CD8+ T Cells: GITR Matters

As many members of the tumor necrosis factor receptor superfamily, glucocorticoid-induced TNFR-related gene (GITR) plays multiple roles mostly in the cells of immune system. CD8+ T cells are key players in the immunity against viruses and tumors, and GITR has been demonstrated to be an essential molecule for these cells to mount an immune response. The aim of this paper is to focus on GITR function in CD8+ cells, paying particular attention to numerous and recent studies that suggest its crucial role in mouse disease models

are we able to harness the immunomodulatory power of cytokines for novel autoimmune disease treatments

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Quantifying the Sensitivity and Unclonability of Optical Physical Unclonable Functions

Due to their unmatched entropy, complexity, and security level, optical physical unclonable functions (PUFs) currently receive a lot of interest in the literature.Despite the large body of existing works, herein, one of their core features in detail is studied, namely, their physical unclonability. This article tackles this fundamental and yet largely unaddressed issue. In simulations and/or experiments, the sensitivity of diffraction-based optical responses is investigated with respect to various small alterations such as variation in position, size, and number of the scatterers, as well as perturbations in the spatial alignment between the PUF and the measurement apparatus. The analysis focuses on 2Doptical PUFs because of their relevance in integrated applications and the need to reply to security concerns that can be raised when the physical structure of the geometry is accessible. Among the results of this study, the sensitivity analysis shows that a positional perturbation of scatterers on the order of 30 nm, that is,far below the wavelength of the probing laser light of 632 nm wavelength, is sufficient to invalidate the PUF response and thus detect forgery attempt. These results support and quantify the high adversarial efforts required to clone optical PUFs, even for 2D layouts

Balance between Regulatory T and Th17 Cells in Systemic Lupus Erythematosus: The Old and the New

Pathogenic mechanisms underlying the development of systemic lupus erythematosus (SLE) are very complex and not yet entirely clarified. However, the pivotal role of T lymphocytes in the induction and perpetuation of aberrant immune response is well established. Among T cells, IL-17 producing T helper (Th17) cells and regulatory T (Treg) cells represent an intriguing issue to be addressed in SLE pathogenesis, since an imbalance between the two subsets has been observed in the course of the disease. Treg cells appear to be impaired and therefore unable to counteract autoreactive T lymphocytes. Conversely, Th17 cells accumulate in target organs contributing to local IL-17 production and eventually tissue damage. In this setting, targeting Treg/Th17 balance for therapeutic purposes may represent an intriguing and useful tool for SLE treatment in the next future. In this paper, the current knowledge about Treg and Th17 cells interplay in SLE will be discussed

Enhanced expression of hepatic lipogenic enzymes in an animal model of sedentariness.

The hindlimb-suspended rat was used as animal model to investigate the effects induced by immobilization of the skeletal muscle in the expression of the genes encoding hepatic lipogenic enzymes. Following a 14-day period of immobilization, rats were injected intraperitoneally with radioactive acetate, and the labeling of hepatic lipids and cholesterol was evaluated 15 min after the isotope injection. The incorporation of labeled acetate in lipids and cholesterol was almost three times higher in the liver of immobilized rats than in control animals as a consequence of the enhanced transcription of the genes encoding acetyl-CoA synthase, acetyl-CoA carboxylase, fatty acid synthase, and 3-hydroxy-3-methylglutaryl-CoA reductase. The high expression of the key enzymes for fatty acid and cholesterol synthesis induced by immobilization was not paralleled by an increase of the hepatic sterol-regulatory element binding protein (SREBP)-1 and SREBP-2 mRNA content. However, the expression of the mature form of SREBP-1 and SREBP-2 was higher in the nuclear fraction of immobilized rat liver than in controls due to a significant increase of the cleavage of the native proteins. Immobilization also affected the expression of proteins involved in lipid degradation. In fact, the hepatic content of peroxisome proliferator-activated receptor-alpha (PPARalpha) mRNA and of PPARalpha target genes encoding carnitine palmitoyl transferase-1 and acyl-CoA oxidase were significantly increased upon immobilization

GITR-GITRL System, A Novel Player in Shock and Inflammation

Glucocorticoid-induced TNFR-Related (GITR) protein is a member of the tumor necrosis factor receptor superfamily that modulates acquired and natural immune response. It is expressed in several cells and tissues, including T cells, natural killer cells, and, at lower levels, in cells of innate immunity. GITR is activated by its ligand, GITRL, mainly expressed on antigen presenting and endothelial cells. Recent evidence suggests that the GITR/GITRL system participates in the development of inflammatory responses, including shock, either due to early response of neutrophils and macrophages, or together with autoimmune/allergic pathogenesis. The proinflammatory role of the GITR/GITRL system is due to: 1) modulation of the extravasation process, 2) activation of innate immunity cells, 3) activation of effector T cells also favored by partial inhibition of suppressor T cells and modulation of dendritic function. This review summarizes the in vivo role of the GITR/GITRL system in inflammation and shock, explaining the mechanisms responsible for their effects, considering the interplay among the different cells of the immune system and transduction pathways activated by GITR and GITRL triggering. The hidden aspects about GITR/GITRL function, crucial for treatment planning of inflammatory diseases and shock by modulation of this system is stressed

Flexible Physical Unclonable Functions based on non-deterministically distributed Dye-Doped Fibers and Droplets

The development of new anti-counterfeiting solutions is a constant challenge and involves several research fields. Much interest is devoted to systems that are impossible to clone, based on the Physical Unclonable Function (PUF) paradigm. In this work, new strategies based on electrospinning and electrospraying of dye-doped polymeric materials are presented for the manufacturing of flexible free-standing films that embed different PUF keys. Films can be used to fabricate anticounterfeiting labels having three encryption levels: i) a map of fluorescent polymer droplets, with non deterministic positions on a dense yarn of polymer nanofibers; ii) a characteristic fluorescence spectrum for each label; iii) a challenge-response pairs (CRPs) identification protocol based on the strong nature of the physical unclonable function. The intrinsic uniqueness introduced by the deposition techniques encodes enough complexity into the optical anti-counterfeiting tag to generate thousands of cryptographic keys. The simple and cheap fabrication process as well as the multilevel authentication makes such colored polymeric unclonable tags a practical solution in the secure protection of merchandise in our daily life

GITR-GITRL System, A Novel Player in Shock and Inflammation

Glucocorticoid-induced TNFR-Related (GITR) protein is a member of the tumor necrosis factor receptor superfamily that modulates acquired and natural immune response. It is expressed in several cells and tissues, including T cells, natural killer cells, and, at lower levels, in cells of innate immunity. GITR is activated by its ligand, GITRL, mainly expressed on antigen presenting and endothelial cells. Recent evidence suggests that the GITR/GITRL system participates in the development of inflammatory responses, including shock, either due to early response of neutrophils and macrophages, or together with autoimmune/allergic pathogenesis. The pro-inflammatory role of the GITR/GITRL system is due to: 1) modulation of the extravasation process, 2) activation of innate immunity cells, 3) activation of effector T cells also favored by partial inhibition of suppressor T cells and modulation of dendritic function. This review summarizes the in vivo role of the GITR/GITRL system in inflammation and shock, explaining the mechanisms responsible for their effects, considering the interplay among the different cells of the immune system and transduction pathways activated by GITR and GITRL triggering. The hidden aspects about GITR/GITRL function, crucial for treatment planning of inflammatory diseases and shock by modulation of this system is stressed

Integrated forest management to prevent wildfires under Mediterranean environments

This review presents a multidisciplinary framework for integrating the ecological, regulatory, procedural and technical aspects of forest management for fi res prevention under Mediterranean environments. The aims are to: i) provide a foreground of wildfi re scenario; ii) illustrate the theoretical background of forest fuel management; iii) describe the available fuel management techniques and mechanical operations for fi re prevention in forest and wildland-urban interfaces, with exemplifi cation of case-studies; iv)allocate fi re prevention activities under the hierarchy of forest planning. The review is conceived as an outline commentary discussion targeted to professionals, technicians and government personnel involved in forestry and environmental management

mGluR5 PAMs rescue cortical and behavioural defects in a mouse model of CDKL5 deficiency disorder

Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) is a devastating rare neurodevelopmental disease without a cure, caused by mutations of the serine/threonine kinase CDKL5 highly expressed in the forebrain. CDD is characterized by early-onset seizures, severe intellectual disabilities, autistic-like traits, sensorimotor and cortical visual impairments (CVI). The lack of an effective therapeutic strategy for CDD urgently demands the identification of novel druggable targets potentially relevant for CDD pathophysiology. To this aim, we studied Class I metabotropic glutamate receptors 5 (mGluR5) because of their important role in the neuropathological signs produced by the lack of CDKL5 in-vivo, such as defective synaptogenesis, dendritic spines formation/maturation, synaptic transmission and plasticity. Importantly, mGluR5 function strictly depends on the correct expression of the postsynaptic protein Homer1bc that we previously found atypical in the cerebral cortex of Cdkl5-/y mice. In this study, we reveal that CDKL5 loss tampers with (i) the binding strength of Homer1bc-mGluR5 complexes, (ii) the synaptic localization of mGluR5 and (iii) the mGluR5-mediated enhancement of NMDA-induced neuronal responses. Importantly, we showed that the stimulation of mGluR5 activity by administering in mice specific positive-allosteric-modulators (PAMs), i.e., 3-Cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide (CDPPB) or RO6807794, corrected the synaptic, functional and behavioral defects shown by Cdkl5-/y mice. Notably, in the visual cortex of 2 CDD patients we found changes in synaptic organization that recapitulate those of mutant CDKL5 mice, including the reduced expression of mGluR5, suggesting that these receptors represent a promising therapeutic target for CDD