Plasmodium falciparum secretes extracellular vesicles (PfEVs) that contain parasite-derived RNA. However, the significance of the secreted RNA remains unexplored. Here, we compare secreted and ...intracellular RNA from asexual cultures of six P. falciparum lines. We find that secretion of RNA via extracellular vesicles is not only periodic throughout the asexual intraerythrocytic developmental cycle but is also highly conserved across P. falciparum isolates. We further demonstrate that the phases of RNA secreted via extracellular vesicles are discernibly shifted compared to those of the intracellular RNA within the secreting whole parasite. Finally, transcripts of genes with no known function during the asexual intraerythrocytic developmental cycle are enriched in PfEVs compared to the whole parasite. We conclude that the secretion of extracellular vesicles could be a putative posttranscriptional RNA regulation mechanism that is part of or synergise the classic RNA decay processes to maintain intracellular RNA levels in P. falciparum.
Our understanding of the basis of severe disease in malaria is incomplete. It is clear that pathology is in part related to the pro-inflammatory nature of the host response but a number of other ...factors are also thought to be involved, including the interaction between infected erythrocytes and endothelium. This is a complex system involving several host receptors and a major parasite-derived variant antigen (PfEMP1) expressed on the surface of the infected erythrocyte membrane. Previous studies have suggested a role for ICAM-1 in the pathology of cerebral malaria, although these have been inconclusive. In this study we have examined the cytoadherence patterns of 101 patient isolates from varying clinical syndromes to CD36 and ICAM-1, and have used variant ICAM-1 proteins to further characterise this adhesive phenotype. Our results show that increased binding to CD36 is associated with uncomplicated malaria while ICAM-1 adhesion is raised in parasites from cerebral malaria cases.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
: Although thousands of clinical isolates of
are being sequenced and analysed by short read technology, the data do not resolve the highly variable subtelomeric regions of the genomes that contain ...polymorphic gene families involved in immune evasion and pathogenesis. There is also no current standard definition of the boundaries of these variable subtelomeric regions.
: Using long-read sequence data (Pacific Biosciences SMRT technology), we assembled and annotated the genomes of 15
isolates, ten of which are newly cultured clinical isolates. We performed comparative analysis of the entire genome with particular emphasis on the subtelomeric regions and the internal
genes clusters.
: The nearly complete sequence of these 15 isolates has enabled us to define a highly conserved core genome, to delineate the boundaries of the subtelomeric regions, and to compare these across isolates. We found highly structured variable regions in the genome. Some exported gene families purportedly involved in release of merozoites show copy number variation. As an example of ongoing genome evolution, we found a novel CLAG gene in six isolates. We also found a novel gene that was relatively enriched in the South East Asian isolates compared to those from Africa.
: These 15 manually curated new reference genome sequences with their nearly complete subtelomeric regions and fully assembled genes are an important new resource for the malaria research community. We report the overall conserved structure and pattern of important gene families and the more clearly defined subtelomeric regions.
Primary blast lung injury (PBLI) is an acknowledged cause of death in explosive blast casualties. In contrast to vehicle occupants following an in-vehicle explosion, the injury profile, including ...PBLI incidence, for mounted personnel following an external explosion has yet to be as well defined.
This retrospective study identified 146 cases of UK military personnel killed by improvised explosive devices (IEDs) between November 2007 and July 2010. With the permission of Her Majesty's Coroners, relevant postmortem computed tomography imaging was analyzed. PBLI was diagnosed by postmortem computed tomography. Injury, demographic, and relevant incident data were collected via the UK Joint Theatre Trauma Registry.
Autopsy results were not available for 1 of 146 cases. Of the remaining 145 IED fatalities, 24 had catastrophic injuries (disruptions), making further study impossible, leaving 121 cases; 79 were dismounted (DM), and 42 were mounted (M). PBLI was noted in 58 cases, 33 (79%) of 42 M fatalities and 25 (32%) of 79 DM fatalities (p < 0.0001). Rates of associated thoracic trauma were also significantly greater in the M group (p < 0.006 for all). Fatal head (53% vs. 23%) and thoracic trauma (23% vs. 8%) were both more common in the M group, while fatal lower extremity trauma (7% vs. 48%) was more commonly seen in DM casualties (p < 0.0001 for all).
Following IED strikes, mounted fatalities are primarily caused by head and chest injuries. Lower extremity trauma is the leading cause of death in dismounted fatalities. Mounted fatalities have a high incidence of PBLI, suggesting significant exposure to primary blast. This has not been reported previously. Further work is required to determine the incidence and clinical significance of this severe lung injury in explosive blast survivors. In addition, specific characteristics of the vehicles should be considered.
Author information Affiliations 1. KEMRI/Wellcome Trust Research Programme, P. O. Box 230, 80108, Kilifi, Kenya * Lucy B Ochola * , Bethsheba R Siddondo * , Harold Ocholla * , Eva N Kimani * , Thomas ...N Williams * , Johnstone O Makale * , Britta C Urban * , Pete Bull * & Kevin Marsh 2. Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK * Britta C Urban * , Tadge Szestak * & Alister G Craig 3. Dar es Salaam University College of Education, Faculty of Science, P.O. Box 2329, Dares Salaam, Tanzania * Siana Nyka 4. Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden * Anne Liljander Authors 1. Search for Lucy B Ochola in: * PubMed • * Google Scholar 2. Search for Bethsheba R Siddondo in: * PubMed • * Google Scholar 3. Search for Harold Ocholla in: * PubMed • * Google Scholar 4. Search for Siana Nyka in: * PubMed • * Google Scholar 5. Search for Eva N Kimani in: * PubMed • * Google Scholar 6. Search for Thomas N Williams in: * PubMed • * Google Scholar 7. Search for Johnstone O Makale in: * PubMed • * Google Scholar 8. Search for Anne Liljander in: * PubMed • * Google Scholar 9. Search for Britta C Urban in: * PubMed • * Google Scholar 10. Search for Pete Bull in: * PubMed • * Google Scholar 11. Search for Tadge Szestak in: * PubMed • * Google Scholar 12. Search for Kevin Marsh in: * PubMed • * Google Scholar 13. Search for Alister G Craig in: * PubMed • * Google Scholar Corresponding author Correspondence to Alister G Craig.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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