284 research outputs found

    Local economic inequality in the UK: patterns, determinants, and behavioural consequences

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    I develop a novel, geographically granular measure of economic inequality in the UK based on data covering tens of millions of residential properties. The size of this data allows me to describe and understand the consequences of local inequality in the UK for the first time. The first paper in my thesis explores patterns of local economic inequality, both contemporary levels and changes over the last couple decades. The paper also examines whether salient features of the local environment affect people’s perceptions of economic inequality. Across two surveys, I find that discrepancies in housing quality are indeed a salient aspect affecting people’s perceptions. I then examine the determinants of inequality at different spatial resolutions, from the city down to the neighbourhood level. I find that local composition of skills, housing tenure, and amenities are all important factors. The third, fourth and fifth papers in my thesis examine the consequences of local inequality for a number of important individual and group behaviours. First, I examine whether local inequality affects pro-social spending, providing new insight into a question that has produced conflicting findings. Across two studies covering the US and UK, I find that local inequality interacts positively with income – higher income individuals are more generous in areas of higher inequality, probably because they come into contact with poorer individuals more often. Second, in a paper co-authored with Thiago Oliveira, I explore whether variation in neighbourhood-level inequality in London affects the prevalence of police stop and search behaviour. We find a positive relationship, supporting criminological theories on police behaviour and social order maintenance. Finally, combining data on economic inequality with data on local ethnic composition from the UK census, I examine whether patterns of residential diversity and segregation affects political behaviour. Using Brexit as a case study, I find strong evidence in support of contact rather than conflict theory – neighbourhood economic and social diversity reduces support for Brexit, but the opposite is true for segregation

    Performances de variétés de blés panifiables cultivées en agriculture biologique en conditions peu fertiles

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    Le FiBL et Agroscope ont analysé des variétés de blés panifiables en termes de stabilité du rendement et de la qualité. Il ressort des résultats que le choix variétal doit être adapté au site et que le haut potentiel de rendement ne va pas de pair avec des grains riches en protéines

    IFNAR1-Signalling Obstructs ICOS-mediated Humoral Immunity during Non-lethal Blood-Stage Plasmodium Infection

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    Funding: This work was funded by a Career Development Fellowship (1028634) and a project grant (GRNT1028641) awarded to AHa by the Australian National Health & Medical Research Council (NHMRC). IS was supported by The University of Queensland Centennial and IPRS Scholarships. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

    Soybean Seed Extracts Preferentially Express Genomic Loci of Bradyrhizobium japonicum in the Initial Interaction with Soybean, Glycine max (L.) Merr

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    Initial interaction between rhizobia and legumes actually starts via encounters of both partners in the rhizosphere. In this study, the global expression profiles of Bradyrhizobium japonicum USDA 110 in response to soybean (Glycine max) seed extracts (SSE) and genistein, a major soybean-released isoflavone for nod genes induction of B. japonicum, were compared. SSE induced many genomic loci as compared with genistein (5.0 µM), nevertheless SSE-supplemented medium contained 4.7 µM genistein. SSE markedly induced four predominant genomic regions within a large symbiosis island (681 kb), which include tts genes (type III secretion system) and various nod genes. In addition, SSE-treated cells expressed many genomic loci containing genes for polygalacturonase (cell-wall degradation), exopolysaccharide synthesis, 1-aminocyclopropane-1-carboxylate deaminase, ribosome proteins family and energy metabolism even outside symbiosis island. On the other hand, genistein-treated cells exclusively showed one expression cluster including common nod gene operon within symbiosis island and six expression loci including multidrug resistance, which were shared with SSE-treated cells. Twelve putatively regulated genes were indeed validated by quantitative RT-PCR. Several SSE-induced genomic loci likely participate in the initial interaction with legumes. Thus, these results can provide a basic knowledge for screening novel genes relevant to the B. japonicum- soybean symbiosis

    Export of a Toxoplasma gondii Rhoptry Neck Protein Complex at the Host Cell Membrane to Form the Moving Junction during Invasion

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    One of the most conserved features of the invasion process in Apicomplexa parasites is the formation of a moving junction (MJ) between the apex of the parasite and the host cell membrane that moves along the parasite and serves as support to propel it inside the host cell. The MJ was, up to a recent period, completely unknown at the molecular level. Recently, proteins originated from two distinct post-Golgi specialised secretory organelles, the micronemes (for AMA1) and the neck of the rhoptries (for RON2/RON4/RON5 proteins), have been shown to form a complex. AMA1 and RON4 in particular, have been localised to the MJ during invasion. Using biochemical approaches, we have identified RON8 as an additional member of the complex. We also demonstrated that all RON proteins are present at the MJ during invasion. Using metabolic labelling and immunoprecipitation, we showed that RON2 and AMA1 were able to interact in the absence of the other members. We also discovered that all MJ proteins are subjected to proteolytic maturation during trafficking to their respective organelles and that they could associate as non-mature forms in vitro. Finally, whereas AMA1 has previously been shown to be inserted into the parasite membrane upon secretion, we demonstrated, using differential permeabilization and loading of RON-specific antibodies into the host cell, that the RON complex is targeted to the host cell membrane, where RON4/5/8 remain associated with the cytoplasmic face. Globally, these results point toward a model of MJ organization where the parasite would be secreting and inserting interacting components on either side of the MJ, both at the host and at its own plasma membranes

    Hypoxia Sensitive Metal β-Ketoiminate Complexes Showing Induced Single Strand DNA Breaks and Cancer Cell Death by Apoptosis

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    A series of ruthenium and iridium complexes have been synthesised and characterised with 20 novel crystal structures discussed. The library of β-ketoiminate complexes has been shown to be active against MCF-7 (human breast carcino-ma), HT-29 (human colon carcinoma), A2780 (human ovarian carcinoma) and A2780cis (cisplatin resistant human ovarian carcinoma) cell lines, with selected complexes being more than three times as active as cisplatin against the A2780cis cell line. Complexes have also been shown to be highly active under hypoxic conditions, with the activities of some complexes increasing with a decrease in O2 concentration. The enzyme thioredoxin reductase is over-expressed in cancer cells and complexes reported herein have the advantage of inhibiting this enzyme, with IC50 values measured in the nanomolar range. The anti-cancer activity of these complexes was further investigated to determine whether activity is due to effects on cellular growth or cell survival. The complexes were found to induce significant cancer cell death by apoptosis with levels induced correlating closely with activity in chemosensitivity studies. As a possible cause of cell death, the ability of the complexes to induce damage to cellular DNA was also assessed. The complexes failed to induce double strand DNA break or DNA crosslinking but induced significant levels of single DNA strand breaks indi-cating a different mechanism of action to cisplatin

    Functional Analysis of the Leading Malaria Vaccine Candidate AMA-1 Reveals an Essential Role for the Cytoplasmic Domain in the Invasion Process

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    A key process in the lifecycle of the malaria parasite Plasmodium falciparum is the fast invasion of human erythrocytes. Entry into the host cell requires the apical membrane antigen 1 (AMA-1), a type I transmembrane protein located in the micronemes of the merozoite. Although AMA-1 is evolving into the leading blood-stage malaria vaccine candidate, its precise role in invasion is still unclear. We investigate AMA-1 function using live video microscopy in the absence and presence of an AMA-1 inhibitory peptide. This data reveals a crucial function of AMA-1 during the primary contact period upstream of the entry process at around the time of moving junction formation. We generate a Plasmodium falciparum cell line that expresses a functional GFP-tagged AMA-1. This allows the visualization of the dynamics of AMA-1 in live parasites. We functionally validate the ectopically expressed AMA-1 by establishing a complementation assay based on strain-specific inhibition. This method provides the basis for the functional analysis of essential genes that are refractory to any genetic manipulation. Using the complementation assay, we show that the cytoplasmic domain of AMA-1 is not required for correct trafficking and surface translocation but is essential for AMA-1 function. Although this function can be mimicked by the highly conserved cytoplasmic domains of P. vivax and P. berghei, the exchange with the heterologous domain of the microneme protein EBA-175 or the rhoptry protein Rh2b leads to a loss of function. We identify several residues in the cytoplasmic tail that are essential for AMA-1 function. We validate this data using additional transgenic parasite lines expressing AMA-1 mutants with TY1 epitopes. We show that the cytoplasmic domain of AMA-1 is phosphorylated. Mutational analysis suggests an important role for the phosphorylation in the invasion process, which might translate into novel therapeutic strategies
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