Abundance of conserved CRISPR-Cas9 target sites within the highly polymorphic genomes of Anopheles and Aedes mosquitoes.

A number of recent papers report that standing genetic variation in natural populations includes ubiquitous polymorphisms within target sites for Cas9-based gene drive (CGD) and that these "drive resistant alleles" (DRA) preclude the successful application of CGD for managing these populations. Here we report the results of a survey of 1280 genomes of the mosquitoes Anopheles gambiae, An. coluzzii, and Aedes aegypti in which we determine that ~90% of all protein-encoding CGD target genes in natural populations include at least one target site with no DRAs at a frequency of ≥1.0%. We conclude that the abundance of conserved target sites in mosquito genomes and the inherent flexibility in CGD design obviates the concern that DRAs present in the standing genetic variation of mosquito populations will be detrimental to the deployment of this technology for population modification strategies

Complex genome evolution in Anopheles coluzzii associated with increased insecticide usage in Mali.

In certain cases, a species may have access to important genetic variation present in a related species via adaptive introgression. These novel alleles may interact with their new genetic background, resulting in unexpected phenotypes. In this study, we describe a selective sweep on standing variation on the X chromosome in the mosquito Anopheles coluzzii, a principal malaria vector in West Africa. This event may have been influenced by the recent adaptive introgression of the insecticide resistance gene known as kdr from the sister species Anopheles gambiae. Individuals carrying both kdr and a nearly fixed X-linked haplotype, encompassing at least four genes including the P450 gene CYP9K1 and the cuticular protein CPR125, have rapidly increased in relative frequency. In parallel, a reproductively isolated insecticide-susceptible A. gambiae population (Bamako form) has been driven to local extinction, likely due to strong selection from increased insecticide-treated bed net usage

The effect of organic retarders on grout thickening and setting during deep borehole disposal of high-level radioactive waste

Deep borehole disposal (DBD) is being increasingly seen as a viable and potentially superior alternative to comparatively shallow mined repository concepts for disposal of some high-level radioactive wastes. We report here details of proof-of-concept investigations into the use of cementitious grouts as sealing/ support matrices for use in low temperature DBD scenarios. Using the cementitious grout to fill annular space within the disposal zone will not only support waste packages during placement, but will also provide a low permeability layer around them which will ultimately enhance the safety case for DBD. Grouts based on Class G oil well cement are being developed. The use of retarders to delay the accelerated onset of thickening and setting (caused by the high temperature and pressure in the borehole) is being investigated experimentally. Sodium gluconate and a polycarboxylate additive each provide suf- ficient retardation over the range 90e140 °C in order to be considered for this application. Phosphonate and sulphonate additives provide desirable retardation at 90 °C. The additives did not affect grout composition at 14 days curing and the phases formed are durable at elevated temperature and pressure

The origin of island populations of the African malaria mosquito, Anopheles coluzzii

Funding Information: This work was supported by grants from the UC Irvine Malaria Initiative Program, Open Philanthropy and NIH R56 grant (R56AI130277). We thank the National Malaria Control Program personnel from São Tomé and Príncipe and, Ministry of Health in São Tomé and Príncipe who facilitated our field collections in São Tomé. We thank the Centre International de Recherches Médicales de Franceville (Franceville, Gabon) for the collections in Gabon. Publisher Copyright: © 2021, The Author(s).Anopheles coluzzii is a major malaria vector throughout its distribution in west-central Africa. Here we present a whole-genome study of 142 specimens from nine countries in continental Africa and three islands in the Gulf of Guinea. This sample set covers a large part of this species’ geographic range. Our population genomic analyses included a description of the structure of mainland populations, island populations, and connectivity between them. Three genetic clusters are identified among mainland populations and genetic distances (FST) fits an isolation-by-distance model. Genomic analyses are applied to estimate the demographic history and ancestry for each island. Taken together with the unique biogeography and history of human occupation for each island, they present a coherent explanation underlying levels of genetic isolation between mainland and island populations. We discuss the relationship of our findings to the suitability of São Tomé and Príncipe islands as candidate sites for potential field trials of genetic-based malaria control strategies.publishersversionpublishe

Selective pressures on genomes in molecular evolution

We describe the evolution of macromolecules as an information transmission process and apply tools from Shannon information theory to it. This allows us to isolate three independent, competing selective pressures that we term compression, transmission, and neutrality selection. The first two affect genome length: the pressure to conserve resources by compressing the code, and the pressure to acquire additional information that improves the channel, increasing the rate of information transmission into each offspring. Noisy transmission channels (replication with mutations) gives rise to a third pressure that acts on the actual encoding of information; it maximizes the fraction of mutations that are neutral with respect to the phenotype. This neutrality selection has important implications for the evolution of evolvability. We demonstrate each selective pressure in experiments with digital organisms.Comment: 16 pages, 3 figures, to be published in J. theor. Biolog

Limits on the 2.2-μm contrast ratio of the close-orbiting planet HD 189733b

We obtained 238 spectra of the close-orbiting extrasolar giant planet HD 189733b with resolution R∼ 15 000 during one night of observations with the Near-Infrared High-Resolution Spectrograph (NIRSPEC), at the Keck II Telescope. We have searched for planetary absorption signatures in the 2.0-2.4 μm region where H2O and CO are expected to be the dominant atmospheric opacities. We employ a phase-dependent orbital model and tomographic techniques to search for the planetary absorption signatures in the combined stellar and planetary spectra. Because potential absorption signatures are hidden in the noise of each single exposure, we use a model list of lines to apply a spectral deconvolution. The resulting mean profile possesses a signal-to-noise ratio (S/N) that is 20 times greater than that found in individual lines. Our spectral time series thus yields spectral signatures with a mean S/N = 2720. We are unable to detect a planetary signature at a contrast ratio of log10(Fp/F*) =−3.40, with 63.8 per cent confidence. Our findings are not consistent with model predictions which nevertheless give a good fit to mid-infrared observations of HD 189733b. The 1σ result is a factor of 1.7 times less than the predicted 2.185-μm planet/star flux ratio of log10(Fp/F*) ∼−3.1

Paedophiles in the community: inter-agency conflict, news leaks and the local press

This article explores the leaking of confidential information about secret Home Office plans to house convicted paedophiles within a local community (albeit inside a prison). It argues that a politics of paedophilia has emerged in which inter-agency consensus on the issue of ‘what to do’ with high-profile sex offenders has broken down. Accordingly, the article situates newspaper ‘outing’ of paedophiles in the community in relation to vigilante journalism and leaked information from official agencies. The article then presents research findings from a case study of news events set in train following a whistle-blowing reaction by Prison Officers’ Association officials to Home Office plans. Drawing from a corpus of 10 interviews with journalists and key protagonists in the story, the article discusses both the dynamics of whistle blowing about paedophiles and also what happens after the whistle has blown

The first genome sequence of Anopheles squamous from Macha, Zambia [version 1; peer review: 2 approved]

Despite efforts to minimize the impacts of malaria and reduce the number of primary vectors, malaria has yet to be eliminated in Zambia. Understudied vector species may perpetuate malaria transmission in pre-elimination settings. Anopheles squamosus is one of the most abundantly caught mosquito species in southern Zambia and has previously been found with Plasmodium falciparum sporozoites, a causal agent of human malaria. This species may be a critical vector of malaria transmission, however, there is a lack of genetic information available for An. squamosus. We report the first genome data and the first complete mitogenome (Mt) sequence of An. squamosus. The sequence was extracted from one individual mosquito from the Chidakwa area in Macha, Zambia. The raw reads were obtained using Illumina Novaseq 6000 and assembled through NOVOplasty alignment with related species. The length of the An. squamosus Mt was 15,351 bp, with 77.9 % AT content. The closest match to the whole mitochondrial genome in the phylogenetic tree is the African malaria mosquito, Anopheles gambiae. Its genome data is available through National Center for Biotechnology Information (NCBI) Sequencing Reads Archive (SRA) with accession number SRR22114392. The mitochondrial genome was deposited in NCBI GenBank with the accession number OP776919. The ITS2 containing contig sequence was deposited in GenBank with the accession number OQ241725. Mitogenome annotation and a phylogenetic tree with related Anopheles mosquito species are provided

NOX1 loss-of-function genetic variants in patients with inflammatory bowel disease.

Genetic defects that affect intestinal epithelial barrier function can present with very early-onset inflammatory bowel disease (VEOIBD). Using whole-genome sequencing, a novel hemizygous defect in NOX1 encoding NAPDH oxidase 1 was identified in a patient with ulcerative colitis-like VEOIBD. Exome screening of 1,878 pediatric patients identified further seven male inflammatory bowel disease (IBD) patients with rare NOX1 mutations. Loss-of-function was validated in p.N122H and p.T497A, and to a lesser degree in p.Y470H, p.R287Q, p.I67M, p.Q293R as well as the previously described p.P330S, and the common NOX1 SNP p.D360N (rs34688635) variant. The missense mutation p.N122H abrogated reactive oxygen species (ROS) production in cell lines, ex vivo colonic explants, and patient-derived colonic organoid cultures. Within colonic crypts, NOX1 constitutively generates a high level of ROS in the crypt lumen. Analysis of 9,513 controls and 11,140 IBD patients of non-Jewish European ancestry did not reveal an association between p.D360N and IBD. Our data suggest that loss-of-function variants in NOX1 do not cause a Mendelian disorder of high penetrance but are a context-specific modifier. Our results implicate that variants in NOX1 change brush border ROS within colonic crypts at the interface between the epithelium and luminal microbes