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Sample records for plasmodium permits generation

  1. Hydroelectric Generating Facilities General Permit ...

    EPA Pesticide Factsheets

    2017-08-28

    The Notice of Availability of the Final NPDES General Permits (HYDROGP) for Discharges at Hydroelectric Generating Facilities in Massachusetts (MAG360000) and New Hampshire (NHG360000) and Tribal Lands in the State of Massachusetts was published in the Federal Register on December 7, 2009 (see 74 Fed. Reg. No. 233, pages 64074 - 64075).

  2. UIC Class I Permit: La Paloma Generating Company, LLC

    EPA Pesticide Factsheets

    Documents related to La Paloma Generating Company, LLC's (LPGC) application for a UIC permit renewal (of permit #CA199000001) to operate a Class I injection well facility to dispose of non-hazardous wastewater from the La Paloma Generating Plant.

  3. Hydroelectric Generating Facilities General Permit (HYDROGP) for Massachusetts & New Hampshire

    EPA Pesticide Factsheets

    Documents, links & contacts for the Notice of Availability of the Final NPDES General Permits (HYDROGP) for Discharges at Hydroelectric Generating Facilities in Massachusetts (MAG360000) and New Hampshire (NHG360000) and Tribal Lands in the State of MA.

  4. Carbon tax or carbon permits: The impact on generators' risks

    SciTech Connect

    Green, R.

    2008-07-01

    Volatile fuel prices affect both the cost and price of electricity in a liberalized market. Generators with the price-setting technology will face less risk to their profit margins than those with costs that are not correlated with price, even if those costs are not volatile. Emissions permit prices may respond to relative fuel prices, further increasing volatility. This paper simulates the impact of this on generators' profits, comparing an emissions trading scheme and a carbon tax against predictions for the UK in 2020. The carbon tax reduces the volatility faced by nuclear generators, but raises that faced by fossil fuel stations. Optimal portfolios would contain a higher proportion of nuclear plant if a carbon tax was adopted.

  5. Overlap Extension Barcoding for the Next Generation Sequencing and Genotyping of Plasmodium falciparum in Individual Patients in Western Kenya

    PubMed Central

    Levitt, Brandt; Obala, Andrew; Langdon, Scott; Corcoran, David; O’Meara, Wendy Prudhomme; Taylor, Steve M.

    2017-01-01

    Large-scale molecular epidemiologic studies of Plasmodium falciparum parasites have provided insights into parasite biology and transmission, can identify the spread of drug resistance, and are useful in assessing vaccine targets. The polyclonal nature infections in high transmission settings is problematic for traditional genotyping approaches. Next-generation sequencing (NGS) approaches to parasite genotyping allow sensitive detection of minority variants, disaggregation of complex parasite mixtures, and scalable processing of large samples sets. Therefore, we designed, validated, and applied to field parasites an approach that leverages sequencing of individually barcoded samples in a multiplex manner. We utilize variant barcodes, invariant linker sequences and modular template-specific primers to allow for the simultaneous generation of high-dimensional sequencing data of multiple gene targets. This modularity permits a cost-effective and reproducible way to query many genes at once. In mixtures of reference parasite genomes, we quantitatively detected unique haplotypes comprising as little as 2% of a polyclonal infection. We applied this genotyping approach to field-collected parasites collected in Western Kenya in order to simultaneously obtain parasites genotypes at three unlinked loci. In summary, we present a rapid, scalable, and flexible method for genotyping individual parasites that enables molecular epidemiologic studies of parasite evolution, population structure and transmission. PMID:28117350

  6. Appeal of Air Permit for New Harquahala Generating Company

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  7. A next-generation genetically attenuated Plasmodium falciparum parasite created by triple gene deletion.

    PubMed

    Mikolajczak, Sebastian A; Lakshmanan, Viswanathan; Fishbaugher, Matthew; Camargo, Nelly; Harupa, Anke; Kaushansky, Alexis; Douglass, Alyse N; Baldwin, Michael; Healer, Julie; O'Neill, Matthew; Phuong, Thuan; Cowman, Alan; Kappe, Stefan H I

    2014-09-01

    Immunization with live-attenuated Plasmodium sporozoites completely protects against malaria infection. Genetic engineering offers a versatile platform to create live-attenuated sporozoite vaccine candidates. We previously generated a genetically attenuated parasite (GAP) by deleting the P52 and P36 genes in the NF54 wild-type (WT) strain of Plasmodium falciparum (Pf p52(-)/p36(-) GAP). Preclinical assessment of p52(-)/p36(-) GAP in a humanized mouse model indicated an early and severe liver stage growth defect. However, human exposure to >200 Pf p52(-)/p36(-) GAP-infected mosquito bites in a safety trial resulted in peripheral parasitemia in one of six volunteers, revealing that this GAP was incompletely attenuated. We have now created a triple gene deleted GAP by additionally removing the SAP1 gene (Pf p52(-)/p36(-)/sap1(-) GAP) and employed flippase (FLP)/flippase recognition target (FRT) recombination for drug selectable marker cassette removal. This next-generation GAP was indistinguishable from WT parasites in blood stage and mosquito stage development. Using an improved humanized mouse model transplanted with human hepatocytes and human red blood cells, we show that despite a high-dose sporozoite challenge, Pf p52(-)/p36(-)/sap1(-) GAP did not transition to blood stage infection and appeared to be completely attenuated. Thus, clinical testing of Pf p52(-)/p36(-)/sap1(-) GAP assessing safety, immunogenicity, and efficacy against sporozoite challenge is warranted.

  8. 75 FR 70732 - BPUS Generation Development, LLC; Notice of Preliminary Permit Application Accepted for Filing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-18

    ... Contact: Michael Cutter, Vice President Engineering and Development, Brookfield Renewable Power, Inc., 200... Federal Energy Regulatory Commission BPUS Generation Development, LLC; Notice of Preliminary Permit... November 10, 2010. On October 4, 2010, BPUS Generation Development, LLC filed an application for...

  9. Imaging of Plasmodium liver stages to drive next-generation antimalarial drug discovery.

    PubMed

    Meister, Stephan; Plouffe, David M; Kuhen, Kelli L; Bonamy, Ghislain M C; Wu, Tao; Barnes, S Whitney; Bopp, Selina E; Borboa, Rachel; Bright, A Taylor; Che, Jianwei; Cohen, Steve; Dharia, Neekesh V; Gagaring, Kerstin; Gettayacamin, Montip; Gordon, Perry; Groessl, Todd; Kato, Nobutaka; Lee, Marcus C S; McNamara, Case W; Fidock, David A; Nagle, Advait; Nam, Tae-gyu; Richmond, Wendy; Roland, Jason; Rottmann, Matthias; Zhou, Bin; Froissard, Patrick; Glynne, Richard J; Mazier, Dominique; Sattabongkot, Jetsumon; Schultz, Peter G; Tuntland, Tove; Walker, John R; Zhou, Yingyao; Chatterjee, Arnab; Diagana, Thierry T; Winzeler, Elizabeth A

    2011-12-09

    Most malaria drug development focuses on parasite stages detected in red blood cells, even though, to achieve eradication, next-generation drugs active against both erythrocytic and exo-erythrocytic forms would be preferable. We applied a multifactorial approach to a set of >4000 commercially available compounds with previously demonstrated blood-stage activity (median inhibitory concentration < 1 micromolar) and identified chemical scaffolds with potent activity against both forms. From this screen, we identified an imidazolopiperazine scaffold series that was highly enriched among compounds active against Plasmodium liver stages. The orally bioavailable lead imidazolopiperazine confers complete causal prophylactic protection (15 milligrams/kilogram) in rodent models of malaria and shows potent in vivo blood-stage therapeutic activity. The open-source chemical tools resulting from our effort provide starting points for future drug discovery programs, as well as opportunities for researchers to investigate the biology of exo-erythrocytic forms.

  10. A Next-generation Genetically Attenuated Plasmodium falciparum Parasite Created by Triple Gene Deletion

    PubMed Central

    Mikolajczak, Sebastian A; Lakshmanan, Viswanathan; Fishbaugher, Matthew; Camargo, Nelly; Harupa, Anke; Kaushansky, Alexis; Douglass, Alyse N; Baldwin, Michael; Healer, Julie; O'Neill, Matthew; Phuong, Thuan; Cowman, Alan; Kappe, Stefan H I

    2014-01-01

    Immunization with live-attenuated Plasmodium sporozoites completely protects against malaria infection. Genetic engineering offers a versatile platform to create live-attenuated sporozoite vaccine candidates. We previously generated a genetically attenuated parasite (GAP) by deleting the P52 and P36 genes in the NF54 wild-type (WT) strain of Plasmodium falciparum (Pf p52−/p36− GAP). Preclinical assessment of p52−/p36− GAP in a humanized mouse model indicated an early and severe liver stage growth defect. However, human exposure to >200 Pf p52−/p36− GAP-infected mosquito bites in a safety trial resulted in peripheral parasitemia in one of six volunteers, revealing that this GAP was incompletely attenuated. We have now created a triple gene deleted GAP by additionally removing the SAP1 gene (Pf p52−/p36−/sap1− GAP) and employed flippase (FLP)/flippase recognition target (FRT) recombination for drug selectable marker cassette removal. This next-generation GAP was indistinguishable from WT parasites in blood stage and mosquito stage development. Using an improved humanized mouse model transplanted with human hepatocytes and human red blood cells, we show that despite a high-dose sporozoite challenge, Pf p52−/p36−/sap1− GAP did not transition to blood stage infection and appeared to be completely attenuated. Thus, clinical testing of Pf p52−/p36−/sap1− GAP assessing safety, immunogenicity, and efficacy against sporozoite challenge is warranted. PMID:24827907

  11. GHG PSD Permit: Cheyenne Light, Fuel & Power / Black Hills Power, Inc. – Cheyenne Prairie Generating Station

    EPA Pesticide Factsheets

    This page contains the final PSD permit for the Cheyenne Light, Fuel & Power / Black Hills Power, Inc. Cheyenne Prairie Generating Station, located in Laramie, Wyoming, and operated by Black Hills Service Company.

  12. Title V Operating Permit: Deseret Generation and Transmission Cooperative, Bonanza Power Plant

    EPA Pesticide Factsheets

    Response to Public Comments and Final Operating Permit for the Deseret Generation and Transmission Cooperative Bonanza Power Plant, located within the exterior boundaries of the Uintah and Ouray Indian Reservation in Uintah County, Utah.

  13. Midwest Generation, Waukegan Generating Station; Order Partially Denying And Partially Granting Petition For Objection To Permit

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database.

  14. Generation of quinolone antimalarials targeting the Plasmodium falciparum mitochondrial respiratory chain for the treatment and prophylaxis of malaria

    PubMed Central

    Biagini, Giancarlo A.; Fisher, Nicholas; Shone, Alison E.; Mubaraki, Murad A.; Srivastava, Abhishek; Hill, Alisdair; Antoine, Thomas; Warman, Ashley J.; Davies, Jill; Pidathala, Chandrakala; Amewu, Richard K.; Leung, Suet C.; Sharma, Raman; Gibbons, Peter; Hong, David W.; Pacorel, Bénédicte; Lawrenson, Alexandre S.; Charoensutthivarakul, Sitthivut; Taylor, Lee; Berger, Olivier; Mbekeani, Alison; Stocks, Paul A.; Nixon, Gemma L.; Chadwick, James; Hemingway, Janet; Delves, Michael J.; Sinden, Robert E.; Zeeman, Anne-Marie; Kocken, Clemens H. M.; Berry, Neil G.; O’Neill, Paul M.; Ward, Stephen A.

    2012-01-01

    There is an urgent need for new antimalarial drugs with novel mechanisms of action to deliver effective control and eradication programs. Parasite resistance to all existing antimalarial classes, including the artemisinins, has been reported during their clinical use. A failure to generate new antimalarials with novel mechanisms of action that circumvent the current resistance challenges will contribute to a resurgence in the disease which would represent a global health emergency. Here we present a unique generation of quinolone lead antimalarials with a dual mechanism of action against two respiratory enzymes, NADH:ubiquinone oxidoreductase (Plasmodium falciparum NDH2) and cytochrome bc1. Inhibitor specificity for the two enzymes can be controlled subtly by manipulation of the privileged quinolone core at the 2 or 3 position. Inhibitors display potent (nanomolar) activity against both parasite enzymes and against multidrug-resistant P. falciparum parasites as evidenced by rapid and selective depolarization of the parasite mitochondrial membrane potential, leading to a disruption of pyrimidine metabolism and parasite death. Several analogs also display activity against liver-stage parasites (Plasmodium cynomolgi) as well as transmission-blocking properties. Lead optimized molecules also display potent oral antimalarial activity in the Plasmodium berghei mouse malaria model associated with favorable pharmacokinetic features that are aligned with a single-dose treatment. The ease and low cost of synthesis of these inhibitors fulfill the target product profile for the generation of a potent, safe, and inexpensive drug with the potential for eventual clinical deployment in the control and eradication of falciparum malaria. PMID:22566611

  15. Species and genotype diversity of Plasmodium in malaria patients from Gabon analysed by next generation sequencing.

    PubMed

    Lalremruata, Albert; Jeyaraj, Sankarganesh; Engleitner, Thomas; Joanny, Fanny; Lang, Annika; Bélard, Sabine; Mombo-Ngoma, Ghyslain; Ramharter, Michael; Kremsner, Peter G; Mordmüller, Benjamin; Held, Jana

    2017-10-03

    Six Plasmodium species are known to naturally infect humans. Mixed species infections occur regularly but morphological discrimination by microscopy is difficult and multiplicity of infection (MOI) can only be evaluated by molecular methods. This study investigated the complexity of Plasmodium infections in patients treated for microscopically detected non-falciparum or mixed species malaria in Gabon. Ultra-deep sequencing of nucleus (18S rRNA), mitochondrion, and apicoplast encoded genes was used to evaluate Plasmodium species diversity and MOI in 46 symptomatic Gabonese patients with microscopically diagnosed non-falciparum or mixed species malaria. Deep sequencing revealed a large complexity of confections in patients with uncomplicated malaria, both on species and genotype levels. Mixed infections involved up to four parasite species (Plasmodium falciparum, Plasmodium malariae, Plasmodium ovale curtisi, and P. ovale wallikeri). Multiple genotypes from each species were determined from the asexual 18S rRNA gene. 17 of 46 samples (37%) harboured multiple genotypes of at least one Plasmodium species. The number of genotypes per sample (MOI) was highest in P. malariae (n = 4), followed by P. ovale curtisi (n = 3), P. ovale wallikeri (n = 3), and P. falciparum (n = 2). The highest combined genotype complexity in samples that contained mixed-species infections was seven. Ultra-deep sequencing showed an unexpected breadth of Plasmodium species and within species diversity in clinical samples. MOI of P. ovale curtisi, P. ovale wallikeri and P. malariae infections were higher than anticipated and contribute significantly to the burden of malaria in Gabon.

  16. Midwest Generation Waukegan Generating Station, Order Denying Petition for Objection to Title V Operating Permit

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  17. Order Denying Petition for Objection to Operating Permit for Luminant Generation Company's Sandow 5 Generating Plant

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  18. Petition to Object to Midwest Generation, Joliet Generating Station Title V Permit

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  19. Petition to Object to Midwest Generation, Romeoville Generating Station Title V Permit

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  20. Plasmodium immunomics.

    PubMed

    Doolan, Denise L

    2011-01-01

    The Plasmodium parasite, the causative agent of malaria, is an excellent model for immunomic-based approaches to vaccine development. The Plasmodium parasite has a complex life cycle with multiple stages and stage-specific expression of ∼5300 putative proteins. No malaria vaccine has yet been licensed. Many believe that an effective vaccine will need to target several antigens and multiple stages, and will require the generation of both antibody and cellular immune responses. Vaccine efforts to date have been stage-specific and based on only a very limited number of proteins representing <0.5% of the genome. The recent availability of comprehensive genomic, proteomic and transcriptomic datasets from human and selected non-human primate and rodent malarias provide a foundation to exploit for vaccine development. This information can be mined to identify promising vaccine candidate antigens, by proteome-wide screening of antibody and T cell reactivity using specimens from individuals exposed to malaria and technology platforms such as protein arrays, high throughput protein production and epitope prediction algorithms. Such antigens could be incorporated into a rational vaccine development process that targets specific stages of the Plasmodium parasite life cycle with immune responses implicated in parasite elimination and control. Immunomic approaches which enable the selection of the best possible targets by prioritising antigens according to clinically relevant criteria may overcome the problem of poorly immunogenic, poorly protective vaccines that has plagued malaria vaccine developers for the past 25 years. Herein, current progress and perspectives regarding Plasmodium immunomics are reviewed.

  1. De Novo Generated Human Red Blood Cells in Humanized Mice Support Plasmodium falciparum Infection.

    PubMed

    Amaladoss, Anburaj; Chen, Qingfeng; Liu, Min; Dummler, Sara K; Dao, Ming; Suresh, Subra; Chen, Jianzhu; Preiser, Peter R

    2015-01-01

    Immunodeficient mouse-human chimeras provide a powerful approach to study host specific pathogens like Plasmodium (P.) falciparum that causes human malaria. Existing mouse models of P. falciparum infection require repeated injections of human red blood cells (RBCs). In addition, clodronate lipsomes and anti-neutrophil antibodies are injected to suppress the clearance of human RBCs by the residual immune system of the immunodeficient mice. Engraftment of NOD-scid Il2rg-/- mice with human hematopoietic stem cells leads to reconstitution of human immune cells. Although human B cell reconstitution is robust and T cell reconstitution is reasonable in the recipient mice, human RBC reconstitution is generally poor or undetectable. The poor reconstitution is mainly the result of a deficiency of appropriate human cytokines that are necessary for the development and maintenance of these cell lineages. Delivery of plasmid DNA encoding human erythropoietin and interleukin-3 into humanized mice by hydrodynamic tail-vein injection resulted in significantly enhanced reconstitution of erythrocytes. With this improved humanized mouse, here we show that P. falciparum infects de novo generated human RBCs, develops into schizonts and causes successive reinvasion. We also show that different parasite strains exhibit variation in their ability to infect these humanized mice. Parasites could be detected by nested PCR in the blood samples of humanized mice infected with P. falciparum K1 and HB3 strains for 3 cycles, whereas in other strains such as 3D7, DD2, 7G8, FCR3 and W2mef parasites could only be detected for 1 cycle. In vivo adaptation of K1 strain further improves the infection efficiency and parasites can be detected by microscopy for 3 cycles. The parasitemia ranges between 0.13 and 0.25% at the first cycle of infection, falls between 0.08 and 0.15% at the second cycle, and drops to barely detectable levels at the third cycle of infection. Compared to existing mouse models, our

  2. Acyclic Immucillin Phosphonates. Second-Generation Inhibitors of Plasmodium falciparum Hypoxanthine- Guanine-Xanthine Phosphoribosyltransferase

    SciTech Connect

    Hazelton, Keith Z.; Ho, Meng-Chaio; Cassera, Maria B.; Clinch, Keith; Crump, Douglas R.; Rosario Jr., Irving; Merino, Emilio F.; Almo, Steve C.; Tyler, Peter C.; Schramm, Vern L.

    2012-06-22

    We found that Plasmodium falciparum is the primary cause of deaths from malaria. It is a purine auxotroph and relies on hypoxanthine salvage from the host purine pool. Purine starvation as an antimalarial target has been validated by inhibition of purine nucleoside phosphorylase. Hypoxanthine depletion kills Plasmodium falciparum in cell culture and in Aotus monkey infections. Hypoxanthine-guanine-xanthine phosphoribosyltransferase (HGXPRT) from P. falciparum is required for hypoxanthine salvage by forming inosine 5'-monophosphate, a branchpoint for all purine nucleotide synthesis in the parasite. We present a class of HGXPRT inhibitors, the acyclic immucillin phosphonates (AIPs), and cell permeable AIP prodrugs. The AIPs are simple, potent, selective, and biologically stable inhibitors. The AIP prodrugs block proliferation of cultured parasites by inhibiting the incorporation of hypoxanthine into the parasite nucleotide pool and validates HGXPRT as a target in malaria.

  3. [Involvement of phosphatidylinositol-4,5-bisphosphate binding proteins in the generation of contractile oscillations in the Physarum polycephalum plasmodium].

    PubMed

    Matveeva, N B; Beĭlina, S I; Kliueva, A A; Teplov, V A

    2014-01-01

    Using the Physarum polycephalum, plasmodium, a giant amoeboid cell with the strongly pronounced auto-oscillatory mode of motility, which exhibits regularities of motile behavior common with those of tissue cells and has the same signal systems, the possibility of the participation of phosphatidylinositol-4,5-bisphosphate in the regulation of the contractile activity has been studied. The effect of neomycin as a substrate inhibitor of phospholipase C, which binds with high affinity to phosphatidylinositol-4,5-bisphosphate in the membrane, on force oscillations generated by plasmodial strands under isometric conditions and after the addition of the protein kinase C inhibitors staurosporine, UCN-01, and Ro-318220, separatelyand in combination with the calmodulin inhibitor calmidazolium has been examined. It has been shown that neomycin at pH 7.0 and concentrations of 0.1-5.0 mM stops contractile oscillations for 10-30 min but then they begin to gradually restore; the oscillation period at the initial stage of the restoration is.shorter than it was earlier and then increases due to the elongation of the contraction phase. Analysis of data obtained is in favor of the assumption that the plasmodial membrane contains MARCKS-like proteins and protein kinase C-controlled pools of phosphatidylinositol-4,5-bisphosphate, which can participate in the generation of auto-oscillations observed in the plasmodium.

  4. Plasmodium Immunomics

    PubMed Central

    Doolan, Denise L.

    2010-01-01

    The Plasmodium parasite, the causative agent of malaria, is an excellent model for immunomic-based approaches to vaccine development. The Plasmodium parasite has a complex life cycle with multiple stages and stage-specific expression of ~ 5,300 putative proteins. No malaria vaccine has yet been licensed. Many believe that an effective vaccine will need to target several antigens and multiple stages, and will require the generation of both antibody and cellular immune responses. Vaccine efforts to date have been stage-specific and based on only a very limited number of proteins representing < 0.5% of the genome. The recent availability of comprehensive genomic, proteomic and transcriptomic datasets from human and selected non-human primate and rodent malarias provide a foundation to exploit for vaccine development. This information can be mined to identify promising vaccine candidate antigens, by proteome-wide screening of antibody and T cell reactivity using specimens from individuals exposed to malaria and technology platforms such as protein arrays, high throughput protein production and epitope prediction algorithms. Such antigens could be incorporated into a rational vaccine development process that targets specific stages of the Plasmodium parasite life cycle with immune responses implicated in parasite elimination and control. Immunomic approaches which enable the selection of the best possible targets by prioritizing antigens according to clinically relevant criteria may overcome the problem of poorly immunogenic, poorly protective vaccines that has plagued malaria vaccine developers for the past 25 years. Herein, current progress and perspectives regarding Plasmodium immunomics are reviewed. PMID:20816843

  5. High-Quality Genome Assembly and Annotation for Plasmodium coatneyi, Generated Using Single-Molecule Real-Time PacBio Technology.

    PubMed

    Chien, Jung-Ting; Pakala, Suman B; Geraldo, Juliana A; Lapp, Stacey A; Humphrey, Jay C; Barnwell, John W; Kissinger, Jessica C; Galinski, Mary R

    2016-09-01

    Plasmodium coatneyi is a protozoan parasite species that causes simian malaria and is an excellent model for studying disease caused by the human malaria parasite, P. falciparum Here we report the complete (nontelomeric) genome sequence of P. coatneyi Hackeri generated by the application of only Pacific Biosciences RS II (PacBio RS II) single-molecule real-time (SMRT) high-resolution sequence technology and assembly using the Hierarchical Genome Assembly Process (HGAP). This is the first Plasmodium genome sequence reported to use only PacBio technology. This approach has proven to be superior to short-read only approaches for this species.

  6. Georgia Power Company, Wansley Steam Electric Generating Plant; Petition to Object to Title V Operating Permit

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database.

  7. Thoroughbred Generating Company; Supplement to Petition to Object to Title V Operating Permit

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database.

  8. Petition to Object to Edwardsport Generating Station Title V Operating Permit

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database.

  9. Thoroughbred Generating Company, Muhlenberg County, Kentucky; Order Denying Petition For Objection To Title V Operating Permit

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database.

  10. Wisconsin Public Service, Weston Generating Station; Petition to Object to Issuance of Title V Operating Permit

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database.

  11. Hazardous Waste Permitting

    EPA Pesticide Factsheets

    To provide RCRA hazardous waste permitting regulatory information and resources permitted facilities, hazardous waste generators, and permit writers. To provide the public with information on how they can be involved in the permitting process.

  12. Defining the next generation of Plasmodium vivax diagnostic tests for control and elimination: Target product profiles.

    PubMed

    Ding, Xavier C; Ade, Maria Paz; Baird, J Kevin; Cheng, Qin; Cunningham, Jane; Dhorda, Mehul; Drakeley, Chris; Felger, Ingrid; Gamboa, Dionicia; Harbers, Matthias; Herrera, Socrates; Lucchi, Naomi; Mayor, Alfredo; Mueller, Ivo; Sattabongkot, Jetsumon; Ratsimbason, Arsène; Richards, Jack; Tanner, Marcel; González, Iveth J

    2017-04-01

    The global prevalence of malaria has decreased over the past fifteen years, but similar gains have not been realized against Plasmodium vivax because this species is less responsive to conventional malaria control interventions aimed principally at P. falciparum. Approximately half of all malaria cases outside of Africa are caused by P. vivax. This species places dormant forms in human liver that cause repeated clinical attacks without involving another mosquito bite. The diagnosis of acute patent P. vivax malaria relies primarily on light microscopy. Specific rapid diagnostic tests exist but typically perform relatively poorly compared to those for P. falciparum. Better diagnostic tests are needed for P. vivax. To guide their development, FIND, in collaboration with P. vivax experts, identified the specific diagnostic needs associated with this species and defined a series of three distinct target product profiles, each aimed at a particular diagnostic application: (i) point-of-care of acutely ill patients for clinical care purposes; (ii) point-of-care asymptomatic and otherwise sub-patent residents for public health purposes, e.g., mass screen and treat campaigns; and (iii) ultra-sensitive not point-of-care diagnosis for epidemiological research/surveillance purposes. This report presents and discusses the rationale for these P. vivax-specific diagnostic target product profiles. These contribute to the rational development of fit-for-purpose diagnostic tests suitable for the clinical management, control and elimination of P. vivax malaria.

  13. Assessing the impact of next-generation rapid diagnostic tests on Plasmodium falciparum malaria elimination strategies.

    PubMed

    Slater, Hannah C; Ross, Amanda; Ouédraogo, André Lin; White, Lisa J; Nguon, Chea; Walker, Patrick G T; Ngor, Pengby; Aguas, Ricardo; Silal, Sheetal P; Dondorp, Arjen M; La Barre, Paul; Burton, Robert; Sauerwein, Robert W; Drakeley, Chris; Smith, Thomas A; Bousema, Teun; Ghani, Azra C

    2015-12-03

    Mass-screen-and-treat and targeted mass-drug-administration strategies are being considered as a means to interrupt transmission of Plasmodium falciparum malaria. However, the effectiveness of such strategies will depend on the extent to which current and future diagnostics are able to detect those individuals who are infectious to mosquitoes. We estimate the relationship between parasite density and onward infectivity using sensitive quantitative parasite diagnostics and mosquito feeding assays from Burkina Faso. We find that a diagnostic with a lower detection limit of 200 parasites per microlitre would detect 55% of the infectious reservoir (the combined infectivity to mosquitoes of the whole population weighted by how often each individual is bitten) whereas a test with a limit of 20 parasites per microlitre would detect 83% and 2 parasites per microlitre would detect 95% of the infectious reservoir. Using mathematical models, we show that increasing the diagnostic sensitivity from 200 parasites per microlitre (equivalent to microscopy or current rapid diagnostic tests) to 2 parasites per microlitre would increase the number of regions where transmission could be interrupted with a mass-screen-and-treat programme from an entomological inoculation rate below 1 to one of up to 4. The higher sensitivity diagnostic could reduce the number of treatment rounds required to interrupt transmission in areas of lower prevalence. We predict that mass-screen-and-treat with a highly sensitive diagnostic is less effective than mass drug administration owing to the prophylactic protection provided to uninfected individuals by the latter approach. In low-transmission settings such as those in Southeast Asia, we find that a diagnostic tool with a sensitivity of 20 parasites per microlitre may be sufficient for targeted mass drug administration because this diagnostic is predicted to identify a similar village population prevalence compared with that currently detected using

  14. Next-generation sequencing reveals cryptic mtDNA diversity of Plasmodium relictum in the Hawaiian Islands.

    PubMed

    Jarvi, S I; Farias, M E; Lapointe, D A; Belcaid, M; Atkinson, C T

    2013-12-01

    Next-generation 454 sequencing techniques were used to re-examine diversity of mitochondrial cytochrome b lineages of avian malaria (Plasmodium relictum) in Hawaii. We document a minimum of 23 variant lineages of the parasite based on single nucleotide transitional changes, in addition to the previously reported single lineage (GRW4). A new, publicly available portal (Integroomer) was developed for initial parsing of 454 datasets. Mean variant prevalence and frequency was higher in low elevation Hawaii Amakihi (Hemignathus virens) with Avipoxvirus-like lesions (P = 0·001), suggesting that the variants may be biologically distinct. By contrast, variant prevalence and frequency did not differ significantly among mid-elevation Apapane (Himatione sanguinea) with or without lesions (P = 0·691). The low frequency and the lack of detection of variants independent of GRW4 suggest that multiple independent introductions of P. relictum to Hawaii are unlikely. Multiple variants may have been introduced in heteroplasmy with GRW4 or exist within the tandem repeat structure of the mitochondrial genome. The discovery of multiple mitochondrial lineages of P. relictum in Hawaii provides a measure of genetic diversity within a geographically isolated population of this parasite and suggests the origins and evolution of parasite diversity may be more complicated than previously recognized.

  15. Next-Generation Sequencing of Plasmodium vivax Patient Samples Shows Evidence of Direct Evolution in Drug-Resistance Genes

    PubMed Central

    Flannery, Erika L.; Wang, Tina; Akbari, Ali; Corey, Victoria C.; Gunawan, Felicia; Bright, A. Taylor; Abraham, Matthew; Sanchez, Juan F.; Santolalla, Meddly L.; Baldeviano, G. Christian; Edgel, Kimberly A.; Rosales, Luis A.; Lescano, Andrés G.; Bafna, Vineet; Vinetz, Joseph M.; Winzeler, Elizabeth A.

    2015-01-01

    Understanding the mechanisms of drug resistance in Plasmodium vivax, the parasite that causes the most widespread form of human malaria, is complicated by the lack of a suitable long-term cell culture system for this parasite. In contrast to P. falciparum, which can be more readily manipulated in the laboratory, insights about parasite biology need to be inferred from human studies. Here we analyze the genomes of parasites within 10 human P. vivax infections from the Peruvian Amazon. Using next-generation sequencing we show that some P. vivax infections analyzed from the region are likely polyclonal. Despite their polyclonality we observe limited parasite genetic diversity by showing that three or fewer haplotypes comprise 94% of the examined genomes, suggesting the recent introduction of parasites into this geographic region. In contrast we find more than three haplotypes in putative drug-resistance genes, including the gene encoding dihydrofolate reductase-thymidylate synthase and the P. vivax multidrug resistance associated transporter, suggesting that resistance mutations have arisen independently. Additionally, several drug-resistance genes are located in genomic regions with evidence of increased copy number. Our data suggest that whole genome sequencing of malaria parasites from patients may provide more insight about the evolution of drug resistance than genetic linkage or association studies, especially in geographical regions with limited parasite genetic diversity. PMID:26719854

  16. Next-generation sequencing reveals cryptic mtDNA diversity of Plasmodium relictum in the Hawaiian Islands

    USGS Publications Warehouse

    Jarvi, S.I.; Farias, M.E.; Lapointe, D.A.; Belcaid, M.; Atkinson, C.T.

    2013-01-01

    Next-generation 454 sequencing techniques were used to re-examine diversity of mitochondrial cytochrome b lineages of avian malaria (Plasmodium relictum) in Hawaii. We document a minimum of 23 variant lineages of the parasite based on single nucleotide transitional changes, in addition to the previously reported single lineage (GRW4). A new, publicly available portal (Integroomer) was developed for initial parsing of 454 datasets. Mean variant prevalence and frequency was higher in low elevation Hawaii Amakihi (Hemignathus virens) with Avipoxvirus-like lesions (P = 0·001), suggesting that the variants may be biologically distinct. By contrast, variant prevalence and frequency did not differ significantly among mid-elevation Apapane (Himatione sanguinea) with or without lesions (P = 0·691). The low frequency and the lack of detection of variants independent of GRW4 suggest that multiple independent introductions of P. relictum to Hawaii are unlikely. Multiple variants may have been introduced in heteroplasmy with GRW4 or exist within the tandem repeat structure of the mitochondrial genome. The discovery of multiple mitochondrial lineages of P. relictum in Hawaii provides a measure of genetic diversity within a geographically isolated population of this parasite and suggests the origins and evolution of parasite diversity may be more complicated than previously recognized.

  17. Changes in the superoxide anion generating capacity and respiratory burst enzymes of peripheral blood monocytes of monkeys during acute Plasmodium knowlesi infection.

    PubMed

    Jayshree, R S; Ganguly, N K; Sethi, A K; Mahajan, R C

    1989-09-01

    The superoxide anion generation profile of peripheral blood monocytes of rhesus monkeys was investigated during the different stages of an acute Plasmodium knowlesi infection. An initial increase in superoxide anion was followed by a significant decline (P less than 0.001), paralleled by a drop in NADPH oxidase activity; there was no alteration in the activity of the hexose monophosphate shunt enzymes. This lowered activity of the NADPH oxidase, with the resulting decreased O2 generation, might be responsible for the failure of the animals to control the parasitaemia; as a result they succumbed to the infection.

  18. January 22, 2004 Petition Requesting the Administrator Object to Operating Permit for Midwest Generation's Crawford Generating Station

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  19. January 22, 2004 Petition Requesting the Administrator Object to Operating Permit for Midwest Generation's Fisk Generating Station

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  20. Order Responding to January 22, 2004 Request that the Administrator Object to Operating Permit for Midwest Generation's Fisk Generating Station

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  1. Order Responding to January 22, 2004 Request that the Administrator Object to Operating Permit for Midwest Generation's Crawford Generating Station

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  2. Midwest Generation Joliet and Will County Generating Stations, Order Denying Petition for Objection to Title V Operating Permit

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  3. Midwest Generation Fisk and Crawford Generating Stations, Order Denying Petition for Objection to Title V Operating Permit

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  4. Petition requesting that the Administrator Object to Huntley Steam Generating Plant's Title V Permit

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  5. Petition Requesting that the Administrator Object to Dunkirk Steam Generating Station's Title V Permit

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  6. Salt River Project San Tan Generating Station, Petition to Object to Title V Operating Permit

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  7. Portland Generating Station, Order Denying Petition for Object to Title V Operating Permit

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  8. Petition Requesting the Administrator Object to Title V Operating Permit for Gateway Generating Station

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  9. Midwest Generation, Order Denying Petition for Object to Title V Operating Permits

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  10. January 24, 2003 Petition for the Administrator to Object to Thoroughbred Generating Station's Title V Permit

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  11. Portland Generating Station, Petition to Object to Title V Operating Permit

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  12. Petition to Object to the Cash Creek Generating Station, Henderson County, Kentucky, Title V Operating Permit

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  13. Petition for the Administrator to Object to Title V Permit for San Juan Generating Station

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  14. Order Deneying the Petition to Object to Title V Permit for Edwardsport Generating Station

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  15. Petition Requesting the Administrator Object to Goldendale Generating Station Title V Operating Permit

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  16. Petition Requesting the Administrator Object to the Title V Permit for the Cash Creek Generation Station

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  17. Order Partially Responding to Three Petitions for Luminant Generating Company Title V Permits

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  18. Objection to the Revised Hugh L. Spurlock Generating Station, Maysville, Kentucky, Title V Permit

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  19. Petition Requesting the Administrator Object to Luminant Generating Company's Monticelo Steam Electric Station Title V Permit

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  20. Petition for the Administrator to Object to Operating Permit for Sandow 5 Generating Plant

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  1. Order Denying Petition to Object to Operating Permit for Maui Electric Co., Ltd., Maalaea Generating Station

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  2. Louisiana Generating LLC, Big Cajun II Power Plant, Petition to Object to Title V Operating Permit

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  3. Response to Petition for EPA to Object to Cash Creek Generation Station's Title V Permit

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  4. Comments on the Indiana Department of Environmental Management Proposed Permit for NIPSCO Bailly Generating Station

    EPA Pesticide Factsheets

    This document may be of assistance in applying the New Source Review (NSR) air permitting regulations including the Prevention of Significant Deterioration (PSD) requirements. This document is part of the NSR Policy and Guidance Database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  5. Expansion of Lysine-rich Repeats in Plasmodium Proteins Generates Novel Localization Sequences That Target the Periphery of the Host Erythrocyte*

    PubMed Central

    Davies, Heledd M.; Thalassinos, Konstantinos; Osborne, Andrew R.

    2016-01-01

    Repetitive low complexity sequences, mostly assumed to have no function, are common in proteins that are exported by the malaria parasite into its host erythrocyte. We identify a group of exported proteins containing short lysine-rich tandemly repeated sequences that are sufficient to localize to the erythrocyte periphery, where key virulence-related modifications to the plasma membrane and the underlying cytoskeleton are known to occur. Efficiency of targeting is dependent on repeat number, indicating that novel targeting modules could evolve by expansion of short lysine-rich sequences. Indeed, analysis of fragments of GARP from different species shows that two novel targeting sequences have arisen via the process of repeat expansion in this protein. In the protein Hyp12, the targeting function of a lysine-rich sequence is masked by a neighboring repetitive acidic sequence, further highlighting the importance of repetitive low complexity sequences. We show that sequences capable of targeting the erythrocyte periphery are present in at least nine proteins from Plasmodium falciparum and one from Plasmodium knowlesi. We find these sequences in proteins known to be involved in erythrocyte rigidification and cytoadhesion as well as in previously uncharacterized exported proteins. Together, these data suggest that expansion and contraction of lysine-rich repeats could generate targeting sequences de novo as well as modulate protein targeting efficiency and function in response to selective pressure. PMID:27777305

  6. Magnetic isolation of Plasmodium falciparum schizonts iRBCs to generate a high parasitaemia and synchronized in vitro culture.

    PubMed

    Mata-Cantero, Lydia; Lafuente, Maria J; Sanz, Laura; Rodriguez, Manuel S

    2014-03-21

    The establishment of methods for an in vitro continuous culture of Plasmodium falciparum is essential for gaining knowledge into its biology and for the development of new treatments. Previously, several techniques have been used to synchronize, enrich and concentrate P. falciparum, although obtaining cultures with high parasitaemia continues being a challenging process. Current methods produce high parasitaemia levels of synchronized P. falciparum cultures by frequent changes of culture medium or reducing the haematocrit. However, these methods are time consuming and sometimes lead to the loss of synchrony. A procedure that combines Percoll and sorbitol treatments, the use of magnetic columns, and the optimization of the in vitro culture conditions to reach high parasitaemia levels for synchronized Plasmodium falciparum cultures is described. A new procedure has been established using P. falciparum 3D7, combining previous reported methodologies to achieve in vitro parasite cultures that reach parasitaemia up to 40% at any intra-erythrocytic stage. High parasitaemia levels are obtained only one day after magnetic column purification without compromising the parasite viability and synchrony. The described procedure allows obtaining a large scale synchronized parasite culture at a high parasitaemia with less manipulations than other methods previously described.

  7. Magnetic isolation of Plasmodium falciparum schizonts iRBCs to generate a high parasitaemia and synchronized in vitro culture

    PubMed Central

    2014-01-01

    Background The establishment of methods for an in vitro continuous culture of Plasmodium falciparum is essential for gaining knowledge into its biology and for the development of new treatments. Previously, several techniques have been used to synchronize, enrich and concentrate P. falciparum, although obtaining cultures with high parasitaemia continues being a challenging process. Current methods produce high parasitaemia levels of synchronized P. falciparum cultures by frequent changes of culture medium or reducing the haematocrit. However, these methods are time consuming and sometimes lead to the loss of synchrony. Methods A procedure that combines Percoll and sorbitol treatments, the use of magnetic columns, and the optimization of the in vitro culture conditions to reach high parasitaemia levels for synchronized Plasmodium falciparum cultures is described. Results A new procedure has been established using P. falciparum 3D7, combining previous reported methodologies to achieve in vitro parasite cultures that reach parasitaemia up to 40% at any intra-erythrocytic stage. High parasitaemia levels are obtained only one day after magnetic column purification without compromising the parasite viability and synchrony. Conclusions The described procedure allows obtaining a large scale synchronized parasite culture at a high parasitaemia with less manipulations than other methods previously described. PMID:24655321

  8. Transcriptome sequencing of lentil based on second-generation technology permits large-scale unigene assembly and SSR marker discovery

    PubMed Central

    2011-01-01

    Background Lentil (Lens culinaris Medik.) is a cool-season grain legume which provides a rich source of protein for human consumption. In terms of genomic resources, lentil is relatively underdeveloped, in comparison to other Fabaceae species, with limited available data. There is hence a significant need to enhance such resources in order to identify novel genes and alleles for molecular breeding to increase crop productivity and quality. Results Tissue-specific cDNA samples from six distinct lentil genotypes were sequenced using Roche 454 GS-FLX Titanium technology, generating c. 1.38 × 106 expressed sequence tags (ESTs). De novo assembly generated a total of 15,354 contigs and 68,715 singletons. The complete unigene set was sequence-analysed against genome drafts of the model legume species Medicago truncatula and Arabidopsis thaliana to identify 12,639, and 7,476 unique matches, respectively. When compared to the genome of Glycine max, a total of 20,419 unique hits were observed corresponding to c. 31% of the known gene space. A total of 25,592 lentil unigenes were subsequently annoated from GenBank. Simple sequence repeat (SSR)-containing ESTs were identified from consensus sequences and a total of 2,393 primer pairs were designed. A subset of 192 EST-SSR markers was screened for validation across a panel 12 cultivated lentil genotypes and one wild relative species. A total of 166 primer pairs obtained successful amplification, of which 47.5% detected genetic polymorphism. Conclusions A substantial collection of ESTs has been developed from sequence analysis of lentil genotypes using second-generation technology, permitting unigene definition across a broad range of functional categories. As well as providing resources for functional genomics studies, the unigene set has permitted significant enhancement of the number of publicly-available molecular genetic markers as tools for improvement of this species. PMID:21609489

  9. Transcriptome sequencing of lentil based on second-generation technology permits large-scale unigene assembly and SSR marker discovery.

    PubMed

    Kaur, Sukhjiwan; Cogan, Noel O I; Pembleton, Luke W; Shinozuka, Maiko; Savin, Keith W; Materne, Michael; Forster, John W

    2011-05-25

    Lentil (Lens culinaris Medik.) is a cool-season grain legume which provides a rich source of protein for human consumption. In terms of genomic resources, lentil is relatively underdeveloped, in comparison to other Fabaceae species, with limited available data. There is hence a significant need to enhance such resources in order to identify novel genes and alleles for molecular breeding to increase crop productivity and quality. Tissue-specific cDNA samples from six distinct lentil genotypes were sequenced using Roche 454 GS-FLX Titanium technology, generating c. 1.38 × 106 expressed sequence tags (ESTs). De novo assembly generated a total of 15,354 contigs and 68,715 singletons. The complete unigene set was sequence-analysed against genome drafts of the model legume species Medicago truncatula and Arabidopsis thaliana to identify 12,639, and 7,476 unique matches, respectively. When compared to the genome of Glycine max, a total of 20,419 unique hits were observed corresponding to c. 31% of the known gene space. A total of 25,592 lentil unigenes were subsequently annoated from GenBank. Simple sequence repeat (SSR)-containing ESTs were identified from consensus sequences and a total of 2,393 primer pairs were designed. A subset of 192 EST-SSR markers was screened for validation across a panel 12 cultivated lentil genotypes and one wild relative species. A total of 166 primer pairs obtained successful amplification, of which 47.5% detected genetic polymorphism. A substantial collection of ESTs has been developed from sequence analysis of lentil genotypes using second-generation technology, permitting unigene definition across a broad range of functional categories. As well as providing resources for functional genomics studies, the unigene set has permitted significant enhancement of the number of publicly-available molecular genetic markers as tools for improvement of this species.

  10. Adjuvant poly(N-isopropylacrylamide) generates more efficient monoclonal antibodies against truncated recombinant histidine-rich protein2 of Plasmodium falciparum for malaria diagnosis.

    PubMed

    Verma, Reena; Ravichandran, Ramakrishnan; Jayaprakash, Naatamai S; Kumar, Ashok; Vijayalakshmi, Mookambeswaran A; Venkataraman, Krishnan

    2015-05-01

    Adjuvants play an important role in eliciting immune responses and subsequent generation of antibodies with high specificity. Recently, poly(N-isopropylacrylamide) (PNiPAAm), also known as a "smart" polymer, has been proposed as a potential adjuvant for making antibodies and vaccines. This material exhibits efficient delivery, protection against degradation, and preservation of antigen epitopes. In this work, we used both CFA and smart polymer to develop a highly specific murine monoclonal antibody (mAb) against recombinant truncated histidine rich protein2 (HRP2) of Plasmodium falciparum. Our results indicate that the mAbs developed using these adjuvants were able to recognize recombinant HRP2 and native PfHRP2 protein from spent medium. The mAbs generated against recombinant truncated HRP2 showed better sensitivity to the antigen and importantly mAbs generated using PNiPAAm adjuvant were in the range of 10(8)-10(9) M(-1). The mAbs generated using PNiPAAm are very efficient and sensitive in detecting HRP2. To the best of our knowledge, this is the first report of such comparison having been made between these two adjuvants and we propose that the smart polymer has huge potential as an alternative to CFA. Additionally, we discuss the utility of the mAbs generated through PNiPAAm for specific diagnosis of malaria caused by P. falciparum.

  11. 78 FR 25081 - Reissuance of Final NPDES General Permits for Facilities/Operations That Generate, Treat, and/or...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-29

    ... EPA Region 8 Web page at http://www.epa.gov/region08/water/biosolids/documents.html . Please allow one..., and it will be much quicker to obtain permit coverage with general permits than with individual...)(1) of the Clean Water Act is not necessary for the issuance of these permits and certification will...

  12. The antioxidative effect of de novo generated vitamin B6 in Plasmodium falciparum validated by protein interference.

    PubMed

    Knöckel, Julia; Müller, Ingrid B; Butzloff, Sabine; Bergmann, Bärbel; Walter, Rolf D; Wrenger, Carsten

    2012-04-15

    The malaria parasite Plasmodium falciparum is able to synthesize de novo PLP (pyridoxal 5'-phosphate), the active form of vitamin B6. In the present study, we have shown that the de novo synthesized PLP is used by the parasite to detoxify 1O2 (singlet molecular oxygen), a highly destructive reactive oxygen species arising from haemoglobin digestion. The formation of 1O2 and the response of the parasite were monitored by live-cell fluorescence microscopy, by transcription analysis and by determination of PLP levels in the parasite. Pull-down experiments of transgenic parasites overexpressing the vitamin B6-biosynthetic enzymes PfPdx1 and PfPdx2 clearly demonstrated an interaction of the two proteins in vivo which results in an elevated PLP level from 12.5 μM in wild-type parasites to 36.6 μM in the PfPdx1/PfPdx2-overexpressing cells and thus to a higher tolerance towards 1O2. In contrast, by applying the dominant-negative effect on the cellular level using inactive mutants of PfPdx1 and PfPdx2, P. falciparum becomes susceptible to 1O2. Our results demonstrate clearly the crucial role of vitamin B6 biosynthesis in the detoxification of 1O2 in P. falciparum. Besides the known role of PLP as a cofactor of many essential enzymes, this second important task of the vitamin B6 de novo synthesis as antioxidant emphasizes the high potential of this pathway as a target of new anti-malarial drugs.

  13. Relaxed natural selection alone does not permit transposable element expansion within 4,000 generations in Escherichia coli.

    PubMed

    Plague, Gordon R; Dougherty, Kevin M; Boodram, Krystal S; Boustani, Samantha E; Cao, Huansheng; Manning, Sarah R; McNally, Camille C

    2011-07-01

    Insertion sequences (ISs) are transposable genetic elements in bacterial genomes. IS elements are common among bacteria but are generally rare within free-living species, probably because of the negative fitness effects they have on their hosts. Conversely, ISs frequently proliferate in intracellular symbionts and pathogens that recently transitioned from a free-living lifestyle. IS elements can profoundly influence the genomic evolution of their bacterial hosts, although it is unknown why they often expand in intracellular bacteria. We designed a laboratory evolution experiment with Escherichia coli K-12 to test the hypotheses that IS elements often expand in intracellular bacteria because of relaxed natural selection due to (1) their generally small effective population sizes (N (e)) and thus enhanced genetic drift, and (2) their nutrient rich environment, which makes many biosynthetic genes unnecessary and thus selectively neutral territory for IS insertion. We propagated 12 populations under four experimental conditions: large N (e) versus small N (e), and nutrient rich medium versus minimal medium. We found that relaxed selection over 4,000 generations was not sufficient to permit IS element expansion in any experimental population, thus leading us to hypothesize that IS expansion in intracellular symbionts may often be spurred by enhanced transposition rates, possibly due to environmental stress, coupled with relaxed natural selection.

  14. Relaxed natural selection alone does not permit transposable element expansion within 4,000 generations in Escherichia coli

    PubMed Central

    Plague, Gordon R.; Dougherty, Kevin M.; Boodram, Krystal S.; Boustani, Samantha E.; Cao, Huansheng; Manning, Sarah R.; McNally, Camille C.

    2011-01-01

    Insertion sequences (ISs) are transposable genetic elements in bacterial genomes. IS elements are common among bacteria but are generally rare within free-living species, probably because of the negative fitness effects they have on their hosts. Conversely, ISs frequently proliferate in intracellular symbionts and pathogens that recently transitioned from a free-living lifestyle. IS elements can profoundly influence the genomic evolution of their bacterial hosts, although it is unknown why they often expand in intracellular bacteria. We designed a laboratory evolution experiment with Escherichia coli K-12 to test the hypotheses that IS elements often expand in intracellular bacteria because of relaxed natural selection due to (1) their generally small effective population sizes (Ne) and thus enhanced genetic drift, and (2) their nutrient rich environment, which makes many biosynthetic genes unnecessary and thus selectively neutral territory for IS insertion. We propagated 12 populations under four experimental conditions: large Ne vs. small Ne, and nutrient rich medium vs. minimal medium. We found that relaxed selection over 4,000 generations was not sufficient to permit IS element expansion in any experimental population, thus leading us to hypothesize that IS expansion in intracellular symbionts may often be spurred by enhanced transposition rates, possibly due to environmental stress, coupled with relaxed natural selection. PMID:21751098

  15. Permit Fees

    EPA Pesticide Factsheets

    This site will provide basic information on clean air permitting under the title V operating permits program, provide access to state and regional permitting programs, and maintain access to proposed and final regulatory requirements.

  16. Petition Objecting to the Proposed Revised Title V Operating Permit for the Hugh L. Spurlock Generating Station, Maysville, Kentucky

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  17. Petition to Object to the Proposed Title V Permit for FirstEnergy Generation's Bruce Mansfield Power Station

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  18. July 9, 2002 Petition Requesting the Administrator Object to Bowen Steam-Electric Generating Plant's Operating Permit

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  19. Petition to Object to the Proposed Title V Permit for EME Homer City, LP's Homer City Generating Station

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  20. Petition for the Administrator to Object to Title V Permit for GenOn REMA, LLC's Shawville Generation Station

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  1. Order Responding to November 18, 2001 Petition for the Administrator to Object to Dynergy Northeast Generation's Operating Permit

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  2. January 21, 2004 Petition for the Administrator to Object to the Operating Permit for Midwest Generation's Waukegan, IL Facility

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  3. Order Responding to March 20, 2001 Petition Requesting the Administrator Object to Harquahala Generating Station's Operating Permit

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  4. Order Responding to 2002 Petition Requesting the Administrator Object to Keyspan Generating Far Rockaway Station's Title V Permit

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  5. Supplement to Petition to Object to the Proposed Title V Permit for EME Homer City Generating Station

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  6. Order Responding to a January 7, 2002 Request for the Administrator to Object to Huntley Generating Station's Operating Permit

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  7. Feb. 13, 2008, Petition to Object to the Cash Creek Generating Station, Henderson County, Kentucky, Title V Operating Permit

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  8. Georgia Center for Law in the Public Interest Petition to Object to Georgia Power's Scherer Generating Plant Title V Permit

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  9. Response to the Objection to Wisconsin Power and Light's Edgewater Generating Station, Sheboygan County, Wisconsin Title V Permit

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  10. Order Responding to Petition to Ojbject to Title V Permit for San Juan Generating Station, San Juan County, New Mexico

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  11. Petition to Object to the Madison Gas and Electric Company's Blount Street Generation Station, Dane County, Wisconsin, Title V Permit

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  12. June 22, 2010, Objection to the Revised Hugh L. Spurlock Generating Station, Maysville, Kentucky, Title V Permit

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  13. Petition to Object to the Transalta Centralia Generation, LLC Coal Fired Power Plant, Centralia, Washington, Title V Operating Permit

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  14. Georgia Center for Law in the Public Interest Petition to Object to Georgia Power's Bowen Generating Plant Title V Permit

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  15. Response Denying the Petition to Object to the Reliant Portland electricity generating plant, Northhampton County, Pennsylvania Title V Permit

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  16. Georgia Center for Law in the Public Interest Petition to Object to Georgia Power's Branch Generating Plant Title V Permit

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  17. Georgia Center for Law in the Public Interest Petition to Object to Georgia Power's Hammond Generating Plant Title V Permit

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  18. Order Responding to November 23, 2001 Request that the Administrator Object to Lovett Generating Station's Operating Permit

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  19. Order Responding to September 3, 2013 Petition to Object to Gateway Generating Station, LLC's Title V Permit

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  20. Midwest Generation, LLC, Joliet Generating Station - Order Responding to Petitioner's Request that the Administrator Object to Issuance of a State Operating Permit

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  1. Midwest Generation, LLC, Romeoville Generating Station - Order Responding to Petitioner's Request that the Administrator Object to Issuance of a State Operating Permit

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  2. Use of the atmospheric generators for capnophilic bacteria Genbag-CO2 for the evaluation of in vitro Plasmodium falciparum susceptibility to standard anti-malarial drugs

    PubMed Central

    2011-01-01

    Background The aim of this study was to evaluate the cultivation system in which the proper atmospheric conditions for growing Plasmodium falciparum parasites were maintained in a sealed bag. The Genbag® system associated with the atmospheric generators for capnophilic bacteria Genbag CO2® was used for in vitro susceptibility test of nine standard anti-malarial drugs and compared to standard incubator conditions. Methods The susceptibility of 36 pre-identified parasite strains from a wide panel of countries was assessed for nine standard anti-malarial drugs (chloroquine, quinine, mefloquine, monodesethylamodiaquine, lumefantrine, dihydroartemisinin, atovaquone and pyrimethamine) by the standard 42-hour 3H-hypoxanthine uptake inhibition method using the Genbag CO2® system and compared to controlled incubator conditions (5% CO2 and 10% O2). Results The counts per minute values in the control wells in incubator atmospheric conditions (5% CO2 and 10% O2) were significantly higher than those of Genbag® conditions (2738 cpm vs 2282 cpm, p < 0.0001). The geometric mean IC50 estimated under the incubator atmospheric conditions was significantly lower for atovaquone (1.2 vs 2.1 nM, p = 0.0011) and higher for the quinolines: chloroquine (127 vs 94 nM, p < 0.0001), quinine (580 vs 439 nM, p < 0.0001), monodesethylamodiaquine (41.4 vs 31.8 nM, p < 0.0001), mefloquine (57.5 vs 49.7 nM, p = 0.0011) and lumefantrine (23.8 vs 21.2 nM, p = 0.0044). There was no significant difference of IC50 between the 2 conditions for dihydroartemisinin, doxycycline and pyrimethamine. To reduce this difference in term of anti-malarial susceptibility, a specific cut-off was estimated for each drug under Genbag® conditions by regression. The cut-off was estimated at 77 nM for chloroquine (vs 100 nM in 10% O2), 611 nM for quinine (vs 800 nM), 30 nM for mefloquine (vs 30 nM), 61 nM for monodesethylamodiaquine (vs 80 nM) and 1729 nM for pyrimethamine (vs 2000 nM). Conclusions The atmospheric

  3. Overexpression of Plasmodium berghei ATG8 by Liver Forms Leads to Cumulative Defects in Organelle Dynamics and to Generation of Noninfectious Merozoites

    PubMed Central

    Voss, Christiane; Ehrenman, Karen; Mlambo, Godfree; Mishra, Satish; Kumar, Kota Arun; Sacci, John B.; Sinnis, Photini

    2016-01-01

    ABSTRACT Plasmodium parasites undergo continuous cellular renovation to adapt to various environments in the vertebrate host and insect vector. In hepatocytes, Plasmodium berghei discards unneeded organelles for replication, such as micronemes involved in invasion. Concomitantly, intrahepatic parasites expand organelles such as the apicoplast that produce essential metabolites. We previously showed that the ATG8 conjugation system is upregulated in P. berghei liver forms and that P. berghei ATG8 (PbATG8) localizes to the membranes of the apicoplast and cytoplasmic vesicles. Here, we focus on the contribution of PbATG8 to the organellar changes that occur in intrahepatic parasites. We illustrated that micronemes colocalize with PbATG8-containing structures before expulsion from the parasite. Interference with PbATG8 function by overexpression results in poor development into late liver stages and production of small merosomes that contain immature merozoites unable to initiate a blood infection. At the cellular level, PbATG8-overexpressing P. berghei exhibits a delay in microneme compartmentalization into PbATG8-containing autophagosomes and elimination compared to parasites from the parental strain. The apicoplast, identifiable by immunostaining of the acyl carrier protein (ACP), undergoes an abnormally fast proliferation in mutant parasites. Over time, the ACP staining becomes diffuse in merosomes, indicating a collapse of the apicoplast. PbATG8 is not incorporated into the progeny of mutant parasites, in contrast to parental merozoites in which PbATG8 and ACP localize to the apicoplast. These observations reveal that Plasmodium ATG8 is a key effector in the development of merozoites by controlling microneme clearance and apicoplast proliferation and that dysregulation in ATG8 levels is detrimental for malaria infectivity. PMID:27353755

  4. Manipulating the Plasmodium genome.

    PubMed

    Carvalho, Teresa Gil; Ménard, Robert

    2005-01-01

    Genome manipulation, the primary tool for assigning function to sequence, will be essential for understanding Plasmodium biology and malaria pathogenesis in molecular terms. The first success in transfecting Plasmodium was reported almost ten years ago. Gene-targeting studies have since flourished, as Plasmodium is haploid and integrates DNA only by homologous recombination. These studies have shed new light on the function of many proteins, including vaccine candidates and drug resistance factors. However, many essential proteins, including those involved in parasite invasion of erythrocytes, cannot be characterized in the absence of conditional mutagenesis. Proteins also cannot be identified on a functional basis as random DNA integration has not been achieved. We overview here the ways in which the Plasmodium genome can be manipulated. We also point to the tools that should be established if our goal is to address parasite infectivity in a systematic way and to conduct refined structure-function analysis of selected products.

  5. Wisconsin Public Service - Weston Generating Station; Order Denying in Part and Granting in Part a Petition for Objection to the Title V Operating Permit

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database.

  6. Plasmodium vivax: who cares?

    PubMed Central

    Galinski, Mary R; Barnwell, John W

    2008-01-01

    More attention is being focused on malaria today than any time since the world's last efforts to achieve eradication over 40 years ago. The global community is now discussing strategies aimed at dramatically reducing malarial disease burden and the eventual eradication of all types of malaria, everywhere. As a consequence, Plasmodium vivax, which has long been neglected and mistakenly considered inconsequential, is now entering into the strategic debates taking place on malaria epidemiology and control, drug resistance, pathogenesis and vaccines. Thus, contrary to the past, the malaria research community is becoming more aware and concerned about the widespread spectrum of illness and death caused by up to a couple of hundred million cases of vivax malaria each year. This review brings these issues to light and provides an overview of P. vivax vaccine development, then and now. Progress had been slow, given inherent research challenges and minimal support in the past, but prospects are looking better for making headway in the next few years. P. vivax, known to invade the youngest red blood cells, the reticulocytes, presents a strong challenge towards developing a reliable long-term culture system to facilitate needed research. The P. vivax genome was published recently, and vivax researchers now need to coordinate efforts to discover new vaccine candidates, establish new vaccine approaches, capitalize on non-human primate models for testing, and investigate the unique biological features of P. vivax, including the elusive P. vivax hypnozoites. Comparative studies on both P. falciparum and P. vivax in many areas of research will be essential to eradicate malaria. And to this end, the education and training of future generations of dedicated "malariologists" to advance our knowledge, understanding and the development of new interventions against each of the malaria species infecting humans also will be essential. PMID:19091043

  7. Plasmodium cynomolgi genome sequences provide insight into Plasmodium vivax and the monkey malaria clade

    PubMed Central

    Tachibana, Shin-Ichiro; Sullivan, Steven A.; Kawai, Satoru; Nakamura, Shota; Kim, Hyunjae R.; Goto, Naohisa; Arisue, Nobuko; Palacpac, Nirianne M. Q.; Honma, Hajime; Yagi, Masanori; Tougan, Takahiro; Katakai, Yuko; Kaneko, Osamu; Mita, Toshihiro; Kita, Kiyoshi; Yasutomi, Yasuhiro; Sutton, Patrick L.; Shakhbatyan, Rimma; Horii, Toshihiro; Yasunaga, Teruo; Barnwell, John W.; Escalante, Ananias A.; Carlton, Jane M.; Tanabe, Kazuyuki

    2013-01-01

    Plasmodium cynomolgi, a malaria parasite of Asian Old World monkeys, is the sister taxon of Plasmodium vivax, the most prevalent human malaria species outside Africa. Since P. cynomolgi shares many phenotypic, biologic and genetic characteristics of P. vivax, we generated draft genome sequences of three P. cynomolgi strains and performed comparative genomic analysis between them and P. vivax, as well as a third previously sequenced simian parasite, Plasmodium knowlesi. Here we show that genomes of the monkey malaria clade can be characterized by CNVs in multigene families involved in evasion of the human immune system and invasion of host erythrocytes. We identify genome-wide SNPs, microsatellites, and CNVs in the P. cynomolgi genome, providing a map of genetic variation for mapping parasite traits and studying parasite populations. The P. cynomolgi genome is a critical step in developing a model system for P. vivax research, and to counteract the neglect of P. vivax. PMID:22863735

  8. Secretory transport in Plasmodium.

    PubMed

    Elmendorf, H G; Haldar, K

    1993-03-01

    The asexual blood stage of the human malaria parasite Plasmodium falciparum resides within the mature erythrocyte - a cell that has no intracellular organelles and few biosynthetic activities. However, Plasmodium, as on actively growing and dividing cell, has numerous requirements for the uptake o f nutrients and expulsion of waste. Hence, the parasite must extensively remodel the erythrocyte to facilitate its survival, not only by exporting numerous proteins, but also by providing the requisite machinery for their .trafficking. In this review, Heidi Elmendorf and Kastun Haldar propose a model for secretion in P. falciparum.

  9. Plasmodium and mononuclear phagocytes.

    PubMed

    Mac-Daniel, Laura; Ménard, Robert

    2015-01-01

    Plasmodium, the causative agent of malaria, initially multiplies inside liver cells and then in successive cycles inside erythrocytes, causing the symptoms of the disease. In this review, we discuss interactions between the extracellular and intracellular forms of the Plasmodium parasite and innate immune cells in the mammalian host, with a special emphasis on mononuclear phagocytes. We overview here what is known about the innate immune cells that interact with parasites, mechanisms used by the parasite to evade them, and the protective or detrimental contribution of these interactions on parasite progression through its life cycle and pathology in the host.

  10. Immunization of mice with live-attenuated late liver stage-arresting Plasmodium yoelii parasites generates protective antibody responses to preerythrocytic stages of malaria.

    PubMed

    Keitany, Gladys J; Sack, Brandon; Smithers, Hannah; Chen, Lin; Jang, Ihn K; Sebastian, Leslie; Gupta, Megha; Sather, D Noah; Vignali, Marissa; Vaughan, Ashley M; Kappe, Stefan H I; Wang, Ruobing

    2014-12-01

    Understanding protective immunity to malaria is essential for the design of an effective vaccine to prevent the large number of infections and deaths caused by this parasitic disease. To date, whole-parasite immunization with attenuated parasites is the most effective method to confer sterile protection against malaria infection in clinical trials. Mouse model studies have highlighted the essential role that CD8(+) T cells play in protection against preerythrocytic stages of malaria; however, there is mounting evidence that antibodies are also important in these stages. Here, we show that experimental immunization of mice with Plasmodium yoelii fabb/f(-) (Pyfabb/f(-)), a genetically attenuated rodent malaria parasite that arrests late in the liver stage, induced functional antibodies that inhibited hepatocyte invasion in vitro and reduced liver-stage burden in vivo. These antibodies were sufficient to induce sterile protection from challenge by P. yoelii sporozoites in the absence of T cells in 50% of mice when sporozoites were administered by mosquito bite but not when they were administered by intravenous injection. Moreover, among mice challenged by mosquito bite, a higher proportion of BALB/c mice than C57BL/6 mice developed sterile protection (62.5% and 37.5%, respectively). Analysis of the antibody isotypes induced by immunization with Pyfabb/f(-) showed that, overall, BALB/c mice developed an IgG1-biased response, whereas C57BL/6 mice developed an IgG2b/c-biased response. Our data demonstrate for the first time that antibodies induced by experimental immunization of mice with a genetically attenuated rodent parasite play a protective role during the preerythrocytic stages of malaria. Furthermore, they highlight the importance of considering both the route of challenge and the genetic background of the mouse strains used when interpreting vaccine efficacy studies in animal models of malaria infection. Copyright © 2014, American Society for Microbiology. All

  11. EPA Finalizes Greenhouse Gas Permit for Tenaska Brownsville Generating Plant, $500M facility will bring 600-700 construction jobs to Brownsville, TX, area

    EPA Pesticide Factsheets

    DALLAS - (Jan. 26, 2014) Today, the U.S. Environmental Protection Agency (EPA) issued a final greenhouse gas (GHG) Prevention of Significant Deterioration (PSD) construction permit to Tenaska Brownsville Partners L.P., to construct a natural gas-fir

  12. Plasmodium berghei bio-burden correlates with parasite lactate dehydrogenase: application to murine Plasmodium diagnostics.

    PubMed

    De, Sai Lata; Stanisic, Danielle I; Rivera, Fabian; Batzloff, Michael R; Engwerda, Christian; Good, Michael F

    2016-01-04

    The spectrum of techniques to detect malaria parasites in whole blood is limited to measuring parasites in circulation. One approach that is currently used to enumerate total parasite bio-burden involves the use of bio-luminescent parasites. As an alternative approach, this study describes the use of a commercial ELISA human parasite lactate dehydrogenase (pLDH) detection kit to estimate total parasite bio-burden in murine malaria models. The cross reactivity of pLDH in a commercial human malaria pLDH diagnostic kit was established in different components of blood for different murine malaria models. The use of pLDH as a measure of parasite bio-burden was evaluated by examining pLDH in relation to peripheral blood parasitaemia as determined by microscopy and calculating total parasite bio-burden using a bio-luminescent Plasmodium berghei ANKA luciferase parasite. The pLDH antigen was detected in all four murine Plasmodium species and in all components of Plasmodium-infected blood. A significant correlation (r = 0.6922, P value <0.0001) was observed between total parasite bio-burden, measured as log average radiance, and concentration of pLDH units. This high throughput assay is a suitable measure of total parasite bio-burden in murine malaria infections. Unlike existing methods, it permits the estimation of both circulating and sequestered parasites, allowing a more accurate assessment of parasite bio-burden.

  13. Petition Requesting that the Administrator Object to the Issuance of the Proposed Title V Operating Permit for the Danskammer Generating Station

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  14. Petition to Object to the Proposed Title V Permit for Sunbury Generation, LP's Power Plant Issued by the Pennsylvania Department of Environmental Protection

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  15. Order Denying the Petition to Object to the Transalta Centralia Generation, LLC Coal Fired Power Plant, Centralia, Washington, Title V Operating Permit

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  16. Petition for the Administrator to Object to Title V Operating Permit for Fort Smallwood Complex Brandon Shores and H.A. Wagner Generating Stations

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  17. Order Denying and Granting in Part the Petition to Object to the Cash Creek Generating Station, Henderson County, Kentucky, Title V Operating Permit

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  18. Order Responding to September 27, 2002 Request for the Administrator to Object to the Operating Permit for Consolidated Edison Company's Hudson Avenue Generating Station

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  19. East Kentucky Power Spurlock Generating Station, Order Granting in Part and Denying in Part Petition for Objection to a Title V Permit

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  20. 40 CFR 60.4124 - Hg budget permit revisions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 6 2010-07-01 2010-07-01 false Hg budget permit revisions. 60.4124... Coal-Fired Electric Steam Generating Units Permits § 60.4124 Hg budget permit revisions. Except as provided in § 60.4123(b), the permitting authority will revise the Hg Budget permit, as necessary, in...

  1. Plasmodium knowlesi infection: a diagnostic challenge

    PubMed Central

    Fan, Lijia; Lee, Shir Ying; Koay, Evelyn; Harkensee, Christian

    2013-01-01

    Plasmodium knowlesi malaria is an uncommon, but highly prevalent parasitic infection in parts of Malaysia. This is the case of a 14-year-old Singaporean boy presenting to our emergency department with an 11-day history of fever following a school trip to Malaysia. Hepatosplenomegaly was the only clinical finding; laboratory tests showed thrombocytopaenia, lymphopaenia, mild anaemia and liver transaminitis. Specific malaria antigen tests were negative, but the peripheral blood film showed plasmodia with atypical features, with a parasite load of 0.5%. PCR confirmed the diagnosis of P knowlesi. The patient was successfully treated with chloroquine. The clinical course of P knowlesi malaria is indistinguishable from that of Plasmodium falciparum. This case highlights the importance of taking detailed travel history, careful examination of malaria blood films and judicious use of molecular techniques. Antigen tests alone may have missed a malaria diagnosis altogether, while blood film examination may wrongly identify the species as Plasmodium malariae or P falciparum. Third-generation PCR assays can be used to reliably identify P knowlesi. PMID:23608876

  2. Plasmodium falciparum malaria.

    PubMed

    Shetty, A K; Steele, R W

    1999-01-01

    A 13-year-old adolescent daughter of a missionary presented with fever and jaundice 1 week after returning from Africa. Examination of peripheral blood film revealed the diagnosis of Plasmodium falciparum infection. Therapy with oral quinine and doxycycline was curative. Diagnosis requires a travel history and a high index of suspicion. Because of the frequency of international travel, United States physicians need to be familiar with the presentation and management of imported P falciparum. Preparation for such travel must include careful counseling and optimal use of chemoprophylaxis.

  3. Regulatory and Permitting Issues

    SciTech Connect

    Larry Myer

    2005-12-01

    As part of the West Coast Regional Carbon Sequestration Partnership (WESTCARB), Terralog Technologies USA, Inc., reviewed current state and federal regulations related to carbon dioxide capture and storage within geologic formations and enhanced carbon uptake in terrestrial ecosystems. We have evaluated and summarized the current and possible future permitting requirements for the six states that comprise the West Coast Regional Partnership. Four options exist for CO{sub 2} injection into appropriate geologic formations, including storage in: (1) oil and gas reservoirs, (2) saline formations, (3) unmineable coal beds, and (4) salt caverns. Terrestrial CO{sub 2} sequestration involves improved carbon conservation management (e.g. reduction of deforestation), carbon substitution (e.g., substitution for fossil fuel-based products, energy conservation through urban forestry, biomass for energy generation), and improved carbon storage management (e.g., expanding the storage of carbon in forest ecosystems). The primary terrestrial options for the West Coast Region include: (1) reforestation of under-producing lands (including streamside forest restoration), (2) improved forest management, (3) forest protection and conservation, and (4) fuel treatments for the reduction of risk of uncharacteristically severe fires (potentially with associated biomass energy generation). The permits and/or contracts required for any land-use changes/disturbances and biomass energy generation that may occur as part of WESTCARB's activities have been summarized for each state.

  4. NPDES Permit Writers' Course

    EPA Pesticide Factsheets

    The objective of the NPDES permit writers' course is to provide the basic regulatory framework and technical considerations that support the development of wastewater discharge permits as required under the NPDES Permit Program.

  5. Historical Permit Fee Rates

    EPA Pesticide Factsheets

    This site will provide basic information on clean air permitting under the title V operating permits program, provide access to state and regional permitting programs, and maintain access to proposed and final regulatory requirements. Historical fee rates.

  6. Title V Operating Permits

    EPA Pesticide Factsheets

    This site will provide basic information on clean air permitting under the title V operating permits program, provide access to state and regional permitting programs, and maintain access to proposed and final regulatory requirements.

  7. EPA Issued Operating Permits

    EPA Pesticide Factsheets

    This site will provide basic information on clean air permitting under the title V operating permits program, provide access to state and regional permitting programs, and maintain access to proposed and final regulatory requirements.

  8. Identification and Localization of Minimal MHC-restricted CD8+ T Cell Epitopes within the Plasmodium falciparum AMA1 Protein

    DTIC Science & Technology

    2010-08-24

    Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the...A, Muratova O, Awkal M, et al: Phase 1 clinical trial of apical membrane antigen 1: an asexual blood-stage vaccine for Plasmodium falciparum malaria...PfCP-2.9, an asexual blood-stage vaccine candidate of Plasmodium falciparum. Malar J 2010, 9(1):94. 40. Senger T, Becker MR, Schadlich L, Waterboer T

  9. Wolbachia increases susceptibility to Plasmodium infection in a natural system

    PubMed Central

    Zélé, F.; Nicot, A.; Berthomieu, A.; Weill, M.; Duron, O.; Rivero, A.

    2014-01-01

    Current views about the impact of Wolbachia on Plasmodium infections are almost entirely based on data regarding artificially transfected mosquitoes. This work has shown that Wolbachia reduces the intensity of Plasmodium infections in mosquitoes, raising the exciting possibility of using Wolbachia to control or limit the spread of malaria. Whether natural Wolbachia infections have the same parasite-inhibiting properties is not yet clear. Wolbachia–mosquito combinations with a long evolutionary history are, however, key for understanding what may happen with Wolbachia-transfected mosquitoes after several generations of coevolution. We investigate this issue using an entirely natural mosquito–Wolbachia–Plasmodium combination. In contrast to most previous studies, which have been centred on the quantification of the midgut stages of Plasmodium, we obtain a measurement of parasitaemia that relates directly to transmission by following infections to the salivary gland stages. We show that Wolbachia increases the susceptibility of Culex pipiens mosquitoes to Plasmodium relictum, significantly increasing the prevalence of salivary gland stage infections. This effect is independent of the density of Wolbachia in the mosquito. These results suggest that naturally Wolbachia-infected mosquitoes may, in fact, be better vectors of malaria than Wolbachia-free ones. PMID:24500167

  10. Wolbachia increases susceptibility to Plasmodium infection in a natural system.

    PubMed

    Zélé, F; Nicot, A; Berthomieu, A; Weill, M; Duron, O; Rivero, A

    2014-03-22

    Current views about the impact of Wolbachia on Plasmodium infections are almost entirely based on data regarding artificially transfected mosquitoes. This work has shown that Wolbachia reduces the intensity of Plasmodium infections in mosquitoes, raising the exciting possibility of using Wolbachia to control or limit the spread of malaria. Whether natural Wolbachia infections have the same parasite-inhibiting properties is not yet clear. Wolbachia-mosquito combinations with a long evolutionary history are, however, key for understanding what may happen with Wolbachia-transfected mosquitoes after several generations of coevolution. We investigate this issue using an entirely natural mosquito-Wolbachia-Plasmodium combination. In contrast to most previous studies, which have been centred on the quantification of the midgut stages of Plasmodium, we obtain a measurement of parasitaemia that relates directly to transmission by following infections to the salivary gland stages. We show that Wolbachia increases the susceptibility of Culex pipiens mosquitoes to Plasmodium relictum, significantly increasing the prevalence of salivary gland stage infections. This effect is independent of the density of Wolbachia in the mosquito. These results suggest that naturally Wolbachia-infected mosquitoes may, in fact, be better vectors of malaria than Wolbachia-free ones.

  11. Small molecule screen for candidate antimalarials targeting Plasmodium Kinesin-5.

    PubMed

    Liu, Liqiong; Richard, Jessica; Kim, Sunyoung; Wojcik, Edward J

    2014-06-06

    Plasmodium falciparum and vivax are responsible for the majority of malaria infections worldwide, resulting in over a million deaths annually. Malaria parasites now show measured resistance to all currently utilized drugs. Novel antimalarial drugs are urgently needed. The Plasmodium Kinesin-5 mechanoenzyme is a suitable "next generation" target. Discovered via small molecule screen experiments, the human Kinesin-5 has multiple allosteric sites that are "druggable." One site in particular, unique in its sequence divergence across all homologs in the superfamily and even within the same family, exhibits exquisite drug specificity. We propose that Plasmodium Kinesin-5 shares this allosteric site and likewise can be targeted to uncover inhibitors with high specificity. To test this idea, we performed a screen for inhibitors selective for Plasmodium Kinesin-5 ATPase activity in parallel with human Kinesin-5. Our screen of nearly 2000 compounds successfully identified compounds that selectively inhibit both P. vivax and falciparum Kinesin-5 motor domains but, as anticipated, do not impact human Kinesin-5 activity. Of note is a candidate drug that did not biochemically compete with the ATP substrate for the conserved active site or disrupt the microtubule-binding site. Together, our experiments identified MMV666693 as a selective allosteric inhibitor of Plasmodium Kinesin-5; this is the first identified protein target for the Medicines of Malaria Venture validated collection of parasite proliferation inhibitors. This work demonstrates that chemical screens against human kinesins are adaptable to homologs in disease organisms and, as such, extendable to strategies to combat infectious disease.

  12. Laser-induced inactivation of Plasmodium falciparum

    PubMed Central

    2012-01-01

    Background Haemozoin crystals, produced by Plasmodium during its intra-erythrocytic asexual reproduction cycle, can generate UV light via the laser-induced, non-linear optical process of third harmonic generation (THG). In the current study the feasibility of using haemozoin, constitutively stored in the parasite’s food vacuole, to kill the parasite by irradiation with a near IR laser was evaluated. Methods Cultured Plasmodium parasites at different stages of development were irradiated with a pulsed NIR laser and the viability of parasites at each stage was evaluated from their corresponding growth curves using the continuous culture method. Additional testing for germicidal effects of haemozoin and NIR laser was performed by adding synthetic haemozoin crystals to Escherichia coli in suspension. Cell suspensions were then irradiated with the laser and small aliquots taken and spread on agar plates containing selective agents to determine cell viability (CFU). Results Parasites in the late-trophozoites form as well as trophozoites in early-stage of DNA synthesis were found to be the most sensitive to the treatment with ~4-log reduction in viability after six passes through the laser beam; followed by parasites in ring phase (~2-log reduction). A ~1-log reduction in E. coli viability was obtained following a 60 min irradiation regimen of the bacteria in the presence of 1 μM synthetic haemozoin and a ~2-log reduction in the presence of 10 μM haemozoin. Minimal (≤15%) cell kill was observed in the presence of 10 μM haemin. Conclusions Laser-induced third-harmonic generation by haemozoin can be used to inactivate Plasmodium. This result may have clinical implications for treating severe malaria symptoms by irradiating the patient’s blood through the skin or through dialysis tubing with a NIR laser. PMID:22873646

  13. Attacking Plasmodium vivax

    PubMed Central

    Baird, J. Kevin

    2016-01-01

    Discussions beginning in 2012 ultimately led to a landmark document from the World Health Organization (WHO) titled, Control and Elimination of Plasmodium vivax: A Technical Brief, published in July 2015. That body of work represents multiple expert consultations coordinated by the WHO Global Malaria Program, along with technical consensus gathering from national malaria control programs via the WHO regional offices around the globe. That document thus represents thoroughly vetted state-of-the-art recommendations for dealing specifically with P. vivax, the first assembly of such by the WHO. This supplement to the journal was commissioned by the WHO and compiles the very substantial body of evidence and analysis informing those recommendations. This introductory narrative to the supplement provides the historical and technological context of global strategy for combatting P. vivax and reducing the burdens of morbidity and mortality it imposes. PMID:27708186

  14. Diagnosis and Treatment of Plasmodium vivax Malaria

    PubMed Central

    Baird, J. Kevin; Valecha, Neena; Duparc, Stephan; White, Nicholas J.; Price, Ric N.

    2016-01-01

    The diagnosis and treatment of Plasmodium vivax malaria differs from that of Plasmodium falciparum malaria in fundamentally important ways. This article reviews the guiding principles, practices, and evidence underpinning the diagnosis and treatment of P. vivax malaria. PMID:27708191

  15. [From malaria parasite point of view--Plasmodium falciparum evolution].

    PubMed

    Zerka, Agata; Kaczmarek, Radosław; Jaśkiewicz, Ewa

    2015-12-31

    Malaria is caused by infection with protozoan parasites belonging to the genus Plasmodium, which have arguably exerted the greatest selection pressure on humans in the history of our species. Besides humans, different Plasmodium parasites infect a wide range of animal hosts, from marine invertebrates to primates. On the other hand, individual Plasmodium species show high host specificity. The extraordinary evolution of Plasmodium probably began when a free-living red algae turned parasitic, and culminated with its ability to thrive inside a human red blood cell. Studies on the African apes generated new data on the evolution of malaria parasites in general and the deadliest human-specific species, Plasmodium falciparum, in particular. Initially, it was hypothesized that P. falciparum descended from the chimpanzee malaria parasite P. reichenowi, after the human and the chimp lineage diverged about 6 million years ago. However, a recently identified new species infecting gorillas, unexpectedly showed similarity to P. falciparum and was therefore named P. praefalciparum. That finding spurred an alternative hypothesis, which proposes that P. falciparum descended from its gorilla rather than chimp counterpart. In addition, the gorilla-to-human host shift may have occurred more recently (about 10 thousand years ago) than the theoretical P. falciparum-P. reichenowi split. One of the key aims of the studies on Plasmodium evolution is to elucidate the mechanisms that allow the incessant host shifting and retaining the host specificity, especially in the case of human-specific species. Thorough understanding of these phenomena will be necessary to design effective malaria treatment and prevention strategies.

  16. Expression and characterisation of plasmepsin I from Plasmodium falciparum.

    PubMed

    Moon, R P; Tyas, L; Certa, U; Rupp, K; Bur, D; Jacquet, C; Matile, H; Loetscher, H; Grueninger-Leitch, F; Kay, J; Dunn, B M; Berry, C; Ridley, R G

    1997-03-01

    Two aspartic proteinases, plasmepsins I and II, are present in the digestive vacuole of the human malarial parasite Plasmodium falciparum and are believed to be essential for parasite degradation of haemoglobin. Here we report the expression and kinetic characterisation of functional recombinant plasmepsin I. In order to generate active plasmepsin I from its precursor, an autocatalytic cleavage site was introduced into the propart of the zymogen by mutation of Lys110P to Val (P indicates a propart residue). Appropriate refolding of the mutated zymogen then permitted pH-dependent autocatalytic processing of the zymogen to the active mature proteinase. A purification scheme was devised that removed aggregated and misfolded protein to yield pure, fully processable, proplasmepsin I. Kinetic constants for two synthetic peptide substrates and four inhibitors were determined for both recombinant plasmepsin I and recombinant plasmepsin II. Plasmepsin I had 5-10-fold lower k(cat)/Km values than plasmepsin II for the peptide substrates, while the aspartic proteinase inhibitors, selected for their ability to inhibit P. falciparum growth, were found to have up to 80-fold lower inhibition constants for plasmepsin I compared to plasmepsin II. The most active plasmepsin I inhibitors were antagonistic to the antimalarial action of chloroquine on cultured parasites. Northern blot analysis of RNA, isolated from specific stages of the erythrocytic cycle of P. falciparum, showed that the proplasmepsin I gene is expressed in the ring stages whereas the proplasmepsin II gene is not transcribed until the later trophozoite stage of parasite growth. The differences in kinetic properties and temporal expression of the two plasmepsins suggest they are not functionally redundant but play distinct roles in the parasite.

  17. [Involvement of cyclic adenosine monophosphate in the control of motile behavior of Physarum polycephalum plasmodium].

    PubMed

    Matveeva, N B; Teplov, V A; Nezvetskiĭ, A R; Orlova, T G; Beĭlina, S I

    2012-01-01

    Possible involvement of autocrine factors into the control of motile behavior via a receptor-mediated mechanism was investigated in Physarum polycephalum plasmodium, a multinuclear amoeboid cell with the auto-oscillatory mode of motility. Cyclic adenosine monophosphate (cAMP) and extracellular cAMP-specific phosphodiesterase, its involvement into the control of plasmodium motile behavior was proved by action of its strong inhibitor, were regarded as putative autocrine factors. It was shown that the plasmodium secreted cAMP. When it was introduced into agar support, 0,1-1 mM cAMP induced a delay of the plasmodium spreading and its transition to migration. When locally applied, cAMP at the same concentrations induced typical for attractant action the increase in oscillation frequency and the decrease of ectoplasm elasticity. The ability to exhibit positive chemotaxis in cAMP gradient and the dependence of its realization were shown to depend on the plasmodium state. Chemotaxis test specimens obtained from the migrating plasmodium, unlike those obtained from growing culture, generate alternative fronts which compete effectively with fronts oriented towards the attractant increment. The results obtained support our supposition stated earlier that advance of the Physarum polycephalum plasmodium leading edge is determined by local extracellular cAMP gradients arising from a time delay between secretion and hydrolysis of the nucleotide.

  18. Federal Environmental Permitting Handbook

    SciTech Connect

    Not Available

    1991-05-01

    The handbook consists of eight chapters addressing permitting and licensing requirements under the Resource Conservation and Recovery Act (RCRA), the Comprehensive Environmental Response, Compensation, and Liability Act of 1980, as amended by the Superfund Amendments and Reauthorization Act of 1986 (CERCLA/SARA), the Atomic Energy Act (AEA), the Clean Air Act (CAA), the Clean Water Act (CWA), the Federal Insectide, Fungicide, and Rodenticide Act (FIFRA), the Safe Drinking Water Act (SDWA), and the Toxic Substances Control Act (TSCA). Each chapter consists of: (1) an introduction to the statute and permitting requirements; (2) a diagram illustrating the relationship between permitting requirements under the statute being discussed and permitting requirements from other environmental statutes which may have to be addressed when applying for a particular permit (e.g., when applying for a RCRA permit, permits and permit applications under the CWA, CAA, SDWA, etc. would have to be listed in the RCRA permit application); and, (3) a compilation of the permitting requirements for the regulatory program resulting from the statute. In addition, the Handbook contains a permitting keyword index and a listing of hotline telephone numbers for each of the statutes.

  19. 77 FR 5009 - Clean Air Act Operating Permit Program; Petition for Objection to State Operating Permit for Duke...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-01

    ... object to a Clean Air Act (Act) Title V operating permit for Duke Energy Indiana--Edwardsport Generating... AGENCY Clean Air Act Operating Permit Program; Petition for Objection to State Operating Permit for Duke Energy Indiana--Edwardsport Generating Station AGENCY: Environmental Protection Agency (EPA)....

  20. NH Small MS4 General Permit | Stormwater Permits | NPDES ...

    EPA Pesticide Factsheets

    2017-04-13

    The 2017 New Hampshire Small MS4 General Permit was issued on January 18, 2017. The final permit reflects modifications to the 2013 Draft Small MS4 General Permit and the 2015 Renoticed permit sections.

  1. Vaccination with Altered Peptide Ligands of a Plasmodium berghei Circumsporozoite Protein CD8 T-Cell Epitope: A Model to Generate T Cells Resistant to Immune Interference by Polymorphic Epitopes

    PubMed Central

    Minigo, Gabriela; Flanagan, Katie L.; Slattery, Robyn M.; Plebanski, Magdalena

    2017-01-01

    Many pathogens, including the malaria parasite Plasmodium falciparum, display high levels of polymorphism within T-cell epitope regions of proteins associated with protective immunity. The T-cell epitope variants are often non-cross-reactive. Herein, we show in a murine model, which modifies a protective CD8 T-cell epitope from the circumsporozoite protein (CS) of Plasmodium berghei (SYIPSAEKI), that simultaneous or sequential co-stimulation with two of its putative similarly non-cross-reactive altered peptide ligand (APL) epitopes (SYIPSAEDI or SYIPSAEAI) has radically different effects on immunity. Hence, co-immunization or sequential stimulation in vivo of SYIPSAEKI with its APL antagonist SYIPSAEDI decreases immunity to both epitopes. By contrast, co-immunization with SYIPSAEAI has no apparent initial effect, but it renders the immune response to SYIPSAEKI resistant to being turned off by subsequent immunization with SYIPSAEDI. These results suggest a novel strategy for vaccines that target polymorphic epitopes potentially capable of mutual immune interference in the field, by initiating an immune response by co-immunization with the desired index epitope, together with a carefully selected “potentiator” APL peptide. PMID:28261200

  2. CCS Project Permit Acquisition Protocols

    SciTech Connect

    Lee, Si-Yong; Zaluski, Wade; Matthews, Vince; McPherson, Brian

    2013-06-30

    Geologic carbon storage projects require a vast range of permits prior to deployment. These include land-access permits, drilling permits, seismic survey permits, underground injection control permits, and any number of local and state permits, depending on the location of the project. For the “Characterization of Most Promising Sequestration Formations in the Rocky Mountain Region” (RMCCS) project in particular, critical permits included site access permits, seismic survey permits, and drilling permits for the characterization well. Permits for these and other activities were acquired either prior to or during the project.

  3. Plasmodium vivax Malaria in Cambodia

    PubMed Central

    Siv, Sovannaroth; Roca-Feltrer, Arantxa; Vinjamuri, Seshu Babu; Bouth, Denis Mey; Lek, Dysoley; Rashid, Mohammad Abdur; By, Ngau Peng; Popovici, Jean; Huy, Rekol; Menard, Didier

    2016-01-01

    The Cambodian National Strategic Plan for Elimination of Malaria aims to move step by step toward elimination of malaria across Cambodia with an initial focus on Plasmodium falciparum malaria before achieving elimination of all forms of malaria, including Plasmodium vivax in 2025. The emergence of artemisinin-resistant P. falciparum in western Cambodia over the last decade has drawn global attention to support the ultimate goal of P. falciparum elimination, whereas the control of P. vivax lags much behind, making the 2025 target gradually less achievable unless greater attention is given to P. vivax elimination in the country. The following review presents in detail the past and current situation regarding P. vivax malaria, activities of the National Malaria Control Program, and interventional measures applied. Constraints and obstacles that can jeopardize our efforts to eliminate this parasite species are discussed. PMID:27708187

  4. Tetany with Plasmodium falciparum infection.

    PubMed

    Singh, P S; Singh, Neha

    2012-07-01

    Plasmodium falciparum is a malarial infection with high morbidity and wide spectrum of atypical presentation. Here we report an unusual presentation of malaria as tetany with alteration in calcium,phosphate and magnesium metabolism Hypocalcaemia in malaria can cause prolonged Q-Tc interval which could be arisk factor for quinine cardiotoxicity and sudden death Hence monitoring of serum calcium in severe malarial infection and cautious use of quinine in such patients is very important in management

  5. Permit Shields and NSR

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  6. Global Epidemiology of Plasmodium vivax

    PubMed Central

    Howes, Rosalind E.; Battle, Katherine E.; Mendis, Kamini N.; Smith, David L.; Cibulskis, Richard E.; Baird, J. Kevin; Hay, Simon I.

    2016-01-01

    Plasmodium vivax is the most widespread human malaria, putting 2.5 billion people at risk of infection. Its unique biological and epidemiological characteristics pose challenges to control strategies that have been principally targeted against Plasmodium falciparum. Unlike P. falciparum, P. vivax infections have typically low blood-stage parasitemia with gametocytes emerging before illness manifests, and dormant liver stages causing relapses. These traits affect both its geographic distribution and transmission patterns. Asymptomatic infections, high-risk groups, and resulting case burdens are described in this review. Despite relatively low prevalence measurements and parasitemia levels, along with high proportions of asymptomatic cases, this parasite is not benign. Plasmodium vivax can be associated with severe and even fatal illness. Spreading resistance to chloroquine against the acute attack, and the operational inadequacy of primaquine against the multiple attacks of relapse, exacerbates the risk of poor outcomes among the tens of millions suffering from infection each year. Without strategies accounting for these P. vivax-specific characteristics, progress toward elimination of endemic malaria transmission will be substantially impeded. PMID:27402513

  7. Should Consumers Be Priced Out of Pollution-Permit Markets?

    ERIC Educational Resources Information Center

    Smith, Stefani C.; Yates, Andrew J.

    2003-01-01

    Presents a simple diagrammatic exposition of a pollution-permit market in which firms that generate pollution and consumers who are harmed by pollution are allowed to purchase permits at a single market price. Illustrates that the market equilibrium is efficient only if the endowment of permits is equal to the efficient level of pollution. (JEH)

  8. Should Consumers Be Priced Out of Pollution-Permit Markets?

    ERIC Educational Resources Information Center

    Smith, Stefani C.; Yates, Andrew J.

    2003-01-01

    Presents a simple diagrammatic exposition of a pollution-permit market in which firms that generate pollution and consumers who are harmed by pollution are allowed to purchase permits at a single market price. Illustrates that the market equilibrium is efficient only if the endowment of permits is equal to the efficient level of pollution. (JEH)

  9. NPDES Permit Status Reports

    EPA Pesticide Factsheets

    These reports show the backlog status nationwide, based on EPA databases and input from EPA regions and states. The reports show a snapshot in time, keep in mind that the status of facilities and the universe of permits change.

  10. California Tribal Gasoline Permits

    EPA Pesticide Factsheets

    EPA is proposing a draft general permit under the Clean Air Act Federal Indian Country Minor NSR program for gasoline dispensing facilities, such as gas stations, located in Indian country within the geographical boundaries of California.

  11. Bondad Landfill NPDES Permit

    EPA Pesticide Factsheets

    Under National Pollutant Discharge Elimination System permit number CO-R050005, Transit Waste, LLC is authorized to discharge from the Bondad Landfill facility in La Plata County, Colorado, to an unnamed tributary of the Animas River.

  12. 75 FR 145 - Clean Air Act Operating Permit Program; Petitions for Objection to State Operating Permit for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-04

    ... Operating Permit Program; Petitions for Objection to State Operating Permit for Cash Creek Generation, LLC... Air Quality (KDAQ) to Cash Creek Generation, LLC for its Cash Creek Generating Station located near... emissions; and (8) KDAQ did not respond to Valley Watch comments on increased ozone formation due to the...

  13. 75 FR 55791 - Clean Air Act Operating Permit Program; Petition for Objection to State Operating Permit for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-14

    ... AGENCY Clean Air Act Operating Permit Program; Petition for Objection to State Operating Permit for Alliant Energy--WPL Edgewater Generating Station AGENCY: Environmental Protection Agency (EPA). ACTION: Notice of final order on petition to object to Clean Air Act operating permit. SUMMARY: This document...

  14. Detection of Plasmodium sp. in capybara.

    PubMed

    dos Santos, Leonilda Correia; Curotto, Sandra Mara Rotter; de Moraes, Wanderlei; Cubas, Zalmir Silvino; Costa-Nascimento, Maria de Jesus; de Barros Filho, Ivan Roque; Biondo, Alexander Welker; Kirchgatter, Karin

    2009-07-07

    In the present study, we have microscopically and molecularly surveyed blood samples from 11 captive capybaras (Hydrochaeris hydrochaeris) from the Sanctuary Zoo for Plasmodium sp. infection. One animal presented positive on blood smear by light microscopy. Polymerase chain reaction was carried out accordingly using a nested genus-specific protocol, which uses oligonucleotides from conserved sequences flanking a variable sequence region in the small subunit ribosomal RNA (ssrRNA) of all Plasmodium organisms. This revealed three positive animals. Products from two samples were purified and sequenced. The results showed less than 1% divergence between the two capybara sequences. When compared with GenBank sequences, a 55% similarity was obtained to Toxoplasma gondii and a higher similarity (73-77.2%) was found to ssrRNAs from Plasmodium species that infect reptile, avian, rodents, and human beings. The most similar Plasmodium sequence was from Plasmodium mexicanum that infects lizards of North America, where around 78% identity was found. This work is the first report of Plasmodium in capybaras, and due to the low similarity with other Plasmodium species, we suggest it is a new species, which, in the future could be denominated "Plasmodium hydrochaeri".

  15. In vitro alterations do not reflect a requirement for host cell cycle progression during Plasmodium liver stage infection.

    PubMed

    Hanson, Kirsten K; March, Sandra; Ng, Shengyong; Bhatia, Sangeeta N; Mota, Maria M

    2015-01-01

    Prior to invading nonreplicative erythrocytes, Plasmodium parasites undergo their first obligate step in the mammalian host inside hepatocytes, where each sporozoite replicates to generate thousands of merozoites. While normally quiescent, hepatocytes retain proliferative capacity and can readily reenter the cell cycle in response to diverse stimuli. Many intracellular pathogens, including protozoan parasites, manipulate the cell cycle progression of their host cells for their own benefit, but it is not known whether the hepatocyte cell cycle plays a role during Plasmodium liver stage infection. Here, we show that Plasmodium parasites can be observed in mitotic hepatoma cells throughout liver stage development, where they initially reduce the likelihood of mitosis and ultimately lead to significant acquisition of a binucleate phenotype. However, hepatoma cells pharmacologically arrested in S phase still support robust and complete Plasmodium liver stage development, which thus does not require cell cycle progression in the infected cell in vitro. Furthermore, murine hepatocytes remain quiescent throughout in vivo infection with either Plasmodium berghei or Plasmodium yoelii, as do Plasmodium falciparum-infected primary human hepatocytes, demonstrating that the rapid and prodigious growth of liver stage parasites is accomplished independent of host hepatocyte cell cycle progression during natural infection.

  16. Louisiana Title V General Permits

    SciTech Connect

    Boyer, B.E.; Neal, T.L.

    1995-12-31

    Title V of the Federal Clean Air Act Amendments of 1990 requires federal operating permits for all major sources of air pollution. In 1992, Title 40, Part 70 of the Code of Federal Regulations (40 CFR Part 70) codified the law s requirements. These federal regulations, entitled Operating Permit Program, define the minimum requirements for state administered operating permit programs. The intent of Title V is to put into one document all requirements of an operating permit. General Permits for oil and gas facilities may be preferred if the facility can comply with all permit requirements. If greater flexibility than allowed by the General Permit is required, then the facility should apply for an individual Title V permit. General Permits are designed to streamline the permitting process, shorten the time it takes to obtain approval for initial and modified permits. The advantages of the General Permit include reduced paperwork and greater consistency because the permits are standardized. There should be less uncertainty because permit requirements will be known at the time of application. Approval times for Initial and modified General Permits should be reduced. Lengthy public notice procedures (and possible hearings) will be required for only the initial approval of the General Permit and not for each applicant to the permit. A disadvantage of General Permits is reduced flexibility since the facility must comply with the requirements of a standardized permit.

  17. Hanford Facility RCRA permit handbook

    SciTech Connect

    1996-03-01

    Purpose of this Hanford Facility (HF) RCRA Permit Handbook is to provide, in one document, information to be used for clarification of permit conditions and guidance for implementing the HF RCRA Permit.

  18. Targeting of GFP-Cre to the Mouse Cyp11a1 Locus Both Drives Cre Recombinase Expression in Steroidogenic Cells and Permits Generation of Cyp11a1 Knock Out Mice

    PubMed Central

    O'Hara, Laura; York, Jean Philippe; Zhang, Pumin; Smith, Lee B.

    2014-01-01

    To permit conditional gene targeting of floxed alleles in steroidogenic cell-types we have generated a transgenic mouse line that expresses Cre Recombinase under the regulation of the endogenous Cytochrome P450 side chain cleavage enzyme (Cyp11a1) promoter. Mice Carrying the Cyp11a1-GC (GFP-Cre) allele express Cre Recombinase in fetal adrenal and testis, and adrenal cortex, testicular Leydig cells (and a small proportion of Sertoli cells), theca cells of the ovary, and the hindbrain in postnatal life. Circulating testosterone concentration is unchanged in Cyp11+/GC males, suggesting steroidogenesis is unaffected by loss of one allele of Cyp11a1, mice are grossly normal, and Cre Recombinase functions to recombine floxed alleles of both a YFP reporter gene and the Androgen Receptor (AR) in steroidogenic cells of the testis, ovary, adrenal and hindbrain. Additionally, when bred to homozygosity (Cyp11a1GC/GC), knock-in of GFP-Cre to the endogenous Cyp11a1 locus results in a novel mouse model lacking endogenous Cyp11a1 (P450-SCC) function. This unique dual-purpose model has utility both for those wishing to conditionally target genes within steroidogenic cell types and for studies requiring mice lacking endogenous steroid hormone production. PMID:24404170

  19. A prime/boost PfCS14K(M)/MVA-sPfCS(M) vaccination protocol generates robust CD8(+) T cell and antibody responses to Plasmodium falciparum circumsporozoite protein and protects mice against malaria.

    PubMed

    Vijayan, Aneesh; Mejías-Pérez, Ernesto; Espinosa, Diego A; Raman, Suresh C; Sorzano, Carlos Oscar S; Zavala, Fidel; Esteban, Mariano

    2017-03-15

    Vaccines against the pre-erythrocytic stages of malaria are appealing, since the parasite can be eliminated before disease onset and since they offer the unique possibility of targeting the parasite with both antibodies and T cells. Although the role CD8(+) T cells in pre-erythrocytic malaria stages is well documented, a highly effective T cell-inducing vaccine remains to be advanced. Here we report the development of a prime-boost immunization regimen with the Plasmodium falciparum circumsporozoite protein (PfCS) fused to the oligomer-forming vaccinia virus A27 protein and a modified vaccinia virus Ankara (MVA) vector expressing PfCS. This protocol induced polyfunctional CD8(+) T cells with effector memory phenotype and high PfCS antibody levels. These immune responses correlated with inhibition of liver stage parasitemia in 80% and sterile protection in 40% of mice challenged with a transgenic P. berghei parasite line that expressed PfCS. Our findings underscore the potential of T and B cell immunization strategies in improving protective effectiveness against malaria.

  20. Plasmodium falciparum picks (on) EPCR

    PubMed Central

    Mosnier, Laurent O.; Fairhurst, Rick M.

    2014-01-01

    Of all the outcomes of Plasmodium falciparum infection, the coma of cerebral malaria (CM) is particularly deadly. Malariologists have long wondered how some patients develop this organ-specific syndrome. Data from two recent publications support a novel mechanism of CM pathogenesis in which infected erythrocytes (IEs) express specific virulence proteins that mediate IE binding to the endothelial protein C receptor (EPCR). Malaria-associated depletion of EPCR, with subsequent impairment of the protein C system promotes a proinflammatory, procoagulant state in brain microvessels. PMID:24246501

  1. Control of Plasmodium knowlesi malaria

    NASA Astrophysics Data System (ADS)

    Abdullahi, Mohammed Baba; Hasan, Yahya Abu; Abdullah, Farah Aini

    2015-10-01

    The most significant and efficient measures against Plasmodium knowlesi outbreaks are efficient anti malaria drug, biological control in form of predatory mosquitoes and culling control strategies. In this paper optimal control theory is applied to a system of ordinary differential equation. It describes the disease transmission and Pontryagin's Maximum Principle is applied for analysis of the control. To this end, three control strategies representing biological control, culling and treatment were incorporated into the disease transmission model. The simulation results show that the implementation of the combination strategy during the epidemic is the most cost-effective strategy for disease transmission.

  2. The periodicity of Plasmodium vivax and Plasmodium falciparum in Venezuela.

    PubMed

    Grillet, María-Eugenia; El Souki, Mayida; Laguna, Francisco; León, José Rafael

    2014-01-01

    We investigated the periodicity of Plasmodium vivax and P. falciparum incidence in time-series of malaria data (1990-2010) from three endemic regions in Venezuela. In particular, we determined whether disease epidemics were related to local climate variability and regional climate anomalies such as the El Niño Southern Oscillation (ENSO). Malaria periodicity was found to exhibit unique features in each studied region. Significant multi-annual cycles of 2- to about 6-year periods were identified. The inter-annual variability of malaria cases was coherent with that of SSTs (ENSO), mainly at temporal scales within the 3-6 year periods. Additionally, malaria cases were intensified approximately 1 year after an El Niño event, a pattern that highlights the role of climate inter-annual variability in the epidemic patterns. Rainfall mediated the effect of ENSO on malaria locally. Particularly, rains from the last phase of the season had a critical role in the temporal dynamics of Plasmodium. The malaria-climate relationship was complex and transient, varying in strength with the region and species. By identifying temporal cycles of malaria we have made a first step in predicting high-risk years in Venezuela. Our findings emphasize the importance of analyzing high-resolution spatial-temporal data to better understand malaria transmission dynamics.

  3. 50 CFR 622.50 - Permits, permit moratorium, and endorsements.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ..., AND SOUTH ATLANTIC Shrimp Fishery of the Gulf of Mexico § 622.50 Permits, permit moratorium, and endorsements. (a) Gulf shrimp permit. For a person aboard a vessel to fish for shrimp in the Gulf EEZ or possess shrimp in or from the Gulf EEZ, a commercial vessel permit for Gulf shrimp must have been...

  4. A genetic system to study Plasmodium falciparum protein function.

    PubMed

    Birnbaum, Jakob; Flemming, Sven; Reichard, Nick; Soares, Alexandra Blancke; Mesén-Ramírez, Paolo; Jonscher, Ernst; Bergmann, Bärbel; Spielmann, Tobias

    2017-03-13

    Current systems to study essential genes in the human malaria parasite Plasmodium falciparum are often inefficient and time intensive, and they depend on the genetic modification of the target locus, a process hindered by the low frequency of integration of episomal DNA into the genome. Here, we introduce a method, termed selection-linked integration (SLI), to rapidly select for genomic integration. SLI allowed us to functionally analyze targets at the gene and protein levels, thus permitting mislocalization of native proteins, a strategy known as knock sideways, floxing to induce diCre-based excision of genes and knocking in altered gene copies. We demonstrated the power and robustness of this approach by validating it for more than 12 targets, including eight essential ones. We also localized and inducibly inactivated Kelch13, the protein associated with artemisinin resistance. We expect this system to be widely applicable for P. falciparum and other organisms with limited genetic tractability.

  5. Generations.

    PubMed

    Chambers, David W

    2005-01-01

    Groups naturally promote their strengths and prefer values and rules that give them an identity and an advantage. This shows up as generational tensions across cohorts who share common experiences, including common elders. Dramatic cultural events in America since 1925 can help create an understanding of the differing value structures of the Silents, the Boomers, Gen Xers, and the Millennials. Differences in how these generations see motivation and values, fundamental reality, relations with others, and work are presented, as are some applications of these differences to the dental profession.

  6. Approaches to Streamline Air Permitting for Combined Heat and Power: Permits by Rule and General Permits

    EPA Pesticide Factsheets

    This factsheet provides information about permit by rule (PBR) and general permit (GP) processes, including the factors that contributed to their development and lessons learned from their implementation.

  7. PERMITTING HAZARDOUS WASTE INCINERATORS

    EPA Science Inventory

    This publication is a compilation of information presented at a seminar series designed to address the issues that affect the issuance of hazardous waste incineration permits and to improve the overall understanding of trial burn testing. pecifically, the document provides guidan...

  8. Permit application modifications

    SciTech Connect

    1995-11-01

    This document contains the Permit Application Modifications for the Y-12 Industrial Landfill V site on the Oak Ridge Reservation. These modifications include the assessment of stability of the proposed Landfill V under static and loading conditions. Analyses performed include the general slope stability, veneer stability of the bottom liner and cover system, and a liquefaction potential assessment of the foundation soils.

  9. PERMITTING HAZARDOUS WASTE INCINERATORS

    EPA Science Inventory

    This publication is a compilation of information presented at a seminar series designed to address the issues that affect the issuance of hazardous waste incineration permits and to improve the overall understanding of trial burn testing. pecifically, the document provides guidan...

  10. Florida Proposed Title V Permits

    EPA Pesticide Factsheets

    The following permits have been submitted to EPA Region 4 as Proposed Title V permits. While EPA has the right to a 45-day review period for all Proposed Title V permits, EPA Region 4 targets only a subset of these permits for comprehensive review.

  11. Mississippi Proposed Title V Permits

    EPA Pesticide Factsheets

    The following permits have been submitted to EPA Region 4 as Proposed Title V permits. While EPA has the right to a 45-day review period for all Proposed Title V permits, EPA Region 4 targets only a subset of these permits for comprehensive review.

  12. Tennessee Proposed Title V Permits

    EPA Pesticide Factsheets

    The following permits have been submitted to EPA Region 4 as Proposed Title V permits. While EPA has the right to a 45-day review period for all Proposed Title V permits, EPA Region 4 targets only a subset of these permits for comprehensive review.

  13. Kentucky Proposed Title V Permits

    EPA Pesticide Factsheets

    The following permits have been submitted to EPA Region 4 as Proposed Title V permits. While EPA has the right to a 45-day review period for all Proposed Title V permits, EPA Region 4 targets only a subset of these permits for comprehensive review.

  14. Alabama Proposed Title V Permits

    EPA Pesticide Factsheets

    The following permits have been submitted to EPA Region 4 as Proposed Title V permits. While EPA has the right to a 45-day review period for all Proposed Title V permits, EPA Region 4 targets only a subset of these permits for comprehensive review.

  15. Georgia Proposed Title V Permits

    EPA Pesticide Factsheets

    The following permits have been submitted to EPA Region 4 as Proposed Title V permits. While EPA has the right to a 45-day review period for all Proposed Title V permits, EPA Region 4 targets only a subset of these permits for comprehensive review.

  16. Susceptibility to Plasmodium liver stage infection is altered by hepatocyte polyploidy

    PubMed Central

    Austin, Laura S.; Kaushansky, Alexis; Kappe, Stefan H.I.

    2014-01-01

    Summary Plasmodium parasites infect hepatocytes of their mammalian hosts and within undergo obligate liver stage development. The specific host cell attributes that are important for liver infection remain largely unknown. Several host signaling pathways are perturbed in infected hepatocytes, some of which are important in the generation of hepatocyte polyploidy. To test the functional consequence of polyploidy in liver infection, we infected hepatocytes with the rodent malaria parasite Plasmodium yoelii both in vitro and in vivo and examined the ploidy of infected and uninfected hepatocytes by flow cytometry. In both hepatoma cell lines and in the mouse liver, the fraction of polyploid cells was higher in the infected cell population than in the uninfected cell population. When the data were reanalyzed by comparing the extent of Plasmodium infection within each ploidy subset, we found that infection rates were elevated in more highly polyploid cells and lower in diploid cells. Furthermore, we found that the parasite’s preference for host cells with high ploidy is conserved among rodent malaria species and the human malaria parasite Plasmodium falciparum. This parasite preference for host cells of high ploidy cannot be explained by differences in hepatocyte size or DNA replication. We conclude that Plasmodium preferentially infects and develops in polyploid hepatocytes. PMID:24612025

  17. The role of metacaspase 1 in Plasmodium berghei development and apoptosis.

    PubMed

    Le Chat, Ludovic; Sinden, Robert E; Dessens, Johannes T

    2007-05-01

    The malaria parasite encodes a wide range of proteases necessary to facilitate its many developmental transitions in vertebrate and insect hosts. Amongst these is a predicted cysteine protease structurally related to caspases, named Plasmodium metacaspase 1 (PxMC1). We have generated Plasmodium berghei parasites in which the PbMC1coding sequence is removed and replaced with a green fluorescent reporter gene to investigate the expression of PbMC1, its contribution to parasite development, and its involvement in previously reported apoptosis-like cell death of P. berghei ookinetes. Our results show that the pbmc1 gene is expressed in female gametocytes and all downstream mosquito stages including sporozoites, but not in asexual blood stages. We failed to detect an apparent loss-of-function phenotype, suggesting that PbMC1 constitutes a functionally redundant gene. We discuss these findings in the context of two other putative Plasmodium metacaspases that we describe here.

  18. Logan International Airport NPDES Permit | NPDES Permits in ...

    EPA Pesticide Factsheets

    2017-04-10

    Massport was issued a permit for discharging storm water to Boston Harbor on March 1, 1978. The permit expired five years later. However, EPA administratively continued the permit as allowed by regulations. EPA issued a draft permit and fact sheet (which provides EPA's technical basis for establishing effluent limits and monitoring) for public comment on July 25, 2006. After consideration of the comments received during the comment period which ended on October 23, 2006, EPA is now ready to issue the permit. The response to comments document explains and supports the EPA and MassDEP determinations that form the basis of the permit.

  19. Wind Energy: Offshore Permitting

    DTIC Science & Technology

    2008-05-01

    Technological advancements and tax incentives have driven a global expansion in the development of renewable energy resources. Wind energy , in...particular, is now often cited as the fastest growing commercial energy source in the world. Currently, all U.S. wind energy facilities are based on land...authority to permit and regulate offshore wind energy development within the zones of the oceans under its jurisdiction. The federal government and coastal

  20. The Motor Complex of Plasmodium falciparum

    PubMed Central

    Green, Judith L.; Rees-Channer, Roxanne R.; Howell, Stephen A.; Martin, Stephen R.; Knuepfer, Ellen; Taylor, Helen M.; Grainger, Munira; Holder, Anthony A.

    2008-01-01

    Calcium-dependent protein kinases (CDPKs) of Apicomplexan parasites are crucial for the survival of the parasite throughout its life cycle. CDPK1 is expressed in the asexual blood stages of the parasite, particularly late stage schizonts. We have identified two substrates of Plasmodium falciparum CDPK1: myosin A tail domain-interacting protein (MTIP) and glideosome-associated protein 45 (GAP45), both of which are components of the motor complex that generates the force required by the parasite to actively invade host cells. Indirect immunofluorescence shows that CDPK1 localizes to the periphery of P. falciparum merozoites and is therefore suitably located to act on MTIP and GAP45 at the inner membrane complex. A proportion of both GAP45 and MTIP is phosphorylated in schizonts, and we demonstrate that both proteins can be efficiently phosphorylated by CDPK1 in vitro. A primary phosphorylation of MTIP occurs at serine 47, whereas GAP45 is phosphorylated at two sites, one of which could also be detected in phosphopeptides purified from parasite lysates. Both CDPK1 activity and host cell invasion can be inhibited by the kinase inhibitor K252a, suggesting that CDPK1 is a suitable target for antimalarial drug development. PMID:18768477

  1. Regulation of the Plasmodium Motor Complex

    PubMed Central

    Douse, Christopher H.; Green, Judith L.; Salgado, Paula S.; Simpson, Peter J.; Thomas, Jemima C.; Langsley, Gordon; Holder, Anthony A.; Tate, Edward W.; Cota, Ernesto

    2012-01-01

    The interaction between the C-terminal tail of myosin A (MyoA) and its light chain, myosin A tail domain interacting protein (MTIP), is an essential feature of the conserved molecular machinery required for gliding motility and cell invasion by apicomplexan parasites. Recent data indicate that MTIP Ser-107 and/or Ser-108 are targeted for intracellular phosphorylation. Using an optimized MyoA tail peptide to reconstitute the complex, we show that this region of MTIP is an interaction hotspot using x-ray crystallography and NMR, and S107E and S108E mutants were generated to mimic the effect of phosphorylation. NMR relaxation experiments and other biophysical measurements indicate that the S108E mutation serves to break the tight clamp around the MyoA tail, whereas S107E has a smaller but measurable impact. These data are consistent with physical interactions observed between recombinant MTIP and native MyoA from Plasmodium falciparum lysates. Taken together these data support the notion that the conserved interactions between MTIP and MyoA may be specifically modulated by this post-translational modification. PMID:22932904

  2. Integrated analysis of the Plasmodium species transcriptome.

    PubMed

    Hoo, Regina; Zhu, Lei; Amaladoss, Anburaj; Mok, Sachel; Natalang, Onguma; Lapp, Stacey A; Hu, Guangan; Liew, Kingsley; Galinski, Mary R; Bozdech, Zbynek; Preiser, Peter R

    2016-05-01

    The genome sequence available for different Plasmodium species is a valuable resource for understanding malaria parasite biology. However, comparative genomics on its own cannot fully explain all the species-specific differences which suggests that other genomic aspects such as regulation of gene expression play an important role in defining species-specific characteristics. Here, we developed a comprehensive approach to measure transcriptional changes of the evolutionary conserved syntenic orthologs during the intraerythrocytic developmental cycle across six Plasmodium species. We show significant transcriptional constraint at the mid-developmental stage of Plasmodium species while the earliest stages of parasite development display the greatest transcriptional variation associated with critical functional processes. Modeling of the evolutionary relationship based on changes in transcriptional profile reveal a phylogeny pattern of the Plasmodium species that strictly follows its mammalian hosts. In addition, the work shows that transcriptional conserved orthologs represent potential future targets for anti-malaria intervention as they would be expected to carry out key essential functions within the parasites. This work provides an integrated analysis of orthologous transcriptome, which aims to provide insights into the Plasmodium evolution thereby establishing a framework to explore complex pathways and drug discovery in Plasmodium species with broad host range. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  3. Isoprenoid Biosynthesis in Plasmodium falciparum

    PubMed Central

    Guggisberg, Ann M.; Amthor, Rachel E.

    2014-01-01

    Malaria kills nearly 1 million people each year, and the protozoan parasite Plasmodium falciparum has become increasingly resistant to current therapies. Isoprenoid synthesis via the methylerythritol phosphate (MEP) pathway represents an attractive target for the development of new antimalarials. The phosphonic acid antibiotic fosmidomycin is a specific inhibitor of isoprenoid synthesis and has been a helpful tool to outline the essential functions of isoprenoid biosynthesis in P. falciparum. Isoprenoids are a large, diverse class of hydrocarbons that function in a variety of essential cellular processes in eukaryotes. In P. falciparum, isoprenoids are used for tRNA isopentenylation and protein prenylation, as well as the synthesis of vitamin E, carotenoids, ubiquinone, and dolichols. Recently, isoprenoid synthesis in P. falciparum has been shown to be regulated by a sugar phosphatase. We outline what is known about isoprenoid function and the regulation of isoprenoid synthesis in P. falciparum, in order to identify valuable directions for future research. PMID:25217461

  4. Chemical genetics of Plasmodium falciparum

    PubMed Central

    Guiguemde, W. Armand; Shelat, Anang A.; Bouck, David; Duffy, Sandra; Crowther, Gregory J.; Davis, Paul H.; Smithson, David C.; Connelly, Michele; Clark, Julie; Zhu, Fangyi; Jiménez-Díaz, María B; Martinez, María S; Wilson, Emily B.; Tripathi, Abhai K.; Gut, Jiri; Sharlow, Elizabeth R.; Bathurst, Ian; El Mazouni, Farah; Fowble, Joseph W; Forquer, Isaac; McGinley, Paula L; Castro, Steve; Angulo-Barturen, Iñigo; Ferrer, Santiago; Rosenthal, Philip J.; DeRisi, Joseph L; Sullivan, David J.; Lazo, John S.; Roos, David S.; Riscoe, Michael K.; Phillips, Margaret A.; Rathod, Pradipsinh K.; Van Voorhis, Wesley C.; Avery, Vicky M; Guy, R. Kiplin

    2010-01-01

    Malaria caused by Plasmodium falciparum is a catastrophic disease worldwide (880,000 deaths yearly). Vaccine development has proved difficult and resistance has emerged for most antimalarials. In order to discover new antimalarial chemotypes, we have employed a phenotypic forward chemical genetic approach to assay 309,474 chemicals. Here we disclose structures and biological activity of the entire library, many of which exhibited potent in vitro activity against drug resistant strains, and detailed profiling of 172 representative candidates. A reverse chemical genetic study identified 19 new inhibitors of 4 validated drug targets and 15 novel binders among 61 malarial proteins. Phylochemogenetic profiling in multiple organisms revealed similarities between Toxoplasma gondii and mammalian cell lines and dissimilarities between P. falciparum and related protozoans. One exemplar compound displayed efficacy in a murine model. Overall, our findings provide the scientific community with new starting points for malaria drug discovery. PMID:20485428

  5. Plasmodium vivax Transmission in Africa

    PubMed Central

    Howes, Rosalind E.; Reiner Jr., Robert C.; Battle, Katherine E.; Longbottom, Joshua; Mappin, Bonnie; Ordanovich, Dariya; Tatem, Andrew J.; Drakeley, Chris; Gething, Peter W.; Zimmerman, Peter A.; Smith, David L.; Hay, Simon I.

    2015-01-01

    Malaria in sub-Saharan Africa has historically been almost exclusively attributed to Plasmodium falciparum (Pf). Current diagnostic and surveillance systems in much of sub-Saharan Africa are not designed to identify or report non-Pf human malaria infections accurately, resulting in a dearth of routine epidemiological data about their significance. The high prevalence of Duffy negativity provided a rationale for excluding the possibility of Plasmodium vivax (Pv) transmission. However, review of varied evidence sources including traveller infections, community prevalence surveys, local clinical case reports, entomological and serological studies contradicts this viewpoint. Here, these data reports are weighted in a unified framework to reflect the strength of evidence of indigenous Pv transmission in terms of diagnostic specificity, size of individual reports and corroboration between evidence sources. Direct evidence was reported from 21 of the 47 malaria-endemic countries studied, while 42 countries were attributed with infections of visiting travellers. Overall, moderate to conclusive evidence of transmission was available from 18 countries, distributed across all parts of the continent. Approximately 86.6 million Duffy positive hosts were at risk of infection in Africa in 2015. Analysis of the mechanisms sustaining Pv transmission across this continent of low frequency of susceptible hosts found that reports of Pv prevalence were consistent with transmission being potentially limited to Duffy positive populations. Finally, reports of apparent Duffy-independent transmission are discussed. While Pv is evidently not a major malaria parasite across most of sub-Saharan Africa, the evidence presented here highlights its widespread low-level endemicity. An increased awareness of Pv as a potential malaria parasite, coupled with policy shifts towards species-specific diagnostics and reporting, will allow a robust assessment of the public health significance of Pv, as well

  6. Plasmodium vivax Transmission in Africa.

    PubMed

    Howes, Rosalind E; Reiner, Robert C; Battle, Katherine E; Longbottom, Joshua; Mappin, Bonnie; Ordanovich, Dariya; Tatem, Andrew J; Drakeley, Chris; Gething, Peter W; Zimmerman, Peter A; Smith, David L; Hay, Simon I

    2015-11-01

    Malaria in sub-Saharan Africa has historically been almost exclusively attributed to Plasmodium falciparum (Pf). Current diagnostic and surveillance systems in much of sub-Saharan Africa are not designed to identify or report non-Pf human malaria infections accurately, resulting in a dearth of routine epidemiological data about their significance. The high prevalence of Duffy negativity provided a rationale for excluding the possibility of Plasmodium vivax (Pv) transmission. However, review of varied evidence sources including traveller infections, community prevalence surveys, local clinical case reports, entomological and serological studies contradicts this viewpoint. Here, these data reports are weighted in a unified framework to reflect the strength of evidence of indigenous Pv transmission in terms of diagnostic specificity, size of individual reports and corroboration between evidence sources. Direct evidence was reported from 21 of the 47 malaria-endemic countries studied, while 42 countries were attributed with infections of visiting travellers. Overall, moderate to conclusive evidence of transmission was available from 18 countries, distributed across all parts of the continent. Approximately 86.6 million Duffy positive hosts were at risk of infection in Africa in 2015. Analysis of the mechanisms sustaining Pv transmission across this continent of low frequency of susceptible hosts found that reports of Pv prevalence were consistent with transmission being potentially limited to Duffy positive populations. Finally, reports of apparent Duffy-independent transmission are discussed. While Pv is evidently not a major malaria parasite across most of sub-Saharan Africa, the evidence presented here highlights its widespread low-level endemicity. An increased awareness of Pv as a potential malaria parasite, coupled with policy shifts towards species-specific diagnostics and reporting, will allow a robust assessment of the public health significance of Pv, as well

  7. Phased Permits for PSD

    EPA Pesticide Factsheets

    This document may be of assistance in applying the New Source Review (NSR) air permitting regulations including the Prevention of Significant Deterioration (PSD) requirements. This document is part of the NSR Policy and Guidance Database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  8. Conditional PSD Permits

    EPA Pesticide Factsheets

    This document may be of assistance in applying the New Source Review (NSR) air permitting regulations including the Prevention of Significant Deterioration (PSD) requirements. This document is part of the NSR Policy and Guidance Database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  9. Permit Shields and NSR

    EPA Pesticide Factsheets

    This document may be of assistance in applying the New Source Review (NSR) air permitting regulations including the Prevention of Significant Deterioration (PSD) requirements. This document is part of the NSR Policy and Guidance Database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  10. General Permits for Ocean Dumping

    EPA Pesticide Factsheets

    General permits are issued by EPA for the ocean dumping of certain materials that will have a minimal adverse environmental impact and are generally disposed of in small quantities. Information includes examples and ocean disposal sites for general permits

  11. Lean in Air Permitting Guide

    EPA Pesticide Factsheets

    The Lean in Air Permitting Guide is designed to help air program managers at public agencies better understand the potential value and results that can be achieved by applying Lean improvement methods to air permitting processes.

  12. Inference of the Oxidative Stress Network in Anopheles stephensi upon Plasmodium Infection

    PubMed Central

    Shrinet, Jatin; Nandal, Umesh Kumar; Adak, Tridibes; Bhatnagar, Raj K.; Sunil, Sujatha

    2014-01-01

    Ookinete invasion of Anopheles midgut is a critical step for malaria transmission; the parasite numbers drop drastically and practically reach a minimum during the parasite's whole life cycle. At this stage, the parasite as well as the vector undergoes immense oxidative stress. Thereafter, the vector undergoes oxidative stress at different time points as the parasite invades its tissues during the parasite development. The present study was undertaken to reconstruct the network of differentially expressed genes involved in oxidative stress in Anopheles stephensi during Plasmodium development and maturation in the midgut. Using high throughput next generation sequencing methods, we generated the transcriptome of the An. stephensi midgut during Plasmodium vinckei petteri oocyst invasion of the midgut epithelium. Further, we utilized large datasets available on public domain on Anopheles during Plasmodium ookinete invasion and Drosophila datasets and arrived upon clusters of genes that may play a role in oxidative stress. Finally, we used support vector machines for the functional prediction of the un-annotated genes of An. stephensi. Integrating the results from all the different data analyses, we identified a total of 516 genes that were involved in oxidative stress in An. stephensi during Plasmodium development. The significantly regulated genes were further extracted from this gene cluster and used to infer an oxidative stress network of An. stephensi. Using system biology approaches, we have been able to ascertain the role of several putative genes in An. stephensi with respect to oxidative stress. Further experimental validations of these genes are underway. PMID:25474020

  13. Orangutans not infected with Plasmodium vivax or P. cynomolgi, Indonesia.

    PubMed

    Singh, Balbir; Simon Divis, Paul Cliff

    2009-10-01

    After orangutans in Indonesia were reported as infected with Plasmodium cynomolgi and P. vivax, we conducted phylogenetic analyses of small subunit ribosomal RNA gene sequences of Plasmodium spp. We found that these orangutans are not hosts of P. cynomolgi and P. vivax. Analysis of >or=1 genes is needed to identify Plasmodium spp. infecting orangutans.

  14. Complicated malaria: a rare presentation of Plasmodium ovale.

    PubMed

    Tomar, Laxmikant Ramkumarsingh; Giri, Subhash; Bauddh, Nitesh Kumar; Jhamb, Rajat

    2015-04-01

    Malaria has emerged as a major public health problem worldwide. Complications are commonly seen in Plasmodium falciparum (P. falciparum) and Plasmodium vivax (P. vivax) infection, but due to Plasmodium ovale (P. ovale) infection is rarely described in literature. Here we report a case of severe disease due to P. ovale infection complicated with jaundice, thrombocytopenia, hypotension and acute renal failure.

  15. Proteomic Approaches to Studying Drug Targets and Resistance in Plasmodium

    DTIC Science & Technology

    2004-01-01

    Plasmodium falciparum , the most virulent of human malaria parasites, is creating new challenges in malaria chemotherapy. The entire genome sequences of...P. falciparum and the rodent malaria parasite, P. yoelii yoelii are now available. Extensive genome sequence data from other Plasmodium species...Parasite, Protein, Mass Spectrometry, Genomics, Chloroquine, Artemisinin INTRODUCTION Research on Plasmodium falciparum , a protozoan parasite and

  16. Cell based assays for anti-Plasmodium activity evaluation.

    PubMed

    Mokgethi-Morule, Thabang; N'Da, David D

    2016-03-10

    Malaria remains one of the most common and deadly infectious diseases worldwide. The severity of this global public health challenge is reflected by the approximately 198 million people, who were reportedly infected in 2013 and by the more than 584,000 related deaths in that same year. The rising emergence of drug resistance towards the once effective artemisinin combination therapies (ACTs) has become a serious concern and warrants more robust drug development strategies, with the objective of eradicating malaria infections. The intricate biology and life cycle of Plasmodium parasites complicate the understanding of the disease in such a way that would enhance the development of more effective chemotherapies that would achieve radical clinical cure and that would prevent disease relapse. Phenotypic cell based assays have for long been a valuable approach and involve the screening and analysis of diverse compounds with regards to their activities towards whole Plasmodium parasites in vitro. To achieve the Millennium Development Goal (MDG) of malaria eradication by 2020, new generation drugs that are active against all parasite stages (erythrocytic (blood), exo-erythrocytic (liver stages and gametocytes)) are needed. Significant advances are being made in assay development to overcome some of the practical challenges of assessing drug efficacy, particularly in the liver and transmission stage Plasmodium models. This review discusses primary screening models and the fundamental progress being made in whole cell based efficacy screens of anti-malarial activity. Ongoing challenges and some opportunities for improvements in assay development that would assist in the discovery of effective, safe and affordable drugs for malaria treatments are also discussed.

  17. Helminth Parasites Alter Protection against Plasmodium Infection

    PubMed Central

    Salazar-Castañon, Víctor H.; Legorreta-Herrera, Martha

    2014-01-01

    More than one-third of the world's population is infected with one or more helminthic parasites. Helminth infections are prevalent throughout tropical and subtropical regions where malaria pathogens are transmitted. Malaria is the most widespread and deadliest parasitic disease. The severity of the disease is strongly related to parasite density and the host's immune responses. Furthermore, coinfections between both parasites occur frequently. However, little is known regarding how concomitant infection with helminths and Plasmodium affects the host's immune response. Helminthic infections are frequently massive, chronic, and strong inductors of a Th2-type response. This implies that infection by such parasites could alter the host's susceptibility to subsequent infections by Plasmodium. There are a number of reports on the interactions between helminths and Plasmodium; in some, the burden of Plasmodium parasites increased, but others reported a reduction in the parasite. This review focuses on explaining many of these discrepancies regarding helminth-Plasmodium coinfections in terms of the effects that helminths have on the immune system. In particular, it focuses on helminth-induced immunosuppression and the effects of cytokines controlling polarization toward the Th1 or Th2 arms of the immune response. PMID:25276830

  18. Helminth parasites alter protection against Plasmodium infection.

    PubMed

    Salazar-Castañon, Víctor H; Legorreta-Herrera, Martha; Rodriguez-Sosa, Miriam

    2014-01-01

    More than one-third of the world's population is infected with one or more helminthic parasites. Helminth infections are prevalent throughout tropical and subtropical regions where malaria pathogens are transmitted. Malaria is the most widespread and deadliest parasitic disease. The severity of the disease is strongly related to parasite density and the host's immune responses. Furthermore, coinfections between both parasites occur frequently. However, little is known regarding how concomitant infection with helminths and Plasmodium affects the host's immune response. Helminthic infections are frequently massive, chronic, and strong inductors of a Th2-type response. This implies that infection by such parasites could alter the host's susceptibility to subsequent infections by Plasmodium. There are a number of reports on the interactions between helminths and Plasmodium; in some, the burden of Plasmodium parasites increased, but others reported a reduction in the parasite. This review focuses on explaining many of these discrepancies regarding helminth-Plasmodium coinfections in terms of the effects that helminths have on the immune system. In particular, it focuses on helminth-induced immunosuppression and the effects of cytokines controlling polarization toward the Th1 or Th2 arms of the immune response.

  19. Anopheles Midgut FREP1 Mediates Plasmodium Invasion*

    PubMed Central

    Zhang, Genwei; Niu, Guodong; Franca, Caio M.; Dong, Yuemei; Wang, Xiaohong; Butler, Noah S.; Dimopoulos, George; Li, Jun

    2015-01-01

    Malaria transmission depends on sexual stage Plasmodium parasites successfully invading Anopheline mosquito midguts following a blood meal. However, the molecular mechanisms of Plasmodium invasion of mosquito midguts have not been fully elucidated. Previously, we showed that genetic polymorphisms in the fibrinogen-related protein 1 (FREP1) gene are significantly associated with Plasmodium falciparum infection in Anopheles gambiae, and FREP1 is important for Plasmodium berghei infection of mosquitoes. Here we identify that the FREP1 protein is secreted from the mosquito midgut epithelium and integrated as tetramers into the peritrophic matrix, a chitinous matrix formed inside the midgut lumen after a blood meal feeding. Moreover, we show that the FREP1 can directly bind Plasmodia sexual stage gametocytes and ookinetes. Notably, ablating FREP1 expression or targeting FREP1 with antibodies significantly decreases P. falciparum infection in mosquito midguts. Our data support that the mosquito-expressed FREP1 mediates mosquito midgut invasion by multiple species of Plasmodium parasites via anchoring ookinetes to the peritrophic matrix and enabling parasites to penetrate the peritrophic matrix and the epithelium. Thus, targeting FREP1 can limit malaria transmission. PMID:25991725

  20. 40 CFR 60.47Da - Commercial demonstration permit.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 6 2011-07-01 2011-07-01 false Commercial demonstration permit. 60... Steam Generating Units for Which Construction is Commenced After September 18, 1978 § 60.47Da Commercial... technology may apply to the Administrator for a commercial demonstration permit. The Administrator will...

  1. Wildlife Researchers Running the Permit Maze

    PubMed Central

    Paul, Ellen; Sikes, Robert S.

    2013-01-01

    The study of wildlife, whether in the field or in the lab, may start with a hypothesis, a literature search, or a grant proposal, but in many cases, the work will never happen unless the researcher successfully navigates a maze of permit requirements. A single project can involve multiple permits at the national and state levels, and it can take months to obtain any one permit. Therefore, permits may not have been issued at the time of protocol review, but Public Health Service Policy makes accommodations for this situation. Once in hand, however, the permits convey critical information to the Institutional Animal Care and Use Committee (IACUC): one or more government agencies have determined that the activity will not be detrimental to the population or that any detriment is justified by the scientific knowledge that will be generated. This paper assumes that IACUCs are reviewing all wildlife protocols involving live vertebrates, regardless of the current, albeit temporary, distinction made by Animal and Plant Health Inspection Service Animal Care with regard to birds. PMID:23904528

  2. Title V Permitting Statistics Inventory

    EPA Pesticide Factsheets

    The Title V Permitting Statistics Inventory contains measured and estimated nationwide statistical data, consisting of counts of permitted sources, types of permits issued, and the timeliness of permit issuance, for the operating permits programs being implemented under CAA authority (40 CFR parts 70 and 71). This data is non-source specific. The statutory authority leading to the collection of this information comes from Title V of the Clean Air Act.Prior to July 2008, data collected on state permit programs (part 70) was not equivalent to that collected when EPA was the permitting agency (part 71). Current system includes semiannual data from 2006-present; prior data is archived.Data is currently not publicly available, certain statistical data has been made available in the past, but not currently. This data is mostly used for ICR and PART reporting purposes.

  3. Accurate identification of the six human Plasmodium spp. causing imported malaria, including Plasmodium ovale wallikeri and Plasmodium knowlesi.

    PubMed

    Calderaro, Adriana; Piccolo, Giovanna; Gorrini, Chiara; Rossi, Sabina; Montecchini, Sara; Dell'Anna, Maria Loretana; De Conto, Flora; Medici, Maria Cristina; Chezzi, Carlo; Arcangeletti, Maria Cristina

    2013-09-13

    Accurate identification of Plasmodium infections in non-endemic countries is of critical importance with regard to the administration of a targeted therapy having a positive impact on patient health and management and allowing the prevention of the risk of re-introduction of endemic malaria in such countries. Malaria is no longer endemic in Italy where it is the most commonly imported disease, with one of the highest rates of imported malaria among European non-endemic countries including France, the UK and Germany, and with a prevalence of 24.3% at the University Hospital of Parma. Molecular methods showed high sensitivity and specificity and changed the epidemiology of imported malaria in several non-endemic countries, highlighted a higher prevalence of Plasmodium ovale, Plasmodium vivax and Plasmodium malariae underestimated by microscopy and, not least, brought to light both the existence of two species of P. ovale (Plasmodium ovale curtisi and Plasmodium ovale wallikeri) and the infection in humans by Plasmodium knowlesi, otherwise not detectable by microscopy. In this retrospective study an evaluation of two real-time PCR assays able to identify P. ovale wallikeri, distinguishing it from P. ovale curtisi, and to detect P. knowlesi, respectively, was performed applying them on a subset of 398 blood samples belonging to patients with the clinical suspicion of malaria. These assays revealed an excellent analytical sensitivity and no cross-reactivity versus other Plasmodium spp. infecting humans, suggesting their usefulness for an accurate and complete diagnosis of imported malaria. Among the 128 patients with malaria, eight P. ovale curtisi and four P. ovale wallikeri infections were detected, while no cases of P. knowlesi infection were observed. Real-time PCR assays specific for P. ovale wallikeri and P. knowlesi were included in the panel currently used in the University Hospital of Parma for the diagnosis of imported malaria, accomplishing the goal of

  4. Effect of meteorological variables on Plasmodium vivax and Plasmodium falciparum malaria in outbreak prone districts of Rajasthan, India.

    PubMed

    Lingala, Mercy A L

    2017-03-09

    Malaria is a public health problem caused by Plasmodium parasite and transmitted by anopheline mosquitoes. Arid and semi-arid regions of western India are prone to malaria outbreaks. Malaria outbreak prone districts viz. Bikaner, Barmer and Jodhpur were selected to study the effect of meteorological variables on Plasmodium vivax and Plasmodium falciparum malaria outbreaks for the period of 2009-2012. The data of monthly malaria cases and meteorological variables was analysed using SPSS 20v. Spearman correlation analysis was conducted to examine the strength of the relationship between meteorological variables, P. vivax and P. falciparum malaria cases. Pearson's correlation analysis was carried out among the meteorological variables to observe the independent effect of each independent variable on the outcome. Results indicate that malaria outbreaks have occurred in Bikaner and Barmer due to continuous rains for more than two months. Rainfall has shown to be an important predictor of malaria outbreaks in Rajasthan. P. vivax is more significantly correlated with rainfall, minimum temperature (P<0.01) and less significantly with relative humidity (P<0.05); whereas P. falciparum is significantly correlated with rainfall, relative humidity (P<0.01) and less significantly with temperature (P<0.05). The determination of the lag period for P. vivax is relative humidity and for P. falciparum is temperature. The lag period between malaria cases and rainfall is shorter for P. vivax than P. falciparum. In conclusion, the knowledge generated is not only useful to take prompt malaria control interventions but also helpful to develop better forecasting model in outbreak prone regions. Copyright © 2017 The Author. Published by Elsevier Ltd.. All rights reserved.

  5. Occurrence of Plasmodium in Anatidae

    USGS Publications Warehouse

    Herman, C.M.; Kocan, R.M.

    1970-01-01

    Until a little over a decade ago reports of Plasrnodium in geese, ducks, and swans were the result of examination of single blood smears from wild birds. One would gather from the earlier studies that Anatidae are infrequently infected. During the past decade we have conducted studies on prevalence of Plasmodium by an isodiagnosis technique, inoculating blood from wild birds into captive young geese, ducks, and other species of birds and determining the status of infection in the donors by examination of repetitive blood smears from the recipients. Examination by this technique of a series of adult Canada geese from the Seney National Wildlife Refuge in northern Michigan uncovered a prevalence of 60% during five successive years. Domestic geese were the primary recipients but we found that several other species of geese, ducks, and gulls were also susceptible. Similar studies on Canada geese from other areas (Maryland, New Jersey, New York, and southern Michigan) uncovered infection rates from zero to 27%. Following isolation of Plasmodlum in a single canvasback duck (Aythya valisineria) in southern Michigan by inoculation into a domestic duck, a series of 88 canvasbacks from Chesapeake Bay in Maryland this winter uncovered an infection rate of 27%. The most common parasite observed in both the geese and was as P. circumflexum.

  6. 50 CFR 665.662 - Permits.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... coral MUS in any PRIA precious coral permit area must have a permit issued under § 665.13. (b) Each permit will be valid for fishing only in the permit area specified on the permit. Precious Coral Permit... surrendering to the Regional Administrator any current permit for the precious coral fishery issued under § 665...

  7. 50 CFR 665.662 - Permits.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... coral MUS in any PRIA precious coral permit area must have a permit issued under § 665.13. (b) Each permit will be valid for fishing only in the permit area specified on the permit. Precious Coral Permit... surrendering to the Regional Administrator any current permit for the precious coral fishery issued under § 665...

  8. 50 CFR 665.662 - Permits.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... coral MUS in any PRIA precious coral permit area must have a permit issued under § 665.13. (b) Each permit will be valid for fishing only in the permit area specified on the permit. Precious Coral Permit... surrendering to the Regional Administrator any current permit for the precious coral fishery issued under § 665...

  9. 50 CFR 665.662 - Permits.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... coral MUS in any PRIA precious coral permit area must have a permit issued under § 665.13. (b) Each permit will be valid for fishing only in the permit area specified on the permit. Precious Coral Permit... surrendering to the Regional Administrator any current permit for the precious coral fishery issued under § 665...

  10. The anaemia of Plasmodium vivax malaria

    PubMed Central

    2012-01-01

    Plasmodium vivax threatens nearly half the world’s population and is a significant impediment to achievement of the millennium development goals. It is an important, but incompletely understood, cause of anaemia. This review synthesizes current evidence on the epidemiology, pathogenesis, treatment and consequences of vivax-associated anaemia. Young children are at high risk of clinically significant and potentially severe vivax-associated anaemia, particularly in countries where transmission is intense and relapses are frequent. Despite reaching lower densities than Plasmodium falciparum, Plasmodium vivax causes similar absolute reduction in red blood cell mass because it results in proportionately greater removal of uninfected red blood cells. Severe vivax anaemia is associated with substantial indirect mortality and morbidity through impaired resilience to co-morbidities, obstetric complications and requirement for blood transfusion. Anaemia can be averted by early and effective anti-malarial treatment. PMID:22540175

  11. The anaemia of Plasmodium vivax malaria.

    PubMed

    Douglas, Nicholas M; Anstey, Nicholas M; Buffet, Pierre A; Poespoprodjo, Jeanne R; Yeo, Tsin W; White, Nicholas J; Price, Ric N

    2012-04-27

    Plasmodium vivax threatens nearly half the world's population and is a significant impediment to achievement of the millennium development goals. It is an important, but incompletely understood, cause of anaemia. This review synthesizes current evidence on the epidemiology, pathogenesis, treatment and consequences of vivax-associated anaemia. Young children are at high risk of clinically significant and potentially severe vivax-associated anaemia, particularly in countries where transmission is intense and relapses are frequent. Despite reaching lower densities than Plasmodium falciparum, Plasmodium vivax causes similar absolute reduction in red blood cell mass because it results in proportionately greater removal of uninfected red blood cells. Severe vivax anaemia is associated with substantial indirect mortality and morbidity through impaired resilience to co-morbidities, obstetric complications and requirement for blood transfusion. Anaemia can be averted by early and effective anti-malarial treatment.

  12. Major Histocompatibility Complex and Malaria: Focus on Plasmodium vivax Infection

    PubMed Central

    Lima-Junior, Josué da Costa; Pratt-Riccio, Lilian Rose

    2016-01-01

    The importance of host and parasite genetic factors in malaria resistance or susceptibility has been investigated since the middle of the last century. Nowadays, of all diseases that affect man, malaria still plays one of the highest levels of selective pressure on human genome. Susceptibility to malaria depends on exposure profile, epidemiological characteristics, and several components of the innate and adaptive immune system that influences the quality of the immune response generated during the Plasmodium lifecycle in the vertebrate host. But it is well known that the parasite’s enormous capacity of genetic variation in conjunction with the host genetics polymorphism is also associated with a wide spectrum of susceptibility degrees to complicated or severe forms of the disease. In this scenario, variations in genes of the major histocompatibility complex (MHC) associated with host resistance or susceptibility to malaria have been identified and used as markers in host–pathogen interaction studies, mainly those evaluating the impact on the immune response, acquisition of resistance, or increased susceptibility to infection or vulnerability to disease. However, due to the intense selective pressure, number of cases, and mortality rates, the majority of the reported associations reported concerned Plasmodium falciparum malaria. Studies on the MHC polymorphism and its association with Plasmodium vivax, which is the most widespread Plasmodium and the most prevalent species outside the African continent, are less frequent but equally important. Despite punctual contributions, there are accumulated evidences of human genetic control in P. vivax infection and disease. Herein, we review the current knowledge in the field of MHC and derived molecules (HLA Class I, Class II, TNF-α, LTA, BAT1, and CTL4) regarding P. vivax malaria. We discuss particularly the results of P. vivax studies on HLA class I and II polymorphisms in relation to host susceptibility, naturally

  13. Artemisinin-resistant Plasmodium falciparum malaria

    PubMed Central

    Fairhurst, Rick M.; Dondorp, Arjen M.

    2016-01-01

    For more than five decades, Southeast Asia (SEA) has been fertile ground for the emergence of drug-resistant Plasmodium falciparum malaria. After generating parasites resistant to chloroquine, sulfadoxine, pyrimethamine, quinine, and mefloquine, this region has now spawned parasites resistant to artemisinins – the world's most potent antimalarial drugs. In areas where artemisinin resistance is prevalent, artemisinin combination therapies (ACTs) – the first-line treatments for malaria – are failing fast. This worrisome development threatens to make malaria practically untreatable in SEA, and threatens to compromise global endeavors to eliminate this disease. A recent series of clinical, in-vitro, genomics, and transcriptomics studies in SEA have defined in-vivo and in-vitro phenotypes of artemisinin resistance; identified its causal genetic determinant; explored its molecular mechanism; and assessed its clinical impact. Specifically, these studies have established that artemisinin resistance manifests as slow parasite clearance in patients and increased survival of early ring-stage parasites in vitro; is caused by single nucleotide polymorphisms in the parasite's ‘K13’ gene; is associated with an upregulated “unfolded protein response” pathway that may antagonize the pro-oxidant activity of artemisinins; and selects for partner drug resistance that rapidly leads to ACT failures. In SEA, clinical studies are urgently needed to monitor ACT efficacy where K13 mutations are prevalent; test whether new combinations of currently-available drugs cure ACT failures; and advance new antimalarial compounds through preclinical pipelines and into clinical trials. Intensifying these efforts should help to forestall the spread of artemisinin and partner drug resistance from SEA to Sub-Saharan Africa, where the world's malaria transmission, morbidity, and mortality rates are highest. PMID:27337450

  14. Artemisinin-Resistant Plasmodium falciparum Malaria.

    PubMed

    Fairhurst, Rick M; Dondorp, Arjen M

    2016-06-01

    For more than five decades, Southeast Asia (SEA) has been fertile ground for the emergence of drug-resistant Plasmodium falciparum malaria. After generating parasites resistant to chloroquine, sulfadoxine, pyrimethamine, quinine, and mefloquine, this region has now spawned parasites resistant to artemisinins, the world's most potent antimalarial drugs. In areas where artemisinin resistance is prevalent, artemisinin combination therapies (ACTs)-the first-line treatments for malaria-are failing fast. This worrisome development threatens to make malaria practically untreatable in SEA, and threatens to compromise global endeavors to eliminate this disease. A recent series of clinical, in vitro, genomics, and transcriptomics studies in SEA have defined in vivo and in vitro phenotypes of artemisinin resistance, identified its causal genetic determinant, explored its molecular mechanism, and assessed its clinical impact. Specifically, these studies have established that artemisinin resistance manifests as slow parasite clearance in patients and increased survival of early-ring-stage parasites in vitro; is caused by single nucleotide polymorphisms in the parasite's K13 gene, is associated with an upregulated "unfolded protein response" pathway that may antagonize the pro-oxidant activity of artemisinins, and selects for partner drug resistance that rapidly leads to ACT failures. In SEA, clinical studies are urgently needed to monitor ACT efficacy where K13 mutations are prevalent, test whether new combinations of currently available drugs cure ACT failures, and advance new antimalarial compounds through preclinical pipelines and into clinical trials. Intensifying these efforts should help to forestall the spread of artemisinin and partner drug resistance from SEA to sub-Saharan Africa, where the world's malaria transmission, morbidity, and mortality rates are highest.

  15. Plasmodium falciparum glutaredoxin-like proteins.

    PubMed

    Deponte, Marcel; Becker, Katja; Rahlfs, Stefan

    2005-01-01

    Glutaredoxin-like proteins form a new subgroup of glutaredoxins with a serine replacing the second cysteine in the CxxC-motif of the active site. Yeast Grx5 is the only glutaredoxin-like protein studied biochemically so far. We identified and cloned three genes encoding glutaredoxin-like proteins from the malaria parasite Plasmodium falciparum (Pf Glp1, Pf Glp2, and Pf Glp3) containing a conserved cysteine in the CGFS-, CKFS-, and CKYS-motif, respectively. Here, we describe biochemical properties of Pf Glp1 and Pf Glp2. Cys 99, the only cysteine residue in Pf Glp1, has a pK(a) value as low as 5.5 and is able to mediate covalent homodimerization. Monomeric and dimeric Pf Glp1 react with GSSG and GSH, respectively. Pf Glp2 is monomeric and both of its cysteine residues can be glutathionylated. Molecular models reveal a thioredoxin fold for the putative C-terminal domain of Pf Glp1, Pf Glp2, and Pf Glp3, as well as conserved residues presumably required for glutathione binding. However, Pf Glp1 and Pf Glp2 neither possess activity in a classical glutaredoxin assay nor display activity as glutathione peroxidase or glutathione S-transferase. Mutation of Ser 102 in the CGFS-motif of Pf Glp1 to cysteine did not generate glutaredoxin activity either. We conclude that, despite their ability to react with glutathione, glutaredoxin-like proteins are a mechanistically and functionally heterogeneous group with only little similarities to canonical glutaredoxins.

  16. Buffer Optimization of Thermal Melt Assays of Plasmodium Proteins for Detection of Small-Molecule Ligands

    PubMed Central

    Crowther, Gregory J.; Napuli, Alberto J.; Thomas, Andrew P.; Chung, Diana J.; Kovzun, Kuzma V.; Leibly, David J.; Castaneda, Lisa J.; Bhandari, Janhavi; Damman, Christopher J.; Hui, Raymond; Hol, Wim G. J.; Buckner, Frederick S.; Verlinde, Christophe L. M. J.; Zhang, Zhongsheng; Fan, Erkang; Van Voorhis, Wesley C.

    2010-01-01

    In the last decade, thermal melt/thermal shift assays have become a common tool for identifying ligands and other factors that stabilize specific proteins. Increased stability is indicated by an increase in the protein's melting temperature (Tm). In optimizing the assays for subsequent screening of compound libraries, it is important to minimize the variability of Tm measurements so as to maximize the assay's ability to detect potential ligands. Here we present an investigation of Tm variability in recombinant proteins from Plasmodium parasites. Ligands of Plasmodium proteins are particularly interesting as potential starting points for drugs for malaria, and new drugs are urgently needed. A single standard buffer (100 mM HEPES, pH 7.5, 150 mM NaCl) permitted estimation of Tm for 58 of 61 Plasmodium proteins tested. However, with several proteins, Tm could not be measured with a consistency suitable for high-throughput screening unless alternative protein-specific buffers were employed. We conclude that buffer optimization to minimize variability in Tm measurements increases the success of thermal melt screens involving proteins for which a standard buffer is suboptimal. PMID:19470714

  17. Evoqua RCRA Permit Application and Draft Permit Documents

    EPA Pesticide Factsheets

    Documents pertaining to the proposed RCRA permit for the Evoqua Water Technologies LLC carbon regeneration facility located on the Colorado River Indian Tribes (CRIT) reservation near Parker, Arizona.

  18. Platform for Plasmodium vivax vaccine discovery and development.

    PubMed

    Valencia, Sócrates Herrera; Rodríguez, Diana Carolina; Acero, Diana Lucía; Ocampo, Vanessa; Arévalo-Herrera, Myriam

    2011-08-01

    Plasmodium vivax is the most prevalent malaria parasite on the American continent. It generates a global burden of 80-100 million cases annually and represents a tremendous public health problem, particularly in the American and Asian continents. A malaria vaccine would be considered the most cost-effective measure against this vector-borne disease and it would contribute to a reduction in malaria cases and to eventual eradication. Although significant progress has been achieved in the search for Plasmodium falciparum antigens that could be used in a vaccine, limited progress has been made in the search for P. vivax components that might be eligible for vaccine development. This is primarily due to the lack of in vitro cultures to serve as an antigen source and to inadequate funding. While the most advanced P. falciparum vaccine candidate is currently being tested in Phase III trials in Africa, the most advanced P. vivax candidates have only advanced to Phase I trials. Herein, we describe the overall strategy and progress in P. vivax vaccine research, from antigen discovery to preclinical and clinical development and we discuss the regional potential of Latin America to develop a comprehensive platform for vaccine development.

  19. Platform for Plasmodium vivax vaccine discovery and development

    PubMed Central

    Valencia/, Sócrates Herrera; Rodríguez, Diana Carolina; Acero, Diana Lucía; Ocampo, Vanessa; Arévalo-Herrera, Myriam

    2016-01-01

    Plasmodium vivax is the most prevalent malaria parasite on the American continent. It generates a global burden of 80–100 million cases annually and represents a tremendous public health problem, particularly in the American and Asian continents. A malaria vaccine would be considered the most cost-effective measure against this vector-borne disease and it would contribute to a reduction in malaria cases and to eventual eradication. Although significant progress has been achieved in the search for Plasmodium falciparum antigens that could be used in a vaccine, limited progress has been made in the search for P. vivax components that might be eligible for vaccine development. This is primarily due to the lack of in vitro cultures to serve as an antigen source and to inadequate funding. While the most advanced P. falciparum vaccine candidate is currently being tested in Phase III trials in Africa, the most advanced P. vivax candidates have only advanced to Phase I trials. Herein, we describe the overall strategy and progress in P. vivax vaccine research, from antigen discovery to preclinical and clinical development and we discuss the regional potential of Latin America to develop a comprehensive platform for vaccine development. PMID:21881773

  20. Quinolone-based drugs against Toxoplasma gondii and Plasmodium spp.

    PubMed

    Anquetin, Guillaume; Greiner, Jacques; Vierling, Pierre

    2005-09-01

    Owing to the rapid emergence of multi-resistant strains of Plasmodium spp. (the causative agents of malaria) and the limitations of drugs used against Toxoplasma gondii (an important opportunistic pathogen associated with AIDS and congenital birth defects), the discovery of new therapeutical targets and the development of new drugs are needed. The presence of the prokaryotic-like organelle in apicomplexan parasites (i.e. plastids), which comprise these major human pathogens, may represent a unique target for antibiotics against these protozoa. Quinolones which are known to be highly potent against bacteria were also found to specifically disrupt these parasites. They inhibit DNA replication by interacting with two essential bacterial type II topoisomerases, DNA gyrase and topoisomerase IV. There are some clues that quinolones act on plastids with a similar mechanism of action. After a brief presentation of plasmodium and toxoplasma dedicated to their life cycle, the chemotherapies presently used in clinics to fight against these protozoa and the potential new targets and drugs, we will focus our attention on their plastid which is one of these promising new targets. Then, we will present the various drugs and generations of quinolones, the leading molecules, and their inhibitory effects against these parasites together with their pharmacological properties that have been established from in vitro and in vivo studies. We will also discuss their possible mode of action.

  1. Exoerythrocytic development of Plasmodium gallinaceum in the White Leghorn chicken☆

    PubMed Central

    Frevert, Ute; Späth, Gerald F.; Yee, Herman

    2008-01-01

    Plasmodium gallinaceum typically causes sub-clinical disease with low mortality in its primary host, the Indian jungle fowl Gallus sonnerati. Domestic chickens of European origin, however, are highly susceptible to this avian malaria parasite. Here we describe the development of P. gallinaceum in young White Leghorn chicks with emphasis on the primary exoerythrocytic phase of the infection. Using various regimens for infection, we found that P. gallinaceum induced a transient primary exoerythrocytic infection followed by a fulminant lethal erythrocytic phase. Prerequisite for the appearance of secondary exoerythrocytic stages was the development of a certain level of parasitemia. Once established, secondary exoerythrocytic stages could be propagated from bird to bird for several generations without causing fatalities. Infected brains contained large secondary exoerythrocytic stages in capillary endothelia, while in the liver primary and secondary erythrocytic stages developed primarily in Kupffer cells and remained smaller. At later stages, livers exhibited focal hepatocyte necrosis, Kupffer cell hyperplasia, stellate cell proliferation, inflammatory cell infiltration and granuloma formation. Because P. gallinaceum selectively infected Kupffer cells in the liver and caused a histopathology strikingly similar to mammalian species, this avian Plasmodium species represents an evolutionarily closely related model for studies on the hepatic phase of mammalian malaria. PMID:18005972

  2. Avoiding Title V permitting pitfalls

    SciTech Connect

    Laswell, D.L.

    1993-04-01

    Title V of the 1990 Clean Air Act Amendments requires states to implement new air operating permit programs. States have a great deal of flexibility in developing their permit programs. Industry should work now to ensure that state programs contain the favorable aspects of the federal regulations and do not contain more stringent requirements that are not required under the Clean Air Act. This article outlines areas of the permit program that have the potential to handicap industry`s ability to expand.

  3. Plasmodium cynomolgi genome sequences provide insight into Plasmodium vivax and the monkey malaria clade.

    PubMed

    Tachibana, Shin-Ichiro; Sullivan, Steven A; Kawai, Satoru; Nakamura, Shota; Kim, Hyunjae R; Goto, Naohisa; Arisue, Nobuko; Palacpac, Nirianne M Q; Honma, Hajime; Yagi, Masanori; Tougan, Takahiro; Katakai, Yuko; Kaneko, Osamu; Mita, Toshihiro; Kita, Kiyoshi; Yasutomi, Yasuhiro; Sutton, Patrick L; Shakhbatyan, Rimma; Horii, Toshihiro; Yasunaga, Teruo; Barnwell, John W; Escalante, Ananias A; Carlton, Jane M; Tanabe, Kazuyuki

    2012-09-01

    P. cynomolgi, a malaria-causing parasite of Asian Old World monkeys, is the sister taxon of P. vivax, the most prevalent malaria-causing species in humans outside of Africa. Because P. cynomolgi shares many phenotypic, biological and genetic characteristics with P. vivax, we generated draft genome sequences for three P. cynomolgi strains and performed genomic analysis comparing them with the P. vivax genome, as well as with the genome of a third previously sequenced simian parasite, Plasmodium knowlesi. Here, we show that genomes of the monkey malaria clade can be characterized by copy-number variants (CNVs) in multigene families involved in evasion of the human immune system and invasion of host erythrocytes. We identify genome-wide SNPs, microsatellites and CNVs in the P. cynomolgi genome, providing a map of genetic variation that can be used to map parasite traits and study parasite populations. The sequencing of the P. cynomolgi genome is a critical step in developing a model system for P. vivax research and in counteracting the neglect of P. vivax.

  4. Promoter regions of Plasmodium vivax are poorly or not recognized by Plasmodium falciparum

    PubMed Central

    Azevedo, Mauro F; del Portillo, Hernando A

    2007-01-01

    Background Heterologous promoter analysis in Plasmodium has revealed the existence of conserved cis regulatory elements as promoters from different species can drive expression of reporter genes in heterologous transfection assays. Here, the functional characterization of different Plasmodium vivax promoters in Plasmodium falciparum using luciferase as the reporter gene is presented. Methods Luciferase reporter plasmids harboring the upstream regions of the msp1, dhfr, and vir3 genes as well as the full-length intergenic regions of the vir23/24 and ef-1α genes of P. vivax were constructed and transiently transfected in P. falciparum. Results Only the constructs with the full-length intergenic regions of the vir23/24 and ef-1α genes were recognized by the P. falciparum transcription machinery albeit to values approximately two orders of magnitude lower than those reported by luc plasmids harbouring promoter regions from P. falciparum and Plasmodium berghei. A bioinformatics approach allowed the identification of a motif (GCATAT) in the ef-1α intergenic region that is conserved in five Plasmodium species but is degenerate (GCANAN) in P. vivax. Mutations of this motif in the P. berghei ef-1α promoter region decreased reporter expression indicating it is active in gene expression in Plasmodium. Conclusion Together, this data indicates that promoter regions of P. vivax are poorly or not recognized by the P. falciparum transcription machinery suggesting the existence of P. vivax-specific transcription regulatory elements. PMID:17313673

  5. 50 CFR 622.50 - Permits, permit moratorium, and endorsements.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE FISHERIES OF THE CARIBBEAN, GULF OF MEXICO, AND SOUTH ATLANTIC Shrimp Fishery of the Gulf of Mexico § 622.50 Permits, permit moratorium, and... Fishery Management Plan for the Shrimp Fishery of the Gulf of Mexico (Gulf Shrimp FMP), all commercial...

  6. 2008 Contruction General Permits & Multi-Sector General Permits

    EPA Pesticide Factsheets

    View stormwater notices of intent (NOIs) for construction projects under EPA's 2008 Construction General Permit (CGP), for Low Erosivity Waivers (LEWs) submitted prior to September 10, 2013, or for industrial facilities under EPA's 2008 Multi-Sector General Permit (MSGP) or industrial facilities that are covered under the No Exposure certification.

  7. Congenital Plasmodium falciparum Malaria in Washington, DC.

    PubMed

    Del Castillo, Melissa; Szymanski, Ann Marie; Slovin, Ariella; Wong, Edward C C; DeBiasi, Roberta L

    2017-01-11

    Congenital malaria is rare in the United States, but is an important diagnosis to consider when evaluating febrile infants. Herein, we describe a case of congenital Plasmodium falciparum malaria in a 2-week-old infant born in the United States to a mother who had emigrated from Nigeria 3 months before delivery. © The American Society of Tropical Medicine and Hygiene.

  8. Human Infections with Plasmodium knowlesi, the Philippines

    PubMed Central

    Espino, Fe; Curameng, Peter; Espina, Ronald; Bell, David; Chiodini, Peter; Nolder, Debbie; Sutherland, Colin; Lee, Kim-Sung; Singh, Balbir

    2008-01-01

    Five human cases of infection with the simian malaria parasite Plasmodium knowlesi from Palawan, the Philippines, were confirmed by nested PCR. This study suggests that this zoonotic infection is found across a relatively wide area in Palawan and documents autochthonous cases in the country. PMID:18439369

  9. Epidemiology of Plasmodium vivax Malaria in India.

    PubMed

    Anvikar, Anupkumar R; Shah, Naman; Dhariwal, Akshay C; Sonal, Gagan Singh; Pradhan, Madan Mohan; Ghosh, Susanta K; Valecha, Neena

    2016-12-28

    Historically, malaria in India was predominantly caused by Plasmodium vivax, accounting for 53% of the estimated cases. After the spread of drug-resistant Plasmodium falciparum in the 1990s, the prevalence of the two species remained equivalent at the national level for a decade. By 2014, the proportion of P. vivax has decreased to 34% nationally, but with high regional variation. In 2014, P. vivax accounted for around 380,000 malaria cases in India; almost a sixth of all P. vivax cases reported globally. Plasmodium vivax has remained resistant to control measures, particularly in urban areas. Urban malaria is predominantly caused by P. vivax and is subject to outbreaks, often associated with increased mortality, and triggered by bursts of migration and construction. The epidemiology of P. vivax varies substantially within India, including multiple relapse phenotypes with varying latencies between primary infection and relapse. Moreover, the hypnozoite reservoir maintains transmission potential and enables reestablishment of the parasite in areas in which it was thought eradicated. The burden of malaria in India is complex because of the highly variable malaria eco-epidemiological profiles, transmission factors, and the presence of multiple Plasmodium species and Anopheles vectors. This review of P. vivax malaria in India describes epidemiological trends with particular attention to four states: Gujarat, Karnataka, Haryana, and Odisha.

  10. Plasmodium falciparum Malaria, Southern Algeria, 2007

    PubMed Central

    Gassen, Ibrahim; Khechache, Yacine; Lamali, Karima; Tchicha, Boualem; Brengues, Cécile; Menegon, Michela; Severini, Carlo; Fontenille, Didier; Harrat, Zoubir

    2010-01-01

    An outbreak of Plasmodium falciparum malaria occurred in Tinzaouatine in southern Algeria in 2007. The likely vector, Anopheles gambiae mosquitoes, had not been detected in Algeria. Genes for resistance to chloroquine were detected in the parasite. The outbreak shows the potential for an increase in malaria vectors in Algeria. PMID:20113565

  11. Acute renal failure in Plasmodium malariae infection.

    PubMed

    Neri, S; Pulvirenti, D; Patamia, I; Zoccolo, A; Castellino, P

    2008-04-01

    We report an unusual case of transfusion-transmitted malaria which remained undiagnosed for several months in an Italian woman splenectomised and polytransfused for thalassaemia major. The infecting species was Plasmodium malariae, and the patient developed acute renal failure, severe thrombocytopenia, and hepatic failure. Treatment with chlorochine was followed by a slow, but complete recovery of renal function.

  12. Spatial Epidemiology of Plasmodium vivax, Afghanistan

    PubMed Central

    Leslie, Toby; Kolaczinski, Kate; Mohsen, Engineer; Mehboob, Najeebullah; Saleheen, Sarah; Khudonazarov, Juma; Freeman, Tim; Clements, Archie; Rowland, Mark; Kolaczinski, Jan

    2006-01-01

    Plasmodium vivax is endemic to many areas of Afghanistan. Geographic analysis helped highlight areas of malaria risk and clarified ecologic risk factors for transmission. Remote sensing enabled development of a risk map, thereby providing a valuable tool to help guide malaria control strategies. PMID:17176583

  13. Epidemiology of Plasmodium vivax Malaria in India

    PubMed Central

    Anvikar, Anupkumar R.; Shah, Naman; Dhariwal, Akshay C.; Sonal, Gagan Singh; Pradhan, Madan Mohan; Ghosh, Susanta K.; Valecha, Neena

    2016-01-01

    Historically, malaria in India was predominantly caused by Plasmodium vivax, accounting for 53% of the estimated cases. After the spread of drug-resistant Plasmodium falciparum in the 1990s, the prevalence of the two species remained equivalent at the national level for a decade. By 2014, the proportion of P. vivax has decreased to 34% nationally, but with high regional variation. In 2014, P. vivax accounted for around 380,000 malaria cases in India; almost a sixth of all P. vivax cases reported globally. Plasmodium vivax has remained resistant to control measures, particularly in urban areas. Urban malaria is predominantly caused by P. vivax and is subject to outbreaks, often associated with increased mortality, and triggered by bursts of migration and construction. The epidemiology of P. vivax varies substantially within India, including multiple relapse phenotypes with varying latencies between primary infection and relapse. Moreover, the hypnozoite reservoir maintains transmission potential and enables reestablishment of the parasite in areas in which it was thought eradicated. The burden of malaria in India is complex because of the highly variable malaria eco-epidemiological profiles, transmission factors, and the presence of multiple Plasmodium species and Anopheles vectors. This review of P. vivax malaria in India describes epidemiological trends with particular attention to four states: Gujarat, Karnataka, Haryana, and Odisha. PMID:27708188

  14. Infection of Laboratory-Colonized Anopheles darlingi Mosquitoes by Plasmodium vivax

    PubMed Central

    Moreno, Marta; Tong, Carlos; Guzmán, Mitchel; Chuquiyauri, Raul; Llanos-Cuentas, Alejandro; Rodriguez, Hugo; Gamboa, Dionicia; Meister, Stephan; Winzeler, Elizabeth A.; Maguina, Paula; Conn, Jan E.; Vinetz, Joseph M.

    2014-01-01

    Anopheles darlingi Root is the most important malaria vector in the Amazonia region of South America. However, continuous propagation of An. darlingi in the laboratory has been elusive, limiting entomological, genetic/genomic, and vector–pathogen interaction studies of this mosquito species. Here, we report the establishment of an An. darlingi colony derived from wild-caught mosquitoes obtained in the northeastern Peruvian Amazon region of Iquitos in the Loreto Department. We show that the numbers of eggs, larvae, pupae, and adults continue to rise at least to the F6 generation. Comparison of feeding Plasmodium vivax ex vivo of F4 and F5 to F1 generation mosquitoes showed the comparable presence of oocysts and sporozoites, with numbers that corresponded to blood-stage asexual parasitemia and gametocytemia, confirming P. vivax vectorial capacity in the colonized mosquitoes. These results provide new avenues for research on An. darlingi biology and study of An. darlingi–Plasmodium interactions. PMID:24534811

  15. Plasmodium knowlesi in travellers, update 2014.

    PubMed

    Müller, Mattia; Schlagenhauf, Patricia

    2014-05-01

    Since the initial discovery of Plasmodium knowlesi in Malaysia, cases have been reported from several neighbouring countries. Tourism has also resulted in an increasing number of cases diagnosed in Europe, America, and Oceania. In this review we focus on the risk of the travel-associated acquisition of P. knowlesi malaria. A search of the literature in PubMed was carried out to identify articles and literature on the distribution of P. knowlesi infections in Southeast Asia and details of its acquisition and importation by travellers to other continents. The cut-off date for the search was December 1, 2013. Search words used were: "Plasmodium knowlesi", "Plasmodium knowlesi infections", "Plasmodium knowlesi travellers", "Plasmodium knowlesi prevalence", "Plasmodium knowlesi host", "Plasmodium knowlesi vector" "Plasmodium knowlesi RDT", and "Plasmodium knowlesi Malaysia". Traveller numbers to Malaysia were obtained from the Tourism Malaysia website. A total of 103 articles were found. Using a selection of these and others identified from the reference lists of the papers, we based our review on a total of 66 articles. P. knowlesi malaria appears to be the most common malaria species in Malaysian Borneo and is also widely distributed on the Malaysian mainland. Furthermore, locally transmitted cases of P. knowlesi malaria have been reported in Thailand, the Philippines, Vietnam, Singapore, Myanmar, Indonesian Borneo, and Cambodia. Two cases have been reported from non-endemic countries in Asia (Japan and Taiwan) in people with a history of travel to Malaysia and the Philippines. Twelve cases were imported to their home countries by travellers from other continents: two from the USA, two from the Netherlands, two from Germany, and one each from Spain, France, Sweden, Finland, Australia, and New Zealand. In most cases, the infection was associated with a trip to or near forested areas. The symptoms were fever (n=12), headache (n=6), chills (n=6), nausea (n=4), myalgia (n

  16. 50 CFR 665.262 - Permits.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ...) Any vessel of the United States fishing for, taking, or retaining Hawaii precious coral MUS in any Hawaiian Archipelago precious coral permit area must have a permit issued under § 665.13. (b) Each permit will be valid for fishing only in the permit area specified on the permit. Precious Coral Permit Areas...

  17. 50 CFR 665.262 - Permits.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...) Any vessel of the United States fishing for, taking, or retaining Hawaii precious coral MUS in any Hawaiian Archipelago precious coral permit area must have a permit issued under § 665.13. (b) Each permit will be valid for fishing only in the permit area specified on the permit. Precious Coral Permit Areas...

  18. 50 CFR 665.162 - Permits.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... coral MUS in any American Samoa precious coral permit area must have a permit issued under § 665.13. (b) Each permit will be valid for fishing only in the permit area specified on the permit. Precious Coral... upon surrendering to the Regional Administrator any current permit for the precious coral fishery...

  19. 50 CFR 665.262 - Permits.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ...) Any vessel of the United States fishing for, taking, or retaining Hawaii precious coral MUS in any Hawaiian Archipelago precious coral permit area must have a permit issued under § 665.13. (b) Each permit will be valid for fishing only in the permit area specified on the permit. Precious Coral Permit Areas...

  20. 50 CFR 665.162 - Permits.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... coral MUS in any American Samoa precious coral permit area must have a permit issued under § 665.13. (b) Each permit will be valid for fishing only in the permit area specified on the permit. Precious Coral... upon surrendering to the Regional Administrator any current permit for the precious coral fishery...

  1. 50 CFR 665.162 - Permits.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... coral MUS in any American Samoa precious coral permit area must have a permit issued under § 665.13. (b) Each permit will be valid for fishing only in the permit area specified on the permit. Precious Coral... upon surrendering to the Regional Administrator any current permit for the precious coral fishery...

  2. 50 CFR 665.262 - Permits.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ...) Any vessel of the United States fishing for, taking, or retaining Hawaii precious coral MUS in any Hawaiian Archipelago precious coral permit area must have a permit issued under § 665.13. (b) Each permit will be valid for fishing only in the permit area specified on the permit. Precious Coral Permit Areas...

  3. 50 CFR 665.162 - Permits.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... coral MUS in any American Samoa precious coral permit area must have a permit issued under § 665.13. (b) Each permit will be valid for fishing only in the permit area specified on the permit. Precious Coral... upon surrendering to the Regional Administrator any current permit for the precious coral fishery...

  4. Genome-wide identification of novel intergenic enhancer-like elements: implications in the regulation of transcription in Plasmodium falciparum.

    PubMed

    Ubhe, Suyog; Rawat, Mukul; Verma, Srikant; Anamika, Krishanpal; Karmodiya, Krishanpal

    2017-08-23

    The molecular mechanisms of transcriptional regulation are poorly understood in Plasmodium falciparum. In addition, most of the genes in Plasmodium falciparum are transcriptionally poised and only a handful of cis-regulatory elements are known to operate in transcriptional regulation. Here, we employed an epigenetic signature based approach to identify significance of previously uncharacterised intergenic regions enriched with histone modification marks leading to discovery of enhancer-like elements. We found that enhancer-like elements are significantly enriched with H3K4me1, generate unique non-coding bi-directional RNAs and majority of them can function as cis-regulators. Furthermore, functional enhancer reporter assay demonstrates that the enhancer-like elements regulate transcription of target genes in Plasmodium falciparum. Our study also suggests that the Plasmodium genome segregates functionally related genes into discrete housekeeping and pathogenicity/virulence clusters, presumably for robust transcriptional control of virulence/pathogenicity genes. This report contributes to the understanding of parasite regulatory genomics by identification of enhancer-like elements, defining their epigenetic and transcriptional features and provides a resource of functional cis-regulatory elements that may give insights into the virulence/pathogenicity of Plasmodium falciparum.

  5. Permitted water use in Iowa, 1985

    USGS Publications Warehouse

    Runkle, D.L.; Newman, J.L.; Shields, E.M.

    1985-01-01

    This report summarizes where, how much and for what purpose water is allocated for use in Iowa with permits issued by the Department of Water, Air and Waste Management. In Iowa, from a total permitted water use of 855,175.45 million gallons per year, about 58 percent is from surface-water sources and about 42 percent is from ground-water sources. Streams are 80.5 percent of the total surface-water use and wells make up 80.1 percent of the total ground-water use, with 65.4 percent of ground water coming from surficial aquifers. Power generation is the use category that is permitted the largest amount of total water use, 46.6 percent, with surface water being the source of 96.7 percent and 77.9 percent of the surface water is from streams. The public water suppliers' category is the next largest use type with 15.7 percent of the total permitted water. Ground water constitutes 74.4 percent of the public water supplier category with 51.7 percent from surficial aquifers. Surface water makes up 25.6 percent of this category with 83.0 percent of the surface water withdrawn from streams. Mining comprises 13.4 percent of the total water use and is the third largest water-use category. Ground water is the source of 63.3 percent of permitted mining water use with 94.3 percent of this from quarries and sand and gravel pits. Surface water is the source of 36.7 percent of the permitted mining water use with 97.6 percent from streams. Irrigation is the fourth largest permitted use type using 12.0 percent of the total water use. Eighty-eight percent of irrigation is from ground-water sources where surficial aquifers account for 94.7 percent. Streams are 81.1 percent of irrigational surface-water use. Self-supplied industrial users are permitted 10.6 percent of the total permitted water use with 85.5 percent of this from ground-water sources and 14.5 percent from surface-water sources. Of the self-supplied industrial ground-water use, 47.9 percent comes from surficial aquifers and

  6. In silico identification of genetically attenuated vaccine candidate genes for Plasmodium liver stage.

    PubMed

    Kumar, Hirdesh; Frischknecht, Friedrich; Mair, Gunnar R; Gomes, James

    2015-12-01

    Genetically attenuated parasites (GAPs) that lack genes essential for the liver stage of the malaria parasite, and therefore cause developmental arrest, have been developed as live vaccines in rodent malaria models and recently been tested in humans. The genes targeted for deletion were often identified by trial and error. Here we present a systematic gene - protein and transcript - expression analyses of several Plasmodium species with the aim to identify candidate genes for the generation of novel GAPs. With a lack of liver stage expression data for human malaria parasites, we used data available for liver stage development of Plasmodium yoelii, a rodent malaria model, to identify proteins expressed in the liver stage but absent from blood stage parasites. An orthology-based search was then employed to identify orthologous proteins in the human malaria parasite Plasmodium falciparum resulting in a total of 310 genes expressed in the liver stage but lacking evidence of protein expression in blood stage parasites. Among these 310 possible GAP candidates, we further studied Plasmodium liver stage proteins by phyletic distribution and functional domain analyses and shortlisted twenty GAP-candidates; these are: fabB/F, fabI, arp, 3 genes encoding subunits of the PDH complex, dnaJ, urm1, rS5, ancp, mcp, arh, gk, lisp2, valS, palm, and four conserved Plasmodium proteins of unknown function. Parasites lacking one or several of these genes might yield new attenuated malaria parasites for experimental vaccination studies. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Environment-dependent morphology in plasmodium of true slime mold Physarum polycephalum and a network growth model.

    PubMed

    Takamatsu, Atsuko; Takaba, Eri; Takizawa, Ginjiro

    2009-01-07

    Branching network growth patterns, depending on environmental conditions, in plasmodium of true slime mold Physarum polycephalum were investigated. Surprisingly, the patterns resemble those in bacterial colonies even though the biological mechanisms differ greatly. Bacterial colonies are collectives of microorganisms in which individual organisms have motility and interact through nutritious and chemical fields. In contrast, the plasmodium is a giant amoeba-like multinucleated unicellular organism that forms a network of tubular structures through which protoplasm streams. The cell motility of the plasmodium is generated by oscillation phenomena observed in the partial bodies, which interact through the tubular structures. First, we analyze characteristics of the morphology quantitatively, then we abstract local rules governing the growing process to construct a simple network growth model. This model is independent of specific systems, in which only two rules are applied. Finally, we discuss the mechanism of commonly observed biological pattern formations through comparison with the system of bacterial colonies.

  8. A case of Plasmodium ovale malaria imported from West Africa.

    PubMed

    Kang, Yunjung; Yang, Jinyoung

    2013-04-01

    Malaria is a parasitic infection caused by Plasmodium species. Most of the imported malaria in Korea are due to Plasmodium vivax and Plasmodium falciparum, and Plasmodium ovale infections are very rare. Here, we report a case of a 24-year-old American woman who acquired P. ovale while staying in Ghana, West Africa for 5 months in 2010. The patient was diagnosed with P. ovale malaria based on a Wright-Giemsa stained peripheral blood smear, Plasmodium genus-specific real-time PCR, Plasmodium species-specific nested PCR, and sequencing targeting 18S rRNA gene. The strain identified had a very long incubation period of 19-24 months. Blood donors who have malaria with a very long incubation period could be a potential danger for propagating malaria. Therefore, we should identify imported P. ovale infections not only by morphological findings but also by molecular methods for preventing propagation and appropriate treatment.

  9. Merrimack Station Draft NPDES Permit | NPDES Permits in ...

    EPA Pesticide Factsheets

    2017-02-16

    EPA and the New Hampshire Department of Environmental Services (NHDES) have issued a new Draft National Pollutant Discharge Elimination System (NPDES) permit for the Merrimack Station power plant in Bow, New Hampshire.

  10. 76 FR 34071 - Lock Hydro Friends Fund I; Notice of Preliminary Permit Application Accepted for Filing and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-10

    ..., also known as, a frame module; (4) the frame ] module would contain 2 generating units with a total... Colorado River in Travis County, Texas. The sole purpose of a preliminary permit, if issued, is to grant the permit holder priority to file a license application during the permit term. A preliminary permit...

  11. Parasite Lactate Dehydrogenase for Diagnosis of Plasmodium Falciparum. Phase II.

    DTIC Science & Technology

    1997-04-01

    Diagnosis of Plasmodium Falciparum PRINCIPAL INVESTIGATOR: Robert C. Piper, Ph.D. CONTRACTING ORGANIZATION: Flow, Incorporated Portland, Oregon 97201...Phase 11 (24 Mar 95 - 23 Mar 97) 4. TITLE AND SUBTITLE 5. FUNDING NUMBERS Parasite Lactate Dehydrogenase for Diagnosis of Plasmodium Falciparum DAMD...that infected patients become ill. Four species of Plasmodium infect humans. P. falciparum accounts for -85 % of the world’s malaria. P. falciparum is

  12. Operating Permits Program Review Process

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  13. Operating Permit Program Approval Issues

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  14. Filarial Worms Reduce Plasmodium Infectivity in Mosquitoes

    PubMed Central

    Aliota, Matthew T.; Chen, Cheng-Chen; Dagoro, Henry; Fuchs, Jeremy F.; Christensen, Bruce M.

    2011-01-01

    Background Co-occurrence of malaria and filarial worm parasites has been reported, but little is known about the interaction between filarial worm and malaria parasites with the same Anopheles vector. Herein, we present data evaluating the interaction between Wuchereria bancrofti and Anopheles punctulatus in Papua New Guinea (PNG). Our field studies in PNG demonstrated that An. punctulatus utilizes the melanization immune response as a natural mechanism of filarial worm resistance against invading W. bancrofti microfilariae. We then conducted laboratory studies utilizing the mosquitoes Armigeres subalbatus and Aedes aegypti and the parasites Brugia malayi, Brugia pahangi, Dirofilaria immitis, and Plasmodium gallinaceum to evaluate the hypothesis that immune activation and/or development by filarial worms negatively impact Plasmodium development in co-infected mosquitoes. Ar. subalbatus used in this study are natural vectors of P. gallinaceum and B. pahangi and they are naturally refractory to B. malayi (melanization-based refractoriness). Methodology/Principal Findings Mosquitoes were dissected and Plasmodium development was analyzed six days after blood feeding on either P. gallinaceum alone or after taking a bloodmeal containing both P. gallinaceum and B. malayi or a bloodmeal containing both P. gallinaceum and B. pahangi. There was a significant reduction in the prevalence and mean intensity of Plasmodium infections in two species of mosquito that had dual infections as compared to those mosquitoes that were infected with Plasmodium alone, and was independent of whether the mosquito had a melanization immune response to the filarial worm or not. However, there was no reduction in Plasmodium development when filarial worms were present in the bloodmeal (D. immitis) but midgut penetration was absent, suggesting that factors associated with penetration of the midgut by filarial worms likely are responsible for the observed reduction in malaria parasite infections

  15. 40 CFR 60.4121 - Submission of Hg budget permit applications.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 6 2010-07-01 2010-07-01 false Submission of Hg budget permit... Times for Coal-Fired Electric Steam Generating Units Permits § 60.4121 Submission of Hg budget permit applications. (a) Duty to apply. The Hg designated representative of any Hg Budget source required to have a...

  16. Bifurcation in the chemotactic behavior of Physarum plasmodium

    NASA Astrophysics Data System (ADS)

    Shirakawa, Tomohiro; Gunji, Yukio-Pegio; Sato, Hiroshi; Tsubakino, Hiroto

    2017-07-01

    The plasmodium of true slime mold Physarum polycephalum is a unicellular and multinuclear giant amoeba. Since the cellular organism has some computational abilities, it is attracting much attention in the field of information science. However, previous studies have mainly focused on the optimization behavior of the plasmodium for a single-modality stimulus, and there are few studies on how the organism adapts to multi-modal stimuli. We stimulated the plasmodium with mixture of attractant and repellent stimuli, and we observed bifurcation in the chemotactic behavior of the plasmodium.

  17. Air Emissions Monitoring for Permits

    EPA Pesticide Factsheets

    Operating permits document how air pollution sources will demonstrate compliance with emission limits and also how air pollution sources will monitor, either periodically or continuously, their compliance with emission limits and all other requirements.

  18. City of Wagner NPDES Permit

    EPA Pesticide Factsheets

    Under NPDES permit SD-0020184, the City of Wagner, South Dakota is authorized to discharge from its wastewater treatment facility in Charles Mix County, South Dakota, to an unnamed tributary of Choteau Creek.

  19. Keller Transport, Inc. NPDES Permit

    EPA Pesticide Factsheets

    Under National Pollutant Discharge Elimination System permit number MT-0030805, Keller Transport, Inc. is authorized to discharge from its groundwater remediation treatment facility in Lake County, Montana, to Flathead Lake.

  20. Rocky Mountain Arsenal NPDES Permit

    EPA Pesticide Factsheets

    Under NPDES permit CO-0035009, the U.S. Department of Interior's Fish and Wildlife Service is authorized to discharge from the Rocky Mountain Arsenal recycled water pipeline to Lower Derby Lake in Adams County, Colo.

  1. Wulf Cattle Depot NPDES Permit

    EPA Pesticide Factsheets

    Under NPDES permit SD-0034606, the Wulf Cattle Depot is authorized to discharge and must operate their facility in accordance with effluent limitations, monitoring requirements, and other provisions set forth herein.

  2. Shoshone Utility Organization NPDES Permit

    EPA Pesticide Factsheets

    Under NPDES permit WY-0044580, the Shoshone Utility Organization is authorized to discharge from its wastewater treatment facility located in Fremont County, Wyoming to an unnamed irrigation drainage ditch tributary to the South Fork of the Little Wind R.

  3. Chemtrade Refinery Services NPDES Permit

    EPA Pesticide Factsheets

    Under NPDES permit WY-0034207, Chemtrade Refinery Services, Inc. is authorized to discharge from its wastewater treatment facility located in Fremont County,Wyoming, to an unnamed drainage way that flows into the Little Wind River near St. Stephens, Wyo.

  4. Dakota Magic Casino NPDES Permit

    EPA Pesticide Factsheets

    Under NPDES permit ND-0030813, the Dakota Nation Gaming Enterprise is authorized to discharge from the wastewater treatment facility in Richland County, North Dakota, to a roadside ditch flowing to an unnamed tributary to the Bois de Sioux.

  5. Soap Creek Associates NPDES Permit

    EPA Pesticide Factsheets

    Under National Pollutant Discharge Elimination System permit number MT-0023183, Soap Creek Associates, Inc. is authorized to discharge from its wastewater treatment facility located in West, Bighorn County, Montana, to Soap Creek.

  6. Sugar activation and glycosylation in Plasmodium.

    PubMed

    Cova, Marta; Rodrigues, João A; Smith, Terry K; Izquierdo, Luis

    2015-10-31

    Glycoconjugates are important mediators of host-pathogen interactions and are usually very abundant in the surface of many protozoan parasites. However, in the particular case of Plasmodium species, previous works show that glycosylphosphatidylinositol anchor modifications, and to an unknown extent, a severely truncated N-glycosylation are the only glycosylation processes taking place in the parasite. Nevertheless, a detailed analysis of the parasite genome and the recent identification of the sugar nucleotide precursors biosynthesized by Plasmodium falciparum support a picture in which several overlooked, albeit not very prominent glycosylations may be occurring during the parasite life cycle. In this work, the authors review recent developments in the characterization of the biosynthesis of glycosylation precursors in the parasite, focusing on the outline of the possible fates of these precursors.

  7. Engineered Anopheles Immunity to Plasmodium Infection

    PubMed Central

    Cirimotich, Chris; Souza-Neto, Jayme A.; McLean, Kyle J.; Dimopoulos, George

    2011-01-01

    A causative agent of human malaria, Plasmodium falciparum, is transmitted by Anopheles mosquitoes. The malaria parasite is under intensive attack from the mosquito's innate immune system during its sporogonic development. We have used genetic engineering to create immune-enhanced Anopheles stephensi mosquitoes through blood meal-inducible expression of a transgene encoding the IMD pathway-controlled NF-kB Rel2 transcription factor in the midgut and fat-body tissue. Transgenic mosquitoes showed greater resistance to Plasmodium and microbial infection as a result of timely concerted tissue-specific immune attacks involving multiple effectors. The relatively weak impact of this genetic modification on mosquito fitness under laboratory conditions encourages further investigation of this approach for malaria control. PMID:22216006

  8. Engineered anopheles immunity to Plasmodium infection.

    PubMed

    Dong, Yuemei; Das, Suchismita; Cirimotich, Chris; Souza-Neto, Jayme A; McLean, Kyle J; Dimopoulos, George

    2011-12-01

    A causative agent of human malaria, Plasmodium falciparum, is transmitted by Anopheles mosquitoes. The malaria parasite is under intensive attack from the mosquito's innate immune system during its sporogonic development. We have used genetic engineering to create immune-enhanced Anopheles stephensi mosquitoes through blood meal-inducible expression of a transgene encoding the IMD pathway-controlled NF-kB Rel2 transcription factor in the midgut and fat-body tissue. Transgenic mosquitoes showed greater resistance to Plasmodium and microbial infection as a result of timely concerted tissue-specific immune attacks involving multiple effectors. The relatively weak impact of this genetic modification on mosquito fitness under laboratory conditions encourages further investigation of this approach for malaria control.

  9. Plasmodium Oocysts: Overlooked Targets of Mosquito Immunity.

    PubMed

    Smith, Ryan C; Barillas-Mury, Carolina

    2016-12-01

    Although the ability of mosquitoes to limit Plasmodium infection is well documented, many questions remain as to how malaria parasites are recognized and killed by the mosquito host. Recent evidence suggests that anti-Plasmodium immunity is multimodal, with different immune mechanisms regulating ookinete and oocyst survival. However, most experiments determine the number of mature oocysts, without considering that different immune mechanisms may target different developmental stages of the parasite. Complement-like proteins have emerged as important determinants of early immunity targeting the ookinete stage, yet the mechanisms by which the mosquito late-phase immune response limits oocyst survival are less understood. Here, we describe the known components of the mosquito immune system that limit oocyst development, and provide insight into their possible mechanisms of action. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. The National Solar Permitting Database

    SciTech Connect

    Gunderson, Renic

    2014-08-31

    "The soft costs of solar—costs not associated with hardware—remain stubbornly high. Among the biggest soft costs are those associated with inefficiencies in local permitting and inspection. A study by the National Renewable Energy Laboratory and Lawrence Berkeley National Laboratory estimates that these costs add an average of $0.22/W per residential installation. This project helps reduce non-hardware/balance of system (BOS) costs by creating and maintaining a free and available site of permitting requirements and solar system verification software that installers can use to reduce time, capital, and resource investments in tracking permitting requirements. Software tools to identify best permitting practices can enable government stakeholders to optimize their permitting process and remove superfluous costs and requirements. Like ""a Wikipedia for solar permitting"", users can add, edit, delete, and update information for a given jurisdiction. We incentivize this crowdsourcing approach by recognizing users for their contributions in the form of SEO benefits to their company or organization by linking back to users' websites."

  11. The National Solar Permitting Database

    SciTech Connect

    Gunderson, Renic

    2014-08-31

    "The soft costs of solar — costs not associated with hardware — remain stubbornly high. Among the biggest soft costs are those associated with inefficiencies in local permitting and inspection. A study by the National Renewable Energy Laboratory and Lawrence Berkeley National Laboratory estimates that these costs add an average of $0.22/W per residential installation. This project helps reduce non-hardware/balance of system (BOS) costs by creating and maintaining a free and available site of permitting requirements and solar system verification software that installers can use to reduce time, capital, and resource investments in tracking permitting requirements. Software tools to identify best permitting practices can enable government stakeholders to optimize their permitting process and remove superfluous costs and requirements. Like ""a Wikipedia for solar permitting"", users can add, edit, delete, and update information for a given jurisdiction. We incentivize this crowdsourcing approach by recognizing users for their contributions in the form of SEO benefits to their company or organization by linking back to users' websites."

  12. Plasmodium vivax Malaria Endemicity in Indonesia in 2010

    PubMed Central

    Elyazar, Iqbal R. F.; Gething, Peter W.; Patil, Anand P.; Rogayah, Hanifah; Sariwati, Elvieda; Palupi, Niken W.; Tarmizi, Siti N.; Kusriastuti, Rita; Baird, J. Kevin; Hay, Simon I.

    2012-01-01

    Background Plasmodium vivax imposes substantial morbidity and mortality burdens in endemic zones. Detailed understanding of the contemporary spatial distribution of this parasite is needed to combat it. We used model based geostatistics (MBG) techniques to generate a contemporary map of risk of Plasmodium vivax malaria in Indonesia in 2010. Methods Plasmodium vivax Annual Parasite Incidence data (2006–2008) and temperature masks were used to map P. vivax transmission limits. A total of 4,658 community surveys of P. vivax parasite rate (PvPR) were identified (1985–2010) for mapping quantitative estimates of contemporary endemicity within those limits. After error-checking a total of 4,457 points were included into a national database of age-standardized 1–99 year old PvPR data. A Bayesian MBG procedure created a predicted PvPR1–99 endemicity surface with uncertainty estimates. Population at risk estimates were derived with reference to a 2010 human population surface. Results We estimated 129.6 million people in Indonesia lived at risk of P. vivax transmission in 2010. Among these, 79.3% inhabited unstable transmission areas and 20.7% resided in stable transmission areas. In western Indonesia, the predicted P. vivax prevalence was uniformly low. Over 70% of the population at risk in this region lived on Java and Bali islands, where little malaria transmission occurs. High predicted prevalence areas were observed in the Lesser Sundas, Maluku and Papua. In general, prediction uncertainty was relatively low in the west and high in the east. Conclusion Most Indonesians living with endemic P. vivax experience relatively low risk of infection. However, blood surveys for this parasite are likely relatively insensitive and certainly do not detect the dormant liver stage reservoir of infection. The prospects for P. vivax elimination would be improved with deeper understanding of glucose-6-phosphate dehydrogenase deficiency (G6PDd) distribution, anti-relapse therapy

  13. DNA secondary structures are associated with recombination in major Plasmodium falciparum variable surface antigen gene families

    PubMed Central

    Sander, Adam F.; Lavstsen, Thomas; Rask, Thomas S.; Lisby, Michael; Salanti, Ali; Fordyce, Sarah L.; Jespersen, Jakob S.; Carter, Richard; Deitsch, Kirk W.; Theander, Thor G.; Pedersen, Anders Gorm; Arnot, David E.

    2014-01-01

    Many bacterial, viral and parasitic pathogens undergo antigenic variation to counter host immune defense mechanisms. In Plasmodium falciparum, the most lethal of human malaria parasites, switching of var gene expression results in alternating expression of the adhesion proteins of the Plasmodium falciparum-erythrocyte membrane protein 1 class on the infected erythrocyte surface. Recombination clearly generates var diversity, but the nature and control of the genetic exchanges involved remain unclear. By experimental and bioinformatic identification of recombination events and genome-wide recombination hotspots in var genes, we show that during the parasite’s sexual stages, ectopic recombination between isogenous var paralogs occurs near low folding free energy DNA 50-mers and that these sequences are heavily concentrated at the boundaries of regions encoding individual Plasmodium falciparum-erythrocyte membrane protein 1 structural domains. The recombinogenic potential of these 50-mers is not parasite-specific because these sequences also induce recombination when transferred to the yeast Saccharomyces cerevisiae. Genetic cross data suggest that DNA secondary structures (DSS) act as inducers of recombination during DNA replication in P. falciparum sexual stages, and that these DSS-regulated genetic exchanges generate functional and diverse P. falciparum adhesion antigens. DSS-induced recombination may represent a common mechanism for optimizing the evolvability of virulence gene families in pathogens. PMID:24253306

  14. Plasmodium vivax trophozoites insensitive to chloroquine

    PubMed Central

    Sharrock, Wesley W; Suwanarusk, Rossarin; Lek-Uthai, Usa; Edstein, Michael D; Kosaisavee, Varakorn; Travers, Thomas; Jaidee, Anchalee; Sriprawat, Kanlaya; Price, Ric N; Nosten, François; Russell, Bruce

    2008-01-01

    Background Plasmodium vivax is a major cause of malaria and is still primarily treated with chloroquine. Chloroquine inhibits the polymerization of haem to inert haemozoin. Free haem monomers are thought to catalyze oxidative damage to the Plasmodium spp. trophozoite, the stage when haemoglobin catabolism is maximal. However preliminary in vitro observations on P. vivax clinical isolates suggest that only ring stages (early trophozoites) are sensitive to chloroquine. In this study, the stage specific action of chloroquine was investigated in synchronous cryopreserved isolates of P. vivax. Methods The in vitro chloroquine sensitivity of paired ring and trophozoite stages from 11 cryopreserved P. vivax clinical isolates from Thailand and two Plasmodium falciparum clones (chloroquine resistant K1 and chloroquine sensitive FC27) was measured using a modified WHO microtest method and fluorometric SYBR Green I Assay. The time each stage was exposed to chloroquine treatment was controlled by washing the chloroquine off at 20 hours after the beginning of treatment. Results Plasmodium vivax isolates added to the assay at ring stage had significantly lower median IC50s to chloroquine than the same isolates added at trophozoite stage (median IC50 12 nM vs 415 nM p < 0.01). Although only 36% (4/11) of the SYBR Green I assays for P. vivax were successful, both microscopy and SYBR Green I assays indicated that only P. vivax trophozoites were able to develop to schizonts at chloroquine concentrations above 100 nM. Conclusion Data from this study confirms the diminished sensitivity of P. vivax trophozoites to chloroquine, the stage thought to be the target of this drug. These results raise important questions about the pharmacodynamic action of chloroquine, and highlight a fundamental difference in the activity of chloroquine between P. vivax and P. falciparum. PMID:18505560

  15. Plasmodium malariae in Haitian Refugees, Jamaica

    PubMed Central

    Bryce, Jeanette Horner; Ducasse, Marion Bullock; Howitt, Christina; Barrett, Donnett M.; Morales, Jacob Lorenzo; Ord, Rosalynn; Burke, Martina; Chiodini, Peter L.; Sutherland, Colin J.

    2007-01-01

    Since 1963, reported malaria transmission in Haiti has been restricted to Plasmodium falciparum. However, screening of Haitian refugees in Jamaica in 2004, by microscopic examination, identified P. falciparum, P. vivax, and P. malariae. PCR confirmed the P. malariae and P. falciparum but not P. vivax infections. DNA sequencing and rRNA gene sequences showed transmission of P. malariae. This report confirms that P. malariae is still being transmitted in Haiti. PMID:17553241

  16. 40 CFR 172.5 - The permit.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 24 2014-07-01 2014-07-01 false The permit. 172.5 Section 172.5... PERMITS Federal Issuance of Experimental Use Permits § 172.5 The permit. (a) Issuance. The Experimental Use Permit shall be issued when the Administrator determines that the conditions of section 5 of the...

  17. 40 CFR 172.5 - The permit.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 25 2012-07-01 2012-07-01 false The permit. 172.5 Section 172.5... PERMITS Federal Issuance of Experimental Use Permits § 172.5 The permit. (a) Issuance. The Experimental Use Permit shall be issued when the Administrator determines that the conditions of section 5 of the...

  18. 40 CFR 172.5 - The permit.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 25 2013-07-01 2013-07-01 false The permit. 172.5 Section 172.5... PERMITS Federal Issuance of Experimental Use Permits § 172.5 The permit. (a) Issuance. The Experimental Use Permit shall be issued when the Administrator determines that the conditions of section 5 of the...

  19. 9 CFR 104.2 - Permit authorized.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... permits for importing biological products. They shall be: (1) U.S. Veterinary Biological Product Permit for Research and Evaluation; (2) U.S. Veterinary Biological Product Permit for Distribution and Sale; or (3) U.S. Veterinary Biological Product Permit for Transit Shipment Only. (b) A permit shall not...

  20. 50 CFR 665.242 - Permits.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... in Crustacean Permit Areas 1 or 2 must have a permit issued for that vessel. (4) Harvest of Hawaii crustacean MUS within the Northwestern Hawaiian Islands Marine National Monument is subject to the... limited access permit is valid for fishing only in Crustacean Permit Area 1. (2) Only one permit will...

  1. 50 CFR 665.242 - Permits.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... in Crustacean Permit Areas 1 or 2 must have a permit issued for that vessel. (4) Harvest of Hawaii crustacean MUS within the Northwestern Hawaiian Islands Marine National Monument is subject to the... limited access permit is valid for fishing only in Crustacean Permit Area 1. (2) Only one permit will...

  2. 50 CFR 665.242 - Permits.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... in Crustacean Permit Areas 1 or 2 must have a permit issued for that vessel. (4) Harvest of Hawaii crustacean MUS within the Northwestern Hawaiian Islands Marine National Monument is subject to the... limited access permit is valid for fishing only in Crustacean Permit Area 1. (2) Only one permit will...

  3. 50 CFR 665.242 - Permits.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... in Crustacean Permit Areas 1 or 2 must have a permit issued for that vessel. (4) Harvest of Hawaii crustacean MUS within the Northwestern Hawaiian Islands Marine National Monument is subject to the... limited access permit is valid for fishing only in Crustacean Permit Area 1. (2) Only one permit will...

  4. 50 CFR 665.242 - Permits.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... in Crustacean Permit Areas 1 or 2 must have a permit issued for that vessel. (4) Harvest of Hawaii crustacean MUS within the Northwestern Hawaiian Islands Marine National Monument is subject to the... limited access permit is valid for fishing only in Crustacean Permit Area 1. (2) Only one permit will...

  5. 50 CFR 680.4 - Permits.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... annually or at other times as needed under this part. (3) Transfer. Crab QS and PQS permits issued under § 680.40 and Crab IFQ and IPQ permits issued under this section are transferable, as provided under § 680.41. Crab IFQ hired master permits, Federal crab vessel permits, and RCR permits issued under this...

  6. 40 CFR 72.85 - Permit reopenings.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... REGULATION Permit Revisions § 72.85 Permit reopenings. (a) The permitting authority shall reopen an Acid Rain permit for cause whenever: (1) Any additional requirement under the Acid Rain Program becomes applicable... revoked to assure compliance with Acid Rain Program requirements. (b) In reopening an Acid Rain permit for...

  7. 40 CFR 72.85 - Permit reopenings.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... REGULATION Permit Revisions § 72.85 Permit reopenings. (a) The permitting authority shall reopen an Acid Rain permit for cause whenever: (1) Any additional requirement under the Acid Rain Program becomes applicable... revoked to assure compliance with Acid Rain Program requirements. (b) In reopening an Acid Rain permit for...

  8. 40 CFR 72.85 - Permit reopenings.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... REGULATION Permit Revisions § 72.85 Permit reopenings. (a) The permitting authority shall reopen an Acid Rain permit for cause whenever: (1) Any additional requirement under the Acid Rain Program becomes applicable... revoked to assure compliance with Acid Rain Program requirements. (b) In reopening an Acid Rain permit for...

  9. 40 CFR 72.85 - Permit reopenings.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... REGULATION Permit Revisions § 72.85 Permit reopenings. (a) The permitting authority shall reopen an Acid Rain permit for cause whenever: (1) Any additional requirement under the Acid Rain Program becomes applicable... revoked to assure compliance with Acid Rain Program requirements. (b) In reopening an Acid Rain permit for...

  10. 40 CFR 72.85 - Permit reopenings.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... REGULATION Permit Revisions § 72.85 Permit reopenings. (a) The permitting authority shall reopen an Acid Rain permit for cause whenever: (1) Any additional requirement under the Acid Rain Program becomes applicable... revoked to assure compliance with Acid Rain Program requirements. (b) In reopening an Acid Rain permit for...

  11. 21 CFR 1210.21 - Permit number.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Permit number. 1210.21 Section 1210.21 Food and... IMPORT MILK ACT Permit Control § 1210.21 Permit number. Each permit issued under the Federal Import Milk Act, including each temporary permit, shall bear an individual number. The right to the use of such...

  12. 21 CFR 1210.21 - Permit number.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Permit number. 1210.21 Section 1210.21 Food and... IMPORT MILK ACT Permit Control § 1210.21 Permit number. Each permit issued under the Federal Import Milk Act, including each temporary permit, shall bear an individual number. The right to the use of such...

  13. 40 CFR 172.5 - The permit.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false The permit. 172.5 Section 172.5... PERMITS Federal Issuance of Experimental Use Permits § 172.5 The permit. (a) Issuance. The Experimental Use Permit shall be issued when the Administrator determines that the conditions of section 5 of the...

  14. 21 CFR 1210.21 - Permit number.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Permit number. 1210.21 Section 1210.21 Food and... IMPORT MILK ACT Permit Control § 1210.21 Permit number. Each permit issued under the Federal Import Milk Act, including each temporary permit, shall bear an individual number. The right to the use of such...

  15. 21 CFR 1210.21 - Permit number.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Permit number. 1210.21 Section 1210.21 Food and... IMPORT MILK ACT Permit Control § 1210.21 Permit number. Each permit issued under the Federal Import Milk Act, including each temporary permit, shall bear an individual number. The right to the use of such...

  16. Local Adaptation and Vector-Mediated Population Structure in Plasmodium vivax Malaria

    PubMed Central

    Gonzalez-Ceron, Lilia; Carlton, Jane M.; Gueye, Amy; Fay, Michael; McCutchan, Thomas F.; Su, Xin-zhuan

    2008-01-01

    Plasmodium vivax in southern Mexico exhibits different infectivities to 2 local mosquito vectors, Anopheles pseudopunctipennis and Anopheles albimanus. Previous work has tied these differences in mosquito infectivity to variation in the central repeat motif of the malaria parasite's circumsporozoite (csp) gene, but subsequent studies have questioned this view. Here we present evidence that P. vivax in southern Mexico comprised 3 genetic populations whose distributions largely mirror those of the 2 mosquito vectors. Additionally, laboratory colony feeding experiments indicate that parasite populations are most compatible with sympatric mosquito species. Our results suggest that reciprocal selection between malaria parasites and mosquito vectors has led to local adaptation of the parasite. Adaptation to local vectors may play an important role in generating population structure in Plasmodium. A better understanding of coevolutionary dynamics between sympatric mosquitoes and parasites will facilitate the identification of molecular mechanisms relevant to disease transmission in nature and provide crucial information for malaria control. PMID:18385220

  17. Targeting the hypnozoite reservoir of Plasmodium vivax: the hidden obstacle to malaria elimination.

    PubMed

    Wells, Timothy N C; Burrows, Jeremy N; Baird, J Kevin

    2010-03-01

    Plasmodium vivax is the major species of malaria parasite outside Africa. It is especially problematic in that the infection can relapse in the absence of mosquitoes by activation of dormant hypnozoites in the liver. Medicines that target the erythrocytic stages of Plasmodium falciparum are also active against P. vivax, except where these have been compromised by resistance. However, the only clinical therapy against relapse of vivax malaria is the 8-aminoquinoline, primaquine. This molecule has the drawback of causing haemolysis in genetically sensitive patients and requires 14 days of treatment. New, safer and more-easily administered drugs are urgently needed, and this is a crucial gap in the broader malaria-elimination agenda. New developments in cell biology are starting to open ways to the next generation of drugs against hypnozoites. This search is urgent, given the time needed to develop a new medication.

  18. Epidemiology of Plasmodium vivax in Indonesia

    PubMed Central

    Surjadjaja, Claudia; Surya, Asik; Baird, J. Kevin

    2016-01-01

    Endemic malaria occurs across much of the vast Indonesian archipelago. All five species of Plasmodium known to naturally infect humans occur here, along with 20 species of Anopheles mosquitoes confirmed as carriers of malaria. Two species of plasmodia cause the overwhelming majority and virtually equal shares of malaria infections in Indonesia: Plasmodium falciparum and Plasmodium vivax. The challenge posed by P. vivax is especially steep in Indonesia because chloroquine-resistant strains predominate, along with Chesson-like strains that relapse quickly and multiple times at short intervals in almost all patients. Indonesia's hugely diverse human population carries many variants of glucose-6-phosphate dehydrogenase (G6PD) deficiency, most of them exhibiting severely impaired enzyme activity. Therefore, the patients most likely to benefit from primaquine therapy by preventing aggressive relapse, may also be most likely to suffer harm without G6PD deficiency screening. Indonesia faces the challenge of controlling and eventually eliminating malaria across > 13,500 islands stretching > 5,000 km and an enormous diversity of ecological, ethnographic, and socioeconomic settings, and extensive human migrations. This article describes the occurrence of P. vivax in Indonesia and the obstacles faced in eliminating its transmission. PMID:27708185

  19. Epidemiology of Plasmodium vivax in Indonesia.

    PubMed

    Surjadjaja, Claudia; Surya, Asik; Baird, J Kevin

    2016-12-28

    Endemic malaria occurs across much of the vast Indonesian archipelago. All five species of Plasmodium known to naturally infect humans occur here, along with 20 species of Anopheles mosquitoes confirmed as carriers of malaria. Two species of plasmodia cause the overwhelming majority and virtually equal shares of malaria infections in Indonesia: Plasmodium falciparum and Plasmodium vivax The challenge posed by P. vivax is especially steep in Indonesia because chloroquine-resistant strains predominate, along with Chesson-like strains that relapse quickly and multiple times at short intervals in almost all patients. Indonesia's hugely diverse human population carries many variants of glucose-6-phosphate dehydrogenase (G6PD) deficiency, most of them exhibiting severely impaired enzyme activity. Therefore, the patients most likely to benefit from primaquine therapy by preventing aggressive relapse, may also be most likely to suffer harm without G6PD deficiency screening. Indonesia faces the challenge of controlling and eventually eliminating malaria across > 13,500 islands stretching > 5,000 km and an enormous diversity of ecological, ethnographic, and socioeconomic settings, and extensive human migrations. This article describes the occurrence of P. vivax in Indonesia and the obstacles faced in eliminating its transmission. © The American Society of Tropical Medicine and Hygiene.

  20. Plasmodium simium/Plasmodium vivax infections in southern brown howler monkeys from the Atlantic Forest

    PubMed Central

    Costa, Daniela Camargos; da Cunha, Vanessa Pecini; de Assis, Gabriela Maria Pereira; de Souza, Júlio César; Hirano, Zelinda Maria Braga; de Arruda, Mércia Eliane; Kano, Flora Satiko; Carvalho, Luzia Helena; de Brito, Cristiana Ferreira Alves

    2014-01-01

    Blood infection by the simian parasite, Plasmodium simium, was identified in captive (n = 45, 4.4%) and in wild Alouatta clamitans monkeys (n = 20, 35%) from the Atlantic Forest of southern Brazil. A single malaria infection was symptomatic and the monkey presented clinical and haematological alterations. A high frequency of Plasmodium vivax-specific antibodies was detected among these monkeys, with 87% of the monkeys testing positive against P. vivax antigens. These findings highlight the possibility of malaria as a zoonosis in the remaining Atlantic Forest and its impact on the epidemiology of the disease. PMID:25099335

  1. Plasmodium simium/Plasmodium vivax infections in southern brown howler monkeys from the Atlantic Forest.

    PubMed

    Costa, Daniela Camargos; da Cunha, Vanessa Pecini; de Assis, Gabriela Maria Pereira; de Souza Junior, Júlio César; Hirano, Zelinda Maria Braga; de Arruda, Mércia Eliane; Kano, Flora Satiko; Carvalho, Luzia Helena; de Brito, Cristiana Ferreira Alves

    2014-08-01

    Blood infection by the simian parasite, Plasmodium simium, was identified in captive (n = 45, 4.4%) and in wild Alouatta clamitans monkeys (n = 20, 35%) from the Atlantic Forest of southern Brazil. A single malaria infection was symptomatic and the monkey presented clinical and haematological alterations. A high frequency of Plasmodium vivax-specific antibodies was detected among these monkeys, with 87% of the monkeys testing positive against P. vivax antigens. These findings highlight the possibility of malaria as a zoonosis in the remaining Atlantic Forest and its impact on the epidemiology of the disease.

  2. Evidence for differences in erythrocyte surface receptors for the malarial parasites, Plasmodium falciparum and Plasmodium knowlesi

    PubMed Central

    1977-01-01

    Human erythrocytes lacking various blood group determinants were susceptible to invasion by Plasmodium falciparum including Duffy- negative erythrocytes that are refractory to invasion by Plasmodium knowlesi. Erythrocytes treated with trypsin or neuraminidase had reduced susceptibility of P. falciparum and normal susceptibility to P. knowlesi. Chymotrypsin treatment (0.1 mg/ml) blocked invasion only by P. knowlesi. The differential effect of enzymatic cleavage of determinats from the erythrocyte surface on invasion by these parasites suggests that P. falciparum and P. knowlesi interact with different determinants on the erythrocyte surface. PMID:327014

  3. Antimalarial Benzoxaboroles Target Plasmodium falciparum Leucyl-tRNA Synthetase

    PubMed Central

    Sonoiki, Ebere; Palencia, Andres; Guo, Denghui; Ahyong, Vida; Dong, Chen; Li, Xianfeng; Hernandez, Vincent S.; Zhang, Yong-Kang; Choi, Wai; Gut, Jiri; Legac, Jennifer; Cooper, Roland; Alley, M. R. K.; Freund, Yvonne R.; DeRisi, Joseph; Cusack, Stephen

    2016-01-01

    There is a need for new antimalarials, ideally with novel mechanisms of action. Benzoxaboroles have been shown to be active against bacteria, fungi, and trypanosomes. Therefore, we investigated the antimalarial activity and mechanism of action of 3-aminomethyl benzoxaboroles against Plasmodium falciparum. Two 3-aminomethyl compounds, AN6426 and AN8432, demonstrated good potency against cultured multidrug-resistant (W2 strain) P. falciparum (50% inhibitory concentration [IC50] of 310 nM and 490 nM, respectively) and efficacy against murine Plasmodium berghei infection when administered orally once daily for 4 days (90% effective dose [ED90], 7.4 and 16.2 mg/kg of body weight, respectively). To characterize mechanisms of action, we selected parasites with decreased drug sensitivity by culturing with stepwise increases in concentration of AN6426. Resistant clones were characterized by whole-genome sequencing. Three generations of resistant parasites had polymorphisms in the predicted editing domain of the gene encoding a P. falciparum leucyl-tRNA synthetase (LeuRS; PF3D7_0622800) and in another gene (PF3D7_1218100), which encodes a protein of unknown function. Solution of the structure of the P. falciparum LeuRS editing domain suggested key roles for mutated residues in LeuRS editing. Short incubations with AN6426 and AN8432, unlike artemisinin, caused dose-dependent inhibition of [14C]leucine incorporation by cultured wild-type, but not resistant, parasites. The growth of resistant, but not wild-type, parasites was impaired in the presence of the unnatural amino acid norvaline, consistent with a loss of LeuRS editing activity in resistant parasites. In summary, the benzoxaboroles AN6426 and AN8432 offer effective antimalarial activity and act, at least in part, against a novel target, the editing domain of P. falciparum LeuRS. PMID:27270277

  4. Plasmodium infection alters Anopheles gambiae detoxification gene expression

    PubMed Central

    2010-01-01

    Background Anopheles gambiae has been shown to change its global gene expression patterns upon Plasmodium infection. While many alterations are directly related to the mosquito's innate immune response, parasite invasion is also expected to generate toxic by-products such as free radicals. The current study aimed at identifying which loci coding for detoxification enzymes are differentially expressed as a function of Plasmodium berghei infection in midgut and fat body tissues. Results Using a custom-made DNA microarray, transcript levels of 254 loci primarily belonging to three major detoxification enzyme families (glutathione S-transferases, cytochrome P450 monooxygenases and esterases) were compared in infected and uninfected mosquitoes both during ookinete invasion and the release of sporozoites into the hemocoel. The greatest changes in gene expression were observed in the midgut in response to ookinete invasion. Interestingly, many detoxification genes including a large number of P450s were down-regulated at this stage. In the fat body, while less dramatic, gene expression alterations were also observed and occurred during the ookinete invasion and during the release of sporozoites into the hemocoel. While most gene expression changes were tissue-related, CYP6M2, a CYP previously associated with insecticide resistance, was over-expressed both in the midgut and fat body during ookinete invasion. Conclusions Most toxicity-related reactions occur in the midgut shortly after the ingestion of an infected blood meal. Strong up-regulation of CYP6M2 in the midgut and the fat body as well as its previous association with insecticide resistance shows its broad role in metabolic detoxification. PMID:20482856

  5. Elution of Re-188 from W-188/Re-188 generators with salts of weak acids permits efficient concentration to low volumes using a new tandem cation/anion exchange system

    SciTech Connect

    Guhlke, S. |; Beets, A.L.; Knapp, F.F. Jr.

    1997-05-01

    Re-188, available from a W-188/Re-188 generator, is an important therapeutic radioisotope for bone pain palliation, cancer therapy and intravascular brachytherapy, etc. Because of the relatively low specific activity of reactor-produced W-188 (ORNL HFIR, 296-370 MBq mCi/mg W-186 for 2 cycles), methods of concentrating the Re-188 bolus (10-12 mL) from clinical scale (18.5-37 BGq W-188) generators (5-6 gm alumina) are thus very important. We demonstrate for the first time a new strategy of generator elution with salts of weak acids and specific perrhenate anion {open_quotes}trapping{close_quotes} with QMA anion columns. Re-188 perrhenate is efficiently eluted (65-75%) from the alumina-based generator with 0.15-0.3 M ammonium acetate. An acetic acid solution of Re-188 perrhenic acid is obtained by subsequent on-line passage of the generator eluant through a DOWEX AG 50Wx8 (200-400 mesh, H{sup +} form) column. Since acetic acid is not ionized (< 0.001%) at this pH (< pK{sub a} = 4.76) the perrhenate anion is then specifically trapped on a QMA {open_quotes}Light{close_quotes} anion extraction column. QMA elution with 0.9% NaCl, provides Re-188 perrhenate solution in <1 mL. Concentration of 10-20 mL of Re-188 solution (> 15 BGq) in <1 mL has been demonstrated using this simple new approach, which is also effective for concentration of Tc-99m from low specific activity Mo-99 (n,y) generators. The cation/anion tandem system is inexpensive and disposable and use can be easily automated. The availability of this very simple, efficient system is important for broad use of rhenium-188.

  6. Permitting and licensing new uranium recovery facilities

    SciTech Connect

    Rehmann, M.; Sweeney, K.; Pugsley, C.

    2007-07-01

    With the nuclear renaissance, the uranium mining industry has undergone a dramatic renaissance, as well. This was evidenced with the 2006 National Mining Association (NMA)/Nuclear Regulatory Commission (NRC) workshop drawing its largest attendance ever, with more than 180 attendees representing both established, as well as many new junior firms. And the meeting focused, not on site closure - but on the growing industry and plans for permitting new uranium recovery facilities. With this, the program provided overviews of the programs for permitting and licensing new uranium mines, from both the State and Federal perspectives. A subsequent one-day licensing workshop presented in February 2007 by NRC at its headquarters in Rockville, Maryland drew a crowd of experienced and first-time license applicants. Modern uranium mining is both safer and more environmentally protective than past practices - due largely to the industry's maturing and continuous efforts to improve. This paper will look at the new generation of uranium mining and recovery facilities that are developing in the US, and focus primarily on US permitting and licensing requirements and trends. Understanding these trends is essential to ensuring a vibrant US uranium recovery industry; assured supplies of this important fuel for our energy and the US economy; and environmental protection. (authors)

  7. Water Quality Trading Toolkit for Permit Writers

    EPA Pesticide Factsheets

    The Water Quality Trading Toolkit for Permit Writers is EPA’s first “how-to” manual on designing and implementing water quality trading programs. It helps NPDES permitting authorities incorporate trading provisions into permits.

  8. Special and Research Permits for Ocean Dumping

    EPA Pesticide Factsheets

    Special permits and research permits under the Marine Protection, Research and Sanctuaries Act may be issued by EPA for ocean dumping. Examples and ocean disposal sites for special and research permits are provided.

  9. Emergencies and Emergency Permits for Ocean Dumping

    EPA Pesticide Factsheets

    Emergency permits under the MPRSA are issued if disposed material poses a threat to human health. Information is provided on emergency permit examples and disposal sites. Emergencies to safeguard life at sea does not require an ocean dumping permit.

  10. 40 CFR 72.62 - Draft permit.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... REGULATION Federal Acid Rain Permit Issuance Procedures § 72.62 Draft permit. (a) After the Administrator receives a complete Acid Rain permit application and any supplemental information, the Administrator will...

  11. 40 CFR 72.62 - Draft permit.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... REGULATION Federal Acid Rain Permit Issuance Procedures § 72.62 Draft permit. (a) After the Administrator receives a complete Acid Rain permit application and any supplemental information, the Administrator will...

  12. 40 CFR 72.62 - Draft permit.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... REGULATION Federal Acid Rain Permit Issuance Procedures § 72.62 Draft permit. (a) After the Administrator receives a complete Acid Rain permit application and any supplemental information, the Administrator will...

  13. 40 CFR 72.62 - Draft permit.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... REGULATION Federal Acid Rain Permit Issuance Procedures § 72.62 Draft permit. (a) After the Administrator receives a complete Acid Rain permit application and any supplemental information, the Administrator will...

  14. 40 CFR 72.62 - Draft permit.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... REGULATION Federal Acid Rain Permit Issuance Procedures § 72.62 Draft permit. (a) After the Administrator receives a complete Acid Rain permit application and any supplemental information, the Administrator will...

  15. 36 CFR 9.3 - Access permits.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... MANAGEMENT Mining and Mining Claims § 9.3 Access permits. (a) All special use or other permits dealing with... permits in accordance with these regulations, unless access to a mining claim is by pack animal or...

  16. 30 CFR 778.17 - Permit term.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... MINING AND RECLAMATION OPERATIONS PERMITS AND COAL EXPLORATION SYSTEMS UNDER REGULATORY PROGRAMS PERMIT APPLICATIONS-MINIMUM REQUIREMENTS FOR LEGAL, FINANCIAL, COMPLIANCE, AND RELATED INFORMATION § 778.17 Permit...

  17. 78 FR 36822 - Special Permit Applications

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-19

    ... Pipeline and Hazardous Materials Safety Administration Special Permit Applications AGENCY: Pipeline And Hazardous Materials Safety Administration (PHMSA), DOT. ACTION: Notice of actions on Special Permit..., special permits from the Department of Transportation's Hazardous Material Regulations (49 CFR Part...

  18. First Full Draft Genome Sequence of Plasmodium brasilianum

    PubMed Central

    Ravishankar, Shashidhar; Nayak, Vishal; Patel, Dhruviben S.; Olsen, Christian; Sheth, Mili; Batra, Dhwani; Loparev, Vladimir; Vannberg, Fredrik O.; Udhayakumar, Venkatachalam; Barnwell, John W.

    2017-01-01

    ABSTRACT Plasmodium malariae is a protozoan parasite that can cause human malaria. The simian parasite Plasmodium brasilianum infects New World monkeys from Latin America and is morphologically indistinguishable from P. malariae. Here, we report the first full draft genome sequence for P. brasilianum. PMID:28183758

  19. 40 CFR 52.872 - Operating permits.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Kansas § 52.872 Operating permits. Emission limitations and related provisions which are established in Kansas operating permits as Federally enforceable...

  20. 40 CFR 52.1888 - Operating permits.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) Ohio § 52.1888 Operating permits. Emission limitations and related provisions which are established in Ohio operating permits as federally...

  1. 40 CFR 52.1888 - Operating permits.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) Ohio § 52.1888 Operating permits. Emission limitations and related provisions which are established in Ohio operating permits as federally...

  2. Construction of living cellular automata using the Physarum plasmodium

    NASA Astrophysics Data System (ADS)

    Shirakawa, Tomohiro; Sato, Hiroshi; Ishiguro, Shinji

    2015-04-01

    The plasmodium of Physarum polycephalum is a unicellular and multinuclear giant amoeba that has an amorphous cell body. To clearly observe how the plasmodium makes decisions in its motile and exploratory behaviours, we developed a new experimental system to pseudo-discretize the motility of the organism. In our experimental space that has agar surfaces arranged in a two-dimensional lattice, the continuous and omnidirectional movement of the plasmodium was limited to the stepwise one, and the direction of the locomotion was also limited to four neighbours. In such an experimental system, a cellular automata-like system was constructed using the living cell. We further analysed the exploratory behaviours of the plasmodium by duplicating the experimental results in the simulation models of cellular automata. As a result, it was revealed that the behaviours of the plasmodium are not reproduced by only local state transition rules; and for the reproduction, a kind of historical rule setting is needed.

  3. Mitosis in the Human Malaria Parasite Plasmodium falciparum ▿

    PubMed Central

    Gerald, Noel; Mahajan, Babita; Kumar, Sanjai

    2011-01-01

    Malaria is caused by intraerythrocytic protozoan parasites belonging to Plasmodium spp. (phylum Apicomplexa) that produce significant morbidity and mortality, mostly in developing countries. Plasmodium parasites have a complex life cycle that includes multiple stages in anopheline mosquito vectors and vertebrate hosts. During the life cycle, the parasites undergo several cycles of extreme population growth within a brief span, and this is critical for their continued transmission and a contributing factor for their pathogenesis in the host. As with other eukaryotes, successful mitosis is an essential requirement for Plasmodium reproduction; however, some aspects of Plasmodium mitosis are quite distinct and not fully understood. In this review, we will discuss the current understanding of the architecture and key events of mitosis in Plasmodium falciparum and related parasites and compare them with the traditional mitotic events described for other eukaryotes. PMID:21317311

  4. Response to various periods of mechanical stimuli in Physarum plasmodium

    NASA Astrophysics Data System (ADS)

    Umedachi, Takuya; Ito, Kentaro; Kobayashi, Ryo; Ishiguro, Akio; Nakagaki, Toshiyuki

    2017-06-01

    Response to mechanical stimuli is a fundamental and critical ability for living cells to survive in hazardous conditions or to form adaptive and functional structures against force(s) from the environment. Although this ability has been extensively studied by molecular biology strategies, it is also important to investigate the ability from the viewpoint of biological rhythm phenomena so as to reveal the mechanisms that underlie these phenomena. Here, we use the plasmodium of the true slime mold Physarum polycephalum as the experimental system for investigating this ability. The plasmodium was repetitively stretched for various periods during which its locomotion speed was observed. Since the plasmodium has inherent oscillation cycles of protoplasmic streaming and thickness variation, how the plasmodium responds to various periods of external stretching stimuli can shed light on the other biological rhythm phenomena. The experimental results show that the plasmodium exhibits response to periodic mechanical stimulation and changes its locomotion speed depending on the period of the stretching stimuli.

  5. 40 CFR 96.20 - General NOX Budget trading program permit requirements.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ..., those provisions addressing operating permit applications, operating permit application shield, operating permit duration, operating permit shield, operating permit issuance, operating permit revision and... permit applications, permit application shield, permit duration, permit shield, permit issuance,...

  6. 40 CFR 96.20 - General NOX Budget trading program permit requirements.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ..., those provisions addressing operating permit applications, operating permit application shield, operating permit duration, operating permit shield, operating permit issuance, operating permit revision and... permit applications, permit application shield, permit duration, permit shield, permit issuance,...

  7. 43 CFR 3516.11 - What kinds of permits or leases allow use permits?

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ...) BUREAU OF LAND MANAGEMENT, DEPARTMENT OF THE INTERIOR MINERALS MANAGEMENT (3000) LEASING OF SOLID... permits? Use permits are issued only in support of phosphate and sodium permits and leases. For phosphate permits and leases, BLM may issue you a use permit to use up to 80 acres. For sodium leases, use permits...

  8. EPA's Permit for MWRA Outfall | NPDES Permits in New ...

    EPA Pesticide Factsheets

    2017-04-10

    The Massachusetts Water Resources Authority's (MWRA) Permit from the federal Environmental Protection Agency (EPA) and the Massachusetts Department of Environmental Protection (DEP) for discharges into Massachusetts Bay, as well as for fourteen combined sewer overflows which discharge into boston harbor and the charles, mystic, alewife rivers during wet weather.

  9. Draft NH Small MS4 General Permit | Stormwater Permits ...

    EPA Pesticide Factsheets

    2017-04-10

    The Notice of Availability of the draft NPDES General Permit for Discharges From Small Municipal Separate Storm Sewer Systems located in the State of New Hampshire (NHR040000) was published in the Federal Register on December 23, 2008 (See 73 FR 78786).

  10. Mirant Canal Station Final NPDES Permit | NPDES Permits in ...

    EPA Pesticide Factsheets

    2017-04-10

    EPA and the Massachusetts Department of Environmental Protection (MassDEP) have developed a Final National Pollutant Discharge Elimination System (NPDES) permit for the Mirant Canal Station (MCS, the Station) power plant in Sandwich, Massachusetts to meet the requirements of the Clean Water Act.

  11. Mirant Canal Station Final NPDES Permit | NPDES Permits in ...

    EPA Pesticide Factsheets

    2017-04-10

    EPA and the Massachusetts Department of Environmental Protection (MassDEP) have developed a Final National Pollutant Discharge Elimination System (NPDES) permit for the Mirant Canal Station (MCS, the Station) power plant in Sandwich, Massachusetts to meet the requirements of the Clean Water Act.

  12. In silico comparative genome analysis of malaria parasite Plasmodium falciparum and Plasmodium vivax chromosome 4.

    PubMed

    Taherian Fard, Atefeh; Salman, Amna; Kazemi, Bahram; Bokhari, Habib

    2009-06-01

    Malarial parasite has long been a subject of research for a large community of scientists and has yet to be conquered. One of the main obstacles to effectively control this disease is rapidly evolving genetic structure of Plasmodium parasite itself. In this study, we focused on chromosome 4 of the Plasmodium falciparum and Plasmodium vivax species and carried out comparative studies of genes that are responsible for antigenic variation in respective species. Comparative analysis of genes responsible for antigenic variation (var and vir genes in P. falciparum and P. vivax, respectively) showed significant difference in their respective nucleotide sequence lengths as well as amino acid composition. The possible association of exon's length on pathogenecity of respective Plasmodium species was also investigated, and analysis of gene structure showed that on the whole, exon lengths in P. falciparum are larger compared to P. vivax. Analysis of tandem repeats across the genome has shown that the size of repetitive sequences has a direct effect on chromosomes length, which can also be a potential reason for P. falciparum's greater variability and hence pathogenecity than P. vivax.

  13. Simple Molecular Methods for Early Detection of Chloroquine Drug Resistance in Plasmodium vivax and Plasmodium falciparum.

    PubMed

    Singh, Gurjeet; Singh, Raksha; Urhehar, Anant Dattatraya

    2016-07-01

    Malaria is a human disease of which causes high morbidity and mortality. In Plasmodium falciparum malaria, the resistance to antimalarial drugs, especially chloroquine (CQ) is one of the paramount factors contributing to the global increase in morbidity and mortality, due to malaria. Hence, there is a need for detection of chloroquine drug resistance genes i.e., pfcrt-o (Plasmodium falciparum chloroquine resistance transporter-o) and pfmdr-1 (Plasmodium falciparum multidrug resistance-1) of P. falciparum and pvcrt-o (Plasmodium vivax chloroquine resistance transporter-o) and pvmdr-1 (Plasmodium vivax multidrug resistance-1) of P. vivax by using molecular methods to prevent mortality in malarial cases. To standardize chloroquine drug sensitivity testing by molecular method so as to provide reports of chloroquine within 6-8 hours to physicians for better treatment. This study was conducted over a period of one year from January to December 2014. A Total of 300 blood samples were collected from malaria suspected patient attending MGM Hospital, Kamothe, Navi Mumbai, India. Out of 300 blood samples, 44 were malaria positive as assessed by Thick and Thin blood smear stained, by Leishman's method and examination with light microscope. Chloroquine drug sensitivity testing was performed using WHO III plate method (micro test). Nested PCR was done for detection of pfcrt-o and pfmdr-1 for P. falciparum and pvcrt-o, pvmdr-1 genes for P. vivax. Total 44 samples were included in this study, out of which 22 samples confirmed for Plasmodium falciparum and 22 samples confirmed for Plasmodium vivax. Out of 22 P. falciparum 15 (68.18%) samples were chloroquine resistant. P. vivax showed chloroquine resistance to 5 samples (22.73%) by method similar to WHO III plate method (micro test) and nested PCR. Drug resistance testing by molecular methods is useful for early detection of antimalarial drug resistance. pfmdr-1 along with pfcrt-o can be used as biomarker for chloroquine drug

  14. M17 leucine aminopeptidase of the human malaria parasite Plasmodium vivax.

    PubMed

    Lee, Jung-Yub; Song, Su-Min; Seok, Ji-Woong; Jha, Bijay Kumar; Han, Eun-Taek; Song, Hyun-Ouk; Yu, Hak-Sun; Hong, Yeonchul; Kong, Hyun-Hee; Chung, Dong-Il

    2010-03-01

    Amino acids derived from hemoglobin are essential to protein synthesis required for growth and development of the Plasmodium vivax malaria parasite. M17 leucine aminopeptidase (LAP) is a cytosolic metallo-exopeptidase that catalyzes the removal of amino acids from the peptide generated in the process of hemoglobin degradation. Inhibitors of the enzyme have shown promise as drugs against Plasmodium infections, implicating aminopeptidases as a novel potential anti-malarial chemotherapy target. In this study, we isolated a cDNA encoding a 68kDa P. vivax LAP (PvLAP). Deduced amino acid sequence of PvLAP exhibited significant sequence homology with LAP from Plasmodium falciparum. Biochemical analysis of the recombinant PvLAP protein produced in Escherichia coli demonstrated preferential substrate specificity for the fluorogenic peptide Leu-7-amido-4-methylcoumarin hydroxide and inhibition by EDTA, 1,10-phenanthroline, and bestatin, which are conserved characteristics of the M17 family of LAP. PvLAP was optimally active at slightly alkaline pH and its activity was dependent on divalent metal ions. Based on the biochemical properties and immunofluorescence localization, PvLAP is concluded to represent a LAP in P. vivax. The enzyme is most likely responsible for the catabolism of host hemoglobin and, hence, represents a potential target of both P. falciparum and P. vivax chemotherapy.

  15. The Glutathione Biosynthetic Pathway of Plasmodium Is Essential for Mosquito Transmission

    PubMed Central

    Vega-Rodríguez, Joel; Janse, Chris J.; Pastrana-Mena, Rebecca; Waters, Andrew P.; Coppens, Isabelle; Rodríguez-Orengo, José F.; Jacobs-Lorena, Marcelo; Serrano, Adelfa E.

    2009-01-01

    Infection of red blood cells (RBC) subjects the malaria parasite to oxidative stress. Therefore, efficient antioxidant and redox systems are required to prevent damage by reactive oxygen species. Plasmodium spp. have thioredoxin and glutathione (GSH) systems that are thought to play a major role as antioxidants during blood stage infection. In this report, we analyzed a critical component of the GSH biosynthesis pathway using reverse genetics. Plasmodium berghei parasites lacking expression of gamma-glutamylcysteine synthetase (γ-GCS), the rate limiting enzyme in de novo synthesis of GSH, were generated through targeted gene disruption thus demonstrating, quite unexpectedly, that γ-GCS is not essential for blood stage development. Despite a significant reduction in GSH levels, blood stage forms of pbggcs− parasites showed only a defect in growth as compared to wild type. In contrast, a dramatic effect on development of the parasites in the mosquito was observed. Infection of mosquitoes with pbggcs− parasites resulted in reduced numbers of stunted oocysts that did not produce sporozoites. These results have important implications for the design of drugs aiming at interfering with the GSH redox-system in blood stages and demonstrate that de novo synthesis of GSH is pivotal for development of Plasmodium in the mosquito. PMID:19229315

  16. DNA repair mechanisms and their biological roles in the malaria parasite Plasmodium falciparum.

    PubMed

    Lee, Andrew H; Symington, Lorraine S; Fidock, David A

    2014-09-01

    Research into the complex genetic underpinnings of the malaria parasite Plasmodium falciparum is entering a new era with the arrival of site-specific genome engineering. Previously restricted only to model systems but now expanded to most laboratory organisms, and even to humans for experimental gene therapy studies, this technology allows researchers to rapidly generate previously unattainable genetic modifications. This technological advance is dependent on DNA double-strand break repair (DSBR), specifically homologous recombination in the case of Plasmodium. Our understanding of DSBR in malaria parasites, however, is based largely on assumptions and knowledge taken from other model systems, which do not always hold true in Plasmodium. Here we describe the causes of double-strand breaks, the mechanisms of DSBR, and the differences between model systems and P. falciparum. These mechanisms drive basic parasite functions, such as meiosis, antigen diversification, and copy number variation, and allow the parasite to continually evolve in the contexts of host immune pressure and drug selection. Finally, we discuss the new technologies that leverage DSBR mechanisms to accelerate genetic investigations into this global infectious pathogen.

  17. Plasmepsin 4-Deficient Plasmodium berghei Are Virulence Attenuated and Induce Protective Immunity against Experimental Malaria

    PubMed Central

    Spaccapelo, Roberta; Janse, Chris J.; Caterbi, Sara; Franke-Fayard, Blandine; Bonilla, J. Alfredo; Syphard, Luke M.; Di Cristina, Manlio; Dottorini, Tania; Savarino, Andrea; Cassone, Antonio; Bistoni, Francesco; Waters, Andrew P.; Dame, John B.; Crisanti, Andrea

    2010-01-01

    Plasmodium parasites lacking plasmepsin 4 (PM4), an aspartic protease that functions in the lysosomal compartment and contributes to hemoglobin digestion, have only a modest decrease in the asexual blood-stage growth rate; however, PM4 deficiency in the rodent malaria parasite Plasmodium berghei results in significantly less virulence than that for the parental parasite. P. berghei Δpm4 parasites failed to induce experimental cerebral malaria (ECM) in ECM-susceptible mice, and ECM-resistant mice were able to clear infections. Furthermore, after a single infection, all convalescent mice were protected against subsequent parasite challenge for at least 1 year. Real-time in vivo parasite imaging and splenectomy experiments demonstrated that protective immunity acted through antibody-mediated parasite clearance in the spleen. This work demonstrates, for the first time, that a single Plasmodium gene disruption can generate virulence-attenuated parasites that do not induce cerebral complications and, moreover, are able to stimulate strong protective immunity against subsequent challenge with wild-type parasites. Parasite blood-stage attenuation should help identify protective immune responses against malaria, unravel parasite-derived factors involved in malarial pathologies, such as cerebral malaria, and potentially pave the way for blood-stage whole organism vaccines. PMID:20019192

  18. The glutathione biosynthetic pathway of Plasmodium is essential for mosquito transmission.

    PubMed

    Vega-Rodríguez, Joel; Franke-Fayard, Blandine; Dinglasan, Rhoel R; Janse, Chris J; Pastrana-Mena, Rebecca; Waters, Andrew P; Coppens, Isabelle; Rodríguez-Orengo, José F; Srinivasan, Prakash; Jacobs-Lorena, Marcelo; Serrano, Adelfa E

    2009-02-01

    Infection of red blood cells (RBC) subjects the malaria parasite to oxidative stress. Therefore, efficient antioxidant and redox systems are required to prevent damage by reactive oxygen species. Plasmodium spp. have thioredoxin and glutathione (GSH) systems that are thought to play a major role as antioxidants during blood stage infection. In this report, we analyzed a critical component of the GSH biosynthesis pathway using reverse genetics. Plasmodium berghei parasites lacking expression of gamma-glutamylcysteine synthetase (gamma-GCS), the rate limiting enzyme in de novo synthesis of GSH, were generated through targeted gene disruption thus demonstrating, quite unexpectedly, that gamma-GCS is not essential for blood stage development. Despite a significant reduction in GSH levels, blood stage forms of pbggcs(-) parasites showed only a defect in growth as compared to wild type. In contrast, a dramatic effect on development of the parasites in the mosquito was observed. Infection of mosquitoes with pbggcs(-) parasites resulted in reduced numbers of stunted oocysts that did not produce sporozoites. These results have important implications for the design of drugs aiming at interfering with the GSH redox-system in blood stages and demonstrate that de novo synthesis of GSH is pivotal for development of Plasmodium in the mosquito.

  19. DNA Repair Mechanisms and Their Biological Roles in the Malaria Parasite Plasmodium falciparum

    PubMed Central

    Lee, Andrew H.; Symington, Lorraine S.

    2014-01-01

    SUMMARY Research into the complex genetic underpinnings of the malaria parasite Plasmodium falciparum is entering a new era with the arrival of site-specific genome engineering. Previously restricted only to model systems but now expanded to most laboratory organisms, and even to humans for experimental gene therapy studies, this technology allows researchers to rapidly generate previously unattainable genetic modifications. This technological advance is dependent on DNA double-strand break repair (DSBR), specifically homologous recombination in the case of Plasmodium. Our understanding of DSBR in malaria parasites, however, is based largely on assumptions and knowledge taken from other model systems, which do not always hold true in Plasmodium. Here we describe the causes of double-strand breaks, the mechanisms of DSBR, and the differences between model systems and P. falciparum. These mechanisms drive basic parasite functions, such as meiosis, antigen diversification, and copy number variation, and allow the parasite to continually evolve in the contexts of host immune pressure and drug selection. Finally, we discuss the new technologies that leverage DSBR mechanisms to accelerate genetic investigations into this global infectious pathogen. PMID:25184562

  20. [Erythrocyte polymorphism in Mali: epidemiology and resistance mechanisms against severe Plasmodium falciparum malaria].

    PubMed

    Doumbo, Ogobara

    2007-01-01

    Homo sapiens and Plasmodium falciparum have co-evolved since the beginning of agriculture, 10,000 to 20,000 years ago. By domesticating plants and animals, humans linked their destiny to one of the main vectors of malaria, Anopheles gambiae sl complex. The biological interaction between these three species led to exchanges of genes and biochemical processes with significant mutual influence. Humans acquired mutations with selective protective advantages against serious and fatal forms of this hemosporidiosis. This is the case of hemoglobin S, hemoglobin C, hemoglobin E, thalassemias, ovalocytosis and G6PD deficiency, among others. Many epidemiological studies published since 1949 have shown a geographic link between malaria and certain erythrocyte polymorphisms. The link with hemoglobin C was discovered only recently, in 2000, initially in Mali in the Dogon population, then in Burkina Faso. Epidemiological and molecular and cellular biology studies done in Mali and elsewhere showed that the C and S alleles, and G6PD deficiency [A-], conferred significant protection against lethal forms of Plasmodium falciparum malaria. Molecular genetic studies, based on functional genomics, transcriptomics and proteomics, provided possible explanations. Advances in molecular biology and a better understanding of the immune mechanisms underlying this protection will hopefully lead to the development of effective second- and third-generation malaria vaccines. Epidemiological and fundamental research efforts have identified some of the mechanisms by which these erythrocyte polymorphisms protect against the most lethal hematozoan parasite, Plasmodium falciparum.

  1. 32 CFR 935.152 - Activities for which permit is required.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... permitted, without obtaining a permit. (e) Keeping or maintaining an indigenous animal. (f) Importing, storing, generating, or disposing of hazardous materials. (g) Importing of solid wastes and importing, storing, generating, treating, or disposing of hazardous wastes, as they are defined in the Solid...

  2. 32 CFR 935.152 - Activities for which permit is required.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... permitted, without obtaining a permit. (e) Keeping or maintaining an indigenous animal. (f) Importing, storing, generating, or disposing of hazardous materials. (g) Importing of solid wastes and importing, storing, generating, treating, or disposing of hazardous wastes, as they are defined in the Solid...

  3. Permit-Required Confined Spaces

    DTIC Science & Technology

    1998-01-01

    Permit-Required Confined Spaces U.S. Department of Labor Occupational Safety and Health Administration OSHA 3138 1998 (Revised) Report Documentation...Department of Labor Occupational Safety & Health Administration 200 Constitution Avenue Washington, DC 20210 Performing Organization Report Number OSHA 3138...determine compliance responsibili- ties, which are set forth in OSHA standards themselves and the Occupational Safety and Health Act. Moreover, because

  4. 2016 Title V Operating Permits

    EPA Pesticide Factsheets

    This table lists proposed Title V permits submitted received to by EPA in 2016 and undergoing EPA’s 45 day review, including the start and expiration dates for EPA's 45 day review period. It also shows the start and expiration dates for the public's 60 day

  5. Anopheles stephensi Heme Peroxidase HPX15 Suppresses Midgut Immunity to Support Plasmodium Development

    PubMed Central

    Kajla, Mithilesh; Kakani, Parik; Choudhury, Tania Pal; Kumar, Vikas; Gupta, Kuldeep; Dhawan, Rini; Gupta, Lalita; Kumar, Sanjeev

    2017-01-01

    The heme peroxidase HPX15 is an evolutionary conserved anopheline lineage-specific gene. Previously, we found that this gene is present in the genome of 19 worldwide distributed different species of Anopheles mosquito and its orthologs are absent in other mosquitoes, insects, or human. In addition, 65–99% amino acid identity among these 19 orthologs permitted us to hypothesize that the functional aspects of this gene might be also conserved in different anophelines. In this study, we found that Anopheles stephensi AsHPX15 gene is mainly expressed in the midgut and highly induced after uninfected or Plasmodium berghei-infected blood feeding. RNA interference-mediated silencing of midgut AsHPX15 gene drastically reduced the number of developing P. berghei oocysts. An antiplasmodial gene nitric oxide synthase was induced 13-fold in silenced midguts when compared to the unsilenced controls. Interestingly, the induction of antiplasmodial immunity in AsHPX15-silenced midguts is in absolute agreement with Anopheles gambiae. In A. gambiae, AgHPX15 catalyzes the formation of a dityrosine network at luminal side of the midgut that suppresses the activation of mosquito immunity against the bolus bacteria. Thus, a low-immunity zone created by this mechanism indirectly supports Plasmodium development inside the midgut lumen. These indistinguishable functional behaviors and conserved homology indicates that HPX15 might be a potent target to manipulate the antiplasmodial immunity of the anopheline midgut, and it will open new frontiers in the field of malaria control. PMID:28352267

  6. Mining the Plasmodium genome database to define organellar function: what does the apicoplast do?

    PubMed Central

    Roos, David S; Crawford, Michael J; Donald, Robert G K; Fraunholz, Martin; Harb, Omar S; He, Cynthia Y; Kissinger, Jessica C; Shaw, Michael K; Striepen, Boris

    2002-01-01

    Apicomplexan species constitute a diverse group of parasitic protozoa, which are responsible for a wide range of diseases in many organisms. Despite differences in the diseases they cause, these parasites share an underlying biology, from the genetic controls used to differentiate through the complex parasite life cycle, to the basic biochemical pathways employed for intracellular survival, to the distinctive cell biology necessary for host cell attachment and invasion. Different parasites lend themselves to the study of different aspects of parasite biology: Eimeria for biochemical studies, Toxoplasma for molecular genetic and cell biological investigation, etc. The Plasmodium falciparum Genome Project contributes the first large-scale genomic sequence for an apicomplexan parasite. The Plasmodium Genome Database (http://PlasmoDB.org) has been designed to permit individual investigators to ask their own questions, even prior to formal release of the reference P. falciparum genome sequence. As a case in point, PlasmoDB has been exploited to identify metabolic pathways associated with the apicomplexan plastid, or 'apicoplast' - an essential organelle derived by secondary endosymbiosis of an alga, and retention of the algal plastid. PMID:11839180

  7. 50 CFR 19.31 - State permits.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... PLANTS (CONTINUED) AIRBORNE HUNTING State Permits and Annual Report Requirements § 19.31 State permits. (a) Except as provided in § 19.3, States may issue permits to persons to engage in airborne hunting..., domestic animals, human life or crops. States may not issue permits for the purpose of sport hunting. (b...

  8. Massachusetts Small MS4 General Permit | Stormwater ...

    EPA Pesticide Factsheets

    2017-08-28

    The 2016 Massachusetts Small MS4 General Permit was signed April 4, 2016 and will become effective July 1, 2017. The final permit reflects modifications to the 2014 draft small MS4 general permit released for comment on September 30, 2014 and replaces the 2003 small MS4 general permit for MS4 operators within the Commonwealth of Massachusetts.

  9. 40 CFR 144.33 - Area permits.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) UNDERGROUND INJECTION CONTROL PROGRAM Authorization by Permit § 144.33 Area permits. (a) The Director may issue a permit on an area basis, rather than for each well individually, provided that the permit is for...

  10. 40 CFR 144.33 - Area permits.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) UNDERGROUND INJECTION CONTROL PROGRAM Authorization by Permit § 144.33 Area permits. (a) The Director may issue a permit on an area basis, rather than for each well individually, provided that the permit is for...

  11. 40 CFR 144.33 - Area permits.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) UNDERGROUND INJECTION CONTROL PROGRAM Authorization by Permit § 144.33 Area permits. (a) The Director may issue a permit on an area basis, rather than for each well individually, provided that the permit is for...

  12. 40 CFR 144.33 - Area permits.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) UNDERGROUND INJECTION CONTROL PROGRAM Authorization by Permit § 144.33 Area permits. (a) The Director may issue a permit on an area basis, rather than for each well individually, provided that the permit is for...

  13. 40 CFR 144.33 - Area permits.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) UNDERGROUND INJECTION CONTROL PROGRAM Authorization by Permit § 144.33 Area permits. (a) The Director may issue a permit on an area basis, rather than for each well individually, provided that the permit is for...

  14. 50 CFR 300.112 - Harvesting permits.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... issued a harvesting permit do not require a separate permit, but are covered by the permit issued the... against the launching vessel. (2) Permits issued under this section do not authorize vessels or persons... mammals. No marine mammals may be taken in the course of commercial fishing operations unless the...

  15. 50 CFR 300.112 - Harvesting permits.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... issued a harvesting permit do not require a separate permit, but are covered by the permit issued the... against the launching vessel. (2) Permits issued under this section do not authorize vessels or persons... mammals. No marine mammals may be taken in the course of commercial fishing operations unless the...

  16. North Carolina Proposed Title V Permits

    EPA Pesticide Factsheets

    The following permits have been submitted to EPA Region 4 as Proposed Title V permits. While EPA has the right to a 45-day review period for all Proposed Title V permits, EPA Region 4 targets only a subset of these permits for comprehensive review.

  17. 50 CFR 665.203 - Permits.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 50 Wildlife and Fisheries 11 2011-10-01 2011-10-01 false Permits. 665.203 Section 665.203 Wildlife... single vessel for use with a Ho'omalu Zone permit and a Mau Zone permit at the same time. Mau Zone... permit holder's application. The Ho'omalu Zone and the Mau Zone limited entry systems described in...

  18. PSD Permit Applications In Region 4

    EPA Pesticide Factsheets

    The following permits have been submitted to EPA Region 4 as Proposed Title V permits. While EPA has the right to a 45-day review period for all Proposed Title V permits, EPA Region 4 targets only a subset of these permits for comprehensive review.

  19. 19 CFR 142.24 - Special permit.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... (CONTINUED) ENTRY PROCESS Special Permit for Immediate Delivery § 142.24 Special permit. (a) Conditions for issuance. At the discretion of the port director, a special permit for immediate delivery may be issued on... of a shipment of merchandise under a special permit for immediate delivery, the importer shall note a...

  20. 10 CFR 50.23 - Construction permits.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Construction permits. 50.23 Section 50.23 Energy NUCLEAR... Description of Licenses § 50.23 Construction permits. A construction permit for the construction of a... part 52 of this chapter, the construction permit and operating license are deemed to be combined in a...

  1. South Carolina Proposed Title V Permits

    EPA Pesticide Factsheets

    The following permits have been submitted to EPA Region 4 as Proposed Title V permits. While EPA has the right to a 45-day review period for all Proposed Title V permits, EPA Region 4 targets only a subset of these permits for comprehensive review.

  2. 50 CFR 13.27 - Permit suspension.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 50 Wildlife and Fisheries 1 2010-10-01 2010-10-01 false Permit suspension. 13.27 Section 13.27... GENERAL PERMIT PROCEDURES Permit Administration § 13.27 Permit suspension. (a) Criteria for suspension... Government. Such suspension shall remain in effect until the issuing officer determines that the...

  3. 50 CFR 622.90 - Permits.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ..., DEPARTMENT OF COMMERCE FISHERIES OF THE CARIBBEAN, GULF OF MEXICO, AND SOUTH ATLANTIC Red Drum Fishery of the Gulf of Mexico § 622.90 Permits. (a) Dealer permits and conditions—(1) Permits. For a dealer to first receive Gulf red drum harvested in or from the EEZ, a Gulf and South Atlantic dealer permit must be issued...

  4. 10 CFR 50.23 - Construction permits.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 1 2014-01-01 2014-01-01 false Construction permits. 50.23 Section 50.23 Energy NUCLEAR... Description of Licenses § 50.23 Construction permits. A construction permit for the construction of a... part 52 of this chapter, the construction permit and operating license are deemed to be combined in a...

  5. 10 CFR 50.23 - Construction permits.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 1 2013-01-01 2013-01-01 false Construction permits. 50.23 Section 50.23 Energy NUCLEAR... Description of Licenses § 50.23 Construction permits. A construction permit for the construction of a... part 52 of this chapter, the construction permit and operating license are deemed to be combined in a...

  6. 10 CFR 50.23 - Construction permits.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 1 2012-01-01 2012-01-01 false Construction permits. 50.23 Section 50.23 Energy NUCLEAR... Description of Licenses § 50.23 Construction permits. A construction permit for the construction of a... part 52 of this chapter, the construction permit and operating license are deemed to be combined in a...

  7. Massport Logan International Airport NPDES Permit | NPDES ...

    EPA Pesticide Factsheets

    2017-04-10

    Massport was issued a permit for discharging storm water to Boston Harbor on March 1, 1978. The permit expired five years later. However, EPA administratively continued the permit as allowed by regulations. EPA issued a draft permit and fact sheet (which provides EPA's technical basis for establishing effluent limits and monitoring) for public comment on July 25, 2006.

  8. 50 CFR 665.203 - Permits.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... single vessel for use with a Ho'omalu Zone permit and a Mau Zone permit at the same time. Mau Zone... permit holder's application. The Ho'omalu Zone and the Mau Zone limited entry systems described in this... as described in § 665.13. (2) Ho'omalu Zone limited access permit. In addition to an application...

  9. 50 CFR 665.203 - Permits.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... single vessel for use with a Ho'omalu Zone permit and a Mau Zone permit at the same time. Mau Zone... permit holder's application. The Ho'omalu Zone and the Mau Zone limited entry systems described in this... as described in § 665.13. (2) Ho'omalu Zone limited access permit. In addition to an application...

  10. 50 CFR 665.203 - Permits.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... single vessel for use with a Ho'omalu Zone permit and a Mau Zone permit at the same time. Mau Zone... permit holder's application. The Ho'omalu Zone and the Mau Zone limited entry systems described in this... as described in § 665.13. (2) Ho'omalu Zone limited access permit. In addition to an application...

  11. 50 CFR 19.31 - State permits.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ..., domestic animals, human life or crops. States may not issue permits for the purpose of sport hunting. (b... PLANTS (CONTINUED) AIRBORNE HUNTING State Permits and Annual Report Requirements § 19.31 State permits. (a) Except as provided in § 19.3, States may issue permits to persons to engage in airborne...

  12. 50 CFR 19.31 - State permits.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ..., domestic animals, human life or crops. States may not issue permits for the purpose of sport hunting. (b... PLANTS (CONTINUED) AIRBORNE HUNTING State Permits and Annual Report Requirements § 19.31 State permits. (a) Except as provided in § 19.3, States may issue permits to persons to engage in airborne...

  13. 27 CFR 447.41 - Permit requirement.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 3 2011-04-01 2010-04-01 true Permit requirement. 447.41... WAR Permits § 447.41 Permit requirement. (a) Articles on the U.S. Munitions Import List will not be imported into the United States except pursuant to a permit under this subpart. For articles subject to...

  14. Targeting the gyrase of Plasmodium falciparum with topoisomerase poisons.

    PubMed

    Tang Girdwood, Sonya C; Nenortas, Elizabeth; Shapiro, Theresa A

    2015-06-15

    Drug-resistant malaria poses a major public health problem throughout the world and the need for new antimalarial drugs is growing. The apicoplast, a chloroplast-like organelle essential for malaria parasite survival and with no counterpart in humans, offers an attractive target for selectively toxic new therapies. The apicoplast genome (plDNA) is a 35 kb circular DNA that is served by gyrase, a prokaryotic type II topoisomerase. Gyrase is poisoned by fluoroquinolone antibacterials that stabilize a catalytically inert ternary complex of enzyme, its plDNA substrate, and inhibitor. We used fluoroquinolones to study the gyrase and plDNA of Plasmodium falciparum. New methods for isolating and separating plDNA reveal four topologically different forms and permit a quantitative exam of perturbations that result from gyrase poisoning. In keeping with its role in DNA replication, gyrase is most abundant in late stages of the parasite lifecycle, but several lines of evidence indicate that even in these cells the enzyme is present in relatively low abundance: about 1 enzyme for every two plDNAs or a ratio of 1 gyrase: 70 kb DNA. For a spectrum of quinolones, correlation was generally good between antimalarial activity and gyrase poisoning, the putative molecular mechanism of drug action. However, in P. falciparum there is evidence for off-target toxicity, particularly for ciprofloxacin. These studies highlight the utility of the new methods and of fluoroquinolones as a tool for studying the in situ workings of gyrase and its plDNA substrate. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Surface-expressed enolases of Plasmodium and other pathogens

    PubMed Central

    Ghosh, Anil Kumar; Jacobs-Lorena, Marcelo

    2014-01-01

    Enolase is the eighth enzyme in the glycolytic pathway, a reaction that generates ATP from phosphoenol pyruvate in cytosolic compartments. Enolase is essential, especially for organisms devoid of the Krebs cycle that depend solely on glycolysis for energy. Interestingly, enolase appears to serve a separate function in some organisms, in that it is also exported to the cell surface via a poorly understood mechanism. In these organisms, surface enolase assists in the invasion of their host cells by binding plasminogen, an abundant plasma protease precursor. Binding is mediated by the interaction between a lysine motif of enolase with Kringle domains of plasminogen. The bound plasminogen is then cleaved by specific proteases to generate active plasmin. Plasmin is a potent serine protease that is thought to function in the degradation of the extracellular matrix surrounding the targeted host cell, thereby facilitating pathogen invasion. Recent work revealed that the malaria parasite Plasmodium also expresses surface enolase, and that this feature may be essential for completion of its life cycle. The therapeutic potential of targeting surface enolases of pathogens is discussed. PMID:21881761

  16. Automated estimation of parasitaemia of Plasmodium yoelii-infected mice by digital image analysis of Giemsa-stained thin blood smears.

    PubMed

    Ma, Charles; Harrison, Paul; Wang, Lina; Coppel, Ross L

    2010-12-01

    Parasitaemia, the percentage of infected erythrocytes, is used to measure progress of experimental Plasmodium infection in infected hosts. The most widely used technique for parasitaemia determination is manual microscopic enumeration of Giemsa-stained blood films. This process is onerous, time consuming and relies on the expertise of the experimenter giving rise to person-to-person variability. Here the development of image-analysis software, named Plasmodium AutoCount, which can automatically generate parasitaemia values from Plasmodium-infected blood smears, is reported. Giemsa-stained blood smear images were captured with a camera attached to a microscope and analysed using a programme written in the Python programming language. The programme design involved foreground detection, cell and infection detection, and spurious hit filtering. A number of parameters were adjusted by a calibration process using a set of representative images. Another programme, Counting Aid, written in Visual Basic, was developed to aid manual counting when the quality of blood smear preparation is too poor for use with the automated programme. This programme has been validated for use in estimation of parasitemia in mouse infection by Plasmodium yoelii and used to monitor parasitaemia on a daily basis for an entire challenge infection. The parasitaemia values determined by Plasmodium AutoCount were shown to be highly correlated with the results obtained by manual counting, and the discrepancy between automated and manual counting results were comparable to those found among manual counts of different experimenters. Plasmodium AutoCount has proven to be a useful tool for rapid and accurate determination of parasitaemia from infected mouse blood. For greater accuracy when smear quality is poor, Plasmodium AutoCount, can be used in conjunction with Counting Aid.

  17. No Evidence for Ape Plasmodium Infections in Humans in Gabon

    PubMed Central

    Ollomo, Benjamin; Arnathau, Céline; Roche, Benjamin; Elguero, Eric; Moukodoum, Nancy Diamella; Okougha, Alain-Prince; Mve Ondo, Bertrand; Boundenga, Larson; Houzé, Sandrine; Galan, Maxime; Nkoghé, Dieudonné; Leroy, Eric M.; Durand, Patrick; Paupy, Christophe; Renaud, François; Prugnolle, Franck

    2015-01-01

    African great apes are naturally infected by a multitude of Plasmodium species most of them recently discovered, among which several are closely related to human malaria agents. However, it is still unknown whether these animals can serve as source of infections for humans living in their vicinity. To evaluate this possibility, we analysed the nature of Plasmodium infections from a bank of 4281 human blood samples collected in 210 villages of Gabon, Central Africa. Among them, 2255 were detected positive to Plasmodium using molecular methods (Plasmodium Cytochrome b amplification). A high throughput sequencing technology (454 GS-FLX Titanium technology, Roche) was then used to identify the Plasmodium species present within each positive sample. Overall, we identified with confidence only three species infecting humans in Gabon: P. falciparum, P. malariae and P. ovale. None of the species known to infect non-human primates in Central Africa was found. Our study shows that ape Plasmodium parasites of the subgenus Laverania do not constitute a frequent source of infection for humans. It also suggests that some strong host genetic barriers must exist to prevent the cross species transmission of ape Plasmodium in a context of ever increasing contacts between humans and wildlife. PMID:26039338

  18. No evidence for ape Plasmodium infections in humans in Gabon.

    PubMed

    Délicat-Loembet, Lucresse; Rougeron, Virginie; Ollomo, Benjamin; Arnathau, Céline; Roche, Benjamin; Elguero, Eric; Moukodoum, Nancy Diamella; Okougha, Alain-Prince; Mve Ondo, Bertrand; Boundenga, Larson; Houzé, Sandrine; Galan, Maxime; Nkoghé, Dieudonné; Leroy, Eric M; Durand, Patrick; Paupy, Christophe; Renaud, François; Prugnolle, Franck

    2015-01-01

    African great apes are naturally infected by a multitude of Plasmodium species most of them recently discovered, among which several are closely related to human malaria agents. However, it is still unknown whether these animals can serve as source of infections for humans living in their vicinity. To evaluate this possibility, we analysed the nature of Plasmodium infections from a bank of 4281 human blood samples collected in 210 villages of Gabon, Central Africa. Among them, 2255 were detected positive to Plasmodium using molecular methods (Plasmodium Cytochrome b amplification). A high throughput sequencing technology (454 GS-FLX Titanium technology, Roche) was then used to identify the Plasmodium species present within each positive sample. Overall, we identified with confidence only three species infecting humans in Gabon: P. falciparum, P. malariae and P. ovale. None of the species known to infect non-human primates in Central Africa was found. Our study shows that ape Plasmodium parasites of the subgenus Laverania do not constitute a frequent source of infection for humans. It also suggests that some strong host genetic barriers must exist to prevent the cross species transmission of ape Plasmodium in a context of ever increasing contacts between humans and wildlife.

  19. Prevalence and distribution of human Plasmodium infection in Pakistan.

    PubMed

    Khattak, Aamer A; Venkatesan, Meera; Nadeem, Muhammad F; Satti, Humayoon S; Yaqoob, Adnan; Strauss, Kathy; Khatoon, Lubna; Malik, Salman A; Plowe, Christopher V

    2013-08-28

    Both Plasmodium vivax and Plasmodium falciparum are prevalent in Pakistan, yet up-to-date data on the epidemiology of malaria in Pakistan are not available. This study was undertaken to determine the current prevalence and distribution of Plasmodium species across the country. A malariometric population survey was conducted in 2011 using blood samples collected from 801 febrile patients of all ages in four provinces and the capital city of Islamabad. Microscopically confirmed Plasmodium-positive blood samples were reconfirmed by polymerase chain reaction (PCR). Confirmed parasite-positive samples were subjected to species-specific PCR capable of detecting four species of human malaria. Of the 707 PCR-positive samples, 128 (18%) were P. falciparum, 536 (76%) were P. vivax, and 43 (6%) were mixed P. falciparum and P. vivax. Ninety-four microscopy-positive samples were PCR-negative, and Plasmodium malariae and Plasmodium ovale were not detected. Prevalence of P. vivax ranged from 2.4% in Punjab Province to 10.8% in Sindh Province and prevalence of P. falciparum ranged from 0.1% in Islamabad to 3.8% in Balochistan. Plasmodium infections in Pakistan are largely attributed to P. vivax but P. falciparum and mixed species infections are also prevalent. In addition, regional variation in the prevalence and species composition of malaria is high.

  20. Prevalence and distribution of human Plasmodium infection in Pakistan

    PubMed Central

    2013-01-01

    Background Both Plasmodium vivax and Plasmodium falciparum are prevalent in Pakistan, yet up-to-date data on the epidemiology of malaria in Pakistan are not available. This study was undertaken to determine the current prevalence and distribution of Plasmodium species across the country. Methods A malariometric population survey was conducted in 2011 using blood samples collected from 801 febrile patients of all ages in four provinces and the capital city of Islamabad. Microscopically confirmed Plasmodium-positive blood samples were reconfirmed by polymerase chain reaction (PCR). Confirmed parasite-positive samples were subjected to species-specific PCR capable of detecting four species of human malaria. Results Of the 707 PCR-positive samples, 128 (18%) were P. falciparum, 536 (76%) were P. vivax, and 43 (6%) were mixed P. falciparum and P. vivax. Ninety-four microscopy-positive samples were PCR-negative, and Plasmodium malariae and Plasmodium ovale were not detected. Prevalence of P. vivax ranged from 2.4% in Punjab Province to 10.8% in Sindh Province and prevalence of P. falciparum ranged from 0.1% in Islamabad to 3.8% in Balochistan. Conclusions Plasmodium infections in Pakistan are largely attributed to P. vivax but P. falciparum and mixed species infections are also prevalent. In addition, regional variation in the prevalence and species composition of malaria is high. PMID:23984968

  1. Plasmodium infection decreases fecundity and increases survival of mosquitoes.

    PubMed

    Vézilier, J; Nicot, A; Gandon, S; Rivero, A

    2012-10-07

    Long-lived mosquitoes maximize the chances of Plasmodium transmission. Yet, in spite of decades of research, the effect of Plasmodium parasites on mosquito longevity remains highly controversial. On the one hand, many studies report shorter lifespans in infected mosquitoes. On the other hand, parallel (but separate) studies show that Plasmodium reduces fecundity and imply that this is an adaptive strategy of the parasite aimed at redirecting resources towards longevity. No study till date has, however, investigated fecundity and longevity in the same individuals to see whether this prediction holds. In this study, we follow for both fecundity and longevity in Plasmodium-infected and uninfected mosquitoes using a novel, albeit natural, experimental system. We also explore whether the genetic variations that arise through the evolution of insecticide resistance modulate the effect of Plasmodium on these two life-history traits. We show that (i) a reduction in fecundity in Plasmodium-infected mosquitoes is accompanied by an increase in longevity; (ii) this increase in longevity arises through a trade-off between reproduction and survival; and (iii) in insecticide-resistant mosquitoes, the slope of this trade-off is steeper when the mosquito is infected by Plasmodium (cost of insecticide resistance).

  2. [Relapse of Plasmodium malariae malaria 20 years after living in an endemic area].

    PubMed

    Siala, Emna; Khalfaoui, Moncef; Bouratbine, Aida; Hamdi, Samira; Hili, Kamel; Aoun, Karim

    2005-03-12

    Malaria has been eradicated in Tunisia since 1979. Although it continues to be evoked in the case of fever after travel to an endemic zone, its diagnosis is however difficult during relapses, notably when they are delayed. A 50 year-old man having lived in Mauritania from 1978 to 1982 was hospitalized for interstitial pneumopathy and urarthritis. In spite of treatment with broad spectrum antibiotics, the fever accompanied by abundant sweating persisted. A thick blood drop and blood smear was requested and led to the diagnosis of Plasmodium malariae malaria. This observation recalls the possibility of parasitic upsurge of some plasmodial species. It should prompt physicians to be careful and evoke malaria in the case of fever in subjects having stayed, even several years before, in an endemic zone. This would permit early diagnosis and treatment.

  3. Towards genome-wide experimental genetics in the in vivo malaria model parasite Plasmodium berghei.

    PubMed

    Matz, Joachim M; Kooij, Taco W A

    2015-03-01

    Plasmodium berghei was identified as a parasite of thicket rats (Grammomys dolichurus) and Anopheles dureni mosquitoes in African highland forests. Successful adaptation to a range of rodent and mosquito species established P. berghei as a malaria model parasite. The introduction of stable transfection technology, permitted classical reverse genetics strategies and thus systematic functional profiling of the gene repertoire. In the past 10 years following the publication of the P. berghei genome sequence, many new tools for experimental genetics approaches have been developed and existing ones have been improved. The infection of mice is the principal limitation towards a genome-wide repository of mutant parasite lines. In the past few years, there have been some promising and most welcome developments that allow rapid selection and isolation of recombinant parasites while simultaneously minimising animal usage. Here, we provide an overview of all the currently available tools and methods.

  4. Human Infections and Detection of Plasmodium knowlesi

    PubMed Central

    Daneshvar, Cyrus

    2013-01-01

    SUMMARY Plasmodium knowlesi is a malaria parasite that is found in nature in long-tailed and pig-tailed macaques. Naturally acquired human infections were thought to be extremely rare until a large focus of human infections was reported in 2004 in Sarawak, Malaysian Borneo. Human infections have since been described throughout Southeast Asia, and P. knowlesi is now recognized as the fifth species of Plasmodium causing malaria in humans. The molecular, entomological, and epidemiological data indicate that human infections with P. knowlesi are not newly emergent and that knowlesi malaria is primarily a zoonosis. Human infections were undiagnosed until molecular detection methods that could distinguish P. knowlesi from the morphologically similar human malaria parasite P. malariae became available. P. knowlesi infections cause a spectrum of disease and are potentially fatal, but if detected early enough, infections in humans are readily treatable. In this review on knowlesi malaria, we describe the early studies on P. knowlesi and focus on the epidemiology, diagnosis, clinical aspects, and treatment of knowlesi malaria. We also discuss the gaps in our knowledge and the challenges that lie ahead in studying the epidemiology and pathogenesis of knowlesi malaria and in the prevention and control of this zoonotic infection. PMID:23554413

  5. Human infections and detection of Plasmodium knowlesi.

    PubMed

    Singh, Balbir; Daneshvar, Cyrus

    2013-04-01

    Plasmodium knowlesi is a malaria parasite that is found in nature in long-tailed and pig-tailed macaques. Naturally acquired human infections were thought to be extremely rare until a large focus of human infections was reported in 2004 in Sarawak, Malaysian Borneo. Human infections have since been described throughout Southeast Asia, and P. knowlesi is now recognized as the fifth species of Plasmodium causing malaria in humans. The molecular, entomological, and epidemiological data indicate that human infections with P. knowlesi are not newly emergent and that knowlesi malaria is primarily a zoonosis. Human infections were undiagnosed until molecular detection methods that could distinguish P. knowlesi from the morphologically similar human malaria parasite P. malariae became available. P. knowlesi infections cause a spectrum of disease and are potentially fatal, but if detected early enough, infections in humans are readily treatable. In this review on knowlesi malaria, we describe the early studies on P. knowlesi and focus on the epidemiology, diagnosis, clinical aspects, and treatment of knowlesi malaria. We also discuss the gaps in our knowledge and the challenges that lie ahead in studying the epidemiology and pathogenesis of knowlesi malaria and in the prevention and control of this zoonotic infection.

  6. Severe Plasmodium knowlesi with dengue coinfection.

    PubMed

    Che Rahim, Mohd Jazman; Mohammad, Nurashikin; Besari, Alwi Muhd; Wan Ghazali, Wan Syamimee

    2017-02-20

    We report a case of severe Plasmodium knowlesi and dengue coinfection in a previously healthy 59-year-old Malay man who presented with worsening shortness of breath, high-grade fever with chills and rigors, dry cough, myalgia, arthralgia, chest discomfort and poor appetite of 1 week duration. There was a history mosquito fogging around his neighbourhood in his hometown. Further history revealed that he went to a forest in Jeli (northern part of Kelantan) 3 weeks prior to the event. Initially he was treated as severe dengue with plasma leakage complicated with type 1 respiratory failure as evidenced by positive serum NS1-antigen and thrombocytopenia. Blood for malarial parasite (BFMP) was sent for test as there was suspicion of malaria due to persistent thrombocytopenia despite recovering from dengue infection and the presence of a risk factor. The test revealed high count of malaria parasite. Confirmatory PCR identified the parasite to be Plasmodium knowlesi Intravenous artesunate was administered to the patient immediately after acquiring the BFMP result. Severe malaria was complicated with acute kidney injury and septicaemic shock. Fortunately the patient made full recovery and was discharged from the ward after 2 weeks of hospitalisation. 2017 BMJ Publishing Group Ltd.

  7. Management of relapsing Plasmodium vivax malaria

    PubMed Central

    Chu, Cindy S; White, Nicholas J

    2016-01-01

    ABSTRACT Introduction: Relapses are important contributors to illness and morbidity in Plasmodium vivax and P. ovale infections. Relapse prevention (radical cure) with primaquine is required for optimal management, control and ultimately elimination of Plasmodium vivax malaria. A review was conducted with publications in English, French, Portuguese and Spanish using the search terms ‘P. vivax’ and ‘relapse’. Areas covered: Hypnozoites causing relapses may be activated weeks or months after initial infection. Incidence and temporal patterns of relapse varies geographically. Relapses derive from parasites either genetically similar or different from the primary infection indicating that some derive from previous infections. Malaria illness itself may activate relapse. Primaquine is the only widely available treatment for radical cure. However, it is often not given because of uncertainty over the risks of primaquine induced haemolysis when G6PD deficiency testing is unavailable. Recommended dosing of primaquine for radical cure in East Asia and Oceania is 0.5 mg base/kg/day and elsewhere is 0.25 mg base/kg/day. Alternative treatments are under investigation. Expert commentary: Geographic heterogeneity in relapse patterns and chloroquine susceptibility of P. vivax, and G6PD deficiency epidemiology mean that radical treatment should be given much more than it is today. G6PD testing should be made widely available so primaquine can be given more safely. PMID:27530139

  8. Artemisinins target the SERCA of Plasmodium falciparum.

    PubMed

    Eckstein-Ludwig, U; Webb, R J; Van Goethem, I D A; East, J M; Lee, A G; Kimura, M; O'Neill, P M; Bray, P G; Ward, S A; Krishna, S

    2003-08-21

    Artemisinins are extracted from sweet wormwood (Artemisia annua) and are the most potent antimalarials available, rapidly killing all asexual stages of Plasmodium falciparum. Artemisinins are sesquiterpene lactones widely used to treat multidrug-resistant malaria, a disease that annually claims 1 million lives. Despite extensive clinical and laboratory experience their molecular target is not yet identified. Activated artemisinins form adducts with a variety of biological macromolecules, including haem, translationally controlled tumour protein (TCTP) and other higher-molecular-weight proteins. Here we show that artemisinins, but not quinine or chloroquine, inhibit the SERCA orthologue (PfATP6) of Plasmodium falciparum in Xenopus oocytes with similar potency to thapsigargin (another sesquiterpene lactone and highly specific SERCA inhibitor). As predicted, thapsigargin also antagonizes the parasiticidal activity of artemisinin. Desoxyartemisinin lacks an endoperoxide bridge and is ineffective both as an inhibitor of PfATP6 and as an antimalarial. Chelation of iron by desferrioxamine abrogates the antiparasitic activity of artemisinins and correspondingly attenuates inhibition of PfATP6. Imaging of parasites with BODIPY-thapsigargin labels the cytosolic compartment and is competed by artemisinin. Fluorescent artemisinin labels parasites similarly and irreversibly in an Fe2+-dependent manner. These data provide compelling evidence that artemisinins act by inhibiting PfATP6 outside the food vacuole after activation by iron.

  9. Plasmodium vivax malaria during pregnancy, Bolivia.

    PubMed

    Brutus, Laurent; Santalla, José; Schneider, Dominique; Avila, Juan Carlos; Deloron, Philippe

    2013-10-01

    Plasmodium vivax is a major cause of illness in areas with low transmission of malaria in Latin America, Asia, and the Horn of Africa. However, pregnancy-associated malaria remains poorly characterized in such areas. Using a hospital-based survey of women giving birth and an antenatal survey, we assessed the prevalence rates of Plasmodium spp. infections in pregnant women in Bolivia, and evaluated the consequences of malaria during pregnancy on the health of mothers and newborns. P. vivax infection was detected in 7.9% of pregnant women attending antenatal visits, and placental infection occurred in 2.8% of deliveries; these rates did not vary with parity. Forty-two percent of all P. vivax malaria episodes were symptomatic. P. vivax-infected pregnant women were frequently anemic (6.5%) and delivered babies of reduced birthweight. P. vivax infections during pregnancy are clearly associated with serious adverse outcomes and should be considered in prevention strategies of pregnancy-associated malaria.

  10. Facing Title V permit constraints

    SciTech Connect

    Patankar, U.M.

    1995-06-01

    The new Title V operating permit requirement under state regulations pursuant to the 1990 Clean Air Act Amendments will cover every emission source at a facility. These rules will significantly affect an operation by setting minimum compliance requirements, mandating periodic compliance certification, prescribing complex monitoring, record keeping and reporting procedures and making state and EPA approval of routine operational changes necessary through a permit amendment. The main concern with Title V is its effect on the operational flexibility of a facility, and individual emission sources within that facility. Unless properly addressed in a permit document, the term operational flexibility, so freely used by regulators in the context of the Title V program, can turn into a misnomer and the ability to operate as before may be significantly compromised under Title V. True operational flexibility is essential for businesses to respond to real changes in the marketplace. In the age of automation, just-in-time inventories and increased competition, flexibility to operate can mean the difference between growth and stagnation.

  11. 27 CFR 71.49a - Applications for operating permits and industrial use permits.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... permits and industrial use permits. 71.49a Section 71.49a Alcohol, Tobacco Products and Firearms ALCOHOL... and industrial use permits. If, on examination of an application for an operating permit or an industrial use permit, the appropriate TTB officer has reason to believe: (a) In case of an application to...

  12. 27 CFR 71.48 - Operating permits and industrial use permits.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... industrial use permits. 71.48 Section 71.48 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX... PERMIT PROCEEDINGS Grounds for Citation § 71.48 Operating permits and industrial use permits. Whenever... industrial use permit: (a) Has not in good faith complied with the provisions of 26 U.S.C. chapter 51 or...

  13. Plasmodium falciparum full life cycle and Plasmodium ovale liver stages in humanized mice

    PubMed Central

    Soulard, Valérie; Bosson-Vanga, Henriette; Lorthiois, Audrey; Roucher, Clémentine; Franetich, Jean- François; Zanghi, Gigliola; Bordessoulles, Mallaury; Tefit, Maurel; Thellier, Marc; Morosan, Serban; Le Naour, Gilles; Capron, Frédérique; Suemizu, Hiroshi; Snounou, Georges; Moreno-Sabater, Alicia; Mazier, Dominique

    2015-01-01

    Experimental studies of Plasmodium parasites that infect humans are restricted by their host specificity. Humanized mice offer a means to overcome this and further provide the opportunity to observe the parasites in vivo. Here we improve on previous protocols to achieve efficient double engraftment of TK-NOG mice by human primary hepatocytes and red blood cells. Thus, we obtain the complete hepatic development of P. falciparum, the transition to the erythrocytic stages, their subsequent multiplication, and the appearance of mature gametocytes over an extended period of observation. Furthermore, using sporozoites derived from two P. ovale-infected patients, we show that human hepatocytes engrafted in TK-NOG mice sustain maturation of the liver stages, and the presence of late-developing schizonts indicate the eventual activation of quiescent parasites. Thus, TK-NOG mice are highly suited for in vivo observations on the Plasmodium species of humans. PMID:26205537

  14. BLOOD-STAGE DYNAMICS AND CLINICAL IMPLICATIONS OF MIXED PLASMODIUM VIVAX–PLASMODIUM FALCIPARUM INFECTIONS

    PubMed Central

    MASON, DANIEL P.; McKENZIE, F. ELLIS

    2008-01-01

    We present a mathematical model of the blood-stage dynamics of mixed Plasmodium vivax–Plasmodium falciparum malaria infections in humans. The model reproduces features of such infections found in nature and suggests several phenomena that may merit clinical attention, including the potential recrudescence of a long-standing, low-level P. falciparum infection following a P. vivax infection or relapse and the capacity of an existing P. vivax infection to reduce the peak parasitemia of a P. falciparum superinfection. We simulate the administration of anti-malarial drugs, and illustrate some potential complications in treating mixed-species malaria infections. Notably, our model indicates that when a mixed-species infection is misdiagnosed as a single-species P. vivax infection, treatment for P. vivax can lead to a surge in P. falciparum parasitemia. PMID:10497972

  15. 18 CFR 50.11 - General conditions applicable to permits.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... a copy of, any application to construct a major electric generation facility. ... 18 Conservation of Power and Water Resources 1 2011-04-01 2011-04-01 false General conditions applicable to permits. 50.11 Section 50.11 Conservation of Power and Water Resources FEDERAL...

  16. Minor NSR Permit Application: Chaparral Commerce Center, Scottsdale, AZ

    EPA Pesticide Factsheets

    Minor New Source Review (NSR) Permit application for the two emergency diesel-fired generators (1,500 kW each) to be installed at the Chaparral Commerce Center in the Salt River Pima-Maricopa Indian Community (SRPMIC) in Scottsdale, Arizona.

  17. Use of a colorimetric (DELI) test for the evaluation of chemoresistance of Plasmodium falciparum and Plasmodium vivax to commonly used anti-plasmodial drugs in the Brazilian Amazon

    PubMed Central

    2013-01-01

    Background The emergence and spread of Plasmodium falciparum and Plasmodium vivax resistance to available anti-malarial drugs represents a major drawback in the control of malaria and its associated morbidity and mortality. The aim of this study was to evaluate the chemoresistance profile of P. falciparum and P. vivax to commonly used anti-plasmodial drugs in a malaria-endemic area in the Brazilian Amazon. Methods The study was carried out in Manaus (Amazonas state), in the Brazilian Amazon. A total of 88 P. falciparum and 178 P. vivax isolates was collected from 2004 to 2007. The sensitivity of P. falciparum isolates was determined to chloroquine, quinine, mefloquine and artesunate and the sensitivity of P. vivax isolates was determined to chloroquine and mefloquine, by using the colorimetric DELI test. Results As expected, a high prevalence of P. falciparum isolates resistant to chloroquine (78.1%) was observed. The prevalence of isolates with profile of resistance or decreased sensitivity for quinine, mefloquine and artesunate was 12.7, 21.2 and 11.7%, respectively. In the case of P. vivax, the prevalence of isolates with profile of resistance for chloroquine and mefloquine was 9.8 and 28%, respectively. No differences in the frequencies of isolates with profile of resistance or geometric mean IC50s were seen when comparing the data obtained in 2004, 2005, 2006 and 2007, for all tested anti-malarials. Conclusions The great majority of P. falciparum isolates in the Brazilian malaria-endemic area remain resistant to chloroquine, and the decreased sensitivity to quinine, mefloquine and artesunate observed in 10–20% of the isolates must be taken with concern, especially for artesunate. Plasmodium vivax isolates also showed a significant proportion of isolates with decreased sensitivity to chloroquine (first-line drug) and mainly to mefloquine. The data presented here also confirm the usefulness of the DELI test to generate results able to impact on public health

  18. The cryo-EM structure of the Plasmodium falciparum 20S proteasome and its use in the fight against malaria.

    PubMed

    Li, Hao; Bogyo, Matthew; da Fonseca, Paula C A

    2016-12-01

    Plasmodium falciparum is the parasite responsible for the most severe form of malaria. Its increasing resistance to existing antimalarials represents a major threat to human health and urges the development of new therapeutic strategies to fight malaria. The proteasome is a protease complex essential in all eukaryotes. Accordingly, inhibition of the Plasmodium 20S proteasome is highly toxic for the parasite at all of its infective and developmental stages. Proteasome inhibitors have antimalarial potential both as curative and transmission blocking agents, but in order to have therapeutic application, they must specifically target the Plasmodium proteasome and not its human counterpart. X-ray crystallography has been widely used to determine structures of yeast and mammalian 20S proteasomes with ligands. However, crystallisation of the Plasmodium proteasome is challenging, as only small quantities of the complex can be directly purified from the parasite. Furthermore, most X-ray structures of proteasome-inhibitor complexes require soaking of crystals with high concentrations of ligand, thus preventing analysis of inhibitor subunit specificity. Instead we chose to determine the Plasmodium falciparum 20S proteasome structure, in the presence of a new rationally designed parasite-specific inhibitor, by high-resolution electron cryo-microscopy and single particle analysis. The resulting map, at a resolution of about 3.6 Å, allows a direct molecular analysis of inhibitor/enzyme interactions. Here we present an overview of this structure, and how it provides valuable information that can be used to assist in the design of improved proteasome inhibitors with the potential to be developed as next-generation antimalarial drugs. © 2016 Federation of European Biochemical Societies.

  19. Appeal Procedures for PSD Permits Under The Consolidated Permit Regulations

    EPA Pesticide Factsheets

    This document may be of assistance in applying the New Source Review (NSR) air permitting regulations including the Prevention of Significant Deterioration (PSD) requirements. This document is part of the NSR Policy and Guidance Database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  20. Plasmodium falciparum-infected mice: more than a tour de force.

    PubMed

    Moreno, Alicia; Pérignon, Jean Louis; Morosan, Serban; Mazier, Dominique; Benito, Agustin

    2007-06-01

    Up until recently, the relevance of Plasmodium falciparum-infected humanized mice for malaria studies has been questioned because of the low percentage of mice in which the parasite develops. Advances in the generation of new immunodeficient mouse strains combined with the use of protocols that modulate the innate immune defenses of mice have facilitated the harvesting of exoerythrocytic and intraerythrocytic stages of the parasite. These results renew the hope of working with P. falciparum in a laboratory animal and indicate that the next challenge (i.e. a complete parasite cycle in the same mouse, including transmission to mosquito) could be reached in the future.

  1. Immunization of mice with Plasmodium TCTP delays establishment of Plasmodium infection.

    PubMed

    Taylor, K J; Van, T T H; MacDonald, S M; Meshnick, S R; Fernley, R T; Macreadie, I G; Smooker, P M

    2015-01-01

    Translationally controlled tumour protein (TCTP) may play an important role in the establishment or maintenance of parasitemia in a malarial infection. In this study, the potential of TCTP as a malaria vaccine was investigated in two trials. In the initial vaccine trial, Plasmodium falciparum TCTP (PfTCTP) was expressed in Saccharomyces cerevisiae and used to immunize BALB/c mice. Following challenge with Plasmodium yoelii YM, parasitemia was significantly reduced during the early stages of infection. In the second vaccine trial, the TCTP from P. yoelii and P. berghei was expressed in Escherichia coli and used in several mouse malaria models. A significant reduction in parasitemia in the early stages of infection was observed in BALB/c mice challenged with P. yoelii YM. A significantly reduced parasitemia at each day leading up to a delayed and reduced peak parasitemia was also observed in BALB/c mice challenged with the nonlethal Plasmodium chabaudi (P.c.) chabaudi AS. These results suggest that TCTP has an important role for parasite establishment and may be important for pathogenesis.

  2. Window generator

    NASA Astrophysics Data System (ADS)

    Johnson, William K.; May, Roger A.

    1989-03-01

    The present invention relates generally to video target recognition systems and more specifically to a window generator which receives a field of video data and applies an identification code to rectangular subregions to identify distinct target areas within a given background area. The present invention comprises a window generator which provides a 6 bit target identification number for up to 63 target areas and one background area in a frame of serially scanned data. The window generator receives a field of video data from an image data source. This video data consists of digitized frames of serially scanned data similar to a conventional television screen image, which is divided horizontally in pixels, and vertically in lines. The window generator permits any given frame to be subdivided into specific rectangular subregions, which may be located anywhere on the video picture. By allowing statistics to be collected on the individual subregions (or target areas) the window generator permits local processing of video data within the specified target areas as opposed to processing of video data over the entire video field. One embodiment of the window generator is composed of: a microprocessor, a random access memory (RAM), a comparator, a line memory, two counters, an OR gate, a frame initialization circuit, and a buffer. These elements function as described below.

  3. Plasmodium infection in a Leadbeater's possum (Gymnobelideus leadbeateri).

    PubMed

    Scheelings, T F; McLaren, P J; Tatarczuch, L; Slocombe, R F

    2016-08-01

    A wild-caught, adult female Leadbeater's possum (Gymnobelideus leadbeateri) died while in captivity after suffering from chronic ill-thrift that progressed to acute respiratory distress. On histopathological examination of tissues, the cause of death was determined to be severe acute pneumonia with pulmonary oedema associated with an intracellular protozoan parasite present within erythrocytes. Transmission electron microscopy was performed on lung tissues and organisms consistent for Plasmodium sp. were identified within numerous erythrocytes. Molecular characterisation of the parasite from DNA extracted from tissue blocks of fixed lung determined the organism to belong to the genus Plasmodium (100% similarity to Plasmodium species when a BLAST analysis was performed); however, speciation of the organism was not possible. This is the first report of Plasmodium sp. infection and subsequent disease in a native Australian mammal. The lifecycle of this parasite remains unknown. It is also unknown what effects haemoparasitism may have on the population dynamics of this endangered possum species. © 2016 Australian Veterinary Association.

  4. Colombian Anopheles triannulatus (Diptera: Culicidae) Naturally Infected with Plasmodium spp.

    PubMed Central

    Rosero, Doris A.; Naranjo-Diaz, Nelson; Alvarez, Natalí; Cienfuegos, Astrid V.; Luckhart, Shirley

    2013-01-01

    The role of Anopheles triannulatus as a local vector has not yet been defined for malaria-endemic regions of Colombia. Therefore, the aim of this work was to detect An. triannulatus naturally infected with Plasmodium spp., as an approximation to determining its importance as malaria vector in the country. A total of 510 An. triannulatus were collected in six malaria-endemic localities of NW and SE Colombia from January 2009 to March 2011. In the NW, two specimens were naturally infected; one with Plasmodium vivax VK247, collected biting on humans and the other with Plasmodium falciparum, collected resting on cattle. In the SE, two specimens were positive for P. falciparum. Although these results show An. triannulatus naturally infected with Plasmodium, further studies are recommended to demonstrate the epidemiological importance of this species in malaria-endemic regions of Colombia. PMID:27335865

  5. 30 CFR 941.773 - Requirements for permits and permit processing.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... DAKOTA § 941.773 Requirements for permits and permit processing. (a) Part 773 of this chapter... permits, leases and certificates required by the State of South Dakota including compliance with: (1) Air...

  6. 30 CFR 941.773 - Requirements for permits and permit processing.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... DAKOTA § 941.773 Requirements for permits and permit processing. (a) Part 773 of this chapter... permits, leases and certificates required by the State of South Dakota including compliance with: (1) Air...

  7. 30 CFR 941.773 - Requirements for permits and permit processing.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... DAKOTA § 941.773 Requirements for permits and permit processing. (a) Part 773 of this chapter... permits, leases and certificates required by the State of South Dakota including compliance with: (1) Air...

  8. 30 CFR 941.773 - Requirements for permits and permit processing.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... DAKOTA § 941.773 Requirements for permits and permit processing. (a) Part 773 of this chapter... permits, leases and certificates required by the State of South Dakota including compliance with: (1) Air...

  9. 30 CFR 941.773 - Requirements for permits and permit processing.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... DAKOTA § 941.773 Requirements for permits and permit processing. (a) Part 773 of this chapter... permits, leases and certificates required by the State of South Dakota including compliance with: (1) Air...

  10. Placental histopathological changes associated with Plasmodium vivax infection during pregnancy.

    PubMed

    Souza, Rodrigo M; Ataíde, Ricardo; Dombrowski, Jamille G; Ippólito, Vanessa; Aitken, Elizabeth H; Valle, Suiane N; Álvarez, José M; Epiphanio, Sabrina; Epiphânio, Sabrina; Marinho, Claudio R F

    2013-01-01

    Histological evidence of Plasmodium in the placenta is indicative of placental malaria, a condition associated with severe outcomes for mother and child. Histological lesions found in placentas from Plasmodium-exposed women include syncytial knotting, syncytial rupture, thickening of the placental barrier, necrosis of villous tissue and intervillositis. These histological changes have been associated with P. falciparum infections, but little is known about the contribution of P. vivax to such changes. We conducted a cross-sectional study with pregnant women at delivery and assigned them to three groups according to their Plasmodium exposure during pregnancy: no Plasmodium exposure (n = 41), P. vivax exposure (n = 59) or P. falciparum exposure (n = 19). We evaluated their placentas for signs of Plasmodium and placental lesions using ten histological parameters: syncytial knotting, syncytial rupture, placental barrier thickness, villi necrosis, intervillous space area, intervillous leucocytes, intervillous mononucleates, intervillous polymorphonucleates, parasitized erythrocytes and hemozoin. Placentas from P. vivax-exposed women showed little evidence of Plasmodium or hemozoin but still exhibited more lesions than placentas from women not exposed to Plasmodium, especially when infections occurred twice or more during pregnancy. In the Brazilian state of Acre, where diagnosis and primary treatment are readily available and placental lesions occur in the absence of detected placental parasites, relying on the presence of Plasmodium in the placenta to evaluate Plasmodium-induced placental pathology is not feasible. Multivariate logistic analysis revealed that syncytial knotting (odds ratio [OR], 4.21, P = 0.045), placental barrier thickness (OR, 25.59, P = 0.021) and mononuclear cells (OR, 4.02, P = 0.046) were increased in placentas from P. vivax-exposed women when compared to women not exposed to Plasmodium during pregnancy. A vivax-score was

  11. Seroepidemiology of Plasmodium species infections in Zimbabwean population.

    PubMed

    Amanfo, Seth A; Mduluza, Takafira; Midzi, Nicholas; Cavanagh, David R; Mutapi, Francisca

    2016-05-10

    Individuals living in malaria-endemic regions may be exposed to more than one Plasmodium species; there is paucity of data on the distribution of the different species of Plasmodium in affected populations, in part due to the diagnostic method of microscopy, which cannot easily differentiate between the species. Sero-epidemiological data can overcome some of the shortcomings of microscopy. The specificity of IgG antibodies to recombinant merozoite surface protein 1 (MSP-119) derived from four human Plasmodium species (Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae, Plasmodium ovale) was investigated using competition enzyme-linked immunosorbent assay. Subsequently, these antigens were used to determine the exposure prevalence to the different Plasmodium species in serum samples of participants. One-hundred individuals, aged five-18 years, from each of the three Plasmodium meso-endemic Zimbabwean villages (Burma Valley, Mutoko, Chiredzi) were recruited in the study. The study demonstrated that the host serum reactivity to MSP-119 antigens was species-specific and that no cross-reactivity occurred. The overall prevalence of antibody response to MSP-119 antigens was 61 % in Burma Valley, 31 % in Mutoko and 32 % in Chiredzi. Single species IgG responses to MSP-119 were most frequent against P. falciparum, followed by P. malariae and P. ovale, with responses to P. vivax being the least prevalent. Interestingly, 78-87 and 50 % of sera with IgG responses to P. malariae and P. ovale MSP-119, respectively, also had IgG specific response for P. falciparum MSP-119 antigens, indicating that exposure to these species is a common occurrence in these populations. Single species IgG responses to the non-falciparum species were at a very low frequency, ranging between 0 and 13 % for P. malariae. There is evidence of a higher exposure to the non-falciparum parasite species than previously reported in Zimbabwe. The recombinant MSP-119 antigens could be used as

  12. PCR-based detection of Plasmodium in Anopheles mosquitoes: a comparison of a new high-throughput assay with existing methods.

    PubMed

    Bass, Chris; Nikou, Dimitra; Blagborough, Andrew M; Vontas, John; Sinden, Robert E; Williamson, Martin S; Field, Linda M

    2008-09-15

    Detection of the four malaria-causing Plasmodium species (Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale and Plasmodium malariae) within their mosquito hosts is an essential component of vector control programmes. Several PCR protocols have been developed for this purpose. Many of these methods, while sensitive, require multiple PCR reactions to detect and discriminate all four Plasmodium species. In this study a new high-throughput assay was developed and compared with three previously described PCR techniques. A new assay based on TaqMan SNP genotyping was developed to detect all four Plasmodium species and discriminate P. falciparum from P. vivax, P. ovale and P. malariae. The sensitivity and the specificity of the new assay was compared to three alternative PCR approaches and to microscopic dissection of salivary glands in a blind trial of 96 single insect samples that included artificially infected Anopheles stephensi mosquitoes. The performance of the assays was then compared using more than 450 field-collected specimens that had been stored on silica gel, in ethanol or in isopropanol. The TaqMan assay was found to be highly specific when using Plasmodium genomic DNA as template. Tests of analytical sensitivity and the results of the blind trial showed the TaqMan assay to be the most sensitive of the four methods followed by the 'gold standard' nested PCR approach and the results generated using these two methods were in good concordance. The sensitivity of the other two methods and their agreement with the nested PCR and TaqMan approaches varied considerably. In trials using field collected specimens two of the methods (including the nested protocol) showed a high degree of non-specific amplification when using DNA derived from mosquitoes stored in ethanol or isopropanol. The TaqMan method appeared unaffected when using the same samples. This study describes a new high-throughput TaqMan assay that very effectively detects the four Plasmodium

  13. Drug Evaluation in the Plasmodium Falciparum - Aotus Model.

    DTIC Science & Technology

    1992-03-23

    AOTUS MODEL PRINCIPAL INVESTIGATOR: Richard N. Rossan, Ph.D. CONTRACTING ORGANIZATION: PROMED TRADING, S.A. P.O. Box 025426, PTY-051 Miami, Florida...91 - 2/28/92) 4. TITLE AND SUBTITLE S. FUNDING NUMBERS DRUG EVALUATION IN THE PLASMODIUM FALCIPARUM - Contract No. AOTUS MODEL DAMD17-91-C-1072 6C...words) Tne Panamanian Autus - PLasmodium falciparum model was used to evaluate potential antimalaria drugs. Neither protriptylene nor tetrandrine, each

  14. Drug Evaluation in the Plasmodium Falciparum - Aotus Model

    DTIC Science & Technology

    1993-03-23

    Rossan, RN, Harper, JS III, Davidson, DE Jr., Escajadillo , A. and Christensen, HA.1985. Comparison of Plasmodium falc1parum infections in Panamanian and...Malaria. Amsterdam. 6. Pollack, S, Rossan, RN, Davidson, DE, Escajadillo , A., 1987. Desferrioxamine suppresses Plasmodium falciparum in Aotus monkeys. Proc...Soc Expt Biol Med. 184:162-164.- 7. Panton, LJ, Rossan, RN, Escajadillo , A, Matsumoto, Y, Lee, AT, Labroo, VM, Kirk, KL, Cohen, LA, Airkawa, M, Howard

  15. Active and Passive Immunization against Plasmodium Yoelii Sporozoites

    DTIC Science & Technology

    1990-01-01

    reverse if necessary and identify by block number) FIELD GROUP SUB-GROUP malaria vaccine ; thiocyanate elution; Plasmodium yoelii; humoral immunity...G.H. Lowell1,4 R.L. Beaudoin,’ & S.L. Hoffman’ Three subunit vaccines based on the major repeat. (0GPGAP)n, and flanking iegions of the Plasmodium yoeui...with subunit vaccines containing OGPGAP but were not protected 9 :- .~v against challenge with 40-200 sporozoites. To determine if antibody avidity

  16. Using Click Chemistry to Identify Potential Drug Targets in Plasmodium

    DTIC Science & Technology

    2016-06-01

    AWARD NUMBER: W81XWH-13-1-0429 TITLE: Using "Click Chemistry " to Identify Potential Drug Targets in Plasmodium PRINCIPAL INVESTIGATOR...29Mar2016 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER W81XWH-13-1-0429 Using click chemistry to identify potential drug targets in Plasmodium 5b...Al-Tsp derivatives begins. Two classes of Tsp derivatives (Al-Tsp) are appropriate for click chemistry (Fig. 1). Class I derivatives carry a

  17. Plasmodium knowlesi infection imported to Germany, January 2013.

    PubMed

    Orth, H; Jensen, B O; Holtfreter, M C; Kocheril, S J; Mallach, S; MacKenzie, C; Müller-Stöver, I; Henrich, B; Imwong, M; White, N J; Häussinger, D; Richter, J

    2013-10-03

    Plasmodium knowlesi was known as a plasmodium of macaques until P. knowlesi transmission to humans was recognised in Borneo and later throughout South-East Asia. We describe here a case of a P. knowlesi infection imported to Germany from Thailand. The patient had not taken antimalarial chemoprophylaxis and suffered from daily fever attacks. Microscopy revealed trophozoites and gametocytes resembling P. malariae. P. knowlesi malaria was confirmed by PCR.

  18. Plasmodium vivax malaria associated with acute post infectious glomerulonephritis.

    PubMed

    Kanodia, Kamal V; Vanikar, Aruna V; Kute, Vivek Balkrishna; Trivedi, Hargovind L

    2013-08-01

    Malaria remains a major health problem in many parts of the world leading to high morbidity and mortality related to renal dysfunction and relapsing nature of Plasmodium vivax malaria. Acute renal failure occurs commonly in Plasmodium falciparum malaria, although its rare occurrences have been reported in P. vivax malaria also. We reported a rare case of P. vivax malaria monoinfection associated with acute post infectious glomerulonephritis.

  19. Using Click Chemistry to Identify Potential Drug Targets in Plasmodium

    DTIC Science & Technology

    2015-04-01

    mammalian cycle. Inhibiting this step can block malaria at an early step. However, few anti-malar ials target l iver infection by sporozo ites. Our...step of the Plasmodium mammalian cycle. Inhibiting this step can block malaria at an early step. However, few anti-malarials target liver infection...intrahepatic development 2. Keywords Plasmodium, sporozoites, liver infection, kinase, drugs, malaria 3. Accomplishments • What were the major

  20. Plasmodium falciparum Malaria Endemicity in Indonesia in 2010

    PubMed Central

    Elyazar, Iqbal R. F.; Gething, Peter W.; Patil, Anand P.; Rogayah, Hanifah; Kusriastuti, Rita; Wismarini, Desak M.; Tarmizi, Siti N.; Baird, J. Kevin; Hay, Simon I.

    2011-01-01

    Background Malaria control programs require a detailed understanding of the contemporary spatial distribution of infection risk to efficiently allocate resources. We used model based geostatistics (MBG) techniques to generate a contemporary map of Plasmodium falciparum malaria risk in Indonesia in 2010. Methods Plasmodium falciparum Annual Parasite Incidence (PfAPI) data (2006–2008) were used to map limits of P. falciparum transmission. A total of 2,581 community blood surveys of P. falciparum parasite rate (PfPR) were identified (1985–2009). After quality control, 2,516 were included into a national database of age-standardized 2–10 year old PfPR data (PfPR2–10) for endemicity mapping. A Bayesian MBG procedure was used to create a predicted surface of PfPR2–10 endemicity with uncertainty estimates. Population at risk estimates were derived with reference to a 2010 human population count surface. Results We estimate 132.8 million people in Indonesia, lived at risk of P. falciparum transmission in 2010. Of these, 70.3% inhabited areas of unstable transmission and 29.7% in stable transmission. Among those exposed to stable risk, the vast majority were at low risk (93.39%) with the reminder at intermediate (6.6%) and high risk (0.01%). More people in western Indonesia lived in unstable rather than stable transmission zones. In contrast, fewer people in eastern Indonesia lived in unstable versus stable transmission areas. Conclusion While further feasibility assessments will be required, the immediate prospects for sustained control are good across much of the archipelago and medium term plans to transition to the pre-elimination phase are not unrealistic for P. falciparum. Endemicity in areas of Papua will clearly present the greatest challenge. This P. falciparum endemicity map allows malaria control agencies and their partners to comprehensively assess the region-specific prospects for reaching pre-elimination, monitor and evaluate the effectiveness of

  1. Plasmodium falciparum malaria endemicity in Indonesia in 2010.

    PubMed

    Elyazar, Iqbal R F; Gething, Peter W; Patil, Anand P; Rogayah, Hanifah; Kusriastuti, Rita; Wismarini, Desak M; Tarmizi, Siti N; Baird, J Kevin; Hay, Simon I

    2011-01-01

    Malaria control programs require a detailed understanding of the contemporary spatial distribution of infection risk to efficiently allocate resources. We used model based geostatistics (MBG) techniques to generate a contemporary map of Plasmodium falciparum malaria risk in Indonesia in 2010. Plasmodium falciparum Annual Parasite Incidence (PfAPI) data (2006-2008) were used to map limits of P. falciparum transmission. A total of 2,581 community blood surveys of P. falciparum parasite rate (PfPR) were identified (1985-2009). After quality control, 2,516 were included into a national database of age-standardized 2-10 year old PfPR data (PfPR(2-10)) for endemicity mapping. A Bayesian MBG procedure was used to create a predicted surface of PfPR(2-10) endemicity with uncertainty estimates. Population at risk estimates were derived with reference to a 2010 human population count surface. We estimate 132.8 million people in Indonesia, lived at risk of P. falciparum transmission in 2010. Of these, 70.3% inhabited areas of unstable transmission and 29.7% in stable transmission. Among those exposed to stable risk, the vast majority were at low risk (93.39%) with the reminder at intermediate (6.6%) and high risk (0.01%). More people in western Indonesia lived in unstable rather than stable transmission zones. In contrast, fewer people in eastern Indonesia lived in unstable versus stable transmission areas. While further feasibility assessments will be required, the immediate prospects for sustained control are good across much of the archipelago and medium term plans to transition to the pre-elimination phase are not unrealistic for P. falciparum. Endemicity in areas of Papua will clearly present the greatest challenge. This P. falciparum endemicity map allows malaria control agencies and their partners to comprehensively assess the region-specific prospects for reaching pre-elimination, monitor and evaluate the effectiveness of future strategies against this 2010 baseline

  2. Chromosome End Repair and Genome Stability in Plasmodium falciparum

    PubMed Central

    Calhoun, Susannah F.; Reed, Jake; Alexander, Noah; Mason, Christopher E.; Deitsch, Kirk W.

    2017-01-01

    ABSTRACT The human malaria parasite Plasmodium falciparum replicates within circulating red blood cells, where it is subjected to conditions that frequently cause DNA damage. The repair of DNA double-stranded breaks (DSBs) is thought to rely almost exclusively on homologous recombination (HR), due to a lack of efficient nonhomologous end joining. However, given that the parasite is haploid during this stage of its life cycle, the mechanisms involved in maintaining genome stability are poorly understood. Of particular interest are the subtelomeric regions of the chromosomes, which contain the majority of the multicopy variant antigen-encoding genes responsible for virulence and disease severity. Here, we show that parasites utilize a competitive balance between de novo telomere addition, also called “telomere healing,” and HR to stabilize chromosome ends. Products of both repair pathways were observed in response to DSBs that occurred spontaneously during routine in vitro culture or resulted from experimentally induced DSBs, demonstrating that both pathways are active in repairing DSBs within subtelomeric regions and that the pathway utilized was determined by the DNA sequences immediately surrounding the break. In combination, these two repair pathways enable parasites to efficiently maintain chromosome stability while also contributing to the generation of genetic diversity. PMID:28790200

  3. Molecular and structural insight into plasmodium falciparum RIO2 kinase.

    PubMed

    Chouhan, Devendra K; Sharon, Ashoke; Bal, Chandralata

    2013-02-01

    Among approximately 65 kinases of the malarial genome, RIO2 (right open reading frame) kinase belonging to the atypical class of kinase is unique because along with a kinase domain, it has a highly conserved N-terminal winged helix (wHTH) domain. The wHTH domain resembles the wing like domain found in DNA binding proteins and is situated near to the kinase domain. Ligand binding to this domain may reposition the kinase domain leading to inhibition of enzyme function and could be utilized as a novel allosteric site to design inhibitor. In the present study, we have generated a model of RIO2 kinase from Plasmodium falciparum utilizing multiple modeling, simulation approach. A novel putative DNA-binding site is identified for the first time in PfRIO2 kinase to understand the DNA binding events involving wHTH domain and flexible loop. Induced fit DNA docking followed by minimization, molecular dynamics simulation, energetic scoring and binding mode studies are used to reveal the structural basis of PfRIO2-ATP-DNA complex. Ser105 as a potential site of phosphorylation is revealed through the structural studies of ATP binding in PfRIO2. Overall the present study discloses the structural facets of unknown PfRIO2 complex and opens an avenue toward exploration of novel drug target.

  4. Plasmodium Drug Targets Outside the Genetic Control of the Parasite

    PubMed Central

    Sullivan, David J.

    2014-01-01

    Drug development often seeks to find “magic bullets” which target microbiologic proteins while not affecting host proteins. Paul Ehrlich tested methylene blue as an antimalarial but this dye was not superior to quinine. Many successful antimalarial therapies are “magic shotguns” which target many Plasmodium pathways with little interference in host metabolism. Two malaria drug classes, the 8-aminoquinolines and the artemisinins interact with cytochrome P450s and host iron protoporphyrin IX or iron, respectively, to generate toxic metabolites and/or radicals, which kill the parasite by interference with many proteins. The non 8-amino antimalarial quinolines like quinine or piperaquine bind heme to inhibit the process of heme crystallization, which results in multiple enzyme inhibition and membrane dysfunction. The quinolines and artemisinins are rapidly parasiticidal in contrast to metal chelators, which have a slower parasite clearance rate with higher drug concentrations. Iron chelators interfere with the artemisinins but otherwise represent a strategy of targeting multiple enzymes containing iron. Interest has been revived in antineoplastic drugs that target DNA metabolism as antimalarials. Specific drug targeting or investigation of the innate immunity directed to the more permeable trophozoite or schizont infected erythrocyte membrane has been under explored. Novel drug classes in the antimalarial development pipeline which either target multiple proteins or unchangeable cellular targets will slow the pace of drug resistance acquisition. PMID:22973888

  5. Recombination Hotspots and Population Structure in Plasmodium falciparum

    PubMed Central

    Mu, Jianbing; Duan, Junhui; McGee, Kate M; Joy, Deirdre A; McVean, Gilean A. T

    2005-01-01

    Understanding the influences of population structure, selection, and recombination on polymorphism and linkage disequilibrium (LD) is integral to mapping genes contributing to drug resistance or virulence in Plasmodium falciparum. The parasite's short generation time, coupled with a high cross-over rate, can cause rapid LD break-down. However, observations of low genetic variation have led to suggestions of effective clonality: selfing, population admixture, and selection may preserve LD in populations. Indeed, extensive LD surrounding drug-resistant genes has been observed, indicating that recombination and selection play important roles in shaping recent parasite genome evolution. These studies, however, provide only limited information about haplotype variation at local scales. Here we describe the first (to our knowledge) chromosome-wide SNP haplotype and population recombination maps for a global collection of malaria parasites, including the 3D7 isolate, whose genome has been sequenced previously. The parasites are clustered according to continental origin, but alternative groupings were obtained using SNPs at 37 putative transporter genes that are potentially under selection. Geographic isolation and highly variable multiple infection rates are the major factors affecting haplotype structure. Variation in effective recombination rates is high, both among populations and along the chromosome, with recombination hotspots conserved among populations at chromosome ends. This study supports the feasibility of genome-wide association studies in some parasite populations. PMID:16144426

  6. Watershed-based point sources permitting strategy and dynamic permit-trading analysis.

    PubMed

    Ning, Shu-Kuang; Chang, Ni-Bin

    2007-09-01

    Permit-trading policy in a total maximum daily load (TMDL) program may provide an additional avenue to produce environmental benefit, which closely approximates what would be achieved through a command and control approach, with relatively lower costs. One of the important considerations that might affect the effective trading mechanism is to determine the dynamic transaction prices and trading ratios in response to seasonal changes of assimilative capacity in the river. Advanced studies associated with multi-temporal spatially varied trading ratios among point sources to manage water pollution hold considerable potential for industries and policy makers alike. This paper aims to present an integrated simulation and optimization analysis for generating spatially varied trading ratios and evaluating seasonal transaction prices accordingly. It is designed to configure a permit-trading structure basin-wide and provide decision makers with a wealth of cost-effective, technology-oriented, risk-informed, and community-based management strategies. The case study, seamlessly integrating a QUAL2E simulation model with an optimal waste load allocation (WLA) scheme in a designated TMDL study area, helps understand the complexity of varying environmental resources values over space and time. The pollutants of concern in this region, which are eligible for trading, mainly include both biochemical oxygen demand (BOD) and ammonia-nitrogen (NH3-N). The problem solution, as a consequence, suggests an array of waste load reduction targets in a well-defined WLA scheme and exhibits a dynamic permit-trading framework among different sub-watersheds in the study area. Research findings gained in this paper may extend to any transferable dynamic-discharge permit (TDDP) program worldwide.

  7. Hanford Site Solid Waste Landfill permit application

    SciTech Connect

    Not Available

    1991-01-01

    Daily activities at the Hanford Site generate sanitary solid waste (nonhazardous and nonradioactive) that is transported to and permanently disposed of at the Hanford Site Solid Waste Landfill. This permit application describes the manner in which the solid Waste Landfill will be operated under Washington State Department of Ecology Minimum Functional Standards for Solid Waste Handling, Washington Administrative Code 173-304. The solid Waste Landfill is owned by the US Department of Energy -- Richland Operations Office and is used for disposal of solid waste generated at the US Department of Energy Hanford Site. The jurisdictional health department's permit application form for the Solid Waste Landfill is provided in Chapter 1.0. Chapter 2.0 provides a description of the Hanford Site and the Solid Waste Landfill and reviews applicable locational, general facility, and landfilling standards. Chapter 3.0 discusses the characteristics and quantity of the waste disposed of in the Solid Waste Landfill. Chapter 4.0 reviews the regional and site geology and hydrology and the groundwater and vadose zone quality beneath the landfill. Chapters 5.0, 6.0, and 7.0 contain the plan of operation, closure plan, and postclosure plan, respectively. The plan of operation describes the routine operation and maintenance of the Solid Waste Landfill, the environmental monitoring program, and the safety and emergency plans. Chapter 5.0 also addresses the operational cover, environmental controls, personnel requirements, inspections, recordkeeping, reporting, and site security. The postclosure plan describes requirements for final cover maintenance and environmental monitoring equipment following final closure. Chapter 8.0 discusses the integration of closure and postclosure activities between the Solid Waste Landfill and adjacent Nonradioactive Dangerous Waste Landfill. 76 refs., 48 figs, 15 tabs.

  8. Forest Products Industry Permitting Information

    EPA Pesticide Factsheets

    This document may be of assistance in applying the New Source Review (NSR) air permitting regulations including the Prevention of Significant Deterioration (PSD) requirements. This document is part of the NSR Policy and Guidance Database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  9. 40 CFR 72.81 - Permit modifications.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... compliance deadline extension; and (5) Changes in a thermal energy plan that result in any addition or... replacement of thermal energy. (c)(1) Permit modifications shall follow the permit issuance requirements...

  10. 40 CFR 72.81 - Permit modifications.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... compliance deadline extension; and (5) Changes in a thermal energy plan that result in any addition or... replacement of thermal energy. (c)(1) Permit modifications shall follow the permit issuance requirements...

  11. 40 CFR 72.81 - Permit modifications.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... compliance deadline extension; and (5) Changes in a thermal energy plan that result in any addition or... replacement of thermal energy. (c)(1) Permit modifications shall follow the permit issuance requirements...

  12. 78 FR 18420 - Special Permit Applications Actions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-26

    ... Pipeline and Hazardous Materials Safety Administration Special Permit Applications Actions AGENCY: Pipeline and Hazardous Materials Safety Administration (PHMSA), DOT. ACTION: Notice of actions on special... processing of, special permits from the Department of Transportation's Hazardous Material Regulations (49...

  13. 45 CFR 670.13 - Permit administration.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... authorize the permit holder to designate agents to act on behalf of the permit holder. (f) Marine mammals... mammal which is a marine mammal as defined by the Marine Mammal Protection Act of 1972 (16 U.S.C....

  14. Crossfire-Bonds Gravel Pit NPDES Permit

    EPA Pesticide Factsheets

    This is an NPDES permit and statement of basis. The Crossfire-Bonds Gravel Pit is authorized to discharge to Deer Canyon. Authorization for discharge is limited to only those outfalls specifically listed in the permit.

  15. 300 area TEDF permit compliance monitoring plan

    SciTech Connect

    BERNESKI, L.D.

    1998-11-20

    This document presents the permit compliance monitoring plan for the 300 Area Treated Effluent Disposal Facility (TEDF). It addresses the compliance with the National Pollutant Discharge Elimination System (NPDES) permit and Department of Natural Resources Aquatic Lands Sewer Outfall Lease.

  16. 9 CFR 104.3 - Permit application.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Internet at (http://www.aphis.usda.gov/animal_health/vet_biologics/vb_forms.shtml) and application for a... Internet at (http://www.aphis.usda.gov/animal_health/permits/vet_bio_permits.shtml). (b) The application...

  17. 9 CFR 104.3 - Permit application.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Internet at (http://www.aphis.usda.gov/animal_health/vet_biologics/vb_forms.shtml) and application for a... Internet at (http://www.aphis.usda.gov/animal_health/permits/vet_bio_permits.shtml). (b) The application...

  18. 9 CFR 104.3 - Permit application.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Internet at (http://www.aphis.usda.gov/animal_health/vet_biologics/vb_forms.shtml) and application for a... Internet at (http://www.aphis.usda.gov/animal_health/permits/vet_bio_permits.shtml). (b) The application...

  19. Riverview Estates Wastewater Treatment Facility NPDES Permit

    EPA Pesticide Factsheets

    Under National Pollutant Discharge Elimination System permit number ND-0031143, the Riverview Estates Wastewater Treatment Facility is authorized to discharge from its wastewater treatment facility in designated locations as described in the permit.

  20. Air Force Academy MS4 NPDES Permit

    EPA Pesticide Factsheets

    Under NPDES permit CO-R042007, the U.S. Air Force Academy is authorized to discharge from all municipal separate storm sewer system outfalls to the receiving waters specified in the permit in El Paso County, Colorado.

  1. 30 CFR 774.15 - Permit renewals.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... MINING AND RECLAMATION OPERATIONS PERMITS AND COAL EXPLORATION SYSTEMS UNDER REGULATORY PROGRAMS REVISION... comments or objections on the renewal, to each party to any informal conference held on the permit...

  2. 30 CFR 774.15 - Permit renewals.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... MINING AND RECLAMATION OPERATIONS PERMITS AND COAL EXPLORATION SYSTEMS UNDER REGULATORY PROGRAMS REVISION... comments or objections on the renewal, to each party to any informal conference held on the permit...

  3. Rosebud Casino and Hotel NPDES Proposed Permit

    EPA Pesticide Factsheets

    Indian Country, Minor Permit, proposed permit SD-0034584, Rosebud Casino and Hotel, South Dakota, is authorized to discharge from its wastewater treatment facility in Todd County, South Dakota to an unnamed drainageway(s) tributary to Rock Creek.

  4. 50 CFR 665.462 - Permits.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ..., DEPARTMENT OF COMMERCE (CONTINUED) FISHERIES IN THE WESTERN PACIFIC Mariana Archipelago Fisheries § 665.462... in any Mariana Archipelago precious coral permit area must have a permit issued under § 665.13. (b...

  5. Denver VA Hospital MS4 NPDES Permit

    EPA Pesticide Factsheets

    Under NPDES permit CO-R042008, the Veterans Administration (Medical Center, Denver Campus) is authorized to discharge from all municipal separate storm sewer system outfalls to the receiving waters specified in the permit in the City of Denver, Colorado.

  6. Fluidic, Inc Minor New Source Permit Application

    EPA Pesticide Factsheets

    Documents related to the Minor New Source Review Permit for Fluidic, Inc, Salt River Pima-Maricopa, near Scottsdale, AZ. This is an application for a Tribal Minor New Source Review (NSR) Permit that is currently under review.

  7. 27 CFR 447.41 - Permit requirement.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... WAR Permits § 447.41 Permit requirement. (a) Articles on the U.S. Munitions Import List will not be...), XVI, and XX; and (ii) Nuclear weapons strategic delivery systems and all specifically designed...

  8. Clean Air Act Permitting in Nevada

    EPA Pesticide Factsheets

    Information on Clean Air Act permitting in Nevada in Nevada and EPA's oversight. Clean Air Act permitting in Nevada is the shared responsibility of one state and two local agencies, along with EPA Region 9.

  9. EPA's Draft 2017 Construction General Permit (CGP)

    EPA Pesticide Factsheets

    EPA is preparing to reissue the Construction General Permit (CGP). The general permit, issued under the Clean Water Act's National Pollutant Discharge Elimination System, authorizes stormwater discharges from construction activities.

  10. Proteasome Inhibitors Block Development of Plasmodium spp.

    PubMed Central

    Gantt, Soren M.; Myung, Joon Mo; Briones, Marcelo R. S.; Li, Wei Dong; Corey, E. J.; Omura, Satoshi; Nussenzweig, Victor; Sinnis, Photini

    1998-01-01

    Proteasomes degrade most of the proteins inside eukaryotic cells, including transcription factors and regulators of cell cycle progression. Here we show that nanomolar concentrations of lactacystin, a specific irreversible inhibitor of the 20S proteasome, inhibit development of the exoerythrocytic and erythrocytic stages of the malaria parasite. Although lactacystin-treated Plasmodium berghei sporozoites are still invasive, their development into exoerythrocytic forms (EEF) is inhibited in vitro and in vivo. Erythrocytic schizogony of P. falciparum in vitro is also profoundly inhibited when drug treatment of the synchronized parasites is prior, but not subsequent, to the initiation of DNA synthesis, suggesting that the inhibitory effect of lactacystin is cell cycle specific. Lactacystin reduces P. berghei parasitemia in rats, but the therapeutic index is very low. Along with other studies showing that lactacystin inhibits stage-specific transformation in Trypanosoma and Entamoeba spp., these findings highlight the potential of proteasome inhibitors as drugs for the treatment of diseases caused by protozoan parasites. PMID:9756786

  11. Desferrioxamine suppresses Plasmodium falciparum in Aotus monkeys.

    PubMed

    Pollack, S; Rossan, R N; Davidson, D E; Escajadillo, A

    1987-02-01

    Clinical observation has suggested that iron deficiency may be protective in malaria, and we have found that desferrioxamine (DF), an iron-specific chelating agent, inhibited Plasmodium falciparum growth in vitro. It was difficult to be confident that DF would be effective in an intact animal, however, because continuous exposure to DF was required in vitro and, in vivo, DF is rapidly excreted. Also, the in vitro effect of DF was overcome by addition of iron to the culture and in vivo there are potentially high local iron concentrations when iron is absorbed from the diet or released from reticuloendothelial cells. We now show that DF given by constant subcutaneous infusion does suppress parasitemia in P. falciparum-infected Aotus monkeys.

  12. Gametocytogenesis : the puberty of Plasmodium falciparum

    PubMed Central

    Talman, Arthur M; Domarle, Olivier; McKenzie, F Ellis; Ariey, Frédéric; Robert, Vincent

    2004-01-01

    The protozoan Plasmodium falciparum has a complex life cycle in which asexual multiplication in the vertebrate host alternates with an obligate sexual reproduction in the anopheline mosquito. Apart from the apparent recombination advantages conferred by sex, P. falciparum has evolved a remarkable biology and adaptive phenotypes to insure its transmission despite the dangers of sex. This review mainly focuses on the current knowledge on commitment to sexual development, gametocytogenesis and the evolutionary significance of various aspects of gametocyte biology. It goes further than pure biology to look at the strategies used to improve successful transmission. Although gametocytes are inevitable stages for transmission and provide a potential target to fight malaria, they have received less attention than the pathogenic asexual stages. There is a need for research on gametocytes, which are a fascinating stage, responsible to a large extent for the success of P. falciparum. PMID:15253774

  13. Plasmodium malariae blood-stage dynamics.

    PubMed

    McKenzie, F E; Jeffery, G M; Collins, W E

    2001-06-01

    We examine the dynamics of parasitemia, fever, and gametocytemia reflected in the preintervention charts of 180 malaria-naive U.S. neurosyphilis patients infected with the USPHS strain of Plasmodium malariae, for malariatherapy, focusing on the 84 charts for which more than 35 days of patency preceded intervention and daily records encompassed 92% or more of the duration of each infection. Inoculum size did not influence any outcome variable. Fevers (days with temperatures > or =101 F) followed patterns that fit recognized brood structures more often than did our approximations of merogony cycles (via local peaks in parasitemia), but neither closely fit textbook quartan patterns. There were no discernable patterns in gametocytemia. Successful transmission to mosquitoes increased following subcurative drug treatment but did not depend on detectable gametocytemia.

  14. Inhibition of Plasmodium Liver Infection by Ivermectin.

    PubMed

    Mendes, António M; Albuquerque, Inês S; Machado, Marta; Pissarra, Joana; Meireles, Patrícia; Prudêncio, Miguel

    2017-02-01

    Avermectins are powerful endectocides with an established potential to reduce the incidence of vector-borne diseases. Here, we show that several avermectins inhibit the hepatic stage of Plasmodium infection in vitro Notably, ivermectin potently inhibits liver infection in vivo by impairing parasite development inside hepatocytes. This impairment has a clear impact on the ensuing blood stage parasitemia, reducing disease severity and enhancing host survival. Ivermectin has been proposed as a tool to control malaria transmission because of its effects on the mosquito vector. Our study extends the effect of ivermectin to the early stages of mammalian host infection and supports the inclusion of this multipurpose drug in malaria control strategies. Copyright © 2017 Mendes et al.

  15. Plasmodium falciparum drug resistance in Angola.

    PubMed

    Fançony, Cláudia; Brito, Miguel; Gil, Jose Pedro

    2016-02-09

    Facing chloroquine drug resistance, Angola promptly adopted artemisinin-based combination therapy as the first-line to treat malaria. Currently, the country aims to consolidate malaria control, while preparing for the elimination of the disease, along with others African countries in the region. However, the remarkable capacity of Plasmodium to develop drug resistance represents an alarming threat for those achievements. Herein, the available, but relatively scarce and dispersed, information on malaria drug resistance in Angola, is reviewed and discussed. The review aims to inform but also to encourage future research studies that monitor and update the information on anti-malarial drug efficacy and prevalence of molecular markers of drug resistance, key fields in the context and objectives of elimination.

  16. Wanted Plasmodium falciparum, dead or alive

    PubMed Central

    Sow, Fatimata; Nyonda, Mary; Bienvenu, Anne-Lise; Picot, Stephane

    2015-01-01

    Mechanisms of cell death in unicellular parasites have been subjects of debate for the last decade, with studies demonstrating evidence of apoptosis or non-apoptosis like mechanisms, including necrosis, and autophagy. Recent clarifications on the definition of regulated or accidental cell death by The Nomenclature Committee on Cell Death provides an opportunity to reanalyze some data, re-evaluate conclusions in the light of parasite diversity, and to propose alternative arguments in the context of malaria drug resistance, considering lack of really new drugs in the pipeline. Deciphering the mechanisms of death may help in detection of new drug targets and the design of innovative drugs. However, classifications have been evolving rapidly since initial description of “programmed cell death”, leading to some uncertainty as to whether Plasmodium cell death is accidental or regulated. PMID:28357297

  17. Development of vaccines for Plasmodium vivax malaria.

    PubMed

    Mueller, Ivo; Shakri, Ahmad Rushdi; Chitnis, Chetan E

    2015-12-22

    Plasmodium vivax continues to cause significant morbidity outside Africa with more than 50% of malaria cases in many parts of South and South-east Asia, Pacific islands, Central and South America being attributed to P. vivax infections. The unique biology of P. vivax, including its ability to form latent hypnozoites that emerge months to years later to cause blood stage infections, early appearance of gametocytes before clinical symptoms are apparent and a shorter development cycle in the vector makes elimination of P. vivax using standard control tools difficult. The availability of an effective vaccine that provides protection and prevents transmission would be a valuable tool in efforts to eliminate P. vivax. Here, we review the latest developments related to P. vivax malaria vaccines and discuss the challenges as well as directions toward the goal of developing highly efficacious vaccines against P. vivax malaria.

  18. Inhibition of Plasmodium Liver Infection by Ivermectin

    PubMed Central

    Mendes, António M.; Albuquerque, Inês S.; Machado, Marta; Pissarra, Joana; Meireles, Patrícia

    2016-01-01

    ABSTRACT Avermectins are powerful endectocides with an established potential to reduce the incidence of vector-borne diseases. Here, we show that several avermectins inhibit the hepatic stage of Plasmodium infection in vitro. Notably, ivermectin potently inhibits liver infection in vivo by impairing parasite development inside hepatocytes. This impairment has a clear impact on the ensuing blood stage parasitemia, reducing disease severity and enhancing host survival. Ivermectin has been proposed as a tool to control malaria transmission because of its effects on the mosquito vector. Our study extends the effect of ivermectin to the early stages of mammalian host infection and supports the inclusion of this multipurpose drug in malaria control strategies. PMID:27895022

  19. Epidemiology of Plasmodium vivax Malaria in Peru.

    PubMed

    Rosas-Aguirre, Angel; Gamboa, Dionicia; Manrique, Paulo; Conn, Jan E; Moreno, Marta; Lescano, Andres G; Sanchez, Juan F; Rodriguez, Hugo; Silva, Hermann; Llanos-Cuentas, Alejandro; Vinetz, Joseph M

    2016-12-28

    Malaria in Peru, dominated by Plasmodium vivax, remains a public health problem. The 1990s saw newly epidemic malaria emerge, primarily in the Loreto Department in the Amazon region, including areas near to Iquitos, the capital city, but sporadic malaria transmission also occurred in the 1990s-2000s in both north-coastal Peru and the gold mining regions of southeastern Peru. Although a Global Fund-supported intervention (PAMAFRO, 2005-2010) was temporally associated with a decrease of malaria transmission, from 2012 to the present, both P. vivax and Plasmodium falciparum malaria cases have rapidly increased. The Peruvian Ministry of Health continues to provide artemesinin-based combination therapy for microscopy-confirmed cases of P. falciparum and chloroquine-primaquine for P. vivax Malaria transmission continues in remote areas nonetheless, where the mobility of humans and parasites facilitates continued reintroduction outside of ongoing surveillance activities, which is critical to address for future malaria control and elimination efforts. Ongoing P. vivax research gaps in Peru include the following: identification of asymptomatic parasitemics, quantification of the contribution of patent and subpatent parasitemics to mosquito transmission, diagnosis of nonparasitemic hypnozoite carriers, and implementation of surveillance for potential emergence of chloroquine- and 8-aminoquinoline-resistant P. vivax Clinical trials of tafenoquine in Peru have been promising, and glucose-6-phosphate dehydrogenase deficiency in the region has not been observed to be a limitation to its use. Larger-scale challenges for P. vivax (and malaria in general) in Peru include logistical difficulties in accessing remote riverine populations, consequences of government policy and poverty trends, and obtaining international funding for malaria control and elimination. © The American Society of Tropical Medicine and Hygiene.

  20. Epidemiology of Plasmodium vivax Malaria in Peru

    PubMed Central

    Rosas-Aguirre, Angel; Gamboa, Dionicia; Manrique, Paulo; Conn, Jan E.; Moreno, Marta; Lescano, Andres G.; Sanchez, Juan F.; Rodriguez, Hugo; Silva, Hermann; Llanos-Cuentas, Alejandro; Vinetz, Joseph M.

    2016-01-01

    Malaria in Peru, dominated by Plasmodium vivax, remains a public health problem. The 1990s saw newly epidemic malaria emerge, primarily in the Loreto Department in the Amazon region, including areas near to Iquitos, the capital city, but sporadic malaria transmission also occurred in the 1990s–2000s in both north-coastal Peru and the gold mining regions of southeastern Peru. Although a Global Fund-supported intervention (PAMAFRO, 2005–2010) was temporally associated with a decrease of malaria transmission, from 2012 to the present, both P. vivax and Plasmodium falciparum malaria cases have rapidly increased. The Peruvian Ministry of Health continues to provide artemesinin-based combination therapy for microscopy-confirmed cases of P. falciparum and chloroquine–primaquine for P. vivax. Malaria transmission continues in remote areas nonetheless, where the mobility of humans and parasites facilitates continued reintroduction outside of ongoing surveillance activities, which is critical to address for future malaria control and elimination efforts. Ongoing P. vivax research gaps in Peru include the following: identification of asymptomatic parasitemics, quantification of the contribution of patent and subpatent parasitemics to mosquito transmission, diagnosis of nonparasitemic hypnozoite carriers, and implementation of surveillance for potential emergence of chloroquine- and 8-aminoquinoline-resistant P. vivax. Clinical trials of tafenoquine in Peru have been promising, and glucose-6-phosphate dehydrogenase deficiency in the region has not been observed to be a limitation to its use. Larger-scale challenges for P. vivax (and malaria in general) in Peru include logistical difficulties in accessing remote riverine populations, consequences of government policy and poverty trends, and obtaining international funding for malaria control and elimination. PMID:27799639

  1. Universal Features of Post-Transcriptional Gene Regulation Are Critical for Plasmodium Zygote Development

    PubMed Central

    Mair, Gunnar R.; Lasonder, Edwin; Garver, Lindsey S.; Franke-Fayard, Blandine M. D.; Carret, Céline K.; Wiegant, Joop C. A. G.; Dirks, Roeland W.; Dimopoulos, George; Janse, Chris J.; Waters, Andrew P.

    2010-01-01

    A universal feature of metazoan sexual development is the generation of oocyte P granules that withhold certain mRNA species from translation to provide coding potential for proteins during early post-fertilization development. Stabilisation of translationally quiescent mRNA pools in female Plasmodium gametocytes depends on the RNA helicase DOZI, but the molecular machinery involved in the silencing of transcripts in these protozoans is unknown. Using affinity purification coupled with mass-spectrometric analysis we identify a messenger ribonucleoprotein (mRNP) from Plasmodium berghei gametocytes defined by DOZI and the Sm-like factor CITH (homolog of worm CAR-I and fly Trailer Hitch). This mRNP includes 16 major factors, including proteins with homologies to components of metazoan P granules and archaeal proteins. Containing translationally silent transcripts, this mRNP integrates eIF4E and poly(A)-binding protein but excludes P body RNA degradation factors and translation-initiation promoting eIF4G. Gene deletion mutants of 2 core components of this mRNP (DOZI and CITH) are fertilization-competent, but zygotes fail to develop into ookinetes in a female gametocyte-mutant fashion. Through RNA-immunoprecipitation and global expression profiling of CITH-KO mutants we highlight CITH as a crucial repressor of maternally supplied mRNAs. Our data define Plasmodium P granules as an ancient mRNP whose protein core has remained evolutionarily conserved from single-cell organisms to germ cells of multi-cellular animals and stores translationally silent mRNAs that are critical for early post-fertilization development during the initial stages of mosquito infection. Therefore, translational repression may offer avenues as a target for the generation of transmission blocking strategies and contribute to limiting the spread of malaria. PMID:20169188

  2. Discordance in drug resistance-associated mutation patterns in marker genes of Plasmodium falciparum and Plasmodium knowlesi during coinfections.

    PubMed

    Tyagi, Rupesh K; Das, Manoj K; Singh, Shiv S; Sharma, Yagya D

    2013-05-01

    Human Plasmodium knowlesi infections have been reported from several South-East Asian countries, excluding India, but its drug susceptibility profile in mixed-infection cases remains unknown. The chloroquine resistance transporter (CRT) and dihydrofolate reductase (DHFR) genes of P. knowlesi and other Plasmodium species were sequenced from clinical isolates obtained from malaria patients living in the Andaman and Nicobar Islands, India. The merozoite surface protein-1 and 18S rRNA genes of P. knowlesi were also sequenced from these isolates. Among 445 samples analysed, only 53 of them had P. knowlesi-specific gene sequences. While 3 of the 53 cases (5.66%) had P. knowlesi monoinfection, the rest were coinfected with Plasmodium falciparum (86.79%, n = 46) or Plasmodium vivax (7.55%, n = 4), but none with Plasmodium malariae or Plasmodium ovale. There was discordance in the drug resistance-associated mutations among the coinfecting Plasmodium species. This is because the P. knowlesi isolates contained wild-type sequences, while P. falciparum isolates had mutations in the CRT and DHFR marker genes associated with a higher level of chloroquine and antifolate drug resistance, respectively. The mutation pattern indicates that the same patient, having a mixed infection, may be harbouring the drug-susceptible P. knowlesi parasite and a highly drug-resistant P. falciparum parasite. A larger human population in South-East Asia may be at risk of P. knowlesi infection than reported so far. The different drug susceptibility genotypes of P. knowlesi from its coinfecting Plasmodium species in mixed infections adds a new dimension to the malaria control programme, requiring formulation of an appropriate drug policy.

  3. 9 CFR 104.3 - Permit application.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Permit application. 104.3 Section 104... VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS PERMITS FOR BIOLOGICAL PRODUCTS § 104.3 Permit application. (a) Each person desiring to import a biological product shall make written...

  4. 45 CFR 670.13 - Permit administration.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... CONSERVATION OF ANTARCTIC ANIMALS AND PLANTS Permits § 670.13 Permit administration. (a) Issuance of the..., endangered species, and migratory birds. If the Director receives a permit application involving any native...)), any species which is an endangered or threatened species under the Endangered Species Act of 1973...

  5. 45 CFR 670.13 - Permit administration.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... CONSERVATION OF ANTARCTIC ANIMALS AND PLANTS Permits § 670.13 Permit administration. (a) Issuance of the..., endangered species, and migratory birds. If the Director receives a permit application involving any native...)), any species which is an endangered or threatened species under the Endangered Species Act of 1973...

  6. 45 CFR 670.13 - Permit administration.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... mammal which is a marine mammal as defined by the Marine Mammal Protection Act of 1972 (16 U.S.C. 1362(5... authorize the permit holder to designate agents to act on behalf of the permit holder. (f) Marine mammals... signed by the Director. Each permit may contain such terms and conditions as are consistent with the Act...

  7. 45 CFR 670.13 - Permit administration.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... mammal which is a marine mammal as defined by the Marine Mammal Protection Act of 1972 (16 U.S.C. 1362(5... authorize the permit holder to designate agents to act on behalf of the permit holder. (f) Marine mammals... signed by the Director. Each permit may contain such terms and conditions as are consistent with the Act...

  8. 40 CFR 71.5 - Permit applications.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... such construction or change in operation, the source must obtain a permit revision before commencing... initial phase II acid rain permits shall be submitted to the permitting authority by January 1, 1996 for... proposed change. To be found complete, an initial or renewal application must remit payment of fees owed...

  9. 40 CFR 70.5 - Permit applications.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... establish. Where an existing part 70 permit would prohibit such construction or change in operation, the.... (iv) Applications for initial phase II acid rain permits shall be submitted to the permitting... information only if it is related to the proposed change. Information required under paragraph (c) of this...

  10. 40 CFR 72.51 - Permit shield.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... REGULATION Acid Rain Permit Contents § 72.51 Permit shield. Each affected unit operated in accordance with the Acid Rain permit that governs the unit and that was issued in compliance with title IV of the Act... operating in compliance with the Acid Rain Program, except as provided in § 72.9(g)(6). ...

  11. 40 CFR 72.51 - Permit shield.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... REGULATION Acid Rain Permit Contents § 72.51 Permit shield. Each affected unit operated in accordance with the Acid Rain permit that governs the unit and that was issued in compliance with title IV of the Act... operating in compliance with the Acid Rain Program, except as provided in § 72.9(g)(6). ...

  12. 40 CFR 72.51 - Permit shield.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... REGULATION Acid Rain Permit Contents § 72.51 Permit shield. Each affected unit operated in accordance with the Acid Rain permit that governs the unit and that was issued in compliance with title IV of the Act... operating in compliance with the Acid Rain Program, except as provided in § 72.9(g)(6). ...

  13. 40 CFR 72.51 - Permit shield.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... REGULATION Acid Rain Permit Contents § 72.51 Permit shield. Each affected unit operated in accordance with the Acid Rain permit that governs the unit and that was issued in compliance with title IV of the Act... operating in compliance with the Acid Rain Program, except as provided in § 72.9(g)(6). ...

  14. 40 CFR 72.51 - Permit shield.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... REGULATION Acid Rain Permit Contents § 72.51 Permit shield. Each affected unit operated in accordance with the Acid Rain permit that governs the unit and that was issued in compliance with title IV of the Act... operating in compliance with the Acid Rain Program, except as provided in § 72.9(g)(6). ...

  15. 30 CFR 815.2 - Permitting information.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 3 2012-07-01 2012-07-01 false Permitting information. 815.2 Section 815.2... Permitting information. Notwithstanding cross-references in other parts which may be otherwise construed, part 772 establishes the notice and permit information requirements for coal exploration. ...

  16. 30 CFR 815.2 - Permitting information.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 3 2011-07-01 2011-07-01 false Permitting information. 815.2 Section 815.2... Permitting information. Notwithstanding cross-references in other parts which may be otherwise construed, part 772 establishes the notice and permit information requirements for coal exploration. ...

  17. 15 CFR 265.17 - Parking permits.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Parking permits. 265.17 Section 265.17... Parking permits. No person, except visitors, shall park a motor vehicle on the site without having a valid parking permit displayed on such motor vehicle in compliance with instructions of the issuing authority...

  18. 15 CFR 265.17 - Parking permits.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 15 Commerce and Foreign Trade 1 2011-01-01 2011-01-01 false Parking permits. 265.17 Section 265.17... Parking permits. No person, except visitors, shall park a motor vehicle on the site without having a valid parking permit displayed on such motor vehicle in compliance with instructions of the issuing authority...

  19. 40 CFR 172.5 - The permit.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Administrator may require that additional studies be conducted during the permit period to gather data to... Use Permit shall be issued when the Administrator determines that the conditions of section 5 of the... Administrator determines are warranted. (b) Duration. Permits will be effective for a specified period of time...

  20. 50 CFR 660.25 - Permits.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 50 Wildlife and Fisheries 13 2014-10-01 2014-10-01 false Permits. 660.25 Section 660.25 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE (CONTINUED) FISHERIES OFF WEST COAST STATES West Coast Groundfish Fisheries § 660.25 Permits. (a) General. Each of the permits...

  1. 30 CFR 774.13 - Permit revisions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 3 2010-07-01 2010-07-01 false Permit revisions. 774.13 Section 774.13 Mineral Resources OFFICE OF SURFACE MINING RECLAMATION AND ENFORCEMENT, DEPARTMENT OF THE INTERIOR SURFACE COAL...; RENEWAL; TRANSFER, ASSIGNMENT, OR SALE OF PERMIT RIGHTS; POST-PERMIT ISSUANCE REQUIREMENTS; AND OTHER...

  2. 30 CFR 774.15 - Permit renewals.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 3 2010-07-01 2010-07-01 false Permit renewals. 774.15 Section 774.15 Mineral Resources OFFICE OF SURFACE MINING RECLAMATION AND ENFORCEMENT, DEPARTMENT OF THE INTERIOR SURFACE COAL...; RENEWAL; TRANSFER, ASSIGNMENT, OR SALE OF PERMIT RIGHTS; POST-PERMIT ISSUANCE REQUIREMENTS; AND OTHER...

  3. 7 CFR 319.37-3 - Permits.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... laurel, nectarine, peach, plum, prune) from Canada and destined to Colorado, Michigan, New York... Protection and Quarantine, Permits, Registrations, Imports and Manuals, Permit Unit, 4700 River Road Unit 136..., Registrations, Imports and Manuals, Permit Unit, 4700 River Road Unit 136, Riverdale, Maryland 20737-1236,...

  4. 50 CFR 21.41 - Depredation permits.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... PLANTS (CONTINUED) MIGRATORY BIRD PERMITS Control of Depredating and Otherwise Injurious Birds § 21.41... permit is required before any person may take, possess, or transport migratory birds for depredation control purposes. No permit is required merely to scare or herd depredating migratory birds other than...

  5. 50 CFR 21.41 - Depredation permits.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... PLANTS (CONTINUED) MIGRATORY BIRD PERMITS Control of Depredating and Otherwise Injurious Birds § 21.41... permit is required before any person may take, possess, or transport migratory birds for depredation control purposes. No permit is required merely to scare or herd depredating migratory birds other than...

  6. 50 CFR 21.41 - Depredation permits.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... PLANTS (CONTINUED) MIGRATORY BIRD PERMITS Control of Depredating and Otherwise Injurious Birds § 21.41... permit is required before any person may take, possess, or transport migratory birds for depredation control purposes. No permit is required merely to scare or herd depredating migratory birds other than...

  7. 40 CFR 230.7 - General permits.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    .... (a) Conditions for the issuance of General permits. A General permit for a category of activities... restrictions on the discharge in § 230.10 and if the permitting authority determines that: (1) The activities... environment; (2) The activities in such category will have only minimal adverse effects when...

  8. 36 CFR 13.112 - Permit revocation.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 false Permit revocation. 13.112... NATIONAL PARK SYSTEM UNITS IN ALASKA Cabins General Provisions § 13.112 Permit revocation. (a) The... request for a hearing concerning the revocation, based on the cause listed above, of a permit or...

  9. 36 CFR 228.60 - Prospecting permits.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... conferred. On acquired National Forest lands, prospecting permits may be issued which grant the permittee... negotiated sale. (b) Limitations. Mineral material may be removed from lands under a prospecting permit only... prospecting permit may not cover more than 640 acres. No individual or group may have an interest at any one...

  10. 30 CFR 736.25 - Permit fees.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Resources OFFICE OF SURFACE MINING RECLAMATION AND ENFORCEMENT, DEPARTMENT OF THE INTERIOR PERMANENT...) Applicability. An applicant for a new permit to conduct surface coal mining operations under a Federal program... permit application, the lands contained in the permit application are declared unsuitable for...

  11. 5 CFR 734.202 - Permitted activities.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Permitted activities. 734.202 Section 734... (CONTINUED) POLITICAL ACTIVITIES OF FEDERAL EMPLOYEES Permitted Activities § 734.202 Permitted activities. Employees may take an active part in political activities, including political management and political...

  12. 32 CFR 855.9 - Permit renewal.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Defense Department of Defense (Continued) DEPARTMENT OF THE AIR FORCE AIRCRAFT CIVIL AIRCRAFT USE OF UNITED STATES AIR FORCE AIRFIELDS Civil Aircraft Landing Permits § 855.9 Permit renewal. When a landing permit expires, DD Forms 2401 and 2400 must be resubmitted for continued use of Air Force airfields. Note...

  13. 32 CFR 855.9 - Permit renewal.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Defense Department of Defense (Continued) DEPARTMENT OF THE AIR FORCE AIRCRAFT CIVIL AIRCRAFT USE OF UNITED STATES AIR FORCE AIRFIELDS Civil Aircraft Landing Permits § 855.9 Permit renewal. When a landing permit expires, DD Forms 2401 and 2400 must be resubmitted for continued use of Air Force airfields. Note...

  14. 32 CFR 855.9 - Permit renewal.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Defense Department of Defense (Continued) DEPARTMENT OF THE AIR FORCE AIRCRAFT CIVIL AIRCRAFT USE OF UNITED STATES AIR FORCE AIRFIELDS Civil Aircraft Landing Permits § 855.9 Permit renewal. When a landing permit expires, DD Forms 2401 and 2400 must be resubmitted for continued use of Air Force airfields. Note...

  15. 32 CFR 855.9 - Permit renewal.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Defense Department of Defense (Continued) DEPARTMENT OF THE AIR FORCE AIRCRAFT CIVIL AIRCRAFT USE OF UNITED STATES AIR FORCE AIRFIELDS Civil Aircraft Landing Permits § 855.9 Permit renewal. When a landing permit expires, DD Forms 2401 and 2400 must be resubmitted for continued use of Air Force airfields. Note...

  16. 32 CFR 855.9 - Permit renewal.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Defense Department of Defense (Continued) DEPARTMENT OF THE AIR FORCE AIRCRAFT CIVIL AIRCRAFT USE OF UNITED STATES AIR FORCE AIRFIELDS Civil Aircraft Landing Permits § 855.9 Permit renewal. When a landing permit expires, DD Forms 2401 and 2400 must be resubmitted for continued use of Air Force airfields. Note...

  17. 40 CFR 147.2926 - Permit transfers.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 22 2010-07-01 2010-07-01 false Permit transfers. 147.2926 Section 147.2926 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED... II Wells § 147.2926 Permit transfers. (a) Permits may be transferred to another permittee: (1) If...

  18. 40 CFR 147.2924 - Area permits.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 22 2010-07-01 2010-07-01 false Area permits. 147.2924 Section 147.2924 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED... II Wells § 147.2924 Area permits. (a) Area permits may be issued for more than one injection well...

  19. 40 CFR 147.2928 - Permit termination.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 23 2011-07-01 2011-07-01 false Permit termination. 147.2928 Section 147.2928 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS...-Class II Wells § 147.2928 Permit termination. (a) Permits may be terminated for the following...

  20. 40 CFR 147.2926 - Permit transfers.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 23 2011-07-01 2011-07-01 false Permit transfers. 147.2926 Section 147.2926 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED... II Wells § 147.2926 Permit transfers. (a) Permits may be transferred to another permittee: (1) If...