SIRT1 activity in peripheral blood mononuclear cells correlates with altered lung function in patients with chronic obstructive pulmonary disease

Background. Oxidative stress is a recognized pathogenic mechanism in chronic obstructive pulmonary disease (COPD). Expression of the NAD+-dependent deacetylase Sirtuin 1 (SIRT1), an antiaging molecule with a key role in oxidative stress response, has been described as decreased in the lung of COPD patients. No studies so far investigated whether systemic SIRT1 activity was associated to decreased lung function in this disease. Methods. We measured SIRT1 protein expression and activity in peripheral blood mononuclear cells (PBMCs) and total oxidative status (TOS), total antioxidant capacity (TEAC), and oxidative stress index (TOS/TEAC) in the plasma of 25 COPD patients, 20 healthy nonsmokers (HnS), and 20 healthy smokers (HS). Results. The activity of SIRT1 was significantly lower in COPD patients compared to both control groups while protein expression decreased progressively (HnS > HS > COPD). TOS levels were significantly lower in HnS than in smoke-associated subjects (COPD and HS), while TEAC levels were progressively lower according (HnS > HS > COPD). In COPD patients, SIRT1 activity, but not protein levels, correlated significantly with both lung function parameters (FEV1/FVC and FEV1) and TEAC. Conclusions. These findings suggest loss of SIRT1-driven antioxidant activity as relevant in COPD pathogenesis and identify SIRT1 activity as a potential convenient biomarker for identification of mild/moderate, stable COPD

Genetic diversity of the African malaria vector Anopheles gambiae

The sustainability of malaria control in Africa is threatened by the rise of insecticide resistance in Anopheles mosquitoes, which transmit the disease1. To gain a deeper understanding of how mosquito populations are evolving, here we sequenced the genomes of 765 specimens of Anopheles gambiae and Anopheles coluzzii sampled from 15 locations across Africa, and identified over 50 million single nucleotide polymorphisms within the accessible genome. These data revealed complex population structure and patterns of gene flow, with evidence of ancient expansions, recent bottlenecks, and local variation in effective population size. Strong signals of recent selection were observed in insecticide-resistance genes, with several sweeps spreading over large geographical distances and between species. The design of new tools for mosquito control using gene-drive systems will need to take account of high levels of genetic diversity in natural mosquito populations

Genome variation and population structure among 1142 mosquitoes of the African malaria vector species Anopheles gambiae and Anopheles coluzzii

Mosquito control remains a central pillar of efforts to reduce malaria burden in sub-Saharan Africa. However, insecticide resistance is entrenched in malaria vector populations, and countries with a high malaria burden face a daunting challenge to sustain malaria control with a limited set of surveillance and intervention tools. Here we report on the second phase of a project to build an open resource of high-quality data on genome variation among natural populations of the major African malaria vector species Anopheles gambiae and Anopheles coluzzii. We analyzed whole genomes of 1142 individual mosquitoes sampled from the wild in 13 African countries, as well as a further 234 individuals comprising parents and progeny of 11 laboratory crosses. The data resource includes high-confidence single-nucleotide polymorphism (SNP) calls at 57 million variable sites, genome-wide copy number variation (CNV) calls, and haplotypes phased at biallelic SNPs. We use these data to analyze genetic population structure and characterize genetic diversity within and between populations. We illustrate the utility of these data by investigating species differences in isolation by distance, genetic variation within proposed gene drive target sequences, and patterns of resistance to pyrethroid insecticides. This data resource provides a foundation for developing new operational systems for molecular surveillance and for accelerating research and development of new vector control tools. It also provides a unique resource for the study of population genomics and evolutionary biology in eukaryotic species with high levels of genetic diversity under strong anthropogenic evolutionary pressures

Resistance to pirimiphos-methyl in West African Anopheles is spreading via duplication and introgression of the Ace1 locus

Vector population control using insecticides is a key element of current strategies to prevent malaria transmission in Africa. The introduction of effective insecticides, such as the organophosphate pirimiphos-methyl, is essential to overcome the recurrent emergence of resistance driven by the highly diverse Anopheles genomes. Here, we use a population genomic approach to investigate the basis of pirimiphos-methyl resistance in the major malaria vectors Anopheles gambiae and A. coluzzii. A combination of copy number variation and a single non-synonymous substitution in the acetylcholinesterase gene, Ace1, provides the key resistance diagnostic in an A. coluzzii population from Coˆte d’Ivoire that we used for sequence-based association mapping, with replication in other West African populations. The Ace1 substitution and duplications occur on a unique resistance haplotype that evolved in A. gambiae and introgressed into A. coluzzii, and is now common in West Africa primarily due to selection imposed by other organophosphate or carbamate insecticides. Our findings highlight the predictive value of this complex resistance haplotype for phenotypic resistance and clarify its evolutionary history, providing tools to for molecular surveillance of the current and future effectiveness of pirimiphos-methyl based interventions

An open dataset of Plasmodium falciparum genome variation in 7,000 worldwide samples.

MalariaGEN is a data-sharing network that enables groups around the world to work together on the genomic epidemiology of malaria. Here we describe a new release of curated genome variation data on 7,000 Plasmodium falciparum samples from MalariaGEN partner studies in 28 malaria-endemic countries. High-quality genotype calls on 3 million single nucleotide polymorphisms (SNPs) and short indels were produced using a standardised analysis pipeline. Copy number variants associated with drug resistance and structural variants that cause failure of rapid diagnostic tests were also analysed.  Almost all samples showed genetic evidence of resistance to at least one antimalarial drug, and some samples from Southeast Asia carried markers of resistance to six commonly-used drugs. Genes expressed during the mosquito stage of the parasite life-cycle are prominent among loci that show strong geographic differentiation. By continuing to enlarge this open data resource we aim to facilitate research into the evolutionary processes affecting malaria control and to accelerate development of the surveillance toolkit required for malaria elimination

Beliefs about schizophrenia in Italy: a comparative nationwide survey of the general public, mental health professionals, and patients' relatives

OBJECTIVE: This study compared beliefs about the causes, treatments, and psychosocial consequences of schizophrenia in a sample of 714 lay respondents, 465 mental health professionals, and 709 key relatives of patients with this disorder. METHOD: We conducted the survey in 30 Italian geographic areas that we randomly selected after considering location and population density. We used the Questionnaire on the Opinions About Mental Illness (QO) to collect data. RESULTS: Of those surveyed, 34% of the lay respondents, 20% of the professionals, and 68% of the relatives stated that schizophrenia is exclusively caused by psychosocial factors. Lay respondents' opinions on patients' civil rights and social competence tended to be more similar to those expressed by professionals then to those reported by relatives. Lay respondents differed from the other 2 groups in their beliefs regarding the effectiveness of psychological treatments, patients' unpredictability, and whether patients should be admitted to asylums. CONCLUSIONS: These results suggest that the general public needs to be better informed about schizophrenia's main characteristics, available treatments, and risk for dangerous behaviours. The existing gap among the study's target populations could be reduced through campaigns aimed at increasing public awareness of the affective and civil rights of patients