Administration of M. leprae Hsp65 Interferes with the Murine Lupus Progression

The heat shock protein [Hsp] family guides several steps during protein synthesis, are abundant in prokaryotic and eukaryotic cells, and are highly conserved during evolution. The Hsp60 family is involved in assembly and transport of proteins, and is expressed at very high levels during autoimmunity or autoinflammatory phenomena. Here, the pathophysiological role of the wild type [WT] and the point mutated K409A recombinant Hsp65 of M. leprae in an animal model of Systemic Lupus Erythematosus [SLE] was evaluated in vivo using the genetically homogeneous [NZBxNZW]F1 mice. Anti-DNA and anti-Hsp65 antibodies responsiveness was individually measured during the animal's life span, and the mean survival time [MST] was determined. The treatment with WT abbreviates the MST in 46%, when compared to non-treated mice [p<0.001]. An increase in the IgG2a/IgG1 anti-DNA antibodies ratio was also observed in animals injected with the WT Hsp65. Incubation of BALB/c macrophages with F1 serum from WT treated mice resulted in acute cell necrosis; treatment of these cells with serum from K409A treated mice did not cause any toxic effect. Moreover, the involvement of WT correlates with age and is dose-dependent. Our data suggest that Hsp65 may be a central molecule intervening in the progression of the SLE, and that the point mutated K409A recombinant immunogenic molecule, that counteracts the deleterious effect of WT, may act mitigating and delaying the development of SLE in treated mice. This study gives new insights into the general biological role of Hsp and the significant impact of environmental factors during the pathogenesis of this autoimmune process

Validating excised rodent lungs for functional hyperpolarized xenon-129 MRI

Ex vivo rodent lung models are explored for physiological measurements of respiratory function with hyperpolarized (hp) 129Xe MRI. It is shown that excised lung models allow for simplification of the technical challenges involved and provide valuable physiological insights that are not feasible using in vivo MRI protocols. A custom designed breathing apparatus enables MR images of gas distribution on increasing ventilation volumes of actively inhaled hp 129Xe. Straightforward hp 129Xe MRI protocols provide residual lung volume (RV) data and permit for spatially resolved tracking of small hp 129Xe probe volumes during the inhalation cycle. Hp 129Xe MRI of lung function in the excised organ demonstrates the persistence of post mortem airway responsiveness to intravenous methacholine challenges. The presented methodology enables physiology of lung function in health and disease without additional regulatory approval requirements and reduces the technical and logistical challenges with hp gas MRI experiments. The post mortem lung functional data can augment histological measurements and should be of interest for drug development studies

Fogification of industrial robotic systems

To meet the demands of future automation systems, the architecture of traditional control systems such as the industrial robotic systems needs to evolve and new architectural paradigms need to be investigated. While cloud-based platforms provide services such as computational resources on demand, they do not address the requirements of real-time performance expected by control applications. Fog computing is a promising new architectural paradigm that complements the cloud-based platform by addressing its limitations. In this paper, we analyse the existing robot system architecture and propose a fog-based solution for industrial robotic systems that addresses the needs of future automation systems. We also propose the use of Time-Sensitive Networking (TSN) services for real-time communication and OPC-UA for information modelling within this architecture. Additionally, we discuss the main research challenges associated with the proposed architecture.</p

Caracterização imunofenotípica das subpopulações de linfócitos do lavado broncoalveolar de pacientes com silicose Phenotypic characterization of lymphocyte subsets in bronchoalveolar lavage of patients with silicosis

A lavagem broncoalveolar é um procedimento simples e seguro, na avaliação das pneumopatias relacionadas à exposição a poeiras minerais. O objetivo do estudo foi caracterizar as subpopulações celulares no lavado broncoalveolar (LBA) de pacientes silicóticos. A lavagem broncoalveolar foi realizada em 26 trabalhadores com diferentes formas de silicose: forma simples (n = 12), complicada (n = 13) e um paciente com a forma aguda da doença. Como grupo controle, foram incluídos sete indivíduos sadios. Os pacientes com silicose apresentaram intensa pleocitose com predomínio de macrófagos alveolares e tendência à linfocitose. As subpopulações de linfócitos presentes no lavado broncoalveolar (LBA) dos indivíduos sadios apresentaram fenótipo de células maduras. A grande maioria era constituída por células CD2+TCR<FONT FACE=Symbol>ab</FONT> (87,3%) e somente 2,9% das células T apresentaram marcação CD2+TCR<FONT FACE=Symbol>gd</FONT>. A relação CD4/CD8 foi de 1,8, com poucas (16%) células T imaturas duplo-negativas CD4-CD8-. Em contraste, pacientes com silicose apresentaram redução acentuada das subpopulações dos linfócitos maduros CD2+CD4+, CD2+CD8+ e aumento marcante (47%) de células imaturas (DN) duplo-negativas (CD4-CD8-). Não foi observado aumento das células NK (CD56+). A análise do conteúdo protéico e a determinação da relação Ig/albumina permitiram caracterizar produção local de imunoglobulinas no microambiente pulmonar. Como não foi observado aumento percentual de plasmócitos e linfócitos B (CD19+) no LBA desses pacientes, é possível concluir que as células produtoras de imunoglobulinas estão possivelmente localizadas no interstício pulmonar. Estes resultados sugerem que, durante a evolução da silicose, ocorre o desenvolvimento de linfopoese extratímica e surgimento de órgão linfóide terciário, no microambiente pulmonar desses pacientes.<br>Bronchoalveolar lavage is a safe and simple technique to evaluate lung disease related to exposure to mineral dusts. The aim of this study was to characterize the lymphocyte subsets in bronchoalveolar lavage of patients with silicosis. Bronchoalveolar lavage was carried out in 26 workers with different forms of silicosis: simple form (n = 12), complicated (n = 13) and 1 patient with acute form of the disease. As a control group, 7 healthy individuals were included. Compared to the control group, silicotic patients showed intense pleocytosis constituted mainly by alveolar macrophages with slight lymphocytosis. Lymphocyte subsets present in the bronchoalveolar fluid (BAL) of normal individuals were mature lymphocytes with phenotype CD2+TCR<FONT FACE=Symbol>ab</FONT> (87.3%) and only 2.9% were CD2+TCR<FONT FACE=Symbol>gd</FONT>. CD4/CD8 ratio was 1.8 with few (16%) immature double negative T cells subsets (CD4-CD8-). In contrast, silicotic patients showed reduction of the more mature lymphocyte subset CD2+CD4+, CD2+CD8+ and a great increase (47%) of immature (CD4-CD8-) T cell subsets. No increase in the NK (CD56+) cell population was observed. Biochemical analysis of protein contents and determination of the Ig/albumin ratio characterized local immunoglobulin production within the pulmonary microenvironment. Furthermore, lack of increase of plasma cells, as well as the maintenance of the percentage of B lymphocyte population (CD19+) in the BAL of silicotic patients, favors the hypothesis that the cells responsible for Ig production are possibly located in the interstitial space. Altogether the results suggest development of lymphopoiesis and tertiary lymphoid tissue within the pulmonary microenvironment during the clinical course of silicosis