74 resultados para histone modification

em Deakin Research Online - Australia


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Skeletal muscle adaptations to exercise confer many of the health benefits of physical activity and occur partly through alterations in skeletal muscle gene expression. The exact mechanisms mediating altered skeletal muscle gene expression in response to exercise are unknown. However, in recent years, chromatin remodelling through epigenetic histone modifications has emerged as a key regulatory mechanism controlling gene expression in general. The purpose of this study was to examine the effect of exercise on global histone modifications that mediate chromatin remodelling and transcriptional activation in human skeletal muscle in response to exercise. In addition, we sought to examine the signalling mechanisms regulating these processes. Following 60 min of cycling, global histone 3 acetylation at lysine 9 and 14, a modification associated with transcriptional initiation, was unchanged from basal levels, but was increased at lysine 36, a site associated with transcriptional elongation. We examined the regulation of the class IIa histone deacetylases (HDACs), which are enzymes that suppress histone acetylation and have been implicated in the adaptations to exercise. While we found no evidence of proteasomal degradation of the class IIa HDACs, we found that HDAC4 and 5 were exported from the nucleus during exercise, thereby removing their transcriptional repressive function. We also observed activation of the AMP-activated protein kinase (AMPK) and the calcium–calmodulin-dependent protein kinase II (CaMKII) in response to exercise, which are two kinases that induce phosphorylation-dependent class IIa HDAC nuclear export. These data delineate a signalling pathway that might mediate skeletal muscle adaptations in response to exercise.

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The Saccharomyces cerevisiae WD-40 repeat protein Swd2p associates with two functionally distinct multiprotein complexes: the cleavage and polyadenylation factor (CPF) that is involved in pre-mRNA and snoRNA 3′ end formation and the SET1 complex (SET1C) that methylates histone 3 lysine 4. Based on bioinformatic analysis we predict a seven-bladed β-propeller structure for Swd2p proteins. Northern, transcriptional run-on and in vitro 3′ end cleavage analyses suggest that temperature sensitive swd2 strains were defective in 3′ end formation of specific mRNAs and snoRNAs. Protein–protein interaction studies support a role for Swd2p in the assembly of 3′ end formation complexes. Furthermore, histone 3 lysine 4 di-and tri-methylation were adversely affected and telomeres were shortened in swd2 mutants. Underaccumulation of the Set1p methyltransferase accounts for the observed loss of SET1C activity and suggests a requirement for Swd2p for the stability or assembly of this complex. We also provide evidence that the roles of Swd2p as component of CPF and SET1C are functionally independent. Taken together, our results establish a dual requirement for Swd2p in 3′ end formation and histone tail modification.

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During meiosis, combinatorial associations of genetic traits arise from homologous recombination between parental chromosomes. Histone H3 lysine 4 trimethylation marks meiotic recombination hotspots in yeast and mammals, but how this ubiquitous chromatin modification relates to the initiation of double-strand breaks (DSBs) dependent on Spo11 remains unknown. Here, we show that the tethering of a PHD-containing protein, Spp1 (a component of the COMPASS complex), to recombinationally cold regions is sufficient to induce DSB formation. Furthermore, we found that Spp1 physically interacts with Mer2, a key protein of the differentiated chromosomal axis required for DSB formation. Thus, by interacting with H3K4me3 and Mer2, Spp1 promotes recruitment of potential meiotic DSB sites to the chromosomal axis, allowing Spo11 cleavage at nearby nucleosome-depleted regions.

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The present study was designed to develop a Body Modification Scale (BMS) to measure body change among adolescents and to modify an Excessive Exercise Scale (EES) into a shorter form for adolescents. Two hundred and twenty-one girls and 192 boys from Grades 7 to 10 completed the BMS and the EES. Factor analysis revealed three identical factors for the BMS for girls and boys: weight loss, weight gain, and muscle mass. Two identical factors for girls and boys were also revealed for the EES. Both factor structures were further validated on a separate sample of 286 adolescents (140 girls, 146 boys). The BMS and EES demon-strated excellent reliability (alpha > .86) and high test-retest reliability (alpha > .82) over 1 month. Good concurrent validity was also found for the weight loss factor of the BMS. These findings demonstrate the utility of these two scales for use with adolescents.

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The dynamics of fatty acid composition modifications were examined in tissues of Murray cod fed diets containing fish oil (FO), canola oil (CO) and linseed oil (LO) for a 25-week period and subsequently transferred to a FO (finishing/wash-out) diet for a further 16 weeks. At the commencement of the wash-out period, following 25 weeks of vegetable oil substitution diets, the fatty acid compositions of Murray cod fillets were reflective of the respective diets. After transfer to the FO diet, differences decreased in quantity and in numerousness, resulting in a revert to the FO fatty acid composition. Changes in percentages of the fatty acids and total accumulation in the fillet could be described by exponential equations and demonstrated that major modifications occurred in the first days of the finishing period. A dilution model was tested to predict fatty acid composition. In spite of a general reliability of the model (Y=0.9234X+0.4260, R2=0.957, P<0.001, where X is the predicted percentage of fatty acid; Y the observed percentage of fatty acid), in some instances the regression comparing observed and predicted values was markedly different from the line of equity, indicating that the rate of change was higher than predicted (i.e. Y=0.4205X+1.191, R2=0.974, P<0.001, where X is the predicted percentage of α-linolenic acid; Y the observed percentage of α-linolenic acid). Ultimately, using the coefficient of distance (D), it was shown that the fatty acid composition of fish previously fed the vegetable oil diets returned to the average variability of the fillet fatty acid composition of Murray cod after 70 or 97 days (LO and CO respectively).

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Purpose Zinc sulfate is known to inhibit the bitterness of the antimalarial agent quinine [R. S. J. Keast. The effect of zinc on human taste perception. J. Food Sci. 68:1871–1877 (2003)]. In the present work, we investigated whether zinc sulfate would inhibit other bitter-tasting compounds and pharmaceuticals. The utility of zinc as a general bitterness inhibitor is compromised, however, by the fact that it is also a good sweetness inhibitor [R. S. J. Keast, T. Canty, and P. A. S. Breslin. Oral zinc sulfate solutions inhibit sweet taste perception. Chem. Senses 29:513–521 (2004)] and would interfere with the taste of complex formulations. Yet, zinc sulfate does not inhibit the sweetener Na-cyclamate. Thus, we determined whether a mixture of zinc sulfate and Na-cyclamate would be a particularly effective combination for bitterness inhibition (Zn) and masking (cyclamate).

Method We used human taste psychophysical procedures with chemical solutions to assess bitterness blocking.

Results Zinc sulfate significantly inhibited the bitterness of quinine–HCl, Tetralone, and denatonium benzoate (DB) (p < 0.05), but had no significant effect on the bitterness of sucrose octa-acetate, pseudoephedrine (PSE), and dextromethorphan. A second experiment examined the influence of zinc sulfate on bittersweet mixtures. The bitter compounds were DB and PSE, and the sweeteners were sucrose (inhibited by 25 mM zinc sulfate) and Na-cyclamate (not inhibited by zinc sulfate). The combination of zinc sulfate and Na-cyclamate most effectively inhibited DB bitterness (86%) (p < 0.0016), whereas the mixture's inhibition of PSE bitterness was not different from that of Na-cyclamate alone.

Conclusion A combination of Na-cyclamate and zinc sulfate was most effective at inhibiting bitterness. Thus, the combined use of peripheral oral and central cognitive bitterness reduction strategies should be particularly effective for improving the flavor profile of bitter-tasting foods and pharmaceutical formulations.

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Shamanic journeying imagery arguably transcends geographical space and historical time. However, to what extent is the content of the journeying imagery a construction of the shaman's cultural cosmology, belief systems, autobiographical memories, etc? It is suggested that attempts to answer this question are hampered by a fundamental methodological obstacle: how to detect contextual influences on imagery that the shaman cannot report on because they are outside his/her present awareness and memory. A partial solution is presented: Watkins' (1971) Affect Bridge, a hypnoanalytic technique used to uncover the origin of an affect. A nonhypnotic version of the technique developed for inquiry into shamanic journeying imagery is then explicated. Two recent empirical studies conducted by Rock (2006) and Rock, Casey and Baynes (2006), illustrating the utility of the Modified Affect Bridge with regards to investigating experimentally the origin of ostensibly shamanic journeying imagery reported by naive participants, are summarized. A tentative ostensibly shamanic journeying imagery origin typology is formulated and suggestions for future research are advanced.

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We treat naturally pigmented karakul wool with a surface modification system of chlorination and catalytic bleaching, then examine its structure and properties. SEM photos reveal the surface morphology of karakul wool, and the Allworden reaction shows the extent of damage to the epicuticle. The results show that the surface modification removes the bulk of the fiber scales and bleaching increases fiber whiteness. After bleaching, the felting propensity of karakul wool improves slightly and its dye uptake decreases. For modified and bleached karakul wool, the felting propensity decreases, the dyeing rate increases, and equilibrium exhaustion decreases compared with untreated karakul wool.

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Wool fiber was modified by steam explosion in this study. SEM results show that some scales on the fiber surface were cleaved and tiny grooves generated during the explosion. FTIR results suggest no evident changes in the chemical composition of the fiber after the explosion treatment. However, the crystallinity of the fiber decreased slightly as the steam pressure increased based on the X-ray results. In the thermal analysis, DSC results show that the temperature corresponding to vaporization of absorbed water and cleavage of disulfide bonds respectively decreased as the steam pressure increased. The reduction in thermal decomposition energy of the treated fiber indicates that steam explosion might have destroyed some crystals and crosslinks of macromolecular chains in the fiber. The treatment also led to some alterations of the fiber properties, including reduction in strength, moisture regain and solubility in caustic solution.

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A porous Ti–18 at.%Nb–4 at.%Sn (hereafter, Ti–18Nb–4Sn) alloy was prepared by powder metallurgy. The porous structures were examined by scanning electron microscopy and the phase constituents were analysed by X-ray diffraction. Mechanical properties of the porous alloy were investigated using a compressive test. To enhance the bioactivity of the alloy surface, alkali-heat treatment was used to modify the surface. The bioactivity of the pre-treated alloy sample was investigated using a biomimetic process by soaking the sample into simulated body fluid (SBF). Results indicate that the elastic modulus and plateau stress of the porous Ti–18Nb–4Sn alloy decrease with decreasing relative density. The mechanical properties of the porous alloy can be tailored to match those of human bone. After soaking in SBF for 7 days, a hydroxyapatite layer formed on the surface of the pre-treated porous Ti–18Nb–4Sn alloy. The pre-treated porous Ti–18Nb–4Sn alloy therefore has the potential to be a bioactive implant material.

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Caffeine is the worlds most consumed psychoactive chemical and as such is a valuable commodity to the food and beverage industry. Caffeine also activates the bitter taste system causing a potential problem for manufacturers wanting to develop products containing caffeine. In the present study both oral peripheral and central cognitive strategies were used in an attempt to suppress the bitterness of caffeine. Subjects (n = 33) assessed the influence of sodium gluconate (100 mM), zinc lactate (5 mM), sucrose (125 mM and 250 mM), milk (0%, 2% and 4% milk fat), and aromas (coffee, chocolate, mocha) on the bitterness of caffeine (1.5, 3 and 4.5 mM). The oral peripheral strategies proved most effective at suppressing the bitterness of caffeine: zinc lactate (−71%, p < 0.05), non-fat milk (−49%, p < 0.05), and sodium gluconate (−31%). Central cognitive strategies were partially effective: 250 mM sucrose (−47%, p < 0.05) and mocha aroma (−10%) decreased bitterness, while chocolate (+32%) and coffee (+17%) aromas increased perceived bitterness. Overall, zinc lactate was the most effective bitterness inhibitor, however the utility of zinc in foods is negated by its ability to inhibit sweetness.

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The criteria for accepting or rejecting a technology extend beyond the intrinsic properties of the finished product such as physical performance. There are also extrinsic factors such as the history of the product and trust in the manufacturers and suppliers, as well as the perceptions and risk management strategies of various stakeholder groups. A methodology was trialled to take into account the extended supply chain of the product, while simultaneously engaging stakeholders to determine and to understand their perceptual frameworks. Three pine decking products manufactured using different amounts and types of chemical modification were compared using life cycle assessment and the comments of 114 respondents from six stakeholder groups in New Zealand. The results of the perceptual research include a quadrant diagram which allows a visual comparison of the responses of different stakeholders to actual or hypothetical products, aiding the identification of when and why certain technologies may be disqualified from acceptability or become the topic of public debate.

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To help avoid conflict and even market rejection, the design and introduction of new technologies can be aided by consideration of the potential concerns of different stakeholder groups. An assessment of their desired goals for technological change may be useful for pre-empting changes in the  parameters of acceptability for technologies. As part of a research  programme evaluating the parameters of acceptability for bio-based  technologies using life cycle assessment of products and an analysis of the  perceptual frameworks of stakeholders, respondents from four stakeholder  groups in New Zealand were interviewed about the desirable and  undesirable trajectories for chemical modification technologies. Three  examples of pine decking products derived using different amounts and  types of chemical modification served to help explore the contemporary  criteria and rationale for acceptability. The responses of the 70 respondents  in those four groups indicated that new technologies need to be able to  prove their worth with regard to both tangible and intangible qualities if they  are to be accepted into the market in the place of either the existing product  or an inorganic competitor.