Tel : +33 (0)1 44 49 31 47 (Dial 0 only within France) SignificanceDuffy blood group negativity results from a single nucleotide polymorphism (SNP) in the gene promoter, and reaches genetic fixation in many African ethnicities. Because the Duffy protein (Fy) is an important contact point during Plasmodium vivax human red blood cell invasion, Fy-negativity is considered to confer resistance to P. vivax malaria.With recent studies in African countries reporting P. vivax infection in Fy-negative people, we studied Fy expression across erythroid development. Here we report that the FY promoter SNP does not abolish Fy protein expression in erythroid progenitors developing in the bone marrow. These results further emphasizes the importance of reticulocytes as targets for P. vivax blood stage infection and propose a mechanism for P. vivax infections in Fy-negative people. Abstract The gene encoding the Duffy blood group protein (Fy, CD234; additional designations Duffy Antigen Receptor of Chemokines [DARC] and Atypical Chemokine Receptor 1 [ACKR1]) is characterized by a SNP in a GATA-1 transcription factor binding site associated with the erythrocyte silent (ES) phenotype. FY ES homozygous people are viewed to be highly resistant to blood stage infection with Plasmodium vivax. Increasingly, however, studies are reporting P.vivax infections in Fy-negative individuals across malarious African countries where FY ES approaches genetic fixation. This suggests that P. vivax has evolved a Fy-independent RBC invasion pathway, or that the GATA-1 SNP does not abolish Fy expression. Here, we tested the second hypothesis through binding studies to erythroid lineage cells using recombinant P. vivax Duffy binding protein, the parasite's invasion ligand and Fy6-specific antibodies. We first observed variable Fy expression on circulating RBCs, irrespective of FY genotype; FY ES RBCs were periodically Fy-positive. Furthermore, during the in vitro erythroid differentiation of CD34+ cells and on ex vivo bone marrow samples, we observed Fy expression on erythroid precursor cells from FY ES people. Finally, the Fy6-specific nanobody, CA111 was used to capture Fy from the surface of FY ES RBCs. Our findings reveal that the GATA-1 SNP does not fully abolish Fy expression and provide insight on potential susceptibility of Fy-negative people to vivax malaria.
Results from time-of-flight secondary ion mass spectra (TOF-SIMS) of Langmuir-Blodgett monolayers of various isomers (isotactic and syndiotactic) of poly(methyl methacrylate) (PMMA) are reported. A detailed analysis of the repeating pattern of fragment ion clusters yields very different patterns for isotactic PMMA LB layers than for the syndiotactic and atactic forms. This is attributed to the resulting double-helical tertiary structure of isotactic PMMA, a structure that does not form for the syndiotactic and atactic PMMA polymer monolayers. The double-helical structure of isotactic PMMA monolayers is verified using reflection absorption Fourier transform infrared spectroscopy. The repeating patterns of cluster ions in syndiotactic and atactic PMMA monolayers can be explained using statistical chain-breaking models for fragmentation of single isolated polymer chains. The repeating ion patterns from the TOF-SIMS of the isotactic PMMA monolayers are analyzed by considering bond breaking and ion formation between adjacent polymer chains, resulting in a newly proposed ion formation model due to the tertiary structure of the double-helical form. A rearrangement mechanism consistent with all ions that are formed is proposed.
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