Knockdown Resistance to DDT and Pyrethroids in the House Fly (Diptera: Muscidae): From Genetic Trait to Molecular Mechanism

Knockdown resistance to DDT and pyrethrins was the 1st insecticide resistance trait involving reduced target site sensitivity to be identified and isolated genetically. Almost 5 decades later, knockdown resistance continues to threaten the continued effectiveness of pyrethroid insecticides in the control of numerous agricultural pests and vectors of human disease. In this review we summarize progress in the characterization of knockdown resistance in the house fly, Musca domestica L., culminating in the identification of the specific sodium channel gene mutations that cause the reduced neuronal sensitivity to DDT and pyrethroids in knockdown-resistant insect

Adverse prognostic and predictive significance of low DNA-dependent protein kinase catalytic subunit (DNA-PKcs) expression in early-stage breast cancers

Background: DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a serine threonine kinase belonging to the PIKK family (phosphoinositide 3-kinase-like-family of protein kinase), is a critical component of the non-homologous end joining (NHEJ) pathway required for the repair of DNA double strand breaks. DNA-PKcs may be involved in breast cancer pathogenesis. Methods: We evaluated clinicopathological significance of DNA-PKcs protein expression in 1161 tumours and DNA-PKcs mRNA expression in 1950 tumours. We correlated DNA-PKcs to other markers of aggressive phenotypes, DNA repair, apoptosis and cell cycle regulation. Results: Low DNA-PKcs protein expression was associated with higher tumour grade, higher mitotic index, tumour de-differentiation and tumour type (ps<0.05). Absence of BRCA1, low XRCC1/SMUG1/APE1/Polβ were also more likely in low DNA-PKcs expressing tumours (ps<0.05). Low DNA-PKcs protein expression was significantly associated with worse breast cancer specific survival (BCCS) in univariate and multivariate analysis (ps<0.01). At the mRNA level, low DNA-PKcs was associated with PAM50.Her2 and PAM50.LumA molecular phenotypes (ps<0.01) and poor BCSS. In patients with ER positive tumours who received endocrine therapy, low DNA-PKcs (protein and mRNA) was associated with poor survival. In ER negative patients, low DNA-PKcs mRNA remains significantly associated with adverse outcome. Conclusions: Our study suggests that low DNA-PKcs expression may have prognostic and predictive significance in breast cancers

A Vision for Ice Giant Exploration

From Voyager to a Vision for 2050: NASA and ESA have just completed a study of candidate missionsto Uranus and Neptune, the so-called ice giant planets. It is a Pre-Decadal Survey Study, meant to inform the next Planetary Science Decadal Survey about opportunities for missions launching in the 2020's and early 2030's. There have been no space flight missions to the ice giants since the Voyager 2 flybys of Uranus in 1986 and Neptune in 1989. This paper presents some conclusions of that study (hereafter referred to as The Study), and how the results feed into a vision for where planetary science can be in 2050. Reaching that vision will require investments in technology andground-based science in the 2020's, flight during the 2030's along with continued technological development of both ground- and space-based capabilities, and data analysis and additional flights in the 2040's. We first discuss why exploring the ice giants is important. We then summarize the science objectives identified by The Study, and our vision of the science goals for 2050. We then review some of the technologies needed to make this vision a reality

Factors associated with self-efficacy for managing recovery in the trauma intensive care population: A prospective cohort study

Objective: The aim of this paper was to identify factors associated with self-efficacy for managing recovery in the trauma intensive care population. Introduction: Injury accounts for 6.5% of disease burden in Australia, with similar levels being reported in other developed countries. While some studies regarding self-efficacy have identified a relationship to patient recovery post acute injury, others have been inconclusive. This study will identify factors associated with self-efficacy for managing recovery in the trauma intensive care population. Methods: A prospective cohort study of patients aged ≥18 years, admitted to a metropolitan tertiary hospital in South East Queensland between June 2008 and August 2010 for the acute treatment of injury. Demographic, injury, acute care and psychosocial factors were considered. The primary outcome was self-efficacy measured by the 6-item self-efficacy scale (SES) 1 and 6 months post hospital discharge. All factors significant (p < 0.10) on univariate analysis were included in multivariable modelling where p < 0.05 was considered significant. Results: A total of 88 patients were included. The mean self-efficacy score at 1 and 6 months was similar (6.8 vs 6.9 respectively). Self-efficacy at 1 month, psychological distress (K-10) Score and illness perception (K10) Score accounted for 68.4% (adjusted R2) of the variance in 6 month self-efficacy (F3,75) = 57.17, p < 0.001. Illness perception was the strongest contributor to 6 month self-efficacy (beta = −0.516), followed by psychological distress (beta = −0.243) and self-efficacy at 1 month (beta = 0.205). Conclusion: Significant factors associated with self-efficacy for managing recovery at 6 months included 1 month self-efficacy, illness perception and psychological distress. To promote patient recovery, screening patients at 1 month in order to commence relevant interventions could be beneficial

Interrelationships Between the Kinetics of VLDL Subspecies and HDL Catabolism in Abdominal Obesity: A Multicenter Tracer Kinetic Study

Context: Low plasma high-density lipoprotein (HDL) cholesterol is a major abnormality in abdominal obesity. This relates due to accelerated HDL catabolism, but the underlying mechanism requires further elucidation. The relationships between HDL catabolism and other variables that may be modified in abdominal obesity, such as very low-density lipoprotein (VLDL) subspecies (VLDL1, VLDL2) kinetics, liver fat, or visceral adiposity, remain to be investigated. Objectives: Our aim was to study the associations between HDL apolipoprotein (apo)-A-I fractional catabolic rate (FCR) and the kinetics of VLDL subspecies and estimates of liver and visceral and sc fat. Design: We carried out a multicenter in vivo kinetic study using stable isotopes (deuterated leucine and glycerol) in 62 individuals with abdominal obesity. Results: In a multivariate analysis, among the morphological and biological parameters that may predict apoA-I FCR, liver fat (beta = .400, P = .003), and VLDL1-apoB (beta = .307, P = .020) were independently associated with apoA-I FCR. In a multivariate analysis, among the kinetic parameters, VLDL1-triglycerides (TGs) indirect FCR (beta = .357, P = .001), VLDL1-TG production rate (beta = 0.213, P = .048), and apoA-II FCR (beta = .667, P < .0001) were independently associated with apoA-I FCR. After adjustment for VLDL1-TG production rate, liver fat was no more correlated with apoA-I FCR. No association between apoA-I FCR and visceral fat was observed. Conclusions: We show that VLDL1 is an important independent determinant of apoA-I FCR and more precisely that apoA-I FCR is independently associated with both catabolism and the production of VLDL1-TG. In addition, we show an association between liver fat and apoA-I FCR that is mostly mediated by VLDL1-TG production. These data indicate that, in abdominal obesity, dysfunctional VLDL1 metabolism is an important modulator of HDL apoA-I catabolism

Voltage-gated sodium channels as targets for pyrethroid insecticides

The pyrethroid insecticides are a very successful group of compounds that have been used extensively for the control of arthropod pests of agricultural crops and vectors of animal and human disease. Unfortunately, this has led to the development of resistance to the compounds in many species. The mode of action of pyrethroids is known to be via interactions with the voltage-gated sodium channel. Understanding how binding to the channel is affected by amino acid substitutions that give rise to resistance has helped to elucidate the mode of action of the compounds and the molecular basis of their selectivity for insects vs mammals and between insects and other arthropods. Modelling of the channel/pyrethroid interactions, coupled with the ability to express mutant channels in oocytes and study function, has led to knowledge of both how the channels function and potentially how to design novel insecticides with greater species selectivity

Population-Level Effects of Human Papillomavirus Vaccination Programs on Infections with Nonvaccine Genotypes

We analyzed human papillomavirus (HPV) prevalences during prevaccination and postvaccination periods to consider possible changes in nonvaccine HPV genotypes after introduction of vaccines that confer protection against 2 high-risk types, HPV16 and HPV18. Our meta-analysis included 9 studies with data for 13,886 girls and women ≤19 years of age and 23,340 women 20–24 years of age. We found evidence of cross-protection for HPV31 among the younger age group after vaccine introduction but little evidence for reductions of HPV33 and HPV45. For the group this same age group, we also found slight increases in 2 nonvaccine high-risk HPV types (HPV39 and HPV52) and in 2 possible high-risk types (HPV53 and HPV73). However, results between age groups and vaccines used were inconsistent, and the increases had possible alternative explanations; consequently, these data provided no clear evidence for type replacement. Continued monitoring of these HPV genotypes is important

Survey sequencing and radiation hybrid mapping to construct comparative maps.

In MURPHY WJ (ed.) Phylogenomics, Humana Press. (Methods in Molecular Biology, 422)International audienceRadiation hybrid (RH) mapping has become one of the most well-established techniques for economically and efficiently navigating genomes of interest. The success of the technique relies on random chromosome breakage of a target genome, which is then captured by recipient cells missing a preselected marker. Selection for hybrid cells that have DNA fragments bearing the marker of choice, plus a random set of DNA fragments from the initial irradiation, generates a set of cell lines that recapitulates the genome of the target organism several-fold. Markers or genes of interest are analyzed by PCR using DNA isolated from each cell line. Statistical tools are applied to determine both the linear order of markers on each chromosome, and the confidence of each placement. The resolution of the resulting map relies on many factors, most notably the degree of breakage from the initial radiation as well as the number of hybrid clones and mean retention value.A high-resolution RH map of a genome derived from low pass or survey sequencing (coverage from 1 to 2 times) can provide essentially the same comparative data on gene order that is derived from high-coverage (greater than x7) genome sequencing. When combined with fluorescence in situ hybridization, RH maps are complete and ordered blueprints for each chromosome. They give information about the relative order and spacing of genes and markers, and allow investigators to move between target and reference genomes, such as those of mouse or human, with ease although the approach is not limited to mammal genomes

Ethics, politics and migration: Public debates on the free movement of Romanians and Bulgarians in the UK, 2006–2013

Public debates on immigration have become the subject of much concern, particularly in the UK. This article applies an ethical lens to assess changes in public debates over intra-EU migration in six UK national newspapers during 2006 and 2013. It finds an almost complete dominance of communitarian justifications, mainly based on welfare chauvinism, but a notable increase in security-related arguments and a decrease in economic nationalist ideas. Alternative cosmopolitan arguments about immigration go from rare to virtually absent. The discussion links these shifts to a failure of the UK centre-left to overcome historic difficulties in presenting a coherent narrative on immigration policy