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The blood vasculature regulates both the development and function of secondary lymphoid organs by providing a portal for entry of hemopoietic cells. During the development of lymphoid organs in the embryo, blood vessels deliver lymphoid tissue inducer cells that initiate and sustain the development of lymphoid tissues. In adults, the blood vessels are structurally distinct from those in other organs due to the requirement for high levels of lymphocyte recruitment under non-inflammatory conditions. In lymph nodes (LNs) and Peyer's patches, high endothelial venules (HEVs) especially adapted for lymphocyte trafficking form a spatially organized network of blood vessels, which controls both the type of lymphocyte and the site of entry into lymphoid tissues. Uniquely, HEVs express vascular addressins that regulate lymphocyte entry into lymphoid organs and are, therefore, critical to the function of lymphoid organs. Recent studies have demonstrated important roles for CD11c+ dendritic cells in the induction, as well as the maintenance, of vascular addressin expression and, therefore, the function of HEVs. Tertiary lymphoid organs (TLOs) are HEV containing LN-like structures that develop inside organized tissues undergoing chronic immune-mediated inflammation. In autoimmune lesions, the development of TLOs is thought to exacerbate disease. In cancerous tissues, the development of HEVs and TLOs is associated with improved patient outcomes in several cancers. Therefore, it is important to understand what drives the development of HEVs and TLOs and how these structures contribute to pathology. In several human diseases and experimental animal models of chronic inflammation, there are some similarities between the development and function of HEVs within LN and TLOs. This review will summarize current knowledge of how hemopoietic cells with lymphoid tissue-inducing, HEV-inducing, and HEV-maintaining properties are recruited from the bloodstream to induce the development and control the function of lymphoid organs. © 2017 Ager.

Nieuwenhuis M.,CardiffUniversity | Knight C.,University of Exeter | Postmes T.,University of Groningen | Haslam S.A.,University of Queensland
Journal of Experimental Psychology: Applied | Year: 2014

Principles of lean office management increasingly call for space to be stripped of extraneous decorations so that it can flexibly accommodate changing numbers of people and different office functions within the same area. Yet this practice is at odds with evidence that office workers' quality of life can be enriched by office landscaping that involves the use of plants that have no formal work-related function. To examine the impact of these competing approaches, 3 field experiments were conducted in large commercial offices in The Netherlands and the U.K. These examined the impact of lean and "green" offices on subjective perceptions of air quality, concentration, and workplace satisfaction as well as objective measures of productivity. Two studies were longitudinal, examining effects of interventions over subsequent weeks and months. In all 3 experiments enhanced outcomes were observed when offices were enriched by plants. Implications for theory and practice are discussed. © 2014 American Psychological Association.

Shelkovnikova T.A.,CardiffUniversity | Robinson H.K.,CardiffUniversity | Troakes C.,King's College London | Ninkina N.,CardiffUniversity | And 3 more authors.
Human Molecular Genetics | Year: 2014

Paraspeckles are nuclear bodies formed by a set of specialized proteins assembled on the long non-codingRNA NEAT1; they have a role in nuclear retention of hyperedited transcripts and are associated with response to cellular stress. Fused in sarcoma (FUS) protein, linked to a number of neurodegenerative disorders, is an essential paraspeckle component. We have shown that its recruitment to these nuclear structures is mediated by the N-terminal region and requires prion-like activity. FUS interacts with p54nrb/NONO, a major constituent of paraspeckles, in an RNA-dependent manner and responds in the same way as other paraspeckle proteins to alterations in cellular homeostasis such as changes in transcription rates or levels of protein methylation. FUS also regulates NEAT1 levels and paraspeckle formation in cultured cells, and FUS deficiency leads to loss of paraspeckles. Pathological gain-of-function FUS mutations might be expected to affect paraspeckle function in human diseases because mislocalized amyotrophic lateral sclerosis (ALS)-linked FUS variants sequester other paraspeckle proteins into aggregates formed in cultured cells and into neuronal inclusions in a transgenic mouse model of FUSopathy. Furthermore, we detected abundant p54nrb/NONO-positive inclusions in motor neurons of patients with familial forms of ALS caused by FUSmutations, but not in other ALS cases. Our results suggest that both loss and gain of FUS function can trigger disruption of paraspeckle assembly, which may impair protective responses in neurons and thereby contribute to the pathogenesis of FUSopathies. © The Author 2013. Published by Oxford University Press. All rights reserved.

Camberis A.-L.,Macquarie University | McMahon C.A.,Macquarie University | Gibson F.L.,Macquarie University | Boivin J.,CardiffUniversity
Developmental Psychology | Year: 2014

In the context of the trend toward delayed parenthood, this study examines whether older maternal age is associated with greater psychological maturity and whether greater psychological maturity provides any adaptive benefit during the transition to motherhood. A sample of 240 predominantly Englishspeaking Australian women in a metropolitan area expecting their 1st baby (mean age = 32.81 years; 41% conceived after fertility treatment) completed measures of psychological maturity (hardiness, ego development, and ego resiliency) and pregnancy adaptation (maternal fetal attachment and formation of a maternal identity) in the 3rd trimester of pregnancy and a measure of postnatal adjustment at 4-6 months postpartum. Structural equation modeling showed age was positively associated with a latent construct of psychological maturity, and psychological maturity was associated with more optimal adaptation in pregnancy and early motherhood. Both psychological maturity and pregnancy adaptation predicted positive postnatal adjustment. Age was indirectly related to adaptation through its relationship with psychological maturity. The relationships in the model applied regardless of mode of conception (fertility treatment or spontaneous). Potentially confounding contextual factors associated with older age at motherhood, higher education, and maternal and child health were included in the model. These results suggest that psychological maturity is a benefit of motherhood at older ages. © 2014 American Psychological Association.

Treasure T.,University College London | Milosevic M.,University of Novi Sad | Fiorentino F.,Imperial College London | Macbeth F.,CardiffUniversity
Thorax | Year: 2014

Pulmonary metastasectomy is a commonly performed operation and is tending to increase as part of a concept of personalised treatment for advanced cancer. There have been no randomised trials; belief in effectiveness of metastasectomy is based on registry data and surgical follow-up studies. These retrospective series are comprised predominately of solitary or few metastases with primary resection to metastasectomy intervals longer than 2-3 years. Five-year survival rates of 30-50% are recorded, but as case selection is based on favourable prognostic features, an apparent association between metastasectomy and survival cannot be interpreted as causation. Cancers for which lung metastasectomy is used are considered in four pathological groups. In non-seminomatous germ cell tumour, for which chemotherapy is highly effective, excision of residual pulmonary disease guides future treatment and in particular allows an informed decisions as to further chemotherapy. Sarcoma metastasises predominately to lung and pulmonary metastasectomy for both bone and soft tissues sarcoma is routinely considered as a treatment option but without randomised data. The commonest circumstance for lung and liver metastasectomy is colorectal cancer. Repeated resections and ablations are commonplace but without evidence of effectiveness for either. For melanoma, results are particularly poor, but lung metastases are resected when no other treatment options are available. In this review, the available evidence is considered and the conclusion reached is that in the absence of randomised trials there is uncertainty about effectiveness. A randomised controlled trial, Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC), is in progress and randomised trials in sarcoma seem warranted. © 2014 BMJ Publishing Group Ltd & British Thoracic Society.

Ondondo B.,University of Oxford | Jones E.,CardiffUniversity | Godkin A.,CardiffUniversity | Gallimore A.,CardiffUniversity
Frontiers in Immunology | Year: 2013

CD4+Foxp3+ regulatory T cells (Tregs) have a fundamental role in maintaining immune balance by preventing autoreactivity and immune-mediated pathology. However this role of Tregs extends to suppression of anti-tumor immune responses and remains a major obstacle in the development of anti-cancer vaccines and immunotherapies. This feature of Treg activity is exacerbated by the discovery that Treg frequencies are not only elevated in the blood of cancer patients, but are also significantly enriched within tumors in comparison to other sites. These observations have sparked offthe quest to understand the processes through which Tregs become elevated in cancer-bearing hosts and to identify the specific mechanisms leading to their accumulation within the tumor microenvironment. This manuscript reviews the evidence for specific mechanisms of intra-tumoral Treg enrichment and will discuss how this information may be utilized for the purpose of manipulating the balance of tumor-infiltrating T cells in favor of anti-tumor effector cells. © 2013 Ondondo, Jones, Godkin and Gallimore.

Stokes E.,CardiffUniversity
Medical Law Review | Year: 2013

This article seeks to add to current theories of newgovernance by highlighting the predicament facing regulators and regulatees when dealing with new technologies. Using nanotechnologies as a study, it shows that new modes of governance (as opposed to traditional coercive, or command and control regulation) offer promising solutions to highly complex, uncertain, and contested problems of risk, such as those associated with new technologies. In this regard, nanotechnologies provide a useful test bed for the ambitions of newer, better modes of governance because there are not yet any fixed ideas about the appropriate course of action. The article suggests, however, that examples of new governance are less prominent than perhaps expected. Drawing on empirical data, it argues that, when faced with considerable epistemological, political, economic, and ethical uncertainties, regulatory stakeholders often exhibit a preference for more conventional command methods of regulation. That is not to say that new governance is entirely absent from regulatory policies on nanotechnologies, but that new governance is emerging in perhaps more subtle ways than the scholarly and policy literature predicted. © The Author [2013]. Published by Oxford University Press. all rights reserved.

Macken B.,CardiffUniversity | Taylor J.C.,CardiffUniversity | Jones D.M.,CardiffUniversity
Journal of Experimental Psychology: Learning Memory and Cognition | Year: 2014

The advantage for real words over nonwords in serial recall-the lexicality effect-is typically attributed to support for item-level phonology, either via redintegration, whereby partially degraded short-term traces are "cleaned up" via support from long-term representations of the phonological material or via the more robust temporary activation of long-term lexical phonological knowledge that derives from its combination with established lexical and semantic levels of representation. The much smaller effect of lexicality in serial recognition, where the items are re-presented in the recognition cue, is attributed either to the minimal role for redintegration from long-term memory or to the minimal role for item memory itself in such retrieval conditions. We show that the reduced lexicality effect in serial recognition is not a function of the retrieval conditions, but rather because previous demonstrations have used auditory presentation, and we demonstrate a robust lexicality effect for visual serial recognition in a setting where auditory presentation produces no such effect. Furthermore, this effect is abolished under conditions of articulatory suppression. We argue that linguistic knowledge affects the readiness with which verbal material is segmentally recoded via speech motor processes that support rehearsal and therefore affects tasks that involve recoding. On the other hand, auditory perceptual organization affords sequence matching in the absence of such a requirement for segmental recoding and therefore does not show such effects of linguistic knowledge. © 2014 The Author(s).

Yokoi K.,CardiffUniversity
Journal of Computational Physics | Year: 2014

We propose a numerical framework which can simulate free surface flows with complex moving interfaces like droplet splashing as minimizing spurious currents. The numerical framework is based on the CLSVOF (coupled level set and volume-of-fluid) method, the THINC/WLIC (tangent of hyperbola for interface capturing/weighted line interface calculation) scheme, multi-moment methods (CIP-CSL and VSIAM3) and density-scaled CSF (continuum surface force) model within a balanced force formulation. In this paper, we propose a level set based algorithm of the density-scaled balanced CSF model and show that the density-scaled balanced CSF model can reduce spurious currents more than the standard balanced CSF model without using the density-scaling when the exact curvature is not given. We also show that the numerical framework can well capture the physics of droplet splashing. © 2014 Elsevier Inc.

Kirov G.,CardiffUniversity
Human Molecular Genetics | Year: 2015

Over the last few years at least 11 copy number variations (CNVs) have been shown convincingly to increase risk to developing schizophrenia: deletions at 1q21.1, NRXN1, 3q29, 15q11.2, 15q13.3 and 22q11.2, and duplications at 1q21.1, 7q11.23, 15q11.2-q13.1, 16p13.1 and proximal 16p11.2. They are very rare, found cumulatively in 2.4% of patients with schizophrenia and in only 0.5% of controls. They all increase risk for other neurodevelopmental disorders, such as developmental delay and autism spectrum disorders, where they are found at higher rates (3.3%). Their involvement in bipolar affective disorder is much less prominent. All of them affect multiple genes (apart from NRXN1) and cause substantial increases in risk to develop schizophrenia (odds ratios of 2 to over 50). Their penetrance for any neurodevelopmental disorder is high, from ?10% to nearly 100%. Carriers of these CNVs display cognitive deficits, even when free of neuropsychiatric disorders. © The Author 2015. Published by Oxford University Press. All rights reserved.

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