43 results on '"Muskavitch, Marc A. T."'
Search Results
2. Sequencing of Culex quinquefasciatus Establishes a Platform for Mosquito Comparative Genomics
- Author
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Arensburger, Peter, Megy, Karine, Waterhouse, Robert M., Abrudan, Jenica, Amedeo, Paolo, Antelo, Beatriz, Bartholomay, Lyric, Bidwell, Shelby, Caler, Elisabet, Camara, Francisco, Campbell, Corey L., Campbell, Kathryn S., Casola, Claudio, Castro, Marta T., Chandramouliswaran, Ishwar, Chapman, Sinéad B., Christley, Scott, Costas, Javier, Eisenstadt, Eric, Feschotte, Cedric, Fraser-Liggett, Claire, Guigo, Roderic, Haas, Brian, Hammond, Martin, Hansson, Bill S., Hemingway, Janet, Hill, Sharon R., Howarth, Clint, Ignell, Rickard, Kennedy, Ryan C., Kodira, Chinnappa D., Lobo, Neil F., Mao, Chunhong, Mayhew, George, Michel, Kristin, Mori, Akio, Liu, Nannan, Naveira, Horado, Nene, Vishvanath, Nguyen, Nam, Pearson, Matthew D., Pritham, Ellen J., Puiu, Daniela, Qi, Yumin, Ranson, Hilary, Ribeiro, Jose M. C., Roberston, Hugh M., Severson, David W., Shumway, Martin, Stanke, Mario, Strausberg, Robert L., Sun, Cheng, Sutton, Granger, Tubio, Jose Manuel C., Unger, Maria F., Vanlandingham, Dana L., Vilella, Albert J., White, Owen, White, Jared R., Wondji, Charles S., Wortman, Jennifer, Zdobnov, Evgeny M., Birren, Bruce, Christensen, Bruce M., Collins, Frank H., Cornel, Anthony, Dimopoulos, George, Hannick, Linda I., Higgs, Stephen, Lanzaro, Gregory C., Lawson, Daniel, Lee, Norman H., Muskavitch, Marc A. T., Raikhel, Alexander S., and Atkinson, Peter W.
- Published
- 2010
3. Pathogenomics of Culex quinquefasciatus and Meta-Analysis of Infection Responses to Diverse Pathogens
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Bartholomay, Lyric C., Waterhouse, Robert M., Mayhew, George F., Campbell, Corey L., Michel, Kristin, Zou, Zhen, Ramirez, Jose L., Das, Suchismita, Alvarez, Kanwal, Arensburger, Peter, Bryant, Bart, Chapman, Sinead B., Dong, Yuemei, Erickson, Sara M., Karunaratne, S. H. P. Parakrama, Kokoza, Vladimir, Kodira, Chinnappa D., Pignatelli, Patricia, Shin, Sang Woon, Vanlandingham, Dana L., Atkinson, Peter W., Birren, Bruce, Christophides, George K., Clem, Rollie J., Hemingway, Janet, Higgs, Stephen, Megy, Karine, Ranson, Hilary, Zdobnov, Evgeny M., Raikhel, Alexander S., Christensen, Bruce M., Dimopoulos, George, and Muskavitch, Marc A. T.
- Published
- 2010
4. Modulation of TRPA1 thermal sensitivity enables sensory discrimination in Drosophila
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Kang, Kyeongjin, Panzano, Vincent C., Chang, Elaine C., Ni, Lina, Dainis, Alexandra M., Jenkins, Adam M., Regna, Kimberly, Muskavitch, Marc A. T., and Garrity, Paul A.
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- 2012
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5. RNAi Trigger Delivery into Anopheles gambiae Pupae
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Regna, Kimberly, primary, Harrison, Rachel M., primary, Heyse, Shannon A., primary, Chiles, Thomas C., primary, Michel, Kristin, primary, and Muskavitch, Marc A. T., primary
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- 2016
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6. Highly evolvable malaria vectors: The genomes of 16 Anopheles mosquitoes
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Neafsey, Daniel E., primary, Waterhouse, Robert M., additional, Abai, Mohammad R., additional, Aganezov, Sergey S., additional, Alekseyev, Max A., additional, Allen, James E., additional, Amon, James, additional, Arcà, Bruno, additional, Arensburger, Peter, additional, Artemov, Gleb, additional, Assour, Lauren A., additional, Basseri, Hamidreza, additional, Berlin, Aaron, additional, Birren, Bruce W., additional, Blandin, Stephanie A., additional, Brockman, Andrew I., additional, Burkot, Thomas R., additional, Burt, Austin, additional, Chan, Clara S., additional, Chauve, Cedric, additional, Chiu, Joanna C., additional, Christensen, Mikkel, additional, Costantini, Carlo, additional, Davidson, Victoria L. M., additional, Deligianni, Elena, additional, Dottorini, Tania, additional, Dritsou, Vicky, additional, Gabriel, Stacey B., additional, Guelbeogo, Wamdaogo M., additional, Hall, Andrew B., additional, Han, Mira V., additional, Hlaing, Thaung, additional, Hughes, Daniel S. T., additional, Jenkins, Adam M., additional, Jiang, Xiaofang, additional, Jungreis, Irwin, additional, Kakani, Evdoxia G., additional, Kamali, Maryam, additional, Kemppainen, Petri, additional, Kennedy, Ryan C., additional, Kirmitzoglou, Ioannis K., additional, Koekemoer, Lizette L., additional, Laban, Njoroge, additional, Langridge, Nicholas, additional, Lawniczak, Mara K. N., additional, Lirakis, Manolis, additional, Lobo, Neil F., additional, Lowy, Ernesto, additional, MacCallum, Robert M., additional, Mao, Chunhong, additional, Maslen, Gareth, additional, Mbogo, Charles, additional, McCarthy, Jenny, additional, Michel, Kristin, additional, Mitchell, Sara N., additional, Moore, Wendy, additional, Murphy, Katherine A., additional, Naumenko, Anastasia N., additional, Nolan, Tony, additional, Novoa, Eva M., additional, O’Loughlin, Samantha, additional, Oringanje, Chioma, additional, Oshaghi, Mohammad A., additional, Pakpour, Nazzy, additional, Papathanos, Philippos A., additional, Peery, Ashley N., additional, Povelones, Michael, additional, Prakash, Anil, additional, Price, David P., additional, Rajaraman, Ashok, additional, Reimer, Lisa J., additional, Rinker, David C., additional, Rokas, Antonis, additional, Russell, Tanya L., additional, Sagnon, N’Fale, additional, Sharakhova, Maria V., additional, Shea, Terrance, additional, Simão, Felipe A., additional, Simard, Frederic, additional, Slotman, Michel A., additional, Somboon, Pradya, additional, Stegniy, Vladimir, additional, Struchiner, Claudio J., additional, Thomas, Gregg W. C., additional, Tojo, Marta, additional, Topalis, Pantelis, additional, Tubio, José M. C., additional, Unger, Maria F., additional, Vontas, John, additional, Walton, Catherine, additional, Wilding, Craig S., additional, Willis, Judith H., additional, Wu, Yi-Chieh, additional, Yan, Guiyun, additional, Zdobnov, Evgeny M., additional, Zhou, Xiaofan, additional, Catteruccia, Flaminia, additional, Christophides, George K., additional, Collins, Frank H., additional, Cornman, Robert S., additional, Crisanti, Andrea, additional, Donnelly, Martin J., additional, Emrich, Scott J., additional, Fontaine, Michael C., additional, Gelbart, William, additional, Hahn, Matthew W., additional, Hansen, Immo A., additional, Howell, Paul I., additional, Kafatos, Fotis C., additional, Kellis, Manolis, additional, Lawson, Daniel, additional, Louis, Christos, additional, Luckhart, Shirley, additional, Muskavitch, Marc A. T., additional, Ribeiro, José M., additional, Riehle, Michael A., additional, Sharakhov, Igor V., additional, Tu, Zhijian, additional, Zwiebel, Laurence J., additional, and Besansky, Nora J., additional
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- 2015
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7. Metabolic and Target-Site Mechanisms Combine to Confer Strong DDT Resistance in Anopheles gambiae
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Mitchell, Sara N., primary, Rigden, Daniel J., additional, Dowd, Andrew J., additional, Lu, Fang, additional, Wilding, Craig S., additional, Weetman, David, additional, Dadzie, Samuel, additional, Jenkins, Adam M., additional, Regna, Kimberly, additional, Boko, Pelagie, additional, Djogbenou, Luc, additional, Muskavitch, Marc A. T., additional, Ranson, Hilary, additional, Paine, Mark J. I., additional, Mayans, Olga, additional, and Donnelly, Martin J., additional
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- 2014
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8. CYP6 P450 Enzymes and ACE-1 Duplication Produce Extreme and Multiple Insecticide Resistance in the Malaria Mosquito Anopheles gambiae
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Edi, Constant V., primary, Djogbénou, Luc, additional, Jenkins, Adam M., additional, Regna, Kimberly, additional, Muskavitch, Marc A. T., additional, Poupardin, Rodolphe, additional, Jones, Christopher M., additional, Essandoh, John, additional, Kétoh, Guillaume K., additional, Paine, Mark J. I., additional, Koudou, Benjamin G., additional, Donnelly, Martin J., additional, Ranson, Hilary, additional, and Weetman, David, additional
- Published
- 2014
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9. Genetic Dissection of Anopheles gambiae Gut Epithelial Responses to Serratia marcescens
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Stathopoulos, Stavros, primary, Neafsey, Daniel E., additional, Lawniczak, Mara K. N., additional, Muskavitch, Marc A. T., additional, and Christophides, George K., additional
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- 2014
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10. The Evolution of the Anopheles 16 Genomes Project
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Neafsey, Daniel E, primary, Christophides, George K, additional, Collins, Frank H, additional, Emrich, Scott J, additional, Fontaine, Michael C, additional, Gelbart, William, additional, Hahn, Matthew W, additional, Howell, Paul I, additional, Kafatos, Fotis C, additional, Lawson, Daniel, additional, Muskavitch, Marc A T, additional, Waterhouse, Robert M, additional, Williams, Louise J, additional, and Besansky, Nora J, additional
- Published
- 2013
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11. Malaria infection does not affect the sensitivity of peripheral receptor neurons in Anopheles stephensi
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Grant, Alan J, primary, Muskavitch, Marc A T, additional, and O’Connell, Robert J, additional
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- 2013
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12. Breakdown in the Process of Incipient Speciation in Anopheles gambiae
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Nwakanma, Davis C, primary, Neafsey, Daniel E, additional, Jawara, Musa, additional, Adiamoh, Majidah, additional, Lund, Emily, additional, Rodrigues, Amabelia, additional, Loua, Kovana M, additional, Konate, Lassana, additional, Sy, Ngayo, additional, Dia, Ibrahima, additional, Awolola, T Samson, additional, Muskavitch, Marc A T, additional, and Conway, David J, additional
- Published
- 2013
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13. A critical role for the Drosophila dopamine D1-like receptor Dop1R2 at the onset of metamorphosis.
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Regna, Kimberly, Kurshan, Peri T., Harwood, Benjamin N., Jenkins, Adam M., Chao-Qiang Lai, Muskavitch, Marc A. T., Kopin, Alan S., and Draper, Isabelle
- Subjects
DOPAMINE ,RNA interference ,G protein coupled receptors ,DROSOPHILA ,ECDYSONE - Abstract
Background: Insect metamorphosis relies on temporal and spatial cues that are precisely controlled. Previous studies in Drosophila have shown that untimely activation of genes that are essential to metamorphosis results in growth defects, developmental delay and death. Multiple factors exist that safeguard these genes against dysregulated expression. The list of identified negative regulators that play such a role in Drosophila development continues to expand. Results: By using RNAi transgene-induced gene silencing coupled to spatio/temporal assessment, we have unraveled an important role for the Drosophila dopamine 1-like receptor, Dop1R2, in development. We show that Dop1R2 knockdown leads to pre-adult lethality. In adults that escape death, abnormal wing expansion and/or melanization defects occur. Furthermore we show that salivary gland expression of this GPCR during the late larval/prepupal stage is essential for the flies to survive through adulthood. In addition to RNAi-induced effects, treatment of larvae with the high affinity D1-like receptor antagonist flupenthixol, also results in developmental arrest, and in morphological defects comparable to those seen in Dop1R2 RNAi flies. To examine the basis for pupal lethality in Dop1R2 RNAi flies, we carried out transcriptome analysis. These studies revealed up-regulation of genes that respond to ecdysone, regulate morphogenesis and/or modulate defense/immunity. Conclusion: Taken together our findings suggest a role for Dop1R2 in the repression of genes that coordinate metamorphosis. Premature release of this inhibition is not tolerated by the developing fly. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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14. Patterns of Genomic Differentiation between Ecologically Differentiated M and S Forms of Anopheles gambiae in West and Central Africa
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Reidenbach, Kyanne R., primary, Neafsey, Daniel E., additional, Costantini, Carlo, additional, Sagnon, N’Fale, additional, Simard, Frédéric, additional, Ragland, Gregory J., additional, Egan, Scott P., additional, Feder, Jeffrey L., additional, Muskavitch, Marc A. T., additional, and Besansky, Nora J., additional
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- 2012
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15. Modulation of TRPA1 thermal sensitivity enables sensory discrimination in Drosophila
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Kang, Kyeongjin, primary, Panzano, Vincent C., additional, Chang, Elaine C., additional, Ni, Lina, additional, Dainis, Alexandra M., additional, Jenkins, Adam M., additional, Regna, Kimberly, additional, Muskavitch, Marc A. T., additional, and Garrity, Paul A., additional
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- 2011
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16. A Screen for Modifiers of Notch Signaling Uncovers Amun, a Protein With a Critical Role in Sensory Organ Development
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Shalaby, Nevine A, primary, Parks, Annette L, additional, Morreale, Eric J, additional, Osswalt, Marisa C, additional, Pfau, Kristen M, additional, Pierce, Eric L, additional, and Muskavitch, Marc A T, additional
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- 2009
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17. Long non-coding RNA discovery across the genus anopheles reveals conserved secondary structures within and beyond the Gambiae complex.
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Jenkins, Adam M., Waterhouse, Robert M., and Muskavitch, Marc A. T.
- Subjects
NON-coding RNA ,NUCLEOPROTEINS ,NUCLEIC acids ,EPIGENETICS ,GENETIC regulation ,RNA - Abstract
Background: Long non-coding RNAs (lncRNAs) have been defined as mRNA-like transcripts longer than 200 nucleotides that lack significant protein-coding potential, and many of them constitute scaffolds for ribonucleoprotein complexes with critical roles in epigenetic regulation. Various lncRNAs have been implicated in the modulation of chromatin structure, transcriptional and post-transcriptional gene regulation, and regulation of genomic stability in mammals, Caenorhabditis elegans, and Drosophila melanogaster. The purpose of this study is to identify the lncRNA landscape in the malaria vector An. gambiae and assess the evolutionary conservation of lncRNAs and their secondary structures across the Anopheles genus. Results: Using deep RNA sequencing of multiple Anopheles gambiae life stages, we have identified 2,949 lncRNAs and more than 300 previously unannotated putative protein-coding genes. The lncRNAs exhibit differential expression profiles across life stages and adult genders. We find that across the genus Anopheles, lncRNAs display much lower sequence conservation than protein-coding genes. Additionally, we find that lncRNA secondary structure is highly conserved within the Gambiae complex, but diverges rapidly across the rest of the genus Anopheles. Conclusions: This study offers one of the first lncRNA secondary structure analyses in vector insects. Our description of lncRNAs in An. gambiae offers the most comprehensive genome-wide insights to date into lncRNAs in this vector mosquito, and defines a set of potential targets for the development of vector-based interventions that may further curb the human malaria burden in disease-endemic countries. [ABSTRACT FROM AUTHOR]
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- 2015
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18. Evolution of an Epigenetic Gene Ensemble within the Genus Anopheles.
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Jenkins, Adam M. and Muskavitch, Marc A. T.
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EPIGENETICS , *ANOPHELES , *MOSQUITOES , *HOMEOSTASIS , *PHYSIOLOGICAL control systems - Abstract
Epigenetic control of gene expression has important implications for the regulation of developmental processes, for mediating homeostasis and responses to the external environment, and for transgenerational inheritance of gene expression patterns. Genes that mediate epigenetic control have been well-characterized in Drosophila melanogaster, and we have identified and analyzed an orthologous gene ensemble in Anopheles gambiae that comprises 169 orthologs related to a 215-member epigenetic gene ensemble in D. melanogaster. We find that this ensemble is highly conserved among anopheline mosquitoes, as we identify only seven gene family expansion/contraction events within the ensemble among 12mosquito species we have studied within the genus Anopheles. Comparative analyses of the epigenetic gene expression across the genera Drosophila and Anopheles reveal distinct tissue-associated expression patterns in the two genera, but similar temporal expression patterns. The A. gambiae complex and D. melanogaster subgroup epigenetic gene ensembles exhibit similar evolutionary rates, as assessed by their respective dN/dS values. These differences in tissue-associated expression patterns, in contrast to similarities in evolutionary rates and temporal expression patterns, may imply that some members of the epigenetic gene ensemble have been redeployed within one or both genera, in comparison to the most recent common ancestor of these two clades. Members of this epigenetic gene ensemble may constitute another set of potential targets for vector control and enable further reductions in the burden of humanmalaria, by analogy to recent success in development of small molecule antagonists for mammalian epigenetic machinery. [ABSTRACT FROM AUTHOR]
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- 2015
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19. Structure–Function Analysis of Delta Trafficking, Receptor Binding and Signaling in Drosophila
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Parks, Annette L, primary, Stout, Jane R, additional, Shepard, Scott B, additional, Klueg, Kristin M, additional, Dos Santos, Ana A, additional, Parody, Todd R, additional, Vaskova, Martina, additional, and Muskavitch, Marc A T, additional
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- 2006
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20. Print Media Coverage of Antibiotic Resistance
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Desilva, Malini, primary, Muskavitch, Marc A. T., additional, and Roche, John P., additional
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- 2004
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21. Limited Precision in Print Media Communication of West Nile Virus Risks
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Roche, John P., primary and Muskavitch, Marc A. T., additional
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- 2003
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22. Ligand endocytosis drives receptor dissociation and activation in the Notch pathway
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Parks, Annette L., primary, Klueg, Kristin M., additional, Stout, Jane R., additional, and Muskavitch, Marc A. T., additional
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- 2000
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23. Metabolic and Target-Site Mechanisms Combine to Confer Strong DDT Resistance in Anopheles gambiae.
- Author
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Mitchell, Sara N., Rigden, Daniel J., Dowd, Andrew J., Lu, Fang, Wilding, Craig S., Weetman, David, Dadzie, Samuel, Jenkins, Adam M., Regna, Kimberly, Boko, Pelagie, Djogbenou, Luc, Muskavitch, Marc A. T., Ranson, Hilary, Paine, Mark J. I., Mayans, Olga, and Donnelly, Martin J.
- Subjects
DDT (Insecticide) ,ANOPHELES gambiae ,METABOLIC detoxification ,GENETIC polymorphisms ,RECOMBINANT proteins ,X-ray crystallography - Abstract
The development of resistance to insecticides has become a classic exemplar of evolution occurring within human time scales. In this study we demonstrate how resistance to DDT in the major African malaria vector Anopheles gambiae is a result of both target-site resistance mechanisms that have introgressed between incipient species (the M- and S-molecular forms) and allelic variants in a DDT-detoxifying enzyme. Sequencing of the detoxification enzyme, Gste2, from DDT resistant and susceptible strains of An. gambiae, revealed a non-synonymous polymorphism (I114T), proximal to the DDT binding domain, which segregated with strain phenotype. Recombinant protein expression and DDT metabolism analysis revealed that the proteins from the susceptible strain lost activity at higher DDT concentrations, characteristic of substrate inhibition. The effect of I114T on GSTE2 protein structure was explored through X-ray crystallography. The amino acid exchange in the DDT-resistant strain introduced a hydroxyl group nearby the hydrophobic DDT-binding region. The exchange does not result in structural alterations but is predicted to facilitate local dynamics and enzyme activity. Expression of both wild-type and 114T alleles the allele in Drosophila conferred an increase in DDT tolerance. The 114T mutation was significantly associated with DDT resistance in wild caught M-form populations and acts in concert with target-site mutations in the voltage gated sodium channel (Vgsc-1575Y and Vgsc-1014F) to confer extreme levels of DDT resistance in wild caught An. gambiae. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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24. Genetic Dissection of Anopheles gambiae Gut Epithelial Responses to Serratia marcescens.
- Author
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Stathopoulos, Stavros, Neafsey, Daniel E., Lawniczak, Mara K. N., Muskavitch, Marc A. T., and Christophides, George K.
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ANOPHELES gambiae ,MALARIA transmission ,PLASMODIUM ,GENE expression in viruses ,GENE expression profiling ,SINGLE nucleotide polymorphisms - Abstract
Genetic variation in the mosquito Anopheles gambiae profoundly influences its ability to transmit malaria. Mosquito gut bacteria are shown to influence the outcome of infections with Plasmodium parasites and are also thought to exert a strong drive on genetic variation through natural selection; however, a link between antibacterial effects and genetic variation is yet to emerge. Here, we combined SNP genotyping and expression profiling with phenotypic analyses of candidate genes by RNAi-mediated silencing and 454 pyrosequencing to investigate this intricate biological system. We identified 138 An. gambiae genes to be genetically associated with the outcome of Serratia marcescens infection, including the peptidoglycan recognition receptor PGRPLC that triggers activation of the antibacterial IMD/REL2 pathway and the epidermal growth factor receptor EGFR. Silencing of three genes encoding type III fibronectin domain proteins (FN3Ds) increased the Serratia load and altered the gut microbiota composition in favor of Enterobacteriaceae. These data suggest that natural genetic variation in immune-related genes can shape the bacterial population structure of the mosquito gut with high specificity. Importantly, FN3D2 encodes a homolog of the hypervariable pattern recognition receptor Dscam, suggesting that pathogen-specific recognition may involve a broader family of immune factors. Additionally, we showed that silencing the gene encoding the gustatory receptor Gr9 that is also associated with the Serratia infection phenotype drastically increased Serratia levels. The Gr9 antibacterial activity appears to be related to mosquito feeding behavior and to mostly rely on changes of neuropeptide F expression, together suggesting a behavioral immune response following Serratia infection. Our findings reveal that the mosquito response to oral Serratia infection comprises both an epithelial and a behavioral immune component. [ABSTRACT FROM AUTHOR]
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- 2014
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25. CYP6 P450 Enzymes and ACE-1 Duplication Produce Extreme and Multiple Insecticide Resistance in the Malaria Mosquito Anopheles gambiae.
- Author
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Edi, Constant V., Djogbénou, Luc, Jenkins, Adam M., Regna, Kimberly, Muskavitch, Marc A. T., Poupardin, Rodolphe, Jones, Christopher M., Essandoh, John, Kétoh, Guillaume K., Paine, Mark J. I., Koudou, Benjamin G., Donnelly, Martin J., Ranson, Hilary, and Weetman, David
- Subjects
ANOPHELES gambiae ,INSECTICIDE resistance ,PYRETHROIDS ,MALARIA ,ENZYMES - Abstract
Malaria control relies heavily on pyrethroid insecticides, to which susceptibility is declining in Anopheles mosquitoes. To combat pyrethroid resistance, application of alternative insecticides is advocated for indoor residual spraying (IRS), and carbamates are increasingly important. Emergence of a very strong carbamate resistance phenotype in Anopheles gambiae from Tiassalé, Côte d'Ivoire, West Africa, is therefore a potentially major operational challenge, particularly because these malaria vectors now exhibit resistance to multiple insecticide classes. We investigated the genetic basis of resistance to the most commonly-applied carbamate, bendiocarb, in An. gambiae from Tiassalé. Geographically-replicated whole genome microarray experiments identified elevated P450 enzyme expression as associated with bendiocarb resistance, most notably genes from the CYP6 subfamily. P450s were further implicated in resistance phenotypes by induction of significantly elevated mortality to bendiocarb by the synergist piperonyl butoxide (PBO), which also enhanced the action of pyrethroids and an organophosphate. CYP6P3 and especially CYP6M2 produced bendiocarb resistance via transgenic expression in Drosophila in addition to pyrethroid resistance for both genes, and DDT resistance for CYP6M2 expression. CYP6M2 can thus cause resistance to three distinct classes of insecticide although the biochemical mechanism for carbamates is unclear because, in contrast to CYP6P3, recombinant CYP6M2 did not metabolise bendiocarb in vitro. Strongly bendiocarb resistant mosquitoes also displayed elevated expression of the acetylcholinesterase ACE-1 gene, arising at least in part from gene duplication, which confers a survival advantage to carriers of additional copies of resistant ACE-1 G119S alleles. Our results are alarming for vector-based malaria control. Extreme carbamate resistance in Tiassalé An. gambiae results from coupling of over-expressed target site allelic variants with heightened CYP6 P450 expression, which also provides resistance across contrasting insecticides. Mosquito populations displaying such a diverse basis of extreme and cross-resistance are likely to be unresponsive to standard insecticide resistance management practices. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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26. Cis-interactions between Delta and Notch modulate neurogenic signalling in Drosophila
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Jacobsen, Thomas L., Brennan, Keith, Arias, Alfonso Martinez, and Muskavitch, Marc A. T.
- Abstract
We find that ectopic expression of Delta or Serrate in neurons within developing bristle organs is capable of non-autonomously inducing the transformation of the pre-trichogen cell into a tormogen cell in a wide variety of developmental contexts. The frequencies at which Delta can induce these transformations are dependent on the level of ectopic Delta expression and the levels of endogenous Notch signalling pathway components. The pre-trichogen cell becomes more responsive to Delta- or Serrate-mediated transformation when the level of endogenous Delta is reduced and less responsive when the dosage of endogenous Delta is increased, supporting the hypothesis that Delta interferes autonomously with the ability of a cell to receive either signal. We also find that a dominant-negative form of Notch, ECN, is capable of autonomously interfering with the ability of a cell to generate the Delta signal. When the region of Notch that mediates trans-interactions between Delta and the Notch extracellular domain is removed from ECN, the ability of Delta to signal is restored. Our findings imply that cell-autonomous interactions between Delta and Notch can affect the ability of a cell to generate and to transduce a Delta-mediated signal. Finally, we present evidence that the Fringe protein can interfere with Delta- and Serrate-mediated signalling within developing bristle organs, in contrast to previous reports of the converse effects of Fringe on Delta signalling in the developing wing.
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- 1998
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27. Implications of dynamic patterns of Delta and Notch expression for cellular interactions during Drosophila development
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Kooh, Pamela J., Fehon, Richard G., and Muskavitch, Marc A. T.
- Abstract
Delta and Notch function are required for cell fate specification in numerous tissues during embryonic and postembryonic Drosophila development. Delta is expressed by all members of interacting cell populations within which fates are being specified and is subsequently down-regulated as cells stably adopt particular fates. Multiphasic expression in the derivatives of many germ layers implies successive requirements for Delta function in a number of tissues. At the cellular level, Delta and Notch expression are generally coincident within developing tissues. At the subcellular level, Delta and Notch are localized in apparent endocytic vesicles during down-regulation from the surfaces of interacting cells, implying an interaction consistent with their proposed roles as signal and receptor in cellular interactions during development.
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- 1993
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28. TheNotch locus of Drosophila melanogaster: A molecular analysis
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Artavanis-Tsakonas, Spyros, primary, Grimwade, Brian G., additional, Harrison, Richard G., additional, Markopoulou, Katerina, additional, Muskavitch, Marc A. T., additional, Schlesinger-Bryant, Ruth, additional, Wharton, Kristi, additional, and Yedvobnick, Barry, additional
- Published
- 1983
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29. Molecular genetics of Delta, a locus required for ectodermal differentiation in Drosophila
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Alton, Althea K., primary, Fechtel, Kim, additional, Kopczynski, Casey C., additional, Shepard, Scott B., additional, Kooh, Pamela J., additional, and Muskavitch, Marc A. T., additional
- Published
- 1989
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30. Crepuscular Behavioral Variation and Profiling of Opsin Genes in Anopheles gambiae and Anopheles stephensi (Diptera: Culicidae)
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Jenkins, Adam M. and Muskavitch, Marc A. T.
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- 2015
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31. CYP6 P450 Enzymes and ACE-1 Duplication Produce Extreme and Multiple Insecticide Resistance in the Malaria Mosquito Anopheles gambiae.
- Author
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Edi, Constant V., Djogbénou, Luc, Jenkins, Adam M., Regna, Kimberly, Muskavitch, Marc A. T., Poupardin, Rodolphe, Jones, Christopher M., Essandoh, John, Kétoh, Guillaume K., Paine, Mark J. I., Koudou, Benjamin G., Donnelly, Martin J., Ranson, Hilary, and Weetman, David
- Subjects
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ANOPHELES gambiae , *INSECTICIDE resistance , *PYRETHROIDS , *MALARIA , *ENZYMES - Abstract
Malaria control relies heavily on pyrethroid insecticides, to which susceptibility is declining in Anopheles mosquitoes. To combat pyrethroid resistance, application of alternative insecticides is advocated for indoor residual spraying (IRS), and carbamates are increasingly important. Emergence of a very strong carbamate resistance phenotype in Anopheles gambiae from Tiassalé, Côte d'Ivoire, West Africa, is therefore a potentially major operational challenge, particularly because these malaria vectors now exhibit resistance to multiple insecticide classes. We investigated the genetic basis of resistance to the most commonly-applied carbamate, bendiocarb, in An. gambiae from Tiassalé. Geographically-replicated whole genome microarray experiments identified elevated P450 enzyme expression as associated with bendiocarb resistance, most notably genes from the CYP6 subfamily. P450s were further implicated in resistance phenotypes by induction of significantly elevated mortality to bendiocarb by the synergist piperonyl butoxide (PBO), which also enhanced the action of pyrethroids and an organophosphate. CYP6P3 and especially CYP6M2 produced bendiocarb resistance via transgenic expression in Drosophila in addition to pyrethroid resistance for both genes, and DDT resistance for CYP6M2 expression. CYP6M2 can thus cause resistance to three distinct classes of insecticide although the biochemical mechanism for carbamates is unclear because, in contrast to CYP6P3, recombinant CYP6M2 did not metabolise bendiocarb in vitro. Strongly bendiocarb resistant mosquitoes also displayed elevated expression of the acetylcholinesterase ACE-1 gene, arising at least in part from gene duplication, which confers a survival advantage to carriers of additional copies of resistant ACE-1 G119S alleles. Our results are alarming for vector-based malaria control. Extreme carbamate resistance in Tiassalé An. gambiae results from coupling of over-expressed target site allelic variants with heightened CYP6 P450 expression, which also provides resistance across contrasting insecticides. Mosquito populations displaying such a diverse basis of extreme and cross-resistance are likely to be unresponsive to standard insecticide resistance management practices. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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- View/download PDF
32. Genetic Dissection of Anopheles gambiae Gut Epithelial Responses to Serratia marcescens.
- Author
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Stathopoulos, Stavros, Neafsey, Daniel E., Lawniczak, Mara K. N., Muskavitch, Marc A. T., and Christophides, George K.
- Subjects
- *
ANOPHELES gambiae , *PLASMODIUM , *GENE expression in viruses , *GENE expression profiling , *SINGLE nucleotide polymorphisms ,MALARIA transmission - Abstract
Genetic variation in the mosquito Anopheles gambiae profoundly influences its ability to transmit malaria. Mosquito gut bacteria are shown to influence the outcome of infections with Plasmodium parasites and are also thought to exert a strong drive on genetic variation through natural selection; however, a link between antibacterial effects and genetic variation is yet to emerge. Here, we combined SNP genotyping and expression profiling with phenotypic analyses of candidate genes by RNAi-mediated silencing and 454 pyrosequencing to investigate this intricate biological system. We identified 138 An. gambiae genes to be genetically associated with the outcome of Serratia marcescens infection, including the peptidoglycan recognition receptor PGRPLC that triggers activation of the antibacterial IMD/REL2 pathway and the epidermal growth factor receptor EGFR. Silencing of three genes encoding type III fibronectin domain proteins (FN3Ds) increased the Serratia load and altered the gut microbiota composition in favor of Enterobacteriaceae. These data suggest that natural genetic variation in immune-related genes can shape the bacterial population structure of the mosquito gut with high specificity. Importantly, FN3D2 encodes a homolog of the hypervariable pattern recognition receptor Dscam, suggesting that pathogen-specific recognition may involve a broader family of immune factors. Additionally, we showed that silencing the gene encoding the gustatory receptor Gr9 that is also associated with the Serratia infection phenotype drastically increased Serratia levels. The Gr9 antibacterial activity appears to be related to mosquito feeding behavior and to mostly rely on changes of neuropeptide F expression, together suggesting a behavioral immune response following Serratia infection. Our findings reveal that the mosquito response to oral Serratia infection comprises both an epithelial and a behavioral immune component. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
33. Metabolic and Target-Site Mechanisms Combine to Confer Strong DDT Resistance in Anopheles gambiae.
- Author
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Mitchell, Sara N., Rigden, Daniel J., Dowd, Andrew J., Lu, Fang, Wilding, Craig S., Weetman, David, Dadzie, Samuel, Jenkins, Adam M., Regna, Kimberly, Boko, Pelagie, Djogbenou, Luc, Muskavitch, Marc A. T., Ranson, Hilary, Paine, Mark J. I., Mayans, Olga, and Donnelly, Martin J.
- Subjects
- *
DDT (Insecticide) , *ANOPHELES gambiae , *METABOLIC detoxification , *GENETIC polymorphisms , *RECOMBINANT proteins , *X-ray crystallography - Abstract
The development of resistance to insecticides has become a classic exemplar of evolution occurring within human time scales. In this study we demonstrate how resistance to DDT in the major African malaria vector Anopheles gambiae is a result of both target-site resistance mechanisms that have introgressed between incipient species (the M- and S-molecular forms) and allelic variants in a DDT-detoxifying enzyme. Sequencing of the detoxification enzyme, Gste2, from DDT resistant and susceptible strains of An. gambiae, revealed a non-synonymous polymorphism (I114T), proximal to the DDT binding domain, which segregated with strain phenotype. Recombinant protein expression and DDT metabolism analysis revealed that the proteins from the susceptible strain lost activity at higher DDT concentrations, characteristic of substrate inhibition. The effect of I114T on GSTE2 protein structure was explored through X-ray crystallography. The amino acid exchange in the DDT-resistant strain introduced a hydroxyl group nearby the hydrophobic DDT-binding region. The exchange does not result in structural alterations but is predicted to facilitate local dynamics and enzyme activity. Expression of both wild-type and 114T alleles the allele in Drosophila conferred an increase in DDT tolerance. The 114T mutation was significantly associated with DDT resistance in wild caught M-form populations and acts in concert with target-site mutations in the voltage gated sodium channel (Vgsc-1575Y and Vgsc-1014F) to confer extreme levels of DDT resistance in wild caught An. gambiae. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
34. Distinct intracellular motifs of Delta mediate its ubiquitylation and activation by Mindbomb11 and Neuralized.
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Daskalaki, Aikaterini, Shalaby, Nevine A., Kux, Kristina, Tsoumpekos, Giorgos, Tsibidis, George D., Muskavitch, Marc A. T., and Delidakis, Christos
- Subjects
- *
PROTEINS , *LIGANDS (Biochemistry) , *GENES , *DROSOPHILA melanogaster , *CELLS , *LYSINE - Abstract
DSL proteins are transmembrane ligands of the Notch receptor. They associate with a RING (really interesting new gene) family E3 ubiquitin ligase, either Neuralized (Neur) or Mindbomb 1 (Mib1), as a prerequisite to signaling. Although Neur and Mibl stimulate internalization of DSL ligands, it is not known how ubiquitylation contributes to signaling. We present a molecular dissection of the intracellular domain (ICD) of Drosophila melanogaster Delta (DI), a prototype DSL protein. Using a cell-based assay, we detected ubiquitylation of DI by both Neur and Mib1. The two enzymes use distinct docking sites and displayed different acceptor lysine preferences on the DI ICD. We generated DI variants that selectively perturb its interactions with Neur or Mibl and analyzed their signaling activity in two in vivo contexts. We found an excellent correlation between the ability to undergo ubiquitylation and signaling. Therefore, ubiquitylation of the DSL ICD seems to be a necessary step in the activation of Notch. [ABSTRACT FROM AUTHOR]
- Published
- 2011
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- View/download PDF
35. A critical role for the Drosophila dopamine D1-like receptor Dop1R2 at the onset of metamorphosis.
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Regna K, Kurshan PT, Harwood BN, Jenkins AM, Lai CQ, Muskavitch MA, Kopin AS, and Draper I
- Subjects
- Animals, Animals, Genetically Modified, Drosophila melanogaster growth & development, Drosophila melanogaster metabolism, Gene Expression Profiling methods, Larva genetics, Larva growth & development, Pupa genetics, Pupa growth & development, RNA Interference, Reverse Transcriptase Polymerase Chain Reaction, Drosophila Proteins genetics, Drosophila melanogaster genetics, Gene Expression Regulation, Developmental, Metamorphosis, Biological genetics, Receptors, Dopamine D1 genetics
- Abstract
Background: Insect metamorphosis relies on temporal and spatial cues that are precisely controlled. Previous studies in Drosophila have shown that untimely activation of genes that are essential to metamorphosis results in growth defects, developmental delay and death. Multiple factors exist that safeguard these genes against dysregulated expression. The list of identified negative regulators that play such a role in Drosophila development continues to expand., Results: By using RNAi transgene-induced gene silencing coupled to spatio/temporal assessment, we have unraveled an important role for the Drosophila dopamine 1-like receptor, Dop1R2, in development. We show that Dop1R2 knockdown leads to pre-adult lethality. In adults that escape death, abnormal wing expansion and/or melanization defects occur. Furthermore we show that salivary gland expression of this GPCR during the late larval/prepupal stage is essential for the flies to survive through adulthood. In addition to RNAi-induced effects, treatment of larvae with the high affinity D1-like receptor antagonist flupenthixol, also results in developmental arrest, and in morphological defects comparable to those seen in Dop1R2 RNAi flies. To examine the basis for pupal lethality in Dop1R2 RNAi flies, we carried out transcriptome analysis. These studies revealed up-regulation of genes that respond to ecdysone, regulate morphogenesis and/or modulate defense/immunity., Conclusion: Taken together our findings suggest a role for Dop1R2 in the repression of genes that coordinate metamorphosis. Premature release of this inhibition is not tolerated by the developing fly.
- Published
- 2016
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36. Mosquito genomics. Highly evolvable malaria vectors: the genomes of 16 Anopheles mosquitoes.
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Neafsey DE, Waterhouse RM, Abai MR, Aganezov SS, Alekseyev MA, Allen JE, Amon J, Arcà B, Arensburger P, Artemov G, Assour LA, Basseri H, Berlin A, Birren BW, Blandin SA, Brockman AI, Burkot TR, Burt A, Chan CS, Chauve C, Chiu JC, Christensen M, Costantini C, Davidson VL, Deligianni E, Dottorini T, Dritsou V, Gabriel SB, Guelbeogo WM, Hall AB, Han MV, Hlaing T, Hughes DS, Jenkins AM, Jiang X, Jungreis I, Kakani EG, Kamali M, Kemppainen P, Kennedy RC, Kirmitzoglou IK, Koekemoer LL, Laban N, Langridge N, Lawniczak MK, Lirakis M, Lobo NF, Lowy E, MacCallum RM, Mao C, Maslen G, Mbogo C, McCarthy J, Michel K, Mitchell SN, Moore W, Murphy KA, Naumenko AN, Nolan T, Novoa EM, O'Loughlin S, Oringanje C, Oshaghi MA, Pakpour N, Papathanos PA, Peery AN, Povelones M, Prakash A, Price DP, Rajaraman A, Reimer LJ, Rinker DC, Rokas A, Russell TL, Sagnon N, Sharakhova MV, Shea T, Simão FA, Simard F, Slotman MA, Somboon P, Stegniy V, Struchiner CJ, Thomas GW, Tojo M, Topalis P, Tubio JM, Unger MF, Vontas J, Walton C, Wilding CS, Willis JH, Wu YC, Yan G, Zdobnov EM, Zhou X, Catteruccia F, Christophides GK, Collins FH, Cornman RS, Crisanti A, Donnelly MJ, Emrich SJ, Fontaine MC, Gelbart W, Hahn MW, Hansen IA, Howell PI, Kafatos FC, Kellis M, Lawson D, Louis C, Luckhart S, Muskavitch MA, Ribeiro JM, Riehle MA, Sharakhov IV, Tu Z, Zwiebel LJ, and Besansky NJ
- Subjects
- Animals, Anopheles classification, Base Sequence, Chromosomes, Insect genetics, Drosophila genetics, Humans, Insect Vectors classification, Molecular Sequence Data, Phylogeny, Sequence Alignment, Anopheles genetics, Evolution, Molecular, Genome, Insect, Insect Vectors genetics, Malaria transmission
- Abstract
Variation in vectorial capacity for human malaria among Anopheles mosquito species is determined by many factors, including behavior, immunity, and life history. To investigate the genomic basis of vectorial capacity and explore new avenues for vector control, we sequenced the genomes of 16 anopheline mosquito species from diverse locations spanning ~100 million years of evolution. Comparative analyses show faster rates of gene gain and loss, elevated gene shuffling on the X chromosome, and more intron losses, relative to Drosophila. Some determinants of vectorial capacity, such as chemosensory genes, do not show elevated turnover but instead diversify through protein-sequence changes. This dynamism of anopheline genes and genomes may contribute to their flexible capacity to take advantage of new ecological niches, including adapting to humans as primary hosts., (Copyright © 2015, American Association for the Advancement of Science.)
- Published
- 2015
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- View/download PDF
37. Application of genomics to field investigations of malaria by the international centers of excellence for malaria research.
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Volkman SK, Ndiaye D, Diakite M, Koita OA, Nwakanma D, Daniels RF, Park DJ, Neafsey DE, Muskavitch MA, Krogstad DJ, Sabeti PC, Hartl DL, and Wirth DF
- Subjects
- Animals, Disease Eradication methods, Disease Eradication organization & administration, Disease Transmission, Infectious prevention & control, Genetic Markers, Genetic Variation, Humans, Insect Vectors parasitology, Malaria, Falciparum epidemiology, Malaria, Falciparum parasitology, Plasmodium falciparum genetics, Plasmodium falciparum pathogenicity, Research Design, Genome, Protozoan, Genomics, International Cooperation, Malaria, Falciparum prevention & control, Research organization & administration
- Abstract
Success of the global research agenda toward eradication of malaria will depend on development of new tools, including drugs, vaccines, insecticides and diagnostics. Genomic information, now available for the malaria parasites, their mosquito vectors, and human host, can be leveraged to both develop these tools and monitor their effectiveness. Although knowledge of genomic sequences for the malaria parasites, Plasmodium falciparum and Plasmodium vivax, have helped advance our understanding of malaria biology, simply knowing this sequence information has not yielded a plethora of new interventions to reduce the burden of malaria. Here we review and provide specific examples of how genomic information has increased our knowledge of parasite biology, focusing on P. falciparum malaria. We then discuss how population genetics can be applied toward the epidemiological and transmission-related goals outlined by the International Centers of Excellence for Malaria Research groups recently established by the National Institutes of Health. Finally, we propose genomics is a research area that can promote coordination and collaboration between various ICEMR groups, and that working together as a community can significantly advance the value of this information toward reduction of the global malaria burden., (Copyright © 2011 Elsevier B.V. All rights reserved.)
- Published
- 2012
- Full Text
- View/download PDF
38. Sahel, savana, riverine and urban malaria in West Africa: Similar control policies with different outcomes.
- Author
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Ceesay SJ, Bojang KA, Nwakanma D, Conway DJ, Koita OA, Doumbia SO, Ndiaye D, Coulibaly TF, Diakité M, Traoré SF, Coulibaly M, Ndiaye JL, Sarr O, Gaye O, Konaté L, Sy N, Faye B, Faye O, Sogoba N, Jawara M, Dao A, Poudiougou B, Diawara S, Okebe J, Sangaré L, Abubakar I, Sissako A, Diarra A, Kéita M, Kandeh B, Long CA, Fairhurst RM, Duraisingh M, Perry R, Muskavitch MA, Valim C, Volkman SK, Wirth DF, and Krogstad DJ
- Subjects
- Africa, Western epidemiology, Animals, Antimalarials pharmacology, Artemisinins pharmacology, Communicable Disease Control organization & administration, Culicidae drug effects, Culicidae parasitology, Disease Transmission, Infectious prevention & control, Drug Combinations, Female, Humans, Insect Bites and Stings parasitology, Insecticide-Treated Bednets, Insecticides pharmacology, Malaria, Falciparum drug therapy, Malaria, Falciparum epidemiology, Malaria, Falciparum parasitology, National Health Programs legislation & jurisprudence, National Health Programs organization & administration, Plasmodium falciparum pathogenicity, Pregnancy, Pregnancy Complications, Parasitic drug therapy, Pregnancy Complications, Parasitic parasitology, Pregnancy Complications, Parasitic prevention & control, Prevalence, Pyrimethamine therapeutic use, Seasons, Sulfadoxine therapeutic use, Communicable Disease Control legislation & jurisprudence, Health Policy legislation & jurisprudence, Malaria, Falciparum prevention & control
- Abstract
The study sites for the West African ICEMR are in three countries (The Gambia, Senegal, Mali) and are located within 750 km of each other. In addition, the National Malaria Control Programmes of these countries have virtually identical policies: (1) Artemisinin Combination Therapies (ACTs) for the treatment of symptomatic Plasmodium falciparum infection, (2) Long-Lasting Insecticide-treated bed Nets (LLINs) to reduce the Entomololgic Inoculation Rate (EIR), and (3) sulfadoxine-pyrimethamine for the Intermittent Preventive Treatment of malaria during pregnancy (IPTp). However, the prevalence of P. falciparum malaria and the status of malaria control vary markedly across the four sites with differences in the duration of the transmission season (from 4-5 to 10-11 months), the intensity of transmission (with EIRs from unmeasurably low to 4-5 per person per month), multiplicity of infection (from a mean of 1.0 to means of 2-5) and the status of malaria control (from areas which have virtually no control to areas that are at the threshold of malaria elimination). The most important priority is the need to obtain comparable data on the population-based prevalence, incidence and transmission of malaria before new candidate interventions or combinations of interventions are introduced for malaria control., (Copyright © 2011 Elsevier B.V. All rights reserved.)
- Published
- 2012
- Full Text
- View/download PDF
39. Improving malaria control in West Africa: interruption of transmission as a paradigm shift.
- Author
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Doumbia SO, Ndiaye D, Koita OA, Diakité M, Nwakanma D, Coulibaly M, Traoré SF, Keating J, Milner DA Jr, Ndiaye JL, Sene PD, Ahouidi A, Dieye TN, Gaye O, Okebe J, Ceesay SJ, Ngwa A, Oriero EC, Konaté L, Sy N, Jawara M, Faye O, Kéita M, Cissé M, Sogoba N, Poudiougou B, Diawara S, Sangaré L, Coulibaly T, Seck I, Abubakar I, Gomis J, Mather FJ, Sissako A, Diarra A, Kandeh B, Whalen C, Moyer B, Nnedu O, Thiero O, Bei AK, Daniels R, Miura K, Long CA, Fairhurst RM, Duraisingh M, Muskavitch MA, D'Alessandro U, Conway DJ, Volkman SK, Valim C, Wirth DF, and Krogstad DJ
- Subjects
- Africa, Western epidemiology, Animals, Anopheles parasitology, Antibodies, Protozoan immunology, Antimalarials pharmacology, Communicable Disease Control legislation & jurisprudence, Communicable Disease Control organization & administration, Drug Resistance, Microbial, Genotype, Humans, Immunity, Cellular, Incidence, Malaria, Falciparum epidemiology, Malaria, Falciparum immunology, Malaria, Falciparum parasitology, National Health Programs organization & administration, Parasitemia epidemiology, Parasitemia immunology, Parasitemia parasitology, Parasitemia prevention & control, Plasmodium falciparum drug effects, Plasmodium falciparum genetics, Plasmodium falciparum immunology, Prevalence, Seasons, Sensitivity and Specificity, Communicable Disease Control methods, Disease Transmission, Infectious prevention & control, Malaria, Falciparum prevention & control, Plasmodium falciparum pathogenicity
- Abstract
With the paradigm shift from the reduction of morbidity and mortality to the interruption of transmission, the focus of malaria control broadens from symptomatic infections in children ≤5 years of age to include asymptomatic infections in older children and adults. In addition, as control efforts intensify and the number of interventions increases, there will be decreases in prevalence, incidence and transmission with additional decreases in morbidity and mortality. Expected secondary consequences of these changes include upward shifts in the peak ages for infection (parasitemia) and disease, increases in the ages for acquisition of antiparasite humoral and cellular immune responses and increases in false-negative blood smears and rapid diagnostic tests. Strategies to monitor these changes must include: (1) studies of the entire population (that are not restricted to children ≤5 or ≤10 years of age), (2) study sites in both cities and rural areas (because of increasing urbanization across sub-Saharan Africa) and (3) innovative strategies for surveillance as the prevalence of infection decreases and the frequency of false-negative smears and rapid diagnostic tests increases., (Copyright © 2011 Elsevier B.V. All rights reserved.)
- Published
- 2012
- Full Text
- View/download PDF
40. Notch: the past, the present, and the future.
- Author
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Artavanis-Tsakonas S and Muskavitch MA
- Subjects
- Animals, Humans, Developmental Biology, Neoplasms metabolism, Receptors, Notch metabolism, Signal Transduction
- Abstract
Proliferating investigations of the Notch pathway have given rise to the Notch "field," which has grown exponentially over the past 30 years. This field, founded by investigations of embryology and genetics in Drosophila, now encompasses many metazoa, including humans. The increasingly diverse scope of the field has engendered an expanding understanding that normal Notch pathway function is central to most developmental decision-making in animals, and that pathway dysfunction is implicated in many diseases, including cancer. We provide a personal view of the foundations and rapid evolution of the Notch field; and we discuss a variety of outstanding conundrums and questions regarding Notch biology, for which answers will be found and refined during the next 30 years., (Copyright 2010 Elsevier Inc. All rights reserved.)
- Published
- 2010
- Full Text
- View/download PDF
41. Chemogenomics and parasitology: small molecules and cell-based assays to study infectious processes.
- Author
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Muskavitch MA, Barteneva N, and Gubbels MJ
- Subjects
- Animals, Combinatorial Chemistry Techniques methods, Humans, Malaria drug therapy, Toxoplasmosis drug therapy, Trypanosomiasis drug therapy, Chemistry, Pharmaceutical, Genomics, Malaria parasitology, Toxoplasmosis parasitology, Trypanosomiasis parasitology
- Abstract
Infectious diseases caused by protozoan parasites--malaria, sleeping sickness, leishmaniasis, Chagas' disease, toxoplasmosis--remain chronic problems for humanity. We lack vaccines and have limited drug options effective against protozoa. Research into anti-protozoan drugs has accelerated with improved in vitro cultivation methods, enhanced genetic accessibility, completed genome sequences for key protozoa, and increased prominence of protozoan diseases on the agendas of well-resourced public figures and foundations. Concurrent advances in high-throughput screening (HTS) technologies and availability of diverse small molecule libraries offer the promise of accelerated discovery of new drug targets and new drugs that will reduce disease burdens imposed on humanity by parasitic protozoa. We provide a status report on HTS technologies in hand and cell-based assays under development for biological investigations and drug discovery directed toward the three best-characterized parasitic protozoa: Trypanosoma brucei, Plasmodium falciparum, and Toxoplasma gondii. We emphasize cell growth assays and new insights into parasite cell biology speeding development of better cell-based assays, useful in primary screens for anti-protozoan drug leads and secondary screens to decipher mechanisms of action of leads identified in growth assays. Small molecules that interfere with specific aspects of protozoan biology, identified in such screens, will be valuable tools for dissecting parasite cell biology and developing anti-protozoan drugs. We discuss potential impacts on drug development of new consortia among academic, corporate, and public partners committed to discovery of new, effective anti-protozoan drugs.
- Published
- 2008
- Full Text
- View/download PDF
42. Notch and suppressor of Hairless regulate levels but not patterns of Delta expression in Drosophila.
- Author
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Parks AL, Shalaby NA, and Muskavitch MA
- Subjects
- Animals, Drosophila growth & development, Eye growth & development, Eye metabolism, Intracellular Signaling Peptides and Proteins, Organ Specificity genetics, Pupa growth & development, Pupa metabolism, Signal Transduction genetics, Drosophila genetics, Drosophila Proteins physiology, Gene Expression Regulation, Developmental physiology, Membrane Proteins biosynthesis, Membrane Proteins genetics, Receptors, Notch physiology, Repressor Proteins physiology
- Abstract
The Notch signal transduction pathway is highly conserved and governs many developmental decisions in metazoans. The ligand Delta, and its receptor Notch, are often expressed in complementary patterns during Drosophila postembryonic development. Notch signaling is thought to play a role in generation of these complementary patterns through feedback mechanisms that regulate Delta and Notch expression. We have examined Delta expression during postembryonic development, following global alteration of Notch-dependent or Su(H)-dependent transcriptional regulation. We find that Notch and Su(H) regulate Delta expression in a manner that varies by context. Surprisingly, we find that wild type Delta expression levels are influenced by Su(H)-dependent mechanisms only in regions of high Delta/low Notch expression. In contrast, Delta expression levels in regions of low Delta/high Notch expression appear to be unaffected by Su(H)-mediated regulation. We conclude that Notch pathway feedback regulation is unlikely to contribute to the generation of complementary patterns in the contexts examined., ((c) 2008 Wiley-Liss, Inc.)
- Published
- 2008
- Full Text
- View/download PDF
43. Creation of a GAL4/UAS-coupled inducible gene expression system for use in Drosophila cultured cell lines.
- Author
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Klueg KM, Alvarado D, Muskavitch MA, and Duffy JB
- Subjects
- Animals, Cell Line, DNA-Binding Proteins, Gene Transfer Techniques, Metallothionein genetics, Promoter Regions, Genetic, Drosophila melanogaster genetics, Enhancer Elements, Genetic, Saccharomyces cerevisiae Proteins genetics, Transcription Factors genetics
- Published
- 2002
- Full Text
- View/download PDF
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