Background: Plasmodium vivax merozoite surface protein 3α (PvMSP3α) is a promising vaccine candidate which has shown strong association with immunogenicity and protectiveness. Its use is however complicated by evolutionary plasticity features which enhance immune evasion. Low complexity regions (LCRs) provide plasticity in surface proteins of Plasmodium species, but its implication in vaccine design remain unexplored. Here population genetic, comparative phylogenetic and structural biology analysis was performed on the gene encoding PvMSP3α.
Results: Three LCRs were found in PvMSP3α block II. Both the predicted tertiary structure of the protein and the phylogenetic trees based on this region were influenced by the presence of the LCRs. The LCRs were mainly B cell epitopes within or adjacent. In addition a repeat motif mimicking one of the B cell epitopes was found within the PvMSP3a block II low complexity region. This particular B cell epitope also featured rampant alanine substitutions which might impair antibody binding.
Conclusion: The findings indicate that PvMSP3α block II possesses LCRs which might confer a strong phenotypic plasticity. The phenomenon of phenotypic plasticity and implication of LCRs in malaria immunology in general and vaccine candidate genes in particular merits further exploration.
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http://dx.doi.org/10.1186/s12900-019-0104-0 | DOI Listing |
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Department of Orthopaedics and Trauma, Medical University of Graz, Auenbruggerplatz 5, 8036, Graz, Austria.
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ACS Nano
January 2025
School of Medicine, Nankai University, Tianjin 300071, China.
Designing dual-targeted nanomedicines to enhance tumor delivery efficacy is a complex challenge, largely due to the barrier posed by blood vessels during systemic delivery. Effective transport across endothelial cells is, therefore, a critical topic of study. Herein, we present a synthetic biology-based approach to engineer dual-targeted ferritin nanocages (Dt-FTn) for understanding receptor-mediated transport across tumor endothelial cells.
View Article and Find Full Text PDFMil Med
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Department of Orthopaedic Surgery, Walter Reed National Military Medical Center, Bethesda, MD 20889, USA.
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View Article and Find Full Text PDFNucleic Acids Res
January 2025
Kansai Institute for Photon Science, National Institutes for Quantum Science and Technology (QST), 8-1-7 Umemidai, Kizugawa-shi, Kyoto 619-0215, Japan.
Ionizing radiation induces various types of DNA damage, and the reparability and lethal effects of DNA damage differ depending on its spatial density. Elucidating the structure of radiation-induced clustered DNA damage and its repair processes will enhance our understanding of the lethal impact of ionizing radiation and advance progress toward precise therapeutics. Previously, we developed a method to directly visualize DNA damage using atomic force microscopy (AFM) and classified clustered DNA damage into simple base damage clusters (BDCs), complex BDCs and complex double-strand breaks (DSBs).
View Article and Find Full Text PDFCancer Sci
January 2025
Department of colorectal surgery, The First Affiliated Hospital of Ningbo University, Ningbo, China.
This study analyzed targeted sequencing data from 6530 tissue samples from patients with metastatic Chinese colorectal cancer (CRC) to identify low mutation frequency and subgroup-specific driver genes, using three algorithms for overall CRC as well as across different clinicopathological subgroups. We analyzed 425 cancer-related genes, identifying 101 potential driver genes, including 36 novel to CRC. Notably, some genes demonstrated subgroup specificity; for instance, ERBB4 was found as a male-specific driver gene and mutations of ERBB4 only influenced the prognosis of male patients with CRC.
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