251 research outputs found

    The International Criminal Court in Uganda

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    Chronic helminth infection burden differentially affects haematopoietic cell development while ageing selectively impairs adaptive responses to infection

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    Throughout the lifespan of an individual, the immune system undergoes complex changes while facing novel and chronic infections. Helminths, which infect over one billion people and impose heavy livestock productivity losses, typically cause chronic infections by avoiding and suppressing host immunity. Yet, how age affects immune responses to lifelong parasitic infection is poorly understood. To disentangle the processes involved, we employed supervised statistical learning techniques to identify which factors among haematopoietic stem and progenitor cells (HSPC), and both innate and adaptive responses regulate parasite burdens and how they are affected by host age. Older mice harboured greater numbers of the parasites’ offspring than younger mice. Protective immune responses that did not vary with age were dominated by HSPC, while ageing specifically eroded adaptive immunity, with reduced numbers of naïve T cells, poor T cell responsiveness to parasites, and impaired antibody production. We identified immune factors consistent with previously-reported immune responses to helminths, and also revealed novel interactions between helminths and HSPC maturation. Our approach thus allowed disentangling the concurrent effects of ageing and infection across the full maturation cycle of the immune response and highlights the potential of such approaches to improve understanding of the immune system within the whole organism

    Becoming Allies Accomplices: Problematizing the Intersection of Reflection and Action through Pre-Service Teachers’ Autoethnographies as Praxis

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    Allies would be in strikethrough in the title.This paper explores the phenomenon of pre-service teachers becoming accomplices for racial justice. Using hermeneutic phenomenology, we examine the experiences of three white, female pre-service teachers navigating this terrain.A framework we are naming autoethnography as praxis emerged from this inquiry.Our research interrogates the notion of white allies and the intersection of critical dialogue and action in pre-service teacher education. Building off of perspectives in critical race and critical whiteness studies, this work is grounded in the reality of the material permanence of white supremacy that white teachers must acknowledge and develop tools to dismantle.Autoethnography as praxis moves students from simply analyzing and reporting their experiences (including their emerging understanding of white privilege) through autoethnography to examining how their experiences have shaped and will continue to shape their identities and practices as teachers. By reframing autoethnography as a dialogue between researcher and her texts, we hope to push beyond reflection to action.Autoethnography as praxis also addresses the flaw of white teachers acting as benevolent allies who set their own agenda and position people of color as “needing their assistance.”  It pushes participants to engage their action in reflection, moving them past their own experiences

    Zinc and DHA have opposing effects on the expression levels of histones H3 and H4 in human neuronal cells

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    Zn and DHA have putative neuroprotective effects and these two essential nutrients are known to interact biochemically. We aimed to identify novel protein candidates that are differentially expressed in human neuronal cell line M17 in response to Zn and DHA that would explain the molecular basis of this interaction. Two-dimensional gel electrophoresis and MS were applied to identify major protein expression changes in the protein lysates of human Ml7 neuronal cells that had been grown in the presence and absence of Zn and DHA. Proteomic findings were further investigated using Western immunoblot and real-time PCR analyses. Four protein spots, which had significant differential expression, were identified and selected for in-gel trypsin digestion followed by matrix-assisted laser desorption ionisation MS analysis. The resultant peptide mass fingerprint for each spot allowed their respective identities to be deduced. Two human histone variants H3 and H4 were identified. Both H3 and H4 were downregulated by Zn in the absence of DHA (Zn effect) and upregulated by DHA (DHA effect) in the presence of Zn (physiological condition). These proteomic findings were further supported by Western immunoblot and real-time PCR analyses using H3- and H4-specific monoclonal antibodies and oligonucleotide primers, respectively. We propose that dietary Zn and DHA cause a global effect on gene expression, which is mediated by histones. Such novel information provides possible clues to the molecular basis of neuroprotection by Zn and DHA that may contribute to the future treatment, prevention and management of neurodegenerative diseases such as Alzheimer\u27s disease.<br /

    The crystal structure of PD1, a Haemophilus surface fibril domain

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    The Haemophilus surface fibril (Hsf) is an unusually large trimeric autotransporter adhesin (TAA) expressed by the most virulent strains of H. influenzae. Hsf is known to mediate adhesion between pathogen and host, allowing the establishment of potentially deadly diseases such as epiglottitis, meningitis and pneumonia. While recent research has suggested that this TAA might adopt a novel `hairpin-like' architecture, the characterization of Hsf has been limited to in silico modelling and electron micrographs, with no high-resolution structural data available. Here, the crystal structure of Hsf putative domain 1 (PD1) is reported at 3.3 Å resolution. The structure corrects the previous domain annotation by revealing the presence of an unexpected N-terminal TrpRing domain. PD1 represents the first Hsf domain to be solved, and thus paves the way for further research on the `hairpin-like' hypothesis.Peer reviewe

    Chickens, more than humans, focus the diversity of their immunoglobulin genes on the complementarity-determining region but utilise amino acids, indicative of a more cross-reactive antibody repertoire

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    The mechanisms of B-cell diversification differ greatly between aves and mammals, but both produce B cells and antibodies capable of supporting an effective immune response. To see how differences in the generation of diversity might affect overall repertoire diversity, we have compared the diversity characteristics of immunoglobulin genes from domestic chickens to those from humans. Both use V(D)J gene rearrangement and somatic hypermutation, but only chickens use somatic gene conversion. A range of diversity analysis tools were used to investigate multiple aspects of amino acid diversity at both the germline and repertoire levels. The effect of differing amino acid usages on antibody characteristics was assessed. At both the germline and repertoire levels, chickens exhibited lower amino acid diversity in comparison to the human immunoglobulin genes, especially outside of the complementarity-determining region (CDR). Chickens were also found to possess much larger and more hydrophilic CDR3s with a higher predicted protein binding potential, suggesting that the antigen-binding site in chicken antibodies is more flexible and more polyreactive than that seen in human antibodies

    Psychiatry, subjectivity and emotion - deepening the medical model

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    Morale among psychiatrists continues to be seriously challenged in the face of recruitment difficulties, unfilled posts, diagnostic controversies, service reconfigurations and public criticism of psychiatric care, in addition to other difficulties. In this article, we argue that the positivist paradigm that continues to dominate British psychiatry has led to an undervaluing of subjectivity and of the role of emotions within psychiatric training and practice. Reintegrating the subjective perspective and promoting emotional awareness and reflection may go some way towards restoring faith in the psychiatric specialty

    Effects of a 4-week intervention using semi-custom insoles on perceived pain and patellofemoral loading in targeted subgroups of recreational runners with patellofemoral pain

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    OBJECTIVE: Explore the effects of a 4-week intervention using semi-custom insoles in recreational runners with patellofemoral pain. DESIGN: Mixed methods PARTICIPANTS: Seventeen (10 males and 7 females) recreational runners. SETTING: Laboratory OUTCOME MEASUREMENTS: Participants were separated into specific subgroups, then provided with a pair of semi-custom insoles, for a period of 4-weeks. Lower extremity kinetics/kinematics during running at 4.0 m/s were obtained. In addition, knee pain was examined using the Knee injury and Osteoarthritis Outcome Score-Patellofemoral scale (KOOS-PF). Data were collected before and after wearing the insoles for 4-weeks. RESULTS: Significant improvements were shown for KOOS-PF in both subgroups (strong: (pre)=63.84 & (post)=71.49 and weak and tight: (pre)=53.03 & (post)=72.73), although only improvements in the weak and tight group exceeded the minimum clinically important difference (MCID). In addition, significant reductions in peak patellofemoral stress were shown in both subgroups (strong: (pre)=6.82 & (post)=6.39KPa/BW and weak and tight: (pre)=7.66 & (post)=6.28KPa/BW), although only reductions in the weak and tight group exceeded the MCID. CONCLUSIONS: Semi-custom insoles may be a mechanism to reduce patellofemoral pain symptoms in recreational runners from the weak and tight subgroup. It is proposed that this improvement was mediated through reductions in patellofemoral loading in this subgroup
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