by a "ground state" of nucleosome profiles driven by underlying DNA sequences. DNA sequence preferences are associated with heterogeneous chromatin organization around transcription start sites. Transcription, histone modifications, and DNA methylation alter this "ground state" by having distinct effects on both nucleosome positioning and occupancy. As the transcriptional rate increases, nucleosomes become better positioned. Exons transcribed and included in the final spliced mRNA have distinct nucleosome profiles in comparison to exons not included at exon-exon junctions. Genes marked by the active modification H3K4m3 are characterized by lower nucleosome occupancy before the transcription start site compared to genes marked by the inactive modification H3K27m3, while bivalent domains, genes associated with both marks, lie exactly in the middle. Combinatorial patterns of epigenetic marks (chromatin states are associated with unique nucleosome profiles. Nucleosome organization varies around transcription factor binding in enhancers versus promoters. DNA methylation is associated with increasing nucleosome occupancy and different types of methylations have distinct location preferences within the nucleosome core particle. Finally, computational

  14. Designing nucleosomal force sensors

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    Tompitak, M.; de Bruin, L.; Eslami-Mossallam, B.; Schiessel, H.

    2017-05-01

    About three quarters of our DNA is wrapped into nucleosomes: DNA spools with a protein core. It is well known that the affinity of a given DNA stretch to be incorporated into a nucleosome depends on the geometry and elasticity of the basepair sequence involved, causing the positioning of nucleosomes. Here we show that DNA elasticity can have a much deeper effect on nucleosomes than just their positioning: it affects their "identities". Employing a recently developed computational algorithm, the mutation Monte Carlo method, we design nucleosomes with surprising physical characteristics. Unlike any other nucleosomes studied so far, these nucleosomes are short-lived when put under mechanical tension whereas other physical properties are largely unaffected. This suggests that the nucleosome, the most abundant DNA-protein complex in our cells, might more properly be considered a class of complexes with a wide array of physical properties, and raises the possibility that evolution has shaped various nucleosome species according to their genomic context.

  15. Nature of the Nucleosomal Barrier to RNA Polymerase II | Center for Cancer Research

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    In the cell, RNA polymerase II (pol II) efficiently transcribes DNA packaged into nucleosomes, but in vitro encounters with the nucleosomes induce catalytic inactivation (arrest) of the pol II core enzyme. To determine potential mechanisms making nucleosomes transparent to transcription in vivo, we analyzed the nature of the nucleosome-induced arrest. We found that the arrests have been detected mostly at positions of strong intrinsic pause sites of DNA.

  16. Genome-scale identification of nucleosome organization by using 1000 porcine oocytes at different developmental stages.

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    Chenyu Tao

    Full Text Available The nucleosome is the basic structural unit of chromosomes, and its occupancy and distribution in promoters are crucial for the regulation of gene expression. During the growth process of porcine oocytes, the "growing" oocytes (SF have a much higher transcriptional activity than the "fully grown" oocytes (BF. However, the chromosome status of the two kinds of oocytes remains poorly understood. In this study, we profiled the nucleosome distributions of SF and BF with as few as 1000 oocytes. By comparing the altered regions, we found that SF tended toward nucleosome loss and more open chromosome architecture than BF did. BF had decreased nucleosome occupancy in the coding region and increased nucleosome occupancy in the promoter compared to SF. The nucleosome occupancy of SF was higher than that of BF in the GC-poor regions, but lower than that of BF in the GC-rich regions. The nucleosome distribution around the transcriptional start site (TSS of all the genes of the two samples was basically the same, but the nucleosome occupancy around the TSS of SF was lower than that of BF. GO functional annotation of genes with different nucleosome occupancy in promoter showed the genes were mainly involved in cell, cellular process, and metabolic process biological process. The results of this study revealed the dynamic reorganization of porcine oocytes in different developmental stages and the critical role of nucleosome arrangement during the oocyte growth process.

  17. Structural features based genome-wide characterization and prediction of nucleosome organization

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    Gan Yanglan

    2012-03-01

    Full Text Available Abstract Background Nucleosome distribution along chromatin dictates genomic DNA accessibility and thus profoundly influences gene expression. However, the underlying mechanism of nucleosome formation remains elusive. Here, taking a structural perspective, we systematically explored nucleosome formation potential of genomic sequences and the effect on chromatin organization and gene expression in S. cerevisiae. Results We analyzed twelve structural features related to flexibility, curvature and energy of DNA sequences. The results showed that some structural features such as DNA denaturation, DNA-bending stiffness, Stacking energy, Z-DNA, Propeller twist and free energy, were highly correlated with in vitro and in vivo nucleosome occupancy. Specifically, they can be classified into two classes, one positively and the other negatively correlated with nucleosome occupancy. These two kinds of structural features facilitated nucleosome binding in centromere regions and repressed nucleosome formation in the promoter regions of protein-coding genes to mediate transcriptional regulation. Based on these analyses, we integrated all twelve structural features in a model to predict more accurately nucleosome occupancy in vivo than the existing methods that mainly depend on sequence compositional features. Furthermore, we developed a novel approach, named DLaNe, that located nucleosomes by detecting peaks of structural profiles, and built a meta predictor to integrate information from different structural features. As a comparison, we also constructed a hidden Markov model (HMM to locate nucleosomes based on the profiles of these structural features. The result showed that the meta DLaNe and HMM-based method performed better than the existing methods, demonstrating the power of these structural features in predicting nucleosome positions. Conclusions Our analysis revealed that DNA structures significantly contribute to nucleosome organization and influence

  18. Nucleosome Positioning and Epigenetics

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    Schwab, David; Bruinsma, Robijn

    2008-03-01

    The role of chromatin structure in gene regulation has recently taken center stage in the field of epigenetics, phenomena that change the phenotype without changing the DNA sequence. Recent work has also shown that nucleosomes, a complex of DNA wrapped around a histone octamer, experience a sequence dependent energy landscape due to the variation in DNA bend stiffness with sequence composition. In this talk, we consider the role nucleosome positioning might play in the formation of heterochromatin, a compact form of DNA generically responsible for gene silencing. In particular, we discuss how different patterns of nucleosome positions, periodic or random, could either facilitate or suppress heterochromatin stability and formation.

  19. Genome wide nucleosome mapping for HSV-1 shows nucleosomes are deposited at preferred positions during lytic infection.

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    Oh, Jaewook; Sanders, Iryna F; Chen, Eric Z; Li, Hongzhe; Tobias, John W; Isett, R Benjamin; Penubarthi, Sindura; Sun, Hao; Baldwin, Don A; Fraser, Nigel W

    2015-01-01

    HSV is a large double stranded DNA virus, capable of causing a variety of diseases from the common cold sore to devastating encephalitis. Although DNA within the HSV virion does not contain any histone protein, within 1 h of infecting a cell and entering its nucleus the viral genome acquires some histone protein (nucleosomes). During lytic infection, partial micrococcal nuclease (MNase) digestion does not give the classic ladder band pattern, seen on digestion of cell DNA or latent viral DNA. However, complete digestion does give a mono-nucleosome band, strongly suggesting that there are some nucleosomes present on the viral genome during the lytic infection, but that they are not evenly positioned, with a 200 bp repeat pattern, like cell DNA. Where then are the nucleosomes positioned? Here we perform HSV-1 genome wide nucleosome mapping, at a time when viral replication is in full swing (6 hr PI), using a microarray consisting of 50mer oligonucleotides, covering the whole viral genome (152 kb). Arrays were probed with MNase-protected fragments of DNA from infected cells. Cells were not treated with crosslinking agents, thus we are only mapping tightly bound nucleosomes. The data show that nucleosome deposition is not random. The distribution of signal on the arrays suggest that nucleosomes are located at preferred positions on the genome, and that there are some positions that are not occupied (nucleosome free regions -NFR or Nucleosome depleted regions -NDR), or occupied at frequency below our limit of detection in the population of genomes. Occupancy of only a fraction of the possible sites may explain the lack of a typical MNase partial digestion band ladder pattern for HSV DNA during lytic infection. On average, DNA encoding Immediate Early (IE), Early (E) and Late (L) genes appear to have a similar density of nucleosomes.

  20. Genome wide nucleosome mapping for HSV-1 shows nucleosomes are deposited at preferred positions during lytic infection.

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    Jaewook Oh

    Full Text Available HSV is a large double stranded DNA virus, capable of causing a variety of diseases from the common cold sore to devastating encephalitis. Although DNA within the HSV virion does not contain any histone protein, within 1 h of infecting a cell and entering its nucleus the viral genome acquires some histone protein (nucleosomes. During lytic infection, partial micrococcal nuclease (MNase digestion does not give the classic ladder band pattern, seen on digestion of cell DNA or latent viral DNA. However, complete digestion does give a mono-nucleosome band, strongly suggesting that there are some nucleosomes present on the viral genome during the lytic infection, but that they are not evenly positioned, with a 200 bp repeat pattern, like cell DNA. Where then are the nucleosomes positioned? Here we perform HSV-1 genome wide nucleosome mapping, at a time when viral replication is in full swing (6 hr PI, using a microarray consisting of 50mer oligonucleotides, covering the whole viral genome (152 kb. Arrays were probed with MNase-protected fragments of DNA from infected cells. Cells were not treated with crosslinking agents, thus we are only mapping tightly bound nucleosomes. The data show that nucleosome deposition is not random. The distribution of signal on the arrays suggest that nucleosomes are located at preferred positions on the genome, and that there are some positions that are not occupied (nucleosome free regions -NFR or Nucleosome depleted regions -NDR, or occupied at frequency below our limit of detection in the population of genomes. Occupancy of only a fraction of the possible sites may explain the lack of a typical MNase partial digestion band ladder pattern for HSV DNA during lytic infection. On average, DNA encoding Immediate Early (IE, Early (E and Late (L genes appear to have a similar density of nucleosomes.

  1. Baculoviruses and nucleosome management

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    Volkman, Loy E., E-mail: lvolkman@berkeley.edu

    2015-02-15

    Negatively-supercoiled-ds DNA molecules, including the genomes of baculoviruses, spontaneously wrap around cores of histones to form nucleosomes when present within eukaryotic nuclei. Hence, nucleosome management should be essential for baculovirus genome replication and temporal regulation of transcription, but this has not been documented. Nucleosome mobilization is the dominion of ATP-dependent chromatin-remodeling complexes. SWI/SNF and INO80, two of the best-studied complexes, as well as chromatin modifier TIP60, all contain actin as a subunit. Retrospective analysis of results of AcMNPV time course experiments wherein actin polymerization was blocked by cytochalasin D drug treatment implicate actin-containing chromatin modifying complexes in decatenating baculovirus genomes, shutting down host transcription, and regulating late and very late phases of viral transcription. Moreover, virus-mediated nuclear localization of actin early during infection may contribute to nucleosome management. - Highlights: • Baculoviruses have negatively-supercoiled, circular ds DNA. • Negatively-supercoiled DNA spontaneously forms nucleosomes in the nucleus. • Nucleosomes must be mobilized for replication and transcription to proceed. • Actin-containing chromatin modifiers participate in baculovirus replication.

  2. Nucleosome Positioning and NDR Structure at RNA Polymerase III Promoters

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    Helbo, Alexandra Søgaard; Lay, Fides D; Jones, Peter A

    2017-01-01

    Chromatin is structurally involved in the transcriptional regulation of all genes. While the nucleosome positioning at RNA polymerase II (pol II) promoters has been extensively studied, less is known about the chromatin structure at pol III promoters in human cells. We use a high-resolution analy......Chromatin is structurally involved in the transcriptional regulation of all genes. While the nucleosome positioning at RNA polymerase II (pol II) promoters has been extensively studied, less is known about the chromatin structure at pol III promoters in human cells. We use a high....... The +1 nucleosome is located further downstream than at pol II genes and furthermore displays weak positioning. The variable position of the +1 location is seen not only within individual cell populations and between cell types, but also between different pol III promoter subtypes, suggesting that the +1...... the first high-resolution map of nucleosome positioning and occupancy at human pol III promoters at specific loci and genome wide....

  3. An in vitro-identified high-affinity nucleosome-positioning signal is capable of transiently positioning a nucleosome in vivo

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    Gracey Lia E

    2010-07-01

    Full Text Available Abstract Background The physiological function of eukaryotic DNA occurs in the context of nucleosomal arrays that can expose or obscure defined segments of the genome. Certain DNA sequences are capable of strongly positioning a nucleosome in vitro, suggesting the possibility that favorable intrinsic signals might reproducibly structure chromatin segments. As high-throughput sequencing analyses of nucleosome coverage in vitro and in vivo have become possible, a vigorous debate has arisen over the degree to which intrinsic DNA:nucleosome affinities orchestrate the in vivo positions of nucleosomes, thereby controlling physical accessibility of specific sequences in DNA. Results We describe here the in vivo consequences of placing a synthetic high-affinity nucleosome-positioning signal, the 601 sequence, into a DNA plasmid vector in mice. Strikingly, the 601 sequence was sufficient to position nucleosomes during an early phase after introduction of the DNA into the mice (when the plasmid vector transgene was active. This positioning capability was transient, with a loss of strong positioning at a later time point when the transgenes had become silent. Conclusions These results demonstrate an ability of DNA sequences selected solely for nucleosome affinity to organize chromatin in vivo, and the ability of other mechanisms to overcome these interactions in a dynamic nuclear environment.

  4. Poly-dA:dT tracts form an in vivo nucleosomal turnstile.

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    Carl G de Boer

    Full Text Available Nucleosomes regulate many DNA-dependent processes by controlling the accessibility of DNA, and DNA sequences such as the poly-dA:dT element are known to affect nucleosome binding. We demonstrate that poly-dA:dT tracts form an asymmetric barrier to nucleosome movement in vivo, mediated by ATP-dependent chromatin remodelers. We theorize that nucleosome transit over poly-A elements is more energetically favourable in one direction, leading to an asymmetric arrangement of nucleosomes around these sequences. We demonstrate that different arrangements of poly-A and poly-T tracts result in very different outcomes for nucleosome occupancy in yeast, mouse, and human, and show that yeast takes advantage of this phenomenon in its promoter architecture.

  5. Nucleosome repositioning during differentiation of a human myeloid leukemia cell line

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    Teif, Vladimir B.; Mallm, Jan-Philipp; Sharma, Tanvi; Mark Welch, David B.; Rippe, Karsten; Eils, Roland; Langowski, J?rg; Olins, Ada L.; Olins, Donald E.

    2017-01-01

    ABSTRACT Cell differentiation is associated with changes in chromatin organization and gene expression. In this study, we examine chromatin structure following differentiation of the human myeloid leukemia cell line (HL-60/S4) into granulocytes with retinoic acid (RA) or into macrophage with phorbol ester (TPA). We performed ChIP-seq of histone H3 and its modifications, analyzing changes in nucleosome occupancy, nucleosome repeat length, eu-/heterochromatin redistribution and properties of ep...

  6. Comparative analysis of methods for genome-wide nucleosome cartography.

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    Quintales, Luis; Vázquez, Enrique; Antequera, Francisco

    2015-07-01

    Nucleosomes contribute to compacting the genome into the nucleus and regulate the physical access of regulatory proteins to DNA either directly or through the epigenetic modifications of the histone tails. Precise mapping of nucleosome positioning across the genome is, therefore, essential to understanding the genome regulation. In recent years, several experimental protocols have been developed for this purpose that include the enzymatic digestion, chemical cleavage or immunoprecipitation of chromatin followed by next-generation sequencing of the resulting DNA fragments. Here, we compare the performance and resolution of these methods from the initial biochemical steps through the alignment of the millions of short-sequence reads to a reference genome to the final computational analysis to generate genome-wide maps of nucleosome occupancy. Because of the lack of a unified protocol to process data sets obtained through the different approaches, we have developed a new computational tool (NUCwave), which facilitates their analysis, comparison and assessment and will enable researchers to choose the most suitable method for any particular purpose. NUCwave is freely available at http://nucleosome.usal.es/nucwave along with a step-by-step protocol for its use. © The Author 2014. Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  7. Functional roles of the DNA-binding HMGB domain in the histone chaperone FACT in nucleosome reorganization.

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    McCullough, Laura L; Connell, Zaily; Xin, Hua; Studitsky, Vasily M; Feofanov, Alexey V; Valieva, Maria E; Formosa, Tim

    2018-03-07

    The essential histone chaperone FAcilitates Chromatin Transcription (FACT) promotes both nucleosome assembly and disassembly. FACT is a heterodimer of Spt16 with either SSRP1 or Pob3, differing primarily by the presence of a high-mobility group B (HMGB) DNA-binding domain furnished only by SSRP1. Yeast FACT lacks the intrinsic HMGB domain found in SSRP1-based homologs such as human FACT, but yeast FACT activity is supported by Nhp6, which is a freestanding, single HMGB domain protein. The importance of histone binding by FACT domains has been established, but the roles of DNA binding activity remain poorly understood. Here, we examined these roles by fusing single or multiple HMGB modules to Pob3 to mimic SSRP1 or to test the effects of extended DNA-binding capacity. Human FACT and a yeast mimic both required Nhp6 to support nucleosome reorganization in vitro, indicating that a single intrinsic DNA-binding HMGB module is insufficient for full FACT activity. Three fused HMGB modules supported activity without Nhp6 assistance, but this FACT variant did not efficiently release from nucleosomes and was toxic in vivo. Notably, intrinsic DNA-binding HMGB modules reduced the DNA accessibility and histone H2A-H2B dimer loss normally associated with nucleosome reorganization. We propose that DNA bending by HMGB domains promotes nucleosome destabilization and reorganization by exposing FACT's histone binding sites, but DNA bending also produces DNA curvature needed to accommodate nucleosome assembly. Intrinsic DNA bending activity therefore favors nucleosome assembly by FACT over nucleosome reorganization, but excessive activity impairs FACT release, suggesting a quality control checkpoint during nucleosome assembly. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

  8. Physics behind the mechanical nucleosome positioning code

    Science.gov (United States)

    Zuiddam, Martijn; Everaers, Ralf; Schiessel, Helmut

    2017-11-01

    The positions along DNA molecules of nucleosomes, the most abundant DNA-protein complexes in cells, are influenced by the sequence-dependent DNA mechanics and geometry. This leads to the "nucleosome positioning code", a preference of nucleosomes for certain sequence motives. Here we introduce a simplified model of the nucleosome where a coarse-grained DNA molecule is frozen into an idealized superhelical shape. We calculate the exact sequence preferences of our nucleosome model and find it to reproduce qualitatively all the main features known to influence nucleosome positions. Moreover, using well-controlled approximations to this model allows us to come to a detailed understanding of the physics behind the sequence preferences of nucleosomes.

  9. Unbiased chromatin accessibility profiling by RED-seq uncovers unique features of nucleosome variants in vivo.

    Science.gov (United States)

    Chen, Poshen B; Zhu, Lihua J; Hainer, Sarah J; McCannell, Kurtis N; Fazzio, Thomas G

    2014-12-15

    Differential accessibility of DNA to nuclear proteins underlies the regulation of numerous cellular processes. Although DNA accessibility is primarily determined by the presence or absence of nucleosomes, differences in nucleosome composition or dynamics may also regulate accessibility. Methods for mapping nucleosome positions and occupancies genome-wide (MNase-seq) have uncovered the nucleosome landscapes of many different cell types and organisms. Conversely, methods specialized for the detection of large nucleosome-free regions of chromatin (DNase-seq, FAIRE-seq) have uncovered numerous gene regulatory elements. However, these methods are less successful in measuring the accessibility of DNA sequences within nucelosome arrays. Here we probe the genome-wide accessibility of multiple cell types in an unbiased manner using restriction endonuclease digestion of chromatin coupled to deep sequencing (RED-seq). Using this method, we identified differences in chromatin accessibility between populations of cells, not only in nucleosome-depleted regions of the genome (e.g., enhancers and promoters), but also within the majority of the genome that is packaged into nucleosome arrays. Furthermore, we identified both large differences in chromatin accessibility in distinct cell lineages and subtle but significant changes during differentiation of mouse embryonic stem cells (ESCs). Most significantly, using RED-seq, we identified differences in accessibility among nucleosomes harboring well-studied histone variants, and show that these differences depend on factors required for their deposition. Using an unbiased method to probe chromatin accessibility genome-wide, we uncover unique features of chromatin structure that are not observed using more widely-utilized methods. We demonstrate that different types of nucleosomes within mammalian cells exhibit different degrees of accessibility. These findings provide significant insight into the regulation of DNA accessibility.

  10. The impact of the nucleosome code on protein-coding sequence evolution in yeast.

    Directory of Open Access Journals (Sweden)

    Tobias Warnecke

    2008-11-01

    Full Text Available Coding sequence evolution was once thought to be the result of selection on optimal protein function alone. Selection can, however, also act at the RNA level, for example, to facilitate rapid translation or ensure correct splicing. Here, we ask whether the way DNA works also imposes constraints on coding sequence evolution. We identify nucleosome positioning as a likely candidate to set up such a DNA-level selective regime and use high-resolution microarray data in yeast to compare the evolution of coding sequence bound to or free from nucleosomes. Controlling for gene expression and intra-gene location, we find a nucleosome-free "linker" sequence to evolve on average 5-6% slower at synonymous sites. A reduced rate of evolution in linker is especially evident at the 5' end of genes, where the effect extends to non-synonymous substitution rates. This is consistent with regular nucleosome architecture in this region being important in the context of gene expression control. As predicted, codons likely to generate a sequence unfavourable to nucleosome formation are enriched in linker sequence. Amino acid content is likewise skewed as a function of nucleosome occupancy. We conclude that selection operating on DNA to maintain correct positioning of nucleosomes impacts codon choice, amino acid choice, and synonymous and non-synonymous rates of evolution in coding sequence. The results support the exclusion model for nucleosome positioning and provide an alternative interpretation for runs of rare codons. As the intimate association of histones and DNA is a universal characteristic of genic sequence in eukaryotes, selection on coding sequence composition imposed by nucleosome positioning should be phylogenetically widespread.

  11. Nucleosome Repositioning: A Novel Mechanism for Nicotine- and Cocaine-Induced Epigenetic Changes.

    Directory of Open Access Journals (Sweden)

    Amber N Brown

    Full Text Available Drugs of abuse modify behavior by altering gene expression in the brain. Gene expression can be regulated by changes in DNA methylation as well as by histone modifications, which alter chromatin structure, DNA compaction and DNA accessibility. In order to better understand the molecular mechanisms directing drug-induced changes in chromatin structure, we examined DNA-nucleosome interactions within promoter regions of 858 genes in human neuroblastoma cells (SH-SY5Y exposed to nicotine or cocaine. Widespread, drug- and time-resolved repositioning of nucleosomes was identified at the transcription start site and promoter region of multiple genes. Nicotine and cocaine produced unique and shared changes in terms of the numbers and types of genes affected, as well as repositioning of nucleosomes at sites which could increase or decrease the probability of gene expression based on DNA accessibility. Half of the drug-induced nucleosome positions approximated a theoretical model of nucleosome occupancy based on physical and chemical characteristics of the DNA sequence, whereas the basal or drug naïve positions were generally DNA sequence independent. Thus we suggest that nucleosome repositioning represents an initial dynamic genome-wide alteration of the transcriptional landscape preceding more selective downstream transcriptional reprogramming, which ultimately characterizes the cell- and tissue-specific responses to drugs of abuse.

  12. Nucleosome Repositioning: A Novel Mechanism for Nicotine- and Cocaine-Induced Epigenetic Changes.

    Science.gov (United States)

    Brown, Amber N; Vied, Cynthia; Dennis, Jonathan H; Bhide, Pradeep G

    2015-01-01

    Drugs of abuse modify behavior by altering gene expression in the brain. Gene expression can be regulated by changes in DNA methylation as well as by histone modifications, which alter chromatin structure, DNA compaction and DNA accessibility. In order to better understand the molecular mechanisms directing drug-induced changes in chromatin structure, we examined DNA-nucleosome interactions within promoter regions of 858 genes in human neuroblastoma cells (SH-SY5Y) exposed to nicotine or cocaine. Widespread, drug- and time-resolved repositioning of nucleosomes was identified at the transcription start site and promoter region of multiple genes. Nicotine and cocaine produced unique and shared changes in terms of the numbers and types of genes affected, as well as repositioning of nucleosomes at sites which could increase or decrease the probability of gene expression based on DNA accessibility. Half of the drug-induced nucleosome positions approximated a theoretical model of nucleosome occupancy based on physical and chemical characteristics of the DNA sequence, whereas the basal or drug naïve positions were generally DNA sequence independent. Thus we suggest that nucleosome repositioning represents an initial dynamic genome-wide alteration of the transcriptional landscape preceding more selective downstream transcriptional reprogramming, which ultimately characterizes the cell- and tissue-specific responses to drugs of abuse.

  13. LeNup: Learning Nucleosome positioning from DNA sequences with improved convolutional neural networks.

    Science.gov (United States)

    Zhang, Juhua; Peng, Wenbo; Wang, Lei

    2018-01-10

    Nucleosome positioning plays significant roles in proper genome packing and its accessibility to execute transcription regulation. Despite a multitude of nucleosome positioning resources available on line including experimental datasets of genome-wide nucleosome occupancy profiles and computational tools to the analysis on these data, the complex language of eukaryotic Nucleosome positioning remains incompletely understood. Here, we address this challenge using an approach based on a state-of-the-art machine learning method. We present a novel convolutional neural network (CNN) to understand nucleosome positioning. We combined Inception-like networks with a gating mechanism for the response of multiple patterns and long term association in DNA sequences. We developed the open-source package LeNup based on the CNN to predict nucleosome positioning in Homo sapiens, Caenorhabditis elegans, Drosophila melanogaster as well as Saccharomyces cerevisiae genomes. We trained LeNup on four benchmark datasets. LeNup achieved greater predictive accuracy than previously published methods. LeNup is freely available as Python and Lua script source code under a BSD style license from https://github.com/biomedBit/LeNup. jhzhang@bit.edu.cn. Supplementary data are available at Bioinformatics online. © The Author (2018). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  14. DNA methylation, nucleosome formation and positioning.

    Science.gov (United States)

    Pennings, Sari; Allan, James; Davey, Colin S

    2005-02-01

    Recent mapping of nucleosome positioning on several long gene regions subject to DNA methylation has identified instances of nucleosome repositioning by this base modification. The evidence for an effect of CpG methylation on nucleosome formation and positioning in chromatin is reviewed here in the context of the complex sequence-structure requirements of DNA wrapping around the histone octamer and the role of this epigenetic mark in gene repression.

  15. Translation efficiency in yeasts correlates with nucleosome formation in promoters.

    Science.gov (United States)

    Matushkin, Yu G; Levitsky, V G; Orlov, Yu L; Likhoshvai, V A; Kolchanov, N A

    2013-01-01

    Elongation efficiency index (EEI) was suggested earlier to estimate gene expression efficiency by nucleotide context of coding sequence in unicellular organisms. We have analyzed association between EEI and nucleosome formation potential (NFP) in 5' regulatory regions upstream translation initiation site (TIS) from two yeast species. Theoretical estimations of NFP based on DNA sequence were obtained by Recon method. Experimental estimation of nucleosome occupancy was obtained by high-throughput sequencing data of nucleosomal DNA in Saccharomyces cerevisiae . For the sample of all genes correlation coefficient was calculated between two vectors: vector of NFP values for fixed position relative to TIS and vector of EEI values. Profiles of correlation coefficients of NFP and EEI were counted in (-600; +600) regions relative to TIS for gene sequences extracted from GenBank. We found regions of strong negative dependence between NFP and EEI for all genes as well as for 10% highly expressed genes in Schizosaccharomyces pombe (10% of EEI-highest genes). At the same time, we found positive dependence between NFP and EEI for all genes and for low expressed genes in S. cerevisiae (10% of EEI-lowest genes). The association between NFP and EEI could be explained by evolutionary selection of context characteristics of nucleotide sequences for gene expression optimization.

  16. Characterization of Dnmt1 Binding and DNA Methylation on Nucleosomes and Nucleosomal Arrays.

    Directory of Open Access Journals (Sweden)

    Anna Schrader

    Full Text Available The packaging of DNA into nucleosomes and the organisation into higher order structures of chromatin limits the access of sequence specific DNA binding factors to DNA. In cells, DNA methylation is preferentially occuring in the linker region of nucleosomes, suggesting a structural impact of chromatin on DNA methylation. These observations raise the question whether DNA methyltransferases are capable to recognize the nucleosomal substrates and to modify the packaged DNA. Here, we performed a detailed analysis of nucleosome binding and nucleosomal DNA methylation by the maintenance DNA methyltransferase Dnmt1. Our binding studies show that Dnmt1 has a DNA length sensing activity, binding cooperatively to DNA, and requiring a minimal DNA length of 20 bp. Dnmt1 needs linker DNA to bind to nucleosomes and most efficiently recognizes nucleosomes with symmetric DNA linkers. Footprinting experiments reveal that Dnmt1 binds to both DNA linkers exiting the nucleosome core. The binding pattern correlates with the efficient methylation of DNA linkers. However, the enzyme lacks the ability to methylate nucleosomal CpG sites on mononucleosomes and nucleosomal arrays, unless chromatin remodeling enzymes create a dynamic chromatin state. In addition, our results show that Dnmt1 functionally interacts with specific chromatin remodeling enzymes to enable complete methylation of hemi-methylated DNA in chromatin.

  17. Transcription factor binding sites prediction based on modified nucleosomes.

    Directory of Open Access Journals (Sweden)

    Mohammad Talebzadeh

    Full Text Available In computational methods, position weight matrices (PWMs are commonly applied for transcription factor binding site (TFBS prediction. Although these matrices are more accurate than simple consensus sequences to predict actual binding sites, they usually produce a large number of false positive (FP predictions and so are impoverished sources of information. Several studies have employed additional sources of information such as sequence conservation or the vicinity to transcription start sites to distinguish true binding regions from random ones. Recently, the spatial distribution of modified nucleosomes has been shown to be associated with different promoter architectures. These aligned patterns can facilitate DNA accessibility for transcription factors. We hypothesize that using data from these aligned and periodic patterns can improve the performance of binding region prediction. In this study, we propose two effective features, "modified nucleosomes neighboring" and "modified nucleosomes occupancy", to decrease FP in binding site discovery. Based on these features, we designed a logistic regression classifier which estimates the probability of a region as a TFBS. Our model learned each feature based on Sp1 binding sites on Chromosome 1 and was tested on the other chromosomes in human CD4+T cells. In this work, we investigated 21 histone modifications and found that only 8 out of 21 marks are strongly correlated with transcription factor binding regions. To prove that these features are not specific to Sp1, we combined the logistic regression classifier with the PWM, and created a new model to search TFBSs on the genome. We tested the model using transcription factors MAZ, PU.1 and ELF1 and compared the results to those using only the PWM. The results show that our model can predict Transcription factor binding regions more successfully. The relative simplicity of the model and capability of integrating other features make it a superior method

  18. Cell-free DNA Comprises an In Vivo Nucleosome Footprint that Informs Its Tissues-Of-Origin.

    Science.gov (United States)

    Snyder, Matthew W; Kircher, Martin; Hill, Andrew J; Daza, Riza M; Shendure, Jay

    2016-01-14

    Nucleosome positioning varies between cell types. By deep sequencing cell-free DNA (cfDNA), isolated from circulating blood plasma, we generated maps of genome-wide in vivo nucleosome occupancy and found that short cfDNA fragments harbor footprints of transcription factors. The cfDNA nucleosome occupancies correlate well with the nuclear architecture, gene structure, and expression observed in cells, suggesting that they could inform the cell type of origin. Nucleosome spacing inferred from cfDNA in healthy individuals correlates most strongly with epigenetic features of lymphoid and myeloid cells, consistent with hematopoietic cell death as the normal source of cfDNA. We build on this observation to show how nucleosome footprints can be used to infer cell types contributing to cfDNA in pathological states such as cancer. Since this strategy does not rely on genetic differences to distinguish between contributing tissues, it may enable the noninvasive monitoring of a much broader set of clinical conditions than currently possible. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. From nucleosome to chromosome: a dynamic organization of genetic information

    NARCIS (Netherlands)

    Fransz, P.F.; Jong, de J.H.S.G.M.

    2011-01-01

    Gene activity is controlled at different levels of chromatin organization, which involve genomic sequences, nucleosome structure, chromatin folding and chromosome arrangement. These levels are interconnected and influence each other. At the basic level nucleosomes generally occlude the DNA sequence

  20. From nucleosome to chromosome : a dynamic organization of genetic information

    NARCIS (Netherlands)

    Fransz, P.; de Jong, H.

    2011-01-01

    Gene activity is controlled at different levels of chromatin organization, which involve genomic sequences, nucleosome structure, chromatin folding and chromosome arrangement. These levels are interconnected and influence each other. At the basic level nucleosomes generally occlude the DNA sequence

  1. A positioned +1 nucleosome enhances promoter-proximal pausing

    OpenAIRE

    Jimeno-Gonz?lez, Silvia; Ceballos-Ch?vez, Mar?a; Reyes, Jos? C.

    2015-01-01

    Chromatin distribution is not uniform along the human genome. In most genes there is a promoter-associated nucleosome free region (NFR) followed by an array of nucleosomes towards the gene body in which the first (+1) nucleosome is strongly positioned. The function of this characteristic chromatin distribution in transcription is not fully understood. Here we show in vivo that the +1 nucleosome plays a role in modulating RNA polymerase II (RNAPII) promoter-proximal pausing. When a +1 nucleoso...

  2. Painting a perspective on the landscape of nucleosome positioning.

    Science.gov (United States)

    Johnson, Steven M

    2010-06-01

    DNA sequence influences the position of nucleosomes and chromatin architecture. The extent to which underlying DNA sequence affects nucleosome positioning is currently a topic of considerable discussion and active experimentation. To contribute to the discussion, I will outline a few of the methods, data and arguments that I find compelling and believe will ultimately resolve the question of what positions nucleosomes. Basically, I will give a portrait of my current perspective on what influences the landscape of nucleosome positioning and chromatin architecture.

  3. Nucleosome dynamics: HMGB1 facilitates nucleosome restructuring and collaborates in estrogen-responsive gene expression

    Directory of Open Access Journals (Sweden)

    William M. Scovell

    2016-12-01

    Full Text Available The genome in the human cell is extraordinarily compacted in the nucleus. As a result, much of the DNA is inaccessible and functionally inert. Notwithstanding the highly efficient packaging, mechanisms have evolved to render DNA sites accessible that then enable a multitude of factors to carry out ongoing and vital functions. The compaction is derived from DNA complexation within nucleosomes, which can further consolidate into a higher-order chromatin structure. The nucleosome and nucleosomal DNA are not static in nature, but are dynamic, undergoing structural and functional changes as the cell responds to stresses and/or metabolic or environmental cues. We are only beginning to understand the forces and the complexes that engage the nucleosome to unearth the tightly bound and inaccessible DNA sequences and provide an opening to more accessible target sites. In many cases, current findings support a major role for the action of ATP-dependent chromatin remodeling complexes (CRCs in providing an avenue to factor accessibility that leads to the activation of transcription. The estrogen receptor α (ERα does not bind to the estrogen response element (ERE in the canonical nucleosome. However, evidence will be presented that HMGB1 restructures the nucleosome in an ATP-independent manner and also facilitates access and strong binding of ERα to ERE. The features that appear important in the mechanism of action for HMGB1 will be highlighted, in addition to the characteristic features of the restructured nucleosome. These findings, together with previous evidence, suggest a collaborative role for HMGB1 in the step-wise transcription of estrogen-responsive genes. In addition, alternate mechanistic pathways will be discussed, with consideration that “HMGB1 restructuring” of the nucleosome may generally be viewed as a perturbation of the equilibrium of an ensemble of nearly isoenergetic nucleosome states in an energy landscape that is driven by

  4. Nucleosomal TATA-switch: competing orientations of TATA on the nucleosome.

    Science.gov (United States)

    Hapala, Jan; Trifonov, Edward N

    2013-09-15

    Transcription is known to be affected by the rotational setting of the transcription response elements within nucleosomes. We studied the rotational positioning of the TATA box, the most universal promoter motif. We applied a bioinformatic high-resolution nucleosome mapping technique to eukaryotic promoters. Our results show that the nucleosome DNA sequence harboring the TATA box encodes alternative rotational positions for the same piece of DNA. This may serve for switching the gene activity on and off. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. The disequilibrium of nucleosomes distribution along chromosomes plays a functional and evolutionarily role in regulating gene expression.

    Directory of Open Access Journals (Sweden)

    Peng Cui

    Full Text Available To further understand the relationship between nucleosome-space occupancy (NO and global transcriptional activity in mammals, we acquired a set of genome-wide nucleosome distribution and transcriptome data from the mouse cerebrum and testis based on ChIP (H3-seq and RNA-seq, respectively. We identified a nearly consistent NO patterns among three mouse tissues--cerebrum, testis, and ESCs--and found, through clustering analysis for transcriptional activation, that the NO variations among chromosomes are closely associated with distinct expression levels between house-keeping (HK genes and tissue-specific (TS genes. Both TS and HK genes form clusters albeit the obvious majority. This feature implies that NO patterns, i.e. nucleosome binding and clustering, are coupled with gene clustering that may be functionally and evolutionarily conserved in regulating gene expression among different cell types.

  6. The disequilibrium of nucleosomes distribution along chromosomes plays a functional and evolutionarily role in regulating gene expression

    KAUST Repository

    Cui, Peng

    2011-08-19

    To further understand the relationship between nucleosome-space occupancy (NO) and global transcriptional activity in mammals, we acquired a set of genome-wide nucleosome distribution and transcriptome data from the mouse cerebrum and testis based on ChIP (H3)-seq and RNA-seq, respectively. We identified a nearly consistent NO patterns among three mouse tissues-cerebrum, testis, and ESCs-and found, through clustering analysis for transcriptional activation, that the NO variations among chromosomes are closely associated with distinct expression levels between house-keeping (HK) genes and tissue-specific (TS) genes. Both TS and HK genes form clusters albeit the obvious majority. This feature implies that NO patterns, i.e. nucleosome binding and clustering, are coupled with gene clustering that may be functionally and evolutionarily conserved in regulating gene expression among different cell types. © 2011 Cui et al.

  7. Nucleosomal DNA fragments in autoimmune diseases

    NARCIS (Netherlands)

    Holdenrieder, Stefan; Eichhorn, Peter; Beuers, Ulrich; Samtleben, Walter; Schoenermarck, Ulf; Zachoval, Reinhart; Nagel, Dorothea; Stieber, Petra

    2006-01-01

    The inadequate response of immune cells to circulating apoptotic products, such as nucleosomal DNA fragments, is assumed to be a potent stimulus for the production of autoantibodies during the pathogenesis and progression of systemic lupus erythematosus (SLE). Here, we analyzed the levels of

  8. Dynamic nucleosome organization at hox promoters during zebrafish embryogenesis.

    Directory of Open Access Journals (Sweden)

    Steven E Weicksel

    Full Text Available Nucleosome organization at promoter regions plays an important role in regulating gene activity. Genome-wide studies in yeast, flies, worms, mammalian embryonic stem cells and transformed cell lines have found well-positioned nucleosomes flanking a nucleosome depleted region (NDR at transcription start sites. This nucleosome arrangement depends on DNA sequence (cis-elements as well as DNA binding factors and ATP-dependent chromatin modifiers (trans-factors. However, little is understood about how the nascent embryonic genome positions nucleosomes during development. This is particularly intriguing since the embryonic genome must undergo a broad reprogramming event upon fusion of sperm and oocyte. Using four stages of early embryonic zebrafish development, we map nucleosome positions at the promoter region of 37 zebrafish hox genes. We find that nucleosome arrangement at the hox promoters is a progressive process that takes place over several stages. At stages immediately after fertilization, nucleosomes appear to be largely disordered at hox promoter regions. At stages after activation of the embryonic genome, nucleosomes are detectable at hox promoters, with positions becoming more uniform and more highly occupied. Since the genomic sequence is invariant during embryogenesis, this progressive change in nucleosome arrangement suggests that trans-factors play an important role in organizing nucleosomes during embryogenesis. Separating hox genes into expressed and non-expressed groups shows that expressed promoters have better positioned and occupied nucleosomes, as well as distinct NDRs, than non-expressed promoters. Finally, by blocking the retinoic acid-signaling pathway, we disrupt early hox gene transcription, but observe no effect on nucleosome positions, suggesting that active hox transcription is not a driving force behind the arrangement of nucleosomes at the promoters of hox genes during early development.

  9. GAGA factor maintains nucleosome-free regions and has a role in RNA polymerase II recruitment to promoters.

    Science.gov (United States)

    Fuda, Nicholas J; Guertin, Michael J; Sharma, Sumeet; Danko, Charles G; Martins, André L; Siepel, Adam; Lis, John T

    2015-03-01

    Previous studies have shown that GAGA Factor (GAF) is enriched on promoters with paused RNA Polymerase II (Pol II), but its genome-wide function and mechanism of action remain largely uncharacterized. We assayed the levels of transcriptionally-engaged polymerase using global run-on sequencing (GRO-seq) in control and GAF-RNAi Drosophila S2 cells and found promoter-proximal polymerase was significantly reduced on a large subset of paused promoters where GAF occupancy was reduced by knock down. These promoters show a dramatic increase in nucleosome occupancy upon GAF depletion. These results, in conjunction with previous studies showing that GAF directly interacts with nucleosome remodelers, strongly support a model where GAF directs nucleosome displacement at the promoter and thereby allows the entry Pol II to the promoter and pause sites. This action of GAF on nucleosomes is at least partially independent of paused Pol II because intergenic GAF binding sites with little or no Pol II also show GAF-dependent nucleosome displacement. In addition, the insulator factor BEAF, the BEAF-interacting protein Chriz, and the transcription factor M1BP are strikingly enriched on those GAF-associated genes where pausing is unaffected by knock down, suggesting insulators or the alternative promoter-associated factor M1BP protect a subset of GAF-bound paused genes from GAF knock-down effects. Thus, GAF binding at promoters can lead to the local displacement of nucleosomes, but this activity can be restricted or compensated for when insulator protein or M1BP complexes also reside at GAF bound promoters.

  10. GAGA factor maintains nucleosome-free regions and has a role in RNA polymerase II recruitment to promoters.

    Directory of Open Access Journals (Sweden)

    Nicholas J Fuda

    2015-03-01

    Full Text Available Previous studies have shown that GAGA Factor (GAF is enriched on promoters with paused RNA Polymerase II (Pol II, but its genome-wide function and mechanism of action remain largely uncharacterized. We assayed the levels of transcriptionally-engaged polymerase using global run-on sequencing (GRO-seq in control and GAF-RNAi Drosophila S2 cells and found promoter-proximal polymerase was significantly reduced on a large subset of paused promoters where GAF occupancy was reduced by knock down. These promoters show a dramatic increase in nucleosome occupancy upon GAF depletion. These results, in conjunction with previous studies showing that GAF directly interacts with nucleosome remodelers, strongly support a model where GAF directs nucleosome displacement at the promoter and thereby allows the entry Pol II to the promoter and pause sites. This action of GAF on nucleosomes is at least partially independent of paused Pol II because intergenic GAF binding sites with little or no Pol II also show GAF-dependent nucleosome displacement. In addition, the insulator factor BEAF, the BEAF-interacting protein Chriz, and the transcription factor M1BP are strikingly enriched on those GAF-associated genes where pausing is unaffected by knock down, suggesting insulators or the alternative promoter-associated factor M1BP protect a subset of GAF-bound paused genes from GAF knock-down effects. Thus, GAF binding at promoters can lead to the local displacement of nucleosomes, but this activity can be restricted or compensated for when insulator protein or M1BP complexes also reside at GAF bound promoters.

  11. Interaction of influenza virus proteins with nucleosomes

    International Nuclear Information System (INIS)

    Garcia-Robles, Inmaculada; Akarsu, Hatice; Mueller, Christoph W.; Ruigrok, Rob W.H.; Baudin, Florence

    2005-01-01

    During influenza virus infection, transcription and replication of the viral RNA take place in the cell nucleus. Directly after entry in the nucleus the viral ribonucleoproteins (RNPs, the viral subunits containing vRNA, nucleoprotein and the viral polymerase) are tightly associated with the nuclear matrix. Here, we have analysed the binding of RNPs, M1 and NS2/NEP proteins to purified nucleosomes, reconstituted histone octamers and purified single histones. RNPs and M1 both bind to the chromatin components but at two different sites, RNP to the histone tails and M1 to the globular domain of the histone octamer. NS2/NEP did not bind to nucleosomes at all. The possible consequences of these findings for nuclear release of newly made RNPs and for other processes during the infection cycle are discussed

  12. Nucleosome breathing and remodeling constrain CRISPR-Cas9 function.

    Science.gov (United States)

    Isaac, R Stefan; Jiang, Fuguo; Doudna, Jennifer A; Lim, Wendell A; Narlikar, Geeta J; Almeida, Ricardo

    2016-04-28

    The CRISPR-Cas9 bacterial surveillance system has become a versatile tool for genome editing and gene regulation in eukaryotic cells, yet how CRISPR-Cas9 contends with the barriers presented by eukaryotic chromatin is poorly understood. Here we investigate how the smallest unit of chromatin, a nucleosome, constrains the activity of the CRISPR-Cas9 system. We find that nucleosomes assembled on native DNA sequences are permissive to Cas9 action. However, the accessibility of nucleosomal DNA to Cas9 is variable over several orders of magnitude depending on dynamic properties of the DNA sequence and the distance of the PAM site from the nucleosome dyad. We further find that chromatin remodeling enzymes stimulate Cas9 activity on nucleosomal templates. Our findings imply that the spontaneous breathing of nucleosomal DNA together with the action of chromatin remodelers allow Cas9 to effectively act on chromatin in vivo.

  13. NucTools: analysis of chromatin feature occupancy profiles from high-throughput sequencing data.

    Science.gov (United States)

    Vainshtein, Yevhen; Rippe, Karsten; Teif, Vladimir B

    2017-02-14

    Biomedical applications of high-throughput sequencing methods generate a vast amount of data in which numerous chromatin features are mapped along the genome. The results are frequently analysed by creating binary data sets that link the presence/absence of a given feature to specific genomic loci. However, the nucleosome occupancy or chromatin accessibility landscape is essentially continuous. It is currently a challenge in the field to cope with continuous distributions of deep sequencing chromatin readouts and to integrate the different types of discrete chromatin features to reveal linkages between them. Here we introduce the NucTools suite of Perl scripts as well as MATLAB- and R-based visualization programs for a nucleosome-centred downstream analysis of deep sequencing data. NucTools accounts for the continuous distribution of nucleosome occupancy. It allows calculations of nucleosome occupancy profiles averaged over several replicates, comparisons of nucleosome occupancy landscapes between different experimental conditions, and the estimation of the changes of integral chromatin properties such as the nucleosome repeat length. Furthermore, NucTools facilitates the annotation of nucleosome occupancy with other chromatin features like binding of transcription factors or architectural proteins, and epigenetic marks like histone modifications or DNA methylation. The applications of NucTools are demonstrated for the comparison of several datasets for nucleosome occupancy in mouse embryonic stem cells (ESCs) and mouse embryonic fibroblasts (MEFs). The typical workflows of data processing and integrative analysis with NucTools reveal information on the interplay of nucleosome positioning with other features such as for example binding of a transcription factor CTCF, regions with stable and unstable nucleosomes, and domains of large organized chromatin K9me2 modifications (LOCKs). As potential limitations and problems we discuss how inter-replicate variability of

  14. Nucleosomal arrangement affects single-molecule transcription dynamics.

    Science.gov (United States)

    Fitz, Veronika; Shin, Jaeoh; Ehrlich, Christoph; Farnung, Lucas; Cramer, Patrick; Zaburdaev, Vasily; Grill, Stephan W

    2016-10-24

    In eukaryotes, gene expression depends on chromatin organization. However, how chromatin affects the transcription dynamics of individual RNA polymerases has remained elusive. Here, we use dual trap optical tweezers to study single yeast RNA polymerase II (Pol II) molecules transcribing along a DNA template with two nucleosomes. The slowdown and the changes in pausing behavior within the nucleosomal region allow us to determine a drift coefficient, χ, which characterizes the ability of the enzyme to recover from a nucleosomal backtrack. Notably, χ can be used to predict the probability to pass the first nucleosome. Importantly, the presence of a second nucleosome changes χ in a manner that depends on the spacing between the two nucleosomes, as well as on their rotational arrangement on the helical DNA molecule. Our results indicate that the ability of Pol II to pass the first nucleosome is increased when the next nucleosome is turned away from the first one to face the opposite side of the DNA template. These findings help to rationalize how chromatin arrangement affects Pol II transcription dynamics.

  15. ISWI chromatin remodellers sense nucleosome modifications to determine substrate preference

    Science.gov (United States)

    Dann, Geoffrey P.; Liszczak, Glen P.; Bagert, John D.; Müller, Manuel M.; Nguyen, Uyen T. T.; Wojcik, Felix; Brown, Zachary Z.; Bos, Jeffrey; Panchenko, Tatyana; Pihl, Rasmus; Pollock, Samuel B.; Diehl, Katharine L.; Allis, C. David; Muir, Tom W.

    2018-01-01

    ATP-dependent chromatin remodellers regulate access to genetic information by controlling nucleosome positions in vivo1. However, the mechanism by which remodellers discriminate between different nucleosome substrates is poorly understood. Many chromatin remodelling proteins possess conserved protein domains that interact with nucleosomal features2. Here we used a quantitative high-throughput approach, based on the use of a DNA-barcoded mononucleosome library, to profile the biochemical activity of human ISWI family remodellers in response to a diverse set of nucleosome modifications. We show that accessory (non-ATPase) subunits of ISWI remodellers can distinguish between differentially modified nucleosomes, directing remodelling activity towards specific nucleosome substrates according to their modification state. Unexpectedly, we show that the nucleosome acidic patch3 is necessary for maximum activity of all ISWI remodellers evaluated. This dependence also extends to CHD and SWI/SNF family remodellers, suggesting that the acidic patch may be generally required for chromatin remodelling. Critically, remodelling activity can be regulated by modifications neighbouring the acidic patch, signifying that it may act as a tunable interaction hotspot for ATP-dependent chromatin remodellers and, by extension, many other chromatin effectors that engage this region of the nucleosome surface4–9. PMID:28767641

  16. Plasma levels of nucleosomes and nucleosome-autoantibody complexes in murine lupus: effects of disease progression and lipopolyssacharide administration.

    NARCIS (Netherlands)

    Licht, R.; Bruggen, M.C.J. van; Oppers-Walgreen, B.; Rijke, T.P.M.; Berden, J.H.M.

    2001-01-01

    OBJECTIVE: To evaluate the effect of disease progression and lipopolysaccharide (LPS) administration on the presence of nucleosomes, antinucleosome reactivity, and nucleosome-Ig complexes in the circulation of MRL and control mice. METHODS: Plasma samples from lupus-prone (MRL/lpr and MRL/+) and

  17. Nucleosome fragility reveals novel functional states of chromatin and poises genes for activation.

    Science.gov (United States)

    Xi, Yuanxin; Yao, Jianhui; Chen, Rui; Li, Wei; He, Xiangwei

    2011-05-01

    The structural complexity of nucleosomes underlies their functional versatility. Here we report a new type of complexity-nucleosome fragility, manifested as high sensitivity to micrococcal nuclease, in contrast to the common presumption that nucleosomes are similar in resistance to MNase digestion. Using differential MNase digestion of chromatin and high-throughput sequencing, we have identified a special group of nucleosomes termed "fragile nucleosomes" throughout the yeast genome, nearly 1000 of which were at previously determined "nucleosome-free" loci. Nucleosome fragility is broadly implicated in multiple chromatin processes, including transcription, translocation, and replication, in correspondence to specific physiological states of cells. In the environmental-stress-response genes, the presence of fragile nucleosomes prior to the occurrence of environmental changes suggests that nucleosome fragility poises genes for swift up-regulation in response to the environmental changes. We propose that nucleosome fragility underscores distinct functional statuses of the chromatin and provides a new dimension for portraying the landscape of genome organization.

  18. Genomic sequence is highly predictive of local nucleosome depletion.

    Directory of Open Access Journals (Sweden)

    Guo-Cheng Yuan

    2008-01-01

    Full Text Available The regulation of DNA accessibility through nucleosome positioning is important for transcription control. Computational models have been developed to predict genome-wide nucleosome positions from DNA sequences, but these models consider only nucleosome sequences, which may have limited their power. We developed a statistical multi-resolution approach to identify a sequence signature, called the N-score, that distinguishes nucleosome binding DNA from non-nucleosome DNA. This new approach has significantly improved the prediction accuracy. The sequence information is highly predictive for local nucleosome enrichment or depletion, whereas predictions of the exact positions are only modestly more accurate than a null model, suggesting the importance of other regulatory factors in fine-tuning the nucleosome positions. The N-score in promoter regions is negatively correlated with gene expression levels. Regulatory elements are enriched in low N-score regions. While our model is derived from yeast data, the N-score pattern computed from this model agrees well with recent high-resolution protein-binding data in human.

  19. Multiscale modelling of nucleosome core particle aggregation

    Science.gov (United States)

    Lyubartsev, Alexander P.; Korolev, Nikolay; Fan, Yanping; Nordenskiöld, Lars

    2015-02-01

    The nucleosome core particle (NCP) is the basic building block of chromatin. Under the influence of multivalent cations, isolated mononucleosomes exhibit a rich phase behaviour forming various columnar phases with characteristic NCP-NCP stacking. NCP stacking is also a regular element of chromatin structure in vivo. Understanding the mechanism of nucleosome stacking and the conditions leading to self-assembly of NCPs is still incomplete. Due to the complexity of the system and the need to describe electrostatics properly by including the explicit mobile ions, novel modelling approaches based on coarse-grained (CG) methods at the multiscale level becomes a necessity. In this work we present a multiscale CG computer simulation approach to modelling interactions and self-assembly of solutions of NCPs induced by the presence of multivalent cations. Starting from continuum simulations including explicit three-valent cobalt(III)hexammine (CoHex3+) counterions and 20 NCPs, based on a previously developed advanced CG NCP model with one bead per amino acid and five beads per two DNA base pair unit (Fan et al 2013 PLoS One 8 e54228), we use the inverse Monte Carlo method to calculate effective interaction potentials for a ‘super-CG’ NCP model consisting of seven beads for each NCP. These interaction potentials are used in large-scale simulations of up to 5000 NCPs, modelling self-assembly induced by CoHex3+. The systems of ‘super-CG’ NCPs form a single large cluster of stacked NCPs without long-range order in agreement with experimental data for NCPs precipitated by the three-valent polyamine, spermidine3+.

  20. Intrinsic Motivation.

    Science.gov (United States)

    the activity. There has been very little research and theorizing which considers the topic of intrinsic motivation , yet there is a substantial amount...reported within the framework of intrinsic motivation , yet the paper reinterprets the work within that framework. It considers several approaches of

  1. Role of nucleosome remodeling in neurodevelopmental and intellectual disability disorders.

    Science.gov (United States)

    López, Alberto J; Wood, Marcelo A

    2015-01-01

    It is becoming increasingly important to understand how epigenetic mechanisms control gene expression during neurodevelopment. Two epigenetic mechanisms that have received considerable attention are DNA methylation and histone acetylation. Human exome sequencing and genome-wide association studies have linked several neurobiological disorders to genes whose products actively regulate DNA methylation and histone acetylation. More recently, a third major epigenetic mechanism, nucleosome remodeling, has been implicated in human developmental and intellectual disability (ID) disorders. Nucleosome remodeling is driven primarily through nucleosome remodeling complexes with specialized ATP-dependent enzymes. These enzymes directly interact with DNA or chromatin structure, as well as histone subunits, to restructure the shape and organization of nucleosome positioning to ultimately regulate gene expression. Of particular interest is the neuron-specific Brg1/hBrm Associated Factor (nBAF) complex. Mutations in nBAF subunit genes have so far been linked to Coffin-Siris syndrome (CSS), Nicolaides-Baraitser syndrome (NBS), schizophrenia, and Autism Spectrum Disorder (ASD). Together, these human developmental and ID disorders are powerful examples of the impact of epigenetic modulation on gene expression. This review focuses on the new and emerging role of nucleosome remodeling in neurodevelopmental and ID disorders and whether nucleosome remodeling affects gene expression required for cognition independently of its role in regulating gene expression required for development.

  2. Role of nucleosome remodeling in neurodevelopmental and intellectual disability disorders

    Directory of Open Access Journals (Sweden)

    Alberto J Lopez

    2015-04-01

    Full Text Available It is becoming increasingly important to understand how epigenetic mechanisms control gene expression during neurodevelopment. Two epigenetic mechanisms that have received considerable attention are DNA methylation and histone acetylation. Human exome sequencing and genome-wide association studies have linked several neurobiological disorders to genes whose products actively regulate DNA methylation and histone acetylation. More recently, a third major epigenetic mechanism, nucleosome remodeling, has been implicated in human developmental and intellectual disability disorders. Nucleosome remodeling is driven primarily through nucleosome remodeling complexes with specialized ATP-dependent enzymes. These enzymes directly interact with DNA or chromatin structure, as well as histone subunits, to restructure the shape and organization of nucleosome positioning to ultimately regulate gene expression. Of particular interest is the neuron-specific Brg1/hBrm Associated Factor (nBAF complex. Mutations in nBAF subunit genes have so far been linked to Coffin-Siris syndrome, Nicolaides-Baraitser syndrome, schizophrenia, and Autism Spectrum Disorder. Together, these human developmental and intellectual disability disorders are powerful examples of the impact of epigenetic modulation on gene expression. This review focuses on the new and emerging role of nucleosome remodeling in neurodevelopmental and intellectual disability disorders and whether nucleosome remodeling affects gene expression required for cognition independently of its role in regulating gene expression required for development.

  3. Dynamic and selective nucleosome repositioning during endotoxin tolerance.

    Science.gov (United States)

    El Gazzar, Mohamed; Liu, Tiefu; Yoza, Barbara K; McCall, Charles E

    2010-01-08

    Sepsis is encoded by a sequel of transcription activation and repression events that initiate, sustain, and resolve severe systemic inflammation. The repression/silencing phase occurs in blood leukocytes of animals and humans following the initiation of systemic inflammation due to developing endotoxin tolerance. We previously reported that NF-kappaB transcription factor RelB and histone H3 lysine methyltransferase G9a directly interact to induce facultative heterochromatin assembly and regulate epigenetic silencing during endotoxin tolerance, which is a major feature of sepsis. The general objective of this study was to assess whether dynamic temporal, structural, and positional changes of nucleosomes influence the sepsis phenotype. We used the THP-1 sepsis cell model to isolate mononucleosomes by rapid cell permeabilization and digestion of chromatin with micrococcal nuclease and then compared tumor necrosis factor alpha (TNFalpha) proximal promoter nucleosome alignment in endotoxin-responsive and -tolerant phenotypes. We found differential and dynamic repositioning of nucleosomes from permissive to repressive locations during the activation and silencing phases of transcription reprogramming and identified the following mechanisms that may participate in the process. 1) Two proximal nucleosomes repositioned to expose the primary NF-kappaB DNA binding site in endotoxin-responsive cells, and this "promoter opening" required the ATP-independent chaperone NAP1 to replace the core histone H2A with the H2A.Z variant. 2) During RelB-dependent endotoxin tolerance, the two nucleosomes repositioned and masked the primary NF-kappaB DNA binding site. 3) Small interfering RNA-mediated inhibition of RelB expression prevented repressive nucleosome repositioning and tolerance induction, but the "open" promoter required endotoxin-induced NF-kappaB p65 promoter binding to initiate transcription, supporting the known requirement of p65 posttranslational modifications for

  4. Regulation of BAZ1A and nucleosome positioning in the nucleus accumbens in response to cocaine.

    Science.gov (United States)

    Sun, HaoSheng; Damez-Werno, Diane M; Scobie, Kimberly N; Shao, Ning-Yi; Dias, Caroline; Rabkin, Jacqui; Wright, Katherine N; Mouzon, Ezekiell; Kabbaj, Mohamed; Neve, Rachael; Turecki, Gustavo; Shen, Li; Nestler, Eric J

    2017-06-14

    Chromatin regulation, in particular ATP-dependent chromatin remodelers, have previously been shown to be important in the regulation of reward-related behaviors in animal models of mental illnesses. Here we demonstrate that BAZ1A, an accessory subunit of the ISWI family of chromatin remodeling complexes, is downregulated in the nucleus accumbens (NAc) of mice exposed repeatedly to cocaine and of cocaine-addicted humans. Viral-mediated overexpression of BAZ1A in mouse NAc reduces cocaine reward as assessed by conditioned place preference (CPP), but increases cocaine-induced locomotor activation. Furthermore, we investigate nucleosome repositioning genome-wide by conducting chromatin immunoprecipitation (ChIP)-sequencing for total H3 in NAc of control mice and after repeated cocaine administration, and find extensive nucleosome occupancy and shift changes across the genome in response to cocaine exposure. These findings implicate BAZ1A in molecular and behavioral plasticity to cocaine and offer new insight into the pathophysiology of cocaine addiction. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  5. The conformational state of the nucleosome entry–exit site modulates TATA box-specific TBP binding

    Science.gov (United States)

    Hieb, Aaron R.; Gansen, Alexander; Böhm, Vera; Langowski, Jörg

    2014-01-01

    The TATA binding protein (TBP) is a critical transcription factor used for nucleating assembly of the RNA polymerase II machinery. TBP binds TATA box elements with high affinity and kinetic stability and in vivo is correlated with high levels of transcription activation. However, since most promoters use less stable TATA-less or TATA-like elements, while also competing with nucleosome occupancy, further mechanistic insight into TBP's DNA binding properties and ability to access chromatin is needed. Using bulk and single-molecule FRET, we find that TBP binds a minimal consensus TATA box as a two-state equilibrium process, showing no evidence for intermediate states. However, upon addition of flanking DNA sequence, we observe non-specific cooperative binding to multiple DNA sites that compete for TATA-box specificity. Thus, we conclude that TBP binding is defined by a branched pathway, wherein TBP initially binds with little sequence specificity and is thermodynamically positioned by its kinetic stability to the TATA box. Furthermore, we observed the real-time access of TBP binding to TATA box DNA located within the DNA entry–exit site of the nucleosome. From these data, we determined salt-dependent changes in the nucleosome conformation regulate TBP's access to the TATA box, where access is highly constrained under physiological conditions, but is alleviated by histone acetylation and TFIIA. PMID:24829456

  6. The conformational state of the nucleosome entry-exit site modulates TATA box-specific TBP binding.

    Science.gov (United States)

    Hieb, Aaron R; Gansen, Alexander; Böhm, Vera; Langowski, Jörg

    2014-07-01

    The TATA binding protein (TBP) is a critical transcription factor used for nucleating assembly of the RNA polymerase II machinery. TBP binds TATA box elements with high affinity and kinetic stability and in vivo is correlated with high levels of transcription activation. However, since most promoters use less stable TATA-less or TATA-like elements, while also competing with nucleosome occupancy, further mechanistic insight into TBP's DNA binding properties and ability to access chromatin is needed. Using bulk and single-molecule FRET, we find that TBP binds a minimal consensus TATA box as a two-state equilibrium process, showing no evidence for intermediate states. However, upon addition of flanking DNA sequence, we observe non-specific cooperative binding to multiple DNA sites that compete for TATA-box specificity. Thus, we conclude that TBP binding is defined by a branched pathway, wherein TBP initially binds with little sequence specificity and is thermodynamically positioned by its kinetic stability to the TATA box. Furthermore, we observed the real-time access of TBP binding to TATA box DNA located within the DNA entry-exit site of the nucleosome. From these data, we determined salt-dependent changes in the nucleosome conformation regulate TBP's access to the TATA box, where access is highly constrained under physiological conditions, but is alleviated by histone acetylation and TFIIA. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  7. Consequences of cisplatin binding on nucleosome structure and dynamics.

    Science.gov (United States)

    Todd, Ryan C; Lippard, Stephen J

    2010-12-22

    The effects of cisplatin binding to DNA were explored at the nucleosome level to incorporate key features of the eukaryotic nuclear environment. An X-ray crystal structure of a site-specifically platinated nucleosome carrying a 1,3-cis-{Pt(NH₃)₂}²+-d(GpTpG) intrastrand cross-link reveals the details of how this adduct dictates the rotational positioning of DNA in the nucleosome. Results from in vitro nucleosome mobility assays indicate that a single platinum adduct interferes with ATP-independent sliding of DNA around the octamer core. Data from in vitro transcription experiments suggest that RNA polymerases can successfully navigate along cisplatin-damaged DNA templates that contain nucleosomes, but stall when the transcription elongation complex physically contacts a platinum cross-link located on the template strand. These results provide information about the effects of cisplatin binding to nuclear DNA and enhance our understanding of the mechanism of transcription inhibition by platinum anticancer compounds. Copyright © 2010 Elsevier Ltd. All rights reserved.

  8. Structural Mechanisms of Nucleosome Recognition by Linker Histones.

    Science.gov (United States)

    Zhou, Bing-Rui; Jiang, Jiansheng; Feng, Hanqiao; Ghirlando, Rodolfo; Xiao, T Sam; Bai, Yawen

    2015-08-20

    Linker histones bind to the nucleosome and regulate the structure of chromatin and gene expression. Despite more than three decades of effort, the structural basis of nucleosome recognition by linker histones remains elusive. Here, we report the crystal structure of the globular domain of chicken linker histone H5 in complex with the nucleosome at 3.5 Å resolution, which is validated using nuclear magnetic resonance spectroscopy. The globular domain sits on the dyad of the nucleosome and interacts with both DNA linkers. Our structure integrates results from mutation analyses and previous cross-linking and fluorescence recovery after photobleach experiments, and it helps resolve the long debate on structural mechanisms of nucleosome recognition by linker histones. The on-dyad binding mode of the H5 globular domain is different from the recently reported off-dyad binding mode of Drosophila linker histone H1. We demonstrate that linker histones with different binding modes could fold chromatin to form distinct higher-order structures. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Reconstitution of Nucleosomes with Differentially Isotope-labeled Sister Histones.

    Science.gov (United States)

    Liokatis, Stamatios

    2017-03-26

    Asymmetrically modified nucleosomes contain the two copies of a histone (sister histones) decorated with distinct sets of Post-translational Modifications (PTMs). They are newly identified species with unknown means of establishment and functional implications. Current analytical methods are inadequate to detect the copy-specific occurrence of PTMs on the nucleosomal sister histones. This protocol presents a biochemical method for the in vitro reconstitution of nucleosomes containing differentially isotope-labeled sister histones. The generated complex can be also asymmetrically modified, after including a premodified histone pool during refolding of histone subcomplexes. These asymmetric nucleosome preparations can be readily reacted with histone-modifying enzymes to study modification cross-talk mechanisms imposed by the asymmetrically pre-incorporated PTM using nuclear magnetic resonance (NMR) spectroscopy. Particularly, the modification reactions in real-time can be mapped independently on the two sister histones by performing different types of NMR correlation experiments, tailored for the respective isotope type. This methodology provides the means to study crosstalk mechanisms that contribute to the formation and propagation of asymmetric PTM patterns on nucleosomal complexes.

  10. Nucleosome Assembly Dynamics Involve Spontaneous Fluctuations in the Handedness of Tetrasomes

    NARCIS (Netherlands)

    Vlijm, R.; Lee, M.; Lipfert, J.; Lusser, A.; Dekker, C.; Dekker, N.H.

    2015-01-01

    DNA wrapping around histone octamers generates nucleosomes, the basic compaction unit of eukaryotic chromatin. Nucleosome stability is carefully tuned to maintain DNA accessibility in transcription, replication, and repair. Using freely orbiting magnetic tweezers, which measure the twist and length

  11. Structure of the CENP-A nucleosome and its implications for centromeric chromatin architecture.

    Science.gov (United States)

    Tachiwana, Hiroaki; Kurumizaka, Hitoshi

    2011-01-01

    Centromeres are dictated by the epigenetic inheritance of the centromeric nucleosome containing the centromere-specific histone H3 variant, CENP-A. The structure of the CENP-A nucleosome has been considered to be the fundamental architecture of the centromeric chromatin. Controversy exists in the literature regarding the CENP-A nucleosome structures, with octasome, hemisome, compact octasome, hexasome, and tetrasome models being reported. Some of these CENP-A nucleosome models may correspond to transient intermediates for the assembly of the mature CENP-A nucleosome; however, their significances are still unclear. Therefore, the structure of the mature CENP-A nucleosome has been eagerly awaited. We reconstituted the human CENP-A nucleosome with its cognate centromeric DNA fragment, and determined its crystal structure. In this review, we describe the structure and the physical properties of the CENP-A nucleosome, and discuss their implications for centromeric chromatin architecture.

  12. Nucleosome fragility reveals novel functional states of chromatin and poises genes for activation

    OpenAIRE

    Xi, Yuanxin; Yao, Jianhui; Chen, Rui; Li, Wei; He, Xiangwei

    2011-01-01

    The structural complexity of nucleosomes underlies their functional versatility. Here we report a new type of complexity—nucleosome fragility, manifested as high sensitivity to micrococcal nuclease, in contrast to the common presumption that nucleosomes are similar in resistance to MNase digestion. Using differential MNase digestion of chromatin and high-throughput sequencing, we have identified a special group of nucleosomes termed “fragile nucleosomes” throughout the yeast genome, nearly 10...

  13. The Effects of Nucleosome Positioning and Chromatin Architecture on Transgene Expression

    Science.gov (United States)

    Kempton, Colton E.

    2017-01-01

    Eukaryotes use proteins to carefully package and compact their genomes to fit into the nuclei of their individual cells. Nucleosomes are the primary level of compaction. Nucleosomes are formed when DNA wraps around an octamer of histone proteins and a nucleosome's position can limit access to genetic regulatory elements. Therefore, nucleosomes…

  14. Plasticity and epigenetic inheritance of centromere-specific histone H3 (CENP-A)-containing nucleosome positioning in the fission yeast.

    Science.gov (United States)

    Yao, Jianhui; Liu, Xingkun; Sakuno, Takeshi; Li, Wenzhu; Xi, Yuanxin; Aravamudhan, Pavithra; Joglekar, Ajit; Li, Wei; Watanabe, Yoshinori; He, Xiangwei

    2013-06-28

    Nucleosomes containing the specific histone H3 variant CENP-A mark the centromere locus on each chromatin and initiate kinetochore assembly. For the common type of regional centromeres, little is known in molecular detail of centromeric chromatin organization, its propagation through cell division, and how distinct organization patterns may facilitate kinetochore assembly. Here, we show that in the fission yeast S. pombe, a relatively small number of CENP-A/Cnp1 nucleosomes are found within the centromeric core and that their positioning relative to underlying DNA varies among genetically homogenous cells. Consistent with the flexible positioning of Cnp1 nucleosomes, a large portion of the endogenous centromere is dispensable for its essential activity in mediating chromosome segregation. We present biochemical evidence that Cnp1 occupancy directly correlates with silencing of the underlying reporter genes. Furthermore, using a newly developed pedigree analysis assay, we demonstrated the epigenetic inheritance of Cnp1 positioning and quantified the rate of occasional repositioning of Cnp1 nucleosomes throughout cell generations. Together, our results reveal the plasticity and the epigenetically inheritable nature of centromeric chromatin organization.

  15. Theoretical analysis of epigenetic cell memory by nucleosome modification

    DEFF Research Database (Denmark)

    Dodd, Ian B; Micheelsen, Mille A; Sneppen, Kim

    2007-01-01

    Chromosomal regions can adopt stable and heritable alternative states resulting in bistable gene expression without changes to the DNA sequence. Such epigenetic control is often associated with alternative covalent modifications of histones. The stability and heritability of the states are thought...... strong bistability that is resistant both to high noise due to random gain or loss of nucleosome modifications and to random partitioning upon DNA replication. However, robust bistability required: (1) cooperativity, the activity of more than one modified nucleosome, in the modification reactions and (2...

  16. The Chd1 Chromatin Remodeler Shifts Nucleosomal DNA Bidirectionally as a Monomer

    Energy Technology Data Exchange (ETDEWEB)

    Qiu, Yupeng; Levendosky, Robert F.; Chakravarthy, Srinivas; Patel, Ashok; Bowman, Gregory D.; Myong, Sua

    2017-10-01

    Chromatin remodelers catalyze dynamic packaging of the genome by carrying out nucleosome assembly/disassembly, histone exchange, and nucleosome repositioning. Remodeling results in evenly spaced nucleosomes, which requires probing both sides of the nucleosome, yet the way remodelers organize sliding activity to achieve this task is not understood. Here, we show that the monomeric Chd1 remodeler shifts DNA back and forth by dynamically alternating between different segments of the nucleosome. During sliding, Chd1 generates unstable remodeling intermediates that spontaneously relax to a pre-remodeled position. We demonstrate that nucleosome sliding is tightly controlled by two regulatory domains: the DNA-binding domain, which interferes with sliding when its range is limited by a truncated linking segment, and the chromodomains, which play a key role in substrate discrimination. We propose that active interplay of the ATPase motor with the regulatory domains may promote dynamic nucleosome structures uniquely suited for histone exchange and chromatin reorganization during transcription.

  17. Nitrated nucleosome levels and neuropsychiatric events in systemic lupus erythematosus;

    DEFF Research Database (Denmark)

    Ferreira, Isabel; Croca, Sara; Raimondo, Maria Gabriella

    2017-01-01

    BACKGROUND: In patients with systemic lupus erythematosus (SLE) there is no serological test that will reliably distinguish neuropsychiatric (NP) events due to active SLE from those due to other causes. Previously we showed that serum levels of nitrated nucleosomes (NN) were elevated in a small n...

  18. Nucleosome fragility is associated with future transcriptional response to developmental cues and stress in C. elegans.

    Science.gov (United States)

    Jeffers, Tess E; Lieb, Jason D

    2017-01-01

    Nucleosomes have structural and regulatory functions in all eukaryotic DNA-templated processes. The position of nucleosomes on DNA and the stability of the underlying histone-DNA interactions affect the access of regulatory proteins to DNA. Both stability and position are regulated through DNA sequence, histone post-translational modifications, histone variants, chromatin remodelers, and transcription factors. Here, we explored the functional implications of nucleosome properties on gene expression and development in Caenorhabditis elegans embryos. We performed a time-course of micrococcal nuclease (MNase) digestion and measured the relative sensitivity or resistance of nucleosomes throughout the genome. Fragile nucleosomes were defined by nucleosomal DNA fragments that were recovered preferentially in early MNase-digestion time points. Nucleosome fragility was strongly and positively correlated with the AT content of the underlying DNA sequence. There was no correlation between promoter nucleosome fragility and the levels of histone modifications or histone variants. Genes with fragile nucleosomes in their promoters tended to be lowly expressed and expressed in a context-specific way, operating in neuronal response, the immune system, and stress response. In addition to DNA-encoded nucleosome fragility, we also found fragile nucleosomes at locations where we expected to find destabilized nucleosomes, for example, at transcription factor binding sites where nucleosomes compete with DNA-binding factors. Our data suggest that in C. elegans promoters, nucleosome fragility is in large part DNA-encoded and that it poises genes for future context-specific activation in response to environmental stress and developmental cues. © 2017 Jeffers and Lieb; Published by Cold Spring Harbor Laboratory Press.

  19. Cryo-EM structure of the nucleosome containing the ALB1 enhancer DNA sequence

    Science.gov (United States)

    Takizawa, Yoshimasa; Tanaka, Hiroki; Machida, Shinichi; Koyama, Masako; Maehara, Kazumitsu; Wade, Paul A.; Wolf, Matthias

    2018-01-01

    Pioneer transcription factors specifically target their recognition DNA sequences within nucleosomes. FoxA is the pioneer transcription factor that binds to the ALB1 gene enhancer in liver precursor cells, and is required for liver differentiation in embryos. The ALB1 enhancer DNA sequence is reportedly incorporated into nucleosomes in cells, although the nucleosome structure containing the targeting sites for FoxA has not been clarified yet. In this study, we determined the nucleosome structure containing the ALB1 enhancer (N1) sequence, by cryogenic electron microscopy at 4.0 Å resolution. The nucleosome structure with the ALB1 enhancer DNA is not significantly different from the previously reported nucleosome structure with the Widom 601 DNA. Interestingly, in the nucleosomes, the ALB1 enhancer DNA contains local flexible regions, as compared to the Widom 601 DNA. Consistently, DNaseI treatments revealed that, in the nucleosome, the ALB1 enhancer (N1) DNA is more accessible than the Widom 601 sequence. The histones also associated less strongly with the ALB1 enhancer (N1) DNA than the Widom 601 DNA in the nucleosome. Therefore, the local histone–DNA contacts may be responsible for the enhanced DNA accessibility in the nucleosome with the ALB1 enhancer DNA. PMID:29563192

  20. An advanced coarse-grained nucleosome core particle model for computer simulations of nucleosome-nucleosome interactions under varying ionic conditions.

    Directory of Open Access Journals (Sweden)

    Yanping Fan

    Full Text Available In the eukaryotic cell nucleus, DNA exists as chromatin, a compact but dynamic complex with histone proteins. The first level of DNA organization is the linear array of nucleosome core particles (NCPs. The NCP is a well-defined complex of 147 bp DNA with an octamer of histones. Interactions between NCPs are of paramount importance for higher levels of chromatin compaction. The polyelectrolyte nature of the NCP implies that nucleosome-nucleosome interactions must exhibit a great influence from both the ionic environment as well as the positively charged and highly flexible N-terminal histone tails, protruding out from the NCP. The large size of the system precludes a modelling analysis of chromatin at an all-atom level and calls for coarse-grained approximations. Here, a model of the NCP that include the globular histone core and the flexible histone tails described by one particle per each amino acid and taking into account their net charge is proposed. DNA wrapped around the histone core was approximated at the level of two base pairs represented by one bead (bases and sugar plus four beads of charged phosphate groups. Computer simulations, using a Langevin thermostat, in a dielectric continuum with explicit monovalent (K(+, divalent (Mg(2+ or trivalent (Co(NH(3(6 (3+ cations were performed for systems with one or ten NCPs. Increase of the counterion charge results in a switch from repulsive NCP-NCP interaction in the presence of K(+, to partial aggregation with Mg(2+ and to strong mutual attraction of all 10 NCPs in the presence of CoHex(3+. The new model reproduced experimental results and the structure of the NCP-NCP contacts is in agreement with available data. Cation screening, ion-ion correlations and tail bridging contribute to the NCP-NCP attraction and the new NCP model accounts for these interactions.

  1. Linker histones: novel insights into structure-specific recognition of the nucleosome.

    Science.gov (United States)

    Cutter, Amber R; Hayes, Jeffrey J

    2017-04-01

    Linker histones (H1s) are a primary component of metazoan chromatin, fulfilling numerous functions, both in vitro and in vivo, including stabilizing the wrapping of DNA around the nucleosome, promoting folding and assembly of higher order chromatin structures, influencing nucleosome spacing on DNA, and regulating specific gene expression. However, many molecular details of how H1 binds to nucleosomes and recognizes unique structural features on the nucleosome surface remain undefined. Numerous, confounding studies are complicated not only by experimental limitations, but the use of different linker histone isoforms and nucleosome constructions. This review summarizes the decades of research that has resulted in several models of H1 association with nucleosomes, with a focus on recent advances that suggest multiple modes of H1 interaction in chromatin, while highlighting the remaining questions.

  2. Nucleosomes in serum as a marker for cell death.

    Science.gov (United States)

    Holdenrieder, S; Stieber, P; Bodenmüller, H; Fertig, G; Fürst, H; Schmeller, N; Untch, M; Seidel, D

    2001-07-01

    The concentration of nucleosomes is elevated in blood of patients with diseases which are associated with enhanced cell death. In order to detect these circulating nucleosomes, we used the Cell Death Detection-ELISAplus (CDDE) from Roche Diagnostics (Mannheim, Germany) (details at http:\\\\biochem.roche.com). For its application in liquid materials we performed various modifications: we introduced a standard curve with nucleosome-rich material, which enabled direct quantification and improved comparability of the values within (CVintraassay:3.0-4.11%) and between several runs (CVinterassay:8.6-13.5%), and tested the analytical specificity of the ELISA. Because of the fast elimination of nucleosomes from circulation and their limited stability, we compared plasma and serum matrix and investigated in detail the pre-analytical handling of serum samples which can considerably influence the test results. Careless venipuncture producing hemolysis, delayed centrifugation and bacterial contamination of the blood samples led to false-positive results; delayed stabilization with EDTA and insufficient storage conditions resulted in false-negative values. At temperatures of -20 degrees C, serum samples which were treated with 10 mM EDTA were stable for at least 6 months. In order to avoid possible interfering factors, we recommend a schedule for the pre-analytical handling of the samples. As the first stage, the possible clinical application was investigated in the sera of 310 persons. Patients with solid tumors (n=220; mean=361 Arbitrary Units (AU)) had considerably higher values than healthy persons (n=50; mean=30 AU; p=0.0001) and patients with inflammatory diseases (n=40; mean= 296 AU; p=0.096). Within the group of patients with tumors, those in advanced stages (UICC 4) showed significantly higher values than those in early stages (UICC 1-3) (p=0.0004).

  3. Cracking the chromatin code: Precise rule of nucleosome positioning

    Science.gov (United States)

    Trifonov, Edward N.

    2011-03-01

    Various aspects of packaging DNA in eukaryotic cells are outlined in physical rather than biological terms. The informational and physical nature of packaging instructions encoded in DNA sequences is discussed with the emphasis on signal processing difficulties - very low signal-to-noise ratio and high degeneracy of the nucleosome positioning signal. As the author has been contributing to the field from its very onset in 1980, the review is mostly focused at the works of the author and his colleagues. The leading concept of the overview is the role of deformational properties of DNA in the nucleosome positioning. The target of the studies is to derive the DNA bendability matrix describing where along the DNA various dinucleotide elements should be positioned, to facilitate its bending in the nucleosome. Three different approaches are described leading to derivation of the DNA deformability sequence pattern, which is a simplified linear presentation of the bendability matrix. All three approaches converge to the same unique sequence motif CGRAAATTTYCG or, in binary form, YRRRRRYYYYYR, both representing the chromatin code.

  4. The Nucleosome Assembly Activity of NAP1 Is Enhanced by Alien▿

    OpenAIRE

    Eckey, Maren; Hong, Wei; Papaioannou, Maria; Baniahmad, Aria

    2007-01-01

    The assembly of nucleosomes into chromatin is essential for the compaction of DNA and inactivation of the DNA template to modulate and repress gene expression. The nucleosome assembly protein 1, NAP1, assembles nucleosomes independent of DNA synthesis and was shown to enhance coactivator-mediated gene expression, suggesting a role for NAP1 in transcriptional regulation. Here, we show that Alien, known to harbor characteristics of a corepressor of nuclear hormone receptors such as of the vitam...

  5. The nucleosome landscape of Plasmodium falciparum reveals chromatin architecture and dynamics of regulatory sequences.

    Science.gov (United States)

    Kensche, Philip Reiner; Hoeijmakers, Wieteke Anna Maria; Toenhake, Christa Geeke; Bras, Maaike; Chappell, Lia; Berriman, Matthew; Bártfai, Richárd

    2016-03-18

    In eukaryotes, the chromatin architecture has a pivotal role in regulating all DNA-associated processes and it is central to the control of gene expression. For Plasmodium falciparum, a causative agent of human malaria, the nucleosome positioning profile of regulatory regions deserves particular attention because of their extreme AT-content. With the aid of a highly controlled MNase-seq procedure we reveal how positioning of nucleosomes provides a structural and regulatory framework to the transcriptional unit by demarcating landmark sites (transcription/translation start and end sites). In addition, our analysis provides strong indications for the function of positioned nucleosomes in splice site recognition. Transcription start sites (TSSs) are bordered by a small nucleosome-depleted region, but lack the stereotypic downstream nucleosome arrays, highlighting a key difference in chromatin organization compared to model organisms. Furthermore, we observe transcription-coupled eviction of nucleosomes on strong TSSs during intraerythrocytic development and demonstrate that nucleosome positioning and dynamics can be predictive for the functionality of regulatory DNA elements. Collectively, the strong nucleosome positioning over splice sites and surrounding putative transcription factor binding sites highlights the regulatory capacity of the nucleosome landscape in this deadly human pathogen. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  6. Stabilization of Nucleosomes by Histone Tails and by FACT Revealed by spFRET Microscopy

    Directory of Open Access Journals (Sweden)

    Maria E. Valieva

    2017-01-01

    Full Text Available A correct chromatin structure is important for cell viability and is tightly regulated by numerous factors. Human protein complex FACT (facilitates chromatin transcription is an essential factor involved in chromatin transcription and cancer development. Here FACT-dependent changes in the structure of single nucleosomes were studied with single-particle Förster resonance energy transfer (spFRET microscopy using nucleosomes labeled with a donor-acceptor pair of fluorophores, which were attached to the adjacent gyres of DNA near the contact between H2A-H2B dimers. Human FACT and its version without the C-terminal domain (CTD and the high mobility group (HMG domain of the structure-specific recognition protein 1 (SSRP1 subunit did not change the structure of the nucleosomes, while FACT without the acidic C-terminal domains of the suppressor of Ty 16 (Spt16 and the SSRP1 subunits caused nucleosome aggregation. Proteolytic removal of histone tails significantly disturbed the nucleosome structure, inducing partial unwrapping of nucleosomal DNA. Human FACT reduced DNA unwrapping and stabilized the structure of tailless nucleosomes. CTD and/or HMG domains of SSRP1 are required for this FACT activity. In contrast, previously it has been shown that yeast FACT unfolds (reorganizes nucleosomes using the CTD domain of SSRP1-like Pol I-binding protein 3 subunit (Pob3. Thus, yeast and human FACT complexes likely utilize the same domains for nucleosome reorganization and stabilization, respectively, and these processes are mechanistically similar.

  7. Removal of histone tails from nucleosome dissects the physical mechanisms of salt-induced aggregation, linker histone H1-induced compaction, and 30-nm fiber formation of the nucleosome array

    International Nuclear Information System (INIS)

    Hizume, Kohji; Nakai, Tonau; Araki, Sumiko; Prieto, Eloise; Yoshikawa, Kenichi; Takeyasu, Kunio

    2009-01-01

    In order to reveal the roles of histone tails in the formation of higher-order chromatin structures, we employed atomic force microscopy (AFM), and an in vitro reconstitution system to examine the properties of reconstituted chromatin composed of tail-less histones and a long DNA (106-kb plasmid) template. The tail-less nucleosomes did not aggregate at high salt concentrations or with an excess amount of core histones, in contrast with the behavior of nucleosomal arrays composed of nucleosomes containing normal, N-terminal tails. Analysis of our nucleosome distributions reveals that the attractive interaction between tail-less nucleosomes is weakened. Addition of linker histone H1 into the tail-less nucleosomal array failed to promote the formation of 30 nm chromatin fibers that are usually formed in the normal nucleosomal array. These results demonstrate that the attractive interaction between nucleosomes via histone tails plays a critical role in the formation of the uniform 30-nm chromatin fiber.

  8. Lysine methyltransferase G9a is not required for DNMT3A/3B anchoring to methylated nucleosomes and maintenance of DNA methylation in somatic cells

    Directory of Open Access Journals (Sweden)

    Sharma Shikhar

    2012-01-01

    Full Text Available Abstract Background DNA methylation, histone modifications and nucleosome occupancy act in concert for regulation of gene expression patterns in mammalian cells. Recently, G9a, a H3K9 methyltransferase, has been shown to play a role in establishment of DNA methylation at embryonic gene targets in ES cells through recruitment of de novo DNMT3A/3B enzymes. However, whether G9a plays a similar role in maintenance of DNA methylation in somatic cells is still unclear. Results Here we show that G9a is not essential for maintenance of DNA methylation in somatic cells. Knockdown of G9a has no measurable effect on DNA methylation levels at G9a-target loci. DNMT3A/3B remain stably anchored to nucleosomes containing methylated DNA even in the absence of G9a, ensuring faithful propagation of methylated states in cooperation with DNMT1 through somatic divisions. Moreover, G9a also associates with nucleosomes in a DNMT3A/3B and DNA methylation-independent manner. However, G9a knockdown synergizes with pharmacologic inhibition of DNMTs resulting in increased hypomethylation and inhibition of cell proliferation. Conclusions Taken together, these data suggest that G9a is not involved in maintenance of DNA methylation in somatic cells but might play a role in re-initiation of de novo methylation after treatment with hypomethylating drugs, thus serving as a potential target for combinatorial treatments strategies involving DNMTs inhibitors.

  9. The Effects of Nucleosome Positioning and Chromatin Architecture on Transgene Expression

    Science.gov (United States)

    Kempton, Colton E.

    Eukaryotes use proteins to carefully package and compact their genomes to fit into the nuclei of their individual cells. Nucleosomes are the primary level of compaction. Nucleosomes are formed when DNA wraps around an octamer of histone proteins and a nucleosome's position can limit access to genetic regulatory elements. Therefore, nucleosomes represent a basic level of gene regulation. DNA and its associated proteins, called chromatin, is usually classified as euchromatin or heterochromatin. Euchromatin is transcriptionally active with loosely packed nucleosomes while heterochromatin is condensed with tightly packed nucleosomes and is transcriptionally silent. In order to become active, heterochromatin must first be remodeled. We have studied the effects of nucleosome positioning on transgene expression in vivo using Caenorhabditis elegans as a model. We show that both location and polarity of the DNA sequence can influence transgene expression. We also discuss some considerations for working with CRISPR/Cas9. A major reason for doing in vitro nucleosome reconstitutions is to determine the effects of DNA sequence on nucleosome formation and position. It has previously been implied that nucleosome reconstitutions are stochastic and not very reproducible. We show that nucleosome reconstitutions are highly reproducible under our reaction conditions. Our results also indicate that a minimum depth of 35X sequencing coverage be maintained for maximal gains in Pearson's correlation coefficients. Communicating science with others is an important skill for any researcher. The rising generation of scientists need mentors who can teach them how to be independent thinkers who can carry out scientific experiments and communicate their finding to others. With this goal in mind, we have devised a scaffolding pedagogical method to help transform undergraduates into confident independent thinkers and researchers.

  10. Genome-wide nucleosome specificity and function of chromatin remodellers in ES cells

    Science.gov (United States)

    de Dieuleveult, Maud; Yen, Kuangyu; Hmitou, Isabelle; Depaux, Arnaud; Boussouar, Fayçal; Dargham, Daria Bou; Jounier, Sylvie; Humbertclaude, Hélène; Ribierre, Florence; Baulard, Céline; Farrell, Nina P.; Park, Bongsoo; Keime, Céline; Carrière, Lucie; Berlivet, Soizick; Gut, Marta; Gut, Ivo; Werner, Michel; Deleuze, Jean-François; Olaso, Robert; Aude, Jean-Christophe; Chantalat, Sophie; Pugh, B. Franklin; Gérard, Matthieu

    2015-01-01

    Summary ATP-dependent chromatin remodellers allow access to DNA for transcription factors and the general transcription machinery, but whether mammalian chromatin remodellers1–3 target specific nucleosomes to regulate transcription is unclear. Here, we present genome-wide remodeller-nucleosome interaction profiles for Chd1, Chd2, Chd4, Chd6, Chd8, Chd9, Brg1 and Ep400 in mouse embryonic stem (ES) cells. These remodellers bind one or both full nucleosomes that flank MNase-defined nucleosome-free promoter regions (NFRs), where they separate divergent transcription. Surprisingly, large CpG-rich NFRs that extend downstream of annotated transcriptional start sites (TSSs) are nevertheless chromatinized with non-nucleosomal or subnucleosomal histone variants (H3.3 and H2A.Z) and modifications (H3K4me3 and H3K27ac). RNA polymerase (pol) II therefore navigates hundreds of bp of altered chromatin in the sense direction before encountering an MNase-resistant nucleosome at the 3′ end of the NFR. Transcriptome analysis upon remodeller depletion reveals reciprocal mechanisms of transcriptional regulation by remodellers. Whereas at active genes individual remodellers play either positive or negative roles via altering nucleosome stability, at polycomb-enriched bivalent genes the same remodellers act in an opposite manner. These findings indicate that remodellers target specific nucleosomes at the edge of NFRs, where they regulate ES cell transcriptional programs. PMID:26814966

  11. Multivalent Interactions by the Set8 Histone Methyltransferase With Its Nucleosome Substrate.

    Science.gov (United States)

    Girish, Taverekere S; McGinty, Robert K; Tan, Song

    2016-04-24

    Set8 is the only mammalian monomethyltransferase responsible for H4K20me1, a methyl mark critical for genomic integrity of eukaryotic cells. We present here a structural model for how Set8 uses multivalent interactions to bind and methylate the nucleosome based on crystallographic and solution studies of the Set8/nucleosome complex. Our studies indicate that Set8 employs its i-SET and c-SET domains to engage nucleosomal DNA 1 to 1.5 turns from the nucleosomal dyad and in doing so, it positions the SET domain for catalysis with H4 Lys20. Surprisingly, we find that a basic N-terminal extension to the SET domain plays an even more prominent role in nucleosome binding, possibly by making an arginine anchor interaction with the nucleosome H2A/H2B acidic patch. We further show that proliferating cell nuclear antigen and the nucleosome compete for binding to Set8 through this basic extension, suggesting a mechanism for how nucleosome binding protects Set8 from proliferating cell nuclear antigen-dependent degradation during the cell cycle. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. The nucleosome assembly activity of NAP1 is enhanced by Alien.

    Science.gov (United States)

    Eckey, Maren; Hong, Wei; Papaioannou, Maria; Baniahmad, Aria

    2007-05-01

    The assembly of nucleosomes into chromatin is essential for the compaction of DNA and inactivation of the DNA template to modulate and repress gene expression. The nucleosome assembly protein 1, NAP1, assembles nucleosomes independent of DNA synthesis and was shown to enhance coactivator-mediated gene expression, suggesting a role for NAP1 in transcriptional regulation. Here, we show that Alien, known to harbor characteristics of a corepressor of nuclear hormone receptors such as of the vitamin D receptor (VDR), binds in vivo and in vitro to NAP1 and modulates its activity by enhancing NAP1-mediated nucleosome assembly on DNA. Furthermore, Alien reduces the accessibility of the histones H3 and H4 for NAP1-promoted assembly reaction. This indicates that Alien sustains and reinforces the formation of nucleosomes. Employing deletion mutants of Alien suggests that different regions of Alien are involved in enhancement of NAP1-mediated nucleosome assembly and in inhibiting the accessibility of the histones H3 and H4. In addition, we provide evidence that Alien is associated with chromatin and with micrococcus nuclease-prepared nucleosome fractions and interacts with the histones H3 and H4. Furthermore, chromatin immunoprecipitation and reimmunoprecipitation experiments suggest that NAP1 and Alien localize to the endogenous CYP24 promoter in vivo, a VDR target gene. Based on these findings, we present here a novel pathway linking corepressor function with nucleosome assembly activity.

  13. Deposition of nucleosomal antigens (histones and DNA) in the epidermal basement membrane in human lupus nephritis.

    NARCIS (Netherlands)

    Grootscholten, C.; Bruggen, M.C.J. van; Pijl, J.W. van der; Jong, E.M.G.J. de; Ligtenberg, G.; Derksen, R.H.W.M.; Berden, J.H.M.

    2003-01-01

    OBJECTIVE: Antinuclear autoantibodies complexed to nucleosomes can bind to heparan sulfate (HS) in the glomerular basement membrane. This binding is due to the binding of the positively charged histones to the strongly anionic HS. Nucleosomes and histones have been identified in glomerular deposits

  14. Nucleosomes and histones are present in glomerular deposits in human lupus nephritis

    NARCIS (Netherlands)

    vanBruggen, MCJ; Kramers, C; Walgreen, B; Elema, JD; Kallenberg, CGM; vandenBorn, J; Smeenk, RJT; Assmann, KJM; Muller, S; Monestier, M; Berden, JHM

    Background. Recently we showed that antinuclear autoantibodies complexed to nucleosomes can bind to heparan sulphate (HS) in the glomerular basement membrane (GEM) via the histone part of the nucleosome. Histones have been identified in glomerular deposits in human and murine lupus nephritis. In

  15. PARP-1 Interaction with and Activation by Histones and Nucleosomes.

    Science.gov (United States)

    Thomas, Colin; Kotova, Elena; Tulin, Alexei V

    2017-01-01

    Poly(ADP-ribose) Polymerase 1 (PARP-1) is an abundant chromatin associated protein, typical for most eukaryotic nuclei. The localization of PARP-1 in chromatin and its enzymatic activation involves multiple interactions of PARP-1 with nucleosomal histones, other proteins, and DNA. We report a set of methods designed to reconstitute PARP-1 regulation in vitro. These methods involve the expression of PARP-1 and PARP-1-regulating proteins using bacterial and eukaryotic systems, purification of these proteins using chromatography, testing of individual interactions in vitro, assembly of active complexes, and reconstitution of PARP-1 regulating reactions in vitro.

  16. Occupational Clusters.

    Science.gov (United States)

    Pottawattamie County School System, Council Bluffs, IA.

    The 15 occupational clusters (transportation, fine arts and humanities, communications and media, personal service occupations, construction, hospitality and recreation, health occupations, marine science occupations, consumer and homemaking-related occupations, agribusiness and natural resources, environment, public service, business and office…

  17. In silico evidence for sequence-dependent nucleosome sliding

    Energy Technology Data Exchange (ETDEWEB)

    Lequieu, Joshua; Schwartz, David C.; de Pablo, Juan J.

    2017-10-18

    Nucleosomes represent the basic building block of chromatin and provide an important mechanism by which cellular processes are controlled. The locations of nucleosomes across the genome are not random but instead depend on both the underlying DNA sequence and the dynamic action of other proteins within the nucleus. These processes are central to cellular function, and the molecular details of the interplay between DNA sequence and nudeosome dynamics remain poorly understood. In this work, we investigate this interplay in detail by relying on a molecular model, which permits development of a comprehensive picture of the underlying free energy surfaces and the corresponding dynamics of nudeosome repositioning. The mechanism of nudeosome repositioning is shown to be strongly linked to DNA sequence and directly related to the binding energy of a given DNA sequence to the histone core. It is also demonstrated that chromatin remodelers can override DNA-sequence preferences by exerting torque, and the histone H4 tail is then identified as a key component by which DNA-sequence, histone modifications, and chromatin remodelers could in fact be coupled.

  18. Nucleosome structure of the yeast CHA1 promoter

    DEFF Research Database (Denmark)

    Moreira, José Manuel Alfonso; Holmberg, S

    1998-01-01

    The Saccharomyces cerevisiae CHA1 gene encodes the catabolic L-serine (L-threonine) dehydratase. We have previously shown that the transcriptional activator protein Cha4p mediates serine/threonine induction of CHA1 expression. We used accessibility to micrococcal nuclease and DNase I to determine...... the in vivo chromatin structure of the CHA1 chromosomal locus, both in the non-induced state and upon induction. Upon activation, a precisely positioned nucleosome (nuc-1) occluding the TATA box and the transcription start site is removed. A strain devoid of Cha4p showed no chromatin alteration under inducing......, in a sir4 deletion strain, repression of CHA1 is partly lost and activator-independent remodeling of nuc-1 is observed. We propose a model for CHA1 activation based on promoter remodeling through interactions of Cha4p with chromatin components other than basal factors and associated proteins....

  19. Generation of Native Chromatin Immunoprecipitation Sequencing Libraries for Nucleosome Density Analysis.

    Science.gov (United States)

    Lorzadeh, Alireza; Lopez Gutierrez, Rodrigo; Jackson, Linda; Moksa, Michelle; Hirst, Martin

    2017-12-12

    We present a modified native chromatin immunoprecipitation sequencing (ChIP-seq) experimental protocol compatible with a Gaussian mixture distribution based analysis methodology (nucleosome density ChIP-seq; ndChIP-seq) that enables the generation of combined measurements of micrococcal nuclease (MNase) accessibility with histone modification genome-wide. Nucleosome position and local density, and the posttranslational modification of their histone subunits, act in concert to regulate local transcription states. Combinatorial measurements of nucleosome accessibility with histone modification generated by ndChIP-seq allows for the simultaneous interrogation of these features. The ndChIP-seq methodology is applicable to small numbers of primary cells inaccessible to cross-linking based ChIP-seq protocols. Taken together, ndChIP-seq enables the measurement of histone modification in combination with local nucleosome density to obtain new insights into shared mechanisms that regulate RNA transcription within rare primary cell populations.

  20. Altered nucleosomes of active nucleolar chromatin contain accessible histone H3 in its hyperacetylated forms

    International Nuclear Information System (INIS)

    Johnson, E.M.; Sterner, R.; Allfrey, V.G.

    1987-01-01

    Chromatin of the organism Physarum polycephalum contains a class of conformationally altered nucleosomes previously localized to the transcribing regions of ribosomal genes in nucleoli. When nuclei are treated with 2-iodo[2-tritium]acetate, the histone H3 sulfhydryl group of the altered nucleosomes is derivatized while that of folded nucleosomes is not, and the labeled histones can then be identified by autoradiography of gels that separate H3 isoforms. The H3 derivatized is predominantly of tri- and tetraacetylated forms. In contrast, total free histone reacted with iodoacetate shows no preferential labeling of isoforms. Selective reaction of acetylated H3 is prevalent in both nucleolar and non-nucleolar chromatin. The results link specific patterns of H3 acetylation to changes in nucleosome conformation that occur during transcription

  1. Understanding the connection between epigenetic DNA methylation and nucleosome positioning from computer simulations.

    Directory of Open Access Journals (Sweden)

    Guillem Portella

    Full Text Available Cytosine methylation is one of the most important epigenetic marks that regulate the process of gene expression. Here, we have examined the effect of epigenetic DNA methylation on nucleosomal stability using molecular dynamics simulations and elastic deformation models. We found that methylation of CpG steps destabilizes nucleosomes, especially when these are placed in sites where the DNA minor groove faces the histone core. The larger stiffness of methylated CpG steps is a crucial factor behind the decrease in nucleosome stability. Methylation changes the positioning and phasing of the nucleosomal DNA, altering the accessibility of DNA to regulatory proteins, and accordingly gene functionality. Our theoretical calculations highlight a simple physical-based explanation on the foundations of epigenetic signaling.

  2. Soft skills turned into hard facts: nucleosome remodelling at developmental switches.

    Science.gov (United States)

    Chioda, M; Becker, P B

    2010-07-01

    Nucleosome remodelling factors are regulators of DNA accessibility in chromatin and lubricators of all major functions of eukaryotic genomes. Their action is transient and reversible, yet can be decisive for irreversible cell-fate decisions during development. In addition to the well-known local actions of nucleosome remodelling factors during transcription initiation, more global and fundamental roles for remodelling complexes in shaping the epigenome during development are emerging.

  3. Herpes simplex virus 1 DNA is in unstable nucleosomes throughout the lytic infection cycle, and the instability of the nucleosomes is independent of DNA replication.

    Science.gov (United States)

    Lacasse, Jonathan J; Schang, Luis M

    2012-10-01

    Herpes simplex virus 1 (HSV-1) DNA is chromatinized during latency and consequently regularly digested by micrococcal nuclease (MCN) to nucleosome-size fragments. In contrast, MCN digests HSV-1 DNA in lytically infected cells to mostly heterogeneous sizes. Yet HSV-1 DNA coimmunoprecipitates with histones during lytic infections. We have shown that at 5 h postinfection, most nuclear HSV-1 DNA is in particularly unstable nucleoprotein complexes and consequently is more accessible to MCN than DNA in cellular chromatin. HSV-1 DNA was quantitatively recovered at this time in complexes with the biophysical properties of mono- to polynucleosomes following a modified MCN digestion developed to detect potential unstable intermediates. We proposed that most HSV-1 DNA is in unstable nucleosome-like complexes during lytic infections. Physiologically, nucleosome assembly typically associates with DNA replication, although DNA replication transiently disrupts nucleosomes. It therefore remained unclear whether the instability of the HSV-1 nucleoprotein complexes was related to the ongoing viral DNA replication. Here we tested whether HSV-1 DNA is in unstable nucleosome-like complexes before, during, or after the peak of viral DNA replication or when HSV-1 DNA replication is inhibited. HSV-1 DNA was quantitatively recovered in complexes fractionating as mono- to polynucleosomes from nuclei harvested at 2, 5, 7, or 9 h after infection, even if viral DNA replication was inhibited. Therefore, most HSV-1 DNA is in unstable nucleosome-like complexes throughout the lytic replication cycle, and the instability of these complexes is surprisingly independent of HSV-1 DNA replication. The specific accessibility of nuclear HSV-1 DNA, however, varied at different times after infection.

  4. Inducible nucleosome depletion at OREBP-binding-sites by hypertonic stress.

    Directory of Open Access Journals (Sweden)

    Edith H Y Tong

    Full Text Available BACKGROUND: Osmotic Response Element-Binding Protein (OREBP, also known as TonEBP or NFAT5, is a unique transcription factor. It is hitherto the only known mammalian transcription factor that regulates hypertonic stress-induced gene transcription. In addition, unlike other monomeric members of the NFAT family, OREBP exists as a homodimer and it is the only transcription factor known to bind naked DNA targets by complete encirclement in vitro. Nevertheless, how OREBP interacts with target DNA, also known as ORE/TonE, and how it elicits gene transcription in vivo, remains unknown. METHODOLOGY: Using hypertonic induction of the aldose reductase (AR gene activation as a model, we showed that OREs contained dynamic nucleosomes. Hypertonic stress induced a rapid and reversible loss of nucleosome(s around the OREs. The loss of nucleosome(s was found to be initiated by an OREBP-independent mechanism, but was significantly potentiated in the presence of OREBP. Furthermore, hypertonic induction of AR gene was associated with an OREBP-dependent hyperacetylation of histones that spanned the 5' upstream sequences and at least some exons of the gene. Nevertheless, nucleosome loss was not regulated by the acetylation status of histone. SIGNIFICANCE: Our findings offer novel insights into the mechanism of OREBP-dependent transcriptional regulation and provide a basis for understanding how histone eviction and transcription factor recruitment are coupled.

  5. Chromatin regulatory mechanisms of gene expression at mononucleosomal level: nucleosome occupancy and epigenetic modifications

    OpenAIRE

    Riffo Campos, Angela Leticia

    2015-01-01

    La cromatina es una compleja estructura compuesta por DNA, RNA y proteínas, que permite compactar el genoma en las células eucariotas. Siendo el cromosoma el nivel más alto de compactación y el nucleosoma la subunidad fundamental de la misma. El nucleosoma está compuesto por un octámero de histonas, siendo H2A, H2B, H3 y H4 las canónicas. Este octámero se encuentra envuelto por 147 pb de DNA doble cadena. Entre los nucleosomas se encuentra una zona de DNA flanqueante y la histona H1 (o H5 en a...

  6. Arabidopsis Chromatin Assembly Factor 1 is required for occupancy and position of a subset of nucleosomes

    Czech Academy of Sciences Publication Activity Database

    Munoz-Viana, R.; Wildhaber, T.; Trejo-Arellano, M.S.; Mozgová, Iva; Hennig, L.

    2017-01-01

    Roč. 92, č. 3 (2017), s. 363-374 ISSN 0960-7412 Institutional support: RVO:61388971 Keywords : Arabidopsis thaliana * chromatin * CAF-1 Subject RIV: EE - Microbiology, Virology OBOR OECD: Microbiology Impact factor: 5.901, year: 2016

  7. Nucleosome structure incorporated histone acetylation site prediction in Arabidopsis thaliana.

    Science.gov (United States)

    Zhao, Chen; Liu, Hui; Li, Jiang; Deng, Youping; Shi, Tieliu

    2010-11-02

    Acetylation is a crucial post-translational modification for histones, and plays a key role in gene expression regulation. Due to limited data and lack of a clear acetylation consensus sequence, a few researches have focused on prediction of lysine acetylation sites. Several systematic prediction studies have been conducted for human and yeast, but less for Arabidopsis thaliana. Concerning the insufficient observation on acetylation site, we analyzed contributions of the peptide-alignment-based distance definition and 3D structure factors in acetylation prediction. We found that traditional structure contributes little to acetylation site prediction. Identified acetylation sites of histones in Arabidopsis thaliana are conserved and cross predictable with that of human by peptide based methods. However, the predicted specificity is overestimated, because of the existence of non-observed acetylable site. Here, by performing a complete exploration on the factors that affect the acetylability of lysines in histones, we focused on the relative position of lysine at nucleosome level, and defined a new structure feature to promote the performance in predicting the acetylability of all the histone lysines in A. thaliana. We found a new spacial correlated acetylation factor, and defined a ε-N spacial location based feature, which contains five core spacial ellipsoid wired areas. By incorporating the new feature, the performance of predicting the acetylability of all the histone lysines in A. Thaliana was promoted, in which the previous mispredicted acetylable lysines were corrected by comparing to the peptide-based prediction.

  8. Structure of centromere chromatin: from nucleosome to chromosomal architecture.

    Science.gov (United States)

    Schalch, Thomas; Steiner, Florian A

    2017-08-01

    The centromere is essential for the segregation of chromosomes, as it serves as attachment site for microtubules to mediate chromosome segregation during mitosis and meiosis. In most organisms, the centromere is restricted to one chromosomal region that appears as primary constriction on the condensed chromosome and is partitioned into two chromatin domains: The centromere core is characterized by the centromere-specific histone H3 variant CENP-A (also called cenH3) and is required for specifying the centromere and for building the kinetochore complex during mitosis. This core region is generally flanked by pericentric heterochromatin, characterized by nucleosomes containing H3 methylated on lysine 9 (H3K9me) that are bound by heterochromatin proteins. During mitosis, these two domains together form a three-dimensional structure that exposes CENP-A-containing chromatin to the surface for interaction with the kinetochore and microtubules. At the same time, this structure supports the tension generated during the segregation of sister chromatids to opposite poles. In this review, we discuss recent insight into the characteristics of the centromere, from the specialized chromatin structures at the centromere core and the pericentromere to the three-dimensional organization of these regions that make up the functional centromere.

  9. Modulations of DNA Contacts by Linker Histones and Post-translational Modifications Determine the Mobility and Modifiability of Nucleosomal H3 Tails.

    Science.gov (United States)

    Stützer, Alexandra; Liokatis, Stamatios; Kiesel, Anja; Schwarzer, Dirk; Sprangers, Remco; Söding, Johannes; Selenko, Philipp; Fischle, Wolfgang

    2016-01-21

    Post-translational histone modifications and linker histone incorporation regulate chromatin structure and genome activity. How these systems interface on a molecular level is unclear. Using biochemistry and NMR spectroscopy, we deduced mechanistic insights into the modification behavior of N-terminal histone H3 tails in different nucleosomal contexts. We find that linker histones generally inhibit modifications of different H3 sites and reduce H3 tail dynamics in nucleosomes. These effects are caused by modulations of electrostatic interactions of H3 tails with linker DNA and largely depend on the C-terminal domains of linker histones. In agreement, linker histone occupancy and H3 tail modifications segregate on a genome-wide level. Charge-modulating modifications such as phosphorylation and acetylation weaken transient H3 tail-linker DNA interactions, increase H3 tail dynamics, and, concomitantly, enhance general modifiability. We propose that alterations of H3 tail-linker DNA interactions by linker histones and charge-modulating modifications execute basal control mechanisms of chromatin function. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Replication-Coupled Nucleosome Assembly and Positioning by ATP-Dependent Chromatin-Remodeling Enzymes

    Directory of Open Access Journals (Sweden)

    Tejas Yadav

    2016-04-01

    Full Text Available During DNA replication, chromatin must be disassembled and faithfully reassembled on newly synthesized genomes. The mechanisms that govern the assembly of chromatin structures following DNA replication are poorly understood. Here, we exploited Okazaki fragment synthesis and other assays to study how nucleosomes are deposited and become organized in S. cerevisiae. We observe that global nucleosome positioning is quickly established on newly synthesized DNA in vivo. Importantly, we find that ATP-dependent chromatin-remodeling enzymes, Isw1 and Chd1, collaborate with histone chaperones to remodel nucleosomes as they are loaded behind a replication fork. Using a whole-genome sequencing approach, we determine that the positioning of newly deposited nucleosomes in vivo is specified by the combined actions of ATP-dependent chromatin-remodeling enzymes and select DNA-binding proteins. Altogether, our data provide in vivo evidence for coordinated “loading and remodeling” of nucleosomes behind the replication fork, allowing for rapid organization of chromatin during S phase.

  11. Solution structure of variant H2A.Z.1 nucleosome investigated by small-angle X-ray and neutron scatterings.

    Science.gov (United States)

    Sugiyama, Masaaki; Horikoshi, Naoki; Suzuki, Yuya; Taguchi, Hiroyuki; Kujirai, Tomoya; Inoue, Rintaro; Oba, Yojiro; Sato, Nobuhiro; Martel, Anne; Porcar, Lionel; Kurumizaka, Hitoshi

    2015-12-01

    Solution structures of nucleosomes containing a human histone variant, H2A.Z.1, were measured by small-angle X-ray and neutron scatterings (SAXS and SANS). SAXS revealed that the outer shape, reflecting the DNA shape, of the H2A.Z.1 nucleosome is almost the same as that of the canonical H2A nucleosome. In contrast, SANS employing a contrast variation technique revealed that the histone octamer of the H2A.Z.1 nucleosome is smaller than that of the canonical nucleosome. The DNA within the H2A.Z.1 nucleosome was more susceptible to micrococcal nuclease than that within the canonical nucleosome. These results suggested that the DNA is loosely wrapped around the histone core in the H2A.Z.1 nucleosome.

  12. Chromatin Regulation of Estrogen-Mediated Transcription in Breast Cancer: Rules for Binding Sites in Nucleosomes and Modified Histones that Enhance ER Binding

    National Research Council Canada - National Science Library

    Chrivia, John C

    2005-01-01

    .... Using gel shift assays, we tested whether ER can bind these nucleosomes. We have also found that the non-histone chromatin protein HMOB2 enhances binding of ER to an ERE located at the center of the nucleosome...

  13. The supercoiling state of DNA determines the handedness of both H3 and CENP-A nucleosomes

    NARCIS (Netherlands)

    Vlijm, R.; Kim, S.H.; De Zwart, P. L.; Dalal, Y.; Dekker, C.

    2017-01-01

    Nucleosomes form the unit structure of the genome in eukaryotes, thereby constituting a fundamental tenet of chromatin biology. In canonical nucleosomes, DNA wraps around the histone octamer in a left-handed toroidal ramp. Here, in single-molecule magnetic tweezers studies of chaperone-assisted

  14. Physical properties of naked DNA influence nucleosome positioning and correlate with transcription start and termination sites in yeast

    Directory of Open Access Journals (Sweden)

    Soler-López Montserrat

    2011-10-01

    Full Text Available Abstract Background In eukaryotic organisms, DNA is packaged into chromatin structure, where most of DNA is wrapped into nucleosomes. DNA compaction and nucleosome positioning have clear functional implications, since they modulate the accessibility of genomic regions to regulatory proteins. Despite the intensive research effort focused in this area, the rules defining nucleosome positioning and the location of DNA regulatory regions still remain elusive. Results Naked (histone-free and nucleosomal DNA from yeast were digested by microccocal nuclease (MNase and sequenced genome-wide. MNase cutting preferences were determined for both naked and nucleosomal DNAs. Integration of their sequencing profiles with DNA conformational descriptors derived from atomistic molecular dynamic simulations enabled us to extract the physical properties of DNA on a genomic scale and to correlate them with chromatin structure and gene regulation. The local structure of DNA around regulatory regions was found to be unusually flexible and to display a unique pattern of nucleosome positioning. Ab initio physical descriptors derived from molecular dynamics were used to develop a computational method that accurately predicts nucleosome enriched and depleted regions. Conclusions Our experimental and computational analyses jointly demonstrate a clear correlation between sequence-dependent physical properties of naked DNA and regulatory signals in the chromatin structure. These results demonstrate that nucleosome positioning around TSS (Transcription Start Site and TTS (Transcription Termination Site (at least in yeast is strongly dependent on DNA physical properties, which can define a basal regulatory mechanism of gene expression.

  15. Transmission of modified nucleosomes from the mouse male germline to the zygote and subsequent remodeling of paternal chromatin.

    NARCIS (Netherlands)

    Heijden, G.W. van der; Derijck, A.H.A.; Ramos, L.; Giele, M.M.; Vlag, J. van der; Boer, P. de

    2006-01-01

    Rapidly after gamete fusion, the sperm nucleus loses its specific chromatin conformation and the DNA is repopulated with maternally derived nucleosomes. We evaluated the nature of paternally derived nucleosomes and the dynamics of sperm chromatin remodeling in the zygote directly after gamete

  16. Dual roles of p300 in chromatin assembly and transcriptional activation in cooperation with nucleosome assembly protein 1 in vitro.

    Science.gov (United States)

    Asahara, Hiroshi; Tartare-Deckert, Sophie; Nakagawa, Takeya; Ikehara, Tsuyoshi; Hirose, Fumiko; Hunter, Tony; Ito, Takashi; Montminy, Marc

    2002-05-01

    In a yeast two-hybrid screen to identify proteins that bind to the KIX domain of the coactivator p300, we obtained cDNAs encoding nucleosome assembly protein 1 (NAP-1), a 60-kDa histone H2A-H2B shuttling protein that promotes histone deposition. p300 associates preferentially with the H2A-H2B-bound form of NAP-1 rather than with the unbound form of NAP-1. Formation of NAP-1-p300 complexes was found to increase during S phase, suggesting a potential role for p300 in chromatin assembly. In micrococcal nuclease and supercoiling assays, addition of p300 promoted efficient chromatin assembly in vitro in conjunction with NAP-1 and ATP-utilizing chromatin assembly and remodeling factor; this effect was dependent in part on the intrinsic histone acetyltransferase activity of p300. Surprisingly, NAP-1 potently inhibited acetylation of core histones by p300, suggesting that efficient assembly requires acetylation of either NAP-1 or p300 itself. As p300 acted cooperatively with NAP-1 in stimulating transcription from a chromatin template in vitro, our results suggest a dual role of NAP-1-p300 complexes in promoting chromatin assembly and transcriptional activation.

  17. Probabilistic inference for nucleosome positioning with MNase-based or sonicated short-read data.

    Directory of Open Access Journals (Sweden)

    Xuekui Zhang

    Full Text Available We describe a model-based method, PING, for predicting nucleosome positions in MNase-Seq and MNase- or sonicated-ChIP-Seq data. PING compares favorably to NPS and TemplateFilter in scalability, accuracy and robustness to low read density. To demonstrate that PING predictions from widely available sonicated data can have sufficient spatial resolution to be to be useful for biological inference, we use Illumina H3K4me1 ChIP-seq data to detect changes in nucleosome positioning around transcription factor binding sites due to tamoxifen stimulation, to discriminate functional and non-functional transcription factor binding sites more effectively than with enrichment profiles, and to confirm that the pioneer transcription factor Foxa2 associates with the accessible major groove of nucleosomal DNA.

  18. Nucleosome Binding Alters the Substrate Bonding Environment of Histone H3 Lysine 36 Methyltransferase NSD2.

    Science.gov (United States)

    Poulin, Myles B; Schneck, Jessica L; Matico, Rosalie E; Hou, Wangfang; McDevitt, Patrick J; Holbert, Marc; Schramm, Vern L

    2016-06-01

    Nuclear receptor-binding SET domain protein 2 (NSD2) is a histone H3 lysine 36 (H3K36)-specific methyltransferase enzyme that is overexpressed in a number of cancers, including multiple myeloma. NSD2 binds to S-adenosyl-l-methionine (SAM) and nucleosome substrates to catalyze the transfer of a methyl group from SAM to the ε-amino group of histone H3K36. Equilibrium binding isotope effects and density functional theory calculations indicate that the SAM methyl group is sterically constrained in complex with NSD2, and that this steric constraint is released upon nucleosome binding. Together, these results show that nucleosome binding to NSD2 induces a significant change in the chemical environment of enzyme-bound SAM.

  19. New insights into nucleosome and chromatin structure: an ordered state or a disordered affair?

    Science.gov (United States)

    Luger, Karolin; Dechassa, Mekonnen L.; Tremethick, David J.

    2012-01-01

    The compaction of genomic DNA into chromatin has profound implications for the regulation of key processes such as transcription, replication and DNA repair. Nucleosomes, the repeating building blocks of chromatin, vary in the composition of their histone protein components. This is the result of the incorporation of variant histones and post-translational modifications of histone amino acid side chains. The resulting changes in nucleosome structure, stability and dynamics affect the compaction of nucleosomal arrays into higher-order structures. It is becoming clear that chromatin structures are not nearly as uniform and regular as previously assumed. This implies that chromatin structure must also be viewed in the context of specific biological functions. PMID:22722606

  20. ATP-Dependent Chromatin Remodeling Factors and Their Roles in Affecting Nucleosome Fiber Composition

    Directory of Open Access Journals (Sweden)

    Alexandra Lusser

    2011-10-01

    Full Text Available ATP-dependent chromatin remodeling factors of the SNF2 family are key components of the cellular machineries that shape and regulate chromatin structure and function. Members of this group of proteins have broad and heterogeneous functions ranging from controlling gene activity, facilitating DNA damage repair, promoting homologous recombination to maintaining genomic stability. Several chromatin remodeling factors are critical components of nucleosome assembly processes, and recent reports have identified specific functions of distinct chromatin remodeling factors in the assembly of variant histones into chromatin. In this review we will discuss the specific roles of ATP-dependent chromatin remodeling factors in determining nucleosome composition and, thus, chromatin fiber properties.

  1. Genome-wide nucleosome map and cytosine methylation levels of an ancient human genome

    DEFF Research Database (Denmark)

    Pedersen, Jakob Skou; Valen, Eivind; Velazquez, Amhed Missael Vargas

    2014-01-01

    Epigenetic information is available from contemporary organisms, but is difficult to track back in evolutionary time. Here, we show that genome-wide epigenetic information can be gathered directly from next-generation sequence reads of DNA isolated from ancient remains. Using the genome sequence...... data generated from hair shafts of a 4000-yr-old Paleo-Eskimo belonging to the Saqqaq culture, we generate the first ancient nucleosome map coupled with a genome-wide survey of cytosine methylation levels. The validity of both nucleosome map and methylation levels were confirmed by the recovery...

  2. Discussing the transformative functioning of occupation

    DEFF Research Database (Denmark)

    Josephsson, Staffan; Madsen, Jacob Østergaard; Aldrich,, Rebecca M.

    ), Narrative - in – action (Ricoeur, Bruner and Mattingly) Personal construct theory (eg Kelly, Sarbin, Little and Baumeister) Intrinsic motivation theory (e g,White, Bandura, Deci & Ryan, etc), and Developmental theory (Piaget, Erikson, Baltes, etc), Importance to occupational science: Occupation is used...

  3. Recent insights from single-molecule studies into nucleosome structure and dynamics

    NARCIS (Netherlands)

    Ordu, O.; Lusser, A; Dekker, N.H.

    2016-01-01

    Eukaryotic DNA is tightly packed into a hierarchically ordered structure called chromatin in order to fit into the micron-scaled nucleus. The basic unit of chromatin is the nucleosome, which consists of a short piece of DNA wrapped around a core of eight histone proteins. In addition to their role

  4. Nanoscale dynamics of centromere nucleosomes and the critical roles of CENP-A

    Science.gov (United States)

    Stumme-Diers, Micah P; Banerjee, Siddhartha; Hashemi, Mohtadin; Sun, Zhiqiang

    2018-01-01

    Abstract In the absence of a functioning centromere, chromosome segregation becomes aberrant, leading to an increased rate of aneuploidy. The highly specific recognition of centromeres by kinetochores suggests that specific structural characteristics define this region, however, the structural details and mechanism underlying this recognition remains a matter of intense investigation. To address this, high-speed atomic force microscopy was used for direct visualization of the spontaneous dynamics of CENP-A nucleosomes at the sub-second time scale. We report that CENP-A nucleosomes change conformation spontaneously and reversibly, utilizing two major pathways: unwrapping, and looping of the DNA; enabling core transfer between neighboring DNA substrates. Along with these nucleosome dynamics we observed that CENP-A stabilizes the histone core against dissociating to histone subunits upon unwrapping DNA, unique from H3 cores which are only capable of such plasticity in the presence of remodeling factors. These findings have implications for the dynamics and integrity of nucleosomes at the centromere. PMID:29040671

  5. Extracellular histones, cell-free DNA, or nucleosomes: differences in immunostimulation.

    Science.gov (United States)

    Marsman, Gerben; Zeerleder, Sacha; Luken, Brenda M

    2016-12-08

    In inflammation, extensive cell death may occur, which results in the release of chromatin components into the extracellular environment. Individually, the purified chromatin components double stranded (ds)DNA and histones have been demonstrated, both in vitro and in vivo, to display various immunostimulatory effects, for example, histones induce cytotoxicity and proinflammatory signaling through toll-like receptor (TLR)2 and 4, while DNA induces signaling through TLR9 and intracellular nucleic acid sensing mechanisms. However, DNA and histones are organized in nucleosomes in the nucleus, and evidence suggests that nucleosomes are released as such in inflammation. The cytotoxicity and proinflammatory signaling induced by nucleosomes have not been studied as extensively as the separate effects brought about by histones and dsDNA, and there appear to be some marked differences. Remarkably, little distinction between the different forms in which histones circulate has been made throughout literature. This is partly due to the limitations of existing techniques to differentiate between histones in their free or DNA-bound form. Here we review the current understanding of immunostimulation induced by extracellular histones, dsDNA and nucleosomes, and discuss the importance of techniques that in their detection differentiate between these different chromatin components.

  6. Extranuclear detection of histones and nucleosomes in activated human lymphoblasts as an early event in apoptosis.

    NARCIS (Netherlands)

    Gabler, C.; Blank, N.; Hieronymus, T.; Schiller, M.; Berden, J.H.M.; Kalden, J.R.; Lorenz, H.M.

    2004-01-01

    OBJECTIVE: To evaluate the presence of histones and nucleosomes in cell lysates of freshly isolated peripheral blood mononuclear cells (PBMC), fully activated lymphoblasts, or lymphoblasts after induction of apoptosis. METHODS: Each histone class (H1, H2A, H2B, H3, and H4) was detected by western

  7. Dynamic Conformations of Nucleosome Arrays in Solution from Small-Angle X-ray Scattering

    Energy Technology Data Exchange (ETDEWEB)

    Howell, Steven C. [George Washington Univ., Washington, DC (United States)

    2016-01-31

    We set out to determine quantitative information regarding the dynamic conformation of nucleosome arrays in solution using experimental SAXS. Toward this end, we developed a CG simulation algorithm for dsDNA which rapidly generates ensembles of structures through Metropolis MC sampling of a Markov chain.

  8. Staphylococcus aureus protease: a probe of exposed, non-basic histone sequences in nucleosomes

    Energy Technology Data Exchange (ETDEWEB)

    Rill, R.L.; Oosterhof, D.K.

    1980-01-01

    The digestion of histones in chicken erythrocyte nucleosome cores and chromatin by Staphylococcus aureus protease was examined. This protease cleaves specifically at acidic residues and prefers glu-X bonds under the conditions used. Only 1 of 24 glutamic and 2 of 13 aspartic acids among all four core histones are located in basic, amino-terminal tails, hence staph. protease is a highly specific probe of exposed non-basic sequences. Staph. protease readily degraded H1, H5, and H3; moderately degraded H2b, and only slightly degraded H2a and H4 in nucleosomes and nucleosome cores. Electrophoresis of core histone fragments from limited digests showed that most glutamic acids were inaccessible, but at least five sites in non-basic sequences were readily cleaved. Tentative assignments of these fragments based on comparisons with products from limited digests of pure histones suggested that most accessible sites in nucleosome cores occur in H3. The most probable sites of H3 cutting are glutamic acids at positions 51, 60, 73, 94, and 97. At least one site in H2b, probably the equivalent of glu-105 in the calf H2b sequence, was accessible. No sites in H2a and H4 appeared highly accessible. H5 was readily cleaved at a site near the amino-terminus. These data substantiate the other evidence that non-basic core histone sequences are located primarily in the nucleosome interior, but that H3 binds to the ends of core DNA and thereby is partly exposed as the upper and lower surfaces of the disk-shaped core.

  9. Occupational Licensing

    OpenAIRE

    Morris M. Kleiner

    2000-01-01

    The study of the regulation of occupations has a long and distinguished tradition in economics. In this paper, I present the central arguments and unresolved issues involving the costs and benefits of occupational licensing. The main benefits that are suggested for occupational licensing involve improving quality for those persons receiving the service. In contrast, the costs attributed to this labor market institution are that it restricts the supply of labor to the occupation and thereby dr...

  10. Occupational Dermatosis

    OpenAIRE

    Solak, Yavuzalp; Yoldaşcan, Elçin; Akbaba, Muhsin; Kurt, Burak

    2018-01-01

    Dermatosesthat occur as a result of primary irritation or sensitization are generallyreferred to as "occupational dermatosis", depending on work done by aperson, vehicle they are using and their workplace or work environment.Skin’s occupational diseases are most frequently reported occupational diseasesafter trauma. It constitutes ~ 50% of all occupational diseases. It isresponsible for ~ 25% of work loss. It is very important because it is bothfrequent and vulnerable. In addition, ...

  11. Occupational mortality

    DEFF Research Database (Denmark)

    Lynge, Elsebeth

    2011-01-01

    INTRODUCTION: This paper aims to present the methods and main results from the Danish occupational mortality studies, and to set the Danish studies into the international context of occupational mortality studies. RESEARCH TOPICS: The first Danish occupational mortality study from 1970...

  12. Intrinsic contractures of the hand.

    Science.gov (United States)

    Paksima, Nader; Besh, Basil R

    2012-02-01

    Contractures of the intrinsic muscles of the fingers disrupt the delicate and complex balance of intrinsic and extrinsic muscles, which allows the hand to be so versatile and functional. The loss of muscle function primarily affects the interphalangeal joints but also may affect etacarpophalangeal joints. The resulting clinical picture is often termed, intrinsic contracture or intrinsic-plus hand. Disruption of the balance between intrinsic and extrinsic muscles has many causes and may be secondary to changes within the intrinsic musculature or the tendon unit. This article reviews diagnosis, etiology, and treatment algorithms in the management of intrinsic contractures of the fingers. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. Predicting Intrinsic Motivation

    Science.gov (United States)

    Martens, Rob; Kirschner, Paul A.

    2004-01-01

    Intrinsic motivation can be predicted from participants' perceptions of the social environment and the task environment (Ryan & Deci, 2000)in terms of control, relatedness and competence. To determine the degree of independence of these factors 251 students in higher vocational education (physiotherapy and hotel management) indicated the…

  14. Occupational Consciousness.

    Science.gov (United States)

    Ramugondo, Elelwani L

    2015-10-02

    Occupational consciousness refers to ongoing awareness of the dynamics of hegemony and recognition that dominant practices are sustained through what people do every day, with implications for personal and collective health. The emergence of the construct in post-apartheid South Africa signifies the country's ongoing struggle with negotiating long-standing dynamics of power that were laid down during colonialism, and maintained under black majority rule. Consciousness, a key component of the new terminology, is framed from post-colonial perspectives - notably work by Biko and Fanon - and grounded in the philosophy of liberation, in order to draw attention to continuing unequal intersubjective relations that play out through human occupation. The paper also draws important links between occupational consciousness and other related constructs, namely occupational possibilities, occupational choice, occupational apartheid, and collective occupation. The use of the term 'consciousness' in sociology, with related or different meanings, is also explored. Occupational consciousness is then advanced as a critical notion that frames everyday doing as a potentially liberating response to oppressive social structures. This paper advances theorizing as a scholarly practice in occupational science, and could potentially expand inter or transdisciplinary work for critical conceptualizations of human occupation.

  15. Occupational Consciousness

    Science.gov (United States)

    Ramugondo, Elelwani L.

    2015-01-01

    Occupational consciousness refers to ongoing awareness of the dynamics of hegemony and recognition that dominant practices are sustained through what people do every day, with implications for personal and collective health. The emergence of the construct in post-apartheid South Africa signifies the country’s ongoing struggle with negotiating long-standing dynamics of power that were laid down during colonialism, and maintained under black majority rule. Consciousness, a key component of the new terminology, is framed from post-colonial perspectives – notably work by Biko and Fanon – and grounded in the philosophy of liberation, in order to draw attention to continuing unequal intersubjective relations that play out through human occupation. The paper also draws important links between occupational consciousness and other related constructs, namely occupational possibilities, occupational choice, occupational apartheid, and collective occupation. The use of the term ‘consciousness’ in sociology, with related or different meanings, is also explored. Occupational consciousness is then advanced as a critical notion that frames everyday doing as a potentially liberating response to oppressive social structures. This paper advances theorizing as a scholarly practice in occupational science, and could potentially expand inter or transdisciplinary work for critical conceptualizations of human occupation. PMID:26549984

  16. Structure and Dynamics of a 197 bp Nucleosome in Complex with Linker Histone H1.

    Science.gov (United States)

    Bednar, Jan; Garcia-Saez, Isabel; Boopathi, Ramachandran; Cutter, Amber R; Papai, Gabor; Reymer, Anna; Syed, Sajad H; Lone, Imtiaz Nisar; Tonchev, Ognyan; Crucifix, Corinne; Menoni, Hervé; Papin, Christophe; Skoufias, Dimitrios A; Kurumizaka, Hitoshi; Lavery, Richard; Hamiche, Ali; Hayes, Jeffrey J; Schultz, Patrick; Angelov, Dimitar; Petosa, Carlo; Dimitrov, Stefan

    2017-05-04

    Linker histones associate with nucleosomes to promote the formation of higher-order chromatin structure, but the underlying molecular details are unclear. We investigated the structure of a 197 bp nucleosome bearing symmetric 25 bp linker DNA arms in complex with vertebrate linker histone H1. We determined electron cryo-microscopy (cryo-EM) and crystal structures of unbound and H1-bound nucleosomes and validated these structures by site-directed protein cross-linking and hydroxyl radical footprinting experiments. Histone H1 shifts the conformational landscape of the nucleosome by drawing the two linkers together and reducing their flexibility. The H1 C-terminal domain (CTD) localizes primarily to a single linker, while the H1 globular domain contacts the nucleosome dyad and both linkers, associating more closely with the CTD-distal linker. These findings reveal that H1 imparts a strong degree of asymmetry to the nucleosome, which is likely to influence the assembly and architecture of higher-order structures. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. The H1 linker histones: multifunctional proteins beyond the nucleosomal core particle.

    Science.gov (United States)

    Hergeth, Sonja P; Schneider, Robert

    2015-11-01

    The linker histone H1 family members are a key component of chromatin and bind to the nucleosomal core particle around the DNA entry and exit sites. H1 can stabilize both nucleosome structure and higher-order chromatin architecture. In general, H1 molecules consist of a central globular domain with more flexible tail regions at both their N- and C-terminal ends. The existence of multiple H1 subtypes and a large variety of posttranslational modifications brings about a considerable degree of complexity and makes studying this protein family challenging. Here, we review recent progress in understanding the function of linker histones and their subtypes beyond their role as merely structural chromatin components. We summarize current findings on the role of H1 in heterochromatin formation, transcriptional regulation and embryogenesis with a focus on H1 subtypes and their specific modifications. © 2015 The Authors.

  18. Intrinsic and Extrinsic Motivation

    OpenAIRE

    Roland Bénabou; Jean Tirole

    2003-01-01

    A central tenet of economics is that individuals respond to incentives. For psychologists and sociologists, in contrast, rewards and punishments are often counterproductive, because they undermine "intrinsic motivation". We reconcile these two views, showing how performance incentives offered by an informed principal (manager, teacher, parent) can adversely impact an agent's (worker, child) perception of the task, or of his own abilities. Incentives are then only weak reinforcers in the short...

  19. Target model of nucleosome particle for track structure calculations and DNA damage modeling

    Czech Academy of Sciences Publication Activity Database

    Michalik, Věslav; Běgusová, Marie

    1994-01-01

    Roč. 66, č. 3 (1994), s. 267-277 ISSN 0955-3002 R&D Projects: GA ČR(CZ) GA204/93/2451; GA AV ČR(CZ) IA135102; GA AV ČR(CZ) IA50405 Keywords : DNA nucleosome * ionizing radiation * theoretical modeling Subject RIV: AQ - Safety, Health Protection, Human - Machine Impact factor: 2.761, year: 1994

  20. Nucleosome–nucleosome interactions via histone tails and linker DNA regulate nuclear rigidity

    Science.gov (United States)

    Shimamoto, Yuta; Tamura, Sachiko; Masumoto, Hiroshi; Maeshima, Kazuhiro

    2017-01-01

    Cells, as well as the nuclei inside them, experience significant mechanical stress in diverse biological processes, including contraction, migration, and adhesion. The structural stability of nuclei must therefore be maintained in order to protect genome integrity. Despite extensive knowledge on nuclear architecture and components, however, the underlying physical and molecular mechanisms remain largely unknown. We address this by subjecting isolated human cell nuclei to microneedle-based quantitative micromanipulation with a series of biochemical perturbations of the chromatin. We find that the mechanical rigidity of nuclei depends on the continuity of the nucleosomal fiber and interactions between nucleosomes. Disrupting these chromatin features by varying cation concentration, acetylating histone tails, or digesting linker DNA results in loss of nuclear rigidity. In contrast, the levels of key chromatin assembly factors, including cohesin, condensin II, and CTCF, and a major nuclear envelope protein, lamin, are unaffected. Together with in situ evidence using living cells and a simple mechanical model, our findings reveal a chromatin-based regulation of the nuclear mechanical response and provide insight into the significance of local and global chromatin structures, such as those associated with interdigitated or melted nucleosomal fibers. PMID:28428255

  1. Two distinct promoter architectures centered on dynamic nucleosomes control ribosomal protein gene transcription.

    Science.gov (United States)

    Knight, Britta; Kubik, Slawomir; Ghosh, Bhaswar; Bruzzone, Maria Jessica; Geertz, Marcel; Martin, Victoria; Dénervaud, Nicolas; Jacquet, Philippe; Ozkan, Burak; Rougemont, Jacques; Maerkl, Sebastian J; Naef, Félix; Shore, David

    2014-08-01

    In yeast, ribosome production is controlled transcriptionally by tight coregulation of the 138 ribosomal protein genes (RPGs). RPG promoters display limited sequence homology, and the molecular basis for their coregulation remains largely unknown. Here we identify two prevalent RPG promoter types, both characterized by upstream binding of the general transcription factor (TF) Rap1 followed by the RPG-specific Fhl1/Ifh1 pair, with one type also binding the HMG-B protein Hmo1. We show that the regulatory properties of the two promoter types are remarkably similar, suggesting that they are determined to a large extent by Rap1 and the Fhl1/Ifh1 pair. Rapid depletion experiments allowed us to define a hierarchy of TF binding in which Rap1 acts as a pioneer factor required for binding of all other TFs. We also uncovered unexpected features underlying recruitment of Fhl1, whose forkhead DNA-binding domain is not required for binding at most promoters, and Hmo1, whose binding is supported by repeated motifs. Finally, we describe unusually micrococcal nuclease (MNase)-sensitive nucleosomes at all RPG promoters, located between the canonical +1 and -1 nucleosomes, which coincide with sites of Fhl1/Ifh1 and Hmo1 binding. We speculate that these "fragile" nucleosomes play an important role in regulating RPG transcriptional output. © 2014 Knight et al.; Published by Cold Spring Harbor Laboratory Press.

  2. Regulation of biosynthesis and intracellular localization of rice and tobacco homologues of nucleosome assembly protein 1.

    Science.gov (United States)

    Dong, Aiwu; Zhu, Yan; Yu, Yu; Cao, Kaiming; Sun, Chongrong; Shen, Wen-Hui

    2003-02-01

    The nucleosome assembly protein 1 (NAP1) is considered to be a conserved histone chaperone, facilitating the assembly of nucleosomes in all eukaryotes. However, studies in yeast and animal cells also indicated that NAP1 proteins have diverse functions likely independent of nucleosome-assembly activity. Here, we describe the isolation and characterization of cDNAs encoding NAP1-like proteins from the monocotyledon rice ( Oryza sativa L.) and the dicotyledon tobacco ( Nicotiana tabacum L.). Northern-blot analysis demonstrated that the two rice NAP1-like genes are predominantly expressed in stem tissues such as root and shoot apical meristems as well as in young flowers. During the cell cycle, all four tobacco NAP1-like genes are highly expressed, with one of them showing a slightly increased expression at the G1/S transition. These results are consistent with a role for plant NAP1-like proteins in cell division. In vitro binding assays revealed that different NAP1-like proteins bind, with distinct relative binding strengths, to different classes of histone. Intracellular localization analyses showed that some NAP1-like proteins could be targeted into the nucleus whereas others are exclusively cytoplasm-localized. It is thus likely that different plant NAP1-like proteins have distinct functions in vivo. Plant NAP1-like proteins were observed to concentrate around the metaphase plate and in the phragmoplast, suggesting a role in mitotic events and cytokinesis.

  3. Nucleosomes containing methylated DNA stabilize DNA methyltransferases 3A/3B and ensure faithful epigenetic inheritance.

    Directory of Open Access Journals (Sweden)

    Shikhar Sharma

    2011-02-01

    Full Text Available How epigenetic information is propagated during somatic cell divisions is still unclear but is absolutely critical for preserving gene expression patterns and cellular identity. Here we show an unanticipated mechanism for inheritance of DNA methylation patterns where the epigenetic mark not only recruits the catalyzing enzyme but also regulates the protein level, i.e. the enzymatic product (5-methylcytosine determines the level of the methylase, thus forming a novel homeostatic inheritance system. Nucleosomes containing methylated DNA stabilize de novo DNA methyltransferases, DNMT3A/3B, allowing little free DNMT3A/3B enzymes to exist in the nucleus. Stabilization of DNMT3A/3B on nucleosomes in methylated regions further promotes propagation of DNA methylation. However, reduction of cellular DNA methylation levels creating more potential CpG substrates counter-intuitively results in a dramatic decrease of DNMT3A/3B proteins due to diminished nucleosome binding and subsequent degradation of the unstable free proteins. These data show an unexpected self-regulatory inheritance mechanism that not only ensures somatic propagation of methylated states by DNMT1 and DNMT3A/3B enzymes but also prevents aberrant de novo methylation by causing degradation of free DNMT3A/3B enzymes.

  4. Nucleosome Density ChIP-Seq Identifies Distinct Chromatin Modification Signatures Associated with MNase Accessibility.

    Science.gov (United States)

    Lorzadeh, Alireza; Bilenky, Misha; Hammond, Colin; Knapp, David J H F; Li, Luolan; Miller, Paul H; Carles, Annaick; Heravi-Moussavi, Alireza; Gakkhar, Sitanshu; Moksa, Michelle; Eaves, Connie J; Hirst, Martin

    2016-11-15

    Nucleosome position, density, and post-translational modification are widely accepted components of mechanisms regulating DNA transcription but still incompletely understood. We present a modified native ChIP-seq method combined with an analytical framework that allows MNase accessibility to be integrated with histone modification profiles. Application of this methodology to the primitive (CD34+) subset of normal human cord blood cells enabled genomic regions enriched in one versus two nucleosomes marked by histone 3 lysine 4 trimethylation (H3K4me3) and/or histone 3 lysine 27 trimethylation (H3K27me3) to be associated with their transcriptional and DNA methylation states. From this analysis, we defined four classes of promoter-specific profiles and demonstrated that a majority of bivalent marked promoters are heterogeneously marked at a single-cell level in this primitive cell type. Interestingly, extension of this approach to human embryonic stem cells revealed an altered relationship between chromatin modification state and nucleosome content at promoters, suggesting developmental stage-specific organization of histone methylation states. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  5. Intrinsic and extrinsic mortality reunited

    DEFF Research Database (Denmark)

    Koopman, Jacob J E; Wensink, Maarten J; Rozing, Maarten P

    2015-01-01

    Intrinsic and extrinsic mortality are often separated in order to understand and measure aging. Intrinsic mortality is assumed to be a result of aging and to increase over age, whereas extrinsic mortality is assumed to be a result of environmental hazards and be constant over age. However......, allegedly intrinsic and extrinsic mortality have an exponentially increasing age pattern in common. Theories of aging assert that a combination of intrinsic and extrinsic stressors underlies the increasing risk of death. Epidemiological and biological data support that the control of intrinsic as well...... as extrinsic stressors can alleviate the aging process. We argue that aging and death can be better explained by the interaction of intrinsic and extrinsic stressors than by classifying mortality itself as being either intrinsic or extrinsic. Recognition of the tight interaction between intrinsic and extrinsic...

  6. Occupational Rhinitis.

    Science.gov (United States)

    Grammer, Leslie C

    2016-05-01

    Occupational rhinitis (OR) involves nasal congestion, rhinorrhea, nasal itching, and/or sneezing resulting from workplace exposures. OR can have a significant negative effect on quality of life and productivity. OR can be divided into allergic or nonallergic subgroups based on the underlying pathogenesis. Certain occupational exposures place employees at greater risk for developing disease. Primary treatment is avoidance of implicated exposures. Antihistamines, saline rinses, and nasal steroids may be useful. OR can coexist with occupational asthma, and rhinitis symptoms have been reported to precede those of the lower respiratory tract. OR is has both medical and socioeconomic implications. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Genome-wide chromatin mapping with size resolution reveals a dynamic sub-nucleosomal landscape in Arabidopsis.

    Science.gov (United States)

    Pass, Daniel Antony; Sornay, Emily; Marchbank, Angela; Crawford, Margaret R; Paszkiewicz, Konrad; Kent, Nicholas A; Murray, James A H

    2017-09-01

    All eukaryotic genomes are packaged as chromatin, with DNA interlaced with both regularly patterned nucleosomes and sub-nucleosomal-sized protein structures such as mobile and labile transcription factors (TF) and initiation complexes, together forming a dynamic chromatin landscape. Whilst details of nucleosome position in Arabidopsis have been previously analysed, there is less understanding of their relationship to more dynamic sub-nucleosomal particles (subNSPs) defined as protected regions shorter than the ~150bp typical of nucleosomes. The genome-wide profile of these subNSPs has not been previously analysed in plants and this study investigates the relationship of dynamic bound particles with transcriptional control. Here we combine differential micrococcal nuclease (MNase) digestion and a modified paired-end sequencing protocol to reveal the chromatin structure landscape of Arabidopsis cells across a wide particle size range. Linking this data to RNAseq expression analysis provides detailed insight into the relationship of identified DNA-bound particles with transcriptional activity. The use of differential digestion reveals sensitive positions, including a labile -1 nucleosome positioned upstream of the transcription start site (TSS) of active genes. We investigated the response of the chromatin landscape to changes in environmental conditions using light and dark growth, given the large transcriptional changes resulting from this simple alteration. The resulting shifts in the suites of expressed and repressed genes show little correspondence to changes in nucleosome positioning, but led to significant alterations in the profile of subNSPs upstream of TSS both globally and locally. We examined previously mapped positions for the TFs PIF3, PIF4 and CCA1, which regulate light responses, and found that changes in subNSPs co-localized with these binding sites. This small particle structure is detected only under low levels of MNase digestion and is lost on more

  8. Hinge and chromoshadow of HP1α participate in recognition of K9 methylated histone H3 in nucleosomes.

    Science.gov (United States)

    Mishima, Yuichi; Watanabe, Makoto; Kawakami, Toru; Jayasinghe, Chanika D; Otani, Junji; Kikugawa, Yusuke; Shirakawa, Masahiro; Kimura, Hiroshi; Nishimura, Osamu; Aimoto, Saburo; Tajima, Shoji; Suetake, Isao

    2013-01-09

    The majority of the genome in eukaryotes is packaged into transcriptionally inactive chromatin. Heterochromatin protein 1 (HP1) is a major player in the establishment and maintenance of heterochromatin. HP1 specifically recognizes a methylated lysine residue at position 9 in histone H3 through its N-terminal chromo domain (CD). To elucidate the binding properties of HP1α to nucleosomes in vitro, we reconstituted nucleosomes containing histone H3 trimethylated at lysine 9. HP1α exhibited high-affinity binding to nucleosomes containing methylated histone H3 in a nucleosome core-number-dependent manner. The hinge region (HR) connecting the CD and C-terminal chromoshadow domain (CSD), and the CSD contributed to the selective binding of HP1α to histone H3 with trimethylated lysine 9 through weak DNA binding and by suppressing the DNA binding, respectively. We propose that not only the specific recognition of lysine 9 methylation of histone H3 by the CD but also the HR and the CSD cooperatively contribute to the selective binding of HP1α to histone H3 lysine 9 methylated nucleosomes. Copyright © 2012 Elsevier Ltd. All rights reserved.

  9. Periodic Distribution of a Putative Nucleosome Positioning Motif in Human, Nonhuman Primates, and Archaea: Mutual Information Analysis

    Science.gov (United States)

    Sosa, Daniela; Miramontes, Pedro; Li, Wentian; Mireles, Víctor; Bobadilla, Juan R.; José, Marco V.

    2013-01-01

    Recently, Trifonov's group proposed a 10-mer DNA motif YYYYYRRRRR as a solution of the long-standing problem of sequence-based nucleosome positioning. To test whether this generic decamer represents a biological meaningful signal, we compare the distribution of this motif in primates and Archaea, which are known to contain nucleosomes, and in Eubacteria, which do not possess nucleosomes. The distribution of the motif is analyzed by the mutual information function (MIF) with a shifted version of itself (MIF profile). We found common features in the patterns of this generic decamer on MIF profiles among primate species, and interestingly we found conspicuous but dissimilar MIF profiles for each Archaea tested. The overall MIF profiles for each chromosome in each primate species also follow a similar pattern. Trifonov's generic decamer may be a highly conserved motif for the nucleosome positioning, but we argue that this is not the only motif. The distribution of this generic decamer exhibits previously unidentified periodicities, which are associated to highly repetitive sequences in the genome. Alu repetitive elements contribute to the most fundamental structure of nucleosome positioning in higher Eukaryotes. In some regions of primate chromosomes, the distribution of the decamer shows symmetrical patterns including inverted repeats. PMID:23841049

  10. Occupational Asthma

    Science.gov (United States)

    ... the enzymes of the bacteria Bacillus subtilis, while bakers may develop an allergy and occupational asthma symptoms ... counts Continuing education center Find an allergist / immunologist Journals Login / My membership Search your symptoms Shop the ...

  11. Occupational Health

    Science.gov (United States)

    Occupational health problems occur at work or because of the kind of work you do. These problems can include ... by exposure to radiation Exposure to germs in health care settings Good job safety and prevention practices ...

  12. Occupational health

    CERN Document Server

    Fingret, Dr Ann

    2013-01-01

    Offers a comprehensive view of health and safety issues at work. An invaluable resource for managers, personnel professionals and occupational health practitioners. Recommended by the Institute of Personnel Management.

  13. Chromatin associated mechanisms in base excision repair - nucleosome remodeling and DNA transcription, two key players.

    Science.gov (United States)

    Menoni, Hervé; Di Mascio, Paolo; Cadet, Jean; Dimitrov, Stefan; Angelov, Dimitar

    2017-06-01

    Genomic DNA is prone to a large number of insults by a myriad of endogenous and exogenous agents. The base excision repair (BER) is the major mechanism used by cells for the removal of various DNA lesions spontaneously or environmentally induced and the maintenance of genome integrity. The presence of persistent DNA damage is not compatible with life, since abrogation of BER leads to early embryonic lethality in mice. There are several lines of evidences showing existence of a link between deficient BER, cancer proneness and ageing, thus illustrating the importance of this DNA repair pathway in human health. Although the enzymology of BER mechanisms has been largely elucidated using chemically defined DNA damage substrates and purified proteins, the complex interplay of BER with another vital process like transcription or when DNA is in its natural state (i.e. wrapped in nucleosome and assembled in chromatin fiber is largely unexplored. Cells use chromatin remodeling factors to overcome the general repression associated with the nucleosomal organization. It is broadly accepted that energy-dependent nucleosome remodeling factors disrupt histones-DNA interactions at the expense of ATP hydrolysis to favor transcription as well as DNA repair. Importantly, unlike transcription, BER is not part of a regulated developmental process but represents a maintenance system that should be efficient anytime and anywhere in the genome. In this review we will discuss how BER can deal with chromatin organization to maintain genetic information. Emphasis will be placed on the following challenging question: how BER is initiated within chromatin? Copyright © 2017 Elsevier Inc. All rights reserved.

  14. PING 2.0: an R/Bioconductor package for nucleosome positioning using next-generation sequencing data.

    Science.gov (United States)

    Woo, Sangsoon; Zhang, Xuekui; Sauteraud, Renan; Robert, François; Gottardo, Raphael

    2013-08-15

    MNase-Seq and ChIP-Seq have evolved as popular techniques to study chromatin and histone modification. Although many tools have been developed to identify enriched regions, software tools for nucleosome positioning are still limited. We introduce a flexible and powerful open-source R package, PING 2.0, for nucleosome positioning using MNase-Seq data or MNase- or sonicated- ChIP-Seq data combined with either single-end or paired-end sequencing. PING uses a model-based approach, which enables nucleosome predictions even in the presence of low read counts. We illustrate PING using two paired-end datasets from Saccharomyces cerevisiae and compare its performance with nucleR and ChIPseqR. PING 2.0 is available from the Bioconductor website at http://bioconductor.org. It can run on Linux, Mac and Windows.

  15. Intrinsic Chevrolets at the SSC

    International Nuclear Information System (INIS)

    Brodsky, S.J.; Collins, J.C.; Ellis, S.D.; Gunion, J.F.; Mueller, A.H.

    1984-01-01

    The possibility of the production at high energy of heavy quarks, supersymmetric particles and other large mass colored systems via the intrinsic twist-six components in the proton wave function is discussed. While the existing data do not rule out the possible relevance of intrinsic charm production at present energies, the extrapolation of such intrinsic contributions to very high masses and energies suggests that they will not play an important role at the SSC

  16. Analysis of the histone protein tail and DNA in nucleosome using molecular dynamics simulation

    Science.gov (United States)

    Fujimori, R.; Komatsu, Y.; Fukuda, M.; Miyakawa, T.; Morikawa, R.; Takasu, M.

    2013-02-01

    We study the effect of the tails of H3 and H4 histones in the nucleosomes, where DNA and histones are packed in the form of chromatin. We perform molecular dynamics simulations of the complex of DNA and histones and calculate the mean square displacement and the gyration radius of the complex of DNA and histones for the cases with tails intact and the cases with tails missing. Our results show that the H3 tails are important for the motion of the histones. We also find that the motion of one tail is affected by other tails, although the tails are distanced apart, suggesting the correlated motion in biological systems.

  17. Regulation of Nucleosome Stacking and Chromatin Compaction by the Histone H4 N-Terminal Tail-H2A Acidic Patch Interaction.

    Science.gov (United States)

    Chen, Qinming; Yang, Renliang; Korolev, Nikolay; Liu, Chuan Fa; Nordenskiöld, Lars

    2017-06-30

    Chromatin folding and dynamics are critically dependent on nucleosome-nucleosome interactions with important contributions from internucleosome binding of the histone H4 N-terminal tail K16-R23 domain to the surface of the H2A/H2B dimer. The H4 Lys16 plays a pivotal role in this regard. Using in vitro reconstituted 12-mer nucleosome arrays, we have investigated the mechanism of the H4 N-terminal tail in maintaining nucleosome-nucleosome stacking and mediating intra- and inter-array chromatin compaction, with emphasis on the role of K16 and the positive charge region, R17-R23. Analytical ultracentrifugation sedimentation velocity experiments and precipitation assays were employed to analyze effects on chromatin folding and self-association, respectively. Effects on chromatin folding caused by various mutations and modifications at position K16 in the H4 histone were studied. Additionally, using charge-quenching mutations, we characterized the importance of the interaction of the residues within the H4 positive charge region R17-R23 with the H2A acidic patch of the adjacent nucleosome. Furthermore, crosslinking experiments were conducted to establish the proximity of the basic tail region to the acidic patch. Our data indicate that the positive charge and length of the side chain of H4 K16 are important for its access to the adjacent nucleosome in the process of nucleosome-nucleosome stacking and array folding. The location and orientation of the H4 R17-R23 domain on the H2A/H2B dimer surface of the neighboring nucleosome core particle (NCP) in the compacted chromatin fiber were established. The dominance of electrostatic interactions in maintaining intra-array interaction was demonstrated. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Intrinsically dynamic population models

    Directory of Open Access Journals (Sweden)

    Robert Schoen

    2005-03-01

    Full Text Available Intrinsically dynamic models (IDMs depict populations whose cumulative growth rate over a number of intervals equals the product of the long term growth rates (that is the dominant roots or dominant eigenvalues associated with each of those intervals. Here the focus is on the birth trajectory produced by a sequence of population projection (Leslie matrices. The elements of a Leslie matrix are represented as straightforward functions of the roots of the matrix, and new relationships are presented linking the roots of a matrix to its Net Reproduction Rate and stable mean age of childbearing. Incorporating mortality changes in the rates of reproduction yields an IDM when the subordinate roots are held constant over time. In IDMs, the birth trajectory generated by any specified sequence of Leslie matrices can be found analytically. In the Leslie model with 15 year age groups, the constant subordinate root assumption leads to reasonable changes in the age pattern of fertility, and equations (27 and (30 provide the population size and structure that result from changing levels of net reproduction. IDMs generalize the fixed rate stable population model. They can characterize any observed population, and can provide new insights into dynamic demographic behavior, including the momentum associated with gradual or irregular paths to zero growth.

  19. Occupational Change: What Makes Changers Different?

    Science.gov (United States)

    Kanchier, Carole; Unruh, Wally R.

    1989-01-01

    This study investigated whether occupational changers differed from nonchangers with respect to (1) personal and demographic variables; (2) experience of the life cycle transition periods; and (3) work values, job satisfaction, and organizational commitment. Changers preferred intrinsic rewards, saw their jobs as vehicles for growth, took risks,…

  20. ATP-independent cooperative binding of yeast Isw1a to bare and nucleosomal DNA.

    Directory of Open Access Journals (Sweden)

    Anne De Cian

    Full Text Available Among chromatin remodeling factors, the ISWI family displays a nucleosome-enhanced ATPase activity coupled to DNA translocation. While these enzymes are known to bind to DNA, their activity has not been fully characterized. Here we use TEM imaging and single molecule manipulation to investigate the interaction between DNA and yeast Isw1a. We show that Isw1a displays a highly cooperative ATP-independent binding to and bridging between DNA segments. Under appropriate tension, rare single nucleation events can sometimes be observed and loop DNA with a regular step. These nucleation events are often followed by binding of successive complexes bridging between nearby DNA segments in a zipper-like fashion, as confirmed by TEM observations. On nucleosomal substrates, we show that the specific ATP-dependent remodeling activity occurs in the context of cooperative Isw1a complexes bridging extranucleosomal DNA. Our results are interpreted in the context of the recently published partial structure of Isw1a and support its acting as a "protein ruler" (with possibly more than one tick.

  1. The Cac2 subunit is essential for productive histone binding and nucleosome assembly in CAF-1

    Energy Technology Data Exchange (ETDEWEB)

    Mattiroli, Francesca; Gu, Yajie; Balsbaugh, Jeremy L.; Ahn, Natalie G.; Luger, Karolin

    2017-04-18

    Nucleosome assembly following DNA replication controls epigenome maintenance and genome integrity. Chromatin assembly factor 1 (CAF-1) is the histone chaperone responsible for histone (H3-H4)2 deposition following DNA synthesis. Structural and functional details for this chaperone complex and its interaction with histones are slowly emerging. Using hydrogen-deuterium exchange coupled to mass spectrometry, combined with in vitro and in vivo mutagenesis studies, we identified the regions involved in the direct interaction between the yeast CAF-1 subunits, and mapped the CAF-1 domains responsible for H3-H4 binding. The large subunit, Cac1 organizes the assembly of CAF-1. Strikingly, H3-H4 binding is mediated by a composite interface, shaped by Cac1-bound Cac2 and the Cac1 acidic region. Cac2 is indispensable for productive histone binding, while deletion of Cac3 has only moderate effects on H3-H4 binding and nucleosome assembly. These results define direct structural roles for yeast CAF-1 subunits and uncover a previously unknown critical function of the middle subunit in CAF-1.

  2. Arginine-phosphate salt bridges between histones and DNA: Intermolecular actuators that control nucleosome architecture

    Science.gov (United States)

    Yusufaly, Tahir I.; Li, Yun; Singh, Gautam; Olson, Wilma K.

    2014-10-01

    Structural bioinformatics and van der Waals density functional theory are combined to investigate the mechanochemical impact of a major class of histone-DNA interactions, namely, the formation of salt bridges between arginine residues in histones and phosphate groups on the DNA backbone. Principal component analysis reveals that the configurational fluctuations of the sugar-phosphate backbone display sequence-specific directionality and variability, and clustering of nucleosome crystal structures identifies two major salt-bridge configurations: a monodentate form in which the arginine end-group guanidinium only forms one hydrogen bond with the phosphate, and a bidentate form in which it forms two. Density functional theory calculations highlight that the combination of sequence, denticity, and salt-bridge positioning enables the histones to apply a tunable mechanochemical stress to the DNA via precise and specific activation of backbone deformations. The results suggest that selection for specific placements of van der Waals contacts, with high-precision control of the spatial distribution of intermolecular forces, may serve as an underlying evolutionary design principle for the structure and function of nucleosomes, a conjecture that is corroborated by previous experimental studies.

  3. FACT, the Bur kinase pathway, and the histone co-repressor HirC have overlapping nucleosome-related roles in yeast transcription elongation.

    Directory of Open Access Journals (Sweden)

    Jennifer R Stevens

    Full Text Available Gene transcription is constrained by the nucleosomal nature of chromosomal DNA. This nucleosomal barrier is modulated by FACT, a conserved histone-binding heterodimer. FACT mediates transcription-linked nucleosome disassembly and also nucleosome reassembly in the wake of the RNA polymerase II transcription complex, and in this way maintains the repression of 'cryptic' promoters found within some genes. Here we focus on a novel mutant version of the yeast FACT subunit Spt16 that supplies essential Spt16 activities but impairs transcription-linked nucleosome reassembly in dominant fashion. This Spt16 mutant protein also has genetic effects that are recessive, which we used to show that certain Spt16 activities collaborate with histone acetylation and the activities of a Bur-kinase/Spt4-Spt5/Paf1C pathway that facilitate transcription elongation. These collaborating activities were opposed by the actions of Rpd3S, a histone deacetylase that restores a repressive chromatin environment in a transcription-linked manner. Spt16 activity paralleling that of HirC, a co-repressor of histone gene expression, was also found to be opposed by Rpd3S. Our findings suggest that Spt16, the Bur/Spt4-Spt5/Paf1C pathway, and normal histone abundance and/or stoichiometry, in mutually cooperative fashion, facilitate nucleosome disassembly during transcription elongation. The recessive nature of these effects of the mutant Spt16 protein on transcription-linked nucleosome disassembly, contrasted to its dominant negative effect on transcription-linked nucleosome reassembly, indicate that mutant FACT harbouring the mutant Spt16 protein competes poorly with normal FACT at the stage of transcription-linked nucleosome disassembly, but effectively with normal FACT for transcription-linked nucleosome reassembly. This functional difference is consistent with the idea that FACT association with the transcription elongation complex depends on nucleosome disassembly, and that the

  4. Nitrated nucleosome levels and neuropsychiatric events in systemic lupus erythematosus; a multi-center retrospective case-control study

    DEFF Research Database (Denmark)

    Ferreira, Isabel; Croca, Sara; Raimondo, Maria Gabriella

    2017-01-01

    BACKGROUND: In patients with systemic lupus erythematosus (SLE) there is no serological test that will reliably distinguish neuropsychiatric (NP) events due to active SLE from those due to other causes. Previously we showed that serum levels of nitrated nucleosomes (NN) were elevated in a small n...

  5. Vaccination with L. infantum chagasi nucleosomal histones confers protection against new world cutaneous leishmaniasis caused by Leishmania braziliensis.

    Science.gov (United States)

    Carneiro, Marcia W; Santos, Diego M; Fukutani, Kiyoshi F; Clarencio, Jorge; Miranda, Jose Carlos; Brodskyn, Claudia; Barral, Aldina; Barral-Netto, Manoel; Soto, Manuel; de Oliveira, Camila I

    2012-01-01

    Nucleosomal histones are intracellular proteins that are highly conserved among Leishmania species. After parasite destruction or spontaneous lysis, exposure to these proteins elicits a strong host immune response. In the present study, we analyzed the protective capability of Leishmania infantum chagasi nucleosomal histones against L. braziliensis infection using different immunization strategies. BALB/c mice were immunized with either a plasmid DNA cocktail (DNA) containing four Leishmania nucleosomal histones or with the DNA cocktail followed by the corresponding recombinant proteins plus CpG (DNA/Protein). Mice were later challenged with L. braziliensis, in the presence of sand fly saliva. Lesion development, parasite load and the cellular immune response were analyzed five weeks after challenge. Immunization with either DNA alone or with DNA/Protein was able to inhibit lesion development. This finding was highlighted by the absence of infected macrophages in tissue sections. Further, parasite load at the infection site and in the draining lymph nodes was also significantly lower in vaccinated animals. This outcome was associated with increased expression of IFN-γ and down regulation of IL-4 at the infection site. The data presented here demonstrate the potential use of L. infantum chagasi nucleosomal histones as targets for the development of vaccines against infection with L. braziliensis, as shown by the significant inhibition of disease development following a live challenge.

  6. The incorporation of the novel histone variant H2AL2 confers unusual structural and functional properties of the nucleosome

    Czech Academy of Sciences Publication Activity Database

    Syed, S.H.; Boulard, M.; Shukla, M.S.; Gautier, T.; Travers, A.; Bednár, Jan; Faivre-Moskalenko, C.; Dimitrov, S.; Angelov, D.

    2009-01-01

    Roč. 37, č. 14 (2009), s. 4684-4695 ISSN 0305-1048 Grant - others:GA MŠk(CZ) LC535; GA ČR(CZ) GA304/05/2168 Program:LC Institutional research plan: CEZ:AV0Z50110509 Keywords : nucleosome * histone * variant Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 7.479, year: 2009

  7. Probing Enhanced Double-Strand Break Formation at Abasic Sites within Clustered Lesions in Nucleosome Core Particles.

    Science.gov (United States)

    Banerjee, Samya; Chakraborty, Supratim; Jacinto, Marco Paolo; Paul, Michael D; Balster, Morgan V; Greenberg, Marc M

    2017-01-10

    DNA is rapidly cleaved under mild alkaline conditions at apyrimidinic/apurinic sites, but the half-life is several weeks in phosphate buffer (pH 7.5). However, abasic sites are ∼100-fold more reactive within nucleosome core particles (NCPs). Histone proteins catalyze the strand scission, and at superhelical location 1.5, the histone H4 tail is largely responsible for the accelerated cleavage. The rate constant for strand scission at an abasic site is enhanced further in a nucleosome core particle when it is part of a bistranded lesion containing a proximal strand break. Cleavage of this form results in a highly deleterious double-strand break. This acceleration is dependent upon the position of the abasic lesion in the NCP and its structure. The enhancement in cleavage rate at an apurinic/apyrimidinic site rapidly drops off as the distance between the strand break and abasic site increases and is negligible once the two forms of damage are separated by 7 bp. However, the enhancement of the rate of double-strand break formation increases when the size of the gap is increased from one to two nucleotides. In contrast, the cleavage rate enhancement at 2-deoxyribonolactone within bistranded lesions is more modest, and it is similar in free DNA and nucleosome core particles. We postulate that the enhanced rate of double-strand break formation at bistranded lesions containing apurinic/apyrimidinic sites within nucleosome core particles is a general phenomenon and is due to increased DNA flexibility.

  8. A D53 repression motif induces oligomerization of TOPLESS corepressors and promotes assembly of a corepressor-nucleosome complex.

    Science.gov (United States)

    Ma, Honglei; Duan, Jingbo; Ke, Jiyuan; He, Yuanzheng; Gu, Xin; Xu, Ting-Hai; Yu, Hong; Wang, Yonghong; Brunzelle, Joseph S; Jiang, Yi; Rothbart, Scott B; Xu, H Eric; Li, Jiayang; Melcher, Karsten

    2017-06-01

    TOPLESS are tetrameric plant corepressors of the conserved Tup1/Groucho/TLE (transducin-like enhancer of split) family. We show that they interact through their TOPLESS domains (TPDs) with two functionally important ethylene response factor-associated amphiphilic repression (EAR) motifs of the rice strigolactone signaling repressor D53: the universally conserved EAR-3 and the monocot-specific EAR-2. We present the crystal structure of the monocot-specific EAR-2 peptide in complex with the TOPLESS-related protein 2 (TPR2) TPD, in which the EAR-2 motif binds the same TPD groove as jasmonate and auxin signaling repressors but makes additional contacts with a second TPD site to mediate TPD tetramer-tetramer interaction. We validated the functional relevance of the two TPD binding sites in reporter gene assays and in transgenic rice and demonstrate that EAR-2 binding induces TPD oligomerization. Moreover, we demonstrate that the TPD directly binds nucleosomes and the tails of histones H3 and H4. Higher-order assembly of TPD complexes induced by EAR-2 binding markedly stabilizes the nucleosome-TPD interaction. These results establish a new TPD-repressor binding mode that promotes TPD oligomerization and TPD-nucleosome interaction, thus illustrating the initial assembly of a repressor-corepressor-nucleosome complex.

  9. Occupational rhinitis affects occupational asthma severity.

    Science.gov (United States)

    Moscato, Gianna; Pala, Gianni; Folletti, Ilenia; Siracusa, Andrea; Quirce, Santiago

    2016-06-16

    The strong interactions between asthma and rhinitis, and the influence of rhinitis in the severity and/or control of asthma, have clearly been demonstrated. Nevertheless, no specific study has been conducted in the occupational setting. The aim of the study was to assess the severity of occupational asthma and rhinitis and evaluate whether rhinitis is a predictor for increased asthma severity. We retrospectively reviewed the clinical charts of 72 patients who received a diagnosis of allergic occupational asthma, with or without associated occupational rhinitis. Our findings suggested that persistent asthma tended to be more common in subjects with associated occupational asthma and rhinitis, and occupational asthma severity was associated with occupational rhinitis severity. Moderate-severe persistent occupational rhinitis is a risk factor for persistent occupational asthma. We demonstrated, for the first time in the occupational setting, a significant association between occupational rhinitis and asthma severity.

  10. A cassette of basic amino acids in histone H2B regulates nucleosome dynamics and access to DNA damage.

    Science.gov (United States)

    Rodriguez, Yesenia; Duan, Mingrui; Wyrick, John J; Smerdon, Michael J

    2018-03-27

    Nucleosome dynamics, such as spontaneous DNA unwrapping, are postulated to have a critical role in regulating the access of DNA repair machinery to DNA lesions within nucleosomes. However, the specific histone domains that regulate nucleosome dynamics and their impact on DNA repair are not well understood. Previous studies have identified the histone H2B repression (or HBR) domain, a highly conserved, basic region in the N-terminal tail of histone H2B, which significantly influences gene expression, chromatin assembly, and DNA damage and repair. However, knowledge about the molecular mechanism(s) that may account for these observations is limited. Here, we characterized the stability and dynamics of ΔHBR mutant nucleosome core particles (NCPs) in vitro by restriction-enzyme accessibility, FRET, and temperature-induced sliding of histone octamers. Our results indicate that ΔHBR NCPs are more dynamic and the steady-state fraction of the ΔHBR NCP population occupying the unwrapped state is larger than that of WT NCPs. Moreover, ΔHBR-histone octamers are more susceptible to temperature-induced sliding on DNA than WT histone octamers. Notably, the activity of base-excision repair (BER) enzymes at uracil lesions and single-nucleotide gaps is enhanced in a site-specific manner in ΔHBR NCPs and correlates well with increased DNA unwrapping in these damaged regions. Finally, removal of the HBR domain is insufficient for completely alleviating the structural constraints imposed by histone octamers on the activity of BER enzymes. In summary, our findings indicate that the conserved HBR domain of histone H2B regulates the accessibility of repair factors to DNA lesions in nucleosomes. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

  11. Intrinsically Passive Handling and Grasping

    NARCIS (Netherlands)

    Stramigioli, Stefano; Scherpen, Jacquelien M.A.; Khodabandehloo, Koorosh

    2000-01-01

    The paper presents a control philosophy called Intrinsically Passive Control, which has the feature to properly behave during interaction with any passive objects. The controlled robot will never become unstable due to the physical structure of the controller.

  12. Towards the theoretical bases of the folding of the 100-A nucleosome filament

    International Nuclear Information System (INIS)

    Chela Flores, J.

    1994-01-01

    We attempt to model DNA packaging at the various stages of ever increasing DNA folding from the 100-A nucleosome filament to various further stages leading up to the metaphase chromosome. We have assumed that a phase transition has induced chromatin into a condensed mode. The mean-field model allows the simultaneous discussion of chromatin with packaging ration η and DNA replication at various stages of folding. We derive a formula correlating (during the S phase of the cell cycle) the DNA polymerase velocity r f (measured in nucleotides per minute) in a relation of inverse proportionality with the degree of DNA packaging: r f = λη -1/2 , where the dimensional constant λ has been determined. This model suggests that in the heterochromatic regions of chromatin there is reduced activity of DNA polymerases. We discuss the possible relevance of our model to late replicating telomeres in yeast and several higher eukaryotes. (author). 28 refs, 3 tabs

  13. Brownian dynamics simulation of the cross-talking effect among modified histones on conformations of nucleosomes

    Science.gov (United States)

    Duan, Zhao-Wen; Li, Wei; Xie, Ping; Dou, Shuo-Xing; Wang, Peng-Ye

    2010-04-01

    Using Brownian dynamics simulation, we studied the effect of histone modifications on conformations of an array of nucleosomes in a segment of chromatin. The simulation demonstrated that the segment of chromatin shows the dynamic behaviour that its conformation can switch between a state with nearly all of the histones being wrapped by DNA and a state with nearly all of the histones being unwrapped by DNA, thus involving the “cross-talking" interactions among the histones. Each state can stay for a sufficiently long time. These conformational states are essential for gene expression or gene silence. The simulation also shows that these conformational states can be inherited by the daughter DNAs during DNA replication, giving a theoretical explanation of the epigenetic phenomenon.

  14. Brownian dynamics simulation of the cross-talking effect among modified histones on conformations of nucleosomes

    International Nuclear Information System (INIS)

    Zhao-Wen, Duan; Wei, Li; Ping, Xie; Shuo-Xing, Dou; Peng-Ye, Wang

    2010-01-01

    Using Brownian dynamics simulation, we studied the effect of histone modifications on conformations of an array of nucleosomes in a segment of chromatin. The simulation demonstrated that the segment of chromatin shows the dynamic behaviour that its conformation can switch between a state with nearly all of the histones being wrapped by DNA and a state with nearly all of the histones being unwrapped by DNA, thus involving the “cross-talking” interactions among the histones. Each state can stay for a sufficiently long time. These conformational states are essential for gene expression or gene silence. The simulation also shows that these conformational states can be inherited by the daughter DNAs during DNA replication, giving a theoretical explanation of the epigenetic phenomenon. (cross-disciplinary physics and related areas of science and technology)

  15. Thermomechanical damage of nucleosome by the shock wave initiated by ion passing through liquid water

    International Nuclear Information System (INIS)

    Yakubovich, Alexander V.; Surdutovich, Eugene; Solov’yov, Andrey V.

    2012-01-01

    We report on the results of full-atom molecular dynamics simulations of the heat spike in the water medium caused by the propagation of the heavy ion in the vicinity of its Bragg peak. High rate of energy transfer from an ion to the molecules of surrounding water environment leads to the rapid increase of the temperature of the molecules in the vicinity of ions trajectory. As a result of an abrupt increase of the temperature we observe the formation of the nanoscale shock wave propagating through the medium. We investigate the thermomechanical damage caused by the shock wave to the nucleosome located in the vicinity of heavy ion trajectory. We observe the substantial deformation of the DNA secondary structure. We show that the produced shock wave can lead to the thermomechanical breakage of the DNA backbone covalent bonds and present estimates for the number of such strand brakes per one cell nucleus.

  16. Occupation: nurse; occupational hazard: radiation

    International Nuclear Information System (INIS)

    Nickson, K.

    1984-01-01

    The work of the occupational health nurses at the Pickering Generating Station is described. A staff of two nurses teach first aid and safety, practice an emergency plan, and monitor personnel for minimum health standards for radiation workers. Special attention is paid to problems which might be aggravated by radiation, such as skin complaints, respiratory diseases, emotional stability, or phobias regarding heights, plastic suits, or radiation itself. Procedures used in treating contaminated personnel are outlined

  17. Occupation: nurse; occupational hazard: radiation

    Energy Technology Data Exchange (ETDEWEB)

    Nickson, K.

    1984-03-01

    The work of the occupational health nurses at the Pickering Generating Station is described. A staff of two nurses teach first aid and safety, practice an emergency plan, and monitor personnel for minimum health standards for radiation workers. Special attention is paid to problems which might be aggravated by radiation, such as skin complaints, respiratory diseases, emotional stability, or phobias regarding heights, plastic suits, or radiation itself. Procedures used in treating contaminated personnel are outlined.

  18. A role for tuned levels of nucleosome remodeler subunit ACF1 during Drosophila oogenesis.

    Science.gov (United States)

    Börner, Kenneth; Jain, Dhawal; Vazquez-Pianzola, Paula; Vengadasalam, Sandra; Steffen, Natascha; Fyodorov, Dmitry V; Tomancak, Pavel; Konev, Alexander; Suter, Beat; Becker, Peter B

    2016-03-15

    The Chromatin Accessibility Complex (CHRAC) consists of the ATPase ISWI, the large ACF1 subunit and a pair of small histone-like proteins, CHRAC-14/16. CHRAC is a prototypical nucleosome sliding factor that mobilizes nucleosomes to improve the regularity and integrity of the chromatin fiber. This may facilitate the formation of repressive chromatin. Expression of the signature subunit ACF1 is restricted during embryonic development, but remains high in primordial germ cells. Therefore, we explored roles for ACF1 during Drosophila oogenesis. ACF1 is expressed in somatic and germline cells, with notable enrichment in germline stem cells and oocytes. The asymmetrical localization of ACF1 to these cells depends on the transport of the Acf1 mRNA by the Bicaudal-D/Egalitarian complex. Loss of ACF1 function in the novel Acf1(7) allele leads to defective egg chambers and their elimination through apoptosis. In addition, we find a variety of unusual 16-cell cyst packaging phenotypes in the previously known Acf1(1) allele, with a striking prevalence of egg chambers with two functional oocytes at opposite poles. Surprisingly, we found that the Acf1(1) deletion--despite disruption of the Acf1 reading frame--expresses low levels of a PHD-bromodomain module from the C-terminus of ACF1 that becomes enriched in oocytes. Expression of this module from the Acf1 genomic locus leads to packaging defects in the absence of functional ACF1, suggesting competitive interactions with unknown target molecules. Remarkably, a two-fold overexpression of CHRAC (ACF1 and CHRAC-16) leads to increased apoptosis and packaging defects. Evidently, finely tuned CHRAC levels are required for proper oogenesis. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. The changing paradigm: estrogen receptor α recognition on DNA and within the dynamic nature of nucleosomes

    Directory of Open Access Journals (Sweden)

    William M. Scovell

    2015-03-01

    Full Text Available Estrogen receptor alpha (ERα plays a major role in the expression of estrogen-responsive genes. Although its conventional binding characteristics have been considered coincident with & exclusively in the class of steroid hormone receptors, increasing evidence challenges this paradigm. ERα was shown to bind to consensus estrogen response element half-sites (cHERE in DNA in the presence of the ubiquitous, abundant & conserved architectural protein, high mobility group protein 1 (HMGB1. It also binds to direct repeats with various spacers, in addition to everted repeats. These in vitro binding sites have been shown to be active in vivo, with both the binding affinity and transcriptional activity increased in the presence of HMGB1. Surprisingly, ERα does not bind to the optimally oriented cERE at the dyad in rotationally phased and translationally positioned nucleosomes. However, the presence of HMGB1 restructures the nucleosome to facilitate increased ERα accessibility, resulting in sequence-specific estrogen receptor binding. The finding that HMGB1 interacts with unbound ERα provides a unique avenue for enhanced ERα activity and possibly an increase in the extent of targeting at estrogen-responsive genes. The findings are consistent with ERα 1 targeting a much wider selection of genomic response elements (half-sites and inverted, direct and everted repeats and 2 exhibiting characteristics of both steroid and non steroid nuclear receptors. Growing evidence already shows a competition occurs at the DNA level between ERα and the non steroid nuclear hormone receptor, thyroid receptor (TR. Collectively, these reports suggest a less restrictive cataloging for estrogen receptor and a broader paradigm for understanding its role in the regulation of estrogen-responsive genes and influence on non steroid hormone receptor activities.

  20. Occupational physiology

    CERN Document Server

    Toomingas, Allan; Tornqvist, Ewa Wigaeus

    2011-01-01

    In a clear and accessible presentation, Occupational Physiology focuses on important issues in the modern working world. Exploring major public health problems-such as musculoskeletal disorders and stress-this book explains connections between work, well-being, and health based on up-to-date research in the field. It provides useful methods for risk assessment and guidelines on arranging a good working life from the perspective of the working individual, the company, and society as a whole.The book focuses on common, stressful situations in different professions. Reviewing bodily demands and r

  1. An all-atom model of the chromatin fiber containing linker histones reveals a versatile structure tuned by the nucleosomal repeat length.

    Directory of Open Access Journals (Sweden)

    Hua Wong

    Full Text Available In the nucleus of eukaryotic cells, histone proteins organize the linear genome into a functional and hierarchical architecture. In this paper, we use the crystal structures of the nucleosome core particle, B-DNA and the globular domain of H5 linker histone to build the first all-atom model of compact chromatin fibers. In this 3D jigsaw puzzle, DNA bending is achieved by solving an inverse kinematics problem. Our model is based on recent electron microscopy measurements of reconstituted fiber dimensions. Strikingly, we find that the chromatin fiber containing linker histones is a polymorphic structure. We show that different fiber conformations are obtained by tuning the linker histone orientation at the nucleosomes entry/exit according to the nucleosomal repeat length. We propose that the observed in vivo quantization of nucleosomal repeat length could reflect nature's ability to use the DNA molecule's helical geometry in order to give chromatin versatile topological and mechanical properties.

  2. Chemical Synthesis of K34-Ubiquitylated H2B for Nucleosome Reconstitution and Single-Particle Cryo-Electron Microscopy Structural Analysis.

    Science.gov (United States)

    Li, Jiabin; He, Qiaoqiao; Liu, Yuntao; Liu, Sanling; Tang, Shan; Li, Chengmin; Sun, Demeng; Li, Xiaorun; Zhou, Min; Zhu, Ping; Bi, Guoqiang; Zhou, Zhenghong; Zheng, Ji-Shen; Tian, Changlin

    2017-01-17

    Post-translational modifications (e.g., ubiquitylation) of histones play important roles in dynamic regulation of chromatin. Histone ubiquitylation has been speculated to directly influence the structure and dynamics of nucleosomes. However, structural information for ubiquitylated nucleosomes is still lacking. Here we report an alternative strategy for total chemical synthesis of homogenous histone H2B-K34-ubiquitylation (H2B-K34Ub) by using acid-cleavable auxiliary-mediated ligation of peptide hydrazides for site-specific ubiquitylation. Synthetic H2B-K34Ub was efficiently incorporated into nucleosomes and further used for single-particle cryo-electron microscopy (cryo-EM) imaging. The cryo-EM structure of the nucleosome containing H2B-K34Ub suggests that two flexible ubiquitin domains protrude between the DNA chains of the nucleosomes. The DNA chains around the H2B-K34 sites shift and provide more space for ubiquitin to protrude. These analyses indicated local and slight structural influences on the nucleosome with ubiquitylation at the H2B-K34 site. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Computer Modeling Reveals that Modifications of the Histone Tail Charges Define Salt-Dependent Interaction of the Nucleosome Core Particles

    OpenAIRE

    Yang, Ye; Lyubartsev, Alexander P.; Korolev, Nikolay; Nordenskiöld, Lars

    2009-01-01

    Coarse-grained Langevin molecular dynamics computer simulations were conducted for systems that mimic solutions of nucleosome core particles (NCPs). The NCP was modeled as a negatively charged spherical particle representing the complex of DNA and the globular part of the histones combined with attached strings of connected charged beads modeling the histone tails. The size, charge, and distribution of the tails relative to the core were built to match real NCPs. Three models of NCPs were con...

  4. Characterization of Partial Intrinsic Symmetries

    NARCIS (Netherlands)

    Shehu, Aurela; Brunton, Alan; Wuhrer, Stefanie; Wand, Michael

    2014-01-01

    We present a mathematical framework and algorithm for characterizing and extracting partial intrinsic symmetries of surfaces, which is a fundamental building block for many modern geometry processing algorithms. Our goal is to compute all “significant” symmetry information of the shape, which we

  5. Reading: Intrinsic versus Extrinsic Motivation.

    Science.gov (United States)

    Ediger, Marlow

    Much debate centers on motivating student in reading achievement. Should students feel motivated from within (intrinsic motivation), or is it better to have extrinsic motivation whereby external stimuli are used to help learners achieve optimally in reading? This paper aims to analyze the two points of view about motivating students in reading…

  6. Intrinsic volumes of symmetric cones

    OpenAIRE

    Amelunxen, Dennis; Bürgisser, Peter

    2012-01-01

    We compute the intrinsic volumes of the cone of positive semidefinite matrices over the real numbers, over the complex numbers, and over the quaternions, in terms of integrals related to Mehta's integral. Several applications for the probabilistic analysis of semidefinite programming are given.

  7. Acoustic resonance spectroscopy intrinsic seals

    International Nuclear Information System (INIS)

    Olinger, C.T.; Burr, T.; Vnuk, D.R.

    1994-01-01

    We have begun to quantify the ability of acoustic resonance spectroscopy (ARS) to detect the removal and replacement of the lid of a simulated special nuclear materials drum. Conceptually, the acoustic spectrum of a container establishcs a baseline fingerprint, which we refer to as an intrinsic seal, for the container. Simply removing and replacing the lid changes some of the resonant frequencies because it is impossible to exactly duplicate all of the stress patterns between the lid and container. Preliminary qualitative results suggested that the ARS intrinsic seal could discriminate between cases where a lid has or has not been removed. The present work is directed at quantifying the utility of the ARS intrinsic seal technique, including the technique's sensitivity to ''nuisance'' effects, such as temperature swings, movement of the container, and placement of the transducers. These early quantitative tests support the potential of the ARS intrinsic seal application, but also reveal a possible sensitivity to nuisance effects that could limit environments or conditions under which the technique is effective

  8. Intrinsic Motivation in Physical Education

    Science.gov (United States)

    Davies, Benjamin; Nambiar, Nathan; Hemphill, Caroline; Devietti, Elizabeth; Massengale, Alexandra; McCredie, Patrick

    2015-01-01

    This article describes ways in which educators can use Harter's perceived competence motivation theory, the achievement goal theory, and self-determination theory to develop students' intrinsic motivation to maintain physical fitness, as demonstrated by the Sound Body Sound Mind curriculum and proven effective by the 2013 University of…

  9. The Scc2/Scc4 complex acts in sister chromatid cohesion and transcriptional regulation by maintaining nucleosome-free regions

    Science.gov (United States)

    Lopez-Serra, Lidia; Kelly, Gavin; Patel, Harshil; Stewart, Aengus; Uhlmann, Frank

    2014-01-01

    The cohesin complex is at the heart of many chromosomal activities, including sister chromatid cohesion and transcriptional regulation1-3. Cohesin loading onto chromosomes depends on the Scc2/Scc4 cohesin loader complex4-6, but the chromatin features that form cohesin loading sites remain poorly understood. Here, we show that the RSC chromatin remodeling complex recruits budding yeast Scc2/Scc4 to broad nucleosome-free regions, that the cohesin loader itself helps to maintain. Consequently, inactivation of the cohesin loader or RSC complex have similar effects on nucleosome positioning, gene expression and sister chromatid cohesion. These results reveal an intimate link between local chromatin structure and higher order chromosome architecture. Our findings pertain to the similarities between two severe human disorders, Cornelia de Lange syndrome, caused by mutations in the human cohesin loader, and Coffin-Siris syndrome, resulting from mutations in human RSC complex components7-9. Both could arise from gene misregulation due to related changes in the nucleosome landscape. PMID:25173104

  10. Image processing occupancy sensor

    Science.gov (United States)

    Brackney, Larry J.

    2016-09-27

    A system and method of detecting occupants in a building automation system environment using image based occupancy detection and position determinations. In one example, the system includes an image processing occupancy sensor that detects the number and position of occupants within a space that has controllable building elements such as lighting and ventilation diffusers. Based on the position and location of the occupants, the system can finely control the elements to optimize conditions for the occupants, optimize energy usage, among other advantages.

  11. Occupational therapy students' perceptions of occupational therapy.

    Science.gov (United States)

    Turpin, Merrill June; Rodger, Sylvia; Hall, Anna R

    2012-10-01

    An understanding of students' perceptions of occupational therapy on entry is required to recognise how professional socialisation occurs through curriculum. Findings pertain to a qualitative study investigating students' perceptions of occupational therapy upon entry to two occupational therapy programmes in Australia. Students commencing Bachelor of Occupational Therapy and Masters of Occupational Therapy Studies programmes participated in the study (n = 462). A purpose-designed questionnaire was distributed to students in the first lecture of each programme. Preliminary analysis comprised identification of keywords/phrases and coding categories were generated from patterns of keywords. Frequency counts and percentages of keywords/phrases within categories were completed. Students' responses were categorised as 'what' occupational therapists do; 'how' they do it; 'why' they do it; and 'who' they work with. In 'what' occupational therapists do students frequently described 'helping' people. Both undergraduate and graduate entry masters students used the term 'rehabilitation' to describe how occupational therapy is done, with graduate entry students occasionally responding with 'through occupation' and 'modifying the environment'. Students perceived the 'why' of occupational therapy as getting back to 'everyday activities', with some students emphasising returning to 'normal' activities or life. Regarding the 'who' category, students also thought occupational therapists worked with people with an 'injury' or 'disability'. Students entered their occupational therapy programmes with perceptions consistent with the general public's views of occupational therapy. However, graduate entry students exposed to a pre-reading package prior to entry had more advanced occupational therapy concepts than undergraduate students. © 2011 The Authors. Australian Occupational Therapy Journal © 2011 Occupational Therapy Australia.

  12. Structural Flexibility of the Nucleosome Core Particle at Atomic Resolution studied by Molecular Dynamics Simulation.

    Energy Technology Data Exchange (ETDEWEB)

    Roccatano, Danilo; Barthel, Andre; Zacharias, Martin W.

    2007-01-24

    The research described in this product was performed in part in the Environmental Molecular Sciences Laboratory, a national scientific user facility sponsored by the Department of Energy's Office of Biological and Environmental Research and located at Pacific Northwest National Laboratory. Comparative explicit solvent molecular dynamics (MD) simulations have been performed on a complete nucleosome core particle with and without N-terminal histone tails for more than 20 ns. Main purpose of the simulations was to study the dynamics of mobile elements such as histone N-terminal tails and how packing and DNA-bending influences the fine structure and dynamics of DNA. Except for the tails, histone and DNA molecules stayed on average close to the crystallographic start structure supporting the quality of the current force field approach. Despite the packing strain, no increase of transitions to noncanonical nucleic acid backbone conformations compared to regular B-DNA was observed. The pattern of kinks and bends along the DNA remained close to the experiment overall. In addition to the local dynamics, the simulations allowed the analysis of the superhelical mobility indicating a limited relative mobility of DNA segments separated by one superhelical turn (mean relative displacement of approximately 60.2 nm, mainly along the superhelical axis). An even higher rigidity was found for relative motions (distance fluctuations) of segments separated by half a superhelical turn (approximately 60.1 nm). The N-terminal tails underwent dramatic conformational rearrangements on the nanosecond time scale toward partially and transiently wrapped states around the DNA. Many of the histone tail changes corresponded to coupled association and folding events from fully solvent-exposed states toward complexes with the major and minor grooves of DNA. The simulations indicate that the rapid conformational changes of the tails can modulate the DNA accessibility within a few nanoseconds

  13. Characterizing and controlling intrinsic biases of lambda exonuclease in nascent strand sequencing reveals phasing between nucleosomes and G-quadruplex motifs around a subset of human replication origins

    DEFF Research Database (Denmark)

    Foulk, M. S.; Urban, J. M.; Casella, Cinzia

    2015-01-01

    Nascent strand sequencing (NS-seq) is used to discover DNA replication origins genome-wide, allowing identification of features for their specification. NS-seq depends on the ability of lambda exonuclease (lambda-exo) to efficiently digest parental DNA while leaving RNA-primer protected nascent...... strands intact. We used genomics and biochemical approaches to determine if lambda-exo digests all parental DNA sequences equally. We report that lambda-exo does not efficiently digest G-quadruplex (G4) structures in a plasmid. Moreover, lambda-exo digestion of nonreplicating genomic DNA (LexoG0) enriches...... GC-rich DNA and G4 motifs genome-wide. We used LexoG0 data to control for nascent strand-independent lambda-exo biases in NSseq and validated this approach at the rDNA locus. The lambda-exo-controlled NS-seq peaks are not GC-rich, and only 35.5% overlap with 6.8% of all G4s, suggesting that G4s...

  14. Interaction of nucleosome assembly proteins abolishes nuclear localization of DGKζ by attenuating its association with importins

    International Nuclear Information System (INIS)

    Okada, Masashi; Hozumi, Yasukazu; Ichimura, Tohru; Tanaka, Toshiaki; Hasegawa, Hiroshi; Yamamoto, Masakazu; Takahashi, Nobuya; Iseki, Ken; Yagisawa, Hitoshi; Shinkawa, Takashi; Isobe, Toshiaki; Goto, Kaoru

    2011-01-01

    Diacylglycerol kinase (DGK) is involved in the regulation of lipid-mediated signal transduction through the metabolism of a second messenger diacylglycerol. Of the DGK family, DGKζ, which contains a nuclear localization signal, localizes mainly to the nucleus but translocates to the cytoplasm under pathological conditions. However, the detailed mechanism of translocation and its functional significance remain unclear. To elucidate these issues, we used a proteomic approach to search for protein targets that interact with DGKζ. Results show that nucleosome assembly protein (NAP) 1-like 1 (NAP1L1) and NAP1-like 4 (NAP1L4) are identified as novel DGKζ binding partners. NAP1Ls constitutively shuttle between the nucleus and the cytoplasm in transfected HEK293 cells. The molecular interaction of DGKζ and NAP1Ls prohibits nuclear import of DGKζ because binding of NAP1Ls to DGKζ blocks import carrier proteins, Qip1 and NPI1, to interact with DGKζ, leading to cytoplasmic tethering of DGKζ. In addition, overexpression of NAP1Ls exerts a protective effect against doxorubicin-induced cytotoxicity. These findings suggest that NAP1Ls are involved in a novel molecular basis for the regulation of nucleocytoplasmic shuttling of DGKζ and provide a clue to examine functional significance of its translocation under pathological conditions.

  15. Nucleosome Core Particle Disassembly and Assembly Kinetics Studied Using Single-Molecule Fluorescence.

    Science.gov (United States)

    Hazan, Noa Plavner; Tomov, Toma E; Tsukanov, Roman; Liber, Miran; Berger, Yaron; Masoud, Rula; Toth, Katalin; Langowski, Joerg; Nir, Eyal

    2015-10-20

    The stability of the nucleosome core particle (NCP) is believed to play a major role in regulation of gene expression. To understand the mechanisms that influence NCP stability, we studied stability and dissociation and association kinetics under different histone protein (NCP) and NaCl concentrations using single-pair Förster resonance energy transfer and alternating laser excitation techniques. The method enables distinction between folded, unfolded, and intermediate NCP states and enables measurements at picomolar to nanomolar NCP concentrations where dissociation and association reactions can be directly observed. We reproduced the previously observed nonmonotonic dependence of NCP stability on NaCl concentration, and we suggest that this rather unexpected behavior is a result of interplay between repulsive and attractive forces within positively charged histones and between the histones and the negatively charged DNA. Higher NaCl concentrations decrease the attractive force between the histone proteins and the DNA but also stabilize H2A/H2B histone dimers, and possibly (H3/H4)2 tetramers. An intermediate state in which one DNA arm is unwrapped, previously observed at high NaCl concentrations, is also explained by this salt-induced stabilization. The strong dependence of NCP stability on ion and histone concentrations, and possibly on other charged macromolecules, may play a role in chromosomal morphology. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  16. Characteristic arrangement of nucleosomes is predictive of chromatin interactions at kilobase resolution.

    Science.gov (United States)

    Zhang, Hui; Li, Feifei; Jia, Yan; Xu, Bingxiang; Zhang, Yiqun; Li, Xiaoli; Zhang, Zhihua

    2017-12-15

    High-throughput chromosome conformation capture (3C) technologies, such as Hi-C, have made it possible to survey 3D genome structure. However, obtaining 3D profiles at kilobase resolution at low cost remains a major challenge. Therefore, we herein present an algorithm for precise identification of chromatin interaction sites at kilobase resolution from MNase-seq data, termed chromatin interaction site detector (CISD), and a CISD-based chromatin loop predictor (CISD_loop) that predicts chromatin-chromatin interactions (CCIs) from low-resolution Hi-C data. We show that the predictions of CISD and CISD_loop overlap closely with chromatin interaction analysis by paired-end tag sequencing (ChIA-PET) anchors and loops, respectively. The validity of CISD/CISD_loop was further supported by a 3C assay at about 5 kb resolution. Finally, we demonstrate that only modest amounts of MNase-seq and Hi-C data are sufficient to achieve ultrahigh resolution CCI maps. Our results suggest that CCIs may result in characteristic nucleosomes arrangement patterns flanking the interaction sites, and our algorithms may facilitate precise and systematic investigations of CCIs on a larger scale than hitherto have been possible. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  17. Refinement of the subunit interaction network within the nucleosome remodelling and deacetylase (NuRD) complex.

    Science.gov (United States)

    Torrado, Mario; Low, Jason K K; Silva, Ana P G; Schmidberger, Jason W; Sana, Maryam; Sharifi Tabar, Mehdi; Isilak, Musa E; Winning, Courtney S; Kwong, Cherry; Bedward, Max J; Sperlazza, Mary J; Williams, David C; Shepherd, Nicholas E; Mackay, Joel P

    2017-12-01

    The nucleosome remodelling and deacetylase (NuRD) complex is essential for the development of complex animals. NuRD has roles in regulating gene expression and repairing damaged DNA. The complex comprises at least six proteins with two or more paralogues of each protein routinely identified when the complex is purified from cell extracts. To understand the structure and function of NuRD, a map of direct subunit interactions is needed. Dozens of published studies have attempted to define direct inter-subunit connectivities. We propose that conclusions reported in many such studies are in fact ambiguous for one of several reasons. First, the expression of many NuRD subunits in bacteria is unlikely to lead to folded, active protein. Second, interaction studies carried out in cells that contain endogenous NuRD complex can lead to false positives through bridging of target proteins by endogenous components. Combining existing information on NuRD structure with a protocol designed to minimize false positives, we report a conservative and robust interaction map for the NuRD complex. We also suggest a 3D model of the complex that brings together the existing data on the complex. The issues and strategies discussed herein are also applicable to the analysis of a wide range of multi-subunit complexes. Micrococcal nuclease (MNase), EC 3.1.31.1; histone deacetylase (HDAC), EC 3.5.1.98. © 2017 Federation of European Biochemical Societies.

  18. Skin vaccination using microneedles coated with a plasmid DNA cocktail encoding nucleosomal histones of Leishmania spp.

    Science.gov (United States)

    Moreno, Esther; Schwartz, Juana; Calvo, Alba; Blanco, Laura; Larrea, Esther; Irache, Juan M; Sanmartín, Carmen; Coulman, Sion A; Soto, Manuel; Birchall, James C; Espuelas, Socorro

    2017-11-25

    Vaccine delivery using microneedles (MNs) represents a safe, easily disposable and painless alternative to traditional needle immunizations. The MN delivery of DNA vaccines to the dermis may result in a superior immune response and/or an equivalent immune response at a lower vaccine dose (dose-sparing). This could be of special interest for immunization programs against neglected tropical diseases such as leishmaniasis. In this work, we loaded a MN device with 60μg of a plasmid DNA cocktail encoding the Leishmania infantum nucleosomal histones H2A, H2B, H3 and H4 and compared its immunogenicity and protective capacity against conventional s.c. or i.d. injection of the plasmid. Mice immunized with MNs showed increased ratios of IFN-γ/IL-10, IFN-γ/IL-13, IFN-γ/IL-4, and IFN-γ/TGF-β in the spleens and lymph nodes compared with mice immunized by s.c. and i.d. routes. Furthermore, CCXCL9, CXCL10 and CCL2 levels were also higher. These data suggest that the nucleic acid immunization using MNs produced a better bias towards a Th1 response. However, none of the immunizations strategies were able to control Leishmania major infection in BALB/c mice, as illustrated by an increase in lesion size and parasite burden. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Dengue virus capsid protein binds core histones and inhibits nucleosome formation in human liver cells.

    Directory of Open Access Journals (Sweden)

    Tonya M Colpitts

    Full Text Available Dengue virus (DENV is a member of the Flaviviridae and a globally (reemerging pathogen that causes serious human disease. There is no specific antiviral or vaccine for dengue virus infection. Flavivirus capsid (C is a structural protein responsible for gathering the viral RNA into a nucleocapsid that forms the core of a mature virus particle. Flaviviral replication is known to occur in the cytoplasm yet a large portion of capsid protein localizes to the nucleus during infection. The reasons for the nuclear presences of capsid are not completely understood. Here, we expressed mature DENV C in a tandem affinity purification assay to identify potential binding partners in human liver cells. DENV C targeted the four core histones, H2A, H2B, H3 and H4. DENV C bound recombinant histones in solution and colocalized with histones in the nucleus and cytoplasm of liver cells during DENV infection. We show that DENV C acts as a histone mimic, forming heterodimers with core histones, binding DNA and disrupting nucleosome formation. We also demonstrate that DENV infection increases the amounts of core histones in livers cells, which may be a cellular response to C binding away the histone proteins. Infection with DENV additionally alters levels of H2A phosphorylation in a time-dependent manner. The interactions of C and histones add an interesting new role for the presence of C in the nucleus during DENV infection.

  20. Dengue virus capsid protein binds core histones and inhibits nucleosome formation in human liver cells.

    Science.gov (United States)

    Colpitts, Tonya M; Barthel, Sebastian; Wang, Penghua; Fikrig, Erol

    2011-01-01

    Dengue virus (DENV) is a member of the Flaviviridae and a globally (re)emerging pathogen that causes serious human disease. There is no specific antiviral or vaccine for dengue virus infection. Flavivirus capsid (C) is a structural protein responsible for gathering the viral RNA into a nucleocapsid that forms the core of a mature virus particle. Flaviviral replication is known to occur in the cytoplasm yet a large portion of capsid protein localizes to the nucleus during infection. The reasons for the nuclear presences of capsid are not completely understood. Here, we expressed mature DENV C in a tandem affinity purification assay to identify potential binding partners in human liver cells. DENV C targeted the four core histones, H2A, H2B, H3 and H4. DENV C bound recombinant histones in solution and colocalized with histones in the nucleus and cytoplasm of liver cells during DENV infection. We show that DENV C acts as a histone mimic, forming heterodimers with core histones, binding DNA and disrupting nucleosome formation. We also demonstrate that DENV infection increases the amounts of core histones in livers cells, which may be a cellular response to C binding away the histone proteins. Infection with DENV additionally alters levels of H2A phosphorylation in a time-dependent manner. The interactions of C and histones add an interesting new role for the presence of C in the nucleus during DENV infection.

  1. Dengue Virus Capsid Protein Binds Core Histones and Inhibits Nucleosome Formation in Human Liver Cells

    Science.gov (United States)

    Colpitts, Tonya M.; Barthel, Sebastian; Wang, Penghua; Fikrig, Erol

    2011-01-01

    Dengue virus (DENV) is a member of the Flaviviridae and a globally (re)emerging pathogen that causes serious human disease. There is no specific antiviral or vaccine for dengue virus infection. Flavivirus capsid (C) is a structural protein responsible for gathering the viral RNA into a nucleocapsid that forms the core of a mature virus particle. Flaviviral replication is known to occur in the cytoplasm yet a large portion of capsid protein localizes to the nucleus during infection. The reasons for the nuclear presences of capsid are not completely understood. Here, we expressed mature DENV C in a tandem affinity purification assay to identify potential binding partners in human liver cells. DENV C targeted the four core histones, H2A, H2B, H3 and H4. DENV C bound recombinant histones in solution and colocalized with histones in the nucleus and cytoplasm of liver cells during DENV infection. We show that DENV C acts as a histone mimic, forming heterodimers with core histones, binding DNA and disrupting nucleosome formation. We also demonstrate that DENV infection increases the amounts of core histones in livers cells, which may be a cellular response to C binding away the histone proteins. Infection with DENV additionally alters levels of H2A phosphorylation in a time-dependent manner. The interactions of C and histones add an interesting new role for the presence of C in the nucleus during DENV infection. PMID:21909430

  2. Genetic identification of a network of factors that functionally interact with the nucleosome remodeling ATPase ISWI.

    Directory of Open Access Journals (Sweden)

    Giosalba Burgio

    2008-06-01

    Full Text Available Nucleosome remodeling and covalent modifications of histones play fundamental roles in chromatin structure and function. However, much remains to be learned about how the action of ATP-dependent chromatin remodeling factors and histone-modifying enzymes is coordinated to modulate chromatin organization and transcription. The evolutionarily conserved ATP-dependent chromatin-remodeling factor ISWI plays essential roles in chromosome organization, DNA replication, and transcription regulation. To gain insight into regulation and mechanism of action of ISWI, we conducted an unbiased genetic screen to identify factors with which it interacts in vivo. We found that ISWI interacts with a network of factors that escaped detection in previous biochemical analyses, including the Sin3A gene. The Sin3A protein and the histone deacetylase Rpd3 are part of a conserved histone deacetylase complex involved in transcriptional repression. ISWI and the Sin3A/Rpd3 complex co-localize at specific chromosome domains. Loss of ISWI activity causes a reduction in the binding of the Sin3A/Rpd3 complex to chromatin. Biochemical analysis showed that the ISWI physically interacts with the histone deacetylase activity of the Sin3A/Rpd3 complex. Consistent with these findings, the acetylation of histone H4 is altered when ISWI activity is perturbed in vivo. These findings suggest that ISWI associates with the Sin3A/Rpd3 complex to support its function in vivo.

  3. Nucleosome acidic patch promotes RNF168- and RING1B/BMI1-dependent H2AX and H2A ubiquitination and DNA damage signaling.

    Directory of Open Access Journals (Sweden)

    Justin W Leung

    2014-03-01

    Full Text Available Histone ubiquitinations are critical for the activation of the DNA damage response (DDR. In particular, RNF168 and RING1B/BMI1 function in the DDR by ubiquitinating H2A/H2AX on Lys-13/15 and Lys-118/119, respectively. However, it remains to be defined how the ubiquitin pathway engages chromatin to provide regulation of ubiquitin targeting of specific histone residues. Here we identify the nucleosome acid patch as a critical chromatin mediator of H2A/H2AX ubiquitination (ub. The acidic patch is required for RNF168- and RING1B/BMI1-dependent H2A/H2AXub in vivo. The acidic patch functions within the nucleosome as nucleosomes containing a mutated acidic patch exhibit defective H2A/H2AXub by RNF168 and RING1B/BMI1 in vitro. Furthermore, direct perturbation of the nucleosome acidic patch in vivo by the expression of an engineered acidic patch interacting viral peptide, LANA, results in defective H2AXub and RNF168-dependent DNA damage responses including 53BP1 and BRCA1 recruitment to DNA damage. The acidic patch therefore is a critical nucleosome feature that may serve as a scaffold to integrate multiple ubiquitin signals on chromatin to compose selective ubiquitinations on histones for DNA damage signaling.

  4. Detecting Nosocomial Intrinsic Infections through Relating Bacterial ...

    African Journals Online (AJOL)

    Sierra Leone Journal of Biomedical Research ... Surgical procedures often lead to both intrinsic and extrinsic infections. ... This study demonstrated surgical procedures as precursory to intrinsic infections and that bacterial pathogens found on wounds and endogenous indicators of surgery are links to intrinsic infection.

  5. Efficient cleavage of single and clustered AP site lesions within mono-nucleosome templates by CHO-K1 nuclear extract contrasts with retardation of incision by purified APE1

    Science.gov (United States)

    Eccles, Laura J.; Menoni, Hervé; Angelov, Dimitar; Lomax, Martine E.; O’Neill, Peter

    2015-01-01

    Clustered DNA damage is a unique characteristic of radiation-induced DNA damage and the formation of these sites poses a serious challenge to the cell’s repair machinery. Within a cell DNA is compacted, with nucleosomes being the first order of higher level structure. However, few data are reported on the efficiency of clustered-lesion processing within nucleosomal DNA templates. Here, we show retardation of cleavage of a single AP site by purified APE1 when contained in nucleosomal DNA, compared to cleavage of an AP site in non-nucleosomal DNA. This retardation seen in nucleosomal DNA was alleviated by incubation with CHO-K1 nuclear extract. When clustered DNA damage sites containing bistranded AP sites were present in nucleosomal DNA, efficient cleavage of the AP sites was observed after treatment with nuclear extract. The resultant DSB formation led to DNA dissociating from the histone core and nucleosomal dispersion. Clustered damaged sites containing bistranded AP site/8-oxoG residues showed no retardation of cleavage of the AP site but retardation of 8-oxoG excision, compared to isolated lesions, thus DSB formation was not seen. An increased understanding of processing of clustered DNA damage in a nucleosomal environment may lead to new strategies to enhance the cytotoxic effects of radiotherapeutics. PMID:26439176

  6. NAP-1, Nucleosome assembly protein 1, a histone chaperone involved in Drosophila telomeres.

    Science.gov (United States)

    López-Panadès, Elisenda; Casacuberta, Elena

    2016-03-01

    Telomere elongation is a function that all eukaryote cells must accomplish in order to guarantee, first, the stability of the end of the chromosomes and second, to protect the genetic information from the inevitable terminal erosion. The targeted transposition of the telomere transposons HeT-A, TART and TAHRE perform this function in Drosophila, while the telomerase mechanism elongates the telomeres in most eukaryotes. In order to integrate telomere maintenance together with cell cycle and metabolism, different components of the cell interact, regulate, and control the proteins involved in telomere elongation. Different partners of the telomerase mechanism have already been described, but in contrast, very few proteins have been related with assisting the telomere transposons of Drosophila. Here, we describe for the first time, the implication of NAP-1 (Nucleosome assembly protein 1), a histone chaperone that has been involved in nuclear transport, transcription regulation, and chromatin remodeling, in telomere biology. We find that Nap-1 and HeT-A Gag, one of the major components of the Drosophila telomeres, are part of the same protein complex. We also demonstrate that their close interaction is necessary to guarantee telomere stability in dividing cells. We further show that NAP-1 regulates the transcription of the HeT-A retrotransposon, pointing to a positive regulatory role of NAP-1 in telomere expression. All these results facilitate the understanding of the transposon telomere maintenance mechanism, as well as the integration of telomere biology with the rest of the cell metabolism. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Intrinsic cylindrical and spherical waves

    International Nuclear Information System (INIS)

    Ludlow, I K

    2008-01-01

    Intrinsic waveforms associated with cylindrical and spherical Bessel functions are obtained by eliminating the factors responsible for the inverse radius and inverse square radius laws of wave power per unit area of wavefront. The resulting expressions are Riccati-Bessel functions for both cases and these can be written in terms of amplitude and phase functions of order v and wave variable z. When z is real, it is shown that a spatial phase angle of the intrinsic wave can be defined and this, together with its amplitude function, is systematically investigated for a range of fixed orders and varying z. The derivatives of Riccati-Bessel functions are also examined. All the component functions exhibit different behaviour in the near field depending on the order being less than, equal to or greater than 1/2. Plots of the phase angle can be used to display the locations of the zeros of the general Riccati-Bessel functions and lead to new relations concerning the ordering of the real zeros of Bessel functions and the occurrence of multiple zeros when the argument of the Bessel function is fixed

  8. Immunization strategies against visceral leishmaniosis with the nucleosomal histones of Leishmania infantum encoded in DNA vaccine or pulsed in dendritic cells.

    Science.gov (United States)

    Carrión, Javier; Folgueira, Cristina; Alonso, Carlos

    2008-05-12

    Immunization of BALB/c mice with a DNA vaccine encoding the nucleosomal histones from Leishmania infantum resulted in a complete failure of protection against visceral leishmaniosis (VL), whereas the adoptive transfer of bone marrow-derived dendritic cells pulsed with the same pathoantigens plays an essential role in controlling parasite growth in half of the cases. Reduction of the visceral parasite burden seems to be related to low persistence of regulatory T-cells in the spleen from vaccinated mice. These results provide clues for the optimization of this vaccine strategy with the four Leishmania nucleosomal histones against L. infantum infection.

  9. Occupational hearing loss

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/001048.htm Occupational hearing loss To use the sharing features on this page, please enable JavaScript. Occupational hearing loss is damage to the inner ear from noise ...

  10. Occupational Noise Exposure

    Science.gov (United States)

    ... Safety and Health Topics / Occupational Noise Exposure Occupational Noise Exposure This page requires that javascript be enabled ... interprets the signal as sound. x What is noise? Noise and vibration are both fluctuations in the ...

  11. Inhibition of Intrinsic Thrombin Generation

    Directory of Open Access Journals (Sweden)

    Thomas W. Stief MD

    2006-01-01

    Full Text Available Background The contact phase of coagulation is of physiologic/pathophysiologic importance, whenever unphysiologic polynegative substances such as cell fragments (microparticles get in contact with blood. There are several clinically used inhibitors of intrinsic thrombin generation. Here the inhibitory concentrations 50% (IC50 of these anticoagulants are measured by the highly specific thrombin generation assay INCA. Methods Unfrozen pooled normal citrated plasma in polystyrole tubes was supplemented at 23°C in duplicate with 0–2 IU/ml low molecular weight heparin (dalteparin, 0–2 IU/ml unfractionated heparin, 0–500 KIU/ml aprotinin, or 0–40 mM arginine. 50 μl plasma or 1 IU/ml thrombin standard were pipetted into a polystyrole microtiter plate with flat bottom. 5 μl SiO 2 /CaCl 2 - reagent (INCA activator were added and after 0–30 min incubation at 37°C 100 μl 2.5 M arginine, pH 8.6, were added; arginine inhibits hemostasis activation and depolymerizes generated fibrin within 20 min at 23°C. The in the physiologic 37°C incubation phase generated thrombin was then chromogenically detected. The intra-assay CV values were < 5%. Results and Discussion The approximate IC50 were 0.01 IU/ml dalteparin, 0.02 IU/ml heparin, 25 KIU/ml aprotinin, and 12 mM arginine. The efficiency of any anticoagulant on intrinsic thrombin generation should be measured for each individual patient. Abbreviations IIa, thrombin; δA, increase in absorbance; APTT, activated partial thromboplastin time; CRT, coagulation reaction time (at 37°C in water-bath; F-wells, polystyrole microtiter plates with flat bottom; IC50, inhibitory concentration 50%; INCA, intrinsic coagulation activity assay; IU, international units; KIU, kallikrein inhibiting unis; LMWH, low molecular weight heparin; mA, milli-absorbance units; PSL, pathromtin SL®; RT, room temperature (23°C; U-wells, polystyrole microtiter plates with round bottom.

  12. Intrinsic rotation with gyrokinetic models

    International Nuclear Information System (INIS)

    Parra, Felix I.; Barnes, Michael; Catto, Peter J.; Calvo, Iván

    2012-01-01

    The generation of intrinsic rotation by turbulence and neoclassical effects in tokamaks is considered. To obtain the complex dependences observed in experiments, it is necessary to have a model of the radial flux of momentum that redistributes the momentum within the tokamak in the absence of a preexisting velocity. When the lowest order gyrokinetic formulation is used, a symmetry of the model precludes this possibility, making small effects in the gyroradius over scale length expansion necessary. These effects that are usually small become important for momentum transport because the symmetry of the lowest order gyrokinetic formulation leads to the cancellation of the lowest order momentum flux. The accuracy to which the gyrokinetic equation needs to be obtained to retain all the physically relevant effects is discussed.

  13. Occupational Therapy (For Parents)

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Occupational Therapy KidsHealth / For Parents / Occupational Therapy What's in this ... care for some kids. Kids Who Might Need Occupational Therapy According to the AOTA, kids with these medical ...

  14. Synthetic biology and occupational risk.

    Science.gov (United States)

    Howard, John; Murashov, Vladimir; Schulte, Paul

    2017-03-01

    Synthetic biology is an emerging interdisciplinary field of biotechnology that involves applying the principles of engineering and chemical design to biological systems. Biosafety professionals have done an excellent job in addressing research laboratory safety as synthetic biology and gene editing have emerged from the larger field of biotechnology. Despite these efforts, risks posed by synthetic biology are of increasing concern as research procedures scale up to industrial processes in the larger bioeconomy. A greater number and variety of workers will be exposed to commercial synthetic biology risks in the future, including risks to a variety of workers from the use of lentiviral vectors as gene transfer devices. There is a need to review and enhance current protection measures in the field of synthetic biology, whether in experimental laboratories where new advances are being researched, in health care settings where treatments using viral vectors as gene delivery systems are increasingly being used, or in the industrial bioeconomy. Enhanced worker protection measures should include increased injury and illness surveillance of the synthetic biology workforce; proactive risk assessment and management of synthetic biology products; research on the relative effectiveness of extrinsic and intrinsic biocontainment methods; specific safety guidance for synthetic biology industrial processes; determination of appropriate medical mitigation measures for lentiviral vector exposure incidents; and greater awareness and involvement in synthetic biology safety by the general occupational safety and health community as well as by government occupational safety and health research and regulatory agencies.

  15. DMS-Seq for In Vivo Genome-wide Mapping of Protein-DNA Interactions and Nucleosome Centers.

    Science.gov (United States)

    Umeyama, Taichi; Ito, Takashi

    2017-10-03

    Protein-DNA interactions provide the basis for chromatin structure and gene regulation. Comprehensive identification of protein-occupied sites is thus vital to an in-depth understanding of genome function. Dimethyl sulfate (DMS) is a chemical probe that has long been used to detect footprints of DNA-bound proteins in vitro and in vivo. Here, we describe a genomic footprinting method, dimethyl sulfate sequencing (DMS-seq), which exploits the cell-permeable nature of DMS to obviate the need for nuclear isolation. This feature makes DMS-seq simple in practice and removes the potential risk of protein re-localization during nuclear isolation. DMS-seq successfully detects transcription factors bound to cis-regulatory elements and non-canonical chromatin particles in nucleosome-free regions. Furthermore, an unexpected preference of DMS confers on DMS-seq a unique potential to directly detect nucleosome centers without using genetic manipulation. We expect that DMS-seq will serve as a characteristic method for genome-wide interrogation of in vivo protein-DNA interactions. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  16. Occupational rhinitis: an update.

    Science.gov (United States)

    Stevens, Whitney W; Grammer, Leslie C

    2015-01-01

    Occupational rhinitis is characterized by nasal congestion, rhinorrhea, nasal itching, and/or sneezing that occur secondary to exposures in the workplace. This disease can be classified into allergic or nonallergic subgroups based upon the underlying disease pathogenesis as well as the type of causative agent. While the true prevalence of occupational rhinitis is unknown, there are certain professions and occupational exposures that place workers at a higher risk for developing the disease. Additionally, occupational rhinitis can be associated with occupational asthma and upper airway symptoms may precede those of the lower respiratory tract. Taken together, occupational rhinitis is an important disease for study given its medical as well as socioeconomic implications. This review will focus on the classification of occupational rhinitis as well the prevalence, diagnosis, and treatment strategies.

  17. Incentives and intrinsic motivation in healthcare

    Directory of Open Access Journals (Sweden)

    Mikel Berdud

    2016-11-01

    Conclusions: The conclusions could act as a guide to support the optimal design of incentive policies and schemes within health organisations when healthcare professionals are intrinsically motivated.

  18. Algebraic description of intrinsic modes in nuclei

    Energy Technology Data Exchange (ETDEWEB)

    Leviatan, A. (Los Alamos National Lab., NM (USA))

    1990-01-01

    We present a procedure for extracting normal modes in algebraic number-conserving systems of interacting bosons relevant for collective states in even-even nuclei. The Hamiltonian is resolved into intrinsic (bandhead related) and collective (in-band related) parts. Shape parameters are introduced through non-spherical boson bases. Intrinsic modes decoupled from the spurious modes are obtained from the intrinsic part of the Hamiltonian in the limit of large number of bosons. Intrinsic states are constructed and serve to evaluate electromagnetic transition rates. The method is illustrated for systems with one type of boson as well as with proton-neutron bosons. (author).

  19. Algebraic description of intrinsic modes in nuclei

    International Nuclear Information System (INIS)

    Leviatan, A.

    1990-01-01

    We present a procedure for extracting normal modes in algebraic number-conserving systems of interacting bosons relevant for collective states in even-even nuclei. The Hamiltonian is resolved into intrinsic (bandhead related) and collective (in-band related) parts. Shape parameters are introduced through non-spherical boson bases. Intrinsic modes decoupled from the spurious modes are obtained from the intrinsic part of the Hamiltonian in the limit of large number of bosons. Intrinsic states are constructed and serve to evaluate electromagnetic transition rates. The method is illustrated for systems with one type of boson as well as with proton-neutron bosons. (author)

  20. Dynamic recruitment of Ets1 to both nucleosome-occupied and -depleted enhancer regions mediates a transcriptional program switch during early T-cell differentiation

    Science.gov (United States)

    Cauchy, Pierre; Maqbool, Muhammad A.; Zacarias-Cabeza, Joaquin; Vanhille, Laurent; Koch, Frederic; Fenouil, Romain; Gut, Marta; Gut, Ivo; Santana, Maria A.; Griffon, Aurélien; Imbert, Jean; Moraes-Cabé, Carolina; Bories, Jean-Christophe; Ferrier, Pierre; Spicuglia, Salvatore; Andrau, Jean-Christophe

    2016-01-01

    Ets1 is a sequence-specific transcription factor that plays an important role during hematopoiesis, and is essential for the transition of CD4−/CD8− double negative (DN) to CD4+/CD8+ double positive (DP) thymocytes. Using genome-wide and functional approaches, we investigated the binding properties, transcriptional role and chromatin environment of Ets1 during this transition. We found that while Ets1 binding at distal sites was associated with active genes at both DN and DP stages, its enhancer activity was attained at the DP stage, as reflected by levels of the core transcriptional hallmarks H3K4me1/3, RNA Polymerase II and eRNA. This dual, stage-specific ability reflected a switch from non-T hematopoietic toward T-cell specific gene expression programs during the DN-to-DP transition, as indicated by transcriptome analyses of Ets1−/− thymic cells. Coincidentally, Ets1 associates more specifically with Runx1 in DN and with TCF1 in DP cells. We also provide evidence that Ets1 predominantly binds distal nucleosome-occupied regions in DN and nucleosome-depleted regions in DP. Finally and importantly, we demonstrate that Ets1 induces chromatin remodeling by displacing H3K4me1-marked nucleosomes. Our results thus provide an original model whereby the ability of a transcription factor to bind nucleosomal DNA changes during differentiation with consequences on its cognate enhancer activity. PMID:26673693

  1. High mobility group protein number17 cross-links primarily to histone H2A in the reconstituted HMG 17 - nucleosome core particle complex

    International Nuclear Information System (INIS)

    Cook, G.R.; Yau, P.; Yasuda, H.; Traut, R.R.; Bradbury, E.M.

    1986-01-01

    The neighbor relationship of lamb thymus High Mobility Group (HMG) protein 17 to native HeLa nucleosome core particle histones in the reconstituted complex has been studied. 125 I-labeled HMG 17 was cross-linking to core histones using the protein-protein cross-linking reagent 2-iminothiolane. Specific cross-linked products were separated on a two-dimensional Triton-acid-urea/SDS gel system, located by autoradiography, excised and quantified. Disulfide bonds in the cross links were then cleaved and the protein constituents were identified by SDS gel electrophoresis. HMG 17 cross-linked primarily to histone H2A while lower levels of cross-linking occurred between HMG 17 and the other histones. In contrast, cross-linking between two HMG 17 molecules bound on the same nucleosome was relatively rare. It is concluded that the same nucleosome was relatively rare. It is concluded that H2A comprises part of the HMG 17 binding site but that HMG 17 is sufficiently elongated and mobile to permit cross-linking to the other histones and to a second HMG 17 molecule. These results are in agreement with the current model for the structure of the nucleosome and the proposed binding sites for HMG 17

  2. Anti-dsDNA, anti-nucleosome and anti-C1q antibodies as disease activity markers in patients with systemic lupus erythematosus

    Directory of Open Access Journals (Sweden)

    Živković Valentina

    2014-01-01

    Full Text Available Introduction. In spite of the growing number of reports on the study of anti-nucleosome and anti-C1q antibodies, there are still controversies on their significance as disease activity markers in patients with systemic lupus erythematosus (SLE and their use in everyday clinical practice. Objective. Our aim was to assess the presence of anti-dsDNA, anti-nucleosome and anti-C1q antibodies in SLE patients, as well as to establish their sensitivity, specificity, positive and negative predictive value, and their correlation with SLE and lupus nephritis clinical activity. Methods. The study enrolled 85 patients aged 45.3±9.7 years on the average, with SLE of average duration 10.37±7.99 years, hospitalized at the Institute „Niška Banja“ during 2011, and 30 healthy individuals as controls. Disease activity was assessed using Systemic Lupus Erythematosus Disease Activity Index (SLEDAI. In all examinees the levels of anti-dsDNA, anti-nucleosome and anti-C1q antibodies were measured using the ELISA method with Alegria Test Strips Orgentec (Germany. Results. Patients with active lupus nephritis had a higher presence of anti-C1q antibodies and higher co-positivity of anti-dsDNA, anti-nucleosome, and anti-C1q antibodies compared to those with inactive lupus nephritis (77.77% vs. 21.74%; p<0.01. SLE patients with SLEDAI ≥11 had a higher presence of antinucleosome (93.75% vs. 64.15%; p<0.01 and anti-C1q antibodies (46.87% vs. 22.64%; p<0.05, as well as a higher mean level of anti-nucleosome antibodies (107.79±83.46 U/ml vs. 57.81±63.15 U/ml; p<0.05, compared to those with SLEDAI of 0-10. There was a positive correlation between the SLEDAI and the level of anti-dsDNA (r=0.290; p<0.01, anti-nucleosome (r=0.443; p<0.001, and anti-C1q antibodies (r=0.382; p<0.001. Only anti-C1q antibodies demonstrated correlation with proteinuria (r=0.445; p<0.001. Conclusion. Anti-nucleosome and anti-C1q antibodies demonstrated association with SLE and lupus nephritis

  3. Geochemical indicators of intrinsic bioremediation

    International Nuclear Information System (INIS)

    Borden, R.C.; Gomez, C.A.; Becker, M.T.

    1995-01-01

    A detailed field investigation has been completed at a gasoline-contaminated aquifer near Rocky Point, NC, to examine possible indicators of intrinsic bioremediation and identify factors that may significantly influence the rae and extent of bioremediation. The dissolved plume of benzene, toluene, ethylbenzene, and xylene (BTEX) in ground water is naturally degrading. Toluene and o-xylene are most rapidly degraded followed by m-, p-xylene, and benzene. Ethylbenzene appears to degrade very slowly under anaerobic conditions present in the center of the plume. The rate and extent of biodegradation appears to be strongly influenced by the type and quantity of electron acceptors present in the aquifer. At the upgradient edge of the plume, nitrate, ferric iron, and oxygen are used as terminal electron acceptors during hydrocarbon biodegradation. The equivalent of 40 to 50 mg/l of hydrocarbon is degraded based on the increase in dissolved CO 2 relative to background ground water. Immediately downgradient of the source area, sulfate and iron are the dominant electron acceptors. Toluene and o-xylene are rapidly removed in this region. Once the available oxygen, nitrate, and sulfate are consumed, biodegradation is limited and appears to be controlled by mixing and aerobic biodegradation at the plume fringes

  4. Protein intrinsic disorder in plants.

    Science.gov (United States)

    Pazos, Florencio; Pietrosemoli, Natalia; García-Martín, Juan A; Solano, Roberto

    2013-09-12

    To some extent contradicting the classical paradigm of the relationship between protein 3D structure and function, now it is clear that large portions of the proteomes, especially in higher organisms, lack a fixed structure and still perform very important functions. Proteins completely or partially unstructured in their native (functional) form are involved in key cellular processes underlain by complex networks of protein interactions. The intrinsic conformational flexibility of these disordered proteins allows them to bind multiple partners in transient interactions of high specificity and low affinity. In concordance, in plants this type of proteins has been found in processes requiring these complex and versatile interaction networks. These include transcription factor networks, where disordered proteins act as integrators of different signals or link different transcription factor subnetworks due to their ability to interact (in many cases simultaneously) with different partners. Similarly, they also serve as signal integrators in signaling cascades, such as those related to response to external stimuli. Disordered proteins have also been found in plants in many stress-response processes, acting as protein chaperones or protecting other cellular components and structures. In plants, it is especially important to have complex and versatile networks able to quickly and efficiently respond to changing environmental conditions since these organisms cannot escape and have no other choice than adapting to them. Consequently, protein disorder can play an especially important role in plants, providing them with a fast mechanism to obtain complex, interconnected and versatile molecular networks.

  5. Protein intrinsic disorder in plants

    Directory of Open Access Journals (Sweden)

    Florencio ePazos

    2013-09-01

    Full Text Available To some extent contradicting the classical paradigm of the relationship between protein 3D structure and function, now it is clear that large portions of the proteomes, especially in higher organisms, lack a fixed structure and still perform very important functions. Proteins completely or partially unstructured in their native (functional form are involved in key cellular processes underlain by complex networks of protein interactions. The intrinsic conformational flexibility of these disordered proteins allows them to bind multiple partners in transient interactions of high specificity and low affinity. In concordance, in plants this type of proteins has been found in processes requiring these complex and versatile interaction networks. These include transcription factor networks, where disordered proteins act as integrators of different signals or link different transcription factor subnetworks due to their ability to interact (in many cases simultaneously with different partners. Similarly, they also serve as signal integrators in signalling cascades, such as those related to response to external stimuli. Disordered proteins have also been found in plants in many stress-response processes, acting as protein chaperones or protecting other cellular components and structures. In plants, it is especially important to have complex and versatile networks able to quickly and efficiently respond to changing environmental conditions since these organisms can not escape and have no other choice than adapting to them. Consequently, protein disorder can play an especially important role in plants, providing them with a fast mechanism to obtain complex, interconnected and versatile molecular networks.

  6. Genome-Wide Mapping Targets of the Metazoan Chromatin Remodeling Factor NURF Reveals Nucleosome Remodeling at Enhancers, Core Promoters and Gene Insulators.

    Directory of Open Access Journals (Sweden)

    So Yeon Kwon

    2016-04-01

    Full Text Available NURF is a conserved higher eukaryotic ISWI-containing chromatin remodeling complex that catalyzes ATP-dependent nucleosome sliding. By sliding nucleosomes, NURF is able to alter chromatin dynamics to control transcription and genome organization. Previous biochemical and genetic analysis of the specificity-subunit of Drosophila NURF (Nurf301/Enhancer of Bithorax (E(bx has defined NURF as a critical regulator of homeotic, heat-shock and steroid-responsive gene transcription. It has been speculated that NURF controls pathway specific transcription by co-operating with sequence-specific transcription factors to remodel chromatin at dedicated enhancers. However, conclusive in vivo demonstration of this is lacking and precise regulatory elements targeted by NURF are poorly defined. To address this, we have generated a comprehensive map of in vivo NURF activity, using MNase-sequencing to determine at base pair resolution NURF target nucleosomes, and ChIP-sequencing to define sites of NURF recruitment. Our data show that, besides anticipated roles at enhancers, NURF interacts physically and functionally with the TRF2/DREF basal transcription factor to organize nucleosomes downstream of active promoters. Moreover, we detect NURF remodeling and recruitment at distal insulator sites, where NURF functionally interacts with and co-localizes with DREF and insulator proteins including CP190 to establish nucleosome-depleted domains. This insulator function of NURF is most apparent at subclasses of insulators that mark the boundaries of chromatin domains, where multiple insulator proteins co-associate. By visualizing the complete repertoire of in vivo NURF chromatin targets, our data provide new insights into how chromatin remodeling can control genome organization and regulatory interactions.

  7. LEADERSHIP STYLE AND EMPLOYEES' INTRINSIC JOB ...

    African Journals Online (AJOL)

    Abstract. This study investigates the impact of leadership style on employees' intrinsic job satisfaction in the Cross River State Newspaper Corporation, Calabar,. Nigeria. The study examined the problem of dissatisfaction in the work place as far as intrinsic factors of job satisfaction are concerned. Structured questionnaire ...

  8. Intrinsic bioremediation of landfills interim report

    International Nuclear Information System (INIS)

    Brigmon, R.L.; Fliermans, C.B.

    1997-01-01

    Intrinsic bioremediation is a risk management option that relies on natural biological and physical processes to contain the spread of contamination from a source. Evidence is presented in this report that intrinsic bioremediation is occurring at the Sanitary Landfill is fundamental to support incorportion into a Corrective Action Plan (CAP)

  9. Differential scanning microcalorimetry of intrinsically disordered proteins.

    Science.gov (United States)

    Permyakov, Sergei E

    2012-01-01

    Ultrasensitive differential scanning calorimetry (DSC) is an indispensable thermophysical technique enabling to get direct information on enthalpies accompanying heating/cooling of dilute biopolymer solutions. The thermal dependence of protein heat capacity extracted from DSC data is a valuable source of information on intrinsic disorder level of a protein. Application details and limitations of DSC technique in exploration of protein intrinsic disorder are described.

  10. Intrinsic bioremediation of landfills interim report

    Energy Technology Data Exchange (ETDEWEB)

    Brigmon, R.L. [Westinghouse Savannah River Company, Aiken, SC (United States); Fliermans, C.B.

    1997-07-14

    Intrinsic bioremediation is a risk management option that relies on natural biological and physical processes to contain the spread of contamination from a source. Evidence is presented in this report that intrinsic bioremediation is occurring at the Sanitary Landfill is fundamental to support incorportion into a Corrective Action Plan (CAP).

  11. An Intrinsic Coordinate System for Fingerprint Matching

    NARCIS (Netherlands)

    Bazen, A.M.; Gerez, Sabih H.; Bigun, J.; Smeraldi, F.

    2001-01-01

    In this paper, an intrinsic coordinate system is proposed for fingerprints. First the fingerprint is partitioned in regular regions, which are regions that contain no singular points. In each regular region, the intrinsic coordinate system is defined by the directional field. When using the

  12. Inference for occupancy and occupancy dynamics

    Science.gov (United States)

    O'Connell, Allan F.; Bailey, Larissa L.; O'Connell, Allan F.; Nichols, James D.; Karanth, K. Ullas

    2011-01-01

    This chapter deals with the estimation of occupancy as a state variable to assess the status of, and track changes in, species distributions when sampling with camera traps. Much of the recent interest in occupancy estimation and modeling originated from the models developed by MacKenzie et al. (2002, 2003), although similar methods were developed independently (Azuma et al. 1990; Bayley and Petersen 2001; Nichols and Karanth, 2002; Tyre et al. 2003), all of which deal with species occurrence information and imperfect detection. Less than a decade after these publications, the modeling and estimation of species occurrence and occupancy dynamics have increased significantly. Special features of scientific journals have explored innovative uses of detection–nondetection data with occupancy models (Vojta 2005), and an entire volume has synthesized the use and application of occupancy estimation methods (MacKenzie et al. 2006). Reviews of the topical concepts, philosophical considerations, and various sampling designs that can be used for occupancy estimation are now readily available for a range of audiences (MacKenzie and Royle 2005; MacKenzie et al. 2006; Bailey et al. 2007; Royle and Dorazio 2008; Conroy and Carroll 2009; Kendall and White 2009; Hines et al. 2010; Link and Barker 2010). As a result, it would be pointless here to recast all that these publications have so eloquently articulated, but that said, a review of any scientific topic requires sufficient context and relevant background information, especially when relatively new methodologies and techniques such as occupancy estimation and camera traps are involved. This is especially critical in a digital age where new information is published at warp speed, making it increasingly difficult to stay abreast of theoretical advances and research developments.

  13. The nucleosome (histone-DNA complex) is the TLR9-specific immunostimulatory component of Plasmodium falciparum that activates DCs.

    Science.gov (United States)

    Gowda, Nagaraj M; Wu, Xianzhu; Gowda, D Channe

    2011-01-01

    The systemic clinical symptoms of Plasmodium falciparum infection such as fever and chills correspond to the proinflammatory cytokines produced in response to the parasite components released during the synchronized rupture of schizonts. We recently demonstrated that, among the schizont-released products, merozoites are the predominant components that activate dendritic cells (DCs) by TLR9-specific recognition to induce the maturation of cells and to produce proinflammatory cytokines. We also demonstrated that DNA is the active constituent and that formation of a DNA-protein complex is essential for the entry of parasite DNA into cells for recognition by TLR9. However, the nature of endogenous protein-DNA complex in the parasite is not known. In this study, we show that parasite nucleosome constitute the major protein-DNA complex involved in the activation of DCs by parasite nuclear material. The parasite components were fractionated into the nuclear and non-nuclear materials. The nuclear material was further fractionated into chromatin and the proteins loosely bound to chromatin. Polynucleosomes and oligonucleosomes were prepared from the chromatin. These were tested for their ability to activate DCs obtained by the FLT3 ligand differentiation of bone marrow cells from the wild type, and TLR2(-/-), TLR9(-/-) and MyD88(-/-) mice. DCs stimulated with the nuclear material and polynucleosomes as well as mono- and oligonucleosomes efficiently induced the production of proinflammatory cytokines in a TLR9-dependent manner, demonstrating that nucleosomes (histone-DNA complex) represent the major TLR9-specific DC-immunostimulatory component of the malaria parasite nuclear material. Thus, our data provide a significant insight into the activation of DCs by malaria parasites and have important implications for malaria vaccine development.

  14. The nucleosome (histone-DNA complex is the TLR9-specific immunostimulatory component of Plasmodium falciparum that activates DCs.

    Directory of Open Access Journals (Sweden)

    Nagaraj M Gowda

    Full Text Available The systemic clinical symptoms of Plasmodium falciparum infection such as fever and chills correspond to the proinflammatory cytokines produced in response to the parasite components released during the synchronized rupture of schizonts. We recently demonstrated that, among the schizont-released products, merozoites are the predominant components that activate dendritic cells (DCs by TLR9-specific recognition to induce the maturation of cells and to produce proinflammatory cytokines. We also demonstrated that DNA is the active constituent and that formation of a DNA-protein complex is essential for the entry of parasite DNA into cells for recognition by TLR9. However, the nature of endogenous protein-DNA complex in the parasite is not known. In this study, we show that parasite nucleosome constitute the major protein-DNA complex involved in the activation of DCs by parasite nuclear material. The parasite components were fractionated into the nuclear and non-nuclear materials. The nuclear material was further fractionated into chromatin and the proteins loosely bound to chromatin. Polynucleosomes and oligonucleosomes were prepared from the chromatin. These were tested for their ability to activate DCs obtained by the FLT3 ligand differentiation of bone marrow cells from the wild type, and TLR2(-/-, TLR9(-/- and MyD88(-/- mice. DCs stimulated with the nuclear material and polynucleosomes as well as mono- and oligonucleosomes efficiently induced the production of proinflammatory cytokines in a TLR9-dependent manner, demonstrating that nucleosomes (histone-DNA complex represent the major TLR9-specific DC-immunostimulatory component of the malaria parasite nuclear material. Thus, our data provide a significant insight into the activation of DCs by malaria parasites and have important implications for malaria vaccine development.

  15. Outcomes of Occupational Self-Efficacy in Older Workers

    Science.gov (United States)

    Paggi, Michelle E.; Jopp, Daniela S.

    2016-01-01

    Because of the increasing number of older workers, it is important to develop models of work-related constructs for this population. The present article developed a model surrounding occupational self-efficacy, testing its relation to other factors (e.g., intrinsic job motivation), predictors (e.g., self-perceptions of aging), and outcomes (e.g., job satisfaction). Employed adults of ages 50 and older (n= 313) were recruited via organizations and social media sites. Study participants (M= 59.7, SD= 6.1, range = 50–78) volunteered to fill out an Internet survey. Occupational self-efficacy predicted job satisfaction, and intrinsic job motivation fully mediated this relationship. More negative self-perceptions of aging predicted poorer occupational self-efficacy. Occupational self-efficacy also predicted life satisfaction. Expected retirement age and job performance were unrelated to occupational self-efficacy. These findings may inform workplace interventions that seek to maintain or increase older worker job and life satisfaction. PMID:26394821

  16. Outcomes of Occupational Self-Efficacy in Older Workers.

    Science.gov (United States)

    Paggi, Michelle E; Jopp, Daniela S

    2015-04-01

    Because of the increasing number of older workers, it is important to develop models of work-related constructs for this population. The present article developed a model surrounding occupational self-efficacy, testing its relation to other factors (e.g., intrinsic job motivation), predictors (e.g., self-perceptions of aging), and outcomes (e.g., job satisfaction). Employed adults of ages 50 and older (n = 313) were recruited via organizations and social media sites. Study participants (M = 59.7, SD = 6.1, range = 50-78) volunteered to fill out an Internet survey. Occupational self-efficacy predicted job satisfaction, and intrinsic job motivation fully mediated this relationship. More negative self-perceptions of aging predicted poorer occupational self-efficacy. Occupational self-efficacy also predicted life satisfaction. Expected retirement age and job performance were unrelated to occupational self-efficacy. These findings may inform workplace interventions that seek to maintain or increase older worker job and life satisfaction. © The Author(s) 2015.

  17. Algebraic description of intrinsic modes in nuclei

    International Nuclear Information System (INIS)

    Leviatan, A.

    1989-01-01

    We present a procedure for extracting normal modes in algebraic number-conserving systems of interacting bosons relevant for collective states in even-even nuclei. The Hamiltonian is resolved into intrinsic (bandhead related) and collective (in-band related) parts. Shape parameters are introduced through non-spherical boson bases. Intrinsic modes decoupled from the spurious modes are obtained from the intinsic part of the Hamiltonian in the limit of large number of bosons. Intrinsic states are constructed and serve to evaluate electromagnetic transition rates. The method is illustrated for systems with one type of boson as well as with proton-neutron bosons. 28 refs., 1 fig

  18. Algebraic description of intrinsic modes in nuclei

    Energy Technology Data Exchange (ETDEWEB)

    Leviatan, A.

    1989-01-01

    We present a procedure for extracting normal modes in algebraic number-conserving systems of interacting bosons relevant for collective states in even-even nuclei. The Hamiltonian is resolved into intrinsic (bandhead related) and collective (in-band related) parts. Shape parameters are introduced through non-spherical boson bases. Intrinsic modes decoupled from the spurious modes are obtained from the intinsic part of the Hamiltonian in the limit of large number of bosons. Intrinsic states are constructed and serve to evaluate electromagnetic transition rates. The method is illustrated for systems with one type of boson as well as with proton-neutron bosons. 28 refs., 1 fig.

  19. Arabidopsis ATRX Modulates H3.3 Occupancy and Fine-Tunes Gene Expression

    KAUST Repository

    Duc, Céline

    2017-07-07

    Histones are essential components of the nucleosome, the major chromatin subunit that structures linear DNA molecules and regulates access of other proteins to DNA. Specific histone chaperone complexes control the correct deposition of canonical histones and their variants to modulate nucleosome structure and stability. In this study, we characterize the Arabidopsis Alpha Thalassemia-mental Retardation X-linked (ATRX) ortholog and show that ATRX is involved in histone H3 deposition. Arabidopsis ATRX mutant alleles are viable, but show developmental defects and reduced fertility. Their combination with mutants of the histone H3.3 chaperone HIRA (Histone Regulator A) results in impaired plant survival, suggesting that HIRA and ATRX function in complementary histone deposition pathways. Indeed, ATRX loss of function alters cellular histone H3.3 pools and in consequence modulates the H3.1/H3.3 balance in the cell. H3.3 levels are affected especially at genes characterized by elevated H3.3 occupancy, including the 45S ribosomal DNA (45S rDNA) loci, where loss of ATRX results in altered expression of specific 45S rDNA sequence variants. At the genome-wide scale, our data indicate that ATRX modifies gene expression concomitantly to H3.3 deposition at a set of genes characterized both by elevated H3.3 occupancy and high expression. Altogether, our results show that ATRX is involved in H3.3 deposition and emphasize the role of histone chaperones in adjusting genome expression.

  20. Dimensions of Occupational Prestige

    Science.gov (United States)

    Haug, Marie R.; Widdison, Harold A.

    1975-01-01

    Eight dimensions of occupational prestige are examined for their effect on the general prestige ratings accorded various occupations within the medical profession. Stepwise multiple regression analyzes the relative weight of these dimension among 410 persons. The findings suggested that public stereotypes exert a normative pressure on individual…

  1. Leadership and Occupational Stress

    Science.gov (United States)

    Stickle, Fred E.; Scott, Kelly

    2016-01-01

    In a leadership position, it is important to understand what stress is and how it affects others. In an occupational setting, stressors vary according to personality types, gender, and occupational rank. The purpose of this manuscript is to review the foundations of stress and to explore how personality characteristics influence stress.…

  2. The Heath Occupational Model.

    Science.gov (United States)

    Heath, William E.

    1990-01-01

    Career development programs must identify occupational needs of adults. A model based on Maslow's hierarchy develops occupational questions related to individual motivations (physiology, safety, love, esteem, and self-actualization). Individual needs are then compared with characteristics and benefits of proposed jobs, companies, or careers. (SK)

  3. CAUSES OF OCCUPATIONAL INJURIES

    NARCIS (Netherlands)

    KINGMA, J

    1994-01-01

    The causes of occupational injuries (N = 2,365) were investigated. Accidents with machinery and hand tools were the two main causes (49.9%). 89% of the patients with occupational injuries were male. The highest risk group were in the age category of 19 years or less (51.9%). This age group also

  4. Occupational skin diseases

    DEFF Research Database (Denmark)

    Mahler, V; Aalto-Korte, K; Alfonso, J H

    2017-01-01

    in Science and Technology (COST) Action TD 1206 (StanDerm) (www.standerm.eu). RESULTS: Besides a national health service or a statutory health insurance, most European member states implemented a second insurance scheme specifically geared at occupational diseases [insurance against occupational risks......BACKGROUND: Work-related skin diseases (WSD) are caused or worsened by a professional activity. Occupational skin diseases (OSD) need to fulfil additional legal criteria which differ from country to country. OSD range amongst the five most frequently notified occupational diseases (musculoskeletal...... diseases, neurologic diseases, lung diseases, diseases of the sensory organs, skin diseases) in Europe. OBJECTIVE: To retrieve information and compare the current state of national frameworks and pathways to manage patients with occupational skin disease with regard to prevention, diagnosis, treatment...

  5. Occupational stress among dentists

    DEFF Research Database (Denmark)

    Moore, Rod

    2011-01-01

    Dentists report a high degree of occupational stress.(Cooper, Mallinger, and Kahn, 1978;Coster, Carstens, and Harris, 1987;DiMatteo, Shugars, and Hays, 1993;Hakeberg et al., 1992;Möller and Spangenberg, 1996;Moore, 2000;Myers and Myers, 2004;O'Shea, Corah, and Ayer, 1984) This chapter reviews...... the literature of studies that elaborate on the circumstances of occupational stress of dentists. These will include the frequency of occurrence of occupational stress among dentists in several countries, frequency and intensity of identified stressors specific to dentistry, as well as the consequences...... of this occupational stress. The literature on consequences includes effects on dentists' physical health, personal and occupational performance, including "burnout" phenomena, as well as topics of alcohol or substance abuse and reports of suicidal behaviour among dentists. One specific and less conventionally...

  6. Occupational medicine and toxicology

    Directory of Open Access Journals (Sweden)

    Fischer Axel

    2006-02-01

    Full Text Available Abstract This editorial is to announce the Journal of Occupational Medicine and Toxicology, a new Open Access, peer-reviewed, online journal published by BioMed Central. Occupational medicine and toxicology belong to the most wide ranging disciplines of all medical specialties. The field is devoted to the diagnosis, prevention, management and scientific analysis of diseases from the fields of occupational and environmental medicine and toxicology. It also covers the promotion of occupational and environmental health. The complexity of modern industrial processes has dramatically changed over the past years and today's areas include effects of atmospheric pollution, carcinogenesis, biological monitoring, ergonomics, epidemiology, product safety and health promotion. We hope that the launch of the Journal of Occupational Medicine and Toxicology will aid in the advance of these important areas of research bringing together multi-disciplinary research findings.

  7. The Occupations of Literacy: Occupational Therapy's Role

    Science.gov (United States)

    Frolek Clark, Gloria

    2016-01-01

    Nationally, student proficiency in reading and writing is very low and requires ongoing focus from state and local agencies. With almost 25% of occupational therapists working in early intervention and school settings (AOTA, 2015), their role of facilitating literacy (e.g., reading, writing, speaking and listening) is critical. Occupational…

  8. Intrinsic endometriosis of ureter: a case report

    International Nuclear Information System (INIS)

    Hong, Myung Sun; Kim, Ho Chul; Yun, Ku Sup; Choi, Chul Soon; Bae, Sang Hoon; Kim, Sung Yong; Shin, Hyung Sik

    1995-01-01

    Endometriosis is a rare cause of an ureteral obstruction. We report a case of intrinsic ureteral endometriosis resulting in severe hydroureteronephrosis. The diagnosis of ureteral endometriosis may be considered in women with flank pain and ureteric obstruction within true pelvis

  9. The Intrinsic Dynamics of Psychological Process

    NARCIS (Netherlands)

    Vallacher, Robin R.; van Geert, Paul; Nowak, Andrzej

    2015-01-01

    Psychological processes unfold on various timescales in accord with internally generated patterns. The intrinsic dynamism of psychological process is difficult to investigate using traditional methods emphasizing cause–effect relations, however, and therefore is rarely incorporated into social

  10. Deuterium NMR, induced and intrinsic cholesteric lyomesophases

    International Nuclear Information System (INIS)

    Alcantara, M.R.

    1982-01-01

    Induced and intrinsic cholesteric lyotropic mesophases were studied. Induced cholesteric lyomesophases based on potassium laurate (KL) system, with small amounts of cholesterol added, were studied by deuterium NMR and by polarizing microscopy. Order profiles obtained from deuterium NMR of KL perdenderated chains in both induced cholesteric and normal mesophases were compared. The intrinsic cholesteric lyotropic mesophases were based on the amphiphile potassium N-lauroyl serinate (KLNS) in the resolved levo form. The study of the type I intrinsic cholesteric mesophase was made by optical microscopy under polarized light and the type II intrinsic cholesteric lyomesophase was characterized by deuterium NMR. The new texture was explained by the use of the theory of disclinations developed for thermotropic liquid crystals, specially for cholesteric type. (M.J.C.) [pt

  11. Intrinsic and acquired resistance mechanisms in enterococcus

    Science.gov (United States)

    Hollenbeck, Brian L.; Rice, Louis B.

    2012-01-01

    Enterococci have the potential for resistance to virtually all clinically useful antibiotics. Their emergence as important nosocomial pathogens has coincided with increased expression of antimicrobial resistance by members of the genus. The mechanisms underlying antibiotic resistance in enterococci may be intrinsic to the species or acquired through mutation of intrinsic genes or horizontal exchange of genetic material encoding resistance determinants. This paper reviews the antibiotic resistance mechanisms in Enterococcus faecium and Enterococcus faecalis and discusses treatment options. PMID:23076243

  12. The intrinsic resistome of bacterial pathogens

    Directory of Open Access Journals (Sweden)

    Jorge Andrés Olivares Pacheco

    2013-04-01

    Full Text Available Intrinsically resistant bacteria have emerged as a relevant health problem in the last years. Those bacterial species, several of them with an environmental origin, present naturally a low-level susceptibility to several drugs. It has been proposed that intrinsic resistance is mainly the consequence of the impermeability of cellular envelopes, the activity of multidrug efflux pumps or the lack of appropriate targets for a given family of drugs. However, recently published articles indicate that the characteristic phenotype of susceptibility to antibiotics of a given bacterial species depends on the concerted activity of several elements, what has been named as intrinsic resistome. These determinants comprise not just classical resistance genes. Other elements, several of them involved in basic bacterial metabolic processes, are of relevance for the intrinsic resistance of bacterial pathogens. In the present review we analyse recent publications on the intrinsic resistomes of Escherichia coli and Pseudomonas aeruginosa. We present as well information on the role that global regulators of bacterial metabolism, as Crc from P. aeruginosa, may have on modulating bacterial susceptibility to antibiotics. Finally, we discuss the possibility of searching inhibitors of the intrinsic resistome in the aim of improving the activity of drugs currently in use for clinical practice.

  13. Incentives and intrinsic motivation in healthcare.

    Science.gov (United States)

    Berdud, Mikel; Cabasés, Juan M; Nieto, Jorge

    It has been established in the literature that workers within public organisations are intrinsically motivated. This paper is an empirical study of the healthcare sector using methods of qualitative analysis research, which aims to answer the following hypotheses: 1) doctors are intrinsically motivated; 2) economic incentives and control policies may undermine doctors' intrinsic motivation; and 3) well-designed incentives may encourage doctors' intrinsic motivation. We conducted semi-structured interviews à-la-Bewley with 16 doctors from Navarre's Healthcare Service (Servicio Navarro de Salud-Osasunbidea), Spain. The questions were based on current theories of intrinsic motivation and incentives to test the hypotheses. Interviewees were allowed to respond openly without time constraints. Relevant information was selected, quantified and analysed by using the qualitative concepts of saturation and codification. The results seem to confirm the hypotheses. Evidence supporting hypotheses 1 and 2 was gathered from all interviewees, as well as indications of the validity of hypothesis 3 based on interviewees' proposals of incentives. The conclusions could act as a guide to support the optimal design of incentive policies and schemes within health organisations when healthcare professionals are intrinsically motivated. Copyright © 2016 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.

  14. BURNOUT AND OCCUPATIONAL PARTICIPATION

    Science.gov (United States)

    Eren, Hakan; Huri, Meral; Bağış, Nilsun; Başıbüyük, Onur; Şahin, Sedef; Umaroğlu, Mutlu; Orhan, Kaan

    2016-11-01

    The aim of the present study was to investigate the prevalence of burnout and occupational participation limitation among dental students in a dental school in Turkey. Four hundred fifty-eight dental students (females=153; males=305) were included in the study. The age range varied from 17-to-38 years. Maslach Burnout Inventory-Student Version (MBI-SV) and Canadian Occupational Performance Measure (COPM) were used to gather data. Descriptive analyses, t-test, and Kruskall-Wallis test for independent groups were used for data analyses. The results indicated that 26% of all the students have burnout in terms of emotional exhaustion (25%), cynicism (18%), and academic efficacy (14%). The results showed that burnout is statistically significant in relation to demographics (pstudents showed considerably decreased occupational performance and satisfaction scores, which suggested occupational participation limitations. Occupational performance and satisfaction scores were inversely correlated with emotional exhaustion and cynicism, while directly correlated with reduced academic efficacy (pburnout and occupational participation limitation can be seen among dental students. Students with burnout may also have occupational participation limitation. Enriching dental education programs with different psychological strategies may be useful for education of healthy dentists and improve the quality of oral and dental health services.

  15. The interplay between polymerase organization and nucleosome occupancy along DNA : How dynamic roadblocks on the DNA induce the formation of RNA polymerase pelotons

    NARCIS (Netherlands)

    van den Berg, A.A.

    2017-01-01

    During transcription RNA polymerase (RNAP) moves along a DNA molecule to copy the information on the DNA to an RNA molecule. Many textbook pictures show an RNAP sliding along empty DNA, but in reality it is crowded on the DNA and RNAP competes for space with many proteins such as other RNAP’s and

  16. Occupational Mortality, Background on

    DEFF Research Database (Denmark)

    Lynge, Elsebeth

    2016-01-01

    in England and Wales from 1851 to 1979–1983, and these studies have provided key data on social inequalities in health. Death certificate studies have been used for identification of occupational groups with high excess risks from specific diseases. Follow-up studies require linkage of individual records......The study of occupational mortality involves the systematic tabulation of mortality by occupational or socioeconomic groups. Three main methods are used to conduct these studies: cross-sectional studies, death certificate studies, and follow-up studies. Cross-sectional studies were undertaken...

  17. Expanding the Functionality of Speech Recognition in Radiology: Creating a Real-Time Methodology for Measurement and Analysis of Occupational Stress and Fatigue

    OpenAIRE

    Reiner, Bruce I.

    2012-01-01

    While occupational stress and fatigue have been well described throughout medicine, the radiology community is particularly susceptible due to declining reimbursements, heightened demands for service deliverables, and increasing exam volume and complexity. The resulting occupational stress can be variable in nature and dependent upon a number of intrinsic and extrinsic stressors. Intrinsic stressors largely account for inter-radiologist stress variability and relate to unique attributes of th...

  18. Radiation risk due to occupational exposure

    International Nuclear Information System (INIS)

    Kargbo, A.A

    2012-04-01

    Exposure to ionizing radiation occurs in many occupations. Workers can be exposed to both natural and artificial sources of radiation. Any exposure to ionizing radiation incurs some risk, either to the individual or to the individual's progeny. This dissertation investigated the radiation risk due to occupational exposure in industrial radiography. Analysis of the reported risk estimates to occupational exposure contained in the UNSCEAR report of 2008 in industrial radiography practice was done. The causes of accidents in industrial radiography include: Lack of or inadequate regulatory control, inadequate training, failure to follow operational procedures, human error, equipment malfunction or defect, inadequate maintenance and wilful violation have been identified as primary causes of accidents. To minimise radiation risks in industrial radiography exposure devices and facilities should be designed such that there is intrinsic safety and operational safety ensured by establishing a quality assurance programme, safety culture fostered and maintained among all workers, industrial radiography is performed in compliance with approved local rules, workers engaged have appropriate qualifications and training, available safe operational procedures are followed, a means is provided for detecting incidents and accidents and an analysis of the causes and lessons learned. (author)

  19. Occupational Respiratory Disease

    Science.gov (United States)

    ... time, and duration. A list of previous jobs, hobbies, and smoking habits, if any. Completed occupational health ... Disease Surveillance Last Updated: March 3, 2017 This article was contributed by: familydoctor.org editorial staff Categories: ...

  20. Occupational health in Malaysia.

    Science.gov (United States)

    Rampal, Krishna Gopal; Aw, Tar-Ching; Jefferelli, Shamsul Bahrin

    2002-01-01

    This article provides a detailed examination of Malaysian occupational health agencies and their roles in formulating and enforcing standards, promoting occupational health and safety (OSH), and providing advisory services. Available OSH training is described, and the need for policies and personnel in various industries is outlined. Further, the authors discuss how international models and collaboration have influenced Malaysian OSH, and how some successes can be repeated and failures remedied.

  1. Occupancy in continuous habitat

    Science.gov (United States)

    Efford, Murray G.; Dawson, Deanna K.

    2012-01-01

    The probability that a site has at least one individual of a species ('occupancy') has come to be widely used as a state variable for animal population monitoring. The available statistical theory for estimation when detection is imperfect applies particularly to habitat patches or islands, although it is also used for arbitrary plots in continuous habitat. The probability that such a plot is occupied depends on plot size and home-range characteristics (size, shape and dispersion) as well as population density. Plot size is critical to the definition of occupancy as a state variable, but clear advice on plot size is missing from the literature on the design of occupancy studies. We describe models for the effects of varying plot size and home-range size on expected occupancy. Temporal, spatial, and species variation in average home-range size is to be expected, but information on home ranges is difficult to retrieve from species presence/absence data collected in occupancy studies. The effect of variable home-range size is negligible when plots are very large (>100 x area of home range), but large plots pose practical problems. At the other extreme, sampling of 'point' plots with cameras or other passive detectors allows the true 'proportion of area occupied' to be estimated. However, this measure equally reflects home-range size and density, and is of doubtful value for population monitoring or cross-species comparisons. Plot size is ill-defined and variable in occupancy studies that detect animals at unknown distances, the commonest example being unlimited-radius point counts of song birds. We also find that plot size is ill-defined in recent treatments of "multi-scale" occupancy; the respective scales are better interpreted as temporal (instantaneous and asymptotic) rather than spatial. Occupancy is an inadequate metric for population monitoring when it is confounded with home-range size or detection distance.

  2. Occupational health in Mexico.

    Science.gov (United States)

    Carreón, Tania; Santos-Burgoa, Carlos; Baron, Sherry; Hernández, Sendy

    2002-01-01

    The authors discuss the maquiladoras and child labor, and offer an overview of the history of occupational safety and health in Mexico that covers laws and regulations, social security, unions, and enforcement of legislation. The organization and structure of the various institutions responsible for occupational safety and health (OSH), as well as administrative procedures, are described. This article concludes with a list of the new challenges for OSH in Mexico.

  3. Occupational exposures. Annex H

    International Nuclear Information System (INIS)

    1982-01-01

    This Annex focuses on significant changes in the pattern of occupational exposure which have appeared since the 1972 and 1962 reports, and presents information on trends or particular causes of high exposures. A further objective is to clarify the reasons for which the Committee requires data on occupational exposure, and to suggest areas in which better data collection or analysis may be performed. Data are also reviewed on accidents involving the exposure of workers to substantial radiation doses.

  4. Occupational stressors in nursing

    Directory of Open Access Journals (Sweden)

    N. Nikpeyma

    2009-04-01

    Full Text Available Background and aimsNursing provides a wide range of potential workplace stressors as it is  a profession that requires a high level of skill, teamworking in a variety of situations and provision  of 24-hour delivery of care .Occupational stress is a major factor of Staff sickness an  absenteeism.This study investigates the main occupational stressors in nursing profession in the  hope of identification and reducing it.MethodsIn this study a questionnaire consisting of three parts:demoghraphic data,the nurses  background and questions about occupational stress from Revised index fulfilled by 140 nurses.ResultsLack of reward for work well done(48/6%, Heavy workload(46/4% ,lack of Participation in decisions (39/3% , poor Control of work place(38/4%and lack of job  development (36/4% have been the main sources of Occupational stress for nurses.chronic  diseases, Night Shift working and working hours were positively associated with occupstional  stress.Conclusion Analysis indicated that effects of work factors on occupational stress are more than demoghraphic data. The findings of this study can assist health service organisations to provide an attractive working climate in order to decrease side effects and consequences of occupational stress. Furthermore, understanding this situation can help to develop coping strategies in order to reduce work-related stress.

  5. Occupational Experience, Mobility, and Wages

    DEFF Research Database (Denmark)

    Groes, Fane

    In this paper we present how occupational tenure relates to wage growth and occupational mobility in Danish data. We show that the Danish data produces qualitatively similar results as found in U.S. data with respect to an increase in average wages when experience in an occupation increases. In a...... also is true for workers switching occupation and rm. After ve years of experience in an occupation the average probability of switching any type of occupation, including occupation and rm switches, has fallen from 25% to 12%....

  6. The Relationship Between Burnout and Occupational Stress in Genetic Counselors.

    Science.gov (United States)

    Johnstone, Brittney; Kaiser, Amy; Injeyan, Marie C; Sappleton, Karen; Chitayat, David; Stephens, Derek; Shuman, Cheryl

    2016-08-01

    Burnout represents a critical disruption in an individual's relationship with work, resulting in a state of exhaustion in which one's occupational value and capacity to perform are questioned. Burnout can negatively affect an individual's personal life, as well as employers in terms of decreased work quality, patient/client satisfaction, and employee retention. Occupational stress is a known contributor to burnout and occurs as a result of employment requirements and factors intrinsic to the work environment. Empirical research examining genetic counselor-specific burnout is limited; however, existing data suggests that genetic counselors are at increased risk for burnout. To investigate the relationship between occupational stress and burnout in genetic counselors, we administered an online survey to members of three genetic counselor professional organizations. Validated measures included the Maslach Burnout Inventory-General Survey (an instrument measuring burnout on three subscales: exhaustion, cynicism, and professional efficacy) and the Occupational Stress Inventory-Revised (an instrument measuring occupational stress on 14 subscales). Of the 353 respondents, more than 40 % had either considered leaving or left their job role due to burnout. Multiple regression analysis yielded significant predictors for burnout risk. The identified sets of predictors account for approximately 59 % of the variance in exhaustion, 58 % of the variance in cynicism, and 43 % of the variance in professional efficacy. Our data confirm that a significant number of genetic counselors experience burnout and that burnout is correlated with specific aspects of occupational stress. Based on these findings, practice and research recommendations are presented.

  7. Population Health and Occupational Therapy.

    Science.gov (United States)

    Braveman, Brent

    2016-01-01

    Occupational therapy practitioners play an important role in improving the health of populations through the development of occupational therapy interventions at the population level and through advocacy to address occupational participation and the multiple determinants of health. This article defines and explores population health as a concept and describes the appropriateness of occupational therapy practice in population health. Support of population health practice as evidenced in the official documents of the American Occupational Therapy Association and the relevance of population health for occupational therapy as a profession are reviewed. Recommendations and directions for the future are included related to celebration of the achievements of occupational therapy practitioners in the area of population health, changes to the Occupational Therapy Practice Framework and educational accreditation standards, and the importance of supporting, recognizing, rewarding, and valuing occupational therapy practitioners who assume roles in which direct care is not their primary function. Copyright © 2016 by the American Occupational Therapy Association, Inc.

  8. Functions of intrinsic disorder in transmembrane proteins

    DEFF Research Database (Denmark)

    Kjaergaard, Magnus; Kragelund, Birthe B.

    2017-01-01

    mechanisms. (3) Trafficking of membrane proteins. (4) Transient membrane associations. (5) Post-translational modifications most notably phosphorylation and (6) disorder-linked isoform dependent function. We finish the review by discussing the future challenges facing the membrane protein community regarding......Intrinsic disorder is common in integral membrane proteins, particularly in the intracellular domains. Despite this observation, these domains are not always recognized as being disordered. In this review, we will discuss the biological functions of intrinsically disordered regions of membrane...... proteins, and address why the flexibility afforded by disorder is mechanistically important. Intrinsically disordered regions are present in many common classes of membrane proteins including ion channels and transporters; G-protein coupled receptors (GPCRs), receptor tyrosine kinases and cytokine...

  9. Management Control, Intrinsic Motivation and Creativity

    DEFF Research Database (Denmark)

    Godt Gregersen, Mikkel

    of the conclusion is that intrinsic motivation and management control can coexist under the conditions that all three basic needs, i.e. autonomy, competence and relatedness, are supported. This can happen when control takes point of departure in the individual employee. The second part of the conclusion......This thesis consists of a cape and three papers. The overall research question is: How can intrinsic motivation and management control coexist in a creative environment and how can coordination be possible in such a context? The cape ties together the research done in the three papers....... It is divided into six sections. The first section introduces the concepts of intrinsic motivation, creativity and management control. This is followed by a section on management control in a creative context. These two sections frame the thesis and introduce the setting in which the research has been done...

  10. Cell intrinsic control of axon regeneration

    Science.gov (United States)

    Mar, Fernando M; Bonni, Azad; Sousa, Mónica M

    2014-01-01

    Although neurons execute a cell intrinsic program of axonal growth during development, following the establishment of connections, the developmental growth capacity declines. Besides environmental challenges, this switch largely accounts for the failure of adult central nervous system (CNS) axons to regenerate. Here, we discuss the cell intrinsic control of axon regeneration, including not only the regulation of transcriptional and epigenetic mechanisms, but also the modulation of local protein translation, retrograde and anterograde axonal transport, and microtubule dynamics. We further explore the causes underlying the failure of CNS neurons to mount a vigorous regenerative response, and the paradigms demonstrating the activation of cell intrinsic axon growth programs. Finally, we present potential mechanisms to support axon regeneration, as these may represent future therapeutic approaches to promote recovery following CNS injury and disease. PMID:24531721

  11. Insulin aggregation tracked by its intrinsic TRES

    Science.gov (United States)

    Chung, Li Hung C.; Birch, David J. S.; Vyshemirsky, Vladislav; Ryadnov, Maxim G.; Rolinski, Olaf J.

    2017-12-01

    Time-resolved emission spectra (TRES) have been used to detect conformational changes of intrinsic tyrosines within bovine insulin at a physiological pH. The approach offers the ability to detect the initial stages of insulin aggregation at the molecular level. The data analysis has revealed the existence of at least three fluorescent species undergoing dielectric relaxation and significant spectral changes due to insulin aggregation. The results indicate the suitability of the intrinsic TRES approach for insulin studies and for monitoring its stability during storage and aggregation in insulin delivery devices.

  12. Intrinsic viscosity of a suspension of cubes

    KAUST Repository

    Mallavajula, Rajesh K.

    2013-11-06

    We report on the viscosity of a dilute suspension of cube-shaped particles. Irrespective of the particle size, size distribution, and surface chemistry, we find empirically that cubes manifest an intrinsic viscosity [η]=3.1±0.2, which is substantially higher than the well-known value for spheres, [η]=2.5. The orientation-dependent intrinsic viscosity of cubic particles is determined theoretically using a finite-element solution of the Stokes equations. For isotropically oriented cubes, these calculations show [η]=3.1, in excellent agreement with our experimental observations. © 2013 American Physical Society.

  13. Intrinsic entropy perturbations from the dark sector

    Science.gov (United States)

    Celoria, Marco; Comelli, Denis; Pilo, Luigi

    2018-03-01

    Perfect fluids are modeled by using an effective field theory approach which naturally gives a self-consistent and unambiguous description of the intrinsic non-adiabatic contribution to pressure variations. We study the impact of intrinsic entropy perturbation on the superhorizon dynamics of the curvature perturbation Script R in the dark sector. The dark sector, made of dark matter and dark energy is described as a single perfect fluid. The non-perturbative vorticity's dynamics and the Weinberg theorem violation for perfect fluids are also studied.

  14. A model of intrinsic symmetry breaking

    International Nuclear Information System (INIS)

    Ge, Li; Li, Sheng; George, Thomas F.; Sun, Xin

    2013-01-01

    Different from the symmetry breaking associated with a phase transition, which occurs when the controlling parameter is manipulated across a critical point, the symmetry breaking presented in this Letter does not need parameter manipulation. Instead, the system itself suddenly undergoes symmetry breaking at a certain time during its evolution, which is intrinsic symmetry breaking. Through a polymer model, it is revealed that the origin of the intrinsic symmetry breaking is nonlinearity, which produces instability at the instance when the evolution crosses an inflexion point, where this instability breaks the original symmetry

  15. Interaction of nucleosome assembly proteins abolishes nuclear localization of DGK{zeta} by attenuating its association with importins

    Energy Technology Data Exchange (ETDEWEB)

    Okada, Masashi; Hozumi, Yasukazu [Department of Anatomy and Cell Biology, Yamagata University School of Medicine, Yamagata 990-9585 (Japan); Ichimura, Tohru [Department of Chemistry, Graduate School of Sciences and Engineering, Tokyo Metropolitan University, Hachioji 192-0397 (Japan); Tanaka, Toshiaki; Hasegawa, Hiroshi; Yamamoto, Masakazu; Takahashi, Nobuya [Department of Anatomy and Cell Biology, Yamagata University School of Medicine, Yamagata 990-9585 (Japan); Iseki, Ken [Department of Emergency and Critical Care Medicine, Yamagata University School of Medicine, Yamagata 990-9585 (Japan); Yagisawa, Hitoshi [Laboratory of Biological Signaling, Graduate School of Life Science, University of Hyogo, Hyogo 678-1297 (Japan); Shinkawa, Takashi; Isobe, Toshiaki [Department of Chemistry, Graduate School of Sciences and Engineering, Tokyo Metropolitan University, Hachioji 192-0397 (Japan); Goto, Kaoru, E-mail: kgoto@med.id.yamagata-u.ac.jp [Department of Anatomy and Cell Biology, Yamagata University School of Medicine, Yamagata 990-9585 (Japan)

    2011-12-10

    Diacylglycerol kinase (DGK) is involved in the regulation of lipid-mediated signal transduction through the metabolism of a second messenger diacylglycerol. Of the DGK family, DGK{zeta}, which contains a nuclear localization signal, localizes mainly to the nucleus but translocates to the cytoplasm under pathological conditions. However, the detailed mechanism of translocation and its functional significance remain unclear. To elucidate these issues, we used a proteomic approach to search for protein targets that interact with DGK{zeta}. Results show that nucleosome assembly protein (NAP) 1-like 1 (NAP1L1) and NAP1-like 4 (NAP1L4) are identified as novel DGK{zeta} binding partners. NAP1Ls constitutively shuttle between the nucleus and the cytoplasm in transfected HEK293 cells. The molecular interaction of DGK{zeta} and NAP1Ls prohibits nuclear import of DGK{zeta} because binding of NAP1Ls to DGK{zeta} blocks import carrier proteins, Qip1 and NPI1, to interact with DGK{zeta}, leading to cytoplasmic tethering of DGK{zeta}. In addition, overexpression of NAP1Ls exerts a protective effect against doxorubicin-induced cytotoxicity. These findings suggest that NAP1Ls are involved in a novel molecular basis for the regulation of nucleocytoplasmic shuttling of DGK{zeta} and provide a clue to examine functional significance of its translocation under pathological conditions.

  16. Splice variants of the SWR1-type nucleosome remodeling factor Domino have distinct functions during Drosophila melanogaster oogenesis.

    Science.gov (United States)

    Börner, Kenneth; Becker, Peter B

    2016-09-01

    SWR1-type nucleosome remodeling factors replace histone H2A by variants to endow chromatin locally with specialized functionality. In Drosophila melanogaster a single H2A variant, H2A.V, combines functions of mammalian H2A.Z and H2A.X in transcription regulation and the DNA damage response. A major role in H2A.V incorporation for the only SWR1-like enzyme in flies, Domino, is assumed but not well documented in vivo. It is also unclear whether the two alternatively spliced isoforms, DOM-A and DOM-B, have redundant or specialized functions. Loss of both DOM isoforms compromises oogenesis, causing female sterility. We systematically explored roles of the two DOM isoforms during oogenesis using a cell type-specific knockdown approach. Despite their ubiquitous expression, DOM-A and DOM-B have non-redundant functions in germline and soma for egg formation. We show that chromatin incorporation of H2A.V in germline and somatic cells depends on DOM-B, whereas global incorporation in endoreplicating germline nurse cells appears to be independent of DOM. By contrast, DOM-A promotes the removal of H2A.V from stage 5 nurse cells. Remarkably, therefore, the two DOM isoforms have distinct functions in cell type-specific development and H2A.V exchange. © 2016. Published by The Company of Biologists Ltd.

  17. Structural Architecture of the Nucleosome Remodeler ISWI Determined from Cross-Linking, Mass Spectrometry, SAXS, and Modeling.

    Science.gov (United States)

    Harrer, Nadine; Schindler, Christina E M; Bruetzel, Linda K; Forné, Ignasi; Ludwigsen, Johanna; Imhof, Axel; Zacharias, Martin; Lipfert, Jan; Mueller-Planitz, Felix

    2018-02-06

    Chromatin remodeling factors assume critical roles by regulating access to nucleosomal DNA. To determine the architecture of the Drosophila ISWI remodeling enzyme, we developed an integrative structural approach that combines protein cross-linking, mass spectrometry, small-angle X-ray scattering, and computational modeling. The resulting structural model shows the ATPase module in a resting state with both ATPase lobes twisted against each other, providing support for a conformation that was recently trapped by crystallography. The autoinhibiting NegC region does not protrude from the ATPase module as suggested previously. The regulatory NTR domain is located near both ATPase lobes. The full-length enzyme is flexible and can adopt a compact structure in solution with the C-terminal HSS domain packing against the ATPase module. Our data imply a series of conformational changes upon activation of the enzyme and illustrate how the NTR, NegC, and HSS domains contribute to regulation of the ATPase module. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Transcription factor 19 interacts with histone 3 lysine 4 trimethylation and controls gluconeogenesis via the nucleosome-remodeling-deacetylase complex.

    Science.gov (United States)

    Sen, Sabyasachi; Sanyal, Sulagna; Srivastava, Dushyant Kumar; Dasgupta, Dipak; Roy, Siddhartha; Das, Chandrima

    2017-12-15

    Transcription factor 19 (TCF19) has been reported as a type 1 diabetes-associated locus involved in maintenance of pancreatic β cells through a fine-tuned regulation of cell proliferation and apoptosis. TCF19 also exhibits genomic association with type 2 diabetes, although the precise molecular mechanism remains unknown. It harbors both a plant homeodomain and a forkhead-associated domain implicated in epigenetic recognition and gene regulation, a phenomenon that has remained unexplored. Here, we show that TCF19 selectively interacts with histone 3 lysine 4 trimethylation through its plant homeodomain finger. Knocking down TCF19 under high-glucose conditions affected many metabolic processes, including gluconeogenesis. We found that TCF19 overexpression represses de novo glucose production in HepG2 cells. The transcriptional repression of key genes, induced by TCF19, coincided with NuRD (nucleosome-remodeling-deacetylase) complex recruitment to the promoters of these genes. TCF19 interacted with CHD4 (chromodomain helicase DNA-binding protein 4), which is a part of the NuRD complex, in a glucose concentration-independent manner. In summary, our results show that TCF19 interacts with an active transcription mark and recruits a co-repressor complex to regulate gluconeogenic gene expression in HepG2 cells. Our study offers critical insights into the molecular mechanisms of transcriptional regulation of gluconeogenesis and into the roles of chromatin readers in metabolic homeostasis. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. Occupational health, cognitive disorders and occupational neuropsychology

    Directory of Open Access Journals (Sweden)

    Leonardo Caixeta

    Full Text Available ABSTRACT Work can be an important etiologic factor in the genesis of some mental disorders including cognitive disability. Occupational neuropsychology constitutes an intriguing new but neglected area of research and clinical practice which deals with the neurocognitive consequences of the work environment and work habits. Neuropsychological knowledge is fundamental to understand cognitive requirements of work competence. Work can impact sleep patterns and mental energy, which in turn can cause neuropsychological symptoms. This report presents relevant evidence to illustrate the relationship between work and cognitive dysfunction.

  20. Enabling occupation: occupation-based and client centred practice in Occupational Therapy

    OpenAIRE

    Tatiana Barcelos Pontes; Helene Polatajko

    2016-01-01

    Occupational therapists have always been dedicated to the human occupation study, however the client hasn’t always been seen as an occupational being, with needs, interests and individual goals. The concern for our clients’ engagement in occupation, rather than the acquisition or restoration of performance components, together with the gradual modification of the concept of occupation from work-related activities to purposeful human activity, requires a broadening of our scope of ...

  1. OCCUPATIONAL EXPOSURE AND COPD

    DEFF Research Database (Denmark)

    Würtz, Else Toft

    Chronic Obstructive Pulmonary Disease (COPD) is a common disease. The main risk factor is smoking although 15% of the COPD cases are expected to be preventable if the occupational exposures from vapour, gas, dust, and fume were eliminated; the population attributable fraction (PAF). The thesis ad...... an impact on the development of COPD ought to be transformed to preventive efforts to eliminate occupational COPD and improve public health.......Chronic Obstructive Pulmonary Disease (COPD) is a common disease. The main risk factor is smoking although 15% of the COPD cases are expected to be preventable if the occupational exposures from vapour, gas, dust, and fume were eliminated; the population attributable fraction (PAF). The thesis...... addresses the association between occupational exposure and COPD in a population-based cohort of Danes aged 45-84-years. 4717 participants were included at baseline and 2624 at the four year follow-up. COPD was defined by spirometry and the occupational exposure was based on specialist defined jobs...

  2. Zoonoses as occupational diseases

    Directory of Open Access Journals (Sweden)

    Giorgio Battelli

    2008-12-01

    Full Text Available Zoonoses are discussed as occupational diseases, with special reference to animal husbandry and related activities. After quoting some historical references, occupational zoonoses are examined in relation to the evolution of the concept of occupational zoonosis, the involvement of the World Health Organization in this field, their socio-economic significance, the principal working activities, zoonoses of greatest importance (with special reference to the Mediterranean region, the evaluation of damage and risks. An outline is made of the transmission of zoonoses from farm workers to animals and the biological hazards from the environment. The present situation of occupational zoonoses and related risks in industrialised and traditional farming activities are presented and the importance of some emerging and re-emerging zoonoses for the health of workers is highlighted. The author concludes by stressing that the prevention of occupational zoonoses must be implemented jointly by both veterinary and medical services through preventive measures and epidemiological surveillance of human and animal health, risk evaluation, diagnosis of infections and prompt reporting. It is hoped that the future will offer better inter-disciplinary collaboration and that legislation will be timely and better tailored to safeguard working health and safety.

  3. Occupational health in Argentina.

    Science.gov (United States)

    Werner, A F

    2000-07-01

    Argentina is within the denominated "new industrialised countries", with the characteristic of having high contrasts in the urban population, based on service and industry, and in the rural population, based on agriculture and cattle, still the main sources of wealth in the country. The process of globalisation and the need to compete hard in international markets have provoked high unemployment and the transfer of workers from a formal market to an informal one. Legislation on occupational health is old and it is in the process of being updated. The system of prevention, assistance and compensation for accidents at work and for occupational illnesses has changed from being optative for employers, to the compulsory hiring of private insurance companies. The Government keeps the role of supervisor of the system. There are enough professionals in occupational health, hygiene and safety but not occupational nurses. The teaching is given by many universities and professional associations, some of which have an active profile in the occupational health of the country.

  4. Predictors of employment in schizophrenia: The importance of intrinsic and extrinsic motivation.

    Science.gov (United States)

    Reddy, L Felice; Llerena, Katiah; Kern, Robert S

    2016-10-01

    Unemployment is a primary functional deficit for the majority of adults with schizophrenia. Research indicates that over two-thirds of adults living in the community with schizophrenia are unemployed. Despite effective programs to assist with job identification and placement, the ability to attain and maintain employment remains a pressing concern. A contributing factor that may be relevant but has received little attention in the work rehabilitation literature is motivation. People with schizophrenia show marked deficits in both intrinsic and extrinsic motivation but these deficits have not been directly examined in relation to work outcomes. The present study sought to examine the relationship between intrinsic and extrinsic motivation and work outcome among a sample of 65 adults with schizophrenia enrolled in a supported employment program. One-third of the participants in the study obtained work. Intrinsic motivation related to valuing and feeling useful in a work role significantly predicted who would obtain employment. Extrinsic motivation related to gaining rewards and avoiding obstacles showed a non-significant trend-level relationship such that workers had higher extrinsic motivation than nonworkers. These findings highlight the importance of considering both intrinsic and extrinsic motivation in work-related interventions and supported employment for individuals with schizophrenia. The results are discussed in terms of clinical implications for improving rehabilitation and occupational outcomes in schizophrenia. Published by Elsevier B.V.

  5. Frustration-induced protein intrinsic disorder.

    Science.gov (United States)

    Matsushita, Katsuyoshi; Kikuchi, Macoto

    2013-03-14

    Spontaneous folding into a specific native structure is the most important property of protein to perform their biological functions within organisms. Spontaneous folding is understood on the basis of an energy landscape picture based on the minimum frustration principle. Therefore, frustration seemingly only leads to protein functional disorder. However, frustration has recently been suggested to have a function in allosteric regulation. Functional frustration has the possibility to be a key to our deeper understanding of protein function. To explore another functional frustration, we theoretically examined structural frustration, which is designed to induce intrinsic disorder of a protein and its function through the coupled folding and binding. We extended the Wako-Saitô-Muñoz-Eaton model to take into account a frustration effect. With the model, we analyzed the binding part of neuron-restrictive silencer factor and showed that designed structural frustration in it induces intrinsic disorder. Furthermore, we showed that the folding and the binding are cooperative in interacting with a target protein. The cooperativity enables an intrinsically disordered protein to exhibit a sharp switch-like folding response to binding chemical potential change. Through this switch-like response, the structural frustration may contribute to the regulation function of interprotein interaction of the intrinsically disordered protein.

  6. Simple intrinsic defects in InAs :

    Energy Technology Data Exchange (ETDEWEB)

    Schultz, Peter Andrew

    2013-03-01

    This Report presents numerical tables summarizing properties of intrinsic defects in indium arsenide, InAs, as computed by density functional theory using semi-local density functionals, intended for use as reference tables for a defect physics package in device models.

  7. INTRINSIC AND EXTRINSIC MOTIVATION IN THE SELECTION ...

    African Journals Online (AJOL)

    A psychological perspective is considered that applies intrinsic and extrinsic motivational concepts to communication phenomena. The paper also tries to develop an analytical understanding of human communication-related behavior with respect to the two types of motives. Proposals are also put forward to communication ...

  8. Intrinsic and Extrinsic Motivation among Collegiate Instrumentalists

    Science.gov (United States)

    Diaz, Frank M.

    2010-01-01

    The purpose of this study was to gather and compare information on measures of intrinsic and extrinsic motivation among instrumentalists enrolled in collegiate ensembles. A survey instrument was developed to gather information concerning demographic data and responses to questions on motivational preference. Participants were undergraduate and…

  9. A rotational integral formula for intrinsic volumes

    DEFF Research Database (Denmark)

    Jensen, Eva Bjørn Vedel; Rataj, J.

    2008-01-01

    A rotational version of the famous Crofton formula is derived. The motivation for deriving the formula comes from local stereology, a new branch of stereology based on sections through fixed reference points. The formula shows how rotational averages of intrinsic volumes measured on sections...

  10. Original Paper Detecting Nosocomial Intrinsic Infections through ...

    African Journals Online (AJOL)

    2011-04-20

    Apr 20, 2011 ... Key Words: Bacterial pathogens, Endogenous indicators, NosocomiaI infection, Surgery. Received 30 October 2010/ Accepted 30 March 2011. INTRODUCTION. Micro-organisms from intrinsic and extrinsic sources have been known to cause nosocomial infections (CDC, 1991). The human body enables.

  11. Organisational Learning and Employees' Intrinsic Motivation

    Science.gov (United States)

    Remedios, Richard; Boreham, Nick

    2004-01-01

    This study examined the effects of organisational learning initiatives on employee motivation. Four initiatives consistent with theories of organisational learning were a priori ranked in terms of concepts that underpin intrinsic-motivation theory. Eighteen employees in a UK petrochemical company were interviewed to ascertain their experiences of…

  12. Intrinsic Motivation, Organizational Justice, and Creativity

    Science.gov (United States)

    Hannam, Kalli; Narayan, Anupama

    2015-01-01

    For employees to generate creative ideas that are not only original, but also useful to their company, they must interact with their workplace environment to determine organizational needs. Therefore, it is important to consider aspects of the individual as well as their environment when studying creativity. Intrinsic motivation, a predictor of…

  13. Discovery of Intrinsic Primitives on Triangle Meshes

    KAUST Repository

    Solomon, Justin

    2011-04-01

    The discovery of meaningful parts of a shape is required for many geometry processing applications, such as parameterization, shape correspondence, and animation. It is natural to consider primitives such as spheres, cylinders and cones as the building blocks of shapes, and thus to discover parts by fitting such primitives to a given surface. This approach, however, will break down if primitive parts have undergone almost-isometric deformations, as is the case, for example, for articulated human models. We suggest that parts can be discovered instead by finding intrinsic primitives, which we define as parts that posses an approximate intrinsic symmetry. We employ the recently-developed method of computing discrete approximate Killing vector fields (AKVFs) to discover intrinsic primitives by investigating the relationship between the AKVFs of a composite object and the AKVFs of its parts. We show how to leverage this relationship with a standard clustering method to extract k intrinsic primitives and remaining asymmetric parts of a shape for a given k. We demonstrate the value of this approach for identifying the prominent symmetry generators of the parts of a given shape. Additionally, we show how our method can be modified slightly to segment an entire surface without marking asymmetric connecting regions and compare this approach to state-of-the-art methods using the Princeton Segmentation Benchmark. © 2011 The Author(s).

  14. Importance of electrostatic interactions in the association of intrinsically disordered histone chaperone Chz1 and histone H2A.Z-H2B.

    Directory of Open Access Journals (Sweden)

    Xiakun Chu

    Full Text Available Histone chaperones facilitate assembly and disassembly of nucleosomes. Understanding the process of how histone chaperones associate and dissociate from the histones can help clarify their roles in chromosome metabolism. Some histone chaperones are intrinsically disordered proteins (IDPs. Recent studies of IDPs revealed that the recognition of the biomolecules is realized by the flexibility and dynamics, challenging the century-old structure-function paradigm. Here we investigate the binding between intrinsically disordered chaperone Chz1 and histone variant H2A.Z-H2B by developing a structure-based coarse-grained model, in which Debye-Hückel model is implemented for describing electrostatic interactions due to highly charged characteristic of Chz1 and H2A.Z-H2B. We find that major structural changes of Chz1 only occur after the rate-limiting electrostatic dominant transition state and Chz1 undergoes folding coupled binding through two parallel pathways. Interestingly, although the electrostatic interactions stabilize bound complex and facilitate the recognition at first stage, the rate for formation of the complex is not always accelerated due to slow escape of conformations with non-native electrostatic interactions at low salt concentrations. Our studies provide an ionic-strength-controlled binding/folding mechanism, leading to a cooperative mechanism of "local collapse or trapping" and "fly-casting" together and a new understanding of the roles of electrostatic interactions in IDPs' binding.

  15. Occupants' window opening behaviour

    DEFF Research Database (Denmark)

    Fabi, Valentina; Andersen, Rune Korsholm; Corgnati, Stefano

    2012-01-01

    systems is proposed, based on studies presented in literature and a general process leading to the effects on energy consumptions is identified.Existing studies on the topic of window opening behaviour are highlighted and a theoretical framework to deal with occupants' interactions with building controls......, aimed at improving or maintaining the preferred indoor environmental conditions, is elaborated. This approach is used to look into the drivers for the actions taken by the occupants (windows opening and closing) and to investigate the existing models in literature of these actions for both residential...... and office buildings. The analysis of the literature highlights how a shared approach on identifying the driving forces for occupants' window opening and closing behaviour has not yet been reached. However, the reporting of variables found not to be drivers may reveal contradictions in the obtained results...

  16. Marketing occupational therapy services.

    Science.gov (United States)

    Kautzmann, L N

    1985-01-01

    The ability to understand and appropriately apply business skills is a key component in the development of a successful private practice. Marketing is one of the business skills occupational therapists need to have in order to take full advantage of the opportunities available to entrepeneurs in the health care industry. The purpose of this article is to present a structured approach to marketing occupational therapy services through the use of a marketing plan. The four components of a marketing plan, a situation analysis, the identification of problems, opportunities, and target markets, the development of a marketing strategy for each targeted market, and a method to monitor the plan, are discussed. Applications to occupational therapy practice are suggested. The use of a marketing plan as a method for organizing and focusing marketing efforts is an effective means of supporting and enhancing the development of a private practice.

  17. Miscarriage and occupational activity

    DEFF Research Database (Denmark)

    Bonde, Jens Peter; Jørgensen, Kristian Tore; Bonzini, Matteo

    2013-01-01

    . METHODS: A search in Medline and EMBASE 1966-2012 identified 30 primary papers reporting the relative risk (RR) of miscarriage according to ≥1 of 5 occupational activities of interest. Following an assessment of completeness of reporting, confounding, and bias, each risk estimate was characterized as more......, N=10). RR for working hours and standing became smaller when analyses were restricted to higher quality studies. CONCLUSIONS: These largely reassuring findings do not provide a strong case for mandatory restrictions in relation to shift work, long working hours, occupational lifting, standing...

  18. Identifying the neural substrates of intrinsic motivation during task performance.

    Science.gov (United States)

    Lee, Woogul; Reeve, Johnmarshall

    2017-10-01

    Intrinsic motivation is the inherent tendency to seek out novelty and challenge, to explore and investigate, and to stretch and extend one's capacities. When people imagine performing intrinsically motivating tasks, they show heightened anterior insular cortex (AIC) activity. To fully explain the neural system of intrinsic motivation, however, requires assessing neural activity while people actually perform intrinsically motivating tasks (i.e., while answering curiosity-inducing questions or solving competence-enabling anagrams). Using event-related functional magnetic resonance imaging, we found that the neural system of intrinsic motivation involves not only AIC activity, but also striatum activity and, further, AIC-striatum functional interactions. These findings suggest that subjective feelings of intrinsic satisfaction (associated with AIC activations), reward processing (associated with striatum activations), and their interactions underlie the actual experience of intrinsic motivation. These neural findings are consistent with the conceptualization of intrinsic motivation as the pursuit and satisfaction of subjective feelings (interest and enjoyment) as intrinsic rewards.

  19. Occupational Orientation: Business, Marketing and Management Occupations. Experimental Curriculum Materials.

    Science.gov (United States)

    Illinois State Office of Education, Springfield.

    These experimental curriculum materials for one of five clusters developed for the occupational orientation program in Illinois include a series of learning activity packages (LAPs) designed to acquaint the student with the wide range of occupational choices available in the business, marketing, and management occupations field. The 31 LAPs, each…

  20. Occupant Controlled Lighting

    DEFF Research Database (Denmark)

    Logadóttir, Ásta

    2011-01-01

    preferences for correlated colour temperature (CCT). The results suggest that the method of adjustment, previously used in the lighting literature, is not adequate to generalize about occupant preferences for illuminance or CCT. Factors that influence occupants’ lighting preference when applying the method...

  1. Coping With Occupational Stress.

    Science.gov (United States)

    O'Brien, Dianne Boswell

    1981-01-01

    Ways of reducing occupational stress include: (1) avoiding the stressful situation; (2) changing the response to the stress; and (3) changing the environment. Administrators can help teachers manage stress by developing communication techniques, steering committees, and support groups. A second part of this article will be published in the January…

  2. Hospitality Occupations. Curriculum Guide.

    Science.gov (United States)

    California State Dept. of Education, Sacramento. Bureau of Homemaking Education.

    This curriculum guide on the hospitality occupations was developed to help secondary and postsecondary home economics teachers prepare individuals for entry-level jobs in the hospitality industry. The content is in seven sections. The first section presents organizational charts of a medium-size hotel, food and beverage division, housekeeping and…

  3. Predicting occupational lung diseases

    NARCIS (Netherlands)

    Suarthana, E.

    2008-01-01

    This thesis aims at demonstrating the development, validation, and application of prediction models for occupational lung diseases. Prediction models are developed to estimate an individual’s probability of the presence or future likelihood of occurrence of an outcome (i.e. disease of interest or

  4. The Structural Location of DNA Lesions in Nucleosome Core Particles Determines Accessibility by Base Excision Repair Enzymes*

    Science.gov (United States)

    Rodriguez, Yesenia; Smerdon, Michael J.

    2013-01-01

    Packaging of DNA into chromatin affects accessibility of DNA regulatory factors involved in transcription, replication, and repair. Evidence suggests that even in the nucleosome core particle (NCP), accessibility to damaged DNA is hindered by the presence of the histone octamer. Base excision repair is the major pathway in mammalian cells responsible for correcting a large number of chemically modified bases. We have measured the repair of site-specific uracil and single nucleotide gaps along the surface of the NCP. Our results indicate that removal of DNA lesions is greatly dependent on their rotational and translational positioning in NCPs. Significantly, the rate of uracil removal with outwardly oriented DNA backbones is 2–10-fold higher than those with inwardly oriented backbones. In general, uracils with inwardly oriented backbones farther away from the dyad center of the NCP are more accessible than those near the dyad. The translational positioning of outwardly oriented gaps is the key factor driving gap filling activity. An outwardly oriented gap near the DNA ends exhibits a 3-fold increase in gap filling activity as compared with one near the dyad with the same rotational orientation. Near the dyad, uracil DNA glycosylase/APE1 removes an outwardly oriented uracil efficiently; however, polymerase β activity is significantly inhibited at this site. These data suggest that the hindrance presented by the location of a DNA lesion is dependent on the structural requirements for enzyme catalysis. Therefore, remodeling at DNA damage sites in NCPs is critical for preventing accumulation of aborted intermediates and ensuring completion of base excision repair. PMID:23543741

  5. Vaccination with a plasmid DNA cocktail encoding the nucleosomal histones of Leishmania confers protection against murine cutaneous leishmaniosis.

    Science.gov (United States)

    Iborra, Salvador; Soto, Manuel; Carrión, Javier; Alonso, Carlos; Requena, Jose M

    2004-09-28

    Leishmania histones are relevant immunogens for the host immune system during both Leishmania infection and disease. In the present paper we have evaluated the prophylactic value of the four Leishmania infantum histones forming the nucleosomal core in the murine model of cutaneous leishmaniasis. In a first stage, the immune response elicited by the intramuscular injection of a mixture of four plasmid DNAs, encoding the L. infantum histones H2A, H2B, H3 and H4, was determined in BALB/c mice. It was found that the immunized animals developed a specific Th1 immune response, which was associated with an antigen-specific production of interferon (IFN-gamma) and a limited humoral response against histones (dominated by antibodies of the IgG2a isotype). According to the pure Th1-type immune response elicited by the DNA vaccination with Leishmania histones, vaccinated mice showed a solid immunity that efficiently controlled the Leishmania major infection. The protection in mice vaccinated with histone-DNAs was associated with a low humoral response against leishmanial antigens, an enhanced IFN-gamma production and little, if any, IL-4 production. The relative contribution of both CD8(+) and CD4(+) T cells to the IFN-gamma production, and the IL-12 dependence were also evaluated. All these data indicated that DNA vaccination with Leishmania histones genes results in a specific Th1-like response during L. major infection, and that both CD4(+) and CD8(+) T cells contribute to the resistance of vaccinated mice to cutaneous leishmaniasis.

  6. A T9G mutation in the prototype TATA-box TCACTATATATAG determines nucleosome formation and synergy with upstream activator sequences in plant promoters.

    Science.gov (United States)

    Ranjan, Amol; Ansari, Suraiya A; Srivastava, Rakesh; Mantri, Shrikant; Asif, Mehar H; Sawant, Samir V; Tuli, Rakesh

    2009-12-01

    We had earlier reported that mutations to G and C at the seventh and eighth positions in the prototype TATA-box TCACTATATATAG inhibited light-dependent activation of transcription from the promoter. In this study, we characterized mutations at the ninth position of the prototype TATA-box. Substitution of T at the ninth position with G or C enhanced transcription from the promoter in transgenic tobacco (Nicotiana tabacum) plants. The effect of T9G/C mutations was not light dependent, although the 9G/C TATA-box showed synergy with the light-responsive element (lre). However, the 9G/C mutants in the presence of lre failed to respond to phytochromes, sugar, and calcium signaling, in contrast to the prototype TATA-box with lre. The 9G/C mutation shifted the point of initiation of transcription, and transcription activation was dependent upon the type of activating element present upstream. The synergy in activation was noticed with lre and legumin activators but not with rbcS, Pcec, and PR-1a activators. The 9G mutation resulted in a micrococcal nuclease-sensitive region over the TATA-box, suggesting a nucleosome-free region, in contrast to the prototype promoter, which had a distinct nucleosome on the TATA-box. Thus, the transcriptional augmentation with mutation at the ninth position might be because of the loss of a repressive nucleosomal structure on the TATA-box. In agreement with our findings, the promoters containing TATAGATA as identified by genome-wide analysis of Arabidopsis (Arabidopsis thaliana) are not tightly repressed.

  7. Occupational Therapy's Role with Autism

    Science.gov (United States)

    Fact Sheet Occupational Therapy’s Role with Autism Autism is a lifelong condition associated with a varied course from early childhood through adulthood. Occupational therapy practitioners are distinctly qualified to ...

  8. Occupational causes of male infertility

    DEFF Research Database (Denmark)

    Bonde, Jens P E

    2013-01-01

    To highlight and discuss the new evidence on occupational and environmental risk to male reproductive function.......To highlight and discuss the new evidence on occupational and environmental risk to male reproductive function....

  9. Mission Critical Occupation (MCO) Charts

    Data.gov (United States)

    Office of Personnel Management — Agencies report resource data and targets for government-wide mission critical occupations and agency specific mission critical and/or high risk occupations. These...

  10. Intrinsic Motivation in Open Source Software Development

    DEFF Research Database (Denmark)

    Bitzer, J.; W., Schrettl,; Schröder, Philipp

    2004-01-01

    This papers sheds light on the puzzling evidence that even though open source software (OSS) is a public good, it is developed for free by highly qualified, young and motivated individuals, and evolves at a rapid pace. We show that once OSS development is understood as the private provision...... of a public good, these features emerge quite naturally. We adapt a dynamic private-provision-of-public-goods model to reflects key aspects of the OSS phenomenon. In particular, instead of relying on extrinsic motives for programmers (e.g. signaling) the present model is driven by intrinsic motives of OSS...... programmers, such as user-programmers, play value or \\emph{homo ludens} payoff, and gift culture benefits. Such intrinsic motives feature extensively in the wider OSS literature and turn out to add new insights to the economic analysis....

  11. Does Aerobic Exercise Influence Intrinsic Brain Activity?

    DEFF Research Database (Denmark)

    Flodin, Pär; Jonasson, Lars S; Riklund, Katrin

    2017-01-01

    Previous studies have indicated that aerobic exercise could reduce age related decline in cognition and brain functioning. Here we investigated the effects of aerobic exercise on intrinsic brain activity. Sixty sedentary healthy males and females (64-78 years) were randomized into either an aerobic...... exercise group or an active control group. Both groups recieved supervised training, 3 days a week for 6 months. Multimodal brain imaging data was acquired before and after the intervention, including 10 min of resting state brain functional magnetic resonance imaging (rs-fMRI) and arterial spin labeling...... group improved more. Contrary to our hypothesis, we did not observe any significant group by time interactions with regard to any measure of intrinsic activity. To further probe putative relationships between fitness and brain activity, we performed post hoc analyses disregarding group belongings...

  12. Documentation Requirements, Intrinsic Motivation, and Worker Absence

    DEFF Research Database (Denmark)

    Andersen, Lotte Bøgh; Kristensen, Nicolai; Pedersen, Lene Holm

    2015-01-01

    Command systems are widely used to monitor public service provision, but little is known about unintended effects on individual workers’ motivation and work effort. Using insights from motivation crowding theory, we estimate a SEM model that captures how Danish childcare assistants and social...... and higher sickness absence. The association is statistically significant, but very small in substantive terms. The result is nevertheless consistent with the expectation in motivation crowding theory and contributes to the literature by including a new, reliable behavioral variable—sickness absence....../healthcare assistants perceive documentation requirements. We analyze how this perception relates to intrinsic motivation measured in a survey and sickness absence as reported in administrative registers, and find that individuals who perceive documentation requirements as controlling have lower intrinsic motivation...

  13. Extrinsic and intrinsic determinants of nerve regeneration

    Directory of Open Access Journals (Sweden)

    Toby A. Ferguson

    2011-01-01

    Full Text Available After central nervous system (CNS injury axons fail to regenerate often leading to persistent neurologic deficit although injured peripheral nervous system (PNS axons mount a robust regenerative response that may lead to functional recovery. Some of the failures of CNS regeneration arise from the many glial-based inhibitory molecules found in the injured CNS, whereas the intrinsic regenerative potential of some CNS neurons is actively curtailed during CNS maturation and limited after injury. In this review, the molecular basis for extrinsic and intrinsic modulation of axon regeneration within the nervous system is evaluated. A more complete understanding of the factors limiting axonal regeneration will provide a rational basis, which is used to develop improved treatments for nervous system injury.

  14. Radiation protection in occupational health

    International Nuclear Information System (INIS)

    1987-01-01

    The document is a training manual for physicians entering the field of occupational medicine for radiation workers. Part 1 contains the general principles for the practice of occupational health, namely health surveillance and the role of the occupational physician in the workplace, and Part 2 provides the essential facts necessary to understand the basic principles of radiation physics, radiobiology, dosimetry and radiation effects which form the basis for occupational radiation health

  15. Occupational chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Omland, Oyvind; Würtz, Else Toft; Aasen, Tor Børvig

    2014-01-01

    Occupational-attributable chronic obstructive pulmonary disease (COPD) presents a substantial health challenge. Focusing on spirometric criteria for airflow obstruction, this review of occupational COPD includes both population-wide and industry-specific exposures.......Occupational-attributable chronic obstructive pulmonary disease (COPD) presents a substantial health challenge. Focusing on spirometric criteria for airflow obstruction, this review of occupational COPD includes both population-wide and industry-specific exposures....

  16. Intrinsic point defects in aluminum antimonide

    OpenAIRE

    Åberg, Daniel; Erhart, Paul; Williamson, Andrew J.; Lordi, Vincenzo

    2010-01-01

    Calculations within density functional theory on the basis of the local density approximation are carried out to study the properties of intrinsic point defects in aluminum antimonide. Special care is taken to address finite-size effects, band gap error, and symmetry reduction in the defect structures. The correction of the band gap is based on a set of GW calculations. The most important defects are identified to be the aluminum interstitial $Al_{i,Al}^{1+}$, the antimony antisites $Sb_{Al}^...

  17. Intrinsic luminescence of alkali silicate glasses

    Energy Technology Data Exchange (ETDEWEB)

    Arbuzov, V.I.; Grabovskis, V.Y.; Tolstoi, M.N.; Vitol, I.K.

    1986-09-01

    This study obtains additional information on L centers and their role in electron excitation and intrinsic luminescence of a whole series. (Li, Na, K, Rb, and Cs) of alkali silicate glasses. The authors compare the features of the interaction with radiation of specimens of glass and crystal of a similar chemical composition, since silicates of alkali metals can be obtained in both the glassy and crystalline states.

  18. Intrinsic work motivation and pension reform acceptance

    OpenAIRE

    Heinemann, Friedrich; Hennighausen, Tanja; Moessinger, Marc-Daniel

    2011-01-01

    Although demographic change leaves pay-as-you-go pension systems unsustainable, reforms, such as a higher pension age, are highly unpopular. This contribution looks into the role of intrinsic motivation as a driver for pension reform acceptance. Theoretical reasoning suggests that this driver should be relevant: The choice among different pension reform options (increasing pension age, increasing contributions, cutting pensions) can be analyzed within the framework of an optimal job separatio...

  19. A structural model of intrinsic motivation

    OpenAIRE

    Aguilar, Javier; González, Daniel; Aguilar, Amira

    2017-01-01

    The main purpose of this research was to develop and test a structural model of intrinsic motivation among students of the University of Sonora to the curriculum of their careers. A secondary objective was to overcome the limitations of the model developed among students of the UNAM. Eight psychometric scales developed by the authors in previous studies were used, which showed satisfactory reliability and validity values. The model tested was similar to the sample of the UNAM, except for the ...

  20. Genome-wide analysis of H3.3 dissociation reveals high nucleosome turnover at distal regulatory regions of embryonic stem cells.

    Science.gov (United States)

    Ha, Misook; Kraushaar, Daniel C; Zhao, Keji

    2014-01-01

    The histone variant H3.3 plays a critical role in maintaining the pluripotency of embryonic stem cells (ESCs) by regulating gene expression programs important for lineage specification. H3.3 is deposited by various chaperones at regulatory sites, gene bodies, and certain heterochromatic sites such as telomeres and centromeres. Using Tet-inhibited expression of epitope-tagged H3.3 combined with ChIP-Seq we undertook genome-wide measurements of H3.3 dissociation rates across the ESC genome and examined the relationship between H3.3-nucleosome turnover and ESC-specific transcription factors, chromatin modifiers, and epigenetic marks. Our comprehensive analysis of H3.3 dissociation rates revealed distinct H3.3 dissociation dynamics at various functional chromatin domains. At transcription start sites, H3.3 dissociates rapidly with the highest rate at nucleosome-depleted regions (NDRs) just upstream of Pol II binding, followed by low H3.3 dissociation rates across gene bodies. H3.3 turnover at transcription start sites, gene bodies, and transcription end sites was positively correlated with transcriptional activity. H3.3 is found decorated with various histone modifications that regulate transcription and maintain chromatin integrity. We find greatly varying H3.3 dissociation rates across various histone modification domains: high dissociation rates at active histone marks and low dissociation rates at heterochromatic marks. Well- defined zones of high H3.3-nucleosome turnover were detected at binding sites of ESC-specific pluripotency factors and chromatin remodelers, suggesting an important role for H3.3 in facilitating protein binding. Among transcription factor binding sites we detected higher H3.3 turnover at distal cis-acting sites compared to proximal genic transcription factor binding sites. Our results imply that fast H3.3 dissociation is a hallmark of interactions between DNA and transcriptional regulators. Our study demonstrates that H3.3 turnover and

  1. Moral Distress, Workplace Health, and Intrinsic Harm.

    Science.gov (United States)

    Weber, Elijah

    2016-05-01

    Moral distress is now being recognized as a frequent experience for many health care providers, and there's good evidence that it has a negative impact on the health care work environment. However, contemporary discussions of moral distress have several problems. First, they tend to rely on inadequate characterizations of moral distress. As a result, subsequent investigations regarding the frequency and consequences of moral distress often proceed without a clear understanding of the phenomenon being discussed, and thereby risk substantially misrepresenting the nature, frequency, and possible consequences of moral distress. These discussions also minimize the intrinsically harmful aspects of moral distress. This is a serious omission. Moral distress doesn't just have a negative impact on the health care work environment; it also directly harms the one who experiences it. In this paper, I claim that these problems can be addressed by first clarifying our understanding of moral distress, and then identifying what makes moral distress intrinsically harmful. I begin by identifying three common mistakes that characterizations of moral distress tend to make, and explaining why these mistakes are problematic. Next, I offer an account of moral distress that avoids these mistakes. Then, I defend the claim that moral distress is intrinsically harmful to the subject who experiences it. I conclude by explaining how acknowledging this aspect of moral distress should reshape our discussions about how best to deal with this phenomenon. © 2015 John Wiley & Sons Ltd.

  2. Intrinsic electron trapping in amorphous oxide

    Science.gov (United States)

    Strand, Jack; Kaviani, Moloud; Afanas’ev, Valeri V.; Lisoni, Judit G.; Shluger, Alexander L.

    2018-03-01

    We demonstrate that electron trapping at intrinsic precursor sites is endemic in non-glass-forming amorphous oxide films. The energy distributions of trapped electron states in ultra-pure prototype amorphous (a)-HfO2 insulator obtained from exhaustive photo-depopulation experiments demonstrate electron states in the energy range of 2–3 eV below the oxide conduction band. These energy distributions are compared to the results of density functional calculations of a-HfO2 models of realistic density. The experimental results can be explained by the presence of intrinsic charge trapping sites formed by under-coordinated Hf cations and elongated Hf–O bonds in a-HfO2. These charge trapping states can capture up to two electrons, forming polarons and bi-polarons. The corresponding trapping sites are different from the dangling-bond type defects responsible for trapping in glass-forming oxides, such as SiO2, in that the traps are formed without bonds being broken. Furthermore, introduction of hydrogen causes formation of somewhat energetically deeper electron traps when a proton is immobilized next to the trapped electron bi-polaron. The proposed novel mechanism of intrinsic charge trapping in a-HfO2 represents a new paradigm for charge trapping in a broad class of non-glass-forming amorphous insulators.

  3. Learning intrinsic excitability in medium spiny neurons.

    Science.gov (United States)

    Scheler, Gabriele

    2013-01-01

    We present an unsupervised, local activation-dependent learning rule for intrinsic plasticity (IP) which affects the composition of ion channel conductances for single neurons in a use-dependent way. We use a single-compartment conductance-based model for medium spiny striatal neurons in order to show the effects of parameterization of individual ion channels on the neuronal membrane potential-curent relationship (activation function). We show that parameter changes within the physiological ranges are sufficient to create an ensemble of neurons with significantly different activation functions. We emphasize that the effects of intrinsic neuronal modulation on spiking behavior require a distributed mode of synaptic input and can be eliminated by strongly correlated input. We show how modulation and adaptivity in ion channel conductances can be utilized to store patterns without an additional contribution by synaptic plasticity (SP). The adaptation of the spike response may result in either "positive" or "negative" pattern learning. However, read-out of stored information depends on a distributed pattern of synaptic activity to let intrinsic modulation determine spike response. We briefly discuss the implications of this conditional memory on learning and addiction.

  4. Occupational stress and its predictors in radiographers

    International Nuclear Information System (INIS)

    Rutter, D.R.; Lovegrove, M.J.

    2008-01-01

    Purpose: The purpose of this study was to establish the level of occupational stress in UK NHS radiographers, and to examine its causes. A total of more than 1600 radiographers sampled nationally completed a postal questionnaire. Four groups were represented - mammography, diagnostics, radiotherapy, and ultrasound - and both junior staff and superintendents were examined. Method: The questionnaire measured role ambiguity, role conflict, work problems, social support from colleagues, and perceived stress. Results: Levels of perceived stress were high in all four groups. The mean was significantly lower in the mammography group than the others, however, and junior staff reported lower levels than superintendents. Role ambiguity, role conflict and work problems all contributed significantly to stress, but the effects were sometimes buffered by social support from colleagues. Conclusion: The implications of the findings are discussed for theory and for policy and practice: occupational stress was predicted by intrinsic features of the job; the levels were similar to those reported by other NHS professionals; and the pattern of findings suggests possible ways to intervene to reduce it

  5. Practical occupational medicine in "practice"

    DEFF Research Database (Denmark)

    Ingemann Larsen, Anders; Schmidt, Jan; Jepsen, Jørgen Riis

    2016-01-01

    In Denmark, the practice of occupational medicine tends to be carried out by specialists in occupational medicine and less so by family physicians. The provision of health service to workers is therefore limited. This constraint may also apply in other developed countries and even more in countries...... with few occupational health resources. This Editorial argues that family physicians are indeed in a position where they can make a major positive difference for their working patients and for the enterprises where they work. Without specialist knowledge in occupational medicine, the family physician...... exposed workers. Such involvement would expand the coverage of occupational health service to patients/workers on a global scale....

  6. Enabling occupation: occupation-based and client centred practice in Occupational Therapy

    Directory of Open Access Journals (Sweden)

    Tatiana Barcelos Pontes

    2016-04-01

    Full Text Available Occupational therapists have always been dedicated to the human occupation study, however the client hasn’t always been seen as an occupational being, with needs, interests and individual goals. The concern for our clients’ engagement in occupation, rather than the acquisition or restoration of performance components, together with the gradual modification of the concept of occupation from work-related activities to purposeful human activity, requires a broadening of our scope of practice. The most current theories related to occupational therapy practice have highlightes the use of client centered and occupational based practices. In occupation-based, client-centred practice the client participates actively in negotiating goals, and client occupational goals are given priority and are placed at the centre of assessment, intervention and outcomes. There are numerous evidences in the literature with significantly positive results supporting these approaches. These approaches are based on the premises that goals and objectives of interventions should be focused in occupation and significant activities to the client and reflect the occupational therapy core values: an occupational-centred perspective that respects client’s choices, goals and values, promoting and supporting the engagement on meaningful activities.

  7. Education and Occupational Outcomes

    DEFF Research Database (Denmark)

    Johnes, Geraint; Freguglia, Ricardo; Spricigo, Gisele

    2016-01-01

    Purpose: The purpose of this paper is to examine the dynamic relationship between policies related to educational provision and both educational participation and occupational outcomes in Brazil, using PNAD and RAIS-Migra data. Design/methodology/approach: Outcomes are examined using: static...... multinomial logit analysis, and structural dynamic discrete choice modelling. The latter approach, coupled with the quality of the RAIS-Migra data source, allows the authors to evaluate the education policy impacts over time. Findings: The main results show that the education level raises the propensity...... that the individual will be in formal sector work or still in education, and reduces the probability of the other outcomes. Transition into non-manual formal sector work following education may, however, occur via a spell of manual work. Originality/value: This is the first study of occupational destination...

  8. Occupational dose constraint

    International Nuclear Information System (INIS)

    Heilbron Filho, Paulo Fernando Lavalle; Xavier, Ana Maria

    2005-01-01

    The revision process of the international radiological protection regulations has resulted in the adoption of new concepts, such as practice, intervention, avoidable and restriction of dose (dose constraint). The latter deserving of special mention since it may involve reducing a priori of the dose limits established both for the public and to individuals occupationally exposed, values that can be further reduced, depending on the application of the principle of optimization. This article aims to present, with clarity, from the criteria adopted to define dose constraint values to the public, a methodology to establish the dose constraint values for occupationally exposed individuals, as well as an example of the application of this methodology to the practice of industrial radiography

  9. MEASURES OF OCCUPATIONAL MISMATCH

    Directory of Open Access Journals (Sweden)

    Monica Mihaela MAER MATEI

    2014-11-01

    Full Text Available The research developed in this paper is based on micro data available in Programme for the International Assessment of Adult Competencies (PIAAC. The research aimed to estimate the size of both forms of labour market mismatch: education mismatch and skill mismatch. The first measure of job mismatch is based on workers’ self-assessment. The second one uses the PIAAC assessment regarding the proficiency for each skill dimension (literacy, numeracy and problem solving in technology rich environments. The labor market mismatch was measured for Spain and Italy datasets for the higher education graduates whose occupations are included in Major Group two Professionals, according to the International Standard Classification of Occupations. The estimation results showed that the two measures of labour market mismatch are not correlated.

  10. Occupational safety motivation

    DEFF Research Database (Denmark)

    Pedersen, Louise; Kines, Pete

    2010-01-01

    Background: Motivation is one of the most important factors for safety behaviour and for implementing change in general. However, theoretical and psychometric studies of safety performance have traditionally treated safety motivation, safety compliance and safety participation unidimensionally....... At the same time many motivation questionnaire items are seldom founded on theory and/or do not account for the theories’ ontological and epistemological differences, e.g. of how knowledge, attitude and action are related. Present questionnaire items tap into occupational safety motivation in asking whether...... or not respondents ‘are’ motivated and whether they feel that safety is important or worthwhile. Another important aspect is ‘what’ motivates workers to comply to and participate in safety. The aim of this article is to introduce a new theory-based occupational safety motivation scale which is validated...

  11. Importance and challenges of measuring intrinsic foot muscle strength

    Science.gov (United States)

    2012-01-01

    Background Intrinsic foot muscle weakness has been implicated in a range of foot deformities and disorders. However, to establish a relationship between intrinsic muscle weakness and foot pathology, an objective measure of intrinsic muscle strength is needed. The aim of this review was to provide an overview of the anatomy and role of intrinsic foot muscles, implications of intrinsic weakness and evaluate the different methods used to measure intrinsic foot muscle strength. Method Literature was sourced from database searches of MEDLINE, PubMed, SCOPUS, Cochrane Library, PEDro and CINAHL up to June 2012. Results There is no widely accepted method of measuring intrinsic foot muscle strength. Methods to estimate toe flexor muscle strength include the paper grip test, plantar pressure, toe dynamometry, and the intrinsic positive test. Hand-held dynamometry has excellent interrater and intrarater reliability and limits toe curling, which is an action hypothesised to activate extrinsic toe flexor muscles. However, it is unclear whether any method can actually isolate intrinsic muscle strength. Also most methods measure only toe flexor strength and other actions such as toe extension and abduction have not been adequately assessed. Indirect methods to investigate intrinsic muscle structure and performance include CT, ultrasonography, MRI, EMG, and muscle biopsy. Indirect methods often discriminate between intrinsic and extrinsic muscles, but lack the ability to measure muscle force. Conclusions There are many challenges to accurately measure intrinsic muscle strength in isolation. Most studies have measured toe flexor strength as a surrogate measure of intrinsic muscle strength. Hand-held dynamometry appears to be a promising method of estimating intrinsic muscle strength. However, the contribution of extrinsic muscles cannot be excluded from toe flexor strength measurement. Future research should clarify the relative contribution of intrinsic and extrinsic muscles

  12. Embracing Creativity in Occupational Therapy

    Directory of Open Access Journals (Sweden)

    Lydia Royeen, MOT, OTR/L

    2015-01-01

    Full Text Available Jen Gash, an occupational therapist and creativity coach living in the UK, provided the cover art for the winter 2015 issue of The Open Journal of Occupational Therapy. The picture is titled “Over the Exe.” Jen uses her inspiration of the Kawa River model in this painting. The painting is of her husband and daughter standing where the river meets the sea. This is a metaphoric representation of rejoining the greater collective. In addition, Jen has a passion for occupational therapists to encompass creativity. A core aspect of occupational therapy is the multi-dimensional concept of occupations; it allows for occupational therapists to incorporate creativity into daily practice. Jen’s goal is for occupational therapy to embrace its creative theoretical roots.

  13. Daily Occupations among asylum seekers

    DEFF Research Database (Denmark)

    Morville, Anne-Le

    2014-01-01

    Asylum seekers often find themselves in a situation where the structure and content of daily occupations have been disrupted and they might have limited access to paid work and education. Studies have shown that asylum seekers experience occupational deprivation and a change in daily occupations...... was to assess whether torture had an influence on the occupational satisfaction and performance, and whether this had changed after ten-months. Forty-three asylum seekers from Afghanistan, Iran and Syria participated at baseline and ten months later 17 were available for inclusion in follow-up studies. Study I......-being and health, all of which had associations to occupational satisfaction, activity level and occupational performance. Torture did not appear to have an influence on satisfaction with daily occupations, but physical torture could be a predictor of decline in ADL motor skills (Study III). On arrival...

  14. Perspective on occupational mortality risks

    International Nuclear Information System (INIS)

    Cohen, B.L.

    1981-01-01

    Occupational risks to radiation workers are compared with other occupational risks on the basis of lost life expectancy (LLE) in a full working lifetime. Usual comparisons with National Safety Council accident death statistics for various industry categories are shown to be unfair because the latter average over a variety of particular industries and occupations within each industry. Correcting for these problems makes some common occupations in some industries 20-50 times more dangerous due to accidents alone than being a radiation worker. If more exposed subgroups of radiation workers are compared with more dangerous subgroups of other occupations, these ratios are maintained. Since radiation causes disease rather than acute injury, a wide range effort is made to estimate average loss of life expectancy from occupational disease; the final estimate for this is 500 days. The average American worker loses more than an order of magnitude more life expectancy from occupational disease than the average radiation worker loses from radiation induced cancer. (author)

  15. PREVENTION OF OCCUPATIONAL ACCIDENTS

    Directory of Open Access Journals (Sweden)

    Jovica Jovanovic

    2004-01-01

    Full Text Available Medical services, physicians and nurses play an essential role in the plant safety program through primary treatment of injured workers and by helping to identify workplace hazards. The physician and nurse should participate in the worksite investigations to identify specific hazard or stresses potentially causing the occupational accidents and injuries and in planning the subsequent hazard control program. Physicians and nurses must work closely and cooperatively with supervisors to ensure the prompt reporting and treatment of all work related health and safety problems. Occupational accidents, work related injuries and fatalities result from multiple causes, affect different segments of the working population, and occur in a myriad of occupations and industrial settings. Multiple factors and risks contribute to traumatic injuries, such as hazardous exposures, workplace and process design, work organization and environment, economics, and other social factors. With such a diversity of theories, it will not be difficult to understand that there does not exist one single theory that is considered right or correct and is universally accepted. These theories are nonetheless necessary, but not sufficient, for developing a frame of reference for understanding accident occurrences. Prevention strategies are also varied, and multiple strategies may be applicable to many settings, including engineering controls, protective equipment and technologies, management commitment to and investment in safety, regulatory controls, and education and training. Research needs are thus broad, and the development and application of interventions involve many disciplines and organizations.

  16. Positive consequences of intrinsically rewarding work: A model to ...

    African Journals Online (AJOL)

    This study sought to empirically test a theoretical model outlining the relationships between intrinsic rewards, intrinsic motivation, work engagement and intention to quit, in an attempt to empirically assess whether intrinsic rewards result in improved levels of motivation, engagement and retention. Using a sample of 587 ...

  17. The value of nature: Economic, intrinsic, or both?

    Science.gov (United States)

    There has been a long standing argument that ecosystems have intrinsic value and therefore there is no need to put a price tag on Mother Nature. The concept of intrinsic value reflects the perspective that nature has value in its own right, independent of human uses. Intrinsic va...

  18. Personalizing Sample Databases with Facebook Information to Increase Intrinsic Motivation

    Science.gov (United States)

    Marzo, Asier; Ardaiz, Oscar; Sanz de Acedo, María Teresa; Sanz de Acedo, María Luisa

    2017-01-01

    Motivation is fundamental for students to achieve successful and complete learning. Motivation can be extrinsic, i.e., driven by external rewards, or intrinsic, i.e., driven by internal factors. Intrinsic motivation is the most effective and must be inspired by the task at hand. Here, a novel strategy is presented to increase intrinsic motivation…

  19. Intrinsic Motivation: An Overlooked Component for Student Success

    Science.gov (United States)

    Augustyniak, Robert A.; Ables, Adrienne Z.; Guilford, Philip; Lujan, Heidi L.; Cortright, Ronald N.; DiCarlo, Stephen E.

    2016-01-01

    Intrinsic motivation to learn involves engaging in learning opportunities because they are seen as enjoyable, interesting, or relevant to meeting one's core psychological needs. As a result, intrinsic motivation is associated with high levels of effort and task performance. Students with greater levels of intrinsic motivation demonstrate strong…

  20. The Development of Intrinsic Motivation for Physical Activity

    Science.gov (United States)

    2005-07-01

    The Development of Intrinsic Motivation for Physical Activity by James Dunigan Beaty Bachelor of Science Central Washington...2. REPORT TYPE N/A 3. DATES COVERED - 4. TITLE AND SUBTITLE The Development of Intrinsic Motivation for Physical Activity 5a. CONTRACT...Government." 3 ABSTRACT The Development of Intrinsic Motivation for Physical Activity by James Dunigan Beaty Cynthia Carruthers, Ph.D

  1. Elements of the Competitive Situation That Affect Intrinsic Motivation.

    Science.gov (United States)

    Reeve, Johnmarshall; Deci, Edward L.

    1996-01-01

    Explores the effects of three elements of the competitive situation (competitive set, competitive outcome, and interpersonal context) on intrinsic motivation in a sample of college students (n=100). Competitive outcome and interpersonal context affected intrinsic motivation: winning increased intrinsic motivation, while pressured interpersonal…

  2. Occupational Health in Mountainous Kyrgyzstan.

    Science.gov (United States)

    Dzhusupov, Kenesh O; Colosio, Claudio; Tabibi, Ramin; Sulaimanova, Cholpon T

    2015-01-01

    In the period of transition from a centralized economy to the market economy, occupational health services in Kyrgyzstan have survived through dramatic, detrimental changes. It is common for occupational health regulations to be ignored and for basic occupational health services across many industrial enterprises and farms to be neglected. The aim of this study was to demonstrate the present situation and challenges facing occupational health services in Kyrgyzstan. The transition from centralized to the market economy in Kyrgyzstan has led to increased layoffs of workers and unemployment. These threats are followed by increased workload, and the health and safety of workers becomes of little concern. Private employers ignore occupational health and safety; consequently, there is under-reporting of occupational diseases and accidents. The majority of enterprises, especially those of small or medium size, are unsanitary, and the health status of workers remains largely unknown. The low official rates of occupational diseases are the result of data being deliberately hidden; lack of coverage of working personnel by medical checkups; incompetent management; and the poor quality of staff, facilities, and equipment. Because Kyrgyzstan is a mountainous country, the main environmental and occupational factor of enterprises is hypoxia. Occupational health specialists have greatly contributed to the development of occupational medicine in the mountains through science and practice. The enforcement of existing strong occupational health legislation and increased financing of occupational health services are needed. The maintenance of credible health monitoring and effective health services for workers, re-establishment of medical services and sanitary-hygienic laboratories in industrial enterprises, and support for scientific investigations on occupational risk assessment will increase the role of occupational health services in improving the health of the working population

  3. Occupational trajectories and occupational cost among Senegalese immigrants in Europe

    Directory of Open Access Journals (Sweden)

    Ognjen Obucina

    2013-03-01

    Full Text Available BACKGROUND Immigration from Africa to Europe has increased substantially in recent decades. The main goal of this paper is to contribute to a better understanding of contemporary international migration processes by analyzing the occupational trajectories and occupational costs of Senegalese immigrants in three major European destination countries (France, Italy, and Spain. OBJECTIVE The first objective is to compare the occupational attainment of the Senegalese immigrants before and after migration to Europe, as well as to establish the determinants of the immigrants' occupational attainment and occupational mobility levels after migration. Another major goal is to estimate the occupational cost of migration from Senegal to Europe. The central question this study intends to answer is how much, in terms of occupational status, Senegalese immigrants renounce by migrating to Europe, in both the short and the long term. METHODS The data stem from the Senegalese sample of the MAFE dataset. The standard OLS techniques are used in the analysis of occupational attainment, while discrete-time multinomial logit is used in the section on occupational mobility. The principal techniques for the estimation of occupational cost of migration are random effects with Mundlak correction and nearest-neighbor matching. RESULTS There is a U-shaped pattern of occupational mobility among Senegalese immigrants in Europe: the average occupational status of this group drops just after arrival in Europe, and then slowly improves with the duration of stay. The multivariate analysis reveals that education acquired in Europe plays an especially important role in the successful participation of this immigrant group in the labor market. The results show that there is a statistically significant occupational cost of migration from Senegal to Europe, but that the cost decreases with the duration of stay in Europe.

  4. Innate and intrinsic antiviral immunity in skin.

    Science.gov (United States)

    Kawamura, Tatsuyoshi; Ogawa, Youichi; Aoki, Rui; Shimada, Shinji

    2014-09-01

    As the body's most exposed interface with the environment, the skin is constantly challenged by potentially pathogenic microbes, including viruses. To sense the invading viruses, various types of cells resident in the skin express many different pattern-recognition receptors (PRRs) such as C-type lectin receptors (CLRs), Toll-like receptors (TLRs), nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs), retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) and cytosolic DNA sensors, that can detect the pathogen-associated molecular patterns (PAMPs) of the viruses. The detection of viral PAMPs initiates two major innate immune signaling cascades: the first involves the activation of the downstream transcription factors, such as interferon regulatory factors (IRFs), nuclear factor kappa B (NF-κB) and activator protein 1 (AP-1), which cooperate to induce the transcription of type I interferons and pro-inflammatory cytokines. The second signaling pathway involves the caspase-1-mediated processing of IL-1β and IL-18 through the formation of an inflammasome complex. Cutaneous innate immunity including the production of the innate cytokines constitutes the first line of host defence that limits the virus dissemination from the skin, and also plays an important role in the activation of adaptive immune response, which represents the second line of defence. More recently, the third immunity "intrinsic immunity" has emerged, that provides an immediate and direct antiviral defense mediated by host intrinsic restriction factors. This review focuses on the recent advances regarding the antiviral immune systems, highlighting the innate and intrinsic immunity against the viral infections in the skin, and describes how viral components are recognized by cutaneous immune systems. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  5. Vaccination with Leishmania infantum acidic ribosomal P0 but not with nucleosomal histones proteins controls Leishmania infantum infection in hamsters.

    Science.gov (United States)

    Pereira, Lais; Abbehusen, Melissa; Teixeira, Clarissa; Cunha, Jurema; Nascimento, Ivan P; Fukutani, Kyioshi; dos-Santos, Washington; Barral, Aldina; de Oliveira, Camila Indiani; Barral-Netto, Manoel; Soto, Manoel; Brodskyn, Cláudia Ida

    2015-02-01

    Several intracellular Leishmania antigens have been identified in order to find a potential vaccine capable of conferring long lasting protection against Leishmania infection. Histones and Acid Ribosomal proteins are already known to induce an effective immune response and have successfully been tested in the cutaneous leishmaniasis mouse model. Here, we investigate the protective ability of L. infantum nucleosomal histones (HIS) and ribosomal acidic protein P0 (LiP0) against L. infantum infection in the hamster model of visceral leishmaniasis using two different strategies: homologous (plasmid DNA only) or heterologous immunization (plasmid DNA plus recombinant protein and adjuvant). Immunization with both antigens using the heterologous strategy presented a high antibody production level while the homologous strategy immunized group showed predominantly a cellular immune response with parasite load reduction. The pcDNA-LiP0 immunized group showed increased expression ratio of IFN-γ/IL-10 and IFN-γ/TGF-β in the lymph nodes before challenge. Two months after infection hamsters immunized with the empty plasmid presented a pro-inflammatory immune response in the early stages of infection with increased expression ratio of IFN-γ/IL-10 and IFN-γ/TGF-β, whereas hamsters immunized with pcDNA-HIS presented an increase only in the ratio IFN-γ/ TGF-β. On the other hand, hamsters immunized with LiP0 did not present any increase in the IFN-γ/TGF-β and IFN-γ/IL-10 ratio independently of the immunization strategy used. Conversely, five months after infection, hamsters immunized with HIS maintained a pro-inflammatory immune response (ratio IFN-γ/ IL-10) while pcDNA-LiP0 immunized hamsters continued showing a balanced cytokine profile of pro and anti-inflammatory cytokines. Moreover we observed a significant reduction in parasite load in the spleen, liver and lymph node in this group compared with controls. Our results suggest that vaccination with L. infantum LiP0

  6. Computer modeling reveals that modifications of the histone tail charges define salt-dependent interaction of the nucleosome core particles.

    Science.gov (United States)

    Yang, Ye; Lyubartsev, Alexander P; Korolev, Nikolay; Nordenskiöld, Lars

    2009-03-18

    Coarse-grained Langevin molecular dynamics computer simulations were conducted for systems that mimic solutions of nucleosome core particles (NCPs). The NCP was modeled as a negatively charged spherical particle representing the complex of DNA and the globular part of the histones combined with attached strings of connected charged beads modeling the histone tails. The size, charge, and distribution of the tails relative to the core were built to match real NCPs. Three models of NCPs were constructed to represent different extents of covalent modification on the histone tails: (nonmodified) recombinant (rNCP), acetylated (aNCP), and acetylated and phosphorylated (paNCP). The simulation cell contained 10 NCPs in a dielectric continuum with explicit mobile counterions and added salt. The NCP-NCP interaction is decisively dependent on the modification state of the histone tails and on salt conditions. Increasing the monovalent salt concentration (KCl) from salt-free to physiological concentration leads to NCP aggregation in solution for rNCP, whereas NCP associates are observed only occasionally in the system of aNCPs. In the presence of divalent salt (Mg(2+)), rNCPs form dense stable aggregates, whereas aNCPs form aggregates less frequently. Aggregates are formed via histone-tail bridging and accumulation of counterions in the regions of NCP-NCP contacts. The paNCPs do not show NCP-NCP interaction upon addition of KCl or in the presence of Mg(2+). Simulations for systems with a gradual substitution of K(+) for Mg(2+), to mimic the Mg(2+) titration of an NCP solution, were performed. The rNCP system showed stronger aggregation that occurred at lower concentrations of added Mg(2+), compared to the aNCP system. Additional molecular dynamics simulations performed with a single NCP in the simulation cell showed that detachment of the tails from the NCP core was modest under a wide range of salt concentrations. This implies that salt-induced tail dissociation of the

  7. Metacognitive mastery and intrinsic motivation in schizophrenia.

    Science.gov (United States)

    Vohs, Jenifer L; Lysaker, Paul H

    2014-01-01

    Deficits in intrinsic motivation (IM) have been linked to poorer outcome in schizophrenia, but its proximal mechanisms remain poorly understood. This study examined whether metacognitive mastery, or the capacity to use knowledge of self, others, and context to identify and cope with psychological difficulties, predicted levels of IM for 6 months among 75 participants with prolonged schizophrenia. Repeated-measures analysis of variance revealed that high metacognitive mastery predicted consistently higher levels of IM; however, intermediate and low mastery did not produce unique IM profiles. The findings suggest that metacognitive mastery may have an important role in IM over time and could be a meaningful treatment target.

  8. Symplectic Structure of Intrinsic Time Gravity

    Directory of Open Access Journals (Sweden)

    Eyo Eyo Ita

    2016-08-01

    Full Text Available The Poisson structure of intrinsic time gravity is analysed. With the starting point comprising a unimodular three-metric with traceless momentum, a trace-induced anomaly results upon quantization. This leads to a revision of the choice of momentum variable to the (mixed index traceless momentric. This latter choice unitarily implements the fundamental commutation relations, which now take on the form of an affine algebra with SU(3 Lie algebra amongst the momentric variables. The resulting relations unitarily implement tracelessness upon quantization. The associated Poisson brackets and Hamiltonian dynamics are studied.

  9. Intrinsically conductive polymer thin film piezoresistors

    DEFF Research Database (Denmark)

    Lillemose, Michael; Spieser, Martin; Christiansen, N.O.

    2008-01-01

    We report on the piezoresistive effect in the intrinsically conductive polymer, polyaniline. A process recipe for indirect patterning of thin film polyaniline has been developed. Using a specially designed chip, the polyaniline thin films have been characterised with respect to resistivity...... and strain sensitivity using two- and four-point measurement method. We have found that polyaniline has a negative gauge factor of K = -4.9, which makes it a candidate for piezoresistive read-out in polymer based MEMS-devices. (C) 2007 Elsevier B.V. All rights reserved....

  10. Intrinsic chirp of single-cycle pulses

    International Nuclear Information System (INIS)

    Lin Qiang; Zheng Jian; Dai Jianming; Ho, I-Chen; Zhang, X.-C.

    2010-01-01

    The Fourier transform-limited electromagnetic pulse has been regarded to be free of chirps for a long time. This is no longer true if the pulse duration goes down to or less than one optical cycle. We report the experimental observation of intrinsic chirps in such pulses with the sub-single-cycle terahertz (THz) waveforms obtained with a standard THz time-domain spectroscopy system. The results confirm the break down of the carrier-envelope (CE) expression for single-cycle optical pulses, and may influence the experimental measurements and theoretical modeling with single-cycle pulses.

  11. [Tool for measuring occupational stress: a nurses' stress inventory].

    Science.gov (United States)

    Stacciarini, J M; Tróccoli, B T

    2000-12-01

    We present an exploratory study aiming at constructing an inventory to measure occupational stress in nurses ("Inventário de Estresse em Enfermeiros"--IEE). A set of items was initially constructed from previously defined categories based on interviews with nurses and then improved through semantic analysis by referees and a pilot-test with nursing students. A sample of 461 nurses--workers from the public services of the Federal District--who answered the IEE was used in the study. Factorial analysis indicated the presence of a second-order global factor and three first-order factors: Interpersonal Relationships, Stressful Career Roles and Intrinsic Job Factors.

  12. The Neglected Intrinsic Resistome of Bacterial Pathogens

    Science.gov (United States)

    Fajardo, Alicia; Martínez-Martín, Nadia; Mercadillo, María; Galán, Juan C.; Ghysels, Bart; Matthijs, Sandra; Cornelis, Pierre; Wiehlmann, Lutz; Tümmler, Burkhard; Baquero, Fernando; Martínez, José L.

    2008-01-01

    Bacteria with intrinsic resistance to antibiotics are a worrisome health problem. It is widely believed that intrinsic antibiotic resistance of bacterial pathogens is mainly the consequence of cellular impermeability and activity of efflux pumps. However, the analysis of transposon-tagged Pseudomonas aeruginosa mutants presented in this article shows that this phenotype emerges from the action of numerous proteins from all functional categories. Mutations in some genes make P. aeruginosa more susceptible to antibiotics and thereby represent new targets. Mutations in other genes make P. aeruginosa more resistant and therefore define novel mechanisms for mutation-driven acquisition of antibiotic resistance, opening a new research field based in the prediction of resistance before it emerges in clinical environments. Antibiotics are not just weapons against bacterial competitors, but also natural signalling molecules. Our results demonstrate that antibiotic resistance genes are not merely protective shields and offer a more comprehensive view of the role of antibiotic resistance genes in the clinic and in nature. PMID:18286176

  13. A tonoplast intrinsic protein in Gardenia jasminoides

    Science.gov (United States)

    Gao, Lan; Li, Hao-Ming

    2017-08-01

    Physiological and molecular studies proved that plasma membrane intrinsic proteins (PIPs) and tonoplast intrinsic proteins (TIPs) subfamily of aquaporins play key functions in plant water homeostasis. Five specialized subgroups (TIP1-5) of TIPs have been found in higher plants, in which the TIP1 and TIP2 isoforms are the largest arbitrary groups. TIPs have high water-transport activity than PIPs, some TIPs can transport other small molecule such as urea, ammonia, hydrogen peroxide, and carbon dioxide. In this work, the structure of the putative tonoplast aquaporin from Gardenia jasminoides (GjTIP) was analyzed. Its transcript level has increased during fruit maturation. A phylogenetic analysis indicates that the protein belongs to TIP1 subfamily. A three-dimensional model structure of GjTIP was built based on crystal structure of an ammonia-permeable AtTIP2-1 from Arabidopsis thaliana. The model structure displayed as a homo-tetramer, each monomer has six trans-membrane and two half-membrane-spanning α helices. The data suggests that the GjTIP has tendency to be a mixed function aquaporin, might involve in water, urea and hydrogen peroxide transport, and the gating machanism founded in some AQPs involving pH and phosphorylation response have not been proved in GjTIP.

  14. Intrinsic regulation of enteroendocrine fate by Numb.

    Science.gov (United States)

    Sallé, Jérémy; Gervais, Louis; Boumard, Benjamin; Stefanutti, Marine; Siudeja, Katarzyna; Bardin, Allison J

    2017-07-03

    How terminal cell fates are specified in dynamically renewing adult tissues is not well understood. Here we explore terminal cell fate establishment during homeostasis using the enteroendocrine cells (EEs) of the adult Drosophila midgut as a paradigm. Our data argue against the existence of local feedback signals, and we identify Numb as an intrinsic regulator of EE fate. Our data further indicate that Numb, with alpha-adaptin, acts upstream or in parallel of known regulators of EE fate to limit Notch signaling, thereby facilitating EE fate acquisition. We find that Numb is regulated in part through its asymmetric and symmetric distribution during stem cell divisions; however, its de novo synthesis is also required during the differentiation of the EE cell. Thus, this work identifies Numb as a crucial factor for cell fate choice in the adult Drosophila intestine. Furthermore, our findings demonstrate that cell-intrinsic control mechanisms of terminal cell fate acquisition can result in a balanced tissue-wide production of terminally differentiated cell types. © 2017 The Authors.

  15. Intrinsic position uncertainty impairs overt search performance.

    Science.gov (United States)

    Semizer, Yelda; Michel, Melchi M

    2017-08-01

    Uncertainty regarding the position of the search target is a fundamental component of visual search. However, due to perceptual limitations of the human visual system, this uncertainty can arise from intrinsic, as well as extrinsic, sources. The current study sought to characterize the role of intrinsic position uncertainty (IPU) in overt visual search and to determine whether it significantly limits human search performance. After completing a preliminary detection experiment to characterize sensitivity as a function of visual field position, observers completed a search task that required localizing a Gabor target within a field of synthetic luminance noise. The search experiment included two clutter conditions designed to modulate the effect of IPU across search displays of varying set size. In the Cluttered condition, the display was tiled uniformly with feature clutter to maximize the effects of IPU. In the Uncluttered condition, the clutter at irrelevant locations was removed to attenuate the effects of IPU. Finally, we derived an IPU-constrained ideal searcher model, limited by the IPU measured in human observers. Ideal searchers were simulated based on the detection sensitivity and fixation sequences measured for individual human observers. The IPU-constrained ideal searcher predicted performance trends similar to those exhibited by the human observers. In the Uncluttered condition, performance decreased steeply as a function of increasing set size. However, in the Cluttered condition, the effect of IPU dominated and performance was approximately constant as a function of set size. Our findings suggest that IPU substantially limits overt search performance, especially in crowded displays.

  16. The neglected intrinsic resistome of bacterial pathogens.

    Directory of Open Access Journals (Sweden)

    Alicia Fajardo

    Full Text Available Bacteria with intrinsic resistance to antibiotics are a worrisome health problem. It is widely believed that intrinsic antibiotic resistance of bacterial pathogens is mainly the consequence of cellular impermeability and activity of efflux pumps. However, the analysis of transposon-tagged Pseudomonas aeruginosa mutants presented in this article shows that this phenotype emerges from the action of numerous proteins from all functional categories. Mutations in some genes make P. aeruginosa more susceptible to antibiotics and thereby represent new targets. Mutations in other genes make P. aeruginosa more resistant and therefore define novel mechanisms for mutation-driven acquisition of antibiotic resistance, opening a new research field based in the prediction of resistance before it emerges in clinical environments. Antibiotics are not just weapons against bacterial competitors, but also natural signalling molecules. Our results demonstrate that antibiotic resistance genes are not merely protective shields and offer a more comprehensive view of the role of antibiotic resistance genes in the clinic and in nature.

  17. Intrinsic terminators in Mycoplasma hyopneumoniae transcription.

    Science.gov (United States)

    Fritsch, Tiago Ebert; Siqueira, Franciele Maboni; Schrank, Irene Silveira

    2015-04-08

    Mycoplasma hyopneumoniae, an important pathogen of swine, exhibits a low guanine and cytosine (GC) content genome. M. hyopneumoniae genome is organised in long transcriptional units and promoter sequences have been mapped upstream of all transcription units. These analysis provided insights into the gene organisation and transcription initiation at the genome scale. However, the presence of transcriptional terminator sequences in the M. hyopneumoniae genome is poorly understood. In silico analyses demonstrated the presence of putative terminators in 82% of the 33 monocistronic units (mCs) and in 74% of the 116 polycistronic units (pCs) considering different classes of terminators. The functional activity of 23 intrinsic terminators was confirmed by RT-PCR and qPCR. Analysis of all terminators found by three software algorithms, combined with experimental results, allowed us to propose a pattern of RNA hairpin formation during the termination process and to predict the location of terminators in the M. hyopneumoniae genome sequence. The stem-loop structures of intrinsic terminators of mycoplasma diverge from the pattern of terminators found in other bacteria due the low content of guanine and cytosine. In M. hyopneumoniae, transcription can end after a transcriptional unit and before its terminator sequence and can also continue past the terminator sequence with RNA polymerases gradually releasing the RNA.

  18. Intrinsically disordered proteins drive membrane curvature.

    Science.gov (United States)

    Busch, David J; Houser, Justin R; Hayden, Carl C; Sherman, Michael B; Lafer, Eileen M; Stachowiak, Jeanne C

    2015-07-24

    Assembly of highly curved membrane structures is essential to cellular physiology. The prevailing view has been that proteins with curvature-promoting structural motifs, such as wedge-like amphipathic helices and crescent-shaped BAR domains, are required for bending membranes. Here we report that intrinsically disordered domains of the endocytic adaptor proteins, Epsin1 and AP180 are highly potent drivers of membrane curvature. This result is unexpected since intrinsically disordered domains lack a well-defined three-dimensional structure. However, in vitro measurements of membrane curvature and protein diffusivity demonstrate that the large hydrodynamic radii of these domains generate steric pressure that drives membrane bending. When disordered adaptor domains are expressed as transmembrane cargo in mammalian cells, they are excluded from clathrin-coated pits. We propose that a balance of steric pressure on the two surfaces of the membrane drives this exclusion. These results provide quantitative evidence for the influence of steric pressure on the content and assembly of curved cellular membrane structures.

  19. Intrinsically secure fast reactors with dense cores

    International Nuclear Information System (INIS)

    Slessarev, Igor

    2007-01-01

    Secure safety, resistance to weapons material proliferation and problems of long-lived wastes remain the most important 'painful points' of nuclear power. Many innovative reactor concepts have been developed aimed at a radical enhancement of safety. The promising potential of innovative nuclear reactors allows for shifting accents in current reactor safety 'strategy' to reveal this worth. Such strategy is elaborated focusing on the priority for intrinsically secure safety features as well as on sure protection being provided by the first barrier of defence. Concerning the potential of fast reactors (i.e. sodium cooled, lead-cooled, etc.), there are no doubts that they are able to possess many favourable intrinsically secure safety features and to lay the proper foundation for a new reactor generation. However, some of their neutronic characteristics have to be radically improved. Among intrinsically secure safety properties, the following core parameters are significantly important: reactivity margin values, reactivity feed-back and coolant void effects. Ways of designing intrinsically secure safety features in fast reactors (titled hereafter as Intrinsically Secure Fast Reactors - ISFR) can be found in the frame of current reactor technologies by radical enhancement of core neutron economy and by optimization of core compositions. Simultaneously, respecting resistance to proliferation, by using non-enriched fuel feed as well as a core breeding gain close to zero, are considered as the important features (long-lived waste problems will be considered in a separate paper). This implies using the following reactor design options as well as closed fuel cycles with natural U as the reactor feed: ·Ultra-plate 'dense cores' of the ordinary (monolithic) type with negative total coolant void effects. ·Modular type cores. Multiple dense modules can be embedded in the common reflector for achieving the desired NPP total power. The modules can be used also independently (as

  20. The Neuroscience of Growth Mindset and Intrinsic Motivation.

    Science.gov (United States)

    Ng, Betsy

    2018-01-26

    Our actions can be triggered by intentions, incentives or intrinsic values. Recent neuroscientific research has yielded some results about the growth mindset and intrinsic motivation. With the advances in neuroscience and motivational studies, there is a global need to utilize this information to inform educational practice and research. Yet, little is known about the neuroscientific interplay between growth mindset and intrinsic motivation. This paper attempts to draw on the theories of growth mindset and intrinsic motivation, together with contemporary ideas in neuroscience, outline the potential for neuroscientific research in education. It aims to shed light on the relationship between growth mindset and intrinsic motivation in terms of supporting a growth mindset to facilitate intrinsic motivation through neural responses. Recent empirical research from the educational neuroscience perspective that provides insights into the interplay between growth mindset and intrinsic motivation will also be discussed.

  1. Accompanied consultations in occupational health.

    Science.gov (United States)

    Hobson, J; Hobson, H; Sharp, R

    2016-04-01

    Accompanied consultations are often reported as difficult by occupational physicians but have not been studied in the occupational health setting. To collect information about accompanied consultations and the impact of the companion on the consultation. We collected data on all accompanied consultations by two occupational physicians working in a private sector occupational health service over the course of 16 months. Accompanied consultations were matched to non-accompanied consultations for comparison. We collected data on 108 accompanied consultations. Accompanied consultations were more likely to be connected with ill health retirement (P Occupational health practitioners may benefit from better understanding of accompanied consultations and guidance on their management. © The Author 2015. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  2. Kanerva's Occupational Dermatology

    DEFF Research Database (Denmark)

    Madsen, Jakob Torp; Andersen, Klaus Ejner

    2012-01-01

    Nanoparticles are ultra small particles less than 100 nm in diameter. Nanoparticles may have altered physical and chemical properties compared to their larger-scale counterparts due to increased surface area. Nanoparticles are used in various industrial products including cosmetics, pharmaceutica......, electronics, paint, and sports equipment. No harmful effects of occupational skin exposure to nanoparticles have been published. Risk assessment must be done on a case-by-case basis for each workplace scenario and for each individual nanoparticle because of lack of knowledge....

  3. Gentrification and Occupancy Rights

    DEFF Research Database (Denmark)

    Huber, Jakob; Wolkenstein, Gregor Fabio

    2018-01-01

    What, if anything, is wrong with gentrification? This paper addresses this question from the perspective of normative political theory. We argue that gentrification is a wrong insofar as it involves a violation of city-dwellers occupancy rights. We distinguish these rights from other forms...... of territorial rights, and discuss the different implications of the argument for urban governance. If we agree on the ultimate importance of being able to pursue one’s located life-plans, the argument goes, we must also agree on limiting the impact on gentrification on people’s lives. Limiting gentrification...

  4. Kanerva's Occupational Dermatology

    DEFF Research Database (Denmark)

    Madsen, Jakob Torp

    Nanoparticles are ultra small particles less than 100 nm in diameter. Nanoparticles may have altered physical and chemical properties compared to their larger-scale counterparts due to increased surface area. Nanoparticles are used in various industrial products including cosmetics, pharmaceutica......, electronics, paint, and sports equipment. No harmful effects of occupational skin exposure to nanoparticles have been published. Risk assessment must be done on a case-by-case basis for each workplace scenario and for each individual nanoparticle because of lack of knowledge....

  5. Occupational exposure to ionizing radiation

    International Nuclear Information System (INIS)

    Snihs, J.O.

    1985-01-01

    An overview of occupational exposure is presented. Concepts and quantities used for radiation protection are explained as well as the ICRP system of dose limitation. The risks correlated to the limits are discussed. However, the actual exposure are often much lower than the limits and the average risk in radiation work is comparable with the average risk in other safe occupations. Actual exposures in various occupations are presented and discussed. (author)

  6. Occupational cancer. 4. enlarged ed.

    International Nuclear Information System (INIS)

    Butz, M.

    1991-01-01

    In the fourth, supplementary edition work related cancer illnesses which from 1978 to 1990 were recognized by the Industrial Professional Associations as occupational diseases are described. This covers: Type of occupational disease, organs affected, causal substances, hazardous professions. In addition, for every occupational-disease, detailed data are presented, e.g. latency periods and ages at death. 16 carcinogenic substances and substance classes are considered in this catalogue including ionizing radiation. (orig./MG) [de

  7. [Occupational allergy to mugwort].

    Science.gov (United States)

    Kurzen, Marina; Bayerl, Christiane; Goerdt, Sergij

    2003-04-01

    Mugwort (Artemisia vulgaris) has traditionally been used as a spice, vegetable and as a herbal medicine. The main representatives of the Artemisia family besides Artemisia vulgaris include Artemisia absinthum and Artemisia dracunculus (estragon). Mugwort pollen allergens are important in triggering late summer and fall pollinosis; in addition cross reactivity occurs between Artemisia vulgaris pollen allergens and celery, carrottes and certain spices belonging to the family of Umbelliferae. A florist with a pre-existing sunflower allergy developed a life-threatening glottal edema after occupational contact with mugwort. She did not suffer from an oral allergy syndrome towards mugwort pollen cross allergens. Skin testing (prick and scratch testing) revealed a strong sensitisation against mugwort and estragon. Specific IgE antibodies against mugwort, sunflower, carrots, celery, fennel and anis were elevated in the peripheral blood. The observation of a severe mugwort allergy with life-threatening complications in a florist underscores the high allergenic potential of Artemisia vulgaris and documents for the first time the occupational significance of this allergy.

  8. Quantum synchronization effects in intrinsic Josephson junctions

    International Nuclear Information System (INIS)

    Machida, M.; Kano, T.; Yamada, S.; Okumura, M.; Imamura, T.; Koyama, T.

    2008-01-01

    We investigate quantum dynamics of the superconducting phase in intrinsic Josephson junctions of layered high-T c superconductors motivated by a recent experimental observation for the switching rate enhancement in the low temperature quantum regime. We pay attention to only the capacitive coupling between neighboring junctions and perform large-scale simulations for the Schroedinger equation derived from the Hamiltonian considering the capacitive coupling alone. The simulation focuses on an issue whether the switching of a junction induces those of the other junctions or not. The results reveal that the superconducting phase dynamics show synchronous behavior with increasing the quantum character, e.g., decreasing the junction plane area and effectively the temperature. This is qualitatively consistent with the experimental result

  9. Intrinsic thermal expansion of crystal defects

    International Nuclear Information System (INIS)

    Ganne, J.-P.

    1981-02-01

    Although the phenomenon of thermal expansion has long been known, the intrinsic thermal expansion coefficient (ITEC) βsub(d) of a point defect, derived from its formation volume vsub(d), has never been measured directly. The differential dilatometer by interferometry built by ASTY and GILDER is described. It has allowed βsub(d) to be measured for several defects. Vacancies and small interstitial loops were produced in aluminium by low temperature (20 K) fast neutron irradiation followed by an anneal up to the beginning of stage III (160 K). The very high value of the measured ratio βsub(d)/β 0 (12+-4) is comparable with a lattice statics calculated (42) value (11.5 0 [fr

  10. Intrinsic topological superfluidity - fluctuations and response

    Science.gov (United States)

    Levin, K.; Wu, Chien-Te; Anderson, Brandon; Boyack, Rufus

    Recent interest in topological superconductivity is based primarily on exploiting proximity effects to obtain this important phase. However, in cold gases it is possible to contemplate ``intrinsic'' topological superfluidity produced with a synthetic spin-orbit coupling and Zeeman field. It is important for such future experiments to establish how low in temperature one needs to go to reach the ordered phase. Similarly, it will be helpful to have a probe of the normal (pseudogap) phase to determine if the ultimate superfluid order will be topological or trivial. In this talk, we address these issues by considering fluctuation effects in such a superfluid, and calculate the critical transition temperature and response functions. We see qualitative signatures of topological superfluidity in spin and charge response functions. We also explore the suppression of superfluidity due to fluctuations, and importantly find that the temperature scales necessary to reach topological superfluidity are reasonably accessible

  11. Major Intrinsic Proteins in Biomimetic Membranes

    DEFF Research Database (Denmark)

    Helix Nielsen, Claus

    2010-01-01

    will generally have finite permeabilities to both electrolytes and non-electrolytes. The feasibility of a biomimetic MIP device thus depends on the relative transport contribution from both protein and biomimetic support matrix. Also the biomimetic matrix must be encapsulated in order to protect it and make....../separation technology, a unique class of membrane transport proteins is especially interesting the major intrinsic proteins (MIPs). Generally, MIPs conduct water molecules and selected solutes in and out of the cell while preventing the passage of other solutes, a property critical for the conservation of the cells...... it sufficiently stable in a final application. Here, I specifically discuss the feasibility of developing osmotic biomimetic MIP membranes, but the technical issues are of general concern in the design of biomimetic membranes capable of supporting selective transmembrane fluxes....

  12. Intrinsic densitometry: In-plant evaluation

    International Nuclear Information System (INIS)

    Nishida, K.; Kurosawa, A.; Masui, J.; Hsue, S.T.

    1994-11-01

    A measurement of the plutonium concentration in a sample is always necessary for nuclear material control and accounting. This report describes the testing of the intrinsic densitometry (ID) technique for implant applications. The authors found that the ID method can determine the plutonium concentrations to between 2 and 3% at concentrations of 100 g/l to 200 g/l with quartz cells and a measurement time of 3600 s. The precision can be improved to 1 to 2% with a higher counting rate. The authors also found that nitric acid concentration and the impurity level of uranium in the product plutonium solution do not affect the concentration measurement. When this technique is applied to plutonium solutions in stainless steel pipes, they found that similar precision in plutonium concentration can be achieved using a high-count-rate detector. The precision, however, is reduced with aged plutonium solutions

  13. On the intrinsic colours of cepheids

    International Nuclear Information System (INIS)

    Efremov, Yu.N.

    1979-01-01

    Some consequences from new data on the photometrically obtained intrinsic colours are considered. It is shown that the small amplitude and almost sinusoidal light-curve cepheids (Cs-subtype) increase their pulsation amplitude towards the red instability strip edge, differing from the other galactic cepheids. This feature is discussed in connection with Efremov's (1968) hypothesis that the Cs-cepheids first cross the instability strip from left to right. The galactic cepheid period-colour relation obtained by Dean, Warren and Cousins (1978) satisfies rather well the LMC cepheid observations and, consequently, considerations for the period-luminosity relations are made. The residuals from the PL relation proposed by us correlate with the colour residuals from the DWC period-colour relation ΔV/delta(B-V) being equal to 2.7. The luminosity effect as a possible cause of the discrepancy between the spectroscopic cepheid colours and the photometric colours is briefly discussed. (Auth.)

  14. Intrinsic Dynamics of Quantum-Dash Lasers

    KAUST Repository

    Chen, Cheng

    2011-10-01

    Temperature-dependent intrinsic modulation response of InAs/InAlGaAs quantum-dash lasers was investigated by using pulse optical injection modulation to minimize the effects of parasitics and self-heating. Compared to typical quantum-well lasers, the quantum-dash lasers were found to have comparable differential gain but approximately twice the gain compression factor, probably due to carrier heating by free-carrier absorption, as opposed to stimulated transition. Therefore, the narrower modulation bandwidth of the quantum-dash lasers than that of quantum-well lasers was attributed to their higher gain compression factor. In addition, as expected, quantum-dash lasers with relatively long and uniform dashes exhibit higher temperature stability than quantum-well lasers. However, the lasers with relatively short and nonuniform dashes exhibit stronger temperature dependence, probably due to their higher surface-to-volume ratio and nonuniform dash sizes. © 2011 IEEE.

  15. Intrinsic thermoelectric power of group VB metals

    Directory of Open Access Journals (Sweden)

    Gunadhor Singh Okram

    2012-03-01

    Full Text Available We have reinvestigated the thermopower of group VB metals in polycrystalline forms in the temperature range of 6-300K, taking into account the critical nature of the sample surface and heat treatment especially for niobium. Strikingly small magnitude, negative sign, phonon drag dip and superconductivity not reported previously were observed in surface-cleaned single crystalline Nb. However, while thermopower magnitudes are small, mixed signs were found in the polycrystalline V, Nb and Ta samples. These properties were therefore interpreted as their intrinsic properties and were briefly discussed taking into account of the existing theory by fitting also the data that give the Fermi energies of 10.94 eV, 5.08 eV and 1.86eV, respectively.

  16. Computer Simulations of Intrinsically Disordered Proteins

    Science.gov (United States)

    Chong, Song-Ho; Chatterjee, Prathit; Ham, Sihyun

    2017-05-01

    The investigation of intrinsically disordered proteins (IDPs) is a new frontier in structural and molecular biology that requires a new paradigm to connect structural disorder to function. Molecular dynamics simulations and statistical thermodynamics potentially offer ideal tools for atomic-level characterizations and thermodynamic descriptions of this fascinating class of proteins that will complement experimental studies. However, IDPs display sensitivity to inaccuracies in the underlying molecular mechanics force fields. Thus, achieving an accurate structural characterization of IDPs via simulations is a challenge. It is also daunting to perform a configuration-space integration over heterogeneous structural ensembles sampled by IDPs to extract, in particular, protein configurational entropy. In this review, we summarize recent efforts devoted to the development of force fields and the critical evaluations of their performance when applied to IDPs. We also survey recent advances in computational methods for protein configurational entropy that aim to provide a thermodynamic link between structural disorder and protein activity.

  17. Intrinsic Ambipolarity and Rotation in Stellarators

    International Nuclear Information System (INIS)

    Helander, P.; Simakov, A. N.

    2008-01-01

    It is shown that collisional plasma transport is intrinsically ambipolar only in quasiaxisymmetric or quasihelically symmetric magnetic configurations. Only in such fields can the plasma rotate freely, and then only in the direction of quasisymmetry. In a non-quasi-symmetric magnetic field, the average radial electric field is determined by parallel viscosity, which in turn is usually governed by collisional processes. Locally, the radial electric field may be affected by turbulent Reynolds stress producing zonal flows, but on a radial average taken over several ion gyroradii, it is determined by parallel viscosity, at least if the turbulence is electrostatic and obeys the conventional gyrokinetic orderings. This differs from the situation in a tokamak, where there is no flow damping by parallel viscosity in the symmetry direction and the turbulent Reynolds stress may affect the global radial electric field

  18. IMPACT OF BARYONIC PHYSICS ON INTRINSIC ALIGNMENTS

    Energy Technology Data Exchange (ETDEWEB)

    Tenneti, Ananth; Gnedin, Nickolay Y. [Particle Astrophysics Center, Fermi National Accelerator Laboratory, Batavia, IL 60510 (United States); Feng, Yu, E-mail: vat@andrew.cmu.edu [Berkeley Center for Cosmological Physics, Department of Physics, University of California Berkeley, Berkeley, CA 94720 (United States)

    2017-01-10

    We explore the effects of specific assumptions in the subgrid models of star formation and stellar and active galactic nucleus feedback on intrinsic alignments of galaxies in cosmological simulations of the “MassiveBlack-II” family. Using smaller-volume simulations, we explore the parameter space of the subgrid star formation and feedback model and find remarkable robustness of the observable statistical measures to the details of subgrid physics. The one observational probe most sensitive to modeling details is the distribution of misalignment angles. We hypothesize that the amount of angular momentum carried away by the galactic wind is the primary physical quantity that controls the orientation of the stellar distribution. Our results are also consistent with a similar study by the EAGLE simulation team.

  19. Occupation and the relevance of primatology to occupational therapy.

    Science.gov (United States)

    Wood, W

    1993-06-01

    The adaptive functions of occupation during the phylogenetic history of the human species and the ontogenetic development of individual primates re examined through a review of relevant research of wild and captive nonhuman primates. This review suggests that the effectiveness of occupation as a therapeutic medium throughout life span development is fundamentally tied to humankind's phylogenetic history. It is accordingly argued that there is considerable justification to maintain occupational therapy's historical commitment to therapeutic occupation as the profession's primary treatment modality. To support this commitment, questions to guide practice and research are identified that emanate from the primate literature and that are highly germane to the therapeutic process in occupational therapy. These questions address: (a) the relationship between the press of the various environments in which occupational therapists practice and subsequent opportunities availed to patients for engagement in occupation; (b) the relationship between the extent to which patients are or are not empowered to exert real control over their use of time and their eventual development of disabling conditions; and (c) the therapeutic efficacy of occupation as compared with other treatment approaches that are not comparably holistic.

  20. Precision Machining Technologies. Occupational Competency Analysis Profile.

    Science.gov (United States)

    Ohio State Univ., Columbus. Vocational Instructional Materials Lab.

    This Occupational Competency Analysis Profile (OCAP), which is one of a series of OCAPs developed to identify the skills that Ohio employers deem necessary to entering a given occupation/occupational area, lists the occupational, academic, and employability skills required of individuals entering the occupation of precision machinist. The…

  1. Are Lithium Ion Cells Intrinsically Safe?

    Science.gov (United States)

    Dubaniewicz, Thomas H; DuCarme, Joseph P

    2013-11-01

    National Institute for Occupational Safety and Health researchers are studying the potential for Li-ion-battery thermal runaway from an internal short circuit in equipment approved as permissible for use in underground coal mines. Researchers used a plastic wedge to induce internal short circuits for thermal runaway susceptibility evaluation purposes, which proved to be a more severe test than the flat plate method for selected Li-ion cells. Researchers conducted cell crush tests within a 20-L chamber filled with 6.5% CH 4 -air to simulate the mining hazard. Results indicate that LG Chem ICR18650S2 LiCoO 2 cells pose a CH 4 explosion hazard from a cell internal short circuit. Under specified test conditions, A123 Systems 26650 LiFePO 4 cells were safer than the LG Chem ICR18650S2 LiCoO 2 cells at a conservative statistical significance level.

  2. Personality traits associated with intrinsic academic motivation in medical students.

    Science.gov (United States)

    Tanaka, Masaaki; Mizuno, Kei; Fukuda, Sanae; Tajima, Seiki; Watanabe, Yasuyoshi

    2009-04-01

    Motivation is one of the most important psychological concepts in education and is related to academic outcomes in medical students. In this study, the relationships between personality traits and intrinsic academic motivation were examined in medical students. The study group consisted of 119 Year 2 medical students at Osaka City University Graduate School of Medicine. They completed questionnaires dealing with intrinsic academic motivation (the Intrinsic Motivation Scale toward Learning) and personality (the Temperament and Character Inventory [TCI]). On simple regression analyses, the TCI dimensions of persistence, self-directedness, co-operativeness and self-transcendence were positively associated with intrinsic academic motivation. On multiple regression analysis adjusted for age and gender, the TCI dimensions of persistence, self-directedness and self-transcendence were positively associated with intrinsic academic motivation. The temperament dimension of persistence and the character dimensions of self-directedness and self-transcendence are associated with intrinsic academic motivation in medical students.

  3. Occupational radiation risk to radiologists

    International Nuclear Information System (INIS)

    Schuettmann, W.

    1981-01-01

    A review is given of the most important publications dealing with attempts to estimate the occupational radiation risk to radiologists by comparing data on their mortality from leukemia and other forms of cancer with respective data for other physicians who were not occupationally exposed to ionizing radiation. (author)

  4. Systematic reviews informing occupational therapy.

    Science.gov (United States)

    Bennett, Sally; Hoffmann, Tammy; McCluskey, Annie; Coghlan, Nicole; Tooth, Leigh

    2013-01-01

    We sought to identify and describe the number, topics, and publishing trends of systematic reviews relevant to occupational therapy indexed in the OTseeker database. We performed a cross-sectional survey of the systematic reviews contained in OTseeker in December 2011. Of the 1,940 systematic reviews indexed in OTseeker, only 53 (2.7%) were published in occupational therapy journals. The most common diagnostic categories were stroke (n = 195, 10.1%) and affective disorders (n = 204, 10.5%). The most common intervention categories were consumer education (n = 644, 33.2%) and psychosocial techniques (n = 571, 29.4%). Only 390 (20.1%) of the 1,940 systematic reviews specifically involved occupational therapy. Occupational therapists need to search broadly to locate relevant systematic reviews or, alternatively, to use databases such as OTseeker. Clarity about the involvement of occupational therapy in reports of future research will improve the ability to identify occupational therapy research for all stakeholders. Finally, occupational therapy practitioners need to read systematic reviews critically to determine whether review conclusions are justified. Copyright © 2013 by the American Occupational Therapy Association, Inc.

  5. Spina bifida and parental occupation

    NARCIS (Netherlands)

    Blatter, B.M.

    1997-01-01

    The aims of this thesis were: (1) to identify parental occupations with an increased risk of spina bifida in offspring; (2) to study whether parental occupational exposure to chemicals or radiation during or shortly before pregnancy is a risk factor for the occurrence of spina bifida. In order to

  6. Occupational ergonomics in space

    Science.gov (United States)

    Stramler, J.

    1992-01-01

    Ergonomics is often defined simply as the study of work. Related or synonymous terms include human factors, human engineering, engineering psychology, and others. Occupational ergonomics is a term that has been proposed to describe the study of the working environment, including the physical consequences resulting from having an improperly designed workplace. The routine space working environment presents some problems not found in the typical Earthbound workplace. These include radiation, intravehicular contamination/pollution, temperature extremes, impact with other objects, limited psychosocial relationships, sensory deprivation, and reduced gravity. These are important workplace considerations, and may affect astronauts either directly at work or at some point during their life as a result of their work under these conditions. Some of the major issues associated with each of these hazards are presented.

  7. Sources of intrinsic rotation in the low-flow ordering

    International Nuclear Information System (INIS)

    Parra, Felix I.; Barnes, Michael; Catto, Peter J.

    2011-01-01

    A low flow, δf gyrokinetic formulation to obtain the intrinsic rotation profiles is presented. The momentum conservation equation in the low-flow ordering contains new terms, neglected in previous first-principles formulations, that may explain the intrinsic rotation observed in tokamaks in the absence of external sources of momentum. The intrinsic rotation profile depends on the density and temperature profiles and on the up-down asymmetry.

  8. Increased intrinsic mitochondrial function in humans with mitochondrial haplogroup H

    DEFF Research Database (Denmark)

    Larsen, Steen; Díez-Sánchez, Carmen; Rabøl, Rasmus

    2014-01-01

    and determined their mitochondrial haplogroup, mitochondrial oxidative phosphorylation capacity (OXPHOS), mitochondrial content (citrate synthase (CS)) and VO2max. Intrinsic mitochondrial function is calculated as mitochondrial OXPHOS capacity divided by mitochondrial content (CS). Haplogroup H showed a 30......% higher intrinsic mitochondrial function compared with the other haplo group U. There was no relationship between haplogroups and VO2max. In skeletal muscle from men with mitochondrial haplogroup H, an increased intrinsic mitochondrial function is present....

  9. The effects of extrinsic rewards on children's intrinsic motivation

    OpenAIRE

    大槻, 千秋

    1981-01-01

    An experiment was conducted with preschool children to test whether a person's intrinsic motivation in an activity may be decreased by extrinsic salient rewards in Japan like in America. Children solved some jigsaw puzzles and received assorted candies, then they were observed how long they did other jigsaw puzzles. The results showed that the effects of extrinsic rewards on intrinsic motivation in an activity varied with the subject's social background. In uptown children's intrinsic motivat...

  10. Do intrinsic and extrinsic motivation relate differently to employee outcomes?

    OpenAIRE

    Kuvaas, Bard; Buch, Robert; Weibel, Antoinette; Dysvik, Anders; Nerstad, Christina

    2017-01-01

    In most theories that address how individual financial incentives affect work performance, researchers have assumed that two types of motivation—intrinsic and extrinsic—mediate the relationship between incentives and performance. Empirically, however, extrinsic motivation is rarely investigated. To explore the predictive validity of these theories of intrinsic and extrinsic motivation in work settings, we tested how both intrinsic and extrinsic motivation affected supervisor-ra...

  11. International Occupational Therapy Research Priorities.

    Science.gov (United States)

    Mackenzie, Lynette; Coppola, Susan; Alvarez, Liliana; Cibule, Lolita; Maltsev, Sergey; Loh, Siew Yim; Mlambo, Tecla; Ikiugu, Moses N; Pihlar, Zdenka; Sriphetcharawut, Sarinya; Baptiste, Sue; Ledgerd, Richard

    2017-04-01

    Occupational therapy is a global profession represented by the World Federation of Occupational Therapists (WFOT). International research priorities are needed for strategic guidance on global occupational therapy practice. The objective of this study was to develop international research priorities to reflect global occupational therapy practice. A Delphi study using three rounds of electronic surveys, distributed to WFOT member organizations and WFOT accredited universities, was conducted. Data were analyzed after each round, and priorities were presented for rating and ranking in order of importance. Forty-six (53%) out of 87 WFOT member countries participated in the Delphi process. Eight research priorities were confirmed by the final electronic survey round. Differences were observed in rankings given by member organizations and university respondents. Despite attrition at Round 3, the final research priorities will help to focus research efforts in occupational therapy globally. Follow-up research is needed to determine how the research priorities are being adopted internationally.

  12. Occupational therapy, culture and diversity

    Directory of Open Access Journals (Sweden)

    Salvador Simó Algado

    2016-01-01

    Full Text Available Occupational behaviour is always an environmental behaviour because the occupation is the dialogue between human beings and their environment. Culture is key dimension in our profession. This article is based on previous research and a new review of the scientific literature on the various meanings associated with culture. In the contemporary context the globalization involves the imposition of the American way of life on a planetary scale. In front of ethnocentrism and racism a diatopical hermeneutics is proposed. A cosmopolitan citizenship can be constructed supporting diversity. The article concludes by reflecting on strategies that can be implemented from occupational therapy to develop a culturally safe occupational therapy. An archaeology of meaning must be developed in front of the Americanization. Occupational therapy needs to develop a powerful political activism in order to build an inclusive society based on human rights and sustainability. Culture and diversity are key elements in this process.

  13. DOE 2012 occupational radiation exposure

    Energy Technology Data Exchange (ETDEWEB)

    none,

    2013-10-01

    The U.S. Department of Energy (DOE) Office of Analysis within the Office of Health, Safety and Security (HSS) publishes the annual DOE Occupational Radiation Exposure Report to provide an overview of the status of radiation protection practices at DOE (including the National Nuclear Security Administration [NNSA]). The DOE 2012 Occupational Radiation Exposure Report provides an evaluation of DOE-wide performance regarding compliance with Title 10, Code of Federal Regulations (C.F.R.), Part 835, Occupational Radiation Protection dose limits and as low as reasonably achievable (ALARA) process requirements. In addition, the report provides data to DOE organizations responsible for developing policies for protection of individuals from the adverse health effects of radiation. The report provides a summary and an analysis of occupational radiation exposure information from the monitoring of individuals involved in DOE activities. Over the past 5-year period, the occupational radiation exposure information is analyzed in terms of aggregate data, dose to individuals, and dose by site.

  14. DOE 2011 occupational radiation exposure

    Energy Technology Data Exchange (ETDEWEB)

    none,

    2012-12-01

    The U.S. Department of Energy (DOE) Office of Analysis within the Office of Health, Safety and Security (HSS) publishes the annual DOE Occupational Radiation Exposure Report to provide an overview of the status of radiation protection practices at DOE (including the National Nuclear Security Administration [NNSA]). The DOE 2011 Occupational Radiation Exposure Report provides an evaluation of DOE-wide performance regarding compliance with Title 10, Code of Federal Regulations (C.F.R.), Part 835, Occupational Radiation Protection dose limits and as low as reasonably achievable (ALARA) process requirements. In addition, the report provides data to DOE organizations responsible for developing policies for protection of individuals from the adverse health effects of radiation. The report provides a summary and an analysis of occupational radiation exposure information from the monitoring of individuals involved in DOE activities. The occupational radiation exposure information is analyzed in terms of aggregate data, dose to individuals, and dose by site over the past five years.

  15. Occupational Trends and Program Priorities

    Directory of Open Access Journals (Sweden)

    Dan Rosenthal

    2001-07-01

    Full Text Available Institutions of higher education that respond to the economic base in their region will remain competitive and be better positioned to obtain public funds and donor support. In addition to mandated program viability standards based on measures such as graduation rate, individual institutions and state coordinating boards can use ten-year occupational trend data to assess future program viability. We used an occupational demand model to determine whether academic programs can meet projected statewide needs for high demand and high growth occupations. For example, computer engineering, the highest growth rate occupation in Alabama, is projected to have 365 annual average job openings, with 93.6% total growth over ten years. But only 46 computer engineering majors graduate annually from all Alabama institutions of higher education. We recommend using an occupational demand model as a planning tool, decision-making tool, and catalyst for collaborative initiatives.

  16. Corporate Cost of Occupational Accidents

    DEFF Research Database (Denmark)

    Rikhardsson, Pall M.; Impgaard, M.

    2004-01-01

    The systematic accident cost analysis (SACA) project was carried out during 2001 by The Aarhus School of Business and PricewaterhouseCoopers Denmark with financial support from The Danish National Working Environment Authority. Its focused on developing and testing a method for evaluating...... occupational costs of companies for use by occupational health and safety professionals. The method was tested in nine Danish companies within three different industry sectors and the costs of 27 selected occupational accidents in these companies were calculated. One of the main conclusions is that the SACA...... method could be used in all of the companies without revisions. The evaluation of accident cost showed that 2/3 of the costs of occupational accidents are visible in the Danish corporate accounting systems reviewed while 1/3 is hidden from management view. The highest cost of occupational accidents...

  17. Interventions for primary (intrinsic tracheomalacia in children

    Directory of Open Access Journals (Sweden)

    Vikas Goyal

    Full Text Available BACKGROUNDTracheomalacia, a disorder of the large airways where the trachea is deformed or malformed during respiration, is commonly seen in tertiary paediatric practice. It is associated with a wide spectrum of respiratory symptoms from life-threatening recurrent apnoea to common respiratory symptoms such as chronic cough and wheeze. Current practice following diagnosis of tracheomalacia includes medical approaches aimed at reducing associated symptoms of tracheomalacia, ventilation modalities of continuous positive airway pressure (CPAP and bi-level positive airway pressure (BiPAP, and surgical approaches aimed at improving the calibre of the airway (airway stenting, aortopexy, tracheopexy.OBJECTIVESTo evaluate the efficacy of medical and surgical therapies for children with intrinsic (primary tracheomalacia.METHODSSearchThe Cochrane Airways Group searched the Cochrane Central Register of Controlled Trials (CENTRAL, the Cochrane Airways Group's Specialized Register, Medline and Embase databases. The Cochrane Airways Group performed the latest searches in March 2012.Selection criteriaAll randomized controlled trials (RCTs of therapies related to symptoms associated with primary or intrinsic tracheomalacia.Data collection and analysisTwo reviewers extracted data from the included study independently and resolved disagreements by consensus.MAIN RESULTSWe included one RCT that compared nebulized recombinant human deoxyribonuclease (rhDNase with placebo in 40 children with airway malacia and a respiratory tract infection. We assessed it to be a RCT with overall low risk of bias. Data analyzed in this review showed that there was no significant difference between groups for the primary outcome of proportion cough-free at two weeks (odds ratio (OR 1.38; 95% confidence interval (CI 0.37 to 5.14. However, the mean change in night time cough diary scores significantly favoured the placebo group (mean difference (MD 1.00; 95% CI 0.17 to 1.83, P = 0

  18. 75 FR 23834 - Occupational Information System

    Science.gov (United States)

    2010-05-04

    ... SOCIAL SECURITY ADMINISTRATION [Docket No. SSA-2010-0018] Occupational Information System AGENCY... Administration Occupational Information System, September 2009.'' The complete Panel report (including appendices... to provide independent advice and recommendations on creating an occupational information system...

  19. Understanding oceanic migrations with intrinsic biogeochemical markers.

    Directory of Open Access Journals (Sweden)

    Raül Ramos

    2009-07-01

    Full Text Available Migratory marine vertebrates move annually across remote oceanic water masses crossing international borders. Many anthropogenic threats such as overfishing, bycatch, pollution or global warming put millions of marine migrants at risk especially during their long-distance movements. Therefore, precise knowledge about these migratory movements to understand where and when these animals are more exposed to human impacts is vital for addressing marine conservation issues. Because electronic tracking devices suffer from several constraints, mainly logistical and financial, there is emerging interest in finding appropriate intrinsic markers, such as the chemical composition of inert tissues, to study long-distance migrations and identify wintering sites. Here, using tracked pelagic seabirds and some of their own feathers which were known to be grown at different places and times within the annual cycle, we proved the value of biogeochemical analyses of inert tissue as tracers of marine movements and habitat use. Analyses of feathers grown in summer showed that both stable isotope signatures and element concentrations can signal the origin of breeding birds feeding in distinct water masses. However, only stable isotopes signalled water masses used during winter because elements mainly accumulated during the long breeding period are incorporated into feathers grown in both summer and winter. Our findings shed new light on the simple and effective assignment of marine organisms to distinct oceanic areas, providing new opportunities to study unknown migration patterns of secretive species, including in relation to human-induced mortality on specific populations in the marine environment.

  20. Exploiting intrinsic fluctuations to identify model parameters.

    Science.gov (United States)

    Zimmer, Christoph; Sahle, Sven; Pahle, Jürgen

    2015-04-01

    Parameterisation of kinetic models plays a central role in computational systems biology. Besides the lack of experimental data of high enough quality, some of the biggest challenges here are identification issues. Model parameters can be structurally non-identifiable because of functional relationships. Noise in measured data is usually considered to be a nuisance for parameter estimation. However, it turns out that intrinsic fluctuations in particle numbers can make parameters identifiable that were previously non-identifiable. The authors present a method to identify model parameters that are structurally non-identifiable in a deterministic framework. The method takes time course recordings of biochemical systems in steady state or transient state as input. Often a functional relationship between parameters presents itself by a one-dimensional manifold in parameter space containing parameter sets of optimal goodness. Although the system's behaviour cannot be distinguished on this manifold in a deterministic framework it might be distinguishable in a stochastic modelling framework. Their method exploits this by using an objective function that includes a measure for fluctuations in particle numbers. They show on three example models, immigration-death, gene expression and Epo-EpoReceptor interaction, that this resolves the non-identifiability even in the case of measurement noise with known amplitude. The method is applied to partially observed recordings of biochemical systems with measurement noise. It is simple to implement and it is usually very fast to compute. This optimisation can be realised in a classical or Bayesian fashion.

  1. Does intrinsic motivation enhance motor cortex excitability?

    Science.gov (United States)

    Radel, Rémi; Pjevac, Dusan; Davranche, Karen; d'Arripe-Longueville, Fabienne; Colson, Serge S; Lapole, Thomas; Gruet, Mathieu

    2016-11-01

    Intrinsic motivation (IM) is often viewed as a spontaneous tendency for action. Recent behavioral and neuroimaging evidence indicate that IM, in comparison to extrinsic motivation (EM), solicits the motor system. Accordingly, we tested whether IM leads to greater excitability of the motor cortex than EM. To test this hypothesis, we used two different tasks to induce the motivational orientation using either words representing each motivational orientation or pictures previously linked to each motivational orientation through associative learning. Single-pulse transcranial magnetic stimulation over the motor cortex was applied when viewing the stimuli. Electromyographic activity was recorded on the contracted first dorsal interosseous muscle. Two indexes of corticospinal excitability (the amplitude of motor-evoked potential and the length of cortical silent period) were obtained through unbiased automatic detection and analyzed using a mixed model that provided both statistical power and a high level of control over all important individual, task, and stimuli characteristics. Across the two tasks and the two indices of corticospinal excitability, the exposure to IM-related stimuli did not lead to a greater corticospinal excitability than EM-related stimuli or than stimuli with no motivational valence (ps > .20). While these results tend to dismiss the advantage of IM at activating the motor cortex, we suggest alternative hypotheses to explain this lack of effect, which deserves further research. © 2016 Society for Psychophysiological Research.

  2. Dynamic Neural Fields with Intrinsic Plasticity.

    Science.gov (United States)

    Strub, Claudius; Schöner, Gregor; Wörgötter, Florentin; Sandamirskaya, Yulia

    2017-01-01

    Dynamic neural fields (DNFs) are dynamical systems models that approximate the activity of large, homogeneous, and recurrently connected neural networks based on a mean field approach. Within dynamic field theory, the DNFs have been used as building blocks in architectures to model sensorimotor embedding of cognitive processes. Typically, the parameters of a DNF in an architecture are manually tuned in order to achieve a specific dynamic behavior (e.g., decision making, selection, or working memory) for a given input pattern. This manual parameters search requires expert knowledge and time to find and verify a suited set of parameters. The DNF parametrization may be particular challenging if the input distribution is not known in advance, e.g., when processing sensory information. In this paper, we propose the autonomous adaptation of the DNF resting level and gain by a learning mechanism of intrinsic plasticity (IP). To enable this adaptation, an input and output measure for the DNF are introduced, together with a hyper parameter to define the desired output distribution. The online adaptation by IP gives the possibility to pre-define the DNF output statistics without knowledge of the input distribution and thus, also to compensate for changes in it. The capabilities and limitations of this approach are evaluated in a number of experiments.

  3. Diffuse intrinsic pontine glioma: poised for progress

    International Nuclear Information System (INIS)

    Warren, Katherine E.

    2012-01-01

    Diffuse intrinsic pontine gliomas (DIPGs) are amongst the most challenging tumors to treat. Surgery is not an option, the effects of radiation therapy are temporary, and no chemotherapeutic agent has demonstrated significant efficacy. Numerous clinical trials of new agents and novel therapeutic approaches have been performed over the course of several decades in efforts to improve the outcome of children with DIPG, yet without success. The diagnosis of DIPG is based on radiographic findings in the setting of a typical clinical presentation, and tissue is not routinely obtained as the standard of care. The paradigm for treating children with these tumors has been based on that for supratentorial high-grade gliomas in adults as the biology of these lesions were presumed to be similar. However, recent pivotal studies demonstrate that DIPGs appear to be their own entity. Simply identifying this fact releases a number of constraints and opens opportunities for biologic investigation of these lesions, setting the stage to move forward in identifying DIPG-specific treatments. This review will summarize the current state of knowledge of DIPG, discuss obstacles to therapy, and summarize results of recent biologic studies.

  4. Intrinsic gain modulation and adaptive neural coding.

    Directory of Open Access Journals (Sweden)

    Sungho Hong

    2008-07-01

    Full Text Available In many cases, the computation of a neural system can be reduced to a receptive field, or a set of linear filters, and a thresholding function, or gain curve, which determines the firing probability; this is known as a linear/nonlinear model. In some forms of sensory adaptation, these linear filters and gain curve adjust very rapidly to changes in the variance of a randomly varying driving input. An apparently similar but previously unrelated issue is the observation of gain control by background noise in cortical neurons: the slope of the firing rate versus current (f-I curve changes with the variance of background random input. Here, we show a direct correspondence between these two observations by relating variance-dependent changes in the gain of f-I curves to characteristics of the changing empirical linear/nonlinear model obtained by sampling. In the case that the underlying system is fixed, we derive relationships relating the change of the gain with respect to both mean and variance with the receptive fields derived from reverse correlation on a white noise stimulus. Using two conductance-based model neurons that display distinct gain modulation properties through a simple change in parameters, we show that coding properties of both these models quantitatively satisfy the predicted relationships. Our results describe how both variance-dependent gain modulation and adaptive neural computation result from intrinsic nonlinearity.

  5. Toward a tripartite model of intrinsic motivation.

    Science.gov (United States)

    Carbonneau, Noémie; Vallerand, Robert J; Lafrenière, Marc-André K

    2012-10-01

    Intrinsic motivation (IM) refers to engaging in an activity for the pleasure inherent in the activity. The present article presents a tripartite model of IM consisting of IM to know (i.e., engaging in an activity to experience pleasure while learning and trying to understand something new), IM toward accomplishment (i.e., engaging in an activity for the pleasure experienced when attempting task mastery), and IM to experience stimulation (i.e., engaging in an activity for feelings of sensory pleasure). The tripartite model of IM posits that each type of IM can result from task, situational, and personality determinants and can lead to specific types of cognitive, affective, and behavioral outcomes. The purpose of this research was to test some predictions derived from this model. Across 4 studies (Study 1: N = 331; Study 2: N = 113; Study 3: N = 58; Study 4: N = 135), the 3 types of IM as well as potential determinants and consequences were assessed. Results revealed that experiencing one type of IM over the others depends in part on people's personality styles. Also, each type of IM was found to predict specific outcomes (i.e., affective states and behavioral choices). The implications of the tripartite model of IM for motivation research are discussed. © 2011 The Authors. Journal of Personality © 2011, Wiley Periodicals, Inc.

  6. Rates, intrinsic linkages, and multistate population dynamics.

    Science.gov (United States)

    Schoen, Robert

    2017-01-01

    Demographic analyses of multistate populations are commonplace, as are situations where population stocks are known but population flows are not. Still, demographic models for multistate populations with changing rates remain at an early stage of development, limiting dynamic analyses and analytical projections. Here, a new approach, the Intrinsic Linkage-Rate Ratio (IL-RR) model, is presented and explored. The key IL parameter, w , is a simple weight for projecting populations. Using the ultimate state composition implied by the prevailing rates, the IL-RR model provides new relationships that connect multistate populations over time and allow analytical population projections. Parameter w reflects population metabolism and scales the level of the transfer rates. Compositional change is driven by the sequence of implicit stable population compositions. The IL-RR approach also provides a new method for estimating transfer rates within an interval from population numbers at the beginning and end of the interval. The new relationships developed advance the ability of demographers to model multistate populations with changing rates and to relate population stocks and flows.

  7. Surgical Treatment Guidelines for Digital Deformity Associated With Intrinsic Muscle Spasticity (Intrinsic Plus Foot) in Adults With Cerebral Palsy.

    Science.gov (United States)

    Boffeli, Troy J; Collier, Rachel C

    2015-01-01

    Intrinsic plus foot deformity has primarily been associated with cerebral palsy and involves spastic contracture of the intrinsic musculature with resultant toe deformities. Digital deformity is caused by a dynamic imbalance between the intrinsic muscles in the foot and extrinsic muscles in the lower leg. Spastic contracture of the toes frequently involves curling under of the lesser digits or contracture of the hallux into valgus or plantarflexion deformity. Patients often present with associated pressure ulcers, deformed toenails, shoe or brace fitting challenges, and pain with ambulation or transfers. Four different patterns of intrinsic plus foot deformity have been observed by the authors that likely relate to the different patterns of muscle involvement. Case examples are provided of the 4 patterns of intrinsic plus foot deformity observed, including global intrinsic plus lesser toe deformity, isolated intrinsic plus lesser toe deformity, intrinsic plus hallux valgus deformity, and intrinsic plus hallux flexus deformity. These case examples are presented to demonstrate each type of deformity and our approach for surgical management according to the contracture pattern. The surgical approach has typically involved tenotomy, capsulotomy, or isolated joint fusion. The main goals of surgical treatment are to relieve pain and reduce pressure points through digital realignment in an effort to decrease the risk of pressure sores and allow more effective bracing to ultimately improve the patient's mobility. Copyright © 2015 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

  8. Occupation and cancer in Britain.

    Science.gov (United States)

    Rushton, L; Bagga, S; Bevan, R; Brown, T P; Cherrie, J W; Holmes, P; Fortunato, L; Slack, R; Van Tongeren, M; Young, C; Hutchings, S J

    2010-04-27

    Prioritising control measures for occupationally related cancers should be evidence based. We estimated the current burden of cancer in Britain attributable to past occupational exposures for International Agency for Research on Cancer (IARC) group 1 (established) and 2A (probable) carcinogens. We calculated attributable fractions and numbers for cancer mortality and incidence using risk estimates from the literature and national data sources to estimate proportions exposed. 5.3% (8019) cancer deaths were attributable to occupation in 2005 (men, 8.2% (6362); women, 2.3% (1657)). Attributable incidence estimates are 13 679 (4.0%) cancer registrations (men, 10 063 (5.7%); women, 3616 (2.2%)). Occupational attributable fractions are over 2% for mesothelioma, sinonasal, lung, nasopharynx, breast, non-melanoma skin cancer, bladder, oesophagus, soft tissue sarcoma, larynx and stomach cancers. Asbestos, shift work, mineral oils, solar radiation, silica, diesel engine exhaust, coal tars and pitches, occupation as a painter or welder, dioxins, environmental tobacco smoke, radon, tetrachloroethylene, arsenic and strong inorganic mists each contribute 100 or more registrations. Industries and occupations with high cancer registrations include construction, metal working, personal and household services, mining, land transport, printing/publishing, retail/hotels/restaurants, public administration/defence, farming and several manufacturing sectors. 56% of cancer registrations in men are attributable to work in the construction industry (mainly mesotheliomas, lung, stomach, bladder and non-melanoma skin cancers) and 54% of cancer registrations in women are attributable to shift work (breast cancer). This project is the first to quantify in detail the burden of cancer and mortality due to occupation specifically for Britain. It highlights the impact of occupational exposures, together with the occupational circumstances and industrial areas where exposures to carcinogenic agents

  9. Occupancy models to study wildlife

    Science.gov (United States)

    Bailey, Larissa; Adams, Michael John

    2005-01-01

    Many wildlife studies seek to understand changes or differences in the proportion of sites occupied by a species of interest. These studies are hampered by imperfect detection of these species, which can result in some sites appearing to be unoccupied that are actually occupied. Occupancy models solve this problem and produce unbiased estimates of occupancy and related parameters. Required data (detection/non-detection information) are relatively simple and inexpensive to collect. Software is available free of charge to aid investigators in occupancy estimation.

  10. Wanted: entrepreneurs in occupational therapy.

    Science.gov (United States)

    Anderson, Kristin M; Nelson, David L

    2011-01-01

    The American Occupational Therapy Association (AOTA) has challenged occupational therapy practitioners to advance the profession so that we may become more "powerful" and "widely recognized" by the year 2017 (AOTA, 2007a). To fully achieve this vision, this article argues that the profession should encourage occupational therapy entrepreneurship. As Herz, Bondoc, Richmond, Richman, and Kroll (2005, p.2) stated, "Entrepreneurship may provide us with the means to achieve the outcomes we need to succeed in the current health care environment." This article also argues the urgency of seizing the many opportunities that entrepreneurship offers and recommends specific actions to be taken by AOTA and by therapists.

  11. Adolescents' Perceptions of Family Connectedness, Intrinsic Religiosity, and Depressed Mood

    Science.gov (United States)

    Houltberg, Benjamin J.; Henry, Carolyn S.; Merten, Michael J.; Robinson, Linda C.

    2011-01-01

    Using a sample of 248 ninth and tenth grade students at public high schools, we examined adolescents' perceptions of family connectedness, intrinsic religiosity, and adolescents' gender in relation to depressed mood and whether intrinsic religiosity and gender moderated the association of aspects of family connectedness to adolescent depressed…

  12. Palatalization and Intrinsic Prosodic Vowel Features in Russian

    Science.gov (United States)

    Ordin, Mikhail

    2011-01-01

    The presented study is aimed at investigating the interaction of palatalization and intrinsic prosodic features of the vowel in CVC (consonant+vowel+consonant) syllables in Russian. The universal nature of intrinsic prosodic vowel features was confirmed with the data from the Russian language. It was found that palatalization of the consonants…

  13. Self-Determination Theory: Intrinsic Motivation and Behavioral Change.

    Science.gov (United States)

    Flannery, Marie

    2017-03-01

    Motivation is a central concept in behavioral change. This article reviews the self-determination theory with an emphasis on "intrinsic motivation," which is facilitated when three basic psychological needs (autonomy, competence, and relatedness) are met. Intrinsic motivation is associated with improved well-being and sustained behavioral change.

  14. Elderly Taiwanese's Intrinsic Risk Factors for Fall-related Injuries

    Directory of Open Access Journals (Sweden)

    In-Fun Li

    2016-09-01

    Conclusion: Elderly Taiwanese inpatients with existing intrinsic conditions of cancer, vertigo, and lower leg weakness were at high risk of falling, resulting in severe injuries. Additional research including controlled trials is necessary to further identify treatable, causal intrinsic risk factors for this elderly group.

  15. Intrinsic antecedents of academic research productivity of a large ...

    African Journals Online (AJOL)

    Kirstam

    Intrinsic antecedents of academic research productivity of a large South African university. 175 influences as given, certain theory predicts that individual intrinsic differences can be associated with differences in individual job performance. Positive affectivity, or affect, can contribute to job satisfaction, as a result of the fit.

  16. Intrinsic religiosity reduces intergroup hostility under mortality salience

    NARCIS (Netherlands)

    De Zavala, Agnieszka Golec; Cichocka, Aleksandra; Orehek, Edward; Abdollahi, Abdolhossein

    Results of three studies indicate that intrinsic religiosity and mortality salience interact to predict intergroup hostility. Study 1, conducted among 200 American Christians and Jews, reveals that under mortality salience, intrinsic (but not extrinsic or quest) religiosity is related to decreased

  17. Extrinsic Rewards and Intrinsic Motivation in Children. Final Report.

    Science.gov (United States)

    Lepper, Mark R.

    Three experiments were conducted to examine the effects of providing extrinsic rewards for engaging in an activity on children's subsequent intrinsic interest in that activity. In each study, preschool children were asked to engage in an activity of initial intrinsic interest in individual experimental sessions. The children agreed to engage in…

  18. Creativity as Mediator for Intrinsic Motivation and Sales Performance

    Science.gov (United States)

    Bodla, Mahmood A.; Naeem, Basharat

    2014-01-01

    Substantial theoretical and empirical literature indicates inconsistent performance implications of intrinsic motivation, suggesting the possibility of some explanatory mechanisms. However, little is known about the factors that might explain intrinsic motivation and sales force performance relation, particularly in highly competitive and…

  19. Intrinsic Motivation and Flow Condition on the Music Teacher's Performance

    Science.gov (United States)

    Torres Delgado, Gabriela

    2017-01-01

    The aim of these research is to identify if music teachers and teachers from other areas are intrinsically or extrinsically motivated, to identify the dimensions of the flow state, and to identify if there is a relationship between intrinsic motivation and flow state in these teachers. The sample was made up of 738 active teachers. The presence of…

  20. Intrinsic antecedents of academic research productivity of a large ...

    African Journals Online (AJOL)

    Across different contexts, the human resources literature suggests that a range of intrinsic factors – typically measured as psychographic, or intrinsic, variables – are antecedents of individual job performance. What is not clear from this literature, however, is the relative contribution of different dimensions of these factors to ...

  1. Senescence-associated intrinsic mechanisms of osteoblast dysfunctions

    DEFF Research Database (Denmark)

    Kassem, Moustapha; Trinquier, Anne Marie-Pierre Emilie

    2011-01-01

    factors, and intrinsic mechanisms caused by the osteoblast cellular senescence. The aim of this review is to provide a summary of the intrinsic senescence mechanisms affecting osteoblastic functions and how they can be targeted in order to abolish age-related osteoblastic dysfunction and bone loss...

  2. Cooperative motion of intrinsic and actuated semiflexible swimmers

    NARCIS (Netherlands)

    Llopis, I.; Pagonabarraga, I.; Lagomarsino, M.C.; Lowe, C.P.

    2013-01-01

    We examine the phenomenon of hydrodynamic-induced cooperativity for pairs of flagellated micro-organism swimmers, of which spermatozoa cells are an example. We consider semiflexible swimmers, where inextensible filaments are driven by an internal intrinsic force and torque-free mechanism (intrinsic

  3. Leadership style and employees' intrinsic job satisfaction in the ...

    African Journals Online (AJOL)

    This study investigates the impact of leadership style on employees' intrinsic job satisfaction in the Cross River State Newspaper Corporation, Calabar, Nigeria. The study examined the problem of dissatisfaction in the work place as far as intrinsic factors of job satisfaction are concerned. Structured questionnaire was used ...

  4. Occupational cancer and radiation

    International Nuclear Information System (INIS)

    Brahams, D.

    1988-01-01

    There have been two High Court actions and seven inquests in the UK, with reference to the debate on occupational hazards of long term, low dose exposure. In July, 1987, two cases alleging that workers in the nuclear industry had contracted cancer due to their exposure to radiation at work had to be abandoned halfway through the trial after the judge had heard the medical evidence. A 57-year old man claimed that Hodgkin's disease had been caused by radiation while at work at Sellafield. However, medical opinion was that Hodgkin's disease had never been accepted as caused by radiation. In the second case a man who had died of stomach cancer at the age of 54 after working for UKAEA at Dounreay for 7 years, had received 190 mSv. The defendants' experts rated the likelihood of radiation as the cause at 3-6%; the plaintiffs' experts had suggested 30-50%. Seven inquest juries sitting in West Cumbria from 1983 to 1988 have brought in three verdicts of death caused by an industrial disease, three open verdicts, and one of natural causes. The men had all worked for BNFL at Sellafield for many years. (author)

  5. Intrinsic motivation and sportsmanship: mediating role of interpersonal relationships.

    Science.gov (United States)

    Núñez, Juan L; Martín-Albo, José; Navarro, José G; Sánchez, Juana M; González-Cutre, David

    2009-06-01

    This study analyzed the mediating role of interpersonal relations between intrinsic motivation and sportsmanship. Athletes (98 men, 97 women), ages 11 to 43 years, completed measures of intrinsic motivation toward sports, self-concept of social and family relations, and sportsmanship orientation. A structural equation model indicated that self-concept of interpersonal relations mediated the relation between intrinsic motivation and sportsmanship. Also, intrinsic motivation was directly and positively associated with self-concept of interpersonal relations, which, in turn, was positively and significantly related to sportsmanship. Variances explained by self-concept of interpersonal relations and by sportsmanship were 32 and 56%, respectively. The motivational interaction between the context of interpersonal relations and the sports context proposed in the hierarchical model of intrinsic and extrinsic motivation was discussed.

  6. Motivating crowding theory - opening the black box of intrinsic motivation

    DEFF Research Database (Denmark)

    Jacobsen, Christian Bøtcher

    2010-01-01

    Public employees work for many other reasons than because they are paid for it. In other words, intrinsic motivation is an important determinant for their performance. Nonetheless, public sector organizations increasingly rely on extrinsic motivation factors such as monetary incentives to motivate...... employees. Motivation crowding theory claims that this may be at the expense of intrinsic motivation, if the extrinsic motivation factor is perceived to be controlling. On the other hand, intrinsic motivation will be enhanced (crowded in), if the extrinsic motivation factor is perceived to be supportive....... Studies have found support for the motivation crowding claim, but have neglected intrinsic motivation. This study opens the black box of intrinsic motivation and finds a meaningful distinction between task motivation and public service motivation. Among 2,772 physiotherapists in the Danish public sector...

  7. Intrinsic Evaporative Cooling by Hygroscopic Earth Materials

    Directory of Open Access Journals (Sweden)

    Alexandra R. Rempel

    2016-08-01

    Full Text Available The phase change of water from liquid to vapor is one of the most energy-intensive physical processes in nature, giving it immense potential for cooling. Diverse evaporative cooling strategies have resulted worldwide, including roof ponds and sprinklers, courtyard fountains, wind catchers with qanats, irrigated green roofs, and fan-assisted evaporative coolers. These methods all require water in bulk liquid form. The evaporation of moisture that has been sorbed from the atmosphere by hygroscopic materials is equally energy-intensive, however, yet has not been examined for its cooling potential. In arid and semi-arid climates, hygroscopic earth buildings occur widely and are known to maintain comfortable indoor temperatures, but evaporation of moisture from their walls and roofs has been regarded as unimportant since water scarcity limits irrigation and rainfall; instead, their cool interiors are attributed to well-established mass effects in delaying the transmission of sensible gains. Here, we investigate the cooling accomplished by daily cycles of moisture sorption and evaporation which, requiring only ambient humidity, we designate as “intrinsic” evaporative cooling. Connecting recent soil science to heat and moisture transport studies in building materials, we use soils, adobe, cob, unfired earth bricks, rammed earth, and limestone to reveal the effects of numerous parameters (temperature and relative humidity, material orientation, thickness, moisture retention properties, vapor diffusion resistance, and liquid transport properties on the magnitude of intrinsic evaporative cooling and the stabilization of indoor relative humidity. We further synthesize these effects into concrete design guidance. Together, these results show that earth buildings in diverse climates have significant potential to cool themselves evaporatively through sorption of moisture from humid night air and evaporation during the following day’s heat. This finding

  8. Occupational Safety and Health Administration

    Science.gov (United States)

    ... Translate UNITED STATES DEPARTMENT OF LABOR Facebook Twitter Instagram RSS Subscribe Search A TO Z INDEX UNITED STATES DEPARTMENT OF LABOR Facebook Twitter Instagram RSS Subscribe Occupational Safety and Health Administration English | ...

  9. Occupational therapy for multiple sclerosis.

    NARCIS (Netherlands)

    Steultjens, E.M.J.; Dekker, J.; Bouter, L.M.; Cardol, M.; Nes, J.C.M. van de; Ende, C.H.M. van den

    2003-01-01

    Background: Multiple sclerosis (MS) patients are referred to occupational therapy with complaints about fatigue, limb weakness, alteration of upper extremity fine motor coordination, loss of sensation and spasticity that causes limitations in performance of activities of daily living and social

  10. DOE 2009 occupational radiation exposure

    Energy Technology Data Exchange (ETDEWEB)

    none,

    2010-09-01

    The U.S. Department of Energy (DOE) Office of Corporate Safety Analysis (HS-30) within the Office of Health, Safety and Security (HSS) publishes the annual DOE Occupational Radiation Exposure Report to provide an overview of the status of radiation protection practices at DOE.* The DOE 2009 Occupational Radiation Exposure Report provides an evaluation of DOE-wide performance regarding compliance with DOE Part 835 dose limits and as low as reasonably achievable (ALARA) process requirements. In addition, the report provides data to DOE organizations responsible for developing policies for protection of individuals from the effects of radiation. The report provides a summary and an analysis of occupational radiation exposure information from the monitoring of individuals involved in DOE activities. The occupational radiation exposure information is analyzed in terms of aggregate data, dose to individuals, and dose by site over the past 5 years.

  11. Occupational contact dermatitis in hairdressers

    DEFF Research Database (Denmark)

    Schwensen, Jakob F; Johansen, Jeanne D; Veien, Niels K

    2014-01-01

    BACKGROUND: Occupational contact dermatitis among hairdressers is frequent, owing to daily exposure to irritants and allergens. OBJECTIVES: To identify sensitization to the most common allergens associated with the occupation of hairdressing. METHODS: Patch test results of 399 hairdressers and 1995...... matched controls with contact dermatitis, registered by the Danish Contact Dermatitis Group between January 2002 and December 2011, were analysed. All patients were patch tested with the European baseline series, and hairdressers were additionally tested with the hairdressing series. RESULTS: Occupational...... with a statistically significant association with the occupation of hairdressing were p-phenylenediamine, thiuram mix, and benzocaine. Frequent sensitizers from the hairdressing series were ammonium persulfate, toluene-2,5-diamine, 3-aminophenol, and 4-aminophenol. Cysteamine hydrochloride and chloroacetamide emerged...

  12. DOE 2010 occupational radiation exposure

    Energy Technology Data Exchange (ETDEWEB)

    none,

    2011-11-01

    The U.S. Department of Energy (DOE) Office of Analysis within the Office of Health, Safety and Security (HSS) publishes the annual DOE Occupational Radiation Exposure Report to provide an overview of the status of radiation protection practices at DOE.* The DOE 2010 Occupational Radiation Exposure Report provides an evaluation of DOE-wide performance regarding compliance with DOE Part 835 dose limits and as low as reasonably achievable (ALARA) process requirements. In addition, the report provides data to DOE organizations responsible for developing policies for protection of individuals from the effects of radiation. The report provides a summary and an analysis of occupational radiation exposure information from the monitoring of individuals involved in DOE activities. The occupational radiation exposure information is analyzed in terms of aggregate data, dose to individuals, and dose by site over the past 5 years.

  13. Sleep in High Stress Occupations

    Science.gov (United States)

    Flynn-Evans, Erin

    2014-01-01

    High stress occupations are associated with sleep restriction, circadian misalignment and demanding workload. This presentation will provide an overview of sleep duration, circadian misalignment and fatigue countermeasures and performance outcomes during spaceflight and commercial aviation.

  14. Spiritual Assessments in Occupational Therapy

    Directory of Open Access Journals (Sweden)

    Barbara Hemphill

    2015-07-01

    Full Text Available Spirituality is recognized as an important concept in the study and practice of medicine, including occupational therapy. This aligns with occupational therapy’s core value of treating people holistically—mind, body, and spirit. Currently, the Joint Commission for the Accreditation of Hospital Organizations ( JCAHO requires that a spiritual assessment be given to patients on admission. To conduct effective spiritual assessments, occupational therapists must distinguish between religion and spirituality. They also must be aware of their own spiritual beliefs and practices and how those might influence their clinical interactions. This article presents spiritual assessment tools that occupational therapists can use in clinical practice; they range from history taking, to questionnaires, to observation scales. Guidelines are presented for selecting among several spiritual assessments. A case study is presented in which a patient’s faith tradition is being challenged, which could affect the outcome of therapy. Finally, treatment and intervention planning and ethical considerations are discussed.

  15. Occupational Health and the Arts.

    Science.gov (United States)

    Hinkamp, David L; McCann, Michael; Babin, Angela

    2017-09-01

    Work in the visual arts, performing arts, and writing can involve exposures to occupational hazards, including hazardous materials, equipment, and conditions, but few art workplaces have strong occupational health resources. Literature searches were conducted for articles that illustrate these concerns. Medical databases were searched for art-related health articles. Other sources were also reviewed, including, unindexed art-health publications, and popular press articles. Information was located that described some exposed populations, art-related hazards, and resulting disorders. Anecdotal reports were used when more complete data were not available. Health hazards in the arts are significant. Occupational health professionals are familiar with most of these concerns and understand their treatment and prevention. The occupational health approach can reduce the health hazards encountered by at-risk art workers. Additional research would benefit these efforts. Resources for further information are available.

  16. Building Bridges Through Meaningful Occupation

    Directory of Open Access Journals (Sweden)

    Jennifer Fortuna

    2017-07-01

    Full Text Available Mary Block, MS, OTR/L, an occupational therapist and artist based in Illinois, provided the cover art for the Summer 2017 issue of The Open Journal of Occupational Therapy (OJOT. Generations is a sculpture made from concrete that measures 240 x100 in. (6.096 x 2.54 m. The piece was commissioned by Mary’s home town, the Village of Deerfield, IL. Mary always knew she wanted to be an artist. When competing paradigms altered Mary’s career path, the field of occupational therapy helped her to shape a new worldview. In uncertain times, meaningful occupation empowered Mary to start over again where she originally began

  17. Going to an Occupational Therapist

    Science.gov (United States)

    ... is to grow , learn, do schoolwork, and play. Occupational therapy (or OT) helps kids who have a physical, sensory, or cognitive disability carry out everyday activities like brushing their teeth or putting on shoes ...

  18. Occupational therapy for rheumatoid arthritis.

    NARCIS (Netherlands)

    Steultjens, E. M.; Dekker, J.; Bouter, L. M.; van Schaardenburg, D.; van Kuyk, M. A.; van den Ende, C. H.

    2004-01-01

    BACKGROUND: For persons with rheumatoid arthritis (RA) the physical, personal, familial, social and vocational consequences are extensive. Occupational therapy (OT), with the aim to facilitate task performance and to decrease the consequences of rheumatoid arthritis for daily life activities, is

  19. Occupational therapy for rheumatoid arthritis.

    NARCIS (Netherlands)

    Steultjens, E.M.J.; Dekker, J.; Bouter, L.M.; Schaardenburg, D.J. van; Kuyk, M.A.H. van; Ende, C.H.M. van den

    2004-01-01

    Background: For persons with rheumatoid arthritis (RA) the physical, personal, familial, social and vocational consequences are extensive. Occupational therapy (OT), with the aim to facilitate task performance and to decrease the consequences of rheumatoid arthritis for daily life activities, is

  20. [Prevention levels in occupational nursing].

    Science.gov (United States)

    Nogueira, Maria Jacyra de Campos

    1982-12-01

    The autor, based in nursing functions concepts of HENDERSON and of HORTA, and in the prevention levels of LEAVELL & CLARK, write about the of the occupational health nursing personnel in Brasil and describes their actions and activities.

  1. DOE 2008 occupational radiation exposure

    Energy Technology Data Exchange (ETDEWEB)

    none,

    2009-10-01

    The U.S. Department of Energy (DOE) Office of Corporate Safety Analysis (HS-30) within the Office of Health, Safety and Security (HSS) publishes the annual DOE Occupational Radiation Exposure Report to provide an overview of the status of radiation protection practices at DOE. The DOE 2008 Occupational Radiation Exposure Report provides an evaluation of DOE-wide performance regarding compliance with DOE Part 835 dose limits and as low as reasonably achievable (ALARA) process requirements. In addition, the report provides data to DOE organizations responsible for developing policies for protection of individuals from the effects of radiation. This report provides a summary and an analysis of occupational radiation exposure information from the monitoring of individuals involved in DOE activities. The occupational radiation exposure information is analyzed in terms of aggregate data, dose to individuals, and dose by site over the past 5 years.

  2. Sleep as an Occupational Need.

    Science.gov (United States)

    Tester, Nicole J; Foss, Joanne Jackson

    In the same way the human body requires food, hydration, and oxygen, it also requires sleep. Even among healthy people, the amount and quality of sleep substantially influence health and quality of life because sleep helps regulate physiological functioning. Given the impact of sleep on participation, the American Occupational Therapy Association reclassified sleep from an activity of daily living to an occupational domain. Poor sleep is a frequent medical complaint, especially among populations with neurological impairment. Occupational therapy practitioners should consider routinely screening for factors affecting their clients' sleep. By addressing such factors, as well as related routines and habits, practitioners can enhance the effectiveness of rehabilitation, promote health and well-being, and increase engagement and life quality. Practitioners should acknowledge the importance of sleep in practice, and the study of sleep should be prioritized by researchers in the field to meet client needs and establish evidence for interventions. Copyright © 2018 by the American Occupational Therapy Association, Inc.

  3. Occupational health and the radiographer

    International Nuclear Information System (INIS)

    Stronach, T.

    1990-01-01

    This paper identifies some of the occupational health hazards faced by radiographers in the hospital environment. There has been very little work done in this area in the past, and as the subject is so large this paper can do little other than raise some of the issues . The hazards addressed include: radiation, ergonomics, chemical, environmental, biological, occupational injury and accident, stress. 14 refs., 2 figs

  4. Occupation and cancer in Britain

    Energy Technology Data Exchange (ETDEWEB)

    Rushton, L.; Bagga, S.; Bevan, R.; Brown, T.P.; Cherrie, J.W.; Holmes, P.; Fortunato, L.; Slack, R.; Van Tongeren, M.; Young, C.; Hutchings, S.J. [University of London Imperial College of Science Technology & Medicine, London (United Kingdom)

    2010-04-27

    Prioritising control measures for occupationally related cancers should be evidence based. We estimated the current burden of cancer in Britain attributable to past occupational exposures for International Agency for Research on Cancer (IARC) group 1 (established) and 2A (probable) carcinogens. We calculated attributable fractions and numbers for cancer mortality and incidence using risk estimates from the literature and national data sources to estimate proportions exposed. 5.3% (8019) cancer deaths were attributable to occupation in 2005 (men, 8.2% (6362); women, 2.3% (1657)). Attributable incidence estimates are 13, 679 (4.0%) cancer registrations (men, 10 063 (5.7%); women, 3616 (2.2%)). Occupational attributable fractions are over 2% for mesothelioma, sinonasal, lung, nasopharynx, breast, non-melanoma skin cancer, bladder, oesophagus, soft tissue sarcoma, larynx and stomach cancers. Asbestos, shift work, mineral oils, solar radiation, silica, diesel engine exhaust, coal tars and pitches, occupation as a painter or welder, dioxins, environmental tobacco smoke, radon, tetrachloroethylene, arsenic and strong inorganic mists each contribute 100 or more registrations. Industries and occupations with high cancer registrations include construction, metal working, personal and household services, mining, land transport, printing/publishing, retail/hotels/restaurants, public administration/defence, farming and several manufacturing sectors. 56% of cancer registrations in men are attributable to work in the construction industry (mainly mesotheliomas, lung, stomach, bladder and non-melanoma skin cancers) and 54% of cancer registrations in women are attributable to shift work (breast cancer).

  5. Occupational risk of building construction

    International Nuclear Information System (INIS)

    Aneziris, O.N.; Topali, E.; Papazoglou, I.A.

    2012-01-01

    This paper presents the quantification of occupational risk of a building construction project. Risk assessment is based on the Occupational Risk Model (ORCA) developed under the Workgroup Occupational Risk Model project (WORM), in the Netherlands, for quantifying occupational risk. This model assesses occupational risk of a worker, by taking into account his various tasks, activities and their hazards. Risk is evaluated for three types of consequences: recoverable injury, permanent injury and death. The occupational risk model is based on a set of 63 bowties, which assess risk owing to different hazards such as fall from ladder, scaffold, roofs, falling object, struck by moving vehicle, contact by moving parts, etc. ORCA calculates the risk profile of a building construction site, consisting of thirty-eight workers in different job positions, such as operators of excavators, loaders, compaction equipment, workers in excavation and framing phases, etc. All risk profiles of workers have been quantified and jobs have been ranked according to their risk. Workers installing timber formworks have the highest fatality risk (1.57×10 −3 /yr), followed by the workers installing reinforcement (1.52×10 −3 /yr).

  6. The cost of occupational dose

    International Nuclear Information System (INIS)

    Fleishman, A.B.; Clark, M.J.

    1980-01-01

    The optimization of radiological protection will routinely involve the balancing of public and occupational exposure, particularly within the nuclear fuel cycle. For example the reduction of public exposure from an effluent stream could lead to increases in occupational exposure from treatment, storage and disposal operations. A methodology is propased for the estimation of the cost of occupational exposure in the UK (Pound man-Sv -1 ) based on valuations of changes in risk. A variable value for the cost of the occupational man-Sv is obtained depending on per caput dose levels. The values at particular per caput dose levels are different for occupational workers and the general public, because of different demography and assumptions on risk perception and aversion. They are however approximately the same when the per caput doses are expressed as percentages of the dose limits for workers and the general public respectively. An example of the application of the derived cost of the occupational man-Sv to an optimisation problem is given. (author)

  7. Occupational dermatoses: An Asian perspective

    Directory of Open Access Journals (Sweden)

    Riti Bhatia

    2017-01-01

    Full Text Available Occupational dermatoses contribute to a significant portion of work-related diseases, especially in Asia, where a major portion of the workforce is in the unorganized sector. This review article is focussed on the frequency and pattern of occupational skin diseases reported across Asian countries and type of allergens implicated in different occupations. The literature was searched systematically using key words 'occupational dermatoses,' 'occupational skin disease' and name of each Asian country. Ninty five full-text articles were considered relevant and evaluated. Some of the dermatoses seen in industrial workers in Asian countries are similar to those in Western countries, including dermatoses due to chromate in construction and electroplating workers, epoxy resin, and chromate in painters, wood dust in workers in the furniture industry, azo dyes in textile workers and formaldehyde and chromates in those working in the leather and dyeing industries, dermatoses in domestic workers, chefs and health-care workers. Dermatoses in workers engaged in agriculture, beedi (tiny cigars manufacture, agarbatti (incense sticks production, fish processing, carpet weaving, sanitation and those working in coffee plantations and coal mines appear to be unique to Asian countries. Recognition of clinical patterns and geographic variations in occupational skin diseases will provide an impetus to further strengthen future research in these areas, as well as improving their management.

  8. Fathers' occupation and pregnancy outcome

    International Nuclear Information System (INIS)

    McDonald, A.D.; McDonald, J.C.; Armstrong, B.; Cherry, N.M.; Nolin, A.D.; Robert, D.

    1989-01-01

    Findings from a survey of 56,067 women in Montreal on maternal occupation and pregnancy outcome have been reported. Paternal occupation recorded in the same survey was analysed for spontaneous abortion in 24 occupational groups retaining the six main sectors of maternal occupation and allowing, by means of logistic regression, for seven potentially confounding variables. In only one of the 24 fathers' occupational groups was there a statistically significant excess of spontaneous abortions-mechanics, repairers, and certain assemblers (O/E = 1.10, 90% CI = 1.02-1.20); subdivision of this group suggested that this excess was mainly attributable to the large group of motor vehicle mechanics (O/E = 1.17). No significant excess of known chromosomally determined defects was found in any of the 24 occupational groups. An association of developmental defects was found with food and beverage processing (18 defects observed compared with 8.02 expected; p < 0.05); however, there was no specificity in type of food, beverage, or congenital defect, and no obvious explanatory mechanism. (author)

  9. Occupational Socialization Processes of Classroom Teachers

    Science.gov (United States)

    Kucukbayram, Canan; Ottekin Demirbolat, Ayse

    2017-01-01

    Purpose: Occupational socialization is a process by which individuals internalize occupational culture. The aim of the present study was to ascertain the views and perceptions of classroom teachers regarding the efficiency of occupational socialization periods and the level of their occupational socialization, and to describe the same by sex and…

  10. Industrial Occupations. Education for Employment Task Lists.

    Science.gov (United States)

    Lake County Area Vocational Center, Grayslake, IL.

    The duties and tasks found in these task lists form the basis of instructional content for secondary, postsecondary, and adult occupational training programs for industrial occupations. The industrial occupations are divided into eight clusters. The clusters and occupations are: construction cluster (bricklayer, carpenter, building maintenance…

  11. Occupational exposure in MRI.

    Science.gov (United States)

    McRobbie, D W

    2012-04-01

    This article reviews occupational exposure in clinical MRI; it specifically considers units of exposure, basic physical interactions, health effects, guideline limits, dosimetry, results of exposure surveys, calculation of induced fields and the status of the European Physical Agents Directive. Electromagnetic field exposure in MRI from the static field B(0), imaging gradients and radiofrequency transmission fields induces electric fields and currents in tissue, which are responsible for various acute sensory effects. The underlying theory and its application to the formulation of incident and induced field limits are presented. The recent International Commission on Non-Ionizing Radiation Protection (ICNIRP) Bundesministerium für Arbeit und Soziales and Institute of Electrical and Electronics Engineers limits for incident field exposure are interpreted in a manner applicable to MRI. Field measurements show that exposure from movement within the B(0) fringe field can exceed ICNIRP reference levels within 0.5 m of the bore entrance. Rate of change of field dB/dt from the imaging gradients is unlikely to exceed the new limits, although incident field limits can be exceeded for radiofrequency (RF) exposure within 0.2-0.5 m of the bore entrance. Dosimetric surveys of routine clinical practice show that staff are exposed to peak values of 42 ± 24% of B(0), with time-averaged exposures of 5.2 ± 2.8 mT for magnets in the range 0.6-4 T. Exposure to time-varying fields arising from movement within the B(0) fringe resulted in peak dB/dt of approximately 2 T s(-1). Modelling of induced electric fields from the imaging gradients shows that ICNIRP-induced field limits are unlikely to be exceeded in most situations; however, movement through the static field may still present a problem. The likely application of the limits is discussed with respect to the reformulation of the European Union (EU) directive and its possible implications for MRI.

  12. Occupational therapy practice in emergency care: Occupational therapists' perspectives.

    Science.gov (United States)

    Spang, Lisa; Holmqvist, Kajsa

    2015-01-01

    Emergency care takes place in a complex work environment that is characterized by critically ill patients, short hospital stays, and a wide variety of different healthcare professionals. Studies of occupational therapists' (OTs) experiences of working within emergency care have shown that they often experience difficulties in explaining the essence of occupational therapy and have to justify their approaches. Much effort has been made in Sweden to help OTs dispel the notion that occupational therapy is difficult to explain, and the aim of this study was to describe how Swedish OTs perceive their work in emergency care. A qualitative descriptive approach was taken, and 14 interviews were conducted with OTs working in emergency care. Qualitative content analysis was used to analyse the data. The overall theme that emerged was "Feeling established through deliberate occupation-based work". The underlying categories showed different strategies used by the OTs to provide occupational therapy in an emergency care context. Deliberate strategies were used to demonstrate the effectiveness of occupational therapy and its approaches to patients and other health care professionals, and this resulted in the OTs feeling both established and needed. Unlike the OTs in previous studies, the Swedish OTs experienced no difficulties in explaining occupational therapy and could make convincing arguments for their interventions. Parallel to their clinical work, the OTs worked with on-going development to find ways to improve their approaches. In summary, these Swedish OTs seem to have been provided with a professional language and the knowledge required to establish themselves in an emergency care setting.

  13. [Occupational risks during pregnancy: Feedback from occupational medical services].

    Science.gov (United States)

    Henrotin, J-B; Vaissière, M; Etaix, M; Dziurla, M; Malard, S; Lafon, D

    2018-01-01

    To describe the follow-up of pregnancies at work and exposures to pregnancy occupational hazards. A cross-sectional study was performed between January and December 2014 in occupational health services of Languedoc-Roussillon region. Eligible workers were interviewed by occupational health physicians (OHPs) after delivery and at the time of returning to work (exposure, anticipation, prevention, communication, sick leave). Occupational skill levels were classified according to the French standard classification of occupations (version 2003) from the French National Institute of Statistics. Socioeconomic deprivation was assessed using the Evaluation of Deprivation and Inequalities in Health Examination (EPICES) individual scale. A total of 1347 workers were recruited. The mean age was at 30.7±4.5 years. Among pregnant workers, there were 54.2% of employees, 30.7% of intermediate occupations, 10.4% of managers and, 4.7% of manual workers. Twenty-two percent of workers were classed as deprived. Also, 43.2% of workers were exposed to three or more occupational hazards during pregnancy. Only 17.7% of workers had medical visits with OHP during pregnancy and 14.7% benefited from workstation adjustments. In contrast, the level of sick leaves was high (74.2%). Our results argue for the need to follow pregnancies at work. However, the low level of prevention activities and the high level of sick leaves raise the question of the management of pregnant women at work. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  14. Occupational deprivation in an asylum centre:

    DEFF Research Database (Denmark)

    Morville, Anne-Le; Erlandsson, Lena-Karin

    2013-01-01

    This article presents a study of three asylum-seeking men from Iran and Afghanistan. It aimed to explore how and if they experienced occupations as occupations in a Danish asylum centre and how their life experience shaped their choice and value of current occupations. In-depth narrative interviews...... explored the participants’ occupational history and its influence on their occupations in the asylum centre. A thematic analysis showed that the participants had been subjected to occupational disruption and deprivation by politically oppressive systems even before their flight. Their occupations...... in Denmark were to a certain extent influenced by their earlier occupations and the current occupational deprivation they all experienced was due to limited possibilities in the centre. Although they tried their best to fill their days and create structure, there was a loss of valued occupations...

  15. VELOCITY EVOLUTION AND THE INTRINSIC COLOR OF TYPE Ia SUPERNOVAE

    International Nuclear Information System (INIS)

    Foley, Ryan J.; Sanders, Nathan E.; Kirshner, Robert P.

    2011-01-01

    To understand how best to use observations of Type Ia supernovae (SNe Ia) to obtain precise and accurate distances, we investigate the relations between spectra of SNe Ia and their intrinsic colors. Using a sample of 1630 optical spectra of 255 SNe, based primarily on data from the CfA Supernova Program, we examine how the velocity evolution and line strengths of Si II λ6355 and Ca II H and K are related to the B – V color at peak brightness. We find that the maximum-light velocity of Si II λ6355 and Ca II H and K and the maximum-light pseudo-equivalent width of Si II λ6355 are correlated with intrinsic color, with intrinsic color having a linear relation with the Si II λ6355 measurements. Ca II H and K does not have a linear relation with intrinsic color, but lower-velocity SNe tend to be intrinsically bluer. Combining the spectroscopic measurements does not improve intrinsic color inference. The intrinsic color scatter is larger for higher-velocity SNe Ia—even after removing a linear trend with velocity—indicating that lower-velocity SNe Ia are more 'standard crayons'. Employing information derived from SN Ia spectra has the potential to improve the measurements of extragalactic distances and the cosmological properties inferred from them.

  16. Some chaotic features of intrinsically coupled Josephson junctions

    International Nuclear Information System (INIS)

    Kolahchi, M.R.; Shukrinov, Yu.M.; Hamdipour, M.; Botha, A.E.; Suzuki, M.

    2013-01-01

    Highlights: ► Intrinsically coupled Josephson junctions model a high-T c superconductor. ► Intrinsically coupled Josephson junctions can act as a chaotic nonlinear system. ► Chaos could be due to resonance overlap. ► Avoiding parameters that lead to chaos is important for the design of resonators. -- Abstract: We look for chaos in an intrinsically coupled system of Josephson junctions. This study has direct applications for the high-T c resonators which require coherence amongst the junctions

  17. Congenital hypertrophy of multiple intrinsic muscles of the foot.

    Science.gov (United States)

    Shiraishi, Tomohiro; Park, Susam; Niu, Atushi; Hasegawa, Hiromi

    2014-12-01

    Congenital hypertrophy of a single intrinsic muscle of the foot is rare, and as far as we know, only six cases have been reported. We describe a case of congenital anomaly that showed hypertrophy of multiple intrinsic muscles of the foot; the affected muscles were all the intrinsic muscles of the foot except the extensor digitorum brevis or extensor hallucis. Other tissues such as adipose tissue, nervous tissue, or osseous tissue showed no abnormalities. To reduce the volume of the foot we removed parts of the enlarged muscles.

  18. Simple intrinsic defects in GaAs : numerical supplement.

    Energy Technology Data Exchange (ETDEWEB)

    Schultz, Peter Andrew

    2012-04-01

    This Report presents numerical tables summarizing properties of intrinsic defects in gallium arsenide, GaAs, as computed by density functional theory. This Report serves as a numerical supplement to the results published in: P.A. Schultz and O.A. von Lilienfeld, 'Simple intrinsic defects in GaAs', Modelling Simul. Mater. Sci Eng., Vol. 17, 084007 (2009), and intended for use as reference tables for a defect physics package in device models. The numerical results for density functional theory calculations of properties of simple intrinsic defects in gallium arsenide are presented.

  19. Helical propensity in an intrinsically disordered protein accelerates ligand binding

    DEFF Research Database (Denmark)

    Iesmantavicius, Vytautas; Dogan, Jakob; Jemth, Per

    2014-01-01

    domain of the activator for thyroid hormone and retinoid receptors (ACTR) is intrinsically disordered and folds upon binding to the nuclear coactivator binding domain (NCBD) of the CREB binding protein. A number of mutants was designed that selectively perturbs the amount of secondary structure......Many intrinsically disordered proteins fold upon binding to other macromolecules. The secondary structure present in the well-ordered complex is often formed transiently in the unbound state. The consequence of such transient structure for the binding process is, however, not clear. The activation...... the notion of preformed secondary structure as an important determinant for molecular recognition in intrinsically disordered proteins....

  20. Intrinsic and collective structure in the interacting boson model

    International Nuclear Information System (INIS)

    Leviatan, A.

    1987-01-01

    A general non-spherical boson basis is introduced to study the excitation modes in the interacting boson model (IBM). A prescription for construction of intrinsic states is presented. The general IBM Hamiltonian is resolved exactly into intrinsic and collective parts. The limit of large boson number is discussed analytically for spectrum and transitions. The method of analysis reveals an underlying intrinsic and collective structure closely linked with symmetry considerations. The suggested new approach seems to be adequate as a tool to obtain the physical content and normal modes in any number conserving algebraic bosonic system. copyright 1987 Academic Press, Inc

  1. Intrinsic and collective structure in the interacting boson model

    Energy Technology Data Exchange (ETDEWEB)

    Leviatan, A.

    1987-11-01

    A general non-spherical boson basis is introduced to study the excitation modes in the interacting boson model (IBM). A prescription for construction of intrinsic states is presented. The general IBM Hamiltonian is resolved exactly into intrinsic and collective parts. The limit of large boson number is discussed analytically for spectrum and transitions. The method of analysis reveals an underlying intrinsic and collective structure closely linked with symmetry considerations. The suggested new approach seems to be adequate as a tool to obtain the physical content and normal modes in any number conserving algebraic bosonic system. copyright 1987 Academic Press, Inc.

  2. Uncovering your hidden occupancy costs.

    Science.gov (United States)

    Apgar, M

    1993-01-01

    Senior managers at large companies may not believe that they can have much impact on the "bricks and mortar" of their cost structure. They may even think that occupancy costs are too insignificant to worry about, too technical to analyze, and too fixed to control. But as real estate consultant Mahlon Apgar argues, occupancy costs can hurt a company's earnings, share value, and overall performance. On the other hand, every dollar saved drops straight to the bottom line. Shearson Lehman Brothers, for example, has found that it can save as much as $20 million annually by reducing occupancy costs in its branch offices and headquarters. Managing occupancy costs isn't easy. But it is timely. As companies strive to improve productivity by consolidating functions and downsizing staff, they are saddled with excess office space. Expansions abroad present completely different market conditions that put a premium on reducing occupancy costs. At the same time, the changing nature of work is challenging deeply held beliefs about the workplace, and, consequently, traditional expectations of office space are giving way to innovations that are less costly and more productive. To manage occupancy costs, managers must be able to identify their components, measure their impact, understand what drives them, and develop options to change them. Four basic tools help diagnose problems: a cost history, a loss analysis, a component analysis, and a lease aging profile. Understanding cost drivers like leasing, location, and layout can give executives the insights they need to reduce occupancy costs while improving the effectiveness of facilities to support day-to-day operations.

  3. The selection of occupancy factors

    International Nuclear Information System (INIS)

    Lakey, J.R.A.

    1977-01-01

    An estimate of the proportion of time that an area is occupied by radiation workers is often used in radiological protection to permit relaxation of exposure rate limits above those for continuous occupation. This proportion is known as an occupancy factor and is used most frequently in X-ray facilities. The strategy for controlling the external exposure of radiation workers must be decided before occupancy factors are selected for the design of the radiation protection facilities. When shielding has to be designed the occupancy factor effects the design objectives and permits increased exposure rates at the shield surface. It is useful to note that the selection of occupancy factors with due regard to the expected spatial variation of the exposure rate can help to reduce the range of the worker's radiation exposure because field gradients are usually steeper close to the shield. When other hazards, such as internal exposure, and other constraints, such as cost of the space consumed, are added, the selection of the optimum set of occupancy factors is more difficult. Two zone occupancy factors are discussed in this paper and proposals are made for a strategy to be used when there is more than one hazard and the designer has to meet constraints imposed by limitations of the facilities available. An important feature of the strategy is the avoidance of high radiation exposure to small groups of workers. The errors involved in assessment of the actual dose received by the radiation worker must be taken into account and in particular the selection of the higher exposure rate limits must be made with attention to the accident potential

  4. Occupational diseases in Poland, 2012

    Directory of Open Access Journals (Sweden)

    Urszula Wilczyńska

    2013-06-01

    Full Text Available Background: The aim of the paper was to present basic statistical data on occupational diseases diagnosed in 2012. Material and Methods: The work was based on the data from "Occupational Disease Reporting Forms" received by the Central Register of Occupational Diseases in 2012. The data comprised information on nosologic units, gender and age of patients, duration of occupational exposure, sections of the national economy and voivodeships. The incidence was specified in terms of the number of cases in relation to paid employees or to employed people. Results: The number of occupational diseases accounted for 2402 cases. The incidence rate was 23 cases per 100 000 paid employees. In spite of the general decline in the number of cases, the incidence of infectious and parasitic diseases increased by 8.6%. The highest incidence was noted for infectious and parasitic diseases (6.8/100 000, pneumoconioses (5.5/100 000, hearing loss (2.1/100 000, diseases of: the peripheral nervous system (2/100 000, voice disorders (1.9/100 000 and the musculo-skeletal system pathologies (1.1/100 000. The pathologies specified above accounted in total for 84% of all occupational diseases. The industrial sectors of the national economy characterized by the highest incidence included mining and quarrying (288.3/100 000 and manufacturing (27.8/100 000. The highest incidence was recorded in the Silesian (46.2/100 000 and the lowest in the Opolskie (4.2/100 000 voivodeships. Conclusions: The downward trend in the incidence of occupational diseases continues. Different incidence of voice disorders among teachers in individual provinces suggests that uniform preventive, diagnostic and certification standards are missing. Med Pr 2013;64(3:317–326

  5. Extending Beyond Qualitative Interviewing to Illuminate the Tacit Nature of Everyday Occupation: Occupational Mapping and Participatory Occupation Methods.

    Science.gov (United States)

    Huot, Suzanne; Rudman, Debbie Laliberte

    2015-07-01

    The study of human occupation requires a variety of methods to fully elucidate its complex, multifaceted nature. Although qualitative approaches have commonly been used within occupational therapy and occupational science, we contend that such qualitative research must extend beyond the sole use of interviews. Drawing on qualitative methodological literature, we discuss the limits of interview methods and outline other methods, particularly visual methods, as productive means to enhance qualitative research. We then provide an overview of our critical ethnographic study that used narrative, visual, and observational methods to explore the occupational transitions experienced by immigrants to Canada. We describe our use of occupational mapping and participatory occupation methods and the contributions of these combined methods. We conclude that adopting a variety of methods can enable a deeper understanding of the tacit nature of everyday occupation, and is key to advancing knowledge regarding occupation and to informing occupational therapy practice.

  6. Occupational asthma caused by palladium

    Energy Technology Data Exchange (ETDEWEB)

    Daenen, M.; Rochette, F.; Demedts, M.; Nemery, B. [K.U. Leuven, Pneumology (Belgium); Rogiers, P. [A.Z. St-Lucas, Brugge (Belgium); Walle, C. Van de [Siemens, Oostkamp (Belgium)

    1999-01-01

    Occupational exposure to complex platinum salts is a well-known cause of occupational asthma. Although there is evidence that platinum refinery workers may also be sensitized to other precious metals, such as palladium or rhodium, no instances of occupational asthma due to an isolated sensitization to palladium have been reported. A case is reported of occupational rhinoconjunctivitis and asthma in a previously healthy worker exposed to the fumes of an electroplating bath containing palladium. There was no exposure to platinum. Sensitization to palladium was documented by skin-prick tests. The skin-prick test was positive with Pd(NH{sub 3}){sub 4}Cl{sub 2}, but not with (NH{sub 4}){sub 2}PdCl{sub 4}. Corresponding salts of platinum were all negative. A bronchial provocation test with Pd(NH{sub 34})Cl{sub 2} (0.0001 % for a total of 315 s, followed by 0.001 % for a total of 210 s) led to an early decrease in forced expiratory volume in one second (-35%). A similar exposure (0.001 % for a total of 16 min) in an unrelated asthmatic gave no reaction. This case shows that an isolated sensitization to palladium can occur and that respiratory exposure to palladium is a novel cause of metal-induced occupational asthma. (au) 24 refs.

  7. DOE 2013 occupational radiation exposure

    Energy Technology Data Exchange (ETDEWEB)

    none,

    2014-11-01

    The Office of Analysis within the U.S. Department of Energy (DOE) Office of Environment, Health, Safety and Security (EHSS) publishes the annual DOE Occupational Radiation Exposure Report to provide an overview of the status of radiation protection practices at DOE (including the National Nuclear Security Administration [NNSA]). The DOE 2013 Occupational Radiation Exposure Report provides an evaluation of DOE-wide performance regarding compliance with Title 10, Code of Federal Regulations (C.F.R.), Part 835, Occupational Radiation Protection dose limits and as low as reasonably achievable (ALARA) process requirements. In addition, the report provides data to DOE organizations responsible for developing policies for protection of individuals from the adverse health effects of radiation. The report provides a summary and an analysis of occupational radiation exposure information from the monitoring of individuals involved in DOE activities. Over the past five-year period, the occupational radiation exposure information has been analyzed in terms of aggregate data, dose to individuals, and dose by site.

  8. Occupational skin cancer and precancer

    Directory of Open Access Journals (Sweden)

    Fifinela Raissa

    2016-12-01

    Full Text Available Occupational skin cancer and precancerous lesions are skin disorders caused by exposure to chemical carcinogens such as polycyclic hydrocarbons and arsenic, or radiation, such as ultraviolet light and ionizing light in the workplace. Annual increase in skin cancer incidence is believed to be related to various factors such as frequent intense sunlight exposure (i.e. at work, recreational activities, and sun-tanning habit, ozone depletion, an increase in number of geriatric population, and an increase of public awareness in skin cancer. The most common occupational skin cancers are basal cell carcinoma, squamous cell carcinoma, and melanoma. Examples of occupational precancerous lesion of the skin are actinic keratosis and Bowen’s disease. Particular diagnostic criteria to diagnose occupational diseases has been developed. Early detection of occupational skin cancer and precancerous lesion is necessary. An effective prevention program consists of primary prevention such as prevention of hazardous material exposure, secondary prevention such as early detection of disease for early intervention, and tertiary prevention such as minimizing long-term impact of the disease.

  9. Occupational burnout among nursing personel

    Directory of Open Access Journals (Sweden)

    Sylwia Wieder-Huszla

    2016-02-01

    Full Text Available Background. Occupational stress and the related burnout syndrome is undoubtedly one of the most important challenges for public health. Objectives . The objective of the study was identifying occupational burnout among nurses. Material and methods . The questionnaire was responded by 408 professionally active male and female nurses, working in the territory of the West Pomeranian Voivodeship. In the evaluation of occupational burnout the standardized Maslach Burnout Inventory (MBI was applied. Results . Mean values of the level of occupational burnout for the study group amounted to 39.3 ± 30.9 with regard to emotional exhaustion, 30.64 ± 27.89 with respect to the depersonalization subscale and 66.26 ± 27.94 – the lowered level of job satisfaction. Conclusions . 1. The studied nursing personnel showed symptoms of occupational burnout in all dimensions of the syndrome, i.e. high levels of emotional exhaustion and depersonalization as well as low job satisfaction. 2. Individuals with higher education scored lower on the emotional exhaustion scale. 3. Emotional exhaustion is influenced by workplace and position.

  10. Modeling Single Occupant Vehicle Behavior in High-Occupancy Toll (HOT) Facilities

    Science.gov (United States)

    2009-12-14

    High-occupancy toll (HOT) lanes are in operation, under construction, and planned for in several major metropolitan areas. The premise behind HOT lanes is to allow single occupant vehicles (SOVs) to access high occupancy vehicle (HOV) lanes (and theo...

  11. Intrinsically motivated learning in natural and artificial systems

    CERN Document Server

    Baldassarre, Gianluca

    2013-01-01

    This book presents the state of the art in research on intrinsically motivated learning and presents novel tools for research. It also identifies related scientific and technological open challenges as well as promising research directions.

  12. Towards hardware-intrinsic security foundations and practice

    CERN Document Server

    Sadeghi, Ahmad-Reza; Tuyls, Pim

    2010-01-01

    Hardware-intrinsic security is a young field dealing with secure secret key storage. This book features contributions from researchers and practitioners with backgrounds in physics, mathematics, cryptography, coding theory and processor theory.

  13. Recent Advances in Intrinsic Self-Healing Cementitious Materials.

    Science.gov (United States)

    Li, Wenting; Dong, Biqin; Yang, Zhengxian; Xu, Jing; Chen, Qing; Li, Haoxin; Xing, Feng; Jiang, Zhengwu

    2018-03-25

    Self-healing is a natural phenomenon whereby living organisms respond to damage. Recently, considerable research efforts have been invested in self-healing cementitious materials that are capable of restoring structural integrity and mechanical properties after being damaged. Inspired by nature, a variety of creative approaches are explored here based on the intrinsic or extrinsic healing mechanism. Research on new intrinsic self-healing cementitious materials with biomimetic features is on the forefront of material science, which provides a promising way to construct resilient and sustainable concrete infrastructures. Here, the current advances in the development of the intrinsic healing cementitious materials are described, and a new definition of intrinsic self-healing discussed. The methods to assess the efficiency of different healing mechanisms are briefly summarized. The critical insights are emphasized to guide the future research on the development of new self-healing cementitious materials. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Intrinsic and extrinsic motivation for stereotypic and repetitive behavior.

    Science.gov (United States)

    Joosten, Annette V; Bundy, Anita C; Einfeld, Stewart L

    2009-03-01

    This study provides evidence for intrinsic and extrinsic motivators for stereotypical and repetitive behavior in children with autism and intellectual disability and children with intellectual disability alone. We modified the Motivation Assessment Scale (MAS) (1988b); dividing it into intrinsic and extrinsic measures and adding items to assess anxiety as an intrinsic motivator. Rasch analysis of data from 279 MASs (74 children) revealed that the items formed two unidimensional scales. Anxiety was a more likely intrinsic motivator than sensory seeking for children with dual diagnoses; the reverse was true for children with intellectual disability only. Escape and gaining a tangible object were the most common extrinsic motivators for those with dual diagnoses and attention and escape for children with intellectual disability.

  15. Values, Norms, and Intrinsic Motivation to Act Proenvironmentally

    NARCIS (Netherlands)

    Steg, Linda

    2016-01-01

    Environmental problems can be reduced if people more consistently engage in proenvironmental actions. In this article, I discuss factors that motivate or inhibit individuals to act proenvironmentally. Many people are intrinsically motivated to engage in proenvironmental actions, because protecting

  16. What is Intrinsic Motivation? A Typology of Computational Approaches.

    Science.gov (United States)

    Oudeyer, Pierre-Yves; Kaplan, Frederic

    2007-01-01

    Intrinsic motivation, centrally involved in spontaneous exploration and curiosity, is a crucial concept in developmental psychology. It has been argued to be a crucial mechanism for open-ended cognitive development in humans, and as such has gathered a growing interest from developmental roboticists in the recent years. The goal of this paper is threefold. First, it provides a synthesis of the different approaches of intrinsic motivation in psychology. Second, by interpreting these approaches in a computational reinforcement learning framework, we argue that they are not operational and even sometimes inconsistent. Third, we set the ground for a systematic operational study of intrinsic motivation by presenting a formal typology of possible computational approaches. This typology is partly based on existing computational models, but also presents new ways of conceptualizing intrinsic motivation. We argue that this kind of computational typology might be useful for opening new avenues for research both in psychology and developmental robotics.

  17. Exploring the link between intrinsic motivation and quality

    Science.gov (United States)

    Christy, Steven M.

    1992-12-01

    This thesis proposes that it is workers' intrinsic motivation that leads them to produce quality work. It reviews two different types of evidence- expert opinion and empirical studies--to attempt to evaluate a link between intrinsic motivation and work quality. The thesis reviews the works of Total Quality writers and behavioral scientists for any connection they might have made between intrinsic motivation and quality. The thesis then looks at the works of Deming and his followers in an attempt to establish a match between Deming's motivational assumptions and the four task rewards in the Thomas/Tymon model of intrinsic motivation: choice, competence, meaningfulness, and progress. Based upon this analysis, it is proposed that the four Thomas/Tymon task rewards are a promising theoretical foundation for explaining the motivational basis of quality for workers in Total Quality organizations.

  18. Does displayed enthusiasm favour recall, intrinsic motivation and time estimation?

    Science.gov (United States)

    Moè, Angelica

    2016-11-01

    Displayed enthusiasm has been shown to relate to intrinsic motivation, vitality, and positive affect, but its effects on recall performance and time estimation have not yet been explored. This research aimed at studying the effects of a delivery style characterised by High Enthusiasm (HE) on recall, time estimation, and intrinsic motivation. In line with previous studies, effects on intrinsic motivation were expected. In addition, higher recall and lower time estimations were hypothesised. In two experiments, participants assigned to a HE condition or to a normal reading control condition listened to a narrative and to a descriptive passage. Then, they were asked to rate perceived time, enthusiasm, pleasure, interest, enjoyment and curiosity, before writing a free recall. Experiment 1 showed that in the HE condition, participants recalled more, were more intrinsically motivated, and expressed lower time estimations compared to the control condition. Experiment 2 confirmed the positive effects of HE reading compared to normal reading, using different passages and a larger sample.

  19. Intrinsic and extrinsic factors influencing large African herbivore movements

    NARCIS (Netherlands)

    Venter, J.A.; Prins, H.H.T.; Mashanova, A.; Boer, de W.F.; Slotow, R.

    2015-01-01

    Understanding environmental as well as anthropogenic factors that influence large herbivore ecological patterns and processes should underpin their conservation and management. We assessed the influence of intrinsic, extrinsic environmental and extrinsic anthropogenic factors on movement behaviour

  20. The Development of Intrinsic Motivation for Physical Activity

    National Research Council Canada - National Science Library

    Beaty, James D

    2005-01-01

    .... Having found this to be so, it is worthy of researchers' efforts to determine the constructs that will move individuals to become more intrinsically motivated to engage in regular exercise and/or physical activity...

  1. Intrinsic and enhanced biodegradation of benzene in strongly reduced aquifers

    NARCIS (Netherlands)

    Heiningen, W.N.M. van; Rijnaarts, H.H.M; Langenhoff, A.A.M.

    1999-01-01

    Laboratory microcosm studies were performed to examine intrinsic and enhanced benzene bioremediation using five different sediment and groundwater samples from three deeply anaerobic aquifers sited in northern Netherlands. The influence of addition of nitrate, sulfate, limited amounts of oxygen, and

  2. An empirical qualitative study of students’ perceived intrinsic motivation

    OpenAIRE

    Pals Svendsen, Lisbet; Mondahl, Margrethe S.; Faizi, Zaki

    2014-01-01

    Foreign language and culture learning suffers from a bad image in Danish Upper Secondary schools and German is not an exception. It means that the majority of Danish Upper Secondary school students are not particularly interested in learning the language. Therefore, intrinsic motivation plays a pivotal role in German language and culture learning in Denmark. One didactic initiative proposed to remedy the lack of intrinsic motivation is the introduction of various ICT (Information and Communic...

  3. A hierarchy of intrinsic timescales across primate cortex.

    Science.gov (United States)

    Murray, John D; Bernacchia, Alberto; Freedman, David J; Romo, Ranulfo; Wallis, Jonathan D; Cai, Xinying; Padoa-Schioppa, Camillo; Pasternak, Tatiana; Seo, Hyojung; Lee, Daeyeol; Wang, Xiao-Jing

    2014-12-01

    Specialization and hierarchy are organizing principles for primate cortex, yet there is little direct evidence for how cortical areas are specialized in the temporal domain. We measured timescales of intrinsic fluctuations in spiking activity across areas and found a hierarchical ordering, with sensory and prefrontal areas exhibiting shorter and longer timescales, respectively. On the basis of our findings, we suggest that intrinsic timescales reflect areal specialization for task-relevant computations over multiple temporal ranges.

  4. Study of Intrinsic motivation in the Ministry for Foreign Affairs

    OpenAIRE

    Lehtimäki, Nora

    2015-01-01

    The purpose of this thesis was to investigate intrinsic motivation of the executive assistants and secretaries in the Ministry for Foreign Affairs. The objective in turn, was to examine how well intrinsic motivation has been achieved among these executive assistants and secretaries. How respondents evaluate their job satisfaction, work environment and motivation was also researched. Lastly, factors that increase or decrease motivation were studied, as well as if there is a need for additional...

  5. Engagement in occupation as an inquiring process

    DEFF Research Database (Denmark)

    Madsen, Jacob Østergaard; Josephsson, Staffan

    2017-01-01

    the situatedness of occupation from the perspective of how situation and occupation work together. We argue that this approach can provide a theoretical understanding of engagement in occupation as a natural inquiry process. Viewing occupation from this perspective, we suggest, reveals its transformative capacity......A number of existing contributions within occupational science have explored the situatedness of occupation by asking what. We identify this perspective as limiting understandings of the relationship of situation and occupation. Instead, we propose using John Dewey’s theory of inquiry to explore......, situating it in the doing of explorative actions, depending on contextual cues. The implications of the suggested situatedness of occupation are discussed, and the authors present ‘enacted situated inquiry’ as a way to further understandings of the relationship of occupation and situation, along...

  6. Intrinsic Losses Based on Information Geometry and Their Applications

    Directory of Open Access Journals (Sweden)

    Yao Rong

    2017-08-01

    Full Text Available One main interest of information geometry is to study the properties of statistical models that do not depend on the coordinate systems or model parametrization; thus, it may serve as an analytic tool for intrinsic inference in statistics. In this paper, under the framework of Riemannian geometry and dual geometry, we revisit two commonly-used intrinsic losses which are respectively given by the squared Rao distance and the symmetrized Kullback–Leibler divergence (or Jeffreys divergence. For an exponential family endowed with the Fisher metric and α -connections, the two loss functions are uniformly described as the energy difference along an α -geodesic path, for some α ∈ { − 1 , 0 , 1 } . Subsequently, the two intrinsic losses are utilized to develop Bayesian analyses of covariance matrix estimation and range-spread target detection. We provide an intrinsically unbiased covariance estimator, which is verified to be asymptotically efficient in terms of the intrinsic mean square error. The decision rules deduced by the intrinsic Bayesian criterion provide a geometrical justification for the constant false alarm rate detector based on generalized likelihood ratio principle.

  7. A dynamic birth-death model via Intrinsic Linkage

    Directory of Open Access Journals (Sweden)

    Robert Schoen

    2013-05-01

    Full Text Available BACKGROUND Dynamic population models, or models with changing vital rates, are only beginning to receive serious attention from mathematical demographers. Despite considerable progress, there is still no general analytical solution for the size or composition of a population generated by an arbitrary sequence of vital rates. OBJECTIVE The paper introduces a new approach, Intrinsic Linkage, that in many cases can analytically determine the birth trajectory of a dynamic birth-death population. METHODS Intrinsic Linkage assumes a weighted linear relationship between (i the time trajectory of proportional increases in births in a population and (ii the trajectory of the intrinsic rates of growth of the projection matrices that move the population forward in time. Flexibility is provided through choice of the weighting parameter, w, that links these two trajectories. RESULTS New relationships are found linking implied intrinsic and observed population patterns of growth. Past experience is "forgotten" through a process of simple exponential decay. When the intrinsic growth rate trajectory follows a polynomial, exponential, or cyclical pattern, the population birth trajectory can be expressed analytically in closed form. Numerical illustrations provide population values and relationships in metastable and cyclically stable models. Plausible projection matrices are typically found for a broad range of values of w, although w appears to vary greatly over time in actual populations. CONCLUSIONS The Intrinsic Linkage approach extends current techniques for dynamic modeling, revealing new relationships between population structures and the changing vital rates that generate them.

  8. Intrinsic honesty and the prevalence of rule violations across societies.

    Science.gov (United States)

    Gächter, Simon; Schulz, Jonathan F

    2016-03-24

    Deception is common in nature and humans are no exception. Modern societies have created institutions to control cheating, but many situations remain where only intrinsic honesty keeps people from cheating and violating rules. Psychological, sociological and economic theories suggest causal pathways to explain how the prevalence of rule violations in people's social environment, such as corruption, tax evasion or political fraud, can compromise individual intrinsic honesty. Here we present cross-societal experiments from 23 countries around the world that demonstrate a robust link between the prevalence of rule violations and intrinsic honesty. We developed an index of the 'prevalence of rule violations' (PRV) based on country-level data from the year 2003 of corruption, tax evasion and fraudulent politics. We measured intrinsic honesty in an anonymous die-rolling experiment. We conducted the experiments with 2,568 young participants (students) who, due to their young age in 2003, could not have influenced PRV in 2003. We find individual intrinsic honesty is stronger in the subject pools of low PRV countries than those of high PRV countries. The details of lying patterns support psychological theories of honesty. The results are consistent with theories of the cultural co-evolution of institutions and values, and show that weak institutions and cultural legacies that generate rule violations not only have direct adverse economic consequences, but might also impair individual intrinsic honesty that is crucial for the smooth functioning of society.

  9. Intrinsically Disordered Side of the Zika Virus Proteome

    Directory of Open Access Journals (Sweden)

    Rajanish Giri

    2016-11-01

    Full Text Available Over the last few decades, concepts of protein intrinsic disorder have been implicated in different biological processes. Recent studies have suggested that intrinsically disordered proteins (IDPs provide structural plasticity and functional diversity to viral proteins that are involved in rapid replication and immune evasion in host cells. In case of Zika virus, the roles of protein intrinsic disorder in mechanisms of pathogenesis are not completely understood. In this study, we have analyzed the prevalence of intrinsic disorder in Zika virus proteome (strain MR 766. Our analyses revealed that Zika virus polyprotein is enriched with intrinsically disordered protein regions (IDPRs and this finding is consistent with previous reports on the involvement of IDPs in shell formation and virulence of the Flaviviridae family. We found abundant IDPRs in Capsid, NS2B, NS3, NS4A, and NS5 proteins that are involved in mature particle formation and replication. In our view, the intrinsic disorder-focused analysis of ZIKV proteins could be important for the development of new disorder-based drugs.

  10. Pre-analytical variables of circulating cell-free nucleosomes containing 5-methylcytosine DNA or histone modification H3K9Me3

    DEFF Research Database (Denmark)

    Rasmussen, Louise; Herzog, Marielle; Rømer, Eva

    2016-01-01

    Aim: To evaluate pre-analytical variables of circulating cell-free nucleosomes containing 5-methylcytosine DNA (5mC) or histone modification H3K9Me3 (H3K9Me3). Materials and methods: Six studies were designed to assess the possible influence of pre-analytical variables. Study 1: influence of stas...... significantly lower levels of 5mC or H3K9Me3 compared to levels in healthy individuals. Conclusion: Levels of 5mC or H3K9Me3 appear stable in most pre-analytical settings if blood samples are stored at room temperature until centrifugation.......3K9Me3 measurements were performed using enzyme-linked immunosorbent assays. Results: Stasis, white-cell and platelet contamination, within-day variations, varying storage time before centrifugation, colonoscopy, and surgical trauma had no significant influence on levels of 5mC or H3K9Me3. Day......-to-day variations of 12.7% and 11.5% (intra-individual) and 98.1% and 60.8% (inter-individual) were shown for 5mC and H3K9Me3, respectively. Levels of 5mC or H3K9Me3 were significantly higher in samples stored at room temperature until centrifugation compared to samples stored on ice. Patients with cancer had...

  11. High-mobility group nucleosome-binding domain 2 protein inhibits the invasion of Klebsiella pneumoniae into mouse lungs in vivo.

    Science.gov (United States)

    Zheng, Shuang; Ren, Laibin; Li, Heng; Shen, Xiaofei; Yang, Xiaolong; Li, Na; Wang, Xinyuan; Guo, Xiaojuan; Wang, Xiaoying; Huang, Ning

    2015-07-01

    Since bacterial invasion into host cells is a critical step in the infection process and the predominance of multiple-antibiotic-resistant Klebsiella (K.) pneumoniae strains, using molecular agents to interfere with K. pneumoniae invasion is an attractive approach for the prevention of infection and suppress the immune inflammatory response. In previous studies by our group, high-mobility group nucleosome-binding domain 2 (HMGN2) protein was shown to exhibit anti-bacterial activity in vitro. The objective of the present study was to investigate the effects of HMGN2 protein on the invasion of K. pneumoniae 03183 in vivo. The results showed that pre-treatment with 128 µg/ml HMGN2 significantly reduced K. pneumoniae 03183 invasion into mouse lungs and increased the mRNA expression of CXCL1 and LCN2 within 2 h. Immunohistochemical staining showed that F-actin expression was significantly decreased, and fluorescence microscopy and western blot analysis further demonstrated that HMGN2 significantly blocked K. pneumoniae 03183-induced actin polymerization. These changes implied that HMGN2 may provide protection against K. pneumoniae 03183 infection in vivo.

  12. Occupational asthma in maritime environments

    DEFF Research Database (Denmark)

    Lucas, David; Loddé, Brice; Jepsen, Jørgen Riis

    2016-01-01

    In 2006 we published our first review based on the available literature on occupational asthma in maritime environments in the “International Maritime Health” journal. Since then, we have obtained a great deal of new knowledge on asthma in seafood workers and fishermen and on the impact...... of exposures from sulphites preservatives, container fumigants etc. in maritime workers. This review aims to provide an update of the current knowledge base about occupational asthma in a maritime context and to provide recommendations regarding medical surveillance of workers at risk....

  13. The Healing Nature of Occupation

    Directory of Open Access Journals (Sweden)

    Jennifer Fortuna

    2017-03-01

    Full Text Available Moses Hamilton, an artist based in Hawaii, provided the cover art for the Spring 2017 edition of The Open Journal of Occupational Therapy (OJOT. “Pali Kai” is a 11”x14” painting made from acrylic on canvas. When a tragic car accident left Hamilton paralyzed from the chest down, mouth painting provided an outlet for selfexpression and stress relief. Participation in a meaningful occupation helped Hamilton find his path in life. With their colorful impressionist-style, Hamilton’s paintings have brought happiness to people all over the world.

  14. Occupational Asthma after Withdrawal from the Occupational Allergen Exposure

    Czech Academy of Sciences Publication Activity Database

    Klusáčková, P.; Pelclová, D.; Lebedová, J.; Marečková, H.; Brabec, Marek

    2006-01-01

    Roč. 44, č. 4 (2006), s. 629-638 ISSN 0019-8366 Source of funding: V - iné verejné zdroje Keywords : occupational asthma * allergen exposure withdrawal Subject RIV: BB - Applied Statistics, Operational Research Impact factor: 0.911, year: 2006 http://www.jniosh.go.jp/en/indu_hel/pdf/indhealth_44_4_629.pdf

  15. Civilian law: from occupational medicine to occupational event.

    Science.gov (United States)

    Mpotos, N; Watelet, J B

    Civilian law:from occupational medicine to occupational event. Despite the growing importance of objective measurements, the health effects of many occupational risk factors are currently not fully quantified. Occupational noise, as a widespread risk factor, is illustrative in this regard; there is a strong body of evidence linking it to an important health outcome (hearing loss), but it is less decisively associated with others (such as psychological disorders). It is also distinct from environmental noise, and therefore falls under the responsibility of employers as well as individuals. Noise-induced hearing loss (NIHL) is, at present, incurable and irreversible. However, it is preventable, if effective and global hearing conservation programmes can be implemented. These programmes should not be isolated efforts, but should be integrated into the overall hazard prevention and control programme of the workplace. Belgian law encompasses a set of provisions for prevention and the protection of the health and safety of workers within the workplace, including aspects pertaining to the hygiene of the workplace and psychosocial aspects at work (stress, violence, bullying and sexual harassment, among others). In principle, combating environmental noise is fully addressed in this country. However, other levels of policy-making also play an important role in this regard. For example, the federal government is in charge of product standards, and therefore also of noise emission standards for products. The interpretation and enforcement of Belgian legislation on well-being at work converts European directives and international agreements on well-being at work into Belgian law.

  16. On the Relationship Between First Occupation and Current Occupational Status

    Science.gov (United States)

    Beck, E. M.; Madans, J. H.

    1974-01-01

    Three alternative models are presented to represent the decreased importance of the status of first job on current occupational status overtime; there is evidence that the effects of first job erode with time. Models not explicitly incorporating labor force experience may suffer a serious specification error. (Author/AJ)

  17. [Prevention of HIV transmission (vertical, occupational and non-occupational)].

    Science.gov (United States)

    Azkune, Harkaitz; Ibarguren, Maialen; Camino, Xabier; Iribarren, José Antonio

    2011-10-01

    In these almost thirty years since the epidemic of HIV infection strategies have been developed to decrease the transmission risk when a non-infected person comes into contact with HIV. One of the key landmarks was the use zidovudine was shown to reduce the risk of HIV infection by vertical transmission from 25% to 8% when given from the second trimester of pregnancy, during partum and for several weeks in the newborn. These strategies have been subsequently perfected until achieving vertical transmission rates less than 1%. Almost at the same time, strategies have been developed in an attempt to reduce the risk of transmission of infection after occupational accidents and, in the last few years prophylaxis after non-occupational exposure has been a field of particular concern. Even in this past year several experiments on pre-exposure prophylaxis have been published, which are generating an intense debate on is applicability. In this article, we analyse the state of the art in the prevention of vertical transmission and occupational and non-occupational prophylaxis, from a perspective of applying this in the developed world. We also review the published data on pre-exposure prophylaxis. Copyright © 2011 Elsevier España, S.L. All rights reserved.

  18. Broadening the occupational therapy toolkit: an executive functioning lens for occupational therapy with children and youth.

    Science.gov (United States)

    Cramm, Heidi; Krupa, Terry; Missiuna, Cheryl; Lysaght, Rosemary M; Parker, Kevin C H

    2013-01-01

    Attention to executive functioning (EF) and its effect on occupational performance is increasing in the occupational therapy literature. This study explored occupational therapists' perceptions of how EF is recognized and addressed within occupational therapy for children and youth. Inductive qualitative content analysis was used to analyze the in-depth interview data from 13 occupational therapists with a range of practice contexts and experience. EF should be explicitly considered during clinical reasoning. System and professional barriers create challenges to occupational therapists, constraining their ability to recognize, label, and address EF performance issues. Occupational therapists who have integrated EF into their practice perspective have acquired knowledge and skills through interprofessional collaborations, client interactions, and professional development opportunities. Occupational therapists working with children and youth need an occupational EF framework and practice resources if they are to integrate an EF lens to more broadly enable occupational performance. Copyright © 2013 by the American Occupational Therapy Association, Inc.

  19. Text Summarization Evaluation: Correlating Human Performance on an Extrinsic Task with Automatic Intrinsic Metrics

    National Research Council Canada - National Science Library

    President, Stacy F; Dorr, Bonnie J

    2006-01-01

    This research describes two types of summarization evaluation methods, intrinsic and extrinsic, and concentrates on determining the level of correlation between automatic intrinsic methods and human...

  20. Towards inclusive occupational therapy: Introducing the CORE approach for inclusive and occupation-focused practice.

    Science.gov (United States)

    Pereira, Robert B

    2017-12-01

    Occupation is a human right and a social determinant of health. It is also taken for granted. Having access to, and participating in, occupation, is intricately linked to positive health and wellbeing. Despite theory and evidence to support the link between occupation, health and wellbeing, occupational therapists can struggle with applying an occupation focus in practice and knowing how to use occupational frameworks to enable occupation. The purpose of this paper is to introduce the Capabilities, Opportunities, Resources and Environments (CORE) approach for inclusive and occupation-focused practice. It provides occupational therapists with a means of operationalising occupational enablement and facilitating social inclusion. The CORE approach is introduced by linking its main ideas to Economist and Nobel Prize Laureate Amartya Sen's capabilities approach, as well as findings from the author's doctoral research into entrenched disadvantage and social inclusion. Practical questions guided by the CORE approach's acronym are given to explore how the approach can be utilised alongside other occupational models and frameworks to encourage strategies for effective enablement through occupation for social inclusion. As experts in enabling occupation, occupational therapists can use the CORE approach to design occupation-focused interventions and promote inclusive occupational therapy. © 2017 Occupational Therapy Australia.