Limited antigenic diversity of Plasmodium falciparum apical membrane antigen 1 supports the development of effective multi-allele vaccines

BackgroundPolymorphism in antigens is a common mechanism for immune evasion used by many important pathogens, and presents major challenges in vaccine development. In malaria, many key immune targets and vaccine candidates show substantial polymorphism. However, knowledge on antigenic diversity of key antigens, the impact of polymorphism on potential vaccine escape, and how sequence polymorphism relates to antigenic differences is very limited, yet crucial for vaccine development. Plasmodium falciparum apical membrane antigen 1 (AMA1) is an important target of naturally-acquired antibodies in malaria immunity and a leading vaccine candidate. However, AMA1 has extensive allelic diversity with more than 60 polymorphic amino acid residues and more than 200 haplotypes in a single population. Therefore, AMA1 serves as an excellent model to assess antigenic diversity in malaria vaccine antigens and the feasibility of multi-allele vaccine approaches. While most previous research has focused on sequence diversity and antibody responses in laboratory animals, little has been done on the cross-reactivity of human antibodies.MethodsWe aimed to determine the extent of antigenic diversity of AMA1, defined by reactivity with human antibodies, and to aid the identification of specific alleles for potential inclusion in a multi-allele vaccine. We developed an approach using a multiple-antigen-competition enzyme-linked immunosorbent assay (ELISA) to examine cross-reactivity of naturally-acquired antibodies in Papua New Guinea and Kenya, and related this to differences in AMA1 sequence.ResultsWe found that adults had greater cross-reactivity of antibodies than children, although the patterns of cross-reactivity to alleles were the same. Patterns of antibody cross-reactivity were very similar between populations (Papua New Guinea and Kenya), and over time. Further, our results show that antigenic diversity of AMA1 alleles is surprisingly restricted, despite extensive sequence polymorphism. Our findings suggest that a combination of three different alleles, if selected appropriately, may be sufficient to cover the majority of antigenic diversity in polymorphic AMA1 antigens. Antigenic properties were not strongly related to existing haplotype groupings based on sequence analysis.ConclusionsAntigenic diversity of AMA1 is limited and a vaccine including a small number of alleles might be sufficient for coverage against naturally-circulating strains, supporting a multi-allele approach for developing polymorphic antigens as malaria vaccines

Pollen metabarcoding reveals broad and species-specific resource use by urban bees

Bee populations are currently undergoing severe global declines driven by the interactive effects of a number of factors. Ongoing urbanisation has the potential to exacerbate bee declines, unless steps are taken to ensure appropriate floral resources are available. Sown wildflower strips are one way in which floral resources can be provided to urban bees. However, the use of these strips by pollinators in urban environments remains little studied. Here, we employ pollen metabarcoding of the rbcL gene to compare the foraging patterns of different bee species observed using urban sown wildflower strips in July 2016, with a goal of identifying which plant species are most important for bees. We also demonstrate the use of a non-destructive method of pollen collection. Bees were found to forage on a wide variety of plant genera and families, including a diverse range of plants from outside the wildflower plots, suggesting that foragers visiting sown wildflower strips also utilize other urban habitats. Particular plants within the wildflower strips dominated metabarcoding data, particularly Papaver rhoeas and Phacelia tanacetifolia. Overall, we demonstrate that pollinators observed in sown wildflower strips use certain sown foodplants as part of a larger urban matrix

The SKA Particle Array Prototype: The First Particle Detector at the Murchison Radio-astronomy Observatory

We report on the design, deployment, and first results from a scintillation detector deployed at the Murchison Radio-astronomy Observatory (MRO). The detector is a prototype for a larger array -- the Square Kilometre Array Particle Array (SKAPA) -- planned to allow the radio-detection of cosmic rays with the Murchison Widefield Array and the low-frequency component of the Square Kilometre Array. The prototype design has been driven by stringent limits on radio emissions at the MRO, and to ensure survivability in a desert environment. Using data taken from Nov.\ 2018 to Feb.\ 2019, we characterize the detector response while accounting for the effects of temperature fluctuations, and calibrate the sensitivity of the prototype detector to through-going muons. This verifies the feasibility of cosmic ray detection at the MRO. We then estimate the required parameters of a planned array of eight such detectors to be used to trigger radio observations by the Murchison Widefield Array.Comment: 17 pages, 14 figures, 3 table

Emplotment as Epic in Archaeological Writing: The Site Monograph as Narrative

To emplot a narrative as epic is to present a story of vast scope and multiple plots as a legitimate member of a tradition of other such stories. This article argues that emplotment as epic is the broadest of three levels of plot in archaeological writings. At that level, the site monograph emerges as a characteristically archaeological form of narrative, fundamental to archaeology as a discipline and a source of chronic anxiety for archaeologists. The ‘stories’ told in site monographs are epic in length, diversity of materials covered and multiplicity of themes, plots and authors. Indeed, the more complexities of that sort the better, since those are features that help to emplot the work as good archaeology

Perspectives of US women participating in a candidate PrEP study: adherence, acceptability and future use intentions

Introduction Limited data exist on acceptability of candidate pre‐exposure prophylaxis (PrEP) regimens among US women. We evaluated PrEP experiences, attitudes and future use intentions among sexually active women who completed the US‐based HIV Prevention Trials Network 069/AIDS Clinical Trials Group 5305 study. Methods Women participated in the study between March 2013 and November 2015. We analysed computer‐assisted self‐interview (CASI) surveys among 130 women and conducted in‐depth interviews among a subset of 26 women from three sites. Interviews were conducted in mid/late‐2015. Results Most women (57%) reported very good/excellent PrEP adherence on CASI, although 21% acknowledged over‐reporting adherence at least some of the time. Commitment to preventing HIV infection, a sense of ownership of the study, and keeping pills stored in a visible location facilitated adherence. Adherence barriers included “simply forgetting” and being away from home. Most women interviewed did not intend to use PrEP in the future because of lack of perceived need due to their own (as opposed to their partners’) low‐risk behaviour and concerns about affordability – but not because of side effects or other characteristics of the regimens. Conclusions Improving HIV prevention options for US women will require access to affordable PrEP as well as expanding women\u27s understanding of relationship‐ and community‐level factors that increase their risk of acquiring HIV

Judicial disagreement need not be political: dissent on the Estonian Supreme Court

I investigate the non-unanimous decisions of judges on the Estonian Supreme Court. I argue that since judges on the court enjoy high de jure independence, dissent frequently, and are integrated in the normal judicial hierarchy, the Estonian Supreme Court is a crucial case for the presumption that judicial disagreement reveals policy preferences. I analyse dissenting opinions using an ideal point response model. Examining the characteristics of cases which discriminated with respect to the recovered dimension, I show that this dimension cannot be interpreted as a meaningful policy dimension, but instead reflects disagreement about the proper scope of constitutional redress

Life path analysis: scaling indicates priming effects of social and habitat factors on dispersal distances

1. Movements of many animals along a life-path can be separated into repetitive ones within home ranges and transitions between home ranges. We sought relationships of social and environmental factors with initiation and distance of transition movements in 114 buzzards Buteo buteo that were marked as nestlings with long-life radio tags. 2. Ex-natal dispersal movements of 51 buzzards in autumn were longer than for 30 later in their first year and than 35 extra-natal movements between home ranges after leaving nest areas. In the second and third springs, distances moved from winter focal points by birds that paired were the same or less than for unpaired birds. No post-nuptial movement exceeded 2 km. 3. Initiation of early ex-natal dispersal was enhanced by presence of many sibs, but also by lack of worm-rich loam soils. Distances travelled were greatest for birds from small broods and with relatively little short grass-feeding habitat near the nest. Later movements were generally enhanced by the absence of loam soils and short grassland, especially with abundance of other buzzards and probable poor feeding habitats (heathland, long grass). 4. Buzzards tended to persist in their first autumn where arable land was abundant, but subsequently showed a strong tendency to move from this habitat. 5. Factors that acted most strongly in ½-km buffers round nests, or round subsequent focal points, usually promoted movement compared with factors acting at a larger scale. Strong relationships between movement distances and environmental characteristics in ½-km buffers, especially during early ex-natal dispersal, suggested that buzzards became primed by these factors to travel far. 6. Movements were also farthest for buzzards that had already moved far from their natal nests, perhaps reflecting genetic predisposition, long-term priming or poor habitat beyond the study area

Personal, Political, Pedagogic: Challenging the binary bind in archaeological teaching, learning and fieldwork

yesIn this paper we consider how we can undercut the various binaries of gender and sexuality in archaeological practice, and particularly in our teaching. We argue that taking an assemblage theory approach enables us to look at the multiplicity of identities of those practicing archaeology as different and intersecting assemblages that bring one another into being through their connections at different scales. In particular, we examine how this approach can be applied to archaeological pedagogy and how this in turn enables us to move away from modern binary distinctions about sex and gender identities from the "bottom up", fostering an approach in our students that will then go on to be developed in professional practice

Performance of a Limiting-Antigen Avidity Enzyme Immunoassay for Cross-Sectional Estimation of HIV Incidence in the United States

Background: A limiting antigen avidity enzyme immunoassay (HIV-1 LAg-Avidity assay) was recently developed for cross-sectional HIV incidence estimation. We evaluated the performance of the LAg-Avidity assay alone and in multi-assay algorithms (MAAs) that included other biomarkers. Methods and Findings: Performance of testing algorithms was evaluated using 2,282 samples from individuals in the United States collected 1 month to >8 years after HIV seroconversion. The capacity of selected testing algorithms to accurately estimate incidence was evaluated in three longitudinal cohorts. When used in a single-assay format, the LAg-Avidity assay classified some individuals infected >5 years as assay positive and failed to provide reliable incidence estimates in cohorts that included individuals with long-term infections. We evaluated >500,000 testing algorithms, that included the LAg-Avidity assay alone and MAAs with other biomarkers (BED capture immunoassay [BED-CEIA], BioRad-Avidity assay, HIV viral load, CD4 cell count), varying the assays and assay cutoffs. We identified an optimized 2-assay MAA that included the LAg-Avidity and BioRad-Avidity assays, and an optimized 4-assay MAA that included those assays, as well as HIV viral load and CD4 cell count. The two optimized MAAs classified all 845 samples from individuals infected >5 years as MAA negative and estimated incidence within a year of sample collection. These two MAAs produced incidence estimates that were consistent with those from longitudinal follow-up of cohorts. A comparison of the laboratory assay costs of the MAAs was also performed, and we found that the costs associated with the optimal two assay MAA were substantially less than with the four assay MAA. Conclusions: The LAg-Avidity assay did not perform well in a single-assay format, regardless of the assay cutoff. MAAs that include the LAg-Avidity and BioRad-Avidity assays, with or without viral load and CD4 cell count, provide accurate incidence estimates

Conservation of genetic uniqueness in remaining populations of red squirrels (Sciurus vulgaris L.) in the South of England

The Eurasian red squirrel (Sciurus vulgaris) is an emblematic species for conservation, and its decline in the British Isles exemplifies the impact that alien introductions can have on native ecosystems. Indeed, red squirrels in this region have declined dramatically over the last 60 years due to the spread of squirrelpox virus following the introduction of the gray squirrel (Sciurus carolinensis). Currently, red squirrel populations in Britain are fragmented and need to be closely monitored in order to assess their viability and the effectiveness of conservation efforts. The situation is even more dramatic in the South of England, where S. vulgaris survives only on islands (Brownsea Island, Furzey Island, and the Isle of Wight). Using the D‐loop, we investigated the genetic diversity and putative ancestry of the squirrels from Southern England and compared them to a European dataset composed of 1,016 samples from 54 populations. We found that our three populations were more closely related to other squirrels from the British Isles than squirrels from Europe, showed low genetic diversity, and also harbored several private haplotypes. Our study demonstrates how genetically unique the Southern English populations are in comparison with squirrels from the continental European range. We report the presence of four private haplotypes, suggesting that these populations may potentially harbor distinct genetic lineages. Our results emphasize the importance of preserving these isolated red squirrel populations for the conservation of the species