890 resultados para Suppression neuronale


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In the coming decades, the mining industry faces the dual challenge of lowering both its water and energy use. This presents a difficulty since technological advances that decrease the use of one can increase the use of the other. Historically, energy and water use have been modelled independently, making it difficult to evaluate the true costs and benefits from water and energy improvements. This paper presents a hierarchical systems model that is able to represent interconnected water and energy use at a whole of site scale. In order to explore the links between water and energy four technologies advancements have been modelled: use of dust suppression additives, the adoption of thickened tailings, the transition to dry processing and the incorporation of a treatment plant. The results show a synergy between decreased water and energy use for dust suppression additives, but a trade-off for the others.

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The proper function of the spindle is crucial to the high fidelity of chromosome segregation and is indispensable for tumor suppression in humans. Centrobin is a recently identified centrosomal protein that has a role in stabilizing the microtubule structure. Here we functionally characterize the defects in centrosome integrity and spindle assembly in Centrobin-depleted cells. Centrobin-depleted cells show a range of spindle abnormalities including unfocused poles that are not associated with centrosomes, S-shaped spindles and mini spindles. These cells undergo mitotic arrest and subsequently often die by apoptosis, as determined by live cell imaging. Co-depletion of Mad2 relieves the mitotic arrest, indicating that cells arrest due to a failure to silence the spindle checkpoint in metaphase. Consistent with this, Centrobin-depleted metaphase cells stained positive for BubR1 and BubR1 S676. Staining with a panel of centrosome markers showed a loss of centrosome anchoring to the mitotic spindle. Furthermore, these cells show less cold-stable microtubules and a shorter distance between kinetochore pairs. These results show a requirement of Centrobin in maintaining centrosome integrity, which in turn promotes anchoring of mitotic spindle to the centrosomes. Furthermore, this anchoring is required for the stability of microtubule–kinetochore attachments and biogenesis of tension-ridden and properly functioning mitotic spindle.

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Approximately half of prostate cancers (PCa) carry TMPRSS2-ERG translocations; however, the clinical impact of this genomic alteration remains enigmatic. Expression of v-ets erythroblastosis virus E26 oncogene like (avian) gene (ERG) promotes prostatic epithelial dysplasia in transgenic mice and acquisition of epithelial-to-mesenchymal transition (EMT) characteristics in human prostatic epithelial cells (PrECs). To explore whether ERG-induced EMT in PrECs was associated with therapeutically targetable transformation characteristics, we established stable populations of BPH-1, PNT1B and RWPE-1 immortalized human PrEC lines that constitutively express flag-tagged ERG3 (fERG). All fERG-expressing populations exhibited characteristics of in vitro and in vivo transformation. Microarray analysis revealed >2000 commonly dysregulated genes in the fERG-PrEC lines. Functional analysis revealed evidence that fERG cells underwent EMT and acquired invasive characteristics. The fERG-induced EMT transcript signature was exemplified by suppressed expression of E-cadherin and keratins 5, 8, 14 and 18; elevated expression of N-cadherin, N-cadherin 2 and vimentin, and of the EMT transcriptional regulators Snail, Zeb1 and Zeb2, and lymphoid enhancer-binding factor-1 (LEF-1). In BPH-1 and RWPE-1-fERG cells, fERG expression is correlated with increased expression of integrin-linked kinase (ILK) and its downstream effectors Snail and LEF-1. Interfering RNA suppression of ERG decreased expression of ILK, Snail and LEF-1, whereas small interfering RNA suppression of ILK did not alter fERG expression. Interfering RNA suppression of ERG or ILK impaired fERG-PrEC Matrigel invasion. Treating fERG-BPH-1 cells with the small molecule ILK inhibitor, QLT-0267, resulted in dose-dependent suppression of Snail and LEF-1 expression, Matrigel invasion and reversion of anchorage-independent growth. These results suggest that ILK is a therapeutically targetable mediator of ERG-induced EMT and transformation in PCa.

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Large scale exome sequencing studies have revealed regions of the genome, which contribute to the castrate resistant prostate cancer (CRPC) phenotype. [1],[2],[3] Such studies have identified mutations in genes, which may have diagnostic/prognostic potential, or which may be targeted therapeutically. Two of these genes include the androgen receptor (AR) and speckle-type POZ protein (SPOP) genes. However, the findings from these exome sequencing studies can only be translated therapeutically once the functional consequences of these mutations have been determined. Here, we highlight the recent study by An et al. [4] which investigated the functional effects of mutations in the SPOP gene that were identified in the aforementioned exome sequencing studies, particularly in the context of SPOP-mediated degradation of the AR.

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The world of classical ballet exerts considerable physical and psychological stress upon those who participate, and yet the process of coping with such stressors is not well understood. Relationships between coping strategies and competitive trait anxiety were investigated among 104 classical dancers (81 females and 23 males) from three professional ballet companies, two private dance schools, and two full-time, university dance courses in Australia. Coping strategies were assessed using the Modified COPE scale (MCOPE: Crocker & Graham, 1995), a 48-item measure of 12 dimensions of coping. Competitive trait anxiety was assessed using the Sport Anxiety Scale (SAS: Smith, Smoll, & Schutz, 1990), a 21-item measure of three anxiety dimensions. Trait anxiety scores, in particular for Somatic Anxiety and Worry, predicted seven of the 12 coping strategies (Suppression of Competing Activities: R2 = 27.1%; Venting of Emotions: R2 = 23.2%; Active Coping: R2 = 14.3%; Denial: R2 = 17.7%; Self-Blame: R2 = 35.7%; Effort: R2 = 16.6%; Wishful Thinking: R2 = 42.3%). High trait anxious dancers reported more frequent use of all categories of coping strategies, some of which are considered to be maladaptive. No effects of gender or status (professional versus students) were identified. Results emphasize the need for the effectiveness of specific coping strategies to be considered during the process of preparing young classical dancers for a career in professional ballet.

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The world of classical ballet exerts considerable physical and psychological stress upon those who participate, and yet the process of coping with such stressors is not well understood. The purpose of the present investigation was to examine relationships between coping strategies and competitive trait anxiety among ballet dancers. Participants were 104 classical dancers (81 females and 23 males) ranging in age from 15 to 35 years (M = 19.4 yr., SD = 3.8 yr.) from three professional ballet companies, two private dance schools, and two full-time, university dance courses in Australia. Participants had a mean of 11.5 years of classical dance training (SD = 5.2 yr.), having started dance training at 6.6 years of age (SD = 3.4 yr.). Coping strategies were assessed using the Modified COPE scale (MCOPE: Crocker & Graham, 1995), a 48-item measure comprising 12 coping subscales (Seeking Social Support for Instrumental Reasons, Seeking Social Support for Emotional Reasons, Behavioral Disengagement, Planning, Suppression of Competing Activities, Venting of Emotions, Humor, Active Coping, Denial, Self-Blame, Effort, and Wishful Thinking). Competitive trait anxiety was assessed using the Sport Anxiety Scale (SAS: Smith, Smoll, & Schutz, 1990), a 21-item measure comprising three anxiety subscales (Somatic Anxiety, Worry, Concentration Disruption). Standard multiple regression analyses showed that trait anxiety scores, in particular for Somatic Anxiety and Worry, were significant predictors of seven of the 12 coping strategies (Suppression of Competing Activities: R2 = 27.1%; Venting of Emotions: R2 = 23.2%; Active Coping: R2 = 14.3%; Denial: R2 = 17.7%; Self-Blame: R2 = 35.7%; Effort: R2 = 16.6%; Wishful Thinking: R2 = 42.3%). High trait anxious dancers reported more frequent use of all categories of coping strategies. A separate two-way MANOVA showed no significant main effect for gender nor status (professional versus students) and no significant interaction effect. The present findings are generally consistent with previous research in the sport psychology domain (Crocker & Graham, 1995; Giacobbi & Weinberg, 2000) which has shown that high trait anxious athletes tend, in particular, to use more maladaptive, emotion-focused coping strategies when compared to low trait anxious athletes; a tendency which has been proposed to lead to negative performance effects. The present results emphasize the need for the effectiveness of specific coping strategies to be considered during the process of preparing young classical dancers for a career in professional ballet. In particular, the results suggest that dancers who are, by nature, anxious about performance may need special attention to help them to learn to cope with performance-related stress. Given the absence of differences in coping strategies between student and professional dancers and between males and females, it appears that such educational efforts should begin at an early career stage for all dancers.

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Oncogene-induced senescence (OIS) is a potent tumor-suppressive mechanism that is thought to come at the cost of aging. The Forkhead box O (FOXO) transcription factors are regulators of life span and tumor suppression. However, whether and how FOXOs function in OIS have been unclear. Here, we show a role for FOXO4 in mediating senescence by the human BRAFV600E oncogene, which arises commonly in melanoma. BRAFV600E signaling through mitogen-activated protein kinase/extracellular signal-regulated kinase kinase resulted in increased reactive oxygen species levels and c-Jun NH 2 terminal kinase-mediated activation of FOXO4 via its phosphorylation on Thr223, Ser226, Thr447, and Thr451. BRAFV600E-induced FOXO4 phosphorylation resulted in p21cip1-mediated cell senescence independent of p16 ink4a or p27kip1. Importantly, melanocyte-specific activation of BRAFV600E in vivo resulted in the formation of skin nevi expressing Thr223/Ser226-phosphorylated FOXO4 and elevated p21cip1. Together, these findings support a model in which FOXOs mediate a trade-off between cancer and aging.

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The mining industry faces three long term strategic risks in relation to its water and energy use: 1) securing enough water and energy to meet increased production; 2) reducing water use, energy consumption and emissions due to social, environmental and economic pressures; and 3) understanding the links between water and energy, so that an improvement in one area does not create an adverse effect in another. This project helps the industry analyse these risks by creating a hierarchical systems model (HSM) that represents the water and energy interactions on a sub-site, site and regional scales; which is coupled with a flexible risk framework. The HSM consists of: components that represent sources of water and energy; activities that use water and energy and off-site destinations of water and produced emissions. It can also represent more complex components on a site, with inbuilt examples including tailings dams and water treatment plants. The HSM also allows multiple sites and other infrastructure to be connected together to explore regional water and energy interactions. By representing water and energy as a single interconnected system the HSM can explore tradeoffs and synergies. For example, on a synthetic case study, which represents a typical site, simulations suggested that while a synergy in terms of water use and energy use could be made when chemical additives were used to enhance dust suppression, there were trade-offs when either thickened tailings or dry processing were used. On a regional scale, the HSM was used to simulate various scenarios, including: mines only withdrawing water when needed; achieving economics-of-scale through use of a single centralised treatment plant rather than smaller decentralised treatment plants; and capturing of fugitive emissions for energy generation. The HSM also includes an integrated risk framework for interpreting model output, so that onsite and off-site impacts of various water and energy management strategies can be compared in a managerial context. The case studies in this report explored company, social and environmental risks for scenarios of regional water scarcity, unregulated saline discharge, and the use of plantation forestry to offset carbon emissions. The HSM was able to represent the non-linear causal relationship at the regional scale, such as the forestry scheme offsetting a small percentage of carbon emissions but causing severe regional water shortages. The HSM software developed in this project will be released as an open source tool to allow industry personnel to easily and inexpensively quantify and explore the links between water use, energy use, and carbon emissions. The tool can be easily adapted to represent specific sites or regions. Case studies conducted in this project highlighted the potential complexity of these links between water, energy, and carbon emissions, as well as the significance of the cumulative effects of these links over time. A deeper understanding of these links is vital for the mining industry in order to progress to more sustainable operations, and the HSM provides an accessible, robust framework for investigating these links.

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OBJECTIVE The effects of free fatty acids (FFA), leptin, tumour necrosis factor (TNF) alpha and body fat distribution on in vivo oxidation of a glucose load were studied in two South African ethnic groups. DESIGN AND MEASUREMENTS Anthropometric and various metabolic indices were measured at fasting and during a 7h oral glucose tolerance test (OGTT). Body composition was measured using bioelectrical impedance analysis and subcutaneous and visceral fat mass was assessed using a five- and two-level CT-scan respectively. Glucose oxidation was evaluated by measuring the ratio of (13)CO(2) to (12)CO(2) in breath following ingestion of 1-(13)C-labelled glucose. SUBJECTS Ten lean black women (LBW), ten obese black women (OBW), nine lean white women (LWW) and nine obese white women (OWW) were investigated after an overnight fast. RESULTS Visceral fat levels were significantly higher (P < 0.01) in obese white than black women, despite similar body mass indexes (BMIs). There were no ethnic differences in glucose oxidation however; in the lean subjects of both ethnic groups the area under the curve (AUC) was higher than in obese subjects (P < 0.05 for both) and was found to correlate negatively with weight (r = -0.69, P < 0.01) after correcting for age. Basal TNF alpha concentrations were similar in all groups. Percentage suppression of FFAs at 30 min of the OCTT was 24 +/- 12% in OWW and - 38 +/- 23% (P < 0.05) in OBW, ie the 30 min FFA level was higher than the fasting level in the latter group. AUC for FFAs during the late postprandial period (120 - 420 min) was significantly higher in OWW than OBW (P < 0.01) and LWW (P < 0.01) and correlated positively with visceral fat mass independent of age (r = 0.78, P < 0.05) in the OWW only. Leptin levels were higher (P < 0.01) both at fasting and during the course of the OCTT in obese women from both ethnic groups compared to the lean women. CONCLUSIONS Glucose oxidation is reduced in obese subjects of both ethnic groups; inter- and intra-ethnic differences were observed in visceral fat mass and FFA production and it is possible that such differences may play a role in the differing prevalences of obesity-related disorders that have been reported in these two populations.

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BACKGROUND Estradiol (E-2) is an important promoter of the growth of both eutopic and ectopic endometrium. The findings with regard to the expression and activity of steroidogenic enzymes in endometrium of controls, in endometrium of endometriosis patients and in endometriotic lesions are not consistent. METHODS In this study, we have looked at the mRNA expression and protein levels of a range of steroidogenic enzymes [aromatase, 17 beta-hydroxysteroid dehydrogenases (17 beta-HSD) type 1, 2 and 4, estrogen sulfotransferase (EST) and steroid sulfatase (STS)l in eutopic and ectopic endometrium of patients (n = 14) with deep-infiltrative endometriosis as well as in disease-free endometrium (n = 48) using real-time PCR and immunocytochemistry. In addition, we evaluated their menstrual cycle-related expression patterns, and investigated their steroid responsiveness in explant cultures. RESULTS Aromatase and 17 beta-HSD type 1 mRNA levels were extremely low in normal human endometrium, while mRNAs for types 2 and 4 17 beta-HSD, EST and STS were readily detectable. Only 17 beta-HSD type 2 and EST genes showed sensitivity to progesterone in normal endometrium. Types 1 and 2 17 beta-HSD and STS protein was detected in normal endometrium using new polyclonal antibodies. CONCLUSIONS In endometriosis lesions, the balance is tilted in favor of enzymes producing E2. This is due to a suppression of types 2 and 4 17 beta-HSD, and an increased expression of aromatase and type 1 17 beta-HSD in ectopic endometrium.

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Piracy is one of the main maritime security concerns in the contemporary world. The number of piracy incidents is increasing rapidly, which is highly problematic for maritime security. Although international law provides universal jurisdiction for the prosecution of maritime pirates, the actual number of prosecutions is alarmingly low compared to the number of incidents of piracy. Despite many states becoming parties to the relevant international conventions, they are reluctant to establish the necessary legal and institutional frameworks at the national level for the prosecution of pirates. The growing incidences of piracy and the consequential problems associated with prosecuting pirates have created doubts about the adequacy of the current international legal system, which is fully dependent on national courts for the prosecution of pirates. This article examines the possible ways for ensuring the effective prosecution of pirates. Contrary to the different proposals forwarded by researchers in the wake of Somali piracy for the establishment of international judicial institutions for the prosecution of pirates, this article argues that the operationalization of national courts through the proper implementation of relevant international legal instruments within domestic legal systems is the most viable solution. However, this article submits that the operationalization of national courts will not be very successful following the altruistic model of universal adjudicative jurisdiction. A state may enact legislation implementing universal jurisdiction but will not be very interested in prosecuting a pirate in its national court if it has no relation with the piratical incident. Rather, it will be successful if the global community seriously implement the Convention for the Suppression of Unlawful Acts against the Safety of Maritime Navigation (SUA Convention), which obligates the states that have some connection with a piratical incident to prosecute pirates in their national courts.

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To reduce the natural convection heat loss from enclosures many researchers used convection suppression devices in the past. In this study a single baffle is used under the top tip to investigate numerically the natural convection heat loss in an attic shaped enclosure which is a cost effective approach. The case considered here is one inclined wall of the enclosure is uniformly heated while the other inclined wall is uniformly cooled with adiabatic bottom wall. The finite volume method has been used to discretize the governing equations, with the QUICK scheme approximating the advection term. The diffusion terms are discretized using central-differencing with second order accuracy. A wide range of governing parameters are studied (Rayleigh number, aspect ratio, baffle length etc.). It is observed that the heat transfer due to natural convection in the enclosure reduces when the baffle length is increased. Effects of other parameters on heat transfer and flow field are described in this study.

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Eosinophilic oesophagitis (EEl is most commonly observed in children and young males, and is estimated to affect one per 10,000 children, and lo/o of adults in Australia. EE causes inflammation of the oesophagus; and an endoscopy, and biopsy showing an increase in eosinophils through the oesophagus is used for diagnosis. People with EE often present with non-specific symptoms to varying degrees of severity that could also suggest swallowing difficulties, or acid reflux; the feeling of food sticking to the throat on the way down (sometimes completely), choking on food, regurgitation of food, and severe acid reflux that does not respond to stomach acid suppression treatment...

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The effects of reductions in cell wall lignin content, manifested by RNA interference suppression of coumaroyl 3'-hydroxylase, on plant growth, water transport, gas exchange, and photosynthesis were evaluated in hybrid poplar trees (Populus alba 3 grandidentata). The growth characteristics of the reduced lignin trees were significantly impaired, resulting in smaller stems and reduced root biomass when compared to wild-type trees, as well as altered leaf morphology and architecture. The severe inhibition of cell wall lignification produced trees with a collapsed xylem phenotype, resulting in compromised vascular integrity, and displayed reduced hydraulic conductivity and a greater susceptibility to wall failure and cavitation. In the reduced lignin trees, photosynthetic carbon assimilation and stomatal conductance were also greatly reduced, however, shoot xylem pressure potential and carbon isotope discrimination were higher and water-use efficiency was lower, inconsistent with water stress. Reductions in assimilation rate could not be ascribed to increased stomatal limitation. Starch and soluble sugars analysis of leaves revealed that photosynthate was accumulating to high levels, suggesting that the trees with substantially reduced cell wall lignin were not carbon limited and that reductions in sink strength were, instead, limiting photosynthesis.

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Objective The aim of this study was to explore the mediating and moderating relationships between emotional perceptions of coeliac disease, negative emotional states, emotion regulation, emotional eating and gluten-free diet adherence. Method Adults with coeliac disease (N = 253) were recruited from state organisations of Coeliac Australia and completed an online questionnaire measuring illness perceptions, emotion regulation strategies, negative emotional states, emotional eating and gluten-free diet adherence. Results Participants' levels of depression and anxiety, but not stress or emotional eating, were associated with gluten-free diet adherence. Emotional perception of coeliac disease was also associated with gluten-free diet adherence, and this relationship was partially mediated by depression and anxiety. Furthermore, the emotion regulation strategies of cognitive reappraisal and expressive suppression moderated the relationship between emotional perceptions and depression, but not emotional perceptions and anxiety. Conclusions Interventions to improve dietary adherence for adults with coeliac disease displaying depressive symptoms should aim to increase the use of cognitive reappraisal and reduce the use of expressive suppression. Future studies should also explore mechanisms that may moderate the relationship between emotional perceptions and anxiety.