651 research outputs found
The role of Plasmodium falciparum var genes in malaria in pregnancy
No full textSequestration of Plasmodium falciparum-infected erythrocytes in the placenta is responsible for many of the harmful effects of malaria during pregnancy. Sequestration occurs as a result of parasite adhesion molecules expressed on the surface of infected erythrocytes binding to host receptors in the placenta such as chondroitin sulphate A (CSA). Identification of the parasite ligand(s) responsible for placental adhesion could lead to the development of a vaccine to induce antibodies to prevent placental sequestration. Such a vaccine would reduce the maternal anaemia and infant deaths that are associated with malaria in pregnancy. Current research indicates that the parasite ligands mediating placental adhesion may be members of the P. falciparum variant surface antigen family PfEMP1, encoded by var genes. Two relatively well-conserved subfamilies of var genes have been implicated in placental adhesion, however, their role remains controversial. This review examines the evidence for and against the involvement of var genes in placental adhesion, and considers whether the most appropriate vaccine candidates have yet been identified
Letter from Arno B. Cammerer to Carl Hayden
No full textLetter from Arno B. Cammerer to Carl Hayden informing him of the removal of the dynamite from Grand Canyon Village to a point near Rowe Well
CR1 Knops blood group alleles are not associated with severe malaria in the Gambia
No full textThe Knops blood group antigen erythrocyte polymorphisms have been associated with reduced falciparum malaria-based in vitro rosette formation (putative malaria virulence factor). Having previously identified single-nucleotide polymorphisms (SNPs) in the human complement receptor 1 (CR1/CD35) gene underlying the Knops antithetical antigens Sl1/Sl2 and McC(a)/McC(b), we have now performed genotype comparisons to test associations between these two molecular variants and severe malaria in West African children living in the Gambia. While SNPs associated with Sl:2 and McC(b+) were equally distributed among malaria-infected children with severe malaria and control children not infected with malaria parasites, high allele frequencies for Sl 2 (0.800, 1,365/1,706) and McC(b) (0.385, 658/1706) were observed. Further, when compared to the Sl 1/McC(a) allele observed in all populations, the African Sl 2/McC(b) allele appears to have evolved as a result of positive selection (modified Nei-Gojobori test Ka-Ks/s.e.=1.77, P-valu
Behaviour of buried pipelines subjected to external loading.
No full textThe research presented in this Thesis was carried out at the University of Sheffield under
the supervision of Dr I. C. Pyrah and Dr W. F. Anderson, and Mr G. Leach at British Gas
Engineering Research Station (ERS). The research was financially supported by a British
Gas Research Scholarship and by the Overseas Research Students Awards Scheme.
The Author would like to express his sincere gratitude to his supervisors for their invaluable
help, guidance and encouragement during the development of the research.
The Author is also grateful to Dr S. R. Mi for his interest and assistance throughout the
research. Special thanks also go to Dr S. J. Wheeler for his supervision during the first year
of the research and sound advice in the initial stage of the work.
The Author would like to express his gratitude to all members of the geotechnics group at
the University of Sheffield for the useful discussions and comments. Special thanks and
appreciation are extended to the staff at the ERS, particularly Mr E. Middleton for
providing the data of the field tests and constructive comments.
The laboratory tests were performed at ERS Soils Laboratory for which the Author is
thankful to the laboratory staff. The Author must also thank British Gas for providing the
computer hardware and software for performing the numerical analyses, and the printing
facilities to produce the Thesis. Thanks also go to Mr D. Reay and Mr B. Bellwood at the
Gas Research Centre of British Gas for ensuring continuous financial support throughout
the award period.
Finally, the Author wishes to thank his family and friends for their endless support and
encouragement throughout the period of study in the UK. Without them, this Thesis may
never have been completed
Plasmodium falciparum:Rosettes do not protect merozoites from invasion-inhibitory antibodies
No full textRosetting is a parasite adhesion phenotype associated with severe malaria in African children. Why parasites form rosettes is unknown, although enhanced invasion or immune evasion have been suggested as possible functions. Previous work showed that rosetting does not enhance parasite invasion under standard in vitro conditions. We hypothesised that rosetting might promote invasion in the presence of host invasion-inhibitory antibodies, by allowing merozoites direct entry into the erythrocytes in the rosette and so minimising exposure to plasma antibodies. We therefore investigated whether rosetting influences invasion in the presence of invasion-inhibitory antibodies to MSP-1. We found no difference in invasion rates between isogenic rosetting and non-rosetting lines from two parasite strains, R29 and TM284, in the presence of MSP-1 antibodies (P = 0.62 and P = 0.63, Student's t test, TM284 and R29, respectively). These results do not support the hypothesis that rosettes protect merozoites from inhibitory antibodies during invasion. The biological function of rosetting remains unknown
Virulence of malaria is associated with differential expression of Plasmodium falciparum var gene subgroups in a case-control study
No full textPlasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is a major pathogenicity factor in falciparum malaria that mediates cytoadherence. PfEMP1 is encoded by approximately 60 var genes per haploid genome. Most var genes are grouped into 3 subgroups: A, B, and C. Evidence is emerging that the specific expression of these subgroups has clinical significance. Using field samples from children from Papua New Guinea with severe, mild, and asymptomatic malaria, we compared proportions of transcripts of var groups, as determined by quantitative polymerase chain reaction. We found a significantly higher proportion of var group B transcripts in children with clinical malaria (mild and severe), whereas a large proportion of var group C transcripts was found in asymptomatic children. These data from naturally infected children clearly show that major differences exist in var gene expression between parasites causing clinical disease and those causing asymptomatic infections. Furthermore, parasites forming rosettes showed a significant up-regulation of var group A transcripts
Erythrocyte complement receptor 1 (CR1) expression level is not associated with polymorphisms in the promoter or 3' untranslated regions of the CR1 gene
No full textComplement receptor 1 (CR1) expression level on erythrocytes is genetically determined and is associated with high (H) and low (L) expression alleles identified by a HindIII restriction fragment-length polymorphism (RFLP) in intron 27 of the CR1 gene. The L allele confers protection against severe malaria in Papua New Guinea, probably because erythrocytes with low CR1 expression, are less able to form pathogenic rosettes with Plasmodium falciparum-infected erythrocytes. Despite the biological importance of erythrocyte CR1, the genetic mutation controlling CR1 expression level remains unknown. We investigated the possibility that mutations in the upstream or 3' untranslated regions of the CR1 gene could control erythrocyte CR1 level. We identified several novel polymorphisms; however, the mutations did not segregate with erythrocyte CR1 expression level or the H and L alleles. Therefore, high and low erythrocyte CR1 levels cannot be explained by polymorphisms in transcriptional control elements in the upstream or 3' untranslated regions of the CR1 gene
Identification of Plasmodium falciparum var1CSA and var2CSA domains that bind IgM natural antibodies
No full textMalaria in pregnancy is responsible for maternal anaemia, low-birth-weight babies and infant deaths. Plasmodium falciparum infected erythrocytes are thought to cause placental pathology by adhering to host receptors such as chondroitin sulphate A (CSA). CSA binding infected erythrocytes also bind IgM natural antibodies from normal human serum, a process that may facilitate placental adhesion or promote immune evasion. The parasite ligands that mediate placental adhesion are thought to be members of the variant erythrocyte surface antigen family P. falciparum erythrocyte membrane protein 1 (PfEMP1), encoded by the var genes. Two var gene sub-families, var1CSA and var2CSA, have been identified as parasite CSA binding ligands and are leading candidates for a vaccine to prevent pregnancy-associated malaria. We investigated whether these two var gene subfamilies implicated in CSA binding are also the molecules responsible for IgM natural antibody binding. By heterologous expression of domains in COS-7 cells, we found that both var1CSA and var2CSA PfEMP1 variants bound IgM, and in both cases the binding region was a DBL epsilon domain occurring proximal to the membrane. None of the domains from a control non-IgM-binding parasite (R29) bound IgM when expressed in COS-7 cells. These results show that PfEMP1 is a parasite ligand for non-immune IgM and are the first demonstration of a specific adhesive function for PfEMP1 epsilon type domains
Identification of the Kna/Knb polymorphism and a method for Knops genotyping
No full textDNA mutations resulting in the McCoy and Swain-Langley polymorphisms have been identified on complement receptor 1 (CR1)-a ligand for rosetting of Plasmodium falciparum-infected RBCs. The molecular identification of the Kna/Knb polymorphism was sought to develop a genotyping method for use in the study of the Knops blood group and malaria
Holopedium atlanticum Rowe, Adamowicz & Hebert, 2007, n. sp.
No full text<i>Holopedium atlanticum</i> n. sp. <p> <b>Synonymy.</b> Individuals from North America previously identified as <i>H. amazonicum</i> should properly be identified as <i>H. atlanticum</i>.</p> <p>Birge (1918): 693, Fig. 1061b</p> <p>Pennak (1953): 364–365, Fig. 227d</p> <p>Brooks (1959): 603, Fig. 27.13</p> <p>Pennak (1978): 365–366, Fig. 254d</p> <p>Pennak (1989): 386–387, Fig. 12d</p> <p>Korovchinsky (1992): 77–78, Figs. 371–373, 375, 377</p> <p> <b>Etymology.</b> <i>atlanticum</i> refers to the distribution of this species in lakes along the eastern Atlantic seaboard of North America.</p> <p> <b>Type locality.</b> Moosehead Lake, Maine (45.633º N, 69.683º W). On Hwy ME-6, in close proximity to the town of Moosehead.</p> <p> <b>Type specimens. Holotype</b>: an ovigerous female in ethanol deposited in the CMN under accession number CMNC 2007-0741 (collection date September 2, 1993).</p> <p> <b>Paratypes</b>: 10 ovigerous females, preserved in ethanol, deposited in the CMN under accession number CMNC 2007-0742 (collection date September 2, 1993).</p> <p> <b>Material examined.</b> Other habitats with <i>H. atlanticum</i> are listed in Appendix A.</p> <p> <b>Morphological description.</b> FEMALE. Representative photomicrographs are shown in Fig. 10. The jelly coat is of the A type, in which the anterior jelly curl arches toward the anterior portion of the jelly coat, and the lateral lobes are undivided (see Montvilo <i>et al.</i> 1987).</p> <p>Adult carapace lengths range from 0.44–1.01 mm (mean 0.73 mm), while carapace heights range from 0.30–1.06 mm (mean 0.74 mm). The H/L ratios range from 0.68–1.37 (mean 1.00). The ventral carapace margin is ordinarily spinulated posteriorly, but smooth anteriorly. Individuals lacking spinulation along the entire ventral valve margin were encountered.</p> <p> Anal spine number ranges from 6–11 (mean 8.35). <i>Holopedium atlanticum</i> lacks a basal spine on each postabdominal claw. Each claw ordinarily has a row of denticles running laterally from the base of the claw to its midpoint, although individuals were observed that lacked claw denticulation.</p> <p> MALE. Males have been found in small numbers in collections from sites in North Carolina in May and June; however, they are typically found in the highest abundance in the autumn (Hegyi 1973). Males of this species were not examined in this study, and thus detailed morphometrics cannot be presented. However, Hegyi (1973) presented a photograph and brief description of a male <i>Holopedium</i> which, based on distributional data, is probably <i>H. atlanticum</i>.</p> <p> <b>Differential diagnosis.</b> Although <i>H. atlanticum</i> is morphologically indistinguishable from <i>H. amazonicum</i>, these two species have allopatric distributions reducing the likelihood of genetic exchange (Fig. 4 c,e). <i>Holopedium atlanticum</i> is distinguished from <i>H. acidophilum</i> by the larger size and greater number of anal spines of the latter species. It differs from members of the <i>H. gibberum</i> complex by the absence of a basal spine on either postabdominal claw. <i>Holopedium atlanticum</i> can be biochemically distinguished from <i>H. acidophilum</i> at the <i>Pgm</i> locus, as <i>H. atlanticum</i> produces an enzyme which migrates slower than that of the latter species. COI mtDNA sequence divergence between <i>H. atlanticum</i> and <i>H. amazonicum</i> averages 12.3%, while the divergence between <i>H. atlanticum</i> and <i>H. acidophilum</i> averages 10.6%. Based on current evidence, individuals showing less than 4.8% divergence from a representative COI mtDNA sequence (GenBank AF 245353) belong to <i>H. atlanticum</i>.</p> <p> <b>Distribution.</b> <i>H. atlanticum</i> was found along the Atlantic coast of North America from New Brunswick and Maine south to Florida, (Fig. 4 c). Populations of <i>Holopedium</i> reported by other workers from the southeastern United States are likely also <i>H. atlanticum</i>. Its range overlaps that of <i>H. glacialis</i> in the northeastern USA and southern New Brunswick, where these species occur sympatrically without hybridization. The extent of range overlap with <i>H. glacialis</i> is unresolved by this study, but several workers have identified <i>H. atlanticum</i> (formerly <i>H. amazonicum</i>) as far north as New Brunswick and <i>H. glacialis</i> (formerly <i>H. gibberum</i>) as far south as Tennessee and possibly South Carolina (Coker 1938, Bunting 1970, Hebert & Finston 1997).</p> <p> <b>Breeding system.</b> Males were not detected in populations collected throughout the summer in this study. In a life history study spanning two years, males were most abundant in early spring and late autumn (Hegyi 1973). In some southern localities, populations persist throughout the winter. Due to the existence of males, this species likely reproduces by cyclic parthenogenesis, but there is very little allozyme variation, suggesting that either this species engages in sexual reproduction infrequently or that variation has been trimmed due to a population bottleneck.</p> <p> A note regarding <i>H. groenlandicum</i> and <i>H. ramasarmii</i></p> <p> While individuals from Greenland were not included in the present study, the recently described species <i>H. groenlandicum</i> (Korovchinsky 2005) can purportedly be distinguished from <i>H. gibberum</i> by its “dorsally low shell and jelly envelope, shorter row of valve marginal spinules which are subdivided in groups, and comparatively longer postabdominal claws.” However, shell shape is a highly variable feature, which may be environmentally influenced (Røen 1962) and can depend upon the locality and presence/absence of fish (CLR pers. obs). The body lengths (0.74 to 1.09mm, mean 1.45mm), carapace heights (0.80 to 1.57mm, mean 1.19mm), and H:L ratios (0.641 to 1.000, mean 0.814) found by Korovchinsky (2005) in the Greenland populations fall within the ranges of values found in <i>H. gibberum</i> and <i>H. glacialis</i> populations in the present study (the preceding ranges and means that were not published in Korovchinsky [2005] were provided to CLR by that author). Jelly coat shape may be influenced by preservation (CLR, pers. obs), and therefore this trait may not be a good feature for diagnosing species. Moreover, the degree of carapace margin spinulation is also a highly variable trait within species (present study), although the discontinuous nature of the spinulation in the Greenland populations is noteworthy. Finally, the length of the postabdominal claws reported by Korovchinsky (2005, his Figure 1) is within the range of claw lengths observed for the <i>H. gibberum</i> s.s. populations studied here. Furthermore, the fact that we detected closely related lineages of <i>H. gibberum</i> s.s. in both northern Europe and North America suggests that similar lineages may be found in intervening arctic areas.</p> <p> Individuals from India were also not included in the present study. Consideration of the differences between either of the species in the <i>H. gibberum</i> complex and <i>H. ramasarmii</i> (Rao <i>et al.</i> 1998) is not currently possible due to the poor description of the latter species, lacking in detail. Korovchinsky (2004) labeled this species <i>incertae sedis</i>.</p> <p> We suggest that genetic evidence is required to determine if <i>H. groenlandicum</i> and <i>H. ramasarmii</i> are distinct species or if they are synonymous with described taxa.</p>Published as part of <i>Rowe, Chad L., Adamowicz, Sarah J. & Hebert, Paul D. N., 2007, Three new cryptic species of the freshwater zooplankton genus Holopedium (Crustacea: Branchiopoda: Ctenopoda), revealed by genetic methods, pp. 1-49 in Zootaxa 1656</i> on pages 34-36, DOI: <a href="http://zenodo.org/record/179852">10.5281/zenodo.179852</a>
- …
