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Full-Text Articles in Medicine and Health Sciences

A Variant Pfcrt Isoform Can Contribute To Plasmodium Falciparum Resistance To The First-Line Partner Drug Piperaquine, Satish K. Dhingra, Devasha Redhi, Jill M. Combrinck, Tomas Yeo, John Okombo, Philipp P. Henrich, Annie N. Cowell, Purva Gupta, Matthew L. Stegman, Jonathan M. Hoke, Roland A. Cooper, Elizabeth Winzeler, Sachel Mok, Timothy J. Egan, David A. Fidock May 2017

A Variant Pfcrt Isoform Can Contribute To Plasmodium Falciparum Resistance To The First-Line Partner Drug Piperaquine, Satish K. Dhingra, Devasha Redhi, Jill M. Combrinck, Tomas Yeo, John Okombo, Philipp P. Henrich, Annie N. Cowell, Purva Gupta, Matthew L. Stegman, Jonathan M. Hoke, Roland A. Cooper, Elizabeth Winzeler, Sachel Mok, Timothy J. Egan, David A. Fidock

Biological Sciences Faculty Publications

Current efforts to reduce the global burden of malaria are threatened by the rapid spread throughout Asia of Plasmodium falciparum resistance to artemisinin-based combination therapies, which includes increasing rates of clinical failure with dihydroartemisinin plus piperaquine (PPQ) in Cambodia. Using zinc finger nuclease-based gene editing, we report that addition of the C101F mutation to the chloroquine (CQ) resistance-conferring PfCRT Dd2 isoform common to Asia can confer PPQ resistance to cultured parasites. Resistance was demonstrated as significantly higher PPQ concentrations causing 90% inhibition of parasite growth (IC90) or 50% parasite killing (50% lethal dose [LD50]). This mutation …


Defining The Risk Of Zika And Chikungunya Virus Transmission In Human Population Centers Of The Eastern United States, Carrie A. Manore, Richard S. Ostfeld, Folashade B. Agusto, Holly Gaff, Shannon L. Ladeau Jan 2017

Defining The Risk Of Zika And Chikungunya Virus Transmission In Human Population Centers Of The Eastern United States, Carrie A. Manore, Richard S. Ostfeld, Folashade B. Agusto, Holly Gaff, Shannon L. Ladeau

Biological Sciences Faculty Publications

The recent spread of mosquito-transmitted viruses and associated disease to the Americas motivates a new, data-driven evaluation of risk in temperate population centers. Temperate regions are generally expected to pose low risk for significant mosquito-borne disease; however, the spread of the Asian tiger mosquito (Aedes albopictus) across densely populated urban areas has established a new landscape of risk. We use a model informed by field data to assess the conditions likely to facilitate local transmission of chikungunya and Zika viruses from an infected traveler to Ae. albopictus and then to other humans in USA cities with variable human …


Impact Of Disease On The Survival Of Three Commercially Fished Species, John M. Hoenig, Maya L. Groner, Matthew W. Smith, Wolfgang K. Vogelbein, David M. Taylor, Donald F. Landers Jr., John T. Swenarton, David T. Gauthier Jan 2017

Impact Of Disease On The Survival Of Three Commercially Fished Species, John M. Hoenig, Maya L. Groner, Matthew W. Smith, Wolfgang K. Vogelbein, David M. Taylor, Donald F. Landers Jr., John T. Swenarton, David T. Gauthier

Biological Sciences Faculty Publications

Recent increases in emergent infectious diseases have raised concerns about the sustainability of some marine species. The complexity and expense of studying diseases in marine systems often dictate that conservation and management decisions are made without quantitative data on population-level impacts of disease. Mark-recapture is a powerful, underutilized, tool for calculating impacts of disease on population size and structure, even in the absence of etiological information. We applied logistic regression models to mark-recapture data to obtain estimates of disease-associated mortality rates in three commercially important marine species: snow crab (Chionoecetes opilio) in Newfoundland, Canada, that experience sporadic epizootics …


Exosomes Serve As Novel Modes Of Tick-Borne Flavivirus Transmission From Arthropod To Human Cells And Facilitates Dissemination Of Viral Rna And Proteins To The Vertebrate Neuronal Cells, Wenshuo Zhou, Michael Woodson, Biswas Neupane, Fengwei Bai, Michael B. Sherman, Kyung H. Choi, Girish Neelakanta, Hameeda Sultana Jan 2017

Exosomes Serve As Novel Modes Of Tick-Borne Flavivirus Transmission From Arthropod To Human Cells And Facilitates Dissemination Of Viral Rna And Proteins To The Vertebrate Neuronal Cells, Wenshuo Zhou, Michael Woodson, Biswas Neupane, Fengwei Bai, Michael B. Sherman, Kyung H. Choi, Girish Neelakanta, Hameeda Sultana

Biological Sciences Faculty Publications

Molecular determinants and mechanisms of arthropod-borne flavivirus transmission to the vertebrate host are poorly understood. In this study, we show for the first time that a cell line from medically important arthropods, such as ticks, secretes extracellular vesicles (EVs) including exosomes that mediate transmission of flavivirus RNA and proteins to the human cells. Our study shows that tick-borne Langat virus (LGTV), a model pathogen closely related to tick-borne encephalitis virus (TBEV), profusely uses arthropod exosomes for transmission of viral RNA and proteins to the human- skin keratinocytes and blood endothelial cells. Cryo-electron microscopy showed the presence of purified arthropod/neuronal exosomes …