Biomedical subjects
Peter Blair
Publications and source records attributed to Peter Blair.
Conservation and developmental control of alternative splicing in maebl among malaria parasites.
Genes of malaria parasites and other unicellular organisms have larger exons with fewer and smaller introns than metaozoans. Such differences in gene structure are perceived to extend to simpler mechanisms for transcriptional control and mRNA processing. Instead, we discovered a surprisingly complex level of post-transcriptional mRNA processing in analysis of maebl transcripts in several Plasmodium species. Mechanisms for internal alternative cis-splicing and exon skipping were active in multiple life cycle stages to change exon structure in the deduced coding sequence (CDS). The major alternatively spliced transcript utilized a less favorable acceptor splice site, which shifted codon triplet usage to a different CDS with a hydrophilic C terminus, changing the canonical type I membrane MAEBL product to a predicted soluble isoform. We found that developmental control of the alternative splicing pattern was distinct from the canonical splicing pattern. Western blot analysis indicated that MAEBL expression was better correlated with the appearance of the canonical ORF1 transcript. Together these data reveal that RNA metabolism in unicellular eukaryotes like Plasmodium is more sophisticated than believed and may have a significant role regulating gene expression in Plasmodium.
Failure to thrive in the term and preterm infants of mothers depressed in the postnatal period: a population-based birth cohort study.
AIMS: To examine the relationship between failure to thrive in preterm and term infants and postnatal depression in their mothers. METHOD: In a whole population birth cohort of 12,391 infants (excluding those born after term or with major congenital abnormalities) failure to thrive over the first nine months was identified using a conditional weight gain criterion which identified the slowest-gaining 5%. Depression symptoms were recorded using the Edinburgh Postnatal Depression Scale (EPDS) at 18 and 32 weeks of pregnancy and at 8 weeks and 8 months after delivery. RESULTS: After the birth, high depression scores were significantly more common in the mothers of infants born preterm, and controlling for depression scores in pregnancy did not eliminate this association after the birth. Failure to thrive was identified in 4.5% of the children born at term (531/11718) and in 8.3% of those born preterm (56/673). The difference was highly significant (chi2 = 20.25 with 1 df, p < .0001). Using a conventional cut-off on the EPDS (score > 12) to identify mothers as 'depressed', the prevalence of failure to thrive in the term infants of mothers depressed at 8 weeks postpartum was 5.0%; in the remainder of the population (controls) it was 4.3%. In mothers depressed at 8 months the prevalence was 4.3% in both groups. The prevalence of failure to thrive in the preterm infants of mothers depressed at 8 weeks was 8.8% (7.0% in controls) and in those depressed at 8 months it was 12.3% (6.7% in controls). None of these differences in prevalence was statistically significant, and significant differences did not emerge from further analyses using more stringent criteria for depression. CONCLUSIONS: Preterm births are specifically associated with high maternal depression scores in the postpartum period, and with a higher prevalence of failure to thrive. High depression scores in the postpartum period are not themselves associated with a higher prevalence of failure to thrive, however, either in infants born at term or in those born preterm.
Antibodies against MAEBL ligand domains M1 and M2 inhibit sporozoite development in vitro.
MAEBL is a type 1 membrane protein that is implicated in the merozoite invasion of erythrocytes and sporozoite invasion of mosquito salivary glands. This apical organelle protein is structurally similar to the ebl erythrocyte binding proteins, such as EBA-175, except that the tandem ligand domains of MAEBL are similar to part of the extracellular domain of apical membrane antigen 1 and not the Duffy binding-like domain. Although midgut and salivary gland sporozoites are morphologically similar, salivary gland sporozoites undergo a period of new gene expression after infecting the salivary glands, display distinct phenotypic differences, and are more infectious for the mammalian host. The objectives of this project were to determine the molecular form of MAEBL in the infectious salivary gland sporozoites and whether the ligand has a role in the sporozoite development to exoerythrocytic stages in hepatocytes. We determined that MAEBL is newly expressed in salivary gland sporozoites and in a form distinct from what is present in the midgut sporozoites or present in erythrocytic stages. Both ligand domains (M1 and M2) were expressed as part of a full-length membrane form of MAEBL in the salivary gland sporozoites in contrast to the other stages that retain only the M2 ligand domain as part of the membrane form of the protein. Antisera developed against the cysteine-rich regions of the extracellular portion of MAEBL inhibited sporozoite development to exoerythrocytic forms in vitro. Together these data indicate that MAEBL has a role in this third developmental stage in the life cycle of the malaria parasite. Thus, MAEBL is another target for pre-erythrocytic-stage vaccine development against malaria parasites.