X-ray Survey Results on Active Galaxy Physics and Evolution

This "pedagogical" review describes the key Chandra and XMM-Newton extragalactic surveys to date and details some of their implications for AGN physics and evolution. We additionally highlight two topics of current widespread interest: (1) X-ray constraints on the AGN content of luminous submillimeter galaxies, and (2) the demography and physics of high-redshift (z > 4) AGN as revealed by X-ray observations. Finally, we discuss prospects for future X-ray surveys with Chandra, XMM-Newton, and upcoming missions.Comment: 26 pages, in Physics of Active Galactic Nuclei at All Scales, eds. Alloin D., Johnson R., Lira P. (Springer-Verlag, Berlin), version with all figures at http://www.astro.psu.edu/users/niel/papers/papers.htm

The genomics of heart failure: design and rationale of the HERMES consortium

Aims The HERMES (HEart failure Molecular Epidemiology for Therapeutic targets) consortium aims to identify the genomic and molecular basis of heart failure.Methods and results The consortium currently includes 51 studies from 11 countries, including 68 157 heart failure cases and 949 888 controls, with data on heart failure events and prognosis. All studies collected biological samples and performed genome-wide genotyping of common genetic variants. The enrolment of subjects into participating studies ranged from 1948 to the present day, and the median follow-up following heart failure diagnosis ranged from 2 to 116 months. Forty-nine of 51 individual studies enrolled participants of both sexes; in these studies, participants with heart failure were predominantly male (34-90%). The mean age at diagnosis or ascertainment across all studies ranged from 54 to 84 years. Based on the aggregate sample, we estimated 80% power to genetic variant associations with risk of heart failure with an odds ratio of >1.10 for common variants (allele frequency > 0.05) and >1.20 for low-frequency variants (allele frequency 0.01-0.05) at P Conclusions HERMES is a global collaboration aiming to (i) identify the genetic determinants of heart failure; (ii) generate insights into the causal pathways leading to heart failure and enable genetic approaches to target prioritization; and (iii) develop genomic tools for disease stratification and risk prediction.</p

Evidence of multiple pyrethroid resistance mechanisms in the malaria vector Anopheles gambiae sensu stricto from Nigeria

Pyrethroid insecticide resistance in Anopheles gambiae sensu stricto is a major concern to malaria vector control programmes. Resistance is mainly due to target-site insensitivity arising from a single point mutation, often referred to as knockdown resistance (kdr). Metabolic-based resistance mechanisms have also been implicated in pyrethroid resistance in East Africa and are currently being investigated in West Africa. Here we report the co-occurrence of both resistance mechanisms in a population of An. gambiae s.s. from Nigeria. Bioassay, synergist and biochemical analysis carried out on resistant and susceptible strains of An. gambiae s.s. from the same geographical area revealed >50% of the West African kdr mutation in the resistant mosquitoes but <3% in the susceptible mosquitoes. Resistant mosquitoes synergized using pyperonyl butoxide before permethrin exposure showed a significant increase in mortality compared with the non-synergized. Biochemical assays showed an increased level of monooxygenase but not glutathione-S-transferase or esterase activities in the resistant mosquitoes. Microarray analysis using the An. gambiae detox-chip for expression of detoxifying genes showed five over-expressed genes in the resistant strain when compared with the susceptible one. Two of these, CPLC8 and CPLC#, are cuticular genes not implicated in pyrethroid metabolism in An. gambiae s.s, and could constitute a novel set of candidate genes that warrant further investigation. © 2008 Royal Society of Tropical Medicine and Hygiene

Impact of the Rift Valley on restriction fragment length polymorphism typing of the major African malaria vector Anopheles funestus (Diptera : Culicidae)

Anopheles funestus Giles (Diptera: Culicidae) is one of Africa's major malaria vectors. To understand population structure within An. funestus, various molecular markers have recently been developed. We investigated the impact of the Rift Valley on one such molecular marker, a polymerase chain reaction-restriction fragment length polymorphism (RFLP). This system distinguishes An. funestus populations into types M, W, and MW. Generally, these types correlate between geographical location and RFLP type, whereby M associates essentially with eastern Africa, W with western and central Africa, and MW with southern Africa. In total, 606 specimens were screened from 12 countries. Specimens from southern African localities were of the expected MW-type with the exception of the sample from Malawi, which showed all three types. The specimens from Tanzania showed the M- and MW-types, whereas specimens from Kenya showed M- and W-types. We also recorded different RFLP types not recorded previously. Type Y was recorded in Malawi, and Z-type was recorded from four localities: Angola, Malawi, Ghana, and Zambia