@article {1274,
	title = {Trypanosoma brucei Orc1 is essential for nuclear DNA replication and affects both VSG silencing and VSG switching.},
	journal = {Mol Microbiol},
	volume = {87},
	year = {2013},
	month = {2013 Jan},
	pages = {196-210},
	abstract = {<p>Binding of the Origin Recognition Complex (ORC) to replication origins is essential for initiation of DNA replication, but ORC has non-essential functions outside of DNA replication, including in heterochromatic gene silencing and telomere maintenance. Trypanosoma brucei, a protozoan parasite that causes human African trypanosomiasis, uses antigenic variation as a major virulence mechanism to evade the host\&$\#$39;s immune attack by expressing its major surface antigen, the Variant Surface Glycoprotein (VSG), in a monoallelic manner. An Orc1/Cdc6 homologue has been identified in T.\&thinsp;brucei, but its role in DNA replication has not been directly confirmed and its potential involvement in VSG repression or switching has not been thoroughly investigated. In this study, we show that TbOrc1 is essential for nuclear DNA replication in mammalian-infectious bloodstream and tsetse procyclic forms (BF and PF). Depletion of TbOrc1 resulted in derepression of telomere-linked silent VSGs in both BF and PF, and increased VSG switching particularly through the in situ transcriptional switching mechanism. TbOrc1 associates with telomere repeats but appears to do so independently of two known T.\&thinsp;brucei telomere proteins, TbRAP1 and TbTRF. We conclude that TbOrc1 has conserved functions in DNA replication and is also required to control telomere-linked VSG expression and VSG switching.</p>
},
	keywords = {Antigenic Variation, DNA Replication, DNA, Protozoan, Gene Silencing, Genes, Protozoan, Membrane Glycoproteins, Origin Recognition Complex, Promoter Regions, Genetic, Trypanosoma brucei brucei, Variant Surface Glycoproteins, Trypanosoma},
	issn = {1365-2958},
	doi = {10.1111/mmi.12093},
	author = {Benmerzouga, Imaan and Concepci{\'o}n-Acevedo, Jeniffer and Kim, Hee-Sook and Vandoros, Anthula V and Cross, George A M and Klingbeil, Michele M and Li, Bibo}
}
@article {383,
	title = {Unraveling the secrets of regulating mitochondrial DNA replication.},
	journal = {Mol Cell},
	volume = {35},
	year = {2009},
	month = {2009 Aug 28},
	pages = {398-400},
	abstract = {In this issue, Liu et al. (2009) report that maxicircle DNA copy number in trypanosomes is regulated by proteolysis of a helicase; the complex kinetoplast DNA system yields a clear view of how mitochondrial DNA replication can be regulated.},
	keywords = {Animals, DNA Helicases, DNA Replication, DNA, Kinetoplast, DNA, Mitochondrial, DNA, Protozoan, Gene Expression Regulation, Mutation, Peptide Hydrolases, Protozoan Proteins, Time Factors, Trypanosoma brucei brucei},
	issn = {1097-4164},
	doi = {10.1016/j.molcel.2009.08.007},
	author = {Klingbeil, Michele M and Shapiro, Theresa A}
}
@article {776,
	title = {Cryptosporidium parvum in children with diarrhea in Mulago Hospital, Kampala, Uganda.},
	journal = {Am J Trop Med Hyg},
	volume = {68},
	year = {2003},
	month = {2003 Jun},
	pages = {710-5},
	abstract = {A cross-sectional case-control study (ratio = 3:1) was conducted over a 15-month period to determine the prevalence and consequences of cryptosporidiosis in hospitalized diarrheic children (0-5 years old) at Mulago Hospital in Kampala, Uganda. Cryptosporidium parvum was detected and genotyped among 2,446 children of whom 1,779 (72.7\%) had diarrhea, and 667 (27.3\%) were age- and sex-matched controls. Of the 1,779 children with diarrhea, 532 (29.9\%) had persistent (> 14 days) diarrhea and 1,247 (70.1\%) had acute diarrhea. Overall, 444 (25.0\%) of the 1,779 children with diarrhea had C. parvum, compared with only 57 (8.5\%) of the 667 children without diarrhea (chi2 = 80.2, P < or = 0.0001). Within this group of infected children, 72.8\% were infected with genotype 1, 18.4\% with genotype 2, and 4.1\% with a mixture of both genotypes, and 4.1\% isolates were either unclassified or C. meleagridis. The prevalence was highest during the rainy months of April to June. Of the 532 children with persistent diarrhea, 166 (31.2\%) had C. parvum compared with 278 (22.3\%) of the 1,247 children with acute diarrhea (chi2 = 15.8, P < or = 0.0001). There was a significant association between C. parvum and malnutrition including stunting, being underweight, and wasting. Unfavorable outcome (death or failure to resolve within 14 days) occurred in 139 (72.8\%) of the 191 children with C. parvum, and in only 65.1\% of the 545 without (odds ratio = 1.117, 95\% confidence interval = 1.005-1.243, P = 0.05), Of the 191 children with C. parvum, 24 (12.6\%) died, compared with 34 (6.2\%) of the 545 without C. parvum (P = 0.005). Mortality rates were higher among children with severe dehydration and persistent diarrhea, and in stunted or underweight children infected with C. parvum. Among Ugandan children, cryptosporidiosis, which remains untreatable, is frequently associated with diarrhea and other serious and unfavorable consequences.},
	keywords = {Animals, Case-Control Studies, Child, Preschool, Cross-Sectional Studies, Cryptosporidiosis, Cryptosporidium parvum, Diarrhea, Diarrhea, Infantile, DNA, Protozoan, Female, Hospitalization, Humans, Infant, Infant, Newborn, Male, Nutrition Disorders, Polymerase Chain Reaction, Polymorphism, Restriction Fragment Length, Prevalence, Uganda},
	issn = {0002-9637},
	author = {Tumwine, James K and Kekitiinwa, Addy and Nabukeera, Nicolette and Akiyoshi, Donna E and Rich, Stephen M and Widmer, Giovanni and Feng, Xiaochuan and Tzipori, Saul}
}
@article {777,
	title = {Sequence diversity and evolution of the malaria vaccine candidate merozoite surface protein-1 (MSP-1) of Plasmodium falciparum.},
	journal = {Gene},
	volume = {304},
	year = {2003},
	month = {2003 Jan 30},
	pages = {65-75},
	abstract = {The merozoite surface protein-1 (MSP-1) of the malaria parasite Plasmodium falciparum is a major blood-stage antigen containing highly polymorphic tripeptide repeats in the domain known as block 2 and several non-repetitive domains that are essentially dimorphic. We have analyzed sequence variation in block 2 repeats and in non-repetitive block 17, as well as other polymorphisms within the MSP-1 gene, in clinical isolates of P. falciparum. Repeat haplotypes were defined as unique combinations of repeat motifs within block 2, whereas block 17 haplotypes were defined as unique combinations of single nucleotide replacements in this domain. A new block 17 haplotype, E-TNG-L, was found in one isolate from Vietnam. MSP-1 alleles, defined as unique combinations of haplotypes in blocks 2 and 17 and other polymorphisms within the molecule, were characterized in 60 isolates from hypoendemic Brazil and 37 isolates from mesoendemic Vietnam. Extensive diversity has been created in block 2 and elsewhere in the molecule, while maintaining significant linkage disequilibrium between polymorphisms across the non-telomeric MSP-1 locus separated by a map distance of more than 4 kb, suggesting that low meiotic recombination rates occur in both parasite populations. These results indicate a role for non-homologous recombination, such as strand-slippage mispairing during mitosis and gene conversion, in creating variation in a malarial antigen under strong diversifying selection.},
	keywords = {Alleles, Animals, Brazil, DNA, Protozoan, Evolution, Molecular, Genetic Variation, Haplotypes, Linkage Disequilibrium, Malaria Vaccines, Merozoite Surface Protein 1, Molecular Sequence Data, Plasmodium falciparum, Polymorphism, Single Nucleotide, Recombination, Genetic, Sequence Analysis, DNA, Tanzania, Thailand, Vietnam},
	issn = {0378-1119},
	author = {Ferreira, Marcelo U and Ribeiro, Weber L and Tonon, Angela P and Kawamoto, Fumihiko and Rich, Stephen M}
}
@article {780,
	title = {Ancient lineages of non-LTR retrotransposons in the primitive eukaryote, Giardia lamblia.},
	journal = {Mol Biol Evol},
	volume = {19},
	year = {2002},
	month = {2002 May},
	pages = {619-30},
	abstract = {Mobile elements that use reverse transcriptase to make new copies of themselves are found in all major lineages of eukaryotes. The non-long terminal repeat (non-LTR) retrotransposons have been suggested to be the oldest of these eukaryotic elements. Phylogenetic analysis of non-LTR elements suggests that they have predominantly undergone vertical transmission, as opposed to the frequent horizontal transmissions found for other mobile elements. One prediction of this vertical model of inheritance is that the oldest lineages of eukaryotes should exclusively harbor the oldest lineages of non-LTR retrotransposons. Here we characterize the non-LTR retrotransposons present in one of the most primitive eukaryotes, the diplomonad Giardia lamblia. Two families of elements were detected in the WB isolate of G. lamblia currently being used for the genome sequencing project. These elements are clearly distinct from all other previously described non-LTR lineages. Phylogenetic analysis indicates that these Genie elements (for Giardia early non-LTR insertion element) are among the oldest known lineages of non-LTR elements consistent with strict vertical descent. Genie elements encode a single open reading frame with a carboxyl terminal endonuclease domain. Genie 1 is site specific, as seven to eight copies are present in a single tandem array of a 771-bp repeat near the telomere of one chromosome. The function of this repeat is not known. One additional, highly divergent, element within the Genie 1 lineage is not located in this tandem array but is near a second telomere. Four different telomere addition sites could be identified within or near the Genie elements on each of these chromosomes. The second lineage of non-LTR elements, Genie 2, is composed of about 10 degenerate copies. Genie 2 elements do not appear to be site specific in their insertion. An unusual aspect of Genie 2 is that all copies contain inverted repeats up to 172 bp in length.},
	keywords = {Animals, Base Sequence, DNA, Protozoan, Evolution, Molecular, Giardia lamblia, Long Interspersed Nucleotide Elements, Molecular Sequence Data, Open Reading Frames, Phylogeny, Repetitive Sequences, Nucleic Acid, Sequence Homology, Nucleic Acid, Telomere},
	issn = {0737-4038},
	author = {Burke, William D and Malik, Harmit S and Rich, Stephen M and Eickbush, Thomas H}
}
@article {787,
	title = {Extensive polymorphism in Cryptosporidium parvum identified by multilocus microsatellite analysis.},
	journal = {Appl Environ Microbiol},
	volume = {66},
	year = {2000},
	month = {2000 Aug},
	pages = {3344-9},
	abstract = {Restriction fragment length polymorphism and DNA sequence analysis discern two main types of Cryptosporidium parvum. We present a survey of length polymorphism at several microsatellite loci for type 1 and type 2 isolates. A total of 14 microsatellite loci were identified from C. parvum DNA sequences deposited in public databases. All repeats were mono-, di-, and trinucleotide repeats of A, AT, and AAT, reflecting the high AT content of the C. parvum genome. Several of these loci showed significant length polymorphism, with as many as seven alleles identified for a single locus. Differences between alleles ranged from 1 to 27 bp. Karyotype analysis using probes flanking three microsatellites localized each marker to an individual chromosomal band, suggesting that these markers are single copy. In a sample of 19 isolates for which at least three microsatellites were typed, a majority of isolates displayed a unique multilocus fingerprint. Microsatellite analysis of isolates passaged between different host species identified genotypic changes consistent with changes in parasite populations.},
	keywords = {Animals, Base Sequence, Cattle, Cryptosporidiosis, Cryptosporidium parvum, DNA, Protozoan, Humans, Karyotyping, Mice, Mice, Knockout, Microsatellite Repeats, Molecular Sequence Data, Polymerase Chain Reaction, Polymorphism, Genetic, Sequence Analysis, DNA},
	issn = {0099-2240},
	author = {Feng, X and Rich, S M and Akiyoshi, D and Tumwine, J K and Kekitiinwa, A and Nabukeera, N and Tzipori, S and Widmer, G}
}
@article {790,
	title = {Evolution of Plasmodium and the recent origin of the world populations of Plasmodium falciparum.},
	journal = {Parassitologia},
	volume = {41},
	year = {1999},
	month = {1999 Sep},
	pages = {55-68},
	abstract = {We have investigated the evolution of Plasmodium parasites by analyzing DNA sequences of several genes. We reach the following conclusions: (1) The four human parasites, P. falciparum, P. malariae, P. ovale, and P. vivax are very remotely related to each other, so that their evolutionary divergence predates the origin of the hominids; several of these parasites became associated with the human lineage by lateral transfer from other hosts. (2) P. falciparum diverged from P. reichenowi about 8 million years ago, consistently with the time of divergence of the human lineage from the apes; a parsimonious inference is that falciparum has been associated with humans since the origin of the hominids. (3) P. malariae is genetically indistinguishable from P. brasilianum, a parasite of New World monkeys; and, similarly. (4) P. vivax is genetically indistinguishable from the New World monkey parasite P. simium. We infer in each of these two cases a very recent lateral transfer between the human and monkey hosts, and explore alternative hypotheses about the direction of the transfer. We have also investigated the population structure of P. falciparum by analyzing 10 genes and conclude that the extant world populations of this parasite have evolved from a single strain within the last several thousand years. The extensive polymorphisms observed in the highly repetitive central region of the Csp gene, as well as the apparently very divergent two classes of alleles at the Msa-1 gene, are consistent with this conclusion.},
	keywords = {Amino Acid Sequence, Animals, Base Sequence, DNA, Protozoan, Evolution, Molecular, Hominidae, Humans, Merozoite Surface Protein 1, Molecular Sequence Data, Plasmodium, Plasmodium falciparum, Polymorphism, Genetic, Sequence Alignment},
	issn = {0048-2951},
	author = {Ayala, F J and Escalante, A A and Rich, S M}
}
@article {793,
	title = {Malaria{\textquoteright}s Eve: evidence of a recent population bottleneck throughout the world populations of Plasmodium falciparum.},
	journal = {Proc Natl Acad Sci U S A},
	volume = {95},
	year = {1998},
	month = {1998 Apr 14},
	pages = {4425-30},
	abstract = {We have analyzed DNA sequences from world-wide geographic strains of Plasmodium falciparum and found a complete absence of synonymous DNA polymorphism at 10 gene loci. We hypothesize that all extant world populations of the parasite have recently derived (within several thousand years) from a single ancestral strain. The upper limit of the 95\% confidence interval for the time when this most recent common ancestor lived is between 24,500 and 57,500 years ago (depending on different estimates of the nucleotide substitution rate); the actual time is likely to be much more recent. The recent origin of the P. falciparum populations could have resulted from either a demographic sweep (P. falciparum has only recently spread throughout the world from a small geographically confined population) or a selective sweep (one strain favored by natural selection has recently replaced all others). The selective sweep hypothesis requires that populations of P. falciparum be effectively clonal, despite the obligate sexual stage of the parasite life cycle. A demographic sweep that started several thousand years ago is consistent with worldwide climatic changes ensuing the last glaciation, increased anthropophilia of the mosquito vectors, and the spread of agriculture. P. falciparum may have rapidly spread from its African tropical origins to the tropical and subtropical regions of the world only within the last 6,000 years. The recent origin of the world-wide P. falciparum populations may account for its virulence, as the most malignant of human malarial parasites.},
	keywords = {Africa, Animals, Asia, Climate, Demography, DNA, Protozoan, Evolution, Molecular, Genes, Protozoan, Humans, Life Cycle Stages, Malaria, Malaria, Falciparum, Netherlands, Phylogeny, Plasmodium, Plasmodium falciparum, Polymorphism, Genetic, South America, Tetrahydrofolate Dehydrogenase, Time},
	issn = {0027-8424},
	author = {Rich, S M and Licht, M C and Hudson, R R and Ayala, F J}
}
