Peptide-mediated Interference of TIR Domain Dimerization in MyD88 Inhibits Interleukin-1-dependent Activation of NF-κB *

Myeloid differentiation factor 88 (MyD88) plays a crucial role in the signaling pathways triggered by interleukin (IL)-1 and Toll-like receptors in several steps of innate host defense. A crucial event in this signaling pathway is represented by dimerization of MyD88, which allows the recruitment of downstream kinases like IRAK-1 and IRAK-4. Herein, we have investigated the function of the Toll/IL-1 receptor (TIR) domain in MyD88 homodimerization in cell-free and in vitro experimental settings by using epta-peptides that mimic the BB-loop region of the conserved TIR domain of different proteins. By using a pull-down assay with purified glutathione S-transferase-MyD88 TIR or co-immunoprecipitation experiments, we found that epta-peptides derived from the TIR domain of MyD88 and IL-18R are the most effective in inhibiting homodimerization with either the isolated TIR or full-length MyD88. Moreover, we demonstrated that a cell permeable analog of MyD88 epta-peptide inhibits homodimerization of MyD88 TIR domains in an in vitro cell system and significantly reduces IL-1 signaling, as assayed by activation of the downstream transcription factor NF-kappaB. Our results indicate that the BB-loop in TIR domain of MyD88 is a good target for specific inhibition of MyD88-mediated signaling in vivo

Prospective life cycle assessment for the full valorization of anchovy fillet leftovers: The LimoFish process

Prospective life cycle assessment models were developed and applied at the laboratory and industrial scale with the aim to evaluate the environmental burdens associated with the LimoFish process used to produce the fish oil “AnchoiOil”, the new organic fertilizer “AnchoisFert” or biogas (by means of anaerobic digestion) after treatment of anchovy fillet leftovers (AnLeft) with agro-solvent d-limonene. Potential impacts for climate change and freshwater eutrophication were estimated at 29.1 kg CO2 eq/kg AnLeft and 1.7E−07 kg PO4 eq/kg AnLeft at laboratory scale, and at 1.5 kg CO2 eq/kg AnLeft and 2.2E−07 kg PO4 eq/kg AnLeft at industrial scale. Electricity consumption is the main contributor to the environmental impact of the process and plays a significant role in the production of d-limonene, for which cold pressing extraction would reduce the related impacts by ∼ 70 %. The use of the solid by-product as organic fertilizer or input to anaerobic digestion would provide additional environmental benefits to the process. The LimoFish process is a successful example of a low impacting strategy to reduce the demand for natural resources and maximize the application of the circular economy principles in the fishing industry

Oxidative stress and gut-derived lipopolysaccharides in children affected by paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections

BACKGROUND: Paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections syndrome (PANDAS) identifies patients with acute onset of obsessive-compulsive and tic disorders. The objective of this study was to evaluate serum NOX2 levels, as well as 8-iso-prostaglandin F2α (8-iso-PGF2α) and lipopolysaccharide (LPS) of PANDAS patients. METHODS: In this study we wanted to compare serum levels of soluble NOX2-dp (sNOX-2-dp), iso-PGF2α and LPS in 60 consecutive subjects, including 30 children affected by PANDAS and 30 controls (CT) matched for age and gender. Serum zonulin was used as intestinal permeability assay. RESULTS: Compared with CT, PANDAS children had increased serum levels of sNOX-2-dp, 8-iso-PGF2α and LPS. Bivariate analysis showed that serum sNOX2-dp was significantly correlated with LPS (Rs = 0.359; p = 0.005), zonulin (Rs = 0.444; p < 0.001) and 8-iso-PGF2α (Rs = 0.704; p < 0.001). Serum LPS significantly correlated with zonulin (Rs = 0.610; p < 0.001), and 8-iso-PGF2α (Rs = 0.591; p = 0.001). Finally, a multiple linear regression analysis showed that serum 8-iso-PGF2α and zonulin were the only independent variables associated with sNOX2-dp (R2 = 68%). CONCLUSION: This study shows that children affected by PANDAS have high circulating levels of sNOX2-dp, isoprostanes and of LPS that could be involved in the process of neuroinflammation

Bit loading for next generation wireless OFDM systems: a "greedy" approach for goodput optimization

Technologies as MIMO and BIC-OFDM have proved attractive performance in harsh multipath scenarios, making them suitable candidates for satisfying the ambitious goals of next generation wireless communication systems. Such techniques require a great deal of parameters to be optimized, for providing the best performance in every possible scenario. The purpose of this thesis is to investigate the performance that a wise bit distribution among the subcarriers of an OFDM system-or "bit loading"-making use of some CSI, could provide, relevant to that achievable by a system which employs a fixed modulation scheme. In doing this, we try to maximize the goodput, which represents the average number of bits belonging to error-free data received by unit of time. As background, we review an heuristic technique called "greedy algorithms", whose key feature is that of trying to arrive at a global optimal solution of a problem, through a series of locally optimal (greedy) choices of many subproblems. So we make use of this methodology for elaborating some iterative sub-optimal bit loading procedures, and by means of simulation tools, we show that their contribution to the raise of the goodput performance is remarkable. The elaborated methods are based on a PER estimation made with the Link Quality Metric "kESM", which has been proved to be a reliable link performance predictor, for multicarrier systems employing a variety of modulation schemes

Evergreen Conservation Capital Indicators and Life Expectancy in Italy

A major development challenge has been to reconcile regional development with the growing evidence of resource depletion and negative environmental impacts of predominantly urban modes of production and consumption. Looking at many relevant European programs, it emerges that state members are engaged in the protection and valorization of environmental resources. In Italy, the conservation of natural capital is an objective shared by public and private actors. The implications that depend on the environmental quality assessment are many and fall in various fields. The level of conservation and valorization of the environmental capital of an area generates several impacts and deep repercussions on the well-being and health of residents. In this contribution, we aim to analyze the relationship between human development and conservative capital, investigating the linkage existing between the quality of natural capital for the different Italian Regions, as well as the ability of various regional governments to enhance its natural resources, and the state of health of residents expressed as life expectancy using the method of Mazziotta and Pareto Index (MPI). The evidences show the existence of a correlation between ECCI and life expectancy at birth and life expectancy in good health. This result shows further that environmental quality can have impacts on residents’ health in a given area

Quality of Sleep in Patients with Celiac Disease

International audienceBackground: Celiac disease (CD) is a chronic disease with a various clinical presentation, including anxiety and depression. Aim: This study investigated the quality of sleep in CD. Methods: The participants were celiacs at diagnosis (C-N); celiacs on gluten free diet at follow-up (C-T); and healthy volunteers (HV). Participants completed the Pittsburgh Sleep Quality Index (PSQI), SF36, Zung and Fatigue scales, and State-Trait Anxiety Inventory (STAI). Results: The PSQI score was higher in C-N and C-T than in HV (p<0.001). A gluten-free diet (GFD) did not improve the PSQI scores (p=0.245) in CD. The other test scores were similar between celiacs at diagnosis and those on a GFD, while significant differences were found between celiacs and volunteers. PSQI score was inversely associated with the quality of the physical (r=–0.327 p=0.002) and mental (r=–0.455, p<0.001) components scores. The sleep quality scores were related to depression (r=0.633, p<0.001), fatigue (r=0.377, p<0.001), state anxiety (r=0.484, p<0.001), and trait anxiety (r=0.467, p<0.001). Conclusions: Sleep disorders are common in CD also during treatment with GFD. Sleep disorders are related to depression, anxiety and fatigue, and inversely related to quality of life scale scores