Interaction of contractile activity and training history on mRNA abundance in skeletal muscle from trained athletes

Skeletal muscle displays enormous plasticity to respond to contractile activity with muscle from strength- (ST) and endurance-trained (ET) athletes representing diverse states of the adaptation continuum. Training adaptation can be viewed as the accumulation of specific proteins. Hence, the altered gene expression that allows for changes in protein concentration is of major importance for any training adaptation. Accordingly, the aim of the present study was to quantify acute subcellular responses in muscle to habitual and unfamiliar exercise. After 24-h diet/exercise control, 13 male subjects (7 ST and 6 ET) performed a random order of either resistance (8 × 5 maximal leg extensions) or endurance exercise (1 h of cycling at 70% peak O2 uptake). Muscle biopsies were taken from vastus lateralis at rest and 3 h after exercise. Gene expression was analyzed using real-time PCR with changes normalized relative to preexercise values. After cycling exercise, peroxisome proliferator-activated receptor-γ coactivator-1α (ET ∼8.5-fold, ST ∼10-fold, P < 0.001), pyruvate dehydrogenase kinase-4 (PDK-4; ET ∼26-fold, ST ∼39-fold), vascular endothelial growth factor (VEGF; ET ∼4.5-fold, ST ∼4-fold), and muscle atrophy F-box protein (MAFbx) (ET ∼2-fold, ST ∼0.4-fold) mRNA increased in both groups, whereas MyoD (∼3-fold), myogenin (∼0.9-fold), and myostatin (∼2-fold) mRNA increased in ET but not in ST (P < 0.05). After resistance exercise PDK-4 (∼7-fold, P < 0.01) and MyoD (∼0.7-fold) increased, whereas MAFbx (∼0.7-fold) and myostatin (∼0.6-fold) decreased in ET but not in ST. We conclude that prior training history can modify the acute gene responses in skeletal muscle to subsequent exercise.

Helping someone with problem drinking: Mental health first aid guidelines - a Delphi expert consensus study

Background Alcohol is a leading risk factor for avoidable disease burden. Research suggests that a drinker's social network can play an integral role in addressing hazardous (i.e., high-risk) or problem drinking. Often however, social networks do not have adequate mental health literacy (i.e., knowledge about mental health problems, like problem drinking, or how to treat them). This is a concern as the response that a drinker receives from their social network can have a substantial impact on their willingness to seek help. This paper describes the development of mental health first aid guidelines that inform community members on how to help someone who may have, or may be developing, a drinking problem (i.e., alcohol abuse or dependence). Methods A systematic review of the research and lay literature was conducted to develop a 285-item survey containing strategies on how to help someone who may have, or may be developing, a drinking problem. Two panels of experts (consumers/carers and clinicians) individually rated survey items, using a Delphi process. Surveys were completed online or via postal mail. Participants were 99 consumers, carers and clinicians with experience or expertise in problem drinking from Australia, Canada, Ireland, New Zealand, the United Kingdom, and the United States. Items that reached consensus on importance were retained and written into guidelines. Results The overall response rate across all three rounds was 68.7% (67.6% consumers/carers, 69.2% clinicians), with 184 first aid strategies rated as essential or important by ≥80% of panel members. The endorsed guidelines provide guidance on how to: recognize problem drinking; approach someone if there is concern about their drinking; support the person to change their drinking; respond if they are unwilling to change their drinking; facilitate professional help seeking and respond if professional help is refused; and manage an alcohol-related medical emergency. Conclusion The guidelines provide a consensus-based resource for community members seeking to help someone with a drinking problem. Improving community awareness and understanding of how to identify and support someone with a drinking problem may lead to earlier recognition of problem drinking and greater facilitation of professional help seeking.

Early signaling responses to divergent exercise stimuli in skeletal muscle from well-trained humans

Skeletal muscle from strength- and endurance-trained individuals represents diverse adaptive states. In this regard, AMPK-PGC-1α signaling mediates several adaptations to endurance training, while up-regulation of the Akt-TSC2-mTOR pathway may underlie increased protein synthesis after resistance exercise. We determined the effect of prior training history on signaling responses in seven strength-trained and six endurance-trained males who undertook 1 h cycling at 70% VO2peak or eight sets of five maximal repetitions of isokinetic leg extensions. Muscle biopsies were taken at rest, immediately and 3 h postexercise. AMPK phosphorylation increased after cycling in strength-trained (54%; P<0.05) but not endurance-trained subjects. Conversely, AMPK was elevated after resistance exercise in endurance- (114%; P<0.05), but not strengthtrained subjects. Akt phosphorylation increased in endurance- (50%; P<0.05), but not strengthtrained subjects after cycling but was unchanged in either group after resistance exercise. TSC2 phosphorylation was decreased (47%; P<0.05) in endurance-trained subjects following resistance exercise, but cycling had little effect on the phosphorylation state of this protein in either group. p70S6K phosphorylation increased in endurance- (118%; P<0.05), but not strength-trained subjects after resistance exercise, but was similar to rest in both groups after cycling. Similarly, phosphorylation of S6 protein, a substrate for p70 S6K, was increased immediately following resistance exercise in endurance- (129%; P<0.05), but not strength-trained subjects. In conclusion, a degree of “response plasticity” is conserved at opposite ends of the endurancehypertrophic adaptation continuum. Moreover, prior training attenuates the exercise specific signaling responses involved in single mode adaptations to training.

CDKN2A is not the principal target of deletions on the short arm of chromosome 9 in neuroendocrine (Merkel cell) carcinoma of the skin

The majority of small-cell lung cancers (SCLCs) express p16 but not pRb. Given our previous study showing loss of pRb in Merkel cell carcinoma (MCC)/neuroendocrine carcinoma of the skin and the clinicopathological similarities between SCLC and MCC, we wished to determine if this was also the case in MCC. Twenty-nine MCC specimens from 23 patients were examined for deletions at 10 loci on 9p and 1 on 9q. No loss of heterozygosity (LOH) was seen in 9 patients including 2 for which tumour and cell line DNAs were examined. Four patients had LOH for all informative loci on 9p. Ten tumours showed more limited regions of loss on 9p, and from these 2 common regions of deletion were determined. Half of all informative cases had LOH at D9S168, the most telomeric marker examined, and 3 specimens showed loss of only D9S168. A second region (IFNA-D9S126) showed LOH in 10 (44%) cases, and case MCC26 showed LOH for only D9S126, implicating genes centromeric of the CDKN2A locus. No mutations in the coding regions of p16 were seen in 7 cell lines tested, and reactivity to anti-p16 antibody was seen in all 11 tumour specimens examined and in 6 of 7 cell lines from 6 patients. Furthermore, all cell lines examined reacted with anti-p14(ARF) antibody. These results suggest that neither transcript of the CDKN2A locus is the target of deletions on 9p in MCC and imply the existence of tumour-suppressor genes mapping both centromeric and telomeric of this locus.

Large scale participatory acoustic sensor data analysis : tools and reputation models to enhance effectiveness

Acoustic sensors play an important role in augmenting the traditional biodiversity monitoring activities carried out by ecologists and conservation biologists. With this ability however comes the burden of analysing large volumes of complex acoustic data. Given the complexity of acoustic sensor data, fully automated analysis for a wide range of species is still a significant challenge. This research investigates the use of citizen scientists to analyse large volumes of environmental acoustic data in order to identify bird species. Specifically, it investigates ways in which the efficiency of a user can be improved through the use of species identification tools and the use of reputation models to predict the accuracy of users with unidentified skill levels. Initial experimental results are reported.

Understanding the legal implications of data sharing, access and reuse in the Australian research landscape

Researchers are increasingly involved in data-intensive research projects that cut across geographic and disciplinary borders. Quality research now often involves virtual communities of researchers participating in large-scale web-based collaborations, opening their earlystage research to the research community in order to encourage broader participation and accelerate discoveries. The result of such large-scale collaborations has been the production of ever-increasing amounts of data. In short, we are in the midst of a data deluge. Accompanying these developments has been a growing recognition that if the benefits of enhanced access to research are to be realised, it will be necessary to develop the systems and services that enable data to be managed and secured. It has also become apparent that to achieve seamless access to data it is necessary not only to adopt appropriate technical standards, practices and architecture, but also to develop legal frameworks that facilitate access to and use of research data. This chapter provides an overview of the current research landscape in Australia as it relates to the collection, management and sharing of research data. The chapter then explains the Australian legal regimes relevant to data, including copyright, patent, privacy, confidentiality and contract law. Finally, this chapter proposes the infrastructure elements that are required for the proper management of legal interests, ownership rights and rights to access and use data collected or generated by research projects.

Corneal markers of diabetic neuropathy

Diabetic neuropathy is a significant clinical problem that currently has no effective therapy, and in advanced cases, leads to foot ulceration and lower limb amputation. The accurate detection, characterization and quantification of this condition are important in order to define at-risk patients, anticipate deterioration, monitor progression, and assess new therapies This review evaluates novel corneal methods of assessing diabetic neuropathy. Two new non-invasive corneal markers have emerged, and in cross-sectional studies have demonstrated their ability to stratify the severity of this disease. Corneal confocal microscopy allows quantification of corneal nerve parameters and non-contact corneal esthesiometry, the functional correlate of corneal structure, assesses the sensitivity of the cornea. Both these techniques are quick to perform, produce little or no discomfort for the patient, and are suitable for clinical settings. Each has advantages and disadvantages over traditional techniques for assessing diabetic neuropathy. Application of these new corneal markers for longitudinal evaluation of diabetic neuropathy has the potential to reduce dependence on more invasive, costly, and time-consuming assessments, such as skin biopsy.

Reliability of ultrasonographic measurement of the architecture of the vastus lateralis and gastrocnemius medialis muscles in older adults

Objective To determine the test-retest reliability of measurements of thickness, fascicle length (Lf) and pennation angle (θ) of the vastus lateralis (VL) and gastrocnemius medialis (GM) muscles in older adults. Participants Twenty-one healthy older adults (11 men and ten women; average age 68·1 ± 5·2 years) participated in this study. Methods Ultrasound images (probe frequency 10 MHz) of the VL at two sites (VL site 1 and 2) were obtained with participants seated with knee at 90º flexion. For GM measures, participants lay prone with ankle fixed at 15º dorsiflexion. Measures were taken on two separate occasions, 7 days apart (T1 and T2). Results The ICCs (95% CI) were: VL site 1 thickness = 0·96(0·90–0·98); VL site 2 thickness = 0·96(0·90–0·98), VL θ = 0·87(0·68–0·95), VL Lf = 0·80(0·50–0·92), GM thickness = 0·97(0·92–0·99), GM θ = 0·85(0·62–0·94) and GM Lf =0·90(0·75–0·96). The 95% ratio limits of agreement (LOAs) for all measures, calculated by multiplying the standard deviation of the ratio of the results between T1 and T2 by 1·96, ranged from 10·59 to 38·01%. Conclusion The ability of these tests to determine a real change in VL and GM muscle architecture is good on a group level but problematic on an individual level as the relatively large 95% ratio LOAs in the current study may encompass the changes in architecture observed in other training studies. Therefore, the current findings suggest that B-mode ultrasonography can be used with confidence by researchers when investigating changes in muscle architecture in groups of older adults, but its use is limited in showing changes in individuals over time.

The Biodex Isokinetic Dynamometer for knee strength assessment in children : advantages and limitations

Objective: To critically appraise the Biodex System 4 isokinetic dynamometer for strength assessment of children. Methods: Appraisal was based on experiences from two independent laboratories involving testing of 213 children. Issues were recorded and the manufacturer was consulted regarding appropriate solutions. Results: The dynamometer had insufficient height adjustment for alignment of the knee for some children, requiring the construction of padding to better fit the child within the dynamometer. Potential for entrapment of the non-testing leg was evident in the passive and eccentric modes and a leg bracket restraint was constructed. Automated gravity correction did not operate when protocols were linked or data was exported to an external device. Conclusions: Limitations were noted, some of which were applicable to knee strength testing in general and others which were specific to use with children. However, most of these obstacles could be overcome, making the Biodex System 4 suitable for assessment of knee strength in children.

Interactive processes link the multiple symptoms of fatigue in sport competition

Muscle physiologists often describe fatigue simply as a decline of muscle force and infer this causes an athlete to slow down. In contrast, exercise scientists describe fatigue during sport competition more holistically as an exercise-induced impairment of performance. The aim of this review is to reconcile the different views by evaluating the many performance symptoms/measures and mechanisms of fatigue. We describe how fatigue is assessed with muscle, exercise or competition performance measures. Muscle performance (single muscle test measures) declines due to peripheral fatigue (reduced muscle cell force) and/or central fatigue (reduced motor drive from the CNS). Peak muscle force seldom falls by >30% during sport but is often exacerbated during electrical stimulation and laboratory exercise tasks. Exercise performance (whole-body exercise test measures) reveals impaired physical/technical abilities and subjective fatigue sensations. Exercise intensity is initially sustained by recruitment of new motor units and help from synergistic muscles before it declines. Technique/motor skill execution deviates as exercise proceeds to maintain outcomes before they deteriorate, e.g. reduced accuracy or velocity. The sensation of fatigue incorporates an elevated rating of perceived exertion (RPE) during submaximal tasks, due to a combination of peripheral and higher CNS inputs. Competition performance (sport symptoms) is affected more by decision-making and psychological aspects, since there are opponents and a greater importance on the result. Laboratory based decision making is generally faster or unimpaired. Motivation, self-efficacy and anxiety can change during exercise to modify RPE and, hence, alter physical performance. Symptoms of fatigue during racing, team-game or racquet sports are largely anecdotal, but sometimes assessed with time-motion analysis. Fatigue during brief all-out racing is described biomechanically as a decline of peak velocity, along with altered kinematic components. Longer sport events involve pacing strategies, central and peripheral fatigue contributions and elevated RPE. During match play, the work rate can decline late in a match (or tournament) and/or transiently after intense exercise bursts. Repeated sprint ability, agility and leg strength become slightly impaired. Technique outcomes, such as velocity and accuracy for throwing, passing, hitting and kicking, can deteriorate. Physical and subjective changes are both less severe in real rather than simulated sport activities. Little objective evidence exists to support exercise-induced mental lapses during sport. A model depicting mind-body interactions during sport competition shows that the RPE centre-motor cortex-working muscle sequence drives overall performance levels and, hence, fatigue symptoms. The sporting outputs from this sequence can be modulated by interactions with muscle afferent and circulatory feedback, psychological and decision-making inputs. Importantly, compensatory processes exist at many levels to protect against performance decrements. Small changes of putative fatigue factors can also be protective. We show that individual fatigue factors including diminished carbohydrate availability, elevated serotonin, hypoxia, acidosis, hyperkalaemia, hyperthermia, dehydration and reactive oxygen species, each contribute to several fatigue symptoms. Thus, multiple symptoms of fatigue can occur simultaneously and the underlying mechanisms overlap and interact. Based on this understanding, we reinforce the proposal that fatigue is best described globally as an exercise-induced decline of performance as this is inclusive of all viewpoints.

Melanoma cell invasiveness is regulated by miR-211 suppression of the BRN2 transcription factor

To identify microRNAs potentially involved in melanomagenesis, we compared microRNA expression profiles between melanoma cell lines and cultured melanocytes. The most differentially expressed microRNA between the normal and tumor cell lines was miR-211. We focused on this pigment-cell-enriched miRNA as it is derived from the microphthalmia-associated transcription factor (MITF)-regulated gene, TRPM1 (melastatin). We find that miR-211 expression is greatly decreased in melanoma cells and melanoblasts compared to melanocytes. Bioinformatic analysis identified a large number of potential targets of miR-211, including POU3F2 (BRN2). Inhibition of miR-211 in normal melanocytes resulted in increased BRN2 protein, indicating that endogenous miR-211 represses BRN2 in differentiated cells. Over-expression of miR-211 in melanoma cell lines changed the invasive potential of the cells in vitro through directly targeting BRN2 translation. We propose a model for the apparent non-overlapping expression levels of BRN2 and MITF in melanoma, mediated by miR-211 expression.

Acoustic component detection for automatic species recognition in environmental monitoring

Automatic species recognition plays an important role in assisting ecologists to monitor the environment. One critical issue in this research area is that software developers need prior knowledge of specific targets people are interested in to build templates for these targets. This paper proposes a novel approach for automatic species recognition based on generic knowledge about acoustic events to detect species. Acoustic component detection is the most critical and fundamental part of this proposed approach. This paper gives clear definitions of acoustic components and presents three clustering algorithms for detecting four acoustic components in sound recordings; whistles, clicks, slurs, and blocks. The experiment result demonstrates that these acoustic component recognisers have achieved high precision and recall rate.