1,078 research outputs found

    Plasmodium falciparum:Rosettes do not protect merozoites from invasion-inhibitory antibodies

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    Rosetting 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

    Identification of Plasmodium falciparum var1CSA and var2CSA domains that bind IgM natural antibodies

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    Malaria 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

    sj-docx-1-uro-10.1177_20514158211033481 – Supplemental material for Setting standards for cystectomy using the British Association of Urological Surgeons Complex Operations Reports, 2016–2018

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    Supplemental material, sj-docx-1-uro-10.1177_20514158211033481 for Setting standards for cystectomy using the British Association of Urological Surgeons Complex Operations Reports, 2016–2018 by Joseph B John, John Pascoe, Sarah Fowler, Edward Rowe, Alexandra Colquhoun, Benjamin Challacombe, Rory Bufacchi, Andrew J Dickinson and John S McGrath in Journal of Clinical Urology</p

    Virulence of malaria is associated with differential expression of Plasmodium falciparum var gene subgroups in a case-control study

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    Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is a major pathogenicity factor in falciparum malaria that mediates cytoadherence. PfEMP1 is encoded by approximately 60 var genes per haploid genome. Most var genes are grouped into 3 subgroups: A, B, and C. Evidence is emerging that the specific expression of these subgroups has clinical significance. Using field samples from children from Papua New Guinea with severe, mild, and asymptomatic malaria, we compared proportions of transcripts of var groups, as determined by quantitative polymerase chain reaction. We found a significantly higher proportion of var group B transcripts in children with clinical malaria (mild and severe), whereas a large proportion of var group C transcripts was found in asymptomatic children. These data from naturally infected children clearly show that major differences exist in var gene expression between parasites causing clinical disease and those causing asymptomatic infections. Furthermore, parasites forming rosettes showed a significant up-regulation of var group A transcripts

    Stages for the More Sustainable Farm

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    Currently, agricultural farm units are faced with a double and most times contradictory challenge, in order to be successful: on the one hand the invested capital has to be profitable and the economic performance has to be maximised. On the other hand, given the socio-environmental situation, it is necessary to preserve and to protect the environment and natural resources. Given the potential conflict of the two aims, since the satisfaction of one implies the underperformance of the other (and vice versa), the question then is: which is the solution to choose? We intend, in this work, to formulate a farm plan with the purpose of reconciling the criteria of environmental sustainability with that of economic competitiveness. For this achievement we proceed to the comparative study of sustainability of different groups of farms identified in the study area (first evaluation cycle) through MESMIS (“Marco para la Evaluación de Sistemas de Manejo de Recursos Naturales Mediante Indicadores de Sustentabilidad” - Framework for Evaluation of Natural-Resource Systems Handling through Sustainability Indicators) methodology, that allowed to select the more sustainable group of farms. Based on the found potentialities and weakness on these production systems, we stepped to the planning of a production unit of bovine meat, which obeys simultaneously to economic and environmental objectives, using Multicriteria Decision. We finished the work with the sustainability evaluation between groups of farms identified previously and the planned farms (second evaluation cycle), based, again, in the MESMIS methodology, to confirm (or not) the greatest sustainability of the last ones. Analyses of the results allow us to confirm the greatest relative sustainability of the planned farm, for the diverse traced scenarios.Decision taking, planning, sustainability, Environmental Economics and Policy, Farm Management,

    Correction to: Uncovering spatiotemporal patterns of atrophy in progressive supranuclear palsy using unsupervised machine learning

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    This is a correction to: William J Scotton, Cameron Shand, Emily Todd, Martina Bocchetta, David M Cash, Lawren VandeVrede, Hilary Heuer, PROSPECT Consortium, 4RTNI Consortium, Alexandra L Young, Neil Oxtoby, Daniel C Alexander, James B Rowe, Huw R Morris, Adam L Boxer, Jonathan D Rohrer, Peter A Wijeratne, Uncovering spatiotemporal patterns of atrophy in progressive supranuclear palsy using unsupervised machine learning, Brain Communications, Volume 5, Issue 2, 2023, https://doi.org/10.1093/braincomms/fcad04

    CR1 Knops blood group alleles are not associated with severe malaria in the Gambia

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    The 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

    A well-conserved Plasmodium falciparum var gene shows an unusual stage-specific transcript pattern

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    The var multicopy gene family encodes Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) variant antigens, which, through their ability to adhere to a variety of host receptors, are thought to be important virulence factors. The predominant expression of a single cytoadherent PfEMP1 type on an infected red blood cell, and the switching between different PfEMP1 types to evade host protective antibody responses, are processes thought to be controlled at the transcriptional level. Contradictory data have been published on the timing of var gene transcription. Reverse transcription-polymerase chain reaction (RT-PCR) data suggested that transcription of the predominant var gene occurs in the later (pigmented trophozoite) stages, whereas Northern blot data indicated such transcripts only in early (ring) stages. We investigated this discrepancy by Northern blot, with probes covering a diverse var gene repertoire. We confirm that almost all var transcript types were detected only in ring stages. However, one type, the well-conserved varCSA transcript, was present constitutively in different laboratory parasites and does not appear to undergo antigenic variation. Although varCSA has been shown to encode a chondroitin sulphate A (CSA)-binding PfEMP1, we find that the presence of full-length varCSA transcripts does not correlate with the CSA-binding phenotype

    TRAGIC NOISE AND RHETORICAL FRIGIDITY IN LYCOPHRON'S ALEXANDRA

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    Abstract This paper seeks to shed fresh light on the aesthetic and stylistic affiliations of Lycophron's Alexandra , approaching the poem from two distinct but complementary angles. First, it explores what can be gained by reading Lycophron's poem against the backdrop of Callimachus’ poetry. It contends that the Alexandra presents a radical and polemical departure from the Alexandrian's poetic programme, pointedly appropriating key Callimachean images while also countering Callimachus’ apparent dismissal of the ‘noisy’ tragic genre. Previous scholarship has noted links between the openings of the Aetia and of the Alexandra , but this article demonstrates that this relationship is only one part of a larger aesthetic divide between the two poets: by embracing the raucous acoustics of tragedy, Lycophron's poem offers a self-conscious and agonistic departure from Callimachus’ aesthetic preferences. Second, this article considers another way of conceiving the aesthetics of the poem beyond a Callimachean frame, highlighting how Lycophron pointedly engages with and evokes earlier Aristotelian literary criticism concerning the ‘frigid’ style: the Alexandra constructs its own independent literary history centred around the alleged name of its author, ‘Lycophron’. The article proposes that this traditional attribution is best understood as a pen name that signposts the poem's stylistic affiliations, aligning it not so much with the Ptolemaic playwright Lycophron of Chalcis but rather with Lycophron the sophist and a larger rhetorical tradition of stylistic frigidity. Ultimately, through these two approaches, the article highlights further aspects of the Alexandra 's aesthetic diversity

    Teaching empathy and emotions : J. M. Coetzee's "The lives of animals" and human-animal studies

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    In "Teaching Empathy and Emotions: J. M. Coetzee's 'The Lives of Animals' and Human-Animal Studies," Alexandra Böhm focuses on one of the most influential novels in the field of HAS. In her article, she delineates the two main difficulties in teaching Coetzee's text: firstly, the text's protagonist, fierce and fearless Australian author Elizabeth Costello, is often less-than-lovable and offers few grounds for identification; secondly, the text's multilayered structure further problematizes the authorial voice. However, by focusing on Costello's reassessment of emotion and empathy, Böhm convincingly demonstrates that Coetzee's text offers possibilities for understanding the key concepts of HAS, such as animal agency, alterity, and the necessity of assuming a non-anthropocentric perspective. In the narrative, Costello employs empathy in her approach to animals, but is this also true of the metadiegetic level of Coetzee's text? Does the text itself suggest how to teach empathy? Alexandra Böhm demonstrates that it is possible to elicit affective responses to these questions through emotion journals and role-playing
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