Effect of high-frequency resistance exercise on adaptive responses in skeletal muscle

PURPOSE: Regulation of skeletal muscle mass is highly dependent on contractile loading. The purpose of this study was to examine changes in growth factor and inflammatory pathways following high-frequency resistance training. METHODS: Using a novel design in which male Sprague-Dawley rats undertook a "stacked" resistance training protocol designed to generate a summation of transient exercise-induced signaling responses (four bouts of three sets × 10 repetitions of squat exercise, separated by 3 h of recovery), we determined the effects of high training frequency on signaling pathways and transcriptional activity regulating muscle mass. RESULTS: The stacked training regimen resulted in acute suppression of insulin-like growth factor 1 mRNA abundance (P < 0.05) and Akt phosphorylation (P < 0.05), an effect that persisted 48 h after the final training bout. Conversely, stacked training elicited a coordinated increase in the expression of tumor necrosis factor alpha, inhibitor kappa B kinase alpha/beta activity (P < 0.05), and p38 mitogen-activated protein kinase phosphorylation (P < 0.05) at 3 h after each training bout. In addition, the stacked series of resistance exercise bouts induced an increase in p70 S6 kinase phosphorylation 3 h after bouts ×3 and ×4, independent of the phosphorylation state of Akt. CONCLUSIONS: Our results indicate that high resistance training frequency extends the transient activation of inflammatory signaling cascades, concomitant with persistent suppression of key mediators of anabolic responses. We provide novel insights into the effects of the timing of exercise-induced overload and recovery on signal transduction pathways and transcriptional activity regulating skeletal muscle mass in vivo.

'Too high in human terms' : the costs of high security imprisonment. Review of Imprisoning Resistance by Bree Carlton and Intractable by Bernie Matthews.

The article discusses the issues of resistance; that is resistance by prisoners to the various manifestations of power operating in high security prisons, as well as that of attempted shifts in the regime from physical to psychological control. Other topics highlighted include legitimacy and 'official discourse', mourning and the construction of 'ungrievable lives' and the importance of finding a way out of the cycle of violence, which high security regimes perpetuate.

Role of intratumoural heterogeneity in cancer drug resistance : molecular and clinical perspectives

Drug resistance continues to be a major barrier to the delivery of curative therapies in cancer. Historically, drug resistance has been associated with over-expression of drug transporters, changes in drug kinetics or amplification of drug targets. However, the emergence of resistance in patients treated with new-targeted therapies has provided new insight into the complexities underlying cancer drug resistance. Recent data now implicate intratumoural heterogeneity as a major driver of drug resistance. Single cell sequencing studies that identified multiple genetically distinct variants within human tumours clearly demonstrate the heterogeneous nature of human tumours. The major contributors to intratumoural heterogeneity are (i) genetic variation, (ii) stochastic processes, (iii) the microenvironment and (iv) cell and tissue plasticity. Each of these factors impacts on drug sensitivity. To deliver curative therapies to patients, modification of current therapeutic strategies to include methods that estimate intratumoural heterogeneity and plasticity will be essential.

Effect of Coulomb blockade, gold resistance, and thermal expansion on the electrical resistance of ultrathin gold films

Controlling the electrical resistance of granular thin films is of great importance for many applications, yet a full understanding of electron transport in such films remains a major challenge. We have studied experimentally and by model calculations the temperature dependence of the electrical resistance of ultrathin gold films at temperatures between 2 K and 300 K. Using sputter deposition, the film morphology was varied from a discontinuous film of weakly coupled meandering islands to a continuous film of strongly coupled coalesced islands. In the weak-coupling regime, we compare the regular island array model, the cotunneling model, and the conduction percolation model with our experimental data. We show that the tunnel barriers and the Coulomb blockade energies are important at low temperatures and that the thermal expansion of the substrate and the island resistance affect the resistance at high temperatures. At low temperatures our experimental data show evidence for a transition from electron cotunneling to sequential tunneling but the data can also be interpreted in terms of conduction percolation. The resistivity and temperature coefficient of resistance of the meandering gold islands are found to resemble those of gold nanowires. We derive a simple expression for the temperature at which the resistance changes from non-metal-like behavior into metal-like behavior. In the case of strong island coupling, the total resistance is solely determined by the Ohmic island resistance.

Deamplification of pfmdr1-Containing Amplicon on Chromosome 5 in Plasmodium falciparum Is Associated with Reduced Resistance to Artelinic Acid In Vitro

Amplification of the Plasmodium falciparum multidrug resistance 1 gene (pfmdr1) has been implicated in multidrug resistance, including in vitro resistance to artelinic acid (AL). The stability and fitness of having multiple copies of pfmdr1 are important factors due to their potential effects on the resistance phenotype of parasites. These factors were investigated by using an AL-resistant line of P. falciparum (W2AL80) and clones originating from W2AL80. A rapid reduction in pfmdr1 copy number (CN) was observed in the uncloned W2AL80 line; 63% of this population reverted to a CN of <3 without exposure to the drug. Deamplification of the pfmdr1 amplicon was then determined in three clones, each initially containing three copies of pfmdr1. Interestingly, two outcomes were observed during 3 months without drug pressure. In one clone, parasites with fewer than 3 copies of pfmdr1 emerged rapidly. In two other clones, the reversion was significantly delayed. In all subclones, the reduction in pfmdr1 CN involved the deamplification of the entire amplicon (19 genes). Importantly, deamplification of the pfmdr1 amplicon resulted in partial reversal of resistance to AL and increased susceptibility to mefloquine. These results demonstrate that multiple copies of the pfmdr1-containing amplicon in AL-resistant parasites are unstable when drug pressure is withdrawn and have practical implications for the maintenance and spread of parasites resistant to artemisinin derivatives.

The emerging role of extracellular vesicle-mediated drug resistance in cancers: Implications in advanced prostate cancer

Emerging evidence has shown that the extracellular vesicles (EVs) regulate various biological processes and can control cell proliferation and survival, as well as being involved in normal cell development and diseases such as cancers. In cancer treatment, development of acquired drug resistance phenotype is a serious issue. Recently it has been shown that the presence of multidrug resistance proteins such as Pgp-1 and enrichment of the lipid ceramide in EVs could have a role in mediating drug resistance. EVs could also mediate multidrug resistance through uptake of drugs in vesicles and thus limit the bioavailability of drugs to treat cancer cells. In this review, we discussed the emerging evidence of the role EVs play in mediating drug resistance in cancers and in particular the role of EVs mediating drug resistance in advanced prostate cancer. The role of EV-associated multidrug resistance proteins, miRNA, mRNA, and lipid as well as the potential interaction(s) among these factors was probed. Lastly, we provide an overview of the current available treatments for advanced prostate cancer, considering where EVs may mediate the development of resistance against these drugs.

The emerging role of microRNAs in resistance to lung cancer treatments

One of the major challenges in the treatment of lung cancer is the development of drug resistance. This represents a major obstacle in the treatment of patients, limiting the efficacy of both conventional chemotherapy and biological therapies. Deciphering the mechanisms of resistance is critical to further understanding the multifactorial pathways involved, and in developing more specific targeted treatments. To date, numerous studies have reported the potential role of microRNAs (miRNAs) in resistance to various cancer treatments. MicroRNAs are a family of small non-coding RNAs that regulate gene expression by sequence-specific targeting of mRNAs causing translational repression or mRNA degradation. More than 1200 validated human miRNAs have been identified to date. While as little as one miRNA can regulate hundreds of targets, a single target can also be affected by multiple miRNAs. Evidence suggests that dysregulation of specific miRNAs may be involved in the acquisition of resistance to a number of cancer treatments, thereby modulating the sensitivity of cancer cells to such therapies. Therefore, targeting miRNAs may be an attractive strategy for developing novel and more effective individualized therapies, improving drug efficiency, and for predicting patient response to different treatments. In this review, we provide an overview on the role of miRNAs in resistance to current lung cancer therapies and novel biological agents.

Between flagged borders, across gendered lands : the voiceless female space in contemporary representations of Australian beach

International and national representations of the beach perpetuate normative female concepts by maintaining dominant masculine myths, such as that of the heroic lifesaver and tanned sunbaker. Female experiences on the beach are traditionally associated with rhetorics of danger and peril, contrasted to the welcomed and protective gaze of the beach male. Conventional understandings of the gaze promote male surveillance of women, and although some resistance exists, the beach primarily remains a place to observe the female form. This article attempts to explore currents of resistance at the beach through a self-reflexive examination of Schoolies. Although the event is fixed within patriarchal codes and structures, small eddies of resistance exist amongst female participants in light of increasing awareness of masculine hegemony. The Australian beach remains a contested site of multiple constructs of gender and national identity. This article reveals the changing tides of resistance.

In Bed with Autobiography: Unravelling the Fabric of Gender and Genre in Women’s Bed(room) Confessions

This thesis consists of a confessional narrative, What My Mother Doesn’t Know, and an accompanying exegesis, And Why I Should (Maybe) Tell Her. The creative piece employs the confessional mode as a subversive device in three separate narratives, each of which situates the bed as a site of resistance. The exegesis investigates how this self-disclosure in a domestic space flouts the governing rules of self-representation, specifically: telling the truth, respecting privacy and displaying normalcy. The female confession, I argue, creates an alternative space in women’s autobiography where notions of truth-telling can be undermined, the political dimensions of personal experience can be uncovered and the discourse of normality can be negotiated. In particular, women’s confessions told in, on or about the bed, dismantle the genre’s illusion of self and confirm the representative aspects of women’s experience. Framed within these parameters of power and powerlessness, the exegesis includes textual analyses of Charlotte Perkins Gilman’s The Yellow Wallpaper (1892), Tracey Emin’s My Bed (1999) and Lauren Slater’s Lying (2000), each of which exposes in a bedroom space, the author’s most obscure, intimate and traumatic experiences. Situated firmly within and against the genre’s traditional masculine domain, the exegesis also includes mediations on the creative work that validate the bed as my fabric for confession.

Weaving yarns : the lived experience of Indigenous Australians with adult-onset disability in Brisbane

Indigenous Australians have lower levels of health than mainstream Australians and (as far as statistics are able to indicate) higher levels of disability, yet there is little information on Indigenous social and cultural constructions of disability or the Indigenous experience of disability. This research seeks to address these gaps by using an ethnographic approach, couched within a critical medical anthropology (CMA) framework and using the “three bodies” approach, to study the lived experience of urban Indigenous people with an adult-onset disability. The research approach takes account of the debate about the legitimacy of research into Indigenous Australians, Foucault‟s governmentality, and the arguments for different models of disability. The possibility of a cultural model of disability is raised. After a series of initial interviews with contacts who were primarily service providers, more detailed ethnographic research was conducted with three Indigenous women in their homes and with four groups of Indigenous women and men at an Indigenous respite centre. The research involved multiple visits over a period extending more than two years, and the establishment of relationships with all participants. An iterative inductive approach utilising constant comparison (i.e. a form of grounded theory) was adopted, enabling the generation and testing of working hypotheses. The findings point to the lack of an Indigenous construct of disability, related to the holistic construction of health among Indigenous Australians. Shame emerges as a factor which affects the way that Indigenous Australians respond to disability, and which operates in apparent contradiction to expectations of community support. Aspects of shame relate to governmentality, suggesting that self-disciplinary mechanisms have been taken up and support the more obvious exertion of government power. A key finding is the strength of Indigenous identity above and beyond other forms of identification, e.g. as a person with a disability, expressed in forms of resistance by individuals and service providers to the categories and procedures of the mainstream. The implications of a holistic construction of health are discussed in relation to the use of CMA, the interpretation of the “three bodies”, governmentality and resistance. The explanatory value of the concept of sympatricity is discussed, as is the potential value of a cultural model of disability which takes into account the cultural politics of a defiant Indigenous identity.

Evaluating Two Mass Screening Methods for Tungro Disease Resistance

Tungro is one of the most destructive viral diseases of rice in South and Southeast Asia. It is associated with two viruses---rice tungro bacilliform virus (RTBV) ,and rice tungro spherical virus (RTSV) (Hibino et al 1978). Both viruses are transmitted by the green leafhopper (GLH) Nephotettix virescens (Ling 1979), However, prior acquisition of RTSV is required for Ihe transmission of RTBV alone (Hibino 1983). Plants infected with both viruses show severe stunting and yellowing. Those infected with RTBV alone show mild stunting but no leaf discoloration whereas those infected with RTSV alone do not show any apparent symptoms (Hibino el al 1978). Since the late 1960s, tungro has been mainly managed through varietal resistance (Khush 1989). The instability of resistant varieties in the field (Dahal et .a1 1990) led to a reexamination of the nature of the incorporated sources of resistance and to the adoption of more precise and more accurate screening methods.

Influence of preexercise muscle glycogen content on transcriptional activity of metabolic and myogenic genes in well-trained humans

To determine whether pre-exercise muscle glycogen content influences the transcription of several early-response genes involved in the regulation of muscle growth, seven male strength-trained subjects performed one-legged cycling exercise to exhaustion to lower muscle glycogen levels (Low) in one leg compared with the leg with normal muscle glycogen (Norm) and then the following day completed a unilateral bout of resistance training (RT). Muscle biopsies from both legs were taken at rest, immediately after RT, and after 3 h of recovery. Resting glycogen content was higher in the control leg (Norm leg) than in the Low leg (435 ± 87 vs. 193 ± 29 mmol/kg dry wt; P < 0.01). RT decreased glycogen content in both legs (P < 0.05), but postexercise values remained significantly higher in the Norm than the Low leg (312 ± 129 vs. 102 ± 34 mmol/kg dry wt; P < 0.01). GLUT4 (3-fold; P < 0.01) and glycogenin mRNA abundance (2.5-fold; not significant) were elevated at rest in the Norm leg, but such differences were abolished after exercise. Preexercise mRNA abundance of atrogenes was also higher in the Norm compared with the Low leg [atrogin: ?14-fold, P < 0.01; RING (really interesting novel gene) finger: ?3-fold, P < 0.05] but decreased for atrogin in Norm following RT (P < 0.05). There were no differences in the mRNA abundance of myogenic regulatory factors and IGF-I in the Norm compared with the Low leg. Our results demonstrate that 1) low muscle glycogen content has variable effects on the basal transcription of select metabolic and myogenic genes at rest, and 2) any differences in basal transcription are completely abolished after a single bout of heavy resistance training. We conclude that commencing resistance exercise with low muscle glycogen does not enhance the activity of genes implicated in promoting hypertrophy.

New modes of governance and the commodification of criminological knowledge

This article explores the influence of new modes of governance on the production of criminological knowledge. In doing so, it examines the rise of discourses on risk and critiques the ways in which academic environments are changing under new managerialist philosophies. The article further explores the increasing 'commodification of criminological knowledge' and analyses its effect on contemporary criminological scholarship. Finally, this article examines the contours of critical criminological scholarship and advocates for a criminology of resistance.

Teacher professional standards : mirage or miracle cure - an archaeology of professionalism in education

This thesis is a problematisation of the development and implementation of professional standards as the mechanism to enhance professionalism and teacher quality in the teaching force within Australia and, more specifically, Queensland. Drawing on tools from Foucauldian archaeological analysis, the dominant discourses of professionalism from the academic literature, Australian federal and state policy documents and narratives from Queensland teachers are examined. These data sets are then cross referenced, analysing the intersections and divergences between the different texts. Findings suggest that through policy, political strategy and derisory statements from various authoritative voices, the managerial discourse of professionalism through professional standards documents has been unduly privileged as a means of regulating teachers, despite the fact that teachers themselves do not share this dominant notion of professionalism. The teachers in this study proffer ‘new classical-practical professionalism’ as a counter discourse, or discourse of resistance, to managerialism. However, an application of Foucault’s theorisations on power-knowledge reveals that their spoken discourses mean they are in fact yielding to the discourse of professional standards as docile bodies.

Integrated health prediction of bridge systems using dynamic object oriented Bayesian networks (DOOBNS)

The serviceability and safety of bridges are crucial to people’s daily lives and to the national economy. Every effort should be taken to make sure that bridges function safely and properly as any damage or fault during the service life can lead to transport paralysis, catastrophic loss of property or even casualties. Nonetheless, aggressive environmental conditions, ever-increasing and changing traffic loads and aging can all contribute to bridge deterioration. With often constrained budget, it is of significance to identify bridges and bridge elements that should be given higher priority for maintenance, rehabilitation or replacement, and to select optimal strategy. Bridge health prediction is an essential underpinning science to bridge maintenance optimization, since the effectiveness of optimal maintenance decision is largely dependent on the forecasting accuracy of bridge health performance. The current approaches for bridge health prediction can be categorised into two groups: condition ratings based and structural reliability based. A comprehensive literature review has revealed the following limitations of the current modelling approaches: (1) it is not evident in literature to date that any integrated approaches exist for modelling both serviceability and safety aspects so that both performance criteria can be evaluated coherently; (2) complex system modelling approaches have not been successfully applied to bridge deterioration modelling though a bridge is a complex system composed of many inter-related bridge elements; (3) multiple bridge deterioration factors, such as deterioration dependencies among different bridge elements, observed information, maintenance actions and environmental effects have not been considered jointly; (4) the existing approaches are lacking in Bayesian updating ability to incorporate a variety of event information; (5) the assumption of series and/or parallel relationship for bridge level reliability is always held in all structural reliability estimation of bridge systems. To address the deficiencies listed above, this research proposes three novel models based on the Dynamic Object Oriented Bayesian Networks (DOOBNs) approach. Model I aims to address bridge deterioration in serviceability using condition ratings as the health index. The bridge deterioration is represented in a hierarchical relationship, in accordance with the physical structure, so that the contribution of each bridge element to bridge deterioration can be tracked. A discrete-time Markov process is employed to model deterioration of bridge elements over time. In Model II, bridge deterioration in terms of safety is addressed. The structural reliability of bridge systems is estimated from bridge elements to the entire bridge. By means of conditional probability tables (CPTs), not only series-parallel relationship but also complex probabilistic relationship in bridge systems can be effectively modelled. The structural reliability of each bridge element is evaluated from its limit state functions, considering the probability distributions of resistance and applied load. Both Models I and II are designed in three steps: modelling consideration, DOOBN development and parameters estimation. Model III integrates Models I and II to address bridge health performance in both serviceability and safety aspects jointly. The modelling of bridge ratings is modified so that every basic modelling unit denotes one physical bridge element. According to the specific materials used, the integration of condition ratings and structural reliability is implemented through critical failure modes. Three case studies have been conducted to validate the proposed models, respectively. Carefully selected data and knowledge from bridge experts, the National Bridge Inventory (NBI) and existing literature were utilised for model validation. In addition, event information was generated using simulation to demonstrate the Bayesian updating ability of the proposed models. The prediction results of condition ratings and structural reliability were presented and interpreted for basic bridge elements and the whole bridge system. The results obtained from Model II were compared with the ones obtained from traditional structural reliability methods. Overall, the prediction results demonstrate the feasibility of the proposed modelling approach for bridge health prediction and underpin the assertion that the three models can be used separately or integrated and are more effective than the current bridge deterioration modelling approaches. The primary contribution of this work is to enhance the knowledge in the field of bridge health prediction, where more comprehensive health performance in both serviceability and safety aspects are addressed jointly. The proposed models, characterised by probabilistic representation of bridge deterioration in hierarchical ways, demonstrated the effectiveness and pledge of DOOBNs approach to bridge health management. Additionally, the proposed models have significant potential for bridge maintenance optimization. Working together with advanced monitoring and inspection techniques, and a comprehensive bridge inventory, the proposed models can be used by bridge practitioners to achieve increased serviceability and safety as well as maintenance cost effectiveness.