144 research outputs found

    Omnidirectional people's gathering monitoring by using deep learning algorithms

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    It has long been recognized as gathering of people is one of the major risk factor in spreading of viral epidemics. Social distancing is then one of the most simple and powerful system to mitigate the spread of infections.We explore here the possibility of monitoring public people’s gathering by using a novel bifocal omnidirectional lens designed by INAF jointly with deep learning-based algorithms. The paper briefly describe how the lens works, the applied deep learning algorithms and the preliminary results of the trials

    HIV-infected T cells are migratory vehicles for viral dissemination

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    After host entry through mucosal surfaces, HIV-1 disseminates to lymphoid tissues to establish a generalized infection of the immune system. The mechanisms by which this virus spreads among permissive target cells locally during early stages of transmission, and systemically during subsequent dissemination are not known1. In vitro studies suggest that formation of virological synapses (VSs) during stable contacts between infected and uninfected T cells greatly increases the efficiency of viral transfer2. It is unclear, however, if T cell contacts are sufficiently stable in vivo to allow for functional synapse formation under the conditions of perpetual cell motility in epithelial3 and lymphoid tissues4. Here, using multiphoton intravital microscopy (MP-IVM), we examined the dynamic behavior of HIV-infected T cells in lymph nodes (LNs) of humanized mice. We found that most productively infected T cells migrated robustly, resulting in their even distribution throughout the LN cortex. A subset of infected cells formed multinucleated syncytia through HIV envelope (Env)-dependent cell fusion. Both uncoordinated motility of syncytia as well as adhesion to CD4+ LN cells led to the formation of long membrane tethers, increasing cell lengths to up to 10 times that of migrating uninfected T cells. Blocking the egress of migratory T cells from LNs into efferent lymph, and thus interrupting T cell recirculation, limited HIV dissemination and strongly reduced plasma viremia. Thus, we have found that HIV-infected T cells are motile, form syncytia, and establish tethering interactions that may facilitate cell-to-cell transmission through VSs. While their migration in LNs spreads infection locally, T cell recirculation through tissues is important for efficient systemic viral spread, suggesting new molecular targets to antagonize HIV infection

    Limited Transplantation of Antigen-Expressing Hematopoietic Stem Cells Induces Long-Lasting Cytotoxic T Cell Responses

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    Harnessing the ability of cytotoxic T lymphocytes (CTLs) to recognize and eradicate tumor or pathogen-infected cells is a critical goal of modern immune-based therapies. Although multiple immunization strategies efficiently induce high levels of antigen-specific CTLs, the initial increase is typically followed by a rapid contraction phase resulting in a sharp decline in the frequency of functional CTLs. We describe a novel approach to immunotherapy based on a transplantation of low numbers of antigen-expressing hematopoietic stem cells (HSCs) following nonmyeloablative or partially myeloablative conditioning. Continuous antigen presentation by a limited number of differentiated transgenic hematopoietic cells results in an induction and prolonged maintenance of fully functional effector T cell responses in a mouse model. Recipient animals display high levels of antigen-specific CTLs four months following transplantation in contrast to dendritic cell-immunized animals in which the response typically declines at 4–6 weeks post-immunization. Majority of HSC-induced antigen-specific CD8+ T cells display central memory phenotype, efficiently kill target cells in vivo, and protect recipients against tumor growth in a preventive setting. Furthermore, we confirm previously published observation that high level engraftment of antigen-expressing HSCs following myeloablative conditioning results in tolerance and an absence of specific cytotoxic activity in vivo. In conclusion, the data presented here supports potential application of immunization by limited transplantation of antigen-expressing HSCs for the prevention and treatment of cancer and therapeutic immunization of chronic infectious diseases such as HIV-1/AIDS

    Clearance of apoptotic cells: implications in health and disease

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    Recent advances in defining the molecular signaling pathways that regulate the phagocytosis of apoptotic cells have improved our understanding of this complex and evolutionarily conserved process. Studies in mice and humans suggest that the prompt removal of dying cells is crucial for immune tolerance and tissue homeostasis. Failed or defective clearance has emerged as an important contributing factor to a range of disease processes. This review addresses how specific molecular alterations of engulfment pathways are linked to pathogenic states. A better understanding of the apoptotic cell clearance process in healthy and diseased states could offer new therapeutic strategies

    Cultivation of human keratinocyte stem cells: current and future clinical applications

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    Cultured human keratinocytes have a wide spectrum of clinical applications. Clinical results reported by several investigators are, however, contradictory. In this review, the authors discuss the biological and surgical issues which play a key role in the clinical outcome of cultured epidermal autografts used for the treatment of massive full-thickness burns. The importance of cultivation of epidermal stem cells and of their transplantation onto a wound bed prepared with donor dermis is emphasised. The paper also reviews recent data showing that: (i) cultured epidermal autografts bearing melanocytes can be used for the treatment of stable vitiligo; (ii) keratinocytes isolated from other lining epithelia, such as oral, urethral and corneal epithelia, can be cultivated and grafted onto patients suffering from disabling epithelial defects; (iii) keratinocyte stem cells can be stably transduced with retroviral vectors and are therefore attractive targets for the gene therapy of genodermatoses

    Human epithelial cells induce human melanocyte growth in vitro but only skin keratinocytes regulate its proper differentiation in the absence of dermis.

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    Human keratinocytes isolated from a skin biopsy and cultured in vitro reconstitute a stratified squamous epithelium suitable for grafting on burned patients. Melanocytes coisolated from the same skin biopsy also proliferate under these culture conditions and maintain differentiated functions (i.e., synthesize melanin granules, regularly intersperse in the basal layer of the cultured epidermis, and transfer melanosomes in the cytoplasm of contiguous keratinocytes) (De Luca, M., A. T. Franzi, F. D'Anna, A. Zicca, E. Albanese, S. Bondanza, and R. Cancedda. 1988. Eur. J. Cell Biol. 46:176-180). Isolated melanocytes in culture grow in the presence of specific growth factors with a mean population doubling time of 4-10 d. In this paper we show that (a) human keratinocytes and oral epithelial cells possess strong and specific melanocyte growth stimulating activity (doubling time, 24 h); (b) melanocyte growth is not autonomous but requires close keratinocyte contact and is regulated to maintain a physiological melanocytes/keratinocytes ratiol and (c) pure skin keratinocytes, but not oral epithelial cells, have all the information required for the proper physiological location and differentiation of melanocytes in the epidermis
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