46 research outputs found

    Embracing the gut microbiota: the new frontier for inflammatory and infectious diseases

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    The gut microbiota provides essential signals for the development and appropriate function of the immune system. Through this critical contribution to immune fitness, the gut microbiota has a key role in health and disease. Recent advances in the technological applications to study microbial communities and their functions have contributed to a rapid increase in host–microbiota research. Although it still remains difficult to define a so‐called ‘normal’ or ‘healthy’ microbial composition, alterations in the gut microbiota have been shown to influence the susceptibility of the host to different diseases. Current translational research combined with recent technological and computational advances have enabled in‐depth study of the link between microbial composition and immune function, addressing the interplay between the gut microbiota and immune responses. As such, beneficial modulation of the gut microbiota is a promising clinical target for many prevalent diseases including inflammatory bowel disease, metabolic abnormalities such as obesity, reduced insulin sensitivity and low‐grade inflammation, allergy and protective immunity against infections.Lieke WJ van den Elsen, Hazel C Poyntz, Laura S Weyrich, Wayne Young, Elizabeth E Forbes‐Blo

    Globular cluster systems and galaxy formation

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    Globular clusters are compact, gravitationally bound systems of up to a million stars. The GCs in the Milky Way contain some of the oldest stars known, and provide important clues to the early formation and continuing evolution of our Galaxy. More generally, GCs are associated with galaxies of all types and masses, from low-mass dwarf galaxies to the most massive early-type galaxies which lie in the centres of massive galaxy clusters. GC systems show several properties which connect tightly with properties of their host galaxies. For example, the total mass of GCs in a system scales linearly with the dark matter halo mass of its host galaxy. Numerical simulations are at the point of being able to resolve globular cluster formation within a cosmological framework. Therefore, GCs link a range of scales, from the physics of star formation in turbulent gas clouds, to the large-scale properties of galaxies and their dark matter. In this Chapter we review some of the basic observational approaches for GC systems, some of their key observational properties, and describe how GCs provide important clues to the formation of their parent galaxies.Comment: 32 pages, 6 figures. Accepted for publication in the book "Reviews in Frontiers of Modern Astrophysics: From Space Debris to Cosmology" (eds Kabath, Jones and Skarka; publisher Springer Nature) funded by the European Union Erasmus+ Strategic Partnership grant "Per Aspera Ad Astra Simul" 2017-1-CZ01-KA203-03556

    Self-love and sociability: the ‘rudiments of commerce’ in the state of nature

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    Istvan Hont’s classic work on the theoretical links between the seventeenth-century natural jurists Hugo Grotius and Samuel Pufendorf and the eighteenth-century Scottish political economists remains a popular trope among intellectual and economic historians of various stamps. Despite this, a common criticism levelled at Hont remains his relative lack of engagement with the relationship between religion and economics in the early modern period. This paper challenges this aspect of Hont’s narrative by drawing attention to an alternative, albeit complementary, assessment of the natural jurisprudential heritage of eighteenth-century British political economy. Specifically, the article attempts to map on to Hont’s thesis the Christian Stoic interpretation of Grotius and Pufendorf which has gained greater currency in recent years. In doing so, the paper argues that Grotius and Pufendorf’s contributions to the ‘unsocial sociability’ debate do not necessarily lead directly to the Scottish school of political economists, as is commonly assumed. Instead, it contends that a reconsideration of Grotius and Pufendorf as neo-Stoic theorists, particularly via scrutiny of their respective adaptations of the traditional Stoic theory of oikeiosis, steers us towards the heart of the early English ‘clerical’ Enlightenment

    A Dutch guideline for the treatment of scoliosis in neuromuscular disorders

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    <p>Abstract</p> <p>Background</p> <p>Children with neuromuscular disorders with a progressive muscle weakness such as Duchenne Muscular Dystrophy and Spinal Muscular Atrophy frequently develop a progressive scoliosis. A severe scoliosis compromises respiratory function and makes sitting more difficult. Spinal surgery is considered the primary treatment option for correcting severe scoliosis in neuromuscular disorders. Surgery in this population requires a multidisciplinary approach, careful planning, dedicated surgical procedures, and specialized after care.</p> <p>Methods</p> <p>The guideline is based on scientific evidence and expert opinions. A multidisciplinary working group representing experts from all relevant specialties performed the research. A literature search was conducted to collect scientific evidence in answer to specific questions posed by the working group. Literature was classified according to the level of evidence.</p> <p>Results</p> <p>For most aspects of the treatment scientific evidence is scarce and only low level cohort studies were found. Nevertheless, a high degree of consensus was reached about the management of patients with scoliosis in neuromuscular disorders. This was translated into a set of recommendations, which are now officially accepted as a general guideline in the Netherlands.</p> <p>Conclusion</p> <p>In order to optimize the treatment for scoliosis in neuromuscular disorders a Dutch guideline has been composed. This evidence-based, multidisciplinary guideline addresses conservative treatment, the preoperative, perioperative, and postoperative care of scoliosis in neuromuscular disorders.</p

    Allergen-specific CTL require perforin expression to suppress allergic airway inflammation.

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    C1 - Journal Articles RefereedAllergen-specific CTL have a protective effect on allergic airway inflammation, a function thought to be mediated by cytokines, especially IFN-γ. However, the contribution of cytotoxic function to this protective effect has not been investigated. We examined the contribution of cytotoxic function to the therapeutic effect of allergen-specific CTL in allergic airway inflammation. We used a murine model of allergic airway inflammation in which mice were sensitized to OVA and then challenged with the same Ag via the intranasal route. CTL were elicited in these mice by immunization with dendritic cells (DC) or by adoptive transfer of in vitro-activated CD8(+) T cells. Hallmark features of allergic asthma, such as infiltration of eosinophils in the bronchoalveolar lavage fluid and mucus production, were assessed. Suppression of allergic airway inflammation by allergen-specific CTL was critically dependent on the expression of perforin, a key component of the cytotoxic machinery. Both perforin-sufficient and perforin-deficient allergen-specific CTL were recovered from the lungs of allergen-sensitized mice and upregulated CD69 expression and secreted the cytokines IFN-γ and TNF-α upon intranasal allergen challenge. However, only perforin-sufficient CTL inhibited eosinophil infiltration in the airway, mucus production, and cytokine accumulation in the bronchoalveolar lavage fluid. Treatment with allergen-specific CTL, but not their perforin-deficient counterparts, was also associated with a decrease in the number of DC in the mediastinal lymph node. Our data suggest that the cytotoxic function of allergen-specific CD8(+) T cells is critical to their ability to moderate allergic airway inflammation

    Eosinophils determine dermal thickening and water loss in an MC903 model of atopic dermatitis

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    Atopic dermatitis (AD) is a highly debilitating disease with significant health impacts worldwide. It has been a difficult disease to treat because of the wide spectrum of clinical manifestations. Therefore, the current clinical management strategies are nonspecific. Previous studies have documented that AD disease progression is precipitated by a combination of skin barrier dysfunction, itch, and immune dysregulation. However, the precise roles played by effector cells and cytokines have not been fully elucidated. To address this, we established a prolonged model of AD, using MC903. The phenotype of this MC903 model closely resembles the one observed in AD patients, including inflammatory parameters, barrier dysfunction, itch, and histopathological characteristics, thereby providing a platform to evaluate targets for the treatment of AD. This model exposed cells and cytokines that are critically associated with disease severity, including eosinophils, TSLP, and IL-4/IL-13. Indeed, eosinophil depletion significantly ameliorated AD pathology, most notably barrier dysfunction, to a similar extent as blocking of the IL-4/IL-13 axis by genetic deletion of STAT6. Thus, this study has identified eosinophils to be critical for the development and maintenance of AD, thereby proposing these effector cells as therapeutic targets for the treatment of AD

    Eosinophils determine dermal thickening and water loss in an MC903 model of atopic dermatitis

    No full text
    Atopic dermatitis (AD) is a highly debilitating disease with significant health impacts worldwide. It has been a difficult disease to treat because of the wide spectrum of clinical manifestations. Therefore, the current clinical management strategies are nonspecific. Previous studies have documented that AD disease progression is precipitated by a combination of skin barrier dysfunction, itch, and immune dysregulation. However, the precise roles played by effector cells and cytokines have not been fully elucidated. To address this, we established a prolonged model of AD, using MC903. The phenotype of this MC903 model closely resembles the one observed in AD patients, including inflammatory parameters, barrier dysfunction, itch, and histopathological characteristics, thereby providing a platform to evaluate targets for the treatment of AD. This model exposed cells and cytokines that are critically associated with disease severity, including eosinophils, TSLP, and IL-4/IL-13. Indeed, eosinophil depletion significantly ameliorated AD pathology, most notably barrier dysfunction, to a similar extent as blocking of the IL-4/IL-13 axis by genetic deletion of STAT6. Thus, this study has identified eosinophils to be critical for the development and maintenance of AD, thereby proposing these effector cells as therapeutic targets for the treatment of AD
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