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3. Successful introgression of wMel Wolbachia into Aedes aegypti populations in Fiji, Vanuatu and Kiribati

Author

Simmons, Cameron P., primary, Donald, Wesley, additional, Tagavi, Lekon, additional, Tarivonda, Len, additional, Quai, Timothy, additional, Tavoa, Raynelyn, additional, Noran, Tebikau, additional, Manikaoti, Erirau, additional, Kareaua, Lavinia, additional, Abwai, Tabomoa Tinte, additional, Chand, Dip, additional, Rama, Vineshwaran, additional, Deo, Vimal, additional, Deo, Kharishma Karti, additional, Tavuii, Aminiasi, additional, Valentine, Wame, additional, Prasad, Raviikash, additional, Seru, Eremasi, additional, Naituku, Leikitah, additional, Ratu, Anaseini, additional, Hesketh, Mark, additional, Kenny, Nichola, additional, Beebe, Sarah C., additional, Goundar, Anjali A., additional, McCaw, Andrew, additional, Buntine, Molly, additional, Green, Ben, additional, Frossard, Tibor, additional, Gilles, Jeremie R. L., additional, Joubert, D. Albert, additional, Wilson, Geoff, additional, Duong, Le Quyen, additional, Bouvier, Jean B, additional, Stanford, Darren, additional, Forder, Carolyn, additional, Duyvestyn, Johanna M., additional, Pacidônio, Etiene C., additional, Flores, Heather A., additional, Wittmeier, Natalie, additional, Retzki, Kate, additional, Ryan, Peter A., additional, Denton, Jai A., additional, Smithyman, Ruth, additional, Tanamas, Stephanie K., additional, Kyrylos, Peter, additional, Dong, Yi, additional, Khalid, Anam, additional, Hodgson, Lauren, additional, Anders, Katherine L., additional, and O’Neill, Scott L., additional

Published
2024
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6. Antiviral Wolbachia strains associate with Aedes aegypti endoplasmic reticulum membranes and induce lipid droplet formation to restrict dengue virus replication

Author

Loterio, Robson K., primary, Monson, Ebony A., additional, Templin, Rachel, additional, de Bruyne, Jyotika T., additional, Flores, Heather A., additional, Mackenzie, Jason M., additional, Ramm, Georg, additional, Helbig, Karla J., additional, Simmons, Cameron P., additional, and Fraser, Johanna E., additional

Published
2024
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7. AntiviralWolbachiastrains associate withAedes aegyptiendoplasmic reticulum membranes and disturb host cell lipid distribution to restrict dengue virus replication.

Author

Kriiger-Loterio, Robson, primary, Monson, Ebony, additional, Templin, Rachel, additional, Bruyne, Jyotika T., additional, Flores, Heather A, additional, Mackenzie, Jason, additional, Ramm, Georg, additional, Helbig, Karla, additional, Simmons, Cameron P, additional, and Fraser, Johanna Elisabeth, additional

Published
2023
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10. Genome evolution of dengue virus serotype 1 under selection by Wolbachia pipientis in Aedes aegypti mosquitoes

Author

Thi Hue Kien, Duong, primary, Edenborough, Kathryn M, additional, da Silva Goncalves, Daniela, additional, Thuy Vi, Tran, additional, Casagrande, Etiene, additional, Thi Le Duyen, Huynh, additional, Thi Long, Vo, additional, Thi Dui, Le, additional, Thi Tuyet Nhu, Vu, additional, Thi Giang, Nguyen, additional, Thi Xuan Trang, Huynh, additional, Lee, Elvina, additional, Donovan-Banfield, I’ah, additional, Thi Thuy Van, Huynh, additional, Minh Nguyet, Nguyen, additional, Thanh Phong, Nguyen, additional, Van Vinh Chau, Nguyen, additional, Wills, Bridget, additional, Yacoub, Sophie, additional, Flores, Heather, additional, and Simmons, Cameron P, additional

Published
2023
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14. Transient Introgression of Wolbachia into Aedes aegypti Populations Does Not Elicit an Antibody Response to Wolbachia Surface Protein in Community Members

Author

Lee, Elvina, primary, Nguyen, Tran Hien, additional, Nguyen, Thu Yen, additional, Vu, Sinh Nam, additional, Tran, Nhu Duong, additional, Nghia, Le Trung, additional, Vien, Quang Mai, additional, Nguyen, Thanh Dong, additional, Kriiger Loterio, Robson, additional, Iturbe-Ormaetxe, Iñaki, additional, Flores, Heather, additional, O’Neill, Scott, additional, Dang, Duc Anh, additional, Simmons, Cameron, additional, and Fraser, Johanna, additional

Published
2022
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17. Genome evolution of dengue virus serotype 1 under selection by Wolbachia pipientis in Aedes aegypti mosquitoes.

Author

Duong Thi Hue Kien, Edenborough, Kathryn, da Silva Goncalves, Daniela, Tran Thuy Vi, Casagrande, Etiene, Huynh Thi Le Duyen, Vo Thi Long, Le Thi Dui, Vu Thi Tuyet Nhu, Nguyen Thi Giang, Huynh Thi Xuan Trang, Lee, Elvina, Donovan-Banfeld, I’ah, Huynh Thi Thuy Van, Nguyen Minh Nguyet, Nguyen Thanh Phong, Nguyen Van Vinh Chau, Wills, Bridget, Yacoub, Sophie, and Flores, Heather

Abstract

The introgression of antiviral strains of Wolbachia into Aedes aegypti mosquito populations is a public health intervention for the control of dengue. Plausibly, dengue virus (DENV) could evolve to bypass the antiviral effects of Wolbachia and undermine this approach. Here, we established a serial-passage system to investigate the evolution of DENV in Ae. aegypti mosquitoes infected with the wMel strain of Wolbachia. Using this system, we report on virus genetic outcomes after twenty passages of serotype 1 of DENV (DENV-1). An amino acid substitution, E203K, in the DENV-1 envelope protein was more frequently detected in the consensus sequence of virus populations passaged in wMel-infected Ae. aegypti than wild-type counterparts. Positive selection at residue 203 was reproducible; it occurred in passaged virus populations from independent DENV-1-infected patients and also in a second, independent experimental system. In wild-type mosquitoes and human cells, the 203K variant was rapidly replaced by the progenitor sequence. These fndings provide proof of concept that wMel-associated selection of virus populations can occur in experimental conditions. Field-based studies are needed to explore whether wMel imparts selective pressure on DENV evolution in locations where wMel is established. [ABSTRACT FROM AUTHOR]

Published
2023
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18. Assessment of fitness and vector competence of a New Caledonia wMel Aedes aegypti strain before field-release

Author

Pocquet, Nicolas, primary, O’Connor, Olivia, additional, Flores, Heather A., additional, Tutagata, Jordan, additional, Pol, Morgane, additional, Hooker, David J., additional, Inizan, Catherine, additional, Russet, Sylvie, additional, Duyvestyn, Johanna M., additional, Pacidônio, Etiene C., additional, Girault, Dominique, additional, da Silva Gonçalves, Daniela, additional, Minier, Marine, additional, Touzain, Frédéric, additional, Chalus, Elodie, additional, Lucien, Kevin, additional, Cheilan, Florie, additional, Derycke, Tristan, additional, Laumond, Sylvie, additional, Simmons, Cameron P., additional, Dupont-Rouzeyrol, Myrielle, additional, and Rossi, Nadège, additional

Published
2021
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19. wMel Wolbachia genome remains stable after 7 years in Australian Aedes aegypti field populations

Author

Dainty, Kimberley R., primary, Hawkey, Jane, additional, Judd, Louise M., additional, Pacidônio, Etiene C., additional, Duyvestyn, Johanna M., additional, Gonçalves, Daniela S., additional, Lin, Silk Yu, additional, O'Donnell, Tanya B., additional, O'Neill, Scott L., additional, Simmons, Cameron P., additional, Holt, Kathryn E., additional, and Flores, Heather A., additional

Published
2021
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26. Multiple Wolbachia strains provide comparative levels of protection against dengue virus infection in Aedes aegypti

Author

Flores, Heather A., primary, Taneja de Bruyne, Jyotika, additional, O’Donnell, Tanya B., additional, Tuyet Nhu, Vu, additional, Thi Giang, Nguyen, additional, Thi Xuan Trang, Huynh, additional, Thi Thuy Van, Huynh, additional, Thi Long, Vo, additional, Thi Dui, Le, additional, Le Anh Huy, Huynh, additional, Thi Le Duyen, Huynh, additional, Thi Van Thuy, Nguyen, additional, Thanh Phong, Nguyen, additional, Van Vinh Chau, Nguyen, additional, Thi Hue Kien, Duong, additional, Thuy Vi, Tran, additional, Wills, Bridget, additional, O’Neill, Scott L., additional, Simmons, Cameron P., additional, and Carrington, Lauren B., additional

Published
2020
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28. COST BENEFIT ANALYSIS OF THE NAVY 2-PIECE FLAME RESISTANT UNIFORM

Author

Dungey, Gibb A., Mohan, Brij, Flores, Heather M., Dillard, John T., Sullivan, Ryan S., and Graduate School of Business and Public Policy (GSBPP)

Subjects
Navy 2-Piece uniform, flame resistant uniform
Abstract

MBA Professional Project This research used afloat uniforms of the United States Navy to explain the costs and benefits of implementing the Navy 2-Piece (PC) flame-resistant uniform. This study examined the history and characteristics of Navy afloat uniforms. It analyzed benefits and costs of implementing the new flame-resistant 2-PC uniform as an additional at sea uniform along with the current improved flame-resistant variant (IFRV) coveralls. The research concluded that even though course of action (COA) 3 (Status Quo) produces the lowest cost, the improved flame-resistant coverall does not provide the versatility and capability that the 2-PC uniform offers sailors to operate in all climates, environments, and workspaces on a daily basis. In comparison to the flame-resistant coverall, the 2-PC has no limitations and delivers the advantages of being deckplate-driven, improving the quality of life and work, satisfying all communities, and offering a better fit and more comfort. COA 2 has a net benefit of -$85,174,785.00, which is not a viable choice as it does not deliver any benefits. Our study has concluded that COA 1 would be the best option, because it will produce a net benefit of $20,637,638.00 while providing numerous non-monetized benefits to our sailors. http://archive.org/details/costbenefitanaly1094561228 Lieutenant Commander, United States Navy Lieutenant Commander, United States Navy Lieutenant Commander, United States Navy

Published
2018

29. COST BENEFIT ANALYSIS OF THE NAVY 2-PIECE FLAME RESISTANT UNIFORM

Author

Dillard, John T., Sullivan, Ryan S., Graduate School of Business and Public Policy (GSBPP), Dungey, Gibb A., Mohan, Brij, Flores, Heather M., Dillard, John T., Sullivan, Ryan S., Graduate School of Business and Public Policy (GSBPP), Dungey, Gibb A., Mohan, Brij, and Flores, Heather M.

Abstract

MBA Professional Project, This research used afloat uniforms of the United States Navy to explain the costs and benefits of implementing the Navy 2-Piece (PC) flame-resistant uniform. This study examined the history and characteristics of Navy afloat uniforms. It analyzed benefits and costs of implementing the new flame-resistant 2-PC uniform as an additional at sea uniform along with the current improved flame-resistant variant (IFRV) coveralls. The research concluded that even though course of action (COA) 3 (Status Quo) produces the lowest cost, the improved flame-resistant coverall does not provide the versatility and capability that the 2-PC uniform offers sailors to operate in all climates, environments, and workspaces on a daily basis. In comparison to the flame-resistant coverall, the 2-PC has no limitations and delivers the advantages of being deckplate-driven, improving the quality of life and work, satisfying all communities, and offering a better fit and more comfort. COA 2 has a net benefit of -$85,174,785.00, which is not a viable choice as it does not deliver any benefits. Our study has concluded that COA 1 would be the best option, because it will produce a net benefit of $20,637,638.00 while providing numerous non-monetized benefits to our sailors., http://archive.org/details/costbenefitanaly1094561228, Lieutenant Commander, United States Navy, Lieutenant Commander, United States Navy, Lieutenant Commander, United States Navy

Published
2019

31. COST BENEFIT ANALYSIS OF THE NAVY 2-PIECE FLAME RESISTANT UNIFORM

Author

Dillard, John T., Sullivan, Ryan S., Graduate School of Business and Public Policy (GSBPP), Dungey, Gibb A., Mohan, Brij, Flores, Heather M., Dillard, John T., Sullivan, Ryan S., Graduate School of Business and Public Policy (GSBPP), Dungey, Gibb A., Mohan, Brij, and Flores, Heather M.

Abstract

This research used afloat uniforms of the United States Navy to explain the costs and benefits of implementing the Navy 2-Piece (PC) flame-resistant uniform. This study examined the history and characteristics of Navy afloat uniforms. It analyzed benefits and costs of implementing the new flame-resistant 2-PC uniform as an additional at sea uniform along with the current improved flame-resistant variant (IFRV) coveralls. The research concluded that even though course of action (COA) 3 (Status Quo) produces the lowest cost, the improved flame-resistant coverall does not provide the versatility and capability that the 2-PC uniform offers sailors to operate in all climates, environments, and workspaces on a daily basis. In comparison to the flame-resistant coverall, the 2-PC has no limitations and delivers the advantages of being deckplate-driven, improving the quality of life and work, satisfying all communities, and offering a better fit and more comfort. COA 2 has a net benefit of -$85,174,785.00, which is not a viable choice as it does not deliver any benefits. Our study has concluded that COA 1 would be the best option, because it will produce a net benefit of $20,637,638.00 while providing numerous non-monetized benefits to our sailors.

Published
2018

34. Antitherapeutic antibody-mediated hepatotoxicity of recombinant human Apo2L/TRAIL in the cynomolgus monkey

Author

Zuch de Zafra, Christina L, primary, Ashkenazi, Avi, additional, Darbonne, Walter C, additional, Cheu, Melissa, additional, Totpal, Klara, additional, Ortega, Shirley, additional, Flores, Heather, additional, Walker, Mark D, additional, Kabakoff, Bruce, additional, Lum, Bert L, additional, Mounho-Zamora, Barbara J, additional, Marsters, Scot A, additional, and Dybdal, Noël O, additional

Published
2016
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43. Self-Association of Therapeutic Proteins.

Author

Murphy, Regina M., Tsai, Amos M., Cromwell, Mary E. M., Felten, Chantal, Flores, Heather, Jun Liu, and Shire, Steven J.

Abstract

Protein aggregation is typically thought of as a denaturation process that results in the formation of precipitate. However, native proteins may reversibly selfassociate to form discrete aggregates of dimer, trimer, and higher molecular weight forms. The rates of reversible aggregate association and dissociation vary dramatically from protein to protein and can lead to misconceptions regarding aggregate content if the incorrect assay is used to determine the extent of aggregation. The implications of the formation of these native aggregate states during pharmaceutical development of therapeutic proteins are numerous. For example, self-association of insulin has been exploited to develop a stable protein formulation. Often, however, the formation of these native-type aggregates is undesired and results in several challenges during product development. These challenges may involve the selection of an appropriate method to accurately monitor the level of aggregation, the development of a robust manufacturing process to minimize the level of aggregate created during production, and the selection of appropriate formulation components to minimize the aggregate content of the final product that is delivered to patients. This chapter will provide case studies demonstrating how self-association of therapeutic proteins resulted in challenges to develop robust methods for measurement of the aggregated state, to control physical properties of the pharmaceutical, and to implement a reasonable manufacturing process to limit the amount of these aggregates. In each case, understanding the thermodynamics and kinetics of aggregate association and dissociation played an essential role in the actions taken. [ABSTRACT FROM AUTHOR]

Published
2006
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44. Navigating an Uneven Terrain.

Author

Flores, Heather Jo

Abstract

The article focuses on the connection between privilege and oppression, the concept of decolonization, and friendships for a successful permaculture movement.

Published
2015

48. Evolutionary And Functional Analysis Of The Drosophila Bag Of Marbles Gene

Author

Flores, Heather

Subjects
Drosophila, Bag of marbles, Germline stem cells
Abstract

Reproduction is fundamentally important for organismal fitness. While it is critical that each step in reproduction proceed correctly, many of the genes that regulate these processes are adaptively evolving in response to both internal and external selective pressures. We have previously shown that the bag of marbles (bam) and benign gonial cell neoplasm (bgcn) genes are evolving under rapid, adaptive evolution in D. melanogaster and D. simulans. These genes act at the earliest stages of reproduction, germline stem cell (GSC) regulation. In the first study, I expand population genetic analyses to genes that play a role in GSC regulation and/or genetically interact with bam. I find that multiple GSC regulatory genes show evidence of rapid, adaptive evolution in D. melanogaster and/or D. simulans. These genes play very different roles in the regulation of GSCs, and their diverse functions and expression patterns suggest that multiple selective pressures are acting to drive the evolution of GSC regulatory genes. In a second study, I focused on bam to determine the functional consequences of bam's sequence divergence. I developed a transgenesis assay to determine the ability of a bam orthologs from D. melanogaster and D. simulans to rescue the male and female sterility of a D. melanogaster bam mutation. I found that while D. simulans can rescue D. melanogaster bam male sterility, it fails to fully rescue female sterility suggesting that the selective pressure driving the evolution of bam is present in the female germline. In the final study, I investigated the hypothesis that the bacterial endosymbiont, Wolbachia pipientis, is driving the adaptive evolution of bam. I found that Wolbachia and bam genetically interact by showing that Wolbachia can rescue the fertility defects of a bam hypomorph. I found that D. melanogaster-specific Wolbachia is unable to accumulate as well in the presence of a D. simulans bam ortholog which is consistent with a model that Wolbachia is co-evolving with bam and supports the hypothesis that Wolbachia is driving the adaptive evolution of bam.

Published
2013

49. Multiple Wolbachia strains provide comparative levels of protection against dengue virus infection in Aedes aegypti

Author

Jyotika Taneja De Bruyne, Huynh Thi Thuy Van, Huynh Le Anh Huy, Huynh Thi Le Duyen, Tanya B. O’Donnell, Vo Thi Long, Le Thi Dui, Nguyen Van Vinh Chau, Lauren B. Carrington, Nguyen Thi Van Thuy, Vu Tuyet Nhu, Tran Thuy Vi, Duong Thi Hue Kien, Nguyen Thi Giang, Bridget Wills, Cameron P. Simmons, Nguyen Thanh Phong, Heather A. Flores, Scott Leslie O'Neill, Huynh Thi Xuan Trang, Flores, Heather A [0000-0001-5003-7547], Thi Van Thuy, Nguyen [0000-0001-7298-5724], Van Vinh Chau, Nguyen [0000-0003-4668-1019], Wills, Bridget [0000-0001-9086-8804], O'Neill, Scott L [0000-0002-4131-3615], Carrington, Lauren B [0000-0001-9273-7912], and Apollo - University of Cambridge Repository

Subjects
Serotype, RNA viruses, Male, Viral Diseases, Physiology, viruses, Artificial Gene Amplification and Extension, Dengue virus, Disease Vectors, medicine.disease_cause, Pathology and Laboratory Medicine, Virus Replication, Mosquitoes, Polymerase Chain Reaction, Dengue fever, Aedes, Abdomen, Medicine and Health Sciences, Biology (General), 0303 health sciences, Transmission (medicine), 030302 biochemistry & molecular biology, Eukaryota, virus diseases, Body Fluids, Insects, Infectious Diseases, Blood, Medical Microbiology, Viral Pathogens, Viruses, Wolbachia, Female, Anatomy, Pathogens, Research Article, Arthropoda, QH301-705.5, Immunology, Viremia, Aedes aegypti, Mosquito Vectors, Biology, Research and Analysis Methods, Microbiology, 03 medical and health sciences, Virology, parasitic diseases, Genetics, medicine, Animals, Saliva, Molecular Biology Techniques, Pest Control, Biological, Microbial Pathogens, Molecular Biology, 030304 developmental biology, Bacteria, Flaviviruses, fungi, Organisms, Biology and Life Sciences, Dengue Virus, biochemical phenomena, metabolism, and nutrition, RC581-607, medicine.disease, biology.organism_classification, Invertebrates, Insect Vectors, Species Interactions, Viral replication, Parasitology, Immunologic diseases. Allergy
Abstract

The insect bacterium Wolbachia pipientis is being introgressed into Aedes aegypti populations as an intervention against the transmission of medically important arboviruses. Here we compare Ae. aegypti mosquitoes infected with wMelCS or wAlbB to the widely used wMel Wolbachia strain on an Australian nuclear genetic background for their susceptibility to infection by dengue virus (DENV) genotypes spanning all four serotypes. All Wolbachia-infected mosquitoes were more resistant to intrathoracic DENV challenge than their wildtype counterparts. Blocking of DENV replication was greatest by wMelCS. Conversely, wAlbB-infected mosquitoes were more susceptible to whole body infection than wMel and wMelCS. We extended these findings via mosquito oral feeding experiments, using viremic blood from 36 acute, hospitalised dengue cases in Vietnam, additionally including wMel and wildtype mosquitoes on a Vietnamese nuclear genetic background. As above, wAlbB was less effective at blocking DENV replication in the abdomen compared to wMel and wMelCS. The transmission potential of all Wolbachia-infected mosquito lines (measured by the presence/absence of infectious DENV in mosquito saliva) after 14 days, was significantly reduced compared to their wildtype counterparts, and lowest for wMelCS and wAlbB. These data support the use of wAlbB and wMelCS strains for introgression field trials and the biocontrol of DENV transmission. Furthermore, despite observing significant differences in transmission potential between wildtype mosquitoes from Australia and Vietnam, no difference was observed between wMel-infected mosquitoes from each background suggesting that Wolbachia may override any underlying variation in DENV transmission potential., Author summary Aedes aegypti transmit a number of medically important arboviruses, including dengue, Zika, chikungunya, Mayaro and yellow fever viruses. Over the past 50 years, the burden of Ae. aegypti-transmitted disease has significantly increased–underscoring how current methods of vector control are unable to cope with this problem. Wolbachia-based biocontrol methods show extreme promise in reducing the global burden of vector-borne disease. The wMel strain, widely being used in field trials around the world, substantially reduces the ability of Ae. aegypti mosquitoes to transmit dengue, Zika, and other viruses. Here we describe a comprehensive comparative study of the viral blocking abilities of wMel to wMelCS and wAlbB which have previously been shown to have stronger viral blocking or an expanded utility in extreme environments, respectively. Using two different methods to measure viral replication and transmission potential, we show that both strains provide improved viral protection over wMel in the lab supporting further examination in field trials. We further compare the transmission potential of wMel in two different genetic backgrounds and find that wMel provides equivalent levels of viral blocking despite differences observed in wildtype mosquitoes, suggesting that viral blocking induced by wMel may override any underlying variation for DENV transmission potential.

Published
2020

50. w Mel Wolbachia genome remains stable after 7 years in Australian Aedes aegypti field populations.

Author

Dainty KR, Hawkey J, Judd LM, Pacidônio EC, Duyvestyn JM, Gonçalves DS, Lin SY, O'Donnell TB, O'Neill SL, Simmons CP, Holt KE, and Flores HA

Subjects
Aedes virology, Animals, Australia, Dengue, Dengue Virus, Evolution, Molecular, Zika Virus, Zika Virus Infection, Aedes microbiology, Genome, Bacterial, Wolbachia genetics
Abstract

Infection of w Mel Wolbachia in Aedes aegypti imparts two signature features that enable its application for biocontrol of dengue. First, the susceptibility of mosquitoes to viruses such as dengue and Zika is reduced. Second, a reproductive manipulation is caused that enables w Mel introgression into wild-type mosquito populations. The long-term success of this method relies, in part, on evolution of the w Mel genome not compromising the critical features that make it an attractive biocontrol tool. This study compared the w Mel Wolbachia genome at the time of initial releases and 1-7 years post-release in Cairns, Australia. Our results show the w Mel genome remains highly conserved up to 7 years post-release in gene sequence, content, synteny and structure. This work suggests the w Mel genome is stable in its new mosquito host and, therefore, provides reassurance on the potential for w Mel to deliver long-term public-health impacts.

Published
2021
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