Futsal and Continuous Exercise Induce Similar Changes in Specific Skeletal Muscle Signalling Proteins

Exercise elicits skeletal-muscle adaptations which are important for improved health outcomes. We compared the effects of a futsal game (FUT) and moderate-intensity continuous exercise (MOD), on the skeletal-muscle protein signalling responses in young, healthy individuals. 16 men undertook an incremental exercise test and a resting muscle biopsy performed >48\u2009h apart. They were then randomly allocated to either FUT (n=12) consisting of 2\u2009x\u200920\u2009min halves, or MOD (n=8) consisting of a work-matched running bout performed at an intensity corresponding to the individual ventilatory threshold 1. Work matching was achieved by means of triaxial accelerometers. Immediately after FUT and MOD, participants underwent a second biopsy to assess exercise-induced changes in protein signalling. Total and phosphorylated protein abundance was assessed via western blotting. Both FUT and MOD altered signalling responses in skeletal muscle. FUT increased total ATF2 protein abundance (p=0.048) and phosphorylation (p=0.029), while no changes occurred with MOD. Both exercise regimes increased ACC phosphorylation (p=0.01) and returned a trend for increased p38MAPK phosphorylation. Futsal may be employed as an alternative to continuous exercise to elicit muscle adaptations which may be associated with improved health outcomes. As only FUT increased ATF2 activation, this protein might be a target of future investigation on exercise-induced signalling

Presentations to general practice before a cancer diagnosis in Victoria: a cross-sectional survey

OBJECTIVE: To assess variations in the number of general practitioner visits preceding a cancer diagnosis, and in the length of the interval between the patient first suspecting a problem and their seeing a hospital specialist. DESIGN, SETTING AND PARTICIPANTS: Analysis of data provided to the Cancer Patient Experience Survey (CPES; survey response rate, 37.7%) by 1552 patients with one of 19 cancer types and treated in one of five Victorian Comprehensive Cancer Centre hospitals, 1 October 2012 - 30 April 2013. MAIN OUTCOME MEASURES: The primary outcome was the proportion of patients who had had three or more GP consultations about cancer-related health problems before being referred to hospital. The secondary outcome was the interval between the patient first suspecting a problem and their seeing a hospital specialist. RESULTS: 34% of the patients included in the final analyses (426 of 1248) had visited a GP at least three times before referral to a hospital doctor. The odds ratios (reference: rectal cancer; adjusted for age, sex, language spoken at home, and socio-economic disadvantage index score) varied according to cancer type, being highest for pancreatic cancer (3.2; 95% CI, 1.02-9.9), thyroid cancer (2.5; 95% CI, 0.9-6.6), vulval cancer (2.5; 95% CI, 0.7-8.7) and multiple myeloma (2.4; 95% CI, 1.1-5.5), and lowest for patients with breast cancer (0.4; 95% CI, 0.2-0.8), cervical cancer (0.5; 95% CI, 0.1-2.1), endometrial cancer (0.5; 95% CI, 0.2-1.4) or melanoma (0.7; 95% CI, 0.3-1.5). Cancer type also affected the duration of the interval from symptom onset to seeing a hospital doctor; it took at least 3 months for more than one-third of patients with prostate or colon cancer to see a hospital doctor. CONCLUSION: Certain cancer types were more frequently associated with multiple GP visits, suggesting they are more challenging to recognise early. In Victoria, longer intervals from the first symptoms to seeing a hospital doctor for colon or prostate cancer may reflect poorer community symptom awareness, later GP referral, or limited access to gastroenterology and urology services.Our study was funded by the Victorian Comprehensive Cancer Centre. Georgios Lyratzopoulos is supported by a Cancer Research UK Clinician Scientist Fellowship (A18180)

Creativity and Autonomy in Swarm Intelligence Systems

This work introduces two swarm intelligence algorithms -- one mimicking the behaviour of one species of ants (\emph{Leptothorax acervorum}) foraging (a `Stochastic Diffusion Search', SDS) and the other algorithm mimicking the behaviour of birds flocking (a `Particle Swarm Optimiser', PSO) -- and outlines a novel integration strategy exploiting the local search properties of the PSO with global SDS behaviour. The resulting hybrid algorithm is used to sketch novel drawings of an input image, exploliting an artistic tension between the local behaviour of the `birds flocking' - as they seek to follow the input sketch - and the global behaviour of the `ants foraging' - as they seek to encourage the flock to explore novel regions of the canvas. The paper concludes by exploring the putative `creativity' of this hybrid swarm system in the philosophical light of the `rhizome' and Deleuze's well known `Orchid and Wasp' metaphor

RNA-DNA differences are rarer in proto-oncogenes than in tumor suppressor genes

It has long been assumed that DNA sequences and corresponding RNA transcripts are almost identical; a recent discovery, however, revealed widespread RNA-DNA differences (RDDs), which represent a largely unexplored aspect of human genome variation. It has been speculated that RDDs can affect disease susceptibility and manifestations; however, almost nothing is known about how RDDs are related to disease. Here, we show that RDDs are rarer in proto-oncogenes than in tumor suppressor genes; the number of RDDs in coding exons, but not in 3′UTR and 5′UTR, is significantly lower in the former than the latter, and this trend is especially pronounced in non-synonymous RDDs, i.e., those cause amino acid changes. A potential mechanism is that, unlike proto-oncogenes, the requirement of tumor suppressor genes to have both alleles affected to cause tumor ‘buffers' these genes to tolerate more RDDs

Observation of squeezed light from one atom excited with two photons

Single quantum emitters like atoms are well-known as non-classical light sources which can produce photons one by one at given times, with reduced intensity noise. However, the light field emitted by a single atom can exhibit much richer dynamics. A prominent example is the predicted ability for a single atom to produce quadrature-squeezed light, with sub-shot-noise amplitude or phase fluctuations. It has long been foreseen, though, that such squeezing would be "at least an order of magnitude more difficult" to observe than the emission of single photons. Squeezed beams have been generated using macroscopic and mesoscopic media down to a few tens of atoms, but despite experimental efforts, single-atom squeezing has so far escaped observation. Here we generate squeezed light with a single atom in a high-finesse optical resonator. The strong coupling of the atom to the cavity field induces a genuine quantum mechanical nonlinearity, several orders of magnitude larger than for usual macroscopic media. This produces observable quadrature squeezing with an excitation beam containing on average only two photons per system lifetime. In sharp contrast to the emission of single photons, the squeezed light stems from the quantum coherence of photon pairs emitted from the system. The ability of a single atom to induce strong coherent interactions between propagating photons opens up new perspectives for photonic quantum logic with single emittersComment: Main paper (4 pages, 3 figures) + Supplementary information (5 pages, 2 figures). Revised versio

Adaptation of gastrointestinal nematode parasites to host genotype: single locus simulation models

Background: Breeding livestock for improved resistance to disease is an increasingly important selection goal. However, the risk of pathogens adapting to livestock bred for improved disease resistance is difficult to quantify. Here, we explore the possibility of gastrointestinal worms adapting to sheep bred for low faecal worm egg count using computer simulation. Our model assumes sheep and worm genotypes interact at a single locus, such that the effect of an A allele in sheep is dependent on worm genotype, and the B allele in worms is favourable for parasitizing the A allele sheep but may increase mortality on pasture. We describe the requirements for adaptation and test if worm adaptation (1) is slowed by non-genetic features of worm infections and (2) can occur with little observable change in faecal worm egg count. Results: Adaptation in worms was found to be primarily influenced by overall worm fitness, viz. the balance between the advantage of the B allele during the parasitic stage in sheep and its disadvantage on pasture. Genetic variation at the interacting locus in worms could be from de novo or segregating mutations, but de novo mutations are rare and segregating mutations are likely constrained to have (near) neutral effects on worm fitness. Most other aspects of the worm infection we modelled did not affect the outcomes. However, the host-controlled mechanism to reduce faecal worm egg count by lowering worm fecundity reduced the selection pressure on worms to adapt compared to other mechanisms, such as increasing worm mortality. Temporal changes in worm egg count were unreliable for detecting adaptation, despite the steady environment assumed in the simulations. Conclusions: Adaptation of worms to sheep selected for low faecal worm egg count requires an allele segregating in worms that is favourable in animals with improved resistance but less favourable in other animals. Obtaining alleles with this specific property seems unlikely. With support from experimental data, we conclude that selection for low faecal worm egg count should be stable over a short time frame (e.g. 20 years). We are further exploring model outcomes with multiple loci and comparing outcomes to other control strategies

Performance of the DNA-citoliq liquid-based cytology system compared with conventional smears

To evaluate the performance of a new, manual, simplified liquid-based system, DNA-Citoliq (Digene Brasil), employed under routine conditions as compared to conventional smears collected from six collaborating private laboratories. Methods: A panel of cytopathologists, who served as the gold standard diagnosis, adjudicated discordant opinions. Results: Of 3206 pairs of slides considered valid for comparison, there were 3008 in full agreement (93.8%), 112 (3.5%) with one diagnostic category discrepancies, and 86 (2.7%) discordant cases. Among the 288 borderline+ by either method, DNA-Citoliq detected abnormalities in 243 (84.4%), and conventional smears (CS) detected abnormalities in 178 (61.8%) (McNemar test, P < 0.000), a 36.5% increased detection of borderline+ cases. Conclusions: For mild dyskaryosis, DNA-Citoliq detected 176 cases and CS 125 cases (McNemar test, P < 0.000); and for moderate+severe dyskaryosis 66 versus 32 cases respectively (McNemar test, P < 0.000)

Subcellular localization of MC4R with ADCY3 at neuronal primary cilia underlies a common pathway for genetic predisposition to obesity.

Most monogenic cases of obesity in humans have been linked to mutations in genes encoding members of the leptin-melanocortin pathway. Specifically, mutations in MC4R, the melanocortin-4 receptor gene, account for 3-5% of all severe obesity cases in humans1-3. Recently, ADCY3 (adenylyl cyclase 3) gene mutations have been implicated in obesity4,5. ADCY3 localizes to the primary cilia of neurons 6 , organelles that function as hubs for select signaling pathways. Mutations that disrupt the functions of primary cilia cause ciliopathies, rare recessive pleiotropic diseases in which obesity is a cardinal manifestation 7 . We demonstrate that MC4R colocalizes with ADCY3 at the primary cilia of a subset of hypothalamic neurons, that obesity-associated MC4R mutations impair ciliary localization and that inhibition of adenylyl cyclase signaling at the primary cilia of these neurons increases body weight. These data suggest that impaired signaling from the primary cilia of MC4R neurons is a common pathway underlying&nbsp;genetic causes of obesity in humans

Genetic Covariance Structure of Reading, Intelligence and Memory in Children

This study investigates the genetic relationship among reading performance, IQ, verbal and visuospatial working memory (WM) and short-term memory (STM) in a sample of 112, 9-year-old twin pairs and their older siblings. The relationship between reading performance and the other traits was explained by a common genetic factor for reading performance, IQ, WM and STM and a genetic factor that only influenced reading performance and verbal memory. Genetic variation explained 83% of the variation in reading performance; most of this genetic variance was explained by variation in IQ and memory performance. We hypothesize, based on these results, that children with reading problems possibly can be divided into three groups: (1) children low in IQ and with reading problems; (2) children with average IQ but a STM deficit and with reading problems; (3) children with low IQ and STM deficits; this group may experience more reading problems than the other two