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Articles 1 - 16 of 16
Full-Text Articles in Life 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
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 …
Interactive Effects Of Climate Change With Nutrients, Mercury, And Freshwater Acidification On Key Taxa In The North Atlantic Landscape Conservation Cooperative Region, Alfred E. Pinkey, Charles T. Driscoll, David C. Evers, Michael J. Hooper, Jeffrey Horan, Jess W. Jones, Rebecca S. Lazarus, Harold G. Marshall, Andrew Milliken, Barnett A. Rattner, John Schmerfold, Donald W. Sparling
Interactive Effects Of Climate Change With Nutrients, Mercury, And Freshwater Acidification On Key Taxa In The North Atlantic Landscape Conservation Cooperative Region, Alfred E. Pinkey, Charles T. Driscoll, David C. Evers, Michael J. Hooper, Jeffrey Horan, Jess W. Jones, Rebecca S. Lazarus, Harold G. Marshall, Andrew Milliken, Barnett A. Rattner, John Schmerfold, Donald W. Sparling
Biological Sciences Faculty Publications
The North Atlantic Landscape Conservation Cooperative LCC (NA LCC) is a public-private partnership that provides information to support conservation decisions that may be affected by global climate change (GCC) and other threats. The NA LCC region extends from southeast Virginia to the Canadian Maritime Provinces. Within this region, the US National Climate Assessment documented increases in air temperature, total precipitation, frequency of heavy precipitation events, and rising sea level, and predicted more drastic changes. Here, we synthesize literature on the effects of GCC interacting with selected contaminant, nutrient, and environmental processes to adversely affect natural resources within this region. Using …
Neurotensin And Cholecystokinin Contract Gallbladder Circular Muscle In Chickens, Teresa F. Degolier, D. R. Brown, Gary E. Duke, M. M. Palmer, J. R. Swenson, Robert E. Carraway
Neurotensin And Cholecystokinin Contract Gallbladder Circular Muscle In Chickens, Teresa F. Degolier, D. R. Brown, Gary E. Duke, M. M. Palmer, J. R. Swenson, Robert E. Carraway
Biological Sciences Faculty Publications
The contractile effects of neurotensin (NT) and cholecystokinin octapeptide (CCK-8) on isolated circular smooth muscle strips of chicken gallbladder were investigated. The NT (0.25-300 nM) produced concentration-dependent contractions on smooth muscle with an EC50 of 8.5 nM (95% confidence limits = 5.3-13.6 nM). In comparison, CCK-8 produced concentration-dependent contractions with an EC50 of 13 nM (95% confidence limits of 9-20 nM). There were no statistical differences in contractile responses when comparing NT and CCK-8 at equimolar concentrations. The NT appears to act directly on smooth muscle tissue in the chicken; the contractile responses were not blocked by 10 μM atropine …
Release Of Avian Neurotensin In Response To Intraluminal Contents In The Duodenum Of Chickens, Teresa F. Degolier, Robert E. Carraway
Release Of Avian Neurotensin In Response To Intraluminal Contents In The Duodenum Of Chickens, Teresa F. Degolier, Robert E. Carraway
Biological Sciences Faculty Publications
Peripheral and hepatic-portal plasma levels of neurotensin (NT) in fed and fasted chickens were determined using RIA. Portal levels of NT1-13 (fed = 61.3 ± 3.9 fmol/mL; fasted = 44.5 ± 3.9 fmol/mL) were significantly higher than peripheral levels (fed = 8.2 ± 3.3 fmol/mL; fasted = 7.8 ± 3.0 fmol/mL) collected from the wing vein, indicating that some NT is metabolized in the liver. Portal plasma levels of NT collected from fed birds were also significantly higher than portal plasma levels of NT collected from fasted birds. Neurotensin, as identified by HPLC, exhibited a 2-fold increase in plasma extracts …
Mitochondrial Dna Instability In Cells Lacking Aconitase Correlates With Iron Citrate Toxicity, Muhammad A. Farooq, Tammy M. Pracheil, Zhejun Dong, Fei Xiao, Zhengchang Liu
Mitochondrial Dna Instability In Cells Lacking Aconitase Correlates With Iron Citrate Toxicity, Muhammad A. Farooq, Tammy M. Pracheil, Zhejun Dong, Fei Xiao, Zhengchang Liu
Biological Sciences Faculty Publications
Aconitase, the second enzyme of the tricarboxylic acid cycle encoded by ACO1 in the budding yeast Saccharomyces cerevisiae, catalyzes the conversion of citrate to isocitrate. aco1 Delta results in mitochondrial DNA (mtDNA) instability. It has been proposed that Aco1 binds to mtDNA and mediates its maintenance. Here we propose an alternative mechanism to account for mtDNA loss in aco1 Delta mutant cells. We found that aco1 Delta activated the RTG pathway, resulting in increased expression of genes encoding citrate synthase. By deleting RTG1, RTG3, or genes encoding citrate synthase, mtDNA instability was prevented in aco1 Delta mutant …
Mutation In The Plasmodium Falciparum Crt Protein Determines The Stereospecific Activity Of Antimalarial Cinchona Alkaloids, Carol E. Griffin, Jonathan M. Hoke, Upeka Samarakoon, Junhui Duan, Jianbing Mu, Michael T. Ferdig, David C. Warhurst, Roland A. Cooper
Mutation In The Plasmodium Falciparum Crt Protein Determines The Stereospecific Activity Of Antimalarial Cinchona Alkaloids, Carol E. Griffin, Jonathan M. Hoke, Upeka Samarakoon, Junhui Duan, Jianbing Mu, Michael T. Ferdig, David C. Warhurst, Roland A. Cooper
Biological Sciences Faculty Publications
The Cinchona alkaloids are quinoline aminoalcohols that occur as diastereomer pairs, typified by (-)-quinine and (+)-quinidine. The potency of (+)-isomers is greater than the (-)-isomers in vitro and in vivo against Plasmodium falciparum malaria parasites. They may act by the inhibition of heme crystallization within the parasite digestive vacuole in a manner similar to chloroquine. Earlier studies showed that a K76I mutation in the digestive vacuole-associated protein, PfCRT (P. falciparum chloroquine resistance transporter), reversed the normal potency order of quinine and quinidine toward P. falciparum. To further explore PfCRT-alkaloid interactions in the malaria parasite, we measured the in …
Extinction Risk And Bottlenecks In The Conservation Of Charismatic Marine Species, Loren Mcclenachan, Andrew B. Cooper, Kent E. Carpenter, Nicholas K. Dulvy
Extinction Risk And Bottlenecks In The Conservation Of Charismatic Marine Species, Loren Mcclenachan, Andrew B. Cooper, Kent E. Carpenter, Nicholas K. Dulvy
Biological Sciences Faculty Publications
The oceans face a biodiversity crisis, but the degree and scale of extinction risk remains poorly characterized. Charismatic species are most likely to gar- ner greatest support for conservation and thus provide a best-case scenario of the status of marine biodiversity. We summarize extinction risk and diagnose impediments to successful conservation for 1,568 species in 16 families of marine animals in the movie Finding Nemo. Sixteen percent (12–34%) of those that have been evaluated are threatened, ranging from 9% (7–28%) of bony fishes to 100% (83–100%) of marine turtles. A lack of scientific knowledge impedes analysis of threat status …
Design, Synthesis, And Evaluation Of 10-N-Substituted Acridones As Novel Chemosensitizers In Plasmodium Falciparum, Jane X. Kelly, Martin J. Smilkstein, Roland A. Cooper, Kristin D. Lane, Robert A. Johnson, Aaron Janowsky, Rozalia A. Dodean, David J. Hinrichs, Rolf Winter, Michael Riscoe
Design, Synthesis, And Evaluation Of 10-N-Substituted Acridones As Novel Chemosensitizers In Plasmodium Falciparum, Jane X. Kelly, Martin J. Smilkstein, Roland A. Cooper, Kristin D. Lane, Robert A. Johnson, Aaron Janowsky, Rozalia A. Dodean, David J. Hinrichs, Rolf Winter, Michael Riscoe
Biological Sciences Faculty Publications
A series of novel 10-N-substituted acridones, bearing alkyl side chains with tertiary amine groups at the terminal position, were designed, synthesized, and evaluated for the ability to enhance the potency of quinoline drugs against multidrug-resistant (MDR) Plasmodium falciparum malaria parasites. A number of acridone derivatives, with side chains bridged three or more carbon atoms apart between the ring nitrogen and terminal nitrogen, demonstrated chloroquine (CQ)-chemosensitizing activity against the MDR strain of P. falciparum (Dd2). Isobolograrn analysis revealed that selected candidates demonstrated significant synergy with CQ in the CQ-resistant (CQR) parasite Dd2 but only additive (or indifferent) interaction in the CQ-sensitive …
Recognizing Toxic Species In Aquatic Habitats: A Potential Concern In Lake Management, Mikolaj Kokocinski, Harold G. Marshall
Recognizing Toxic Species In Aquatic Habitats: A Potential Concern In Lake Management, Mikolaj Kokocinski, Harold G. Marshall
Biological Sciences Faculty Publications
The importance of distinguishing toxic and non-toxic algal species is becoming a more common problem for management decisions associated with various freshwater and estuarine habitats. An example is given where two dinoflagellates, originally unidentified as closely resembling the toxin producing Pfiesteria spp., have been compared to these species. In order to clarify any relationship to Pfiesteria spp., scanning electron microscopy was used to determine the plate tabulation patterns of these dinoflagellates and make comparisons to the tabulation present in Pfiesteria spp. The results indicated significant differences in the plate tabulations of these taxa to distinguish them from Pfiesteria …
Enhancement Of Disease And Pathology By Synergy Of Trichuris Suis And Campylobacter Jejuni In The Colon Of Immunologically Naive Swine, Linda S. Mansfield, David T. Gauthier, Sheila R. Abner, Kathryn M. Jones, Stacey R. Wilder, Joseph F. Urban
Enhancement Of Disease And Pathology By Synergy Of Trichuris Suis And Campylobacter Jejuni In The Colon Of Immunologically Naive Swine, Linda S. Mansfield, David T. Gauthier, Sheila R. Abner, Kathryn M. Jones, Stacey R. Wilder, Joseph F. Urban
Biological Sciences Faculty Publications
Campylobacter jejuni, a leading cause of bacterial gastroenteritis, has different age distribution and disease expression in developing and developed countries, which may be due to the endemnicity of infection and the age of acquisition of immunity. Differences in disease expression are not solely dependent on the C jejuni strain or virulence attributes. Another modulating factor in developing countries may be endemic nematode infections such as Trichuris, which drive type 2 cytokine responses and down-regulate type I immune responses. In this study, three-day-old germfree pigs given dual infections with Trichuris suis and C jejuni had more frequent, more severe …
The Standardized Fish Bioassay Procedure For Detecting And Culturing Actively Toxic Pfiesteria, Used By Two Reference Laboratories For Atlantic And Gulf Coast States, Joann M. Burkholder, Harold G. Marshall, David W. Seaborn, Nora J. Deamer-Melia
The Standardized Fish Bioassay Procedure For Detecting And Culturing Actively Toxic Pfiesteria, Used By Two Reference Laboratories For Atlantic And Gulf Coast States, Joann M. Burkholder, Harold G. Marshall, David W. Seaborn, Nora J. Deamer-Melia
Biological Sciences Faculty Publications
In the absence of purified standards of toxins from Pfiesteria species, appropriately conducted fish bioassays are the "gold standard" that must be used to detect toxic strains of Pfiesteria slop. from natural estuarine water or sediment samples and to culture actively toxic Pfiesteria. In this article, we describe the standardized steps of our fish bioassay as an abbreviated term for a procedure that includes two sets of trials with fish, following the Henle-Koch postulates modified for toxic rather than infectious agents. This procedure was developed in 1991, and has been refined over more than 12 years of experience in …
Pfiesteria Piscicida And Dinoflagellates Similar To Pfiesteria, Harold G. Marshall
Pfiesteria Piscicida And Dinoflagellates Similar To Pfiesteria, Harold G. Marshall
Biological Sciences Faculty Publications
Pfiesteria pisiccida is a microscopic, unicellular organism that is classified as both a mixotrophic and heterotrophic dinoflagellate, which has been associated with both fish deaths and a cause of human illness (Burkholder et al., 1992; Glasglow et al., 1995; Burkholder and Glasgow, 1997). This species possesses a complex life cycle that includes motile forms (e.g. zoospores, gametes, amoebae) and a cyst stage that may remain dormant in the sediment (Burkholder et al, 1995b). Pfiesteria piscicida is known to have toxin and non-toxin producing populations, where cyst transformation into the toxic motile zoospores may be initiated by the presence of certain …
Water Quality Relationships To Concentrations Of Pfiesteria-Like Organisms In Virginia Estuaries For 1998., Everett P. Weber, Harold G. Marshall
Water Quality Relationships To Concentrations Of Pfiesteria-Like Organisms In Virginia Estuaries For 1998., Everett P. Weber, Harold G. Marshall
Biological Sciences Faculty Publications
A series of statistical analyses were performed to identify the relationship between abundance of dinoflagellates grouped as Pfiesteria-like organisms and a set of 25 water quality variables from May through October of 1998 at 41 estuarine locations. Although regions were identified in relation to seasonal density of cells present, there were no strong relationships to specific water quality variables. Factors that may have influenced these results included: a) several species were included in the group analyzed and this composite did not respond as a unit to changing environmental conditions; b) cell concentrations were low and there were a large …
Monitoring Results For Pfiesteria Piscidida And Pfiesteria-Like Organisms From Virginia Waters In 1998, Harold G. Marshall, David W. Seaborn, Jennifer Wolny
Monitoring Results For Pfiesteria Piscidida And Pfiesteria-Like Organisms From Virginia Waters In 1998, Harold G. Marshall, David W. Seaborn, Jennifer Wolny
Biological Sciences Faculty Publications
Results of an extensive 1998 monitoring program for the presence of Pfiesteria-like organisms (PLO) in Virginia estuaries indicate these dinoflagellates are widely distributed in both the water column, and as cysts in the sediment, however Pfiesteria piscicida was not detected at this time. The highest concentrations of PLO were in estuaries along the Virginia shore line of the Potomac River, and in western Chesapeake Bay estuaries from the Little Wicomico River to the Rappahannock River. The most common PLO included Cryptoperidiniopsis sp. and Gymnodinium galatheanum. The lowest PLO concentrations were at ocean side locations. PLO were also …
Toxin Producing Phytoplankton In Chesapeake Bay, Harold G. Marshall
Toxin Producing Phytoplankton In Chesapeake Bay, Harold G. Marshall
Biological Sciences Faculty Publications
Three diatoms and nine dinoflagellates, known to be associated with toxin production, have been identified within Chesapeake Bay. Over the past several decades this number has increased to its present level so that they now represent approximately 1.7% the total number of phytoplankton species reported for the Bay.
Sediment Denitrification Potential In The Elizabeth River, Virginia, Surena Fazeli-Matin, Andrew S. Gordon, Harold G. Marshall
Sediment Denitrification Potential In The Elizabeth River, Virginia, Surena Fazeli-Matin, Andrew S. Gordon, Harold G. Marshall
Biological Sciences Faculty Publications
Sediment denitrification potential from two sites in the Elizabeth River estuary was studied over a nine-month period using the acetylene blockage method. Rates of microbial processes in this environment are of interest because of the high concentration of toxics present in some parts of the system. Highest rates were found in the highly polluted Southern Branch of the Elizabeth River with nitrate amended sediment ranging from 2-262 nmol N20/h per 20ml of sediment and exhibiting maximal rates during spring and fall. Rates in the Main Stem of the Elizabeth River were lower, with less than 1-85 nmol N …