ABO blood group phenotypes influence parity specific immunity to Plasmodium falciparum malaria in Malawian women

Background: Blood group O has been significantly associated with increased placental malaria infection in primiparae and reduced risk of infection in multiparae in the Gambia, an area with markedly seasonal malaria transmission. This study analyses the association between ABO blood group phenotypes in relation to placental malaria pathology and birth outcomes in southern Malawi, an area with perennial malaria transmission. Methods: A cross- sectional study of 647 mother/ child pairs delivering in Montfort Hospital, Chikwawa District between February- June 2004 and January- July 2005 was undertaken. Maternal peripheral and cord blood samples were obtained at delivery. Placental tissue was obtained and malaria histology classified as active, past or no malaria infection. Birth anthropometry was recorded. ABO blood group was measured by agglutination. Results: In primiparae, blood group O was significantly associated with increased risk of active placental infection ( OR 2.18, 95% CI 1.15 - 4.6, p = 0.02) and an increased foetal- placental weight ratio compared to non- O phenotypes ( 5.68 versus 5.45, p = 0.03) In multiparae blood group O was significantly associated with less frequent active placental infection ( OR 0.59, 95% CI 0.36 - 0.98, p = 0.04), and a higher newborn ponderal index compared to non- O phenotypes ( 2.65 versus 2.55, p = 0.007). In multivariate regression parity was independently associated with increased risk of placental malaria ( active andpast infection) in primiparae with blood group O ( p = 0.034) and reduced risk in multiparae with the same phenotype ( p = 0.015). Conclusion: Parity related susceptibility to placental malaria is associated with the mothers ABO phenotype. This interaction influences foetal and placental growth and could be an important modifying factor for pregnancy outcomes. The biological explanation could relate to sialic acid dependent placental membrane differences which vary with ABO blood group

Investigating the regulation and functioning of RNT-1 and BRO-1 in C. elegans

The stem cell-like seam cells of the nematode, Caenorhabditis elegans, represent a tractable and powerful model for studying stem cell biology. rnt-1, the worm homologue of the mammalian RUNX family of transcription factors, together with the CBFβ homologue bro-1, is essential for the proliferation of the seam cells. RUNX genes and CBFβ are important regulators of stem cell development in mammals, and are associated with a variety of cancers. The worm seam cell model offers an opportunity to examine how these genes function in stem cell biology. The aim of this work was to shed light on the genetic network in which bro-1 and rnt-1 function, and to reveal the identity of regulators of these genes as well the downstream targets of the bro-1/rnt-1 pathway. Here, a number of genes that interact with bro-1 and rnt-1 have been identified. ELT-1, a GATA transcription factor, is shown to be a direct regulator of bro-1. Findings which show that the MEIS gene unc-62 acts upstream of bro-1/rnt-1 and regulates the symmetry of seam cell divisions are also presented. The seam cell marker, scm::gfp, is widely used in studies of the seam cells; here the results of an investigation into its identity and functional links are described. In addition, the mechanism underlying spatial regulation of rnt-1 was examined; this led to the discovery of distinct tissue-specific enhancer modules within an intron of this gene. Finally, interactions between pal-1 and bro-1/rnt-1 are reported and described. Together, these findings provide a framework for furthering our understanding of the mechanisms and genes associated with the functioning of bro-1 and rnt-1 in the worm.EThOS - Electronic Theses Online ServiceGBUnited Kingdo