Presently, the only effective treatment for celiac disease is a life-long gluten-free diet. In this work, we used a new mixture of selected sourdough lactobacilli and fungal proteases to eliminate the toxicity of wheat flour during long-time fermentation. Immunological (R5 antibody-based sandwich and competitive enzyme-linked immunosorbent assay [ELISA] and R5 antibody-based Western blot), two-dimensional electrophoresis, and mass spectrometry (matrix-assisted laser desorption ionization-time of flight, strong-cation-exchange-liquid chromatography/capillary liquid chromatography-electrospray ionizationquadrupole-time of flight [SCX-LC/CapLC-ESI-Q-TOF], and high-pressure liquid chromatography-electrospray ionization-ion trap mass spectrometry) analyses were used to determine the gluten concentration. Assays based on the proliferation of peripheral blood mononuclear cells (PBMCs) and gamma interferon production by PBMCs and intestinal T-cell lines (iTCLs) from 12 celiac disease patients were used to determine the protein toxicity of the pepsin-trypsin digests from fermented wheat dough (sourdough). As determined by R5-based sandwich and competitive ELISAs, the residual concentration of gluten in sourdough was 12 ppm. Albumins, globulins, and gliadins were completely hydrolyzed, while ca. 20% of glutenins persisted. Low-molecular-weight epitopes were not detectable by SCX-LC/CapLC-ESI-Q-TOF mass spectrometry and R5-based Western blot analyses. The kinetics of the hydrolysis of the 33-mer by lactobacilli were highly efficient. All proteins extracted from sourdough activated PBMCs and induced gamma interferon production at levels comparable to the negative control. None of the iTCLs demonstrated immunoreactivity towards pepsin-trypsin digests. Bread making was standardized to show the suitability of the detoxified wheat flour. Food processing by selected sourdough lactobacilli and fungal proteases may be considered an efficient approach to eliminate gluten toxicity.

Muscarinic receptors, expressed in several primary and metastatic tumours, appear to be implicated in their growth and propagation. In this work we have demonstrated that M2 muscarinic receptors are expressed in glioblastoma human specimens and in glioblastoma cell lines. Moreover, we have characterized the effects of the M2 agonist arecaidine on cell growth and survival both in two different glioblastoma cell lines (U251MG and U87MG) and in primary cultures obtained from different human biopsies. Cell growth analysis has demonstrated that the M2 agonist arecaidine strongly decreased cell proliferation in both glioma cell lines and primary cultures. This effect was dose and time dependent. FACS analysis has confirmed cell cycle arrest at G1/S and at G2/M phase in U87 cells and U251 respectively. Cell viability analysis has also shown that arecaidine induced severe apoptosis, especially in U251 cells. Chemosensitivity assays have, moreover, shown arecaidine and temozolomide similar effects on glioma cell lines, although IC50 value for arecaidine was significantly lower than temozolomide. In conclusion, we report for the first time that M2 receptor activation has a relevant role in the inhibition of glioma cell growth and survival, suggesting that M2 may be a new interesting therapeutic target to investigate for glioblastoma therapy.

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In this paper we discuss some general aspects of the so-called geometrodynamical approach (GDA) to Chaos and present some results obtained within this framework. We firstly derive a naïve and yet general geometrization procedure, and then specialize the discussion to the descriptions of motion within the frameworks of two among the most representative implementations of the approach, namely the Jacobi and the Finsler geometrodynamics. In order to support the claim that the GDA isn't simply a mere re-transcription of the usual dynamics, but instead can give various hints on the understanding of the qualitative behaviour of dynamical systems (DS's), we then compare, from a formal point of view, the tools used within the usual framework of Hamiltonian dynamics to detect the presence of Chaos with the corresponding ones used within the GDA, i.e., the tangent dynamics and the geodesic deviation equations, respectively, pointing out their general inequivalence. Moreover, to go ahead the mathematical analysis and to highlight both the peculiarities of the methods and the analogies between them, we work out two concrete applications to the study of very different, yet typical in distinct contexts, dynamical systems. The first is the well-known Hénon-Heiles Hamiltonian, which allows to exploit how the Finsler GDA is well suited not only for testing the dynamical behaviour of systems with few degrees of freedom, but even to get deeper insights on the sources of instability.We show the effectiveness of the GDA, both in recovering fully satisfactory agreement with the most well established outcomes and also in helping the understanding of the sources of Chaos. Then, in order to point out the general applicability of the method, we present the results obtained from the geometrical description of a General Relativistic DS, whose peculiarity is well known, as its very nature has been debated since long time, namely the Bianchi IX (BIX) cosmological model. Using the Finsler GDA, we obtain results with a built-in invariance, which give evidence to the non chaotic behaviour of this system, excluding any global exponential instability in the evolution of the geodesic deviation. 2Introduction.