845 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
Interactive processes in a Lanice conchilega (Annelida: Polychaeta) dominated intertidal community
No full textAn investigation was conducted into the factors influencing a soft-sediment intertidal benthic community dominated by the large tube building polychaete Lanice conchilega (Pallas, 1766). The environmental and biological characteristics of a mid-shore sampling site on a relatively sheltered sandflat were monitored over a two year period. A total of 115 taxa were recorded. Temporal variability in the community is discussed in relation to the sporadic occurrence of macroalgae, harsh winter conditions and physical disturbance to the sedimentary environment. Lanice conchilega had a significantly contagious distribution on the shore. The population was analysed using width measurements of both worms and tubes. Recruiting Lanice conchilega juveniles observed during the first year of the study were initially randomly distributed, but as these individuals developed the overall distribution of the population returned to being contagious. The presence of excess tubes towards the end of the sampling period indicated that individual Lanice conchilega were dying, being removed by predation or emigrating. Further sampling was designed to investigate the macrofauna and meiofauna in areas of sediment containing different densities of Lanice conchilega tubes. A consistently significant positive correlation existed between tube density and macrofaunal abundance, which was attributed to sediment-mediated interactions. At higher tube densities, an increase in the depth of sediment above the underlying clay equated to an increase in the volume of available infaunal space. In addition, Lanice conchilega-derived mucus and its associated microbes potentially enhanced levels of food resources available to deposit feeders. Species living at or near the sediment-water interface would also have been positively influenced by any sediment stabilisation in high tube density areas. Possible causes of a positive correlation observed between tube density and Exogone hebes abundance are discussed. No significant relationship existed between tube density and the abundance of macrofaunal juveniles, indicating that any inhibitory or facilitatory Lanice conchilega-juvenile interactions were either insignificant or acting in opposition to produce an overall neutral effect. Details of the developmental morphology of several polychaete species are described. Meiofaunal abundance (in particular nematode and harpacticoid abundance) was consistently greater in samples taken from areas of high tube density. Potential mechanisms responsible for this relationship include the provision of habitat heterogeneity and areas of refuge by tubes, and the enhancement of sediment stability and food resources by mucus. Particle accumulation in high tube density areas also potentially influenced meiofaunal settlement and resettlement patterns
Behaviour of buried pipelines subjected to external loading.
Get PDFThe research presented in this Thesis was carried out at the University of Sheffield under
the supervision of Dr I. C. Pyrah and Dr W. F. Anderson, and Mr G. Leach at British Gas
Engineering Research Station (ERS). The research was financially supported by a British
Gas Research Scholarship and by the Overseas Research Students Awards Scheme.
The Author would like to express his sincere gratitude to his supervisors for their invaluable
help, guidance and encouragement during the development of the research.
The Author is also grateful to Dr S. R. Mi for his interest and assistance throughout the
research. Special thanks also go to Dr S. J. Wheeler for his supervision during the first year
of the research and sound advice in the initial stage of the work.
The Author would like to express his gratitude to all members of the geotechnics group at
the University of Sheffield for the useful discussions and comments. Special thanks and
appreciation are extended to the staff at the ERS, particularly Mr E. Middleton for
providing the data of the field tests and constructive comments.
The laboratory tests were performed at ERS Soils Laboratory for which the Author is
thankful to the laboratory staff. The Author must also thank British Gas for providing the
computer hardware and software for performing the numerical analyses, and the printing
facilities to produce the Thesis. Thanks also go to Mr D. Reay and Mr B. Bellwood at the
Gas Research Centre of British Gas for ensuring continuous financial support throughout
the award period.
Finally, the Author wishes to thank his family and friends for their endless support and
encouragement throughout the period of study in the UK. Without them, this Thesis may
never have been completed
Kepler Uniform Modeling of KOIs: MCMC Notes for Data Release 25
Get PDFThis document describes data products related to the reported planetary parameters and uncertainties for the Kepler Objects of Interest (KOIs) based on a Markov-Chain-Monte-Carlo (MCMC) analysis. Reported parameters, uncertainties and data products can be found at the NASA Exoplanet Archive . The codes used for this data analysis are available on the Github website (Rowe 2016). The relevant paper for details of the calculations is Rowe et al. (2015). The main differences between the model fits discussed here and those in the DR24 catalogue are that the DR25 light curves were used in the analysis, our processing of the MAST light curves took into account different data flags, the number of chains calculated was doubled to 200 000, and the parameters which are reported are based on a damped least-squares fit, instead of the median value from the Markov chain or the chain with the lowest 2 as reported in the past
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
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
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
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
From the Outside-In: the Francisella tularensis Envelope and Virulence
No full textFrancisella tularensis is a highly-infectious bacterium that causes the rapid, and often lethal disease, tularemia. Many studies have been performed to identify and characterize the virulence factors that F. tularensis uses to infect a wide variety of hosts and host cell types, evade immune defenses, and induce severe disease and death. This review focuses on the virulence factors that are present in the F. tularensis envelope, including capsule, LPS, outer membrane, periplasm, inner membrane, secretion systems, and various molecules in each of aforementioned sub-compartments. Whereas no single bacterial molecule or molecular complex single-handedly controls F. tularensis virulence, we review here how diverse bacterial systems work in conjunction to subvert the immune system, attach to and invade host cells, alter phagosome/lysosome maturation pathways, replicate in host cells without being detected, inhibit apoptosis, and induce host cell death for bacterial release and infection of adjacent cells. Given that the F. tularensis envelope is the outermost layer of the bacterium, we highlight herein how many of these molecules directly interact with the host to promote infection and disease. These and future envelope studies are important to advance our collective understanding of F. tularensis virulence mechanisms and offer targets for future vaccine development efforts
Exploiting Kepler’s Heritage: A Transfer Learning Approach for Identifying Exoplanets’ Transits in TESS Data
No full textIn the last decade, exoplanets space missions started to collect a huge amount of photometric observations, with over ∼1,000,000 new light curves generated every month from the Transiting Exoplanet Survey Satellite (TESS) full-frame images alone. In order to analyze such an unprecedented volume of data, automated planet-candidate detection has become an appreciable replacement to human vetting. In this work, we present a Machine Learning approach, based on Deep Neural Networks, to perform a binary classification of TESS light curves in terms of planet candidate and not-planet. Since few TESS labeled data exist to date, we pre-train the network with Kepler DR24 data set, including ≳15,000 labeled light curves. Our pre-trained model is then tested on ExoFOP data, showing an appreciable gain in terms of reliability with respect to a randomly initialized model
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