4,921 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
Psychometric properties of the new patients’ expectations questionnaire
No full textThe authors explore the development of the Patients’ Expectations Questionnaire (PEQ) and examination of psychometric characteristics it encompasses by reviewing surveys of primary care and hospital outpatients before and after their clinic visit. Three scales were developed for Pre-visit Ideal and Realistic expectations, and Post-visit Experiences (met expectations), based on literature review, semi-structured interviews, and subsequently piloted and refined. Patients completed the questionnaire about their ideal and realistic expectations before they saw the doctor, and were asked if their expectations had been met afterwards. The results show the scales met acceptability criteria for reliability (Cronbach’s alphas exceeded ? 0.70), administration mode (interview and self-completion), and sample type (general practice and hospital). Split-half reliability was also acceptable. Adjusted odds ratios showed that post-visit experiences (met expectations), followed by feelings of control in life, and age, were the most powerful independent predictors of overall patient satisfaction ratings with the clinic visit, and independent self-ratings of whether their expectations had been met overall. This leads the authors to conclude that the PEQ as a self-report instrument, has good reliability and validity and covers the main types of patient expectations of ambulatory health care. It has policy potential for monitoring expectation management, and is thus of potential benefit to providers and purchasers of health services, and ultimately to patients
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
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
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
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
The SSC of the Generalised Jahangir’s Graph Jm,k and its Algebraic Characterizations
No full textIn this article, we present important combinatorial and algebraicproperties of spanning simplicial complex (SSC) of the generalised Jahangir’sgraph Jm,k. We describe the relation to find f−vectors associatedto Δs(Jm,k) and determine the Hilbert series for the SR-ring KΔs(Jm,k).In the end, we present the associated primes of the facet ideal IF(Δs(Jm,k))and the Cohen-Macaulay characterization of the SR-ring of Δs(Jm,k).AMS (MOS) Subject Classification Codes: Primary 13-P10, Secondary 13-F20, 13-C14, 13-H10.Corresponding Author: Agha KashifKey Words: Simplicial Complexes, f-vectors, Spanning Trees, Face Ring, Hilbert Series, CohenMacaulay
To <i>JM</i> on Its 75th Anniversary
No full text This article discusses how Journal of Marketing ( JM) has influenced marketing science and practice by publishing articles on substantive topics relevant to customers, managers, organizations, markets, and society. The journal's 75th anniversary coincides with the 50th anniversary of the Marketing Science Institute (MSI). Frequently, JM and MSI have collaborated to address important substantive marketing issues identified in MSI's Research Priorities. The author highlights seminal articles on brand equity; business-to-business marketing (including sales force management); connecting marketing information, metrics, and strategy; consumer behavior; innovation, new product development. and product management; marketing orientation and capabilities; and market research, methodology and services. She also draws attention to articles that have won the Sheth Foundation/ JM Award and the H. Paul Root Award. The article describes how JM‘s knowledge dissemination is amplified by powerful social network effects. Ideas in JM articles diffuse through the business community, influencing the mind-set of managers worldwide. </jats:p
Changing narratives: colonised peoples, criminology and social work
No full textAbstract: There is growing recognition in criminology and social work of the importance of Indigenous knowledges and methodologies. Yet to date there have been limited attempts (particularly in criminology and criminal justice social work) to consider the theoretical and practice implications of Indigenous understandings and approaches to these disciplines. Both disciplines have also been slow to recognise the importance of understanding the way in which colonial effects are perpetuated through knowledge control, particularly in the operation of criminal justice systems.
Our paper thus begins by examining the historical and institutional factors that have contributed to the continuing subjugation of Indigenous knowledges and methodologies. A discussion of the connections between the hegemony of Western science, the construction of race, and the colonial project follows. While herein Western and Indigenous approaches are conceptualised broadly, the dangers of over-simplifying these categories is also acknowledged. The paper proceeds by examining the distinctive character of each approach through a consideration of their ontological, epistemological, axiological, and methodological differences. Whilst acknowledging the considerable challenges which arise in any attempt to develop connections between these differing worldviews, a pathway forward for understanding both theoretically and methodologically the relationship between Western and Indigenous approaches is proposed
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