Aberrant IL-17 levels in rodent models of Autism Spectrum Disorder:a systematic review

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder characterised by stereotyped behaviours, specific interests, and impaired communication skills. Elevated levels of pro-inflammatory cytokines, such as interleukin-17A (IL-17A or IL-17), have been implicated as part of immune alterations that may contribute to this outcome. In this context, rodent models have helped elucidate the role of T-cell activation and IL-17 secretion in the pathogenesis of ASD. Regarding the preclinical findings, the data available is contradictory in offspring but not in the pregnant dams, pointing to IL-17 as one of the main drivers of altered behaviour in some models ASD, whilst there are no alterations described in IL-17 levels in others. To address this gap in the literature, a systematic review of altered IL-17 levels in rodent models of ASD was conducted. In total, 28 studies that explored IL-17 levels were included and observed that this cytokine was generally increased among the different models of ASD. The data compiled in this review can help the choice of animal models to study the role of cytokines in the development of ASD, seeking a parallel with immune alterations observed in individuals with this condition. Systematic Review Registration: PROSPERO, identifier CRD42022306558

Zika virus disrupts gene expression in human myoblasts and myotubes: Relationship with susceptibility to infection

The tropism of Zika virus (ZIKV) has been described in the nervous system, blood, placenta, thymus, and skeletal muscle. We investigated the mechanisms of skeletal muscle susceptibility to ZIKV using an in vitro model of human skeletal muscle myogenesis, in which myoblasts differentiate into myotubes. Myoblasts were permissive to ZIKV infection, generating productive viral particles, while myotubes controlled ZIKV replication. To investigate the underlying mechanisms, we used gene expression profiling. First, we assessed gene changes in myotubes compared with myoblasts in the model without infection. As expected, we observed an increase in genes and pathways related to the contractile muscle system in the myotubes, a reduction in processes linked to proliferation, migration and cytokine production, among others, confirming the myogenic capacity of our system in vitro. A comparison between non-infected and infected myoblasts revealed more than 500 differentially expressed genes (DEGs). In contrast, infected myotubes showed almost 2,000 DEGs, among which we detected genes and pathways highly or exclusively expressed in myotubes, including those related to antiviral and innate immune responses. Such gene modulation could explain our findings showing that ZIKV also invades myotubes but does not replicate in these differentiated cells. In conclusion, we showed that ZIKV largely (but differentially) disrupts gene expression in human myoblasts and myotubes. Identifying genes involved in myotube resistance can shed light on potential antiviral mechanisms against ZIKV infection

Laminin therapy for the promotion of muscle regeneration

AbstractMuscle regeneration is essentially due to activation of satellite cells, which can be isolated and amplified ex vivo, thus representing good candidates for cell therapy. Accumulating data show that the local microenvironment plays a major role during muscle regeneration. In the satellite cell niche, a major extracellular matrix protein is laminin. Human myoblasts transplanted into immunodeficient mice are preferentially located in laminin-enriched areas. Additionally, laminin-111 enhances myoblast proliferation in vitro and increases expression of the α7β1 integrin-type laminin receptor. Intramuscular injection of laminin-111 ameliorates muscular pathology in mdx mice, protecting muscle fibers from damage. Moreover, transplantation of human myoblasts with laminin-111 into Rag/mdx immunodeficient recipients improved efficacy of myoblast transplantation, increasing the number of human dystrophin-positive myofibres. Taken together, these data strongly indicate that exogenous laminin can ameliorate the regeneration process in different models of muscular dystrophies and can be instrumental for improving cell therapy aiming at repairing the degeneration/regeneration process in skeletal muscle

Kablosuz ağlar için bir yazılıma dayalı ağ yaklaşımı

Thesis (M.A.)--Özyeğin University, Graduate School of Sciences and Engineering, Department of Computer Science, May 2015.The tremendous growth in wireless Internet use is showing no signs of slowing down. Existing cellular networks are starting to be insufficient in meeting this demand in part due to their inflexible and expensive equipment as well as complex and non-agile control plane. Software-defined networking (SDN) is emerging as a natural solution for the next generation cellular networks as it enables further Network Functions Virtualization (NFV) opportunities and network programmability. In this dissertation, we advocate an all-SDN network architecture with hierarchical network control capabilities to allow for different grades of performance and complexity in offering core network services and provide service differentiation for 5G systems. As a showcase of this architecture, we first introduce a unified approach to mobility, handoff and routing management and offer Connectivity Management as a Service (CMaaS). CMaaS is offered to application developers and over-the-top service providers to provide a range of options in protecting their flows against subscriber mobility at different price levels. Next, we present the implementation details of a distributed SDN controller specifically crafted to realize the proposed all-SDN architecture and investigate the flow-level performance characteristics of the system.Gün geçtikçe artan internet kullanım oranı hızını kesmeden büyümeye devam etmektedir. Pahalı ve karmaşık olmanın yanı sıra gerekli esneklik ve çeviklikten uzak olan mevcut hücresel ağlar ise bu artan talebi karşılamakta yetersiz kalmaktadır. Sağladıkları Ağ Fonksiyonu Sanallaştırması ve programlanabilirlik kabiliyetleri ile Yazılıma Dayalı Ağlar (YDA) yeni nesil hücresel ağlar için doğal bir çözüm olarak karşımıza çıkmaktadırlar. Bu doktora tezinde, merkezi ağ servislerinde farklı başarım ve karmaşıklık seviyelerine ve 5G sistemlerde servis farklılaştırılmasına imkan sunan, hiyerarşik ağ kontrol donanımına sahip bütün bir YDA ağ mimarisi yaklaşımı savunulmaktadır. Bu mimarının somut bir temsili olarak ilk önce hareketlilik, hücreler arası transfer ve rotalama yönetimini birleşik bir şekilde ele alan Servis Olarak Bağlantı Yönetimi (SOBY) yaklaşımı tanıtılmaktadır. SOBY, uygulama geliştiricileri ve servis sağlayıcıları için, üyelerin hareketliliğinin ağ üzerindeki akışlarına olan etkisinin ücretlendirmeye göre farklılaştırılmasına olanak sağlamaktadır. Devamında, bahsi geçen YDA mimarisi için özel olarak geliştirilmiş yazılımsal yönetici gerçeklemesi ayrıntılandırılarak, sistemin akış başarım karakteristiği incelenmektedir

Laminin-Mediated interactions in Thymocyte Migration and Development

Submitted by sandra infurna ([email protected]) on 2016-04-14T16:08:30Z No. of bitstreams: 1 wilson3_savino_etl_IOC_2015.pdf: 889837 bytes, checksum: 4fa4cdafd4c3d852c3f398c218aa99d2 (MD5)Approved for entry into archive by sandra infurna ([email protected]) on 2016-04-14T16:20:34Z (GMT) No. of bitstreams: 1 wilson3_savino_etl_IOC_2015.pdf: 889837 bytes, checksum: 4fa4cdafd4c3d852c3f398c218aa99d2 (MD5)Made available in DSpace on 2016-04-14T16:20:34Z (GMT). No. of bitstreams: 1 wilson3_savino_etl_IOC_2015.pdf: 889837 bytes, checksum: 4fa4cdafd4c3d852c3f398c218aa99d2 (MD5) Previous issue date: 2015Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil.Intrathymic T-cell differentiation is a key process for the development and maintenance of cell-mediated immunity, and occurs concomitantly to highly regulated migratory events. We have proposed a multivectorial model for describing intrathymic thymocyte migration. One of the individual vectors comprises interactions mediated by laminins (LMs), a heterotrimeric protein family of the extracellular matrix. Several LMs are expressed in the thymus, being produced by microenvironmental cells, particularly thymic epithelial cells (TECs). Also, thymocytes and epithelial cells express integrin-type LM receptors. Functionally, it has been reported that the dy/dy mutant mouse (lacking the LM isoform 211) exhibits defective thymocyte differentiation. Several data show haptotactic effects of LMs upon thymocytes, as well as their adhesion on TECs; both effects being prevented by anti-LM or anti-LM receptor antibodies. Interestingly, LM synergizes with chemokines to enhance thymocyte migration, whereas classe-3 semaphorins and B ephrins, which exhibit chemorepulsive effects in the thymus, downregulate LM-mediated migratory responses of thymocytes. More recently, we showed that knocking down the ITGA6 gene (which encodes the α6 integrin chain of LM receptors) in human TECs modulates a large number of cell migration-related genes and results in changes of adhesion pattern of thymocytes onto the thymic epithelium. Overall, LM-mediated interactions can be placed at the cross-road of the multivectorial process of thymocyte migration, with a direct influence per se, as well as by modulating other molecular interactions associated with the intrathymic-trafficking events

Neuroendocrine Control of Macrophage Development and Function

Submitted by Sandra Infurna ([email protected]) on 2019-02-10T19:28:55Z No. of bitstreams: 1 arnondias_juberg_etal_IOC_2018.pdf: 2042436 bytes, checksum: e62a73d671b9925b43cab1a45f36a80a (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2019-02-10T19:40:25Z (GMT) No. of bitstreams: 1 arnondias_juberg_etal_IOC_2018.pdf: 2042436 bytes, checksum: e62a73d671b9925b43cab1a45f36a80a (MD5)Made available in DSpace on 2019-02-10T19:40:25Z (GMT). No. of bitstreams: 1 arnondias_juberg_etal_IOC_2018.pdf: 2042436 bytes, checksum: e62a73d671b9925b43cab1a45f36a80a (MD5) Previous issue date: 2018Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil / Instituto Nacional de Ciência e Tecnologia em Neuroimunomodulação. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil / Instituto Nacional de Ciência e Tecnologia em Neuroimunomodulação. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil / Instituto Nacional de Ciência e Tecnologia em Neuroimunomodulação. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil / Instituto Nacional de Ciência e Tecnologia em Neuroimunomodulação. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil / Instituto Nacional de Ciência e Tecnologia em Neuroimunomodulação. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil / Instituto Nacional de Ciência e Tecnologia em Neuroimunomodulação. Rio de Janeiro, RJ, Brasil.Macrophages carry out numerous physiological activities that are essential for both systemic and local homeostasis, as well as innate and adaptive immune responses. Their biology is intricately regulated by hormones, neuropeptides, and neurotransmitters, establishing distinct neuroendocrine axes. The control is pleiotropic, including maturation of bone marrow-derived myeloid precursors, cell differentiation into functional subpopulations, cytotoxic activity, phagocytosis, production of inflammatory mediators, antigen presentation, and activation of effector lymphocytes. Additionally, neuroendocrine components modulate macrophage ability to influence tumor growth and to prevent the spreading of infective agents. Interestingly, macrophage-derived factors enhance glucocorticoid production through the stimulation of the hypothalamic–pituitary–adrenal axis. These bidirectional effects highlight a tightly controlled balance between neuroendocrine stimuli and macrophage function in the development of innate and adaptive immune responses. Herein, we discuss how components of neuroendocrine axes impact on macrophage development and function and may ultimately influence inflammation, tissue repair, infection, or cancer progression. The knowledge of the crosstalk between macrophages and endocrine or brain-derived components may contribute to improve and create new approaches with clinical relevance in homeostatic or pathological conditions

HGF potentiates extracellular matrix-driven migration of human myoblasts: involvement of matrix metalloproteinases and MAPK/ERK pathway

International audienceBackground: The hepatocyte growth factor (HGF) is required for the activation of muscle progenitor cells called satellite cells (SC), plays a role in the migration of proliferating SC (myoblasts), and is present as a soluble factor during muscle regeneration, along with extracellular matrix (ECM) molecules. In this study, we aimed at determining whether HGF is able to interact with ECM proteins, particularly laminin 111 and fibronectin, and to modulate human myoblast migration.Methods: We evaluated the expression of the HGF-receptor c-Met, laminin, and fibronectin receptors by immunoblotting, flow cytometry, or immunofluorescence and used Transwell assays to analyze myoblast migration on laminin 111 and fibronectin in the absence or presence of HGF. Zymography was used to check whether HGF could modulate the production of matrix metalloproteinases by human myoblasts, and the activation of MAPK/ERK pathways was evaluated by immunoblotting.Results: We demonstrated that human myoblasts express c-Met, together with laminin and fibronectin receptors. We observed that human laminin 111 and fibronectin have a chemotactic effect on myoblast migration, and this was synergistically increased when low doses of HGF were added. We detected an increase in MMP-2 activity in myoblasts treated with HGF. Conversely, MMP-2 inhibition decreased the HGF-associated stimulation of cell migration triggered by laminin or fibronectin. HGF treatment also induced in human myoblasts activation of MAPK/ERK pathways, whose specific inhibition decreased the HGF-associated stimulus of cell migration triggered by laminin 111 or fibronectin.Conclusions: We demonstrate that HGF induces ERK phosphorylation and MMP production, thus stimulating human myoblast migration on ECM molecules. Conceptually, these data state that the mechanisms involved in the migration of human myoblasts comprise both soluble and insoluble moieties. This should be taken into account to optimize the design of therapeutic cell transplantation strategies by improving the migration of donor cells within the host tissue, a main issue regarding this approach