Creation and time. Byzantine and modern

The volume Creation and Time. Byzantine and Modern by Dr. Elena Ene Drăghici-Vasilescu presents the topic of time and that of creation of the world as they were understood, inter alia, by Aristotle, Basil of Caesarea, Gregory of Nyssa, Dionysius the Areopagite and, in modern times, by Paul Tillich. The author offers a detailed investigation of temporality, movement, and of the relation between those, as well as of notions about the beginning of the universe. Philosophers, historians, and specialists in various humanities, and also a well educated readership can easily read this book, and certainly will find it interesting

Rapamycin and Interleukin-10 Treatment Induces T Regulatory Type 1 Cells That Mediate Antigen-Specific Transplantation Tolerance

Islet transplantation is a cure for type 1 diabetes, but its potential is limited by the need for constant immunosuppression. One solution to this problem is the induction of transplantation tolerance mediated by T regulatory cells. T regulatory type 1 (Tr1) cells are characterized by their production of high levels of interleukin (IL)-10, which is crucial for their differentiation and suppressive function. We investigated the effects of IL-10 administered in combination with rapamycin on the induction of Tr1 cells that could mediate a state of tolerance in diabetic mice after pancreatic islet transplantation. The efficacy of this treatment was compared with IL-10 alone and standard immunosuppression. Stable long-term tolerance that was not reversible by alloantigen rechallenge was achieved only in mice treated with rapamycin plus IL-10. Tr1 cells that produced high levels of IL-10 and suppressed T-cell proliferation were isolated from splenocytes of rapamycin plus IL-10–treated mice after treatment withdrawal. In rapamycin plus IL-10–treated mice, endogenous IL-10 mediated an active state of tolerance, as was observed when the blockade of IL-10 activity rapidly induced graft rejection >100 days after transplantation. CD4+ T-cells from rapamycin plus IL-10–treated mice transferred antigen-specific tolerance in mice that received new transplants. Thus rapamycin plus IL-10 not only prevented allograft rejection but also induced Tr1 cells that mediated stable antigen-specific, long-term tolerance in vivo

The Experimental Development of Bread with Enriched Nutritional Properties Using Organic Sea Buckthorn Pomace

In this study, sea buckthorn (Hippophae rhamnoides L.) pomace resulting from juice extraction was dried and ground in order to obtain a powder that was further used in bread making. Sea buckthorn pomace, an invaluable by-product of the industry, contains bioactive compounds and dietary fibers that promote health. Dried by-products of sea buckthorn are rich sources of nutritional and bioactive compounds, offering great potential for use as nutraceuticals in animal feed, ingredients in functional food, and the pharmaceutical industry. The utilization of sea buckthorn by-products promotes a circular and sustainable economy by implementing innovative methods and strategic approaches to recover high-value products and minimize waste in multiple ways. For this purpose, three organic sea buckthorn varieties were used, namely Mara (M), Clara (C), and Sorana (S). Further, 6%, 8%, and 10% pomace powder were added to wheat flour to prepare functional bread, and its effects on structural, nutritional, and sensorial characteristics were investigated. The volume, porosity, and elasticity of the obtained bread samples were slightly lower compared to the control sample (white bread). The nutritional characteristics revealed that the developed bread presented higher antioxidant activity, polyphenolic content, and crude fiber compared to the control sample. The acceptability test showed that consumer preferences were directed toward the bread samples containing 8% sea buckthorn powder, regardless of the variety, while the addition of 10% pomace powder led to major sensorial changes. The results of this study showed that sea buckthorn pomace powder can be successfully incorporated into bread in order to obtain a food product with enhanced properties

The Wiskott-Aldrich syndrome protein is required for iNKT cell maturation and function

The Wiskott-Aldrich syndrome (WAS) protein (WASp) is a regulator of actin cytoskeleton in hematopoietic cells. Mutations of the WASp gene cause WAS. Although WASp is involved in various immune cell functions, its role in invariant natural killer T (iNKT) cells has never been investigated. Defects of iNKT cells could indeed contribute to several WAS features, such as recurrent infections and high tumor incidence. We found a profound reduction of circulating iNKT cells in WAS patients, directly correlating with the severity of clinical phenotype. To better characterize iNKT cell defect in the absence of WASp, we analyzed was−/− mice. iNKT cell numbers were significantly reduced in the thymus and periphery of was−/− mice as compared with wild-type controls. Moreover analysis of was−/− iNKT cell maturation revealed a complete arrest at the CD44+ NK1.1− intermediate stage. Notably, generation of BM chimeras demonstrated a was−/− iNKT cell-autonomous developmental defect. was−/− iNKT cells were also functionally impaired, as suggested by the reduced secretion of interleukin 4 and interferon γ upon in vivo activation. Altogether, these results demonstrate the relevance of WASp in integrating signals critical for development and functional differentiation of iNKT cells and suggest that defects in these cells may play a role in WAS pathology

Partial correction of immunodeficiency by lentiviral vector gene therapy in mouse models carrying Rag1 hypomorphic mutations

IntroductionRecombination activating genes (RAG) 1 and 2 defects are the most frequent form of severe combined immunodeficiency (SCID). Patients with residual RAG activity have a spectrum of clinical manifestations ranging from Omenn syndrome to delayed-onset combined immunodeficiency, often associated with granulomas and/or autoimmunity (CID-G/AI). Lentiviral vector (LV) gene therapy (GT) has been proposed as an alternative treatment to the standard hematopoietic stem cell transplant and a clinical trial for RAG1 SCID patients recently started. However, GT in patients with hypomorphic RAG mutations poses additional risks, because of the residual endogenous RAG1 expression and the general state of immune dysregulation and associated inflammation.MethodsIn this study, we assessed the efficacy of GT in 2 hypomorphic Rag1 murine models (Rag1F971L/F971L and Rag1R972Q/R972Q), exploiting the same LV used in the clinical trial encoding RAG1 under control of the MND promoter.Results and discussionStarting 6 weeks after transplant, GT-treated mice showed a decrease in proportion of myeloid cells and a concomitant increase of B, T and total white blood cells. However, counts remained lower than in mice transplanted with WT Lin- cells. At euthanasia, we observed a general redistribution of immune subsets in tissues, with the appearance of mature recirculating B cells in the bone marrow. In the thymus, we demonstrated correction of the block at double negative stage, with a modest improvement in the cortical/medullary ratio. Analysis of antigenspecific IgM and IgG serum levels after in vivo challenge showed an amelioration of antibody responses, suggesting that the partial immune correction could confer a clinical benefit. Notably, no overt signs of autoimmunity were detected, with B-cell activating factor decreasing to normal levels and autoantibodies remaining stable after GT. On the other hand, thymic enlargement was frequently observed, although not due to vector integration and insertional mutagenesis. In conclusion, our work shows that GT could partially alleviate the combined immunodeficiency of hypomorphic RAG1 patients and that extensive efficacy and safety studies with alternative models are required before commencing RAG gene therapy in thesehighly complex patients