250 research outputs found

    Diabetes Causes Bone Marrow Autonomic Neuropathy and Impairs Stem Cell Mobilization via Dysregulated p66Shc and Sirt1

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    Diabetes compromises the bone marrow (BM) microenvironment and reduces circulating CD34 + cells. Diabetic autonomic neuropathy (DAN) may impact the BM, because the sympathetic nervous system (SNS) is prominently involved in BM stem cell trafficking. We hypothesize that neuropathy of the BM affects stem cell mobilization and vascular recovery after ischemia in diabetes. We report that, in patients, cardiovascular DAN was associated with fewer circulating CD34 + cells. Experimental diabetes (STZ and Ob/Ob ) or chemical sympathectomy in mice resulted in BM autonomic neuropathy, impaired Lin - cKit + Sca1 + (LKS) cell and endothelial progenitor cells (EPC, CD34 + Flk1 + ) mobilization and vascular recovery after ischemia. DAN increased expression of p66Shc and reduced expression of Sirt1 in mice and humans. p66Shc KO in diabetic mice prevented DAN in the BM, and rescued defective LKS cell and EPC mobilization. Hematopoietic Sirt1 KO mimicked the diabetic mobilization defect, while hematopoietic Sirt1 overexpression in diabetes rescued defective mobilization and vascular repair. Through p66Shc and Sirt1 , diabetes and sympathectomy elevated the expression of various adhesion molecules, including CD62L . CD62L KO partially rescued the defective stem/progenitor cell mobilization. In conclusion, autonomic neuropathy in the BM impairs stem cell mobilization in diabetes with dysregulation of the lifespan regulators p66Shc and Sirt1

    Changes Induced by Exposure of the Human Lung to Glass Fiber–Reinforced Plastic

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    The inhalation of glass dusts mixed in resin, generally known as glass fiber–reinforced plastic (GRP), represents a little-studied occupational hazard. The few studies performed have highlighted nonspecific lung disorders in animals and in humans. In the present study we evaluated the alteration of the respiratory system and the pathogenic mechanisms causing the changes in a group of working men employed in different GRP processing operations and exposed to production dusts. The study was conducted on a sample of 29 male subjects whose mean age was 37 years and mean length of service 11 years. All of the subjects were submitted to a clinical check-up, basic tests, and bronchoalveolar lavage (BAL); microscopic studies and biochemical analysis were performed on the BAL fluid. Tests of respiratory function showed a large number of obstructive syndromes; scanning electron microscopy highlighted qualitative and quantitative alterations of the alveolar macrophages; and transmission electron microscopy revealed the presence of electron-dense cytoplasmatic inclusions indicating intense and active phlogosis (external inflammation). Biochemical analyses highlighted an increase in protein content associated with alterations of the lung oxidant/antioxidant homeostasis. Inhalation of GRP, independent of environmental concentration, causes alterations of the cellular and humoral components of pulmonary interstitium; these alterations are identified microscopically as acute alveolitis

    Quantifying n -Photon Indistinguishability with a Cyclic Integrated Interferometer

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    We report on a universal method to measure the genuine indistinguishability of n photons - a crucial parameter that determines the accuracy of optical quantum computing. Our approach relies on a low-depth cyclic multiport interferometer with N=2n modes, leading to a quantum interference fringe whose visibility is a direct measurement of the genuine n-photon indistinguishability. We experimentally demonstrate this technique for an eight-mode integrated interferometer fabricated using femtosecond laser micromachining and four photons from a quantum dot single-photon source. We measure a four-photon indistinguishability up to 0.81±0.03. This value decreases as we intentionally alter the photon pairwise indistinguishability. The low-depth and low-loss multiport interferometer design provides an original path to evaluate the genuine indistinguishability of resource states of increasing photon number

    The Redox Enzyme p66Shc Contributes to Diabetes and Ischemia-Induced Delay in Cutaneous Wound Healing

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    OBJECTIVE: The redox enzyme p66Shc produces hydrogen peroxide and triggers proapoptotic signals. Genetic deletion of p66Shc prolongs life span and protects against oxidative stress. In the present study, we evaluated the role of p66Shc in an animal model of diabetic wound healing. RESEARCH DESIGN AND METHODS: Skin wounds were created in wild-type (WT) and p66Shc(-/-) control and streptozotocin-induced diabetic mice with or without hind limb ischemia. Wounds were assessed for collagen content, thickness and vascularity of granulation tissue, apoptosis, reepithelialization, and expression of c-myc and beta-catenin. Response to hind limb ischemia was also evaluated. RESULTS: Diabetes delayed wound healing in WT mice with reduced granulation tissue thickness and vascularity, increased apoptosis, epithelial expression of c-myc, and nuclear localization of beta-catenin. These nonhealing features were worsened by hind limb ischemia. Diabetes induced p66Shc expression and activation; wound healing was significantly faster in p66Shc(-/-) than in WT diabetic mice, with or without hind limb ischemia, at 1 and 3 months of diabetes duration and in both SV129 and C57BL/6 genetic backgrounds. Deletion of p66Shc reversed nonhealing features, with increased collagen content and granulation tissue thickness, and reduced apoptosis and expression of c-myc and beta-catenin. p66Shc deletion improved response to hind limb ischemia in diabetic mice in terms of tissue damage, capillary density, and perfusion. Migration of p66Shc(-/-) dermal fibroblasts in vitro was significantly faster than WT fibroblasts under both high glucose and hypoxia. CONCLUSIONS: p66Shc is involved in the delayed wound-healing process in the setting of diabetes and ischemia. Thus, p66Shc may represent a potential therapeutic target against this disabling diabetes complication

    Agricultural machinery adequacy for handling the mombaça grass biomass in agroforestry systems.

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    Abstract: The current scenario of Agroforestry Systems (AFS) worldwide lacks specific machinery, resulting in practically all operations being carried out manually. This leads to a significant physical effort for small-scale farmers and limits the implementation of AFS to small areas. The objective of the study was to evaluate the suitability of existing machines for performing agroforestry tasks. This research utilizes Descriptive Statistics and Exponentially Weighted Moving Average methods to evaluate the data and compare the treatments, where different machines are used to cut Mombaça grass (Megathyrsus maximus Jacq): (i) costal brushcutter (CBC); (ii) tractor-mounted rotary brushcutter (RBC); and (iii) mini grain reaper machine (GRM). The experiments were conducted in Jaguariúna, São Paulo, Brazil. GRM is recommended for achieving greater biomass production, reducing raking time, and minimizing operational costs. CBC is suitable for smaller areas due to its affordability and slow operation, which requires significant physical effort. RBC is recommended for reducing working time, physical effort, and personnel costs, making it suitable for larger-scale contexts
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