Role of Drosophila in Human Disease Research 3.0.

Drosophila melanogaster has become a commonly used animal model for biomedical research in a variety of areas [...]

Diagnostic accuracy of PAT-POPS and ManChEWS for admissions of children from the emergency department

Background The Pennine Acute Trust (PAT) Paediatric Observation Priority Score (PAT-POPS) is a specific emergency department (ED) physiological and observational aggregate scoring system, with scores of 0–18. A higher score indicates greater likelihood of admission. The Manchester Children’s Early Warning System (ManChEWS) assesses six physiological observations to create a trigger score, classified as Green, Amber or Red. Methods Prospectively collected data were used to calculate PAT-POPS and ManChEWS on 2068 patients aged under 16 years (mean 5.6 years, SD 4.6) presenting over 1 month to a UK District General Hospital Paediatric ED. Receiver operating characteristics (ROC) comparison, using STATA V.13, was used to investigate the ability of ManChEWS and PAT-POPS to predict admission to hospital within 72 h of presentation to the ED. Results Comparison of the area under the ROC curve indicates that the ManChEWS ROC is 0.67 (95% CI 0.64 to 0.70) and the PAT-POPS ROC is 0.72 (95% CI 0.68 to 0.75). The difference is statistically significant. At a PAT-POPS cut-off of ≥2, 80% of patients had their admission risk correctly classified ( positive likelihood ratio 3.40, 95% CI 2.90 to 3.98) whereas for ManChEWS with a cut off of ≥Amber only 71% of patients were correctly classified ( positive likelihood ratio 2.18, 95% CI 1.94 to 2.45). Conclusions PAT-POPS is a more accurate predictor of admission risk than ManChEWS. Replacing ManChEWS with PAT-POPS would appear to be clinically appropriate in a paediatric ED. This needs validation in a multicentre study

Novel roles of HP1a and Mcm10 in DNA replication, genome maintenance and photoreceptor cell differentiation.

Both Mcm10 and HP1a are known to be required for DNA replication. However, underlying mechanism is not clarified yet especially for HP1. Knockdown of both HP1a and Mcm10 genes inhibited the progression of S phase in Drosophila eye imaginal discs. Proximity Ligation Assay (PLA) demonstrated that HP1a is in close proximity to DNA replication proteins including Mcm10, RFC140 and DNA polymerase ε 255 kDa subunit in S-phase. This was further confirmed by co-immunoprecipitation assay. The PLA signals between Mcm10 and HP1a are specifically observed in the mitotic cycling cells, but not in the endocycling cells. Interestingly, many cells in the posterior regions of eye imaginal discs carrying a double knockdown of Mcm10 and HP1a induced ectopic DNA synthesis and DNA damage without much of ectopic apoptosis. Therefore, the G1-S checkpoint may be affected by knockdown of both proteins. This event was also the case with other HP family proteins such as HP4 and HP6. In addition, both Mcm10 and HP1a are required for differentiation of photoreceptor cells R1, R6 and R7. Further analyses on several developmental genes involved in the photoreceptor cell differentiation suggest that a role of both proteins is mediated by regulation of the lozenge gene

Socio-economic utility and chemical potential

In statistical physics, the conservation of particle number results in the equalization of the chemical potential throughout a system at equilibrium. In contrast, the homogeneity of utility in socio-economic models is usually thought to rely on the competition between individuals, leading to Nash equilibrium. We show that both views can be reconciled by introducing a notion of chemical potential in a wide class of socio-economic models, and by relating it in a direct way to the equilibrium value of the utility. This approach also allows the dependence of utility across the system to be determined when agents take decisions in a probabilistic way. Numerical simulations of a urban economic model also suggest that our result is valid beyond the initially considered class of solvable models.Comment: 6 pages, 3 figures, final versio

Androgen receptor genotyping in a large Australasian cohort with androgen insensitivity syndrome; identification of four novel mutations

We genotyped the androgen receptor (AR) gene in 31 Australasian patients with androgen insensitivity syndrome (AIS). The entire coding region of AR was examined including analysis of polymorphic CAG and GGN repeats in all patients. AR defects were found in 66.7% (6/9) of patients with complete AIS (CAIS) and 13.6% (3/22) of patients with partial AIS (PAIS). A novel deletion (N858delG) leading to a premature stop codon was found in CAIS patient P1. CAIS patient P2 has a novel deletion (N2676delGAGT) resulting in a stop at codon 787. These mutations would result in inactivation of AR protein. A novel insertion of a cysteine residue in the first zinc finger of the AR DNA-binding domain (N2045_2047dupCTG) was found in CAIS patient P3. PAIS patient P4 has a novel amino acid substitution (Arg760Ser) in the AR ligand binding domain, which may impair ligand binding. Five patients were found to have previously reported AR mutations and no mutations were identified in the remaining patients

Melting as a String-Mediated Phase Transition

We present a theory of the melting of elemental solids as a dislocation-mediated phase transition. We model dislocations near melt as non-interacting closed strings on a lattice. In this framework we derive simple expressions for the melting temperature and latent heat of fusion that depend on the dislocation density at melt. We use experimental data for more than half the elements in the Periodic Table to determine the dislocation density from both relations. Melting temperatures yield a dislocation density of (0.61\pm 0.20) b^{-2}, in good agreement with the density obtained from latent heats, (0.66\pm 0.11) b^{-2}, where b is the length of the smallest perfect-dislocation Burgers vector. Melting corresponds to the situation where, on average, half of the atoms are within a dislocation core.Comment: 18 pages, LaTeX, 3 eps figures, to appear in Phys. Rev.

Incidence and survival for cancer in children and young adults in the North of England, 1968–1995: a report from the Northern Region Young Persons’ Malignant Disease Registry

The Northern Region Young Persons’ Malignant Disease Registry records information on young people under 25 years old diagnosed with cancer in the Northern Region of England. Incidence and survival rates were calculated for children and young adults diagnosed with cancer between 1968 and 1995. There were 2099 (M:F 1.28:1) children (age 0–14 years) and 2217 (M:F 1.23:1) young adults (15–24 years) diagnosed with a first cancer between 1968 and 1995. The age-standardized rate (ASR) for childhood cancer was 121 per million 0 to 14 year-olds per year. For young adults the ASR was 175 per million 15 to 24 year-olds, per year. Incidence of childhood cancer increased over time at a rate of 12 extra cases per million children, per decade (P< 0.001). In young adults incidence rates increased by 16 extra cases per million 15 to 24 year-olds, per decade (P< 0.001). For childhood cancer 5-year survival was 42% for those diagnosed 1968–1977, 57% for 1978–1987 and 71% (95% CI 67–75) for 1988–1995. Survival for young adults over the three periods was 45%, 62% and 73% (95% CI 70–78) respectively. The cumulative risk of developing cancer before the age of 25 is 1 in 285. Over the 28-year period there were significant improvements in survival and modest increases in incidence in both children and young adults. © 2000 Cancer Research Campaig

The Experience of Captaincy in Professional Sport: The Case of Elite Professional Rugby.

The captain is perceived to be an important member of the leadership structure within teams across many professional sports. However, while there is a general acceptance that this is the case there is very little research exploring the role and associated demands at an elite level. As a result, the aim of this study was to explore the captaincy experiences of elite professional rugby union captains. The participants were eight male captains purposefully sampled for this study. Participants were interviewed individually to gain an understanding of each participant’s captaincy experiences. The data were thematically analyzed using interpretative phenomenological analysis. Nine super-ordinate themes emerged in the study: role, skills, requirements, challenges, the coach, development, experience, context and approach. Results suggest that the captaincy role is broader than previously highlighted, particularly at the elite level. Also, the study highlights inconsistencies in the selection of captains and a lack of formal developmental support for elite rugby captains. As a result, future research should explore the development of specific evidence-based approaches to captain selection and development

Decreased MCM2-6 in Drosophila S2 cells does not generate significant DNA damage or cause a marked increase in sensitivity to replication interference.

A reduction in the level of some MCM proteins in human cancer cells (MCM5 in U20S cells or MCM3 in Hela cells) causes a rapid increase in the level of DNA damage under normal conditions of cell proliferation and a loss of viability when the cells are subjected to replication interference. Here we show that Drosophila S2 cells do not appear to show the same degree of sensitivity to MCM2-6 reduction. Under normal cell growth conditions a reduction of >95% in the levels of MCM3, 5, and 6 causes no significant short term alteration in the parameters of DNA replication or increase in DNA damage. MCM depleted cells challenged with HU do show a decrease in the density of replication forks compared to cells with normal levels of MCM proteins, but this produces no consistent change in the levels of DNA damage observed. In contrast a comparable reduction of MCM7 levels has marked effects on viability, replication parameters and DNA damage in the absence of HU treatment