Background It has previously been shown that dual activation of the Liver X Receptors (LXRα and LXRβ) by the agonist, GW3965, enhances pathology in a murine model of collagen-induced arthritis. ...Objective To determine whether LXRα or LXRβ have discrete roles in driving articular inflammation. Methods Arthritis was induced in male C57BL/6 wild-type (WT), LXRα−/−, LXRβ−/− and LXRα/β double KO mice by injection with type II collagen and treated with 30 mg/kg of the LXR agonist GW3965 or vehicle control. The mice were monitored for articular inflammation and cartilage degradation by scoring for clinical signs of arthritis and by histological examination of the joints. Results Administration of 30 mg/kg GW3965 significantly increases the severity of arthritis in WT but not LXRα−/−, LXRβ−/− or LXRα/β KO mice as assessed by an increase in the clinical score, paw thickness and articular histological analysis. Conclusion The proinflammatory effects associated with the administration of GW3965 are mediated specifically through LXRs. The absence of increased disease severity in the LXRα−/− and LXRβ−/− GW3965-treated groups shows for the first time that agonism of both LXRα and LXRβ is required to drive proinflammatory pathways in vivo.
The ripple effects of the Macpherson inquiry were felt by police organizations worldwide. However, the points Macpherson was making were never to be limited to race, ethnicity, or cultural ...difference. Nonetheless, the policies and practices to emerge since the Macpherson report have taken race and cultural difference as a template for the development of an ever-increasing number of siloed responses to vulnerability in the policing process. In this article, we examine the essential need to depart from the historical and siloed framing of police-race relations. Instead, we argue that policies and practices should respond to vulnerability as a fundamental socio-cultural characteristic of all criminal justice encounters. After much public scrutiny, many vulnerable groups have now become the target of non-negotiable, precautionary protocols for police to abide by, in order to address the disadvantage caused by a variety of attributes (such as age, mental health, language). This siloed approach to diversity and the cultural awareness and quota models that emerged from the Macpherson recommendations are no longer adequate for the increasing differentiation of modern societies. We suggest that Macpherson's recommendations, despite their success, have left in their wake a series of institutional artefacts that have ossified policing responses to diversity. As a more realistic template to address a wider understanding of diversity, we propose re-centring vulnerability as a ubiquitous characteristic of all criminal justice encounters through the use of Herring and Henderson's framing of critical diversity (2011).
Honour, violence and heteronormativity Asquith, Nicole L
International journal for crime, justice and social democracy,
2015, Volume:
4, Issue:
3
Journal Article
Peer reviewed
Open access
Honour based violence (HBV) and killings - argument that current construction of HBV as antiquated and deviant Muslim honour code is Islamophobic - better way to understand collective familial ...violence may be as conceptual framework of heteronormativity.
Megakaryocytes (MKs) generate thousands of platelets over their lifespan. The roles of platelets in infection and inflammation has guided an interest to the study of extramedullary thrombopoiesis and ...therefore MKs have been increasingly reported within the spleen and lung. However, the relative abundance of MKs in these organs compared to the bone marrow and the scale of their contribution to the platelet pool in a steady state remain controversial. We investigated the relative abundance of MKs in the adult murine bone marrow, spleen, and lung using whole-mount light-sheet and quantitative histological imaging, flow cytometry, intravital imaging, and an assessment of single-cell RNA sequencing (scRNA-seq) repositories. Flow cytometry revealed significantly higher numbers of hematopoietic stem and progenitor cells and MKs in the murine bone marrow than in spleens or perfused lungs. Two-photon intravital and light-sheet microscopy, as well as quantitative histological imaging, confirmed these findings. Moreover, ex vivo cultured MKs from the bone marrow subjected to static or microfluidic platelet production assays had a higher capacity for proplatelet formation than MKs from other organs. Analysis of previously published murine and human scRNA-seq data sets revealed that only a marginal fraction of MK-like cells can be found within the lung and most likely only marginally contribute to platelet production in the steady state.
Muslim’s women’s visibility and perceived vulnerability make them primary targets of routine Islamophobia in public spaces. This article builds on existing research on intersectionality between ...Islamophobia, gender, and victimisation. It offers fresh data on Islamophobia against women by analysing complaints of interpersonal hostility (N = 73) made to the Islamophobia Register Australia between 2016 and 2017. This quantitative analysis confirms that there is much consistency between Western nations in the nature of Islamophobia directed to women. At the same time, the article brings new perspectives to our understanding of Islamophobic hostility. Drawing on an in-depth analysis of eight case studies, the article illuminates the restrictive impact that routine Islamophobia has on Muslim women’s daily lives, generating a sense of responsibility for their own safety in the absence of bystander intervention. Yet, with comparatively high levels of social capital, participants in our study did not simply acquiesce to stereotypes that deny them the status of ‘ideal’ victim. Instead, they sought to reduce the destructive impact of victimisation through active attempts to raise public awareness and reassert agency. Our study shows that Muslim women’s responses to Islamophobia are not homogeneous. This variation originates in heterogeneity between Muslim women in Western countries.
Psoriasis is a common chronic autoimmune condition of the skin characterized by hyperplasia of epidermal keratinocytes associated with pro‐inflammatory cytokines. IL‐33 is a new member of the IL‐1 ...superfamily that signals through the ST2 receptor and was originally defined as an inducer of T helper 2 (Th2) cytokines. Recently, broader immune activatory potential has been defined for IL‐33 particularly via mast cell activation and neutrophil migration. Here, we show that ST2−/− mice exhibit reduced cutaneous inflammatory responses compared with WT mice in a phorbol ester‐induced model of skin inflammation. Furthermore, injections of IL‐33 into the ears of mice induce an inflammatory skin lesion. This inflammatory response was partially dependent on mast cells as mast cell‐deficient mice (KitW‐sh/W‐sh) showed delayed responses to IL‐33. IL‐33 also recruited neutrophils to the ear, an effect mediated in part by increased production of the chemokine KC (CXCL1). Finally, we show that IL‐33 expression is up‐regulated in the epidermis of clinical psoriatic lesions, compared with healthy skin. These results therefore demonstrate that IL‐33 may play a role in psoriasis‐like plaque inflammation. IL‐33 targeting may provide a new treatment strategy for psoriasis.
Dermal dendritic cells and epidermal Langerhans cells are APCs that migrate from skin to draining lymph nodes (LN) to drive peripheral tolerance and adaptive immunity. Their migration requires the ...chemokine receptor CCR7, which directs egress from the skin via dermal lymphatic vessels and extravasation into the LN parenchyma from lymph in the subcapsular sinus. CCR7 is activated by two chemokines: CCL19 and CCL21. CCL21 alone is sufficient for the migration of APCs from skin to LN. CCL19 and CCL21 also bind atypical chemokine receptor (ACKR) 4. ACKR4-mediated CCL21 scavenging by lymphatic endothelial cells lining the subcapsular sinus ceiling stabilizes interfollicular CCL21 gradients that direct lymph-borne CCR7(+)APCs into the parenchyma of mouse LN. In this study, we show that ACKR4 also aids APC egress from mouse skin under steady-state and inflammatory conditions. ACKR4 plays a particularly prominent role during cutaneous inflammation when it facilitates Langerhans cell egress from skin and enables the accumulation of dermal dendritic cells in skin-draining LN. Stromal cells in mouse skin, predominantly keratinocytes and a subset of dermal lymphatic endothelial cells, express ACKR4 and are capable of ACKR4-dependent chemokine scavenging in situ. ACKR4-mediated scavenging of dermal-derived CCL19, rather than CCL21, is critical during inflammation, because the aberrant trafficking of skin-derived APCs inAckr4-deficient mice is completely rescued by genetic deletion ofCcl19 Thus, ACKR4 on stromal cells aids the egress of APCs from mouse skin, and, during inflammation, facilitates CCR7-dependent cell trafficking by scavenging CCL19.
The debates about how and whether law enforcement and public health share a policy and practice mandate are perplexing. Frontline practice indicates that this intersection is de rigueur, and that ...practitioners from both fields see no reason why they cannot work together beneficially. Indeed, police are as much public health interventionists as health practitioners are public safety facilitators. In this article, we identify the conceptual dissonance that continues to frame the debate about law enforcement and public health, and document the practical synergies that exist (and have always existed) in both fields. We suggest that the divide between law enforcement and public health is futile, and that the shared concept of vulnerability in policing, health and law can do much to foster better collaborative practices, policies and shared understandings.
Tumor necrosis factor α is an inflammatory cytokine which has been linked with many infectious and inflammatory diseases. Detection and quantification of this key biomarker is commonly achieved by ...use of an enzyme-linked immunosorbent assay (ELISA). This fundamental technique uses the spectroscopic detection of a chromogen such as 3,3′,5,5′-tetramethylbenzidine (TMB). Horseradish peroxidase (HRP), bound to the detection antibody, catalyzes the oxidation of TMB by hydrogen peroxide to generate colored products which may be measured spectrophotometrically. In this study we have used a conventional ELISA kit and shown that, by replacing the traditional colorimetric detection with resonance Raman spectroscopy, we can achieve 50 times lower detection limits and the potential for multiplexed analysis is increased. In this approach, the laser wavelength was tuned to be in resonance with an electronic transition of the oxidized TMB. The relative intensity of the enhanced Raman bands is proportional to the amount of TMB, thus providing a means of improved quantification. Furthermore, TMB is one of the most widely used chromogenic substrates for HRP-based detection and commercial ELISA test kits, indicating that this detection technique is applicable to a large number of target analytes.
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