The Optical and Infrared Photometric Evolution of the Recent Stellar Merger, V1309 Sco

Nova Sco 2008 was recently shown to have resulted from the merger of the two stars in the contact binary V1309 Sco. This is the first stellar merger ever observed between two convective stars. We present archival data, new infrared photometry, and Hubble Space Telescope WFC3 imaging of V1309 Sco. Spitzer observations show that it had a large infrared excess in the 3.6 μm to 8 μm range more than a year before the merger. Standard color diagnostics of the pre-merger infrared colors place V1309 Sco in the same region where evolved stars with chemically complex mass loss are located. Since the nova outburst subsided in optical bandpasses in 2008, the merger remnant's brightness in optical bandpasses, near-IR bandpasses, and the Spitzer 3.6 μm and 4.5 μm channels has varied by several magnitudes and in complex ways. A temporary, strong increase in the reddening during 2010 suggests the occurrence of a dust formation event. We point out several peculiarities in the relative fluxes and time behavior of the optical and near-IR magnitudes, which could be explained if some of the photometric bandpasses in the 1–5 μm range are strongly affected by emission lines

SIT for African malaria vectors: Epilogue

As a result of increased support and the diligent application of new and conventional anti-malaria tools, significant reductions in malaria transmission are being accomplished. Historical and current evolutionary responses of vectors and parasites to malaria interventions demonstrate that it is unwise to assume that a limited suite of tools will remain effective indefinitely, thus efforts to develop new interventions should continue. This collection of manuscripts surveys the prospects and technical challenges for applying a novel tool, the sterile insect technique (SIT), against mosquitoes that transmit malaria. The method has been very successful against many agricultural pest insects in area-wide programs, but demonstrations against malaria vectors have not been sufficient to determine its potential relative to current alternatives, much of which will hinge ultimately upon cost. These manuscripts provide an overview of current efforts to develop SIT and identify key research issues that remain

Core-collapse supernova subtypes in luminous infrared galaxies

Acknowledgements. We thank the anonymous referee for useful comments. We thank Marco Fiaschi for carrying out some of the Asiago observations. EK is supported by the Turku Collegium of Science, Medicine and Technology. EK also acknowledge support from the Science and Technology Facilities Council (STFC; ST/P000312/1). ECK acknowledges support from the G.R.E.A.T. research environment and support from The Wenner-Gren Foundations. MF is supported by a Royal Society – Science Foundation Ireland University Research Fellowship. EC, LT, AP, and MT are partially supported by the PRIN-INAF 2017 with the project “Towards the SKA and CTA era: discovery, localization, and physics of transient objects”. HK was funded by the Academy of Finland projects 324504 and 328898. TWC acknowledges the EU Funding under Marie Skłodowska-Curie grant agreement No. 842471. LG was funded by the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 839090. This work has been partially supported by the Spanish grant PGC2018-095317-B-C21 within the European Funds for Regional Development (FEDER). MG is supported by the Polish NCN MAESTRO grant 2014/14/A/ST9/00121. KM acknowledges support from EU H2020 ERC grant no. 758638. TMB was funded by the CONICYT PFCHA / DOCTORADOBECAS CHILE/2017-72180113. MN is supported by a Royal Astronomical Society Research Fellowship. Based on observations collected at the European Organisation for Astronomical Research in the Southern Hemisphere under ESO programmes 67.D-0438, 60.A-9475, 199.D-0143, and 1103.D-0328. Some of the observations reported in this paper were obtained with the Southern African Large Telescope (SALT) under programme 2018-1-DDT-003 (PI: Kankare). Polish participation in SALT is funded by grant No. MNiSW DIR/WK/2016/07. Based on observations made with the Nordic Optical Telescope, operated by the Nordic Optical Telescope Scientific Association at the Observatorio del Roque de los Muchachos, La Palma, Spain, of the Instituto de Astrofisica de Canarias. The data presented here were obtained in part with ALFOSC, which is provided by the Instituto de Astrofisica de Andalucia (IAA) under a joint agreement with the University of Copenhagen and NOTSA. This work is partly based on the NUTS2 programme carried out at the NOT. NUTS2 is funded in part by the Instrument Center for Danish Astrophysics (IDA). The Liverpool Telescope is operated on the island of La Palma by Liverpool John Moores University in the Spanish Observatorio del Roque de los Muchachos of the Instituto de Astrofisica de Canarias with financial support from the UK Science and Technology Facilities Council. This paper is also based on observations collected at the Copernico 1.82 m and Schmidt 67/92 Telescopes operated by INAF – Osservatorio Astronomico di Padova at Asiago, Italy. Based on observations obtained at the Gemini Observatory, which is operated by the Association of Universities for Research in Astronomy, Inc., under a cooperative agreement with the NSF on behalf of the Gemini partnership: the National Science Foundation (United States), the National Research Council (Canada), CONICYT (Chile), Ministerio de Ciencia, Tecnología e Innovación Productiva (Argentina), and Ministério da Ciência, Tecnologia e Inovação (Brazil). Observations were carried out under programme GS-2017A-C-1. This project used data obtained with the Dark Energy Camera (DECam), which was constructed by the Dark Energy Survey (DES) collaboration. Funding for the DES Projects has been provided by the DOE and NSF (USA), MISE (Spain), STFC (UK), HEFCE (UK), NCSA (UIUC), KICP (U. Chicago), CCAPP (Ohio State), MIFPA (Texas A&M University), CNPQ, FAPERJ, FINEP (Brazil), MINECO (Spain), DFG (Germany) and the collaborating institutions in the Dark Energy Survey, which are Argonne Lab, UC Santa Cruz, University of Cambridge, CIEMAT-Madrid, University of Chicago, University College London, DES-Brazil Consortium, University of Edinburgh, ETH Zürich, Fermilab, University of Illinois, ICE (IEEC-CSIC), IFAE Barcelona, Lawrence Berkeley Lab, LMU München and the associated Excellence Cluster Universe, University of Michigan, NOAO, University of Nottingham, Ohio State University, OzDES Membership Consortium, University of Pennsylvania, University of Portsmouth, SLAC National Lab, Stanford University, University of Sussex, and Texas A&M University. Based on observations obtained with the Samuel Oschin 48-inch Telescope at the Palomar Observatory as part of the Zwicky Transient Facility project. ZTF is supported by the National Science Foundation under Grant No. AST-1440341 and a collaboration including Caltech, IPAC, the Weizmann Institute for Science, the Oskar Klein Center at Stockholm University, the University of Maryland, the University of Washington, Deutsches Elektronen-Synchrotron and Humboldt University, Los Alamos National Laboratories, the TANGO Consortium of Taiwan, the University of Wisconsin at Milwaukee, and Lawrence Berkeley National Laboratories. Operations are conducted by COO, IPAC, and UW. Based on observations at Cerro Tololo Inter-American Observatory, National Optical Astronomy Observatory (NOAO Prop. ID 2017A-0260; and PI: Soares-Santos), which is operated by the Association of Universities for Research in Astronomy (AURA) under a cooperative agreement with the National Science Foundation. The Pan-STARRS1 Surveys (PS1) and the PS1 public science archive have been made possible through contributions by the Institute for Astronomy, the University of Hawaii, the Pan-STARRS Project Office, the Max-Planck Society and its participating institutes, the Max Planck Institute for Astronomy, Heidelberg and the Max Planck Institute for Extraterrestrial Physics, Garching, The Johns Hopkins University, Durham University, the University of Edinburgh, the Queen’s University Belfast, the Harvard-Smithsonian Center for Astrophysics, the Las Cumbres Observatory Global Telescope Network Incorporated, the National Central University of Taiwan, the Space Telescope Science Institute, the National Aeronautics and Space Administration under Grant No. NNX08AR22G issued through the Planetary Science Division of the NASA Science Mission Directorate, the National Science Foundation Grant No. AST-1238877, the University of Maryland, Eotvos Lorand University (ELTE), the Los Alamos National Laboratory, and the Gordon and Betty Moore Foundation. Some of the data presented in this paper were obtained from the Mikulski Archive for Space Telescopes (MAST). STScI is operated by the Association of Universities for Research in Astronomy, Inc., under NASA contract NAS5-26555. This work is based in part on archival data obtained with the Spitzer Space Telescope, which is operated by the Jet Propulsion Laboratory, California Institute of Technology under a contract with NASA. This research has made use of NED which is operated by the Jet Propulsion Laboratory, California Institute of Technology, under contract with the National Aeronautics and Space Administration. We have made use of the Weizmann Interactive Supernova Data Repository (Yaron & Gal-Yam 2012, https://wiserep.weizmann.ac.il).1 iraf is distributed by the National Optical Astronomy Observatories, which are operated by the Association of Universities for Research in Astronomy, Inc., under cooperative agreement with the National Science Foundation.The fraction of core-collapse supernovae (CCSNe) occurring in the central regions of galaxies is not well constrained at present. This is partly because large-scale transient surveys operate at optical wavelengths, making it challenging to detect transient sources that occur in regions susceptible to high extinction factors. Here we present the discovery and follow-up observations of two CCSNe that occurred in the luminous infrared galaxy (LIRG) NGC 3256. The first, SN 2018ec, was discovered using the ESO HAWK-I/GRAAL adaptive optics seeing enhancer, and was classified as a Type Ic with a host galaxy extinction of AV = 2.1−0.1+0.3 mag. The second, AT 2018cux, was discovered during the course of follow-up observations of SN 2018ec, and is consistent with a subluminous Type IIP classification with an AV = 2.1 ± 0.4 mag of host extinction. A third CCSN, PSN J10275082−4354034 in NGC 3256, was previously reported in 2014, and we recovered the source in late-time archival Hubble Space Telescope imaging. Based on template light curve fitting, we favour a Type IIn classification for it with modest host galaxy extinction of AV = 0.3−0.3+0.4 mag. We also extend our study with follow-up data of the recent Type IIb SN 2019lqo and Type Ib SN 2020fkb that occurred in the LIRG system Arp 299 with host extinctions of AV = 2.1−0.3+0.1 and AV = 0.4−0.2+0.1 mag, respectively. Motivated by the above, we inspected, for the first time, a sample of 29 CCSNe located within a projected distance of 2.5 kpc from the host galaxy nuclei in a sample of 16 LIRGs. We find, if star formation within these galaxies is modelled assuming a global starburst episode and normal IMF, that there is evidence of a correlation between the starburst age and the CCSN subtype. We infer that the two subgroups of 14 H-poor (Type IIb/Ib/Ic/Ibn) and 15 H-rich (Type II/IIn) CCSNe have different underlying progenitor age distributions, with the H-poor progenitors being younger at 3σ significance. However, we note that the currently available sample sizes of CCSNe and host LIRGs are small, and the statistical comparisons between subgroups do not take into account possible systematic or model errors related to the estimated starburst ages.DOCTORADOBECAS CHILE/2017-72180113Deutsches Elektronen-Synchrotron and Humboldt UniversityEU H2020 ERC 758638IFAE BarcelonaIPACInstituto de Astrofisica de CanariasKICPMIFPAMarie Skłodowska-Curie 839090,PGC2018-095317-B-C21Max Planck Institute for AstronomyMax Planck Institute for Extraterrestrial PhysicsNOAONational Central University of TaiwanNational Optical Astronomy ObservatoriesScience Foundation Ireland UniversityTurku Collegium of Science, Medicine and TechnologyWeizmann Institute for ScienceNational Science Foundation NSFU.S. Department of Energy USDOENational Aeronautics and Space Administration AST-1238877,NNX08AR22G NASAGordon and Betty Moore Foundation NAS5-26555 GBMFMerck Institute for Science Education MISEUniversity of Illinois at Urbana-Champaign UIUCStanford University SUArgonne National Laboratory ANLLawrence Berkeley National Laboratory 2017A-0260 LBNLUniversity of Wisconsin-MilwaukeeOhio State University OSUCalifornia Institute of Technology CITUniversity of ChicagoUniversity of Michigan U-MUniversity of Washington UWJohns Hopkins University JHUTexas A and M University TAMUUniversity of Maryland UMDUniversity of Hawai'i UHLos Alamos National Laboratory LANLUniversity of PortsmouthSmithsonian Astrophysical Observatory SAONational Centre for Supercomputing Applications NCSAHorizon 2020 Framework Programme H2020SLAC National Accelerator Laboratory SLACNational Research Council NRCSpace Telescope Science Institute STScICenter for Cosmology and Astroparticle Physics, Ohio State University CCAPPWenner-Gren StiftelsernaScience and Technology Facilities Council ST/P000312/1 STFCRoyal SocietyRoyal Astronomical Society MNiSW DIR/WK/2016/07 RASUniversity College London UCLEuropean Commission 842471 ECUniversity of NottinghamUniversity of Sussex AST-1440341University of Edinburgh EDQueen's University Belfast QUBDurham UniversityDeutsche Forschungsgemeinschaft DFGSuomen Akatemia 324504,328898Comisión Nacional de Investigación Científica y Tecnológica CONICYTMinisterio de Ciencia, Tecnología e Innovación Productiva MINCyTMinisterio de Economía y Competitividad MINECOMinistério da Ciência, Tecnologia e Inovação MCTILiverpool John Moores University LJMUMax-Planck-Gesellschaft MPGNarodowe Centrum Nauki 2014/14/A/ST9/00121 NCNFundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro FAPERJFinanciadora de Estudos e Projetos FINEPEuropean Regional Development Fund ERDFEötvös Loránd Tudományegyetem ELT

Pyrethroid Resistance in an Anopheles funestus Population from Uganda

Background: The susceptibility status of Anopheles funestus to insecticides remains largely unknown in most parts of Africa because of the difficulty in rearing field-caught mosquitoes of this malaria vector. Here we report the susceptibility status of the An. funestus population from Tororo district in Uganda and a preliminary haracterisation of the putative resistance mechanisms involved. Methodology/Principal Findings: A new forced egg laying technique used in this study significantly increased the numbers of field-caught females laying eggs and generated more than 4000 F1 adults. WHO bioassays indicated that An. funestus in Tororo is resistant to pyrethroids (62% mortality after 1 h exposure to 0.75% permethrin and 28% mortality to 0.05% deltamethrin). Suspected DDT resistance was also observed with 82% mortality. However this population is fully susceptible to bendiocarb (carbamate), malathion (organophosphate) and dieldrin with 100% mortality observed after exposure to each of these insecticides. Sequencing of a fragment of the sodium channel gene containing the 1014 codon conferring pyrethroid/DDT resistance in An. gambiae did not detect the L1014F kdr mutation but a correlation between haplotypes and resistance phenotype was observed indicating that mutations in other exons may be conferring the knockdown resistance in this species. Biochemical assays suggest that resistance in this population is mediated by metabolic resistance with elevated level of GSTs, P450s and pNPA compared to a susceptible strain of Anopheles gambiae. RT-PCR further confirmed the involvement of P450s with a 12-fold over-expression of CYP6P9b in the Tororo population compared to the fully susceptible laboratory colony FANG. Conclusion: This study represents the first report of pyrethroid/DDT resistance in An. funestus from East Africa. With resistance already reported in southern and West Africa, this indicates that resistance in An. funestus may be more widespread than previously assumed and therefore this should be taken into account for the implementation and management of vector control programs in Africa

Distribution of a Knockdown Resistance Mutation (L1014S) in Anopheles gambiae s.s. and Anopheles arabiensis in Western and Southern Kenya

In Kenya, insecticide-treated mosquito nets (ITNs) distributed to pregnant women and children under 5 years old through various programs have resulted in a significant reduction in malaria deaths. All of the World Health Organization-recommended insecticides for mosquito nets are pyrethroids, and vector mosquito resistance to these insecticides is one of the major obstacles to an effective malaria control program. Anopheles gambiae s.s. and Anopheles arabiensis are major malaria vectors that are widely distributed in Kenya. Two point mutations in the voltage-gated sodium channel (L1014F and L1014S) are associated with knockdown resistance (kdr) to DDT and pyrethroids in An. gambiae s.s. While the same point mutations have been reported to be rare in An. arabiensis, some evidence of metabolic resistance has been reported in this species. In order to determine the distribution of the point mutation L1014S in An. gambiae s.s. and An. arabiensis in southern and western Kenya, we collected larvae and screened for the mutation by DNA sequencing. We found high allelic and homozygous frequencies of the L1014S mutation in An. gambiae s.s. The L1014S mutation was also widely distributed in An. arabiensis, although the allelic frequency was lower than in An. gambiae s.s. The same intron sequence (length: 57 base) found in both species indicated that the mutation was introgressed by hybridization. The allelic frequency of L1014S was higher in both species in western regions, demonstrating the strong selection pressure imposed by long-lasting insecticide-treated nets (LLITN)/ITN on the An. gambiae s.s. and An. arabiensis populations in those areas. The present contribution of the L1014S mutation to pyrethroid resistance in An. arabiensis may be negligible. However, the homozygous frequency could increase with continuing selection pressure due to expanded LLITN coverage in the future

Cotton pest management practices and the selection of pyrethroid resistance in Anopheles gambiae population in Northern Benin

<p>Abstract</p> <p>Background</p> <p>Pyrethroid insecticides, carbamate and organophosphate are the classes of insecticides commonly used in agriculture for crop protection in Benin. Pyrethroids remain the only class of insecticides recommended by the WHO for impregnation of bed nets. Unfortunately, the high level of pyrethroid resistance in <it>Anopheles gambiae </it>s.l., threatens to undermine the success of pyrethroid treated nets. This study focuses on the investigation of agricultural practices in cotton growing areas, and their direct impact on larval populations of <it>An. gambiae </it>in surrounding breeding sites.</p> <p>Methods</p> <p>The protocol was based on the collection of agro-sociological data where farmers were subjected to semi-structured questionnaires based on the strategies used for crop protection. This was complemented by bioassay tests to assess the susceptibility of malaria vectors to various insecticides. Molecular analysis was performed to characterize the resistance genes and the molecular forms of <it>An. gambiae</it>. Insecticide residues in soil samples from breeding sites were investigated to determine major factors that can inhibit the normal growth of mosquito larvae by exposing susceptible and resistant laboratory strains.</p> <p>Results</p> <p>There is a common use by local farmers of mineral fertilizer NPK at 200 kg/ha and urea at 50 kg/hectare following insecticide treatments in both the Calendar Control Program (CCP) and the Targeted Intermittent Control Program (TICP). By contrast, no chemicals are involved in Biological Program (BP) where farmers use organic and natural fertilizers which include animal excreta.</p> <p>Susceptibility test results confirmed a high resistance to DDT. Mean mortality of <it>An. gambiae </it>collected from the farms practicing CCP, TICP and BP methods were 33%, 42% and 65% respectively. <it>An. gambiae </it>populations from areas using the CCP and TICP programs showed resistance to permethrin with mortality of 50% and 58% respectively. By contrast, bioassay test results of <it>An. gambiae </it>from BP areas gave a high level of susceptibility to permethrin with an average mortality of 94%.</p> <p>Molecular analysis identified <it>An. gambiae </it>s.s, and <it>An. arabiensis </it>with a high predominance of <it>An. gambiae s.s </it>(90%). The two molecular forms, M and S, were also determined with a high frequency of the S form (96%).</p> <p>The <it>Kdr </it>gene seemed the main target- site resistance mechanism detected in CCP, TICP, and BP areas at the rates ranging from 32 to 78%. The frequency of <it>ace-1R </it>gene was very low (< 0.1).</p> <p>The presence of inhibiting factors in soil samples under insecticide treatments were found and affected negatively in delaying the development of <it>An. gambiae </it>larval populations.</p> <p>Conclusions</p> <p>This research shows that <it>Kdr </it>has spread widely in <it>An. gambiae</it>, mainly in CCP and TICP areas where pyrethroids are extensively used. To reduce the negative impact of pesticides use in cotton crop protection, the application of BP-like programs, which do not appear to select for vector resistance would be useful. These results could serve as scientific evidence of the spread of resistance due to a massive agricultural use of insecticides and contribute to the management of pesticides usage on cotton crops hence reducing the selection pressure of insecticides on <it>An. gambiae </it>populations.</p

Presence of two alternative kdr-like mutations, L1014F and L1014S, and a novel mutation, V1010L, in the voltage gated Na+ channel of Anopheles culicifacies from Orissa, India

<p>Abstract</p> <p>Background</p> <p>Knockdown resistance in insects resulting from mutation(s) in the voltage gated Na⁺channel (VGSC) is one of the mechanisms of resistance against DDT and pyrethroids. Recently a point mutation leading to Leu-to-Phe substitution in the VGSC at residue 1014, a most common <it>kdr </it>mutation in insects, was reported in <it>Anopheles culicifacies</it>-a major malaria vector in the Indian subcontinent. This study reports the presence of two additional amino acid substitutions in the VGSC of an <it>An. culicifacies </it>population from Malkangiri district of Orissa, India.</p> <p>Methods</p> <p><it>Anopheles culicifacies sensu lato (s.l.) </it>samples, collected from a population of Malkangiri district of Orissa (India), were sequenced for part of the second transmembrane segment of VGSC and analyzed for the presence of non-synonymous mutations. A new primer introduced restriction analysis-PCR (PIRA-PCR) was developed for the detection of the new mutation L1014S. The <it>An. culicifacies </it>population was genotyped for the presence of L1014F substitution by an amplification refractory mutation system (ARMS) and for L1014S substitutions by using a new PIRA-PCR developed in this study. The results were validated through DNA sequencing.</p> <p>Results</p> <p>DNA sequencing of <it>An. culicifacies </it>individuals collected from district Malkangiri revealed the presence of three amino acid substitutions in the IIS6 transmembrane segments of VGSC, each one resulting from a single point mutation. Two alternative point mutations, 3042A>T transversion or 3041T>C transition, were found at residue L1014 leading to Leu (TTA)-to-Phe (TTT) or -Ser (TCA) changes, respectively. A third and novel substitution, Val (GTG)-to-Leu (TTG or CTG), was identified at residue V1010 resulting from either of the two transversions–3028G>T or 3028G>C. The L1014S substitution co-existed with V1010L in all the samples analyzed irrespective of the type of point mutation associated with the latter. The PIRA-PCR strategy developed for the identification of the new mutation L1014S was found specific as evident from DNA sequencing results of respective samples. Since L1014S was found tightly linked to V1010L, no separate assay was developed for the latter mutation. Screening of population using PIRA-PCR assays for 1014S and ARMS for 1014F alleles revealed the presence of all the three amino acid substitutions in low frequency.</p> <p>Conclusions</p> <p>This is the first report of the presence of L1014S (homologous to the <it>kdr-e </it>in <it>An. gambiae</it>) and a novel mutation V1010L (resulting from G-to-T or -C transversions) in the VGSC of <it>An. culicifacies </it>in addition to the previously described mutation L1014F. The V1010L substitution was tightly linked to L1014S substitution. A new PIRA-PCR strategy was developed for the detection of L1014S mutation and the linked V1010L mutation.</p

Assessing cardiovascular risk in chronic kidney disease patients prior to kidney transplantation: clinical usefulness of a standardised cardiovascular assessment protocol.

BACKGROUND: Despite pre-kidney-transplant cardiovascular (CV) assessment being routine care to minimise perioperative risk, the utility of such assessment is not well established. The study reviewed the evaluation and outcome of a standardised CV assessment protocol. METHODS: Data were analysed for 231 patients (age 53.4 ± 12.9 years, diabetes 34.6%) referred for kidney transplantation between 1/2/2012-31/12/2014. One hundred forty-three patients were high-risk (age > 60 years, diabetes, CV disease, heart failure, peripheral vascular disease) and offered dobutamine stress echocardiography (DSE); 88 patients were low-risk and offered ECG and echocardiography with/without exercise treadmill test. RESULTS: At the end of follow-up (579 ± 289 days), 35 patients underwent kidney transplantation and 50 were active on the waitlist. There were 24 events (CV or death), none were perioperative. One hundred fifteen patients had DSE with proportionally more events in DSE-positive compared to DSE-negative patients (6/34 vs. 7/81, p = 0.164). In 42 patients who underwent coronary angiography due to a positive DSE or ischaemic heart disease symptoms, 13 (31%) had events, 6 were suspended, 11 removed from waitlist, 3 wait-listed, 1 transplanted and 17 still undergoing assessment. Patients with significant coronary artery disease requiring intervention had poorer event-free survival compared to those without intervention (56% vs. 83% at 2 years, p = 0.044). However, the association became non-significant after correction for CV risk factors (HR = 3.17, 95% CI 0.51-19.59, p = 0.215). CONCLUSIONS: The stratified CV risk assessment protocol using DSE in all high-risk patients was effective in identifying patients with coronary artery disease. The coronary angiograms identified the event-prone patients effectively but coronary interventions were not associated with improved survival

Candidate-gene based GWAS identifies reproducible DNA markers for metabolic pyrethroid resistance from standing genetic variation in East African Anopheles gambiae.

Metabolic resistance to pyrethroid insecticides is widespread in Anopheles mosquitoes and is a major threat to malaria control. DNA markers would aid predictive monitoring of resistance, but few mutations have been discovered outside of insecticide-targeted genes. Isofemale family pools from a wild Ugandan Anopheles gambiae population, from an area where operational pyrethroid failure is suspected, were genotyped using a candidate-gene enriched SNP array. Resistance-associated SNPs were detected in three genes from detoxification superfamilies, in addition to the insecticide target site (the Voltage Gated Sodium Channel gene, Vgsc). The putative associations were confirmed for two of the marker SNPs, in the P450 Cyp4j5 and the esterase Coeae1d by reproducible association with pyrethroid resistance in multiple field collections from Uganda and Kenya, and together with the Vgsc-1014S (kdr) mutation these SNPs explained around 20% of variation in resistance. Moreover, the >20 Mb 2La inversion also showed evidence of association with resistance as did environmental humidity. Sequencing of Cyp4j5 and Coeae1d detected no resistance-linked loss of diversity, suggesting selection from standing variation. Our study provides novel, regionally-validated DNA assays for resistance to the most important insecticide class, and establishes both 2La karyotype variation and humidity as common factors impacting the resistance phenotype