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1.  Plasmodium falciparum: Nitric Oxide Modulates Heme Speciation in Isolated Food Vacuoles 
Experimental parasitology  2010;127(1):1-8.
Nitric oxide (NO) and NO-derived reactive nitrogen species (RNS) are present in the food vacuole (FV) of P. falciparum trophozoites. The product of PFL1555w, a putative cytochrome b5, localizes in the FV membrane, similar to what was previously observed for the product of PF13_0353, a putative cytochrome b5 reductase. These two gene products may contribute to NO generation by denitrification chemistry from nitrate and/or nitrite present in the erythrocyte cytosol. The possible coordination of NO to heme species present in the food vacuole was probed by resonance Raman spectroscopy. The spectroscopic data revealed that in situ generated NO interacts with heme inside the intact FVs to form ferrous heme nitrosyl complexes that influence intra-vacuolar heme solubility. The formation of heme nitrosyl complexes within the FV is a previously unrecognized factor that could affect the equilibrium between soluble and crystallized heme within the FV in vivo.
doi:10.1016/j.exppara.2010.05.006
PMCID: PMC2948613  PMID: 20493843
Protozoa; Plasmodium falciparum; Malaria; Nitric oxide; Heme; Hemozoin; Antimalarials
2.  Comparative and demographic analysis of orangutan genomes 
Locke, Devin P. | Hillier, LaDeana W. | Warren, Wesley C. | Worley, Kim C. | Nazareth, Lynne V. | Muzny, Donna M. | Yang, Shiaw-Pyng | Wang, Zhengyuan | Chinwalla, Asif T. | Minx, Pat | Mitreva, Makedonka | Cook, Lisa | Delehaunty, Kim D. | Fronick, Catrina | Schmidt, Heather | Fulton, Lucinda A. | Fulton, Robert S. | Nelson, Joanne O. | Magrini, Vincent | Pohl, Craig | Graves, Tina A. | Markovic, Chris | Cree, Andy | Dinh, Huyen H. | Hume, Jennifer | Kovar, Christie L. | Fowler, Gerald R. | Lunter, Gerton | Meader, Stephen | Heger, Andreas | Ponting, Chris P. | Marques-Bonet, Tomas | Alkan, Can | Chen, Lin | Cheng, Ze | Kidd, Jeffrey M. | Eichler, Evan E. | White, Simon | Searle, Stephen | Vilella, Albert J. | Chen, Yuan | Flicek, Paul | Ma, Jian | Raney, Brian | Suh, Bernard | Burhans, Richard | Herrero, Javier | Haussler, David | Faria, Rui | Fernando, Olga | Darré, Fleur | Farré, Domènec | Gazave, Elodie | Oliva, Meritxell | Navarro, Arcadi | Roberto, Roberta | Capozzi, Oronzo | Archidiacono, Nicoletta | Valle, Giuliano Della | Purgato, Stefania | Rocchi, Mariano | Konkel, Miriam K. | Walker, Jerilyn A. | Ullmer, Brygg | Batzer, Mark A. | Smit, Arian F. A. | Hubley, Robert | Casola, Claudio | Schrider, Daniel R. | Hahn, Matthew W. | Quesada, Victor | Puente, Xose S. | Ordoñez, Gonzalo R. | López-Otín, Carlos | Vinar, Tomas | Brejova, Brona | Ratan, Aakrosh | Harris, Robert S. | Miller, Webb | Kosiol, Carolin | Lawson, Heather A. | Taliwal, Vikas | Martins, André L. | Siepel, Adam | RoyChoudhury, Arindam | Ma, Xin | Degenhardt, Jeremiah | Bustamante, Carlos D. | Gutenkunst, Ryan N. | Mailund, Thomas | Dutheil, Julien Y. | Hobolth, Asger | Schierup, Mikkel H. | Chemnick, Leona | Ryder, Oliver A. | Yoshinaga, Yuko | de Jong, Pieter J. | Weinstock, George M. | Rogers, Jeffrey | Mardis, Elaine R. | Gibbs, Richard A. | Wilson, Richard K.
Nature  2011;469(7331):529-533.
“Orangutan” is derived from the Malay term “man of the forest” and aptly describes the Southeast Asian great apes native to Sumatra and Borneo. The orangutan species, Pongo abelii (Sumatran) and Pongo pygmaeus (Bornean), are the most phylogenetically distant great apes from humans, thereby providing an informative perspective on hominid evolution. Here we present a Sumatran orangutan draft genome assembly and short read sequence data from five Sumatran and five Bornean orangutan genomes. Our analyses reveal that, compared to other primates, the orangutan genome has many unique features. Structural evolution of the orangutan genome has proceeded much more slowly than other great apes, evidenced by fewer rearrangements, less segmental duplication, a lower rate of gene family turnover and surprisingly quiescent Alu repeats, which have played a major role in restructuring other primate genomes. We also describe the first primate polymorphic neocentromere, found in both Pongo species, emphasizing the gradual evolution of orangutan genome structure. Orangutans have extremely low energy usage for a eutherian mammal1, far lower than their hominid relatives. Adding their genome to the repertoire of sequenced primates illuminates new signals of positive selection in several pathways including glycolipid metabolism. From the population perspective, both Pongo species are deeply diverse; however, Sumatran individuals possess greater diversity than their Bornean counterparts, and more species-specific variation. Our estimate of Bornean/Sumatran speciation time, 400k years ago (ya), is more recent than most previous studies and underscores the complexity of the orangutan speciation process. Despite a smaller modern census population size, the Sumatran effective population size (Ne) expanded exponentially relative to the ancestral Ne after the split, while Bornean Ne declined over the same period. Overall, the resources and analyses presented here offer new opportunities in evolutionary genomics, insights into hominid biology, and an extensive database of variation for conservation efforts.
doi:10.1038/nature09687
PMCID: PMC3060778  PMID: 21270892
3.  Susceptibility of Anopheles gambiae and Anopheles stephensi to tropical isolates of Plasmodium falciparum 
Malaria Journal  2007;6:139.
Background
The susceptibility of anopheline mosquito species to Plasmodium infection is known to be variable with some mosquitoes more permissive to infection than others. Little work, however, has been carried out investigating the susceptibility of major malaria vectors to geographically diverse tropical isolates of Plasmodium falciparum aside from examining the possibility of infection extending its range from tropical regions into more temperate zones.
Methods
This study investigates the susceptibility of two major tropical mosquito hosts (Anopheles gambiae and Anopheles stephensi) to P. falciparum isolates of different tropical geographical origins. Cultured parasite isolates were fed via membrane feeders simultaneously to both mosquito species and the resulting mosquito infections were compared.
Results
Infection prevalence was variable with African parasites equally successful in both mosquito species, Thai parasites significantly more successful in An. stephensi, and PNG parasites largely unsuccessful in both species.
Conclusion
Infection success of P. falciparum was variable according to geographical origin of both the parasite and the mosquito. Data presented raise the possibility that local adaptation of tropical parasites and mosquitoes has a role to play in limiting gene flow between allopatric parasite populations.
doi:10.1186/1475-2875-6-139
PMCID: PMC2148056  PMID: 17958900
4.  Complete Genome Sequence of Rickettsia typhi and Comparison with Sequences of Other Rickettsiae 
Journal of Bacteriology  2004;186(17):5842-5855.
Rickettsia typhi, the causative agent of murine typhus, is an obligate intracellular bacterium with a life cycle involving both vertebrate and invertebrate hosts. Here we present the complete genome sequence of R. typhi (1,111,496 bp) and compare it to the two published rickettsial genome sequences: R. prowazekii and R. conorii. We identified 877 genes in R. typhi encoding 3 rRNAs, 33 tRNAs, 3 noncoding RNAs, and 838 proteins, 3 of which are frameshifts. In addition, we discovered more than 40 pseudogenes, including the entire cytochrome c oxidase system. The three rickettsial genomes share 775 genes: 23 are found only in R. prowazekii and R. typhi, 15 are found only in R. conorii and R. typhi, and 24 are unique to R. typhi. Although most of the genes are colinear, there is a 35-kb inversion in gene order, which is close to the replication terminus, in R. typhi, compared to R. prowazekii and R. conorii. In addition, we found a 124-kb R. typhi-specific inversion, starting 19 kb from the origin of replication, compared to R. prowazekii and R. conorii. Inversions in this region are also seen in the unpublished genome sequences of R. sibirica and R. rickettsii, indicating that this region is a hot spot for rearrangements. Genome comparisons also revealed a 12-kb insertion in the R. prowazekii genome, relative to R. typhi and R. conorii, which appears to have occurred after the typhus (R. prowazekii and R. typhi) and spotted fever (R. conorii) groups diverged. The three-way comparison allowed further in silico analysis of the SpoT split genes, leading us to propose that the stringent response system is still functional in these rickettsiae.
doi:10.1128/JB.186.17.5842-5855.2004
PMCID: PMC516817  PMID: 15317790

Results 1-4 (4)