Mycotoxins nivalenol and deoxynivalenol differently modulate cytokine mRNA expression in Jurkat T cells.

Deoxynivalenol (DON) and its hydroxylated form nivalenol (NIV) are Fusarium mycotoxins that occur in cereal grains alone or in combination. Several studies have shown that these metabolites affect lymphocyte functions. However, the molecular mechanisms underlying their activities are still partially known. To address this issue, we examined the influence of NIV and DON in modulating IFNc, IL-2 and IL-8 mRNA levels in Jurkat T cells. In PMA/ionomycin stimulated cells, pre-incubated with increasing concentrations of NIV, transcription was induced in the range 0.06–2 lM; higher concentrations of NIV were found non-stimulating (4 lM) or inhibitory (8 lM) for IFNc and IL-2 whereas IL-8 was still induced. DON administration elicited a similar profile for IL-8 and IFNc, whilst IL-2 mRNA was induced in a broader range of concentrations. Combination of NIV and DON at 1:1 and 1:10 ratios essentially restored the cytokine transcriptional pattern observed with NIV alone but the level of transcripts, with the exception of IL-8, peaked at lower concentrations suggesting interactive effects. Moreover both mycotoxins caused inhibition of cell proliferation, mediated by induction of apoptosis, confirming previous results and highlighting the usefulness of Jurkat as a T-cell model to study the effects of mycotoxins on the immune functions in humans

Cosmography and constraints on the equation of state of the Universe in various parametrizations

We use cosmography to present constraints on the kinematics of the Universe, without postulating any underlying theoretical model. To this end, we use a Monte Carlo Markov Chain analysis to perform comparisons to the supernova Ia Union 2 compilation, combined with the Hubble Space Telescope measurements of the Hubble constant, and the Hubble parameter datasets. We introduce a sixth order cosmographic parameter and show that it does not enlarge considerably the posterior distribution when comparing to the fifth order results. We also propose a way to construct viable parameter variables to be used as alternatives of the redshift $z$. These can overcome both the problems of divergence and lack of accuracy associated with the use of $z$. Moreover, we show that it is possible to improve the numerical fits by re-parameterizing the cosmological distances. In addition, we constrain the equation of state of the Universe as a whole by the use of cosmography. Thus, we derive expressions which can be directly used to fit the equation of state and the pressure derivatives up to fourth order. To this end, it is necessary to depart from a pure cosmographic analysis and to assume the Friedmann equations as valid. All our results are consistent with the $\Lambda$CDM model, although alternative fluid models, with nearly constant pressure and no cosmological constant, match the results accurately as well.Comment: 23 pages. 1 reference added. Minor correction

Trichothecenes NIV and DON modulate the maturation of murinedendritic cells

Nivalenol (NIV) and Deoxynivalenol (DON), mycotoxins of the trichothecene family are considered very common food contaminants. In this work, we investigated whether the immunotoxic effects ascribed to these trichothecenes may be mediated by perturbations in the activity of dendritic cells (DCs). Murine bone marrow-derived DCs were used to evaluate the effects of NIV and DON on the LPS-induced maturation process.We found that the expression of the class II MHC and of the accessory CD11c molecules, but not of the costimulatory CD86 marker, was down-regulated by NIV and DON exposure in LPS-treated DCs, as well as nitric oxide (NO) production. Interestingly, NIV, but not DON, induced DC necrosis. Moreover, the analysis of the cytokine pattern showed that IL-12 and IL-10 expressions induced by LPS exposure were suppressed by both trichothecenes in a dose-dependent fashion. On the other hand, the secretion of the proinflammatory cytokine TNFa was increased as a direct consequence of DON and NIV exposure. Taken together, our data indicated that the immunotoxicity of NIV and DON was related to the capacity of both trichothecenes to interfere with phenotypic and functional features of maturing DCs

Immune effects of four Fusarium-Toxins ( FB1, ZEA, NIV, DON) on the proliferation of Jurkat cells and porcine lymphocytes: in vitro study.

Fusarium toxins are secondary metabolites produced by fungi belonging to Fusarium spp., commonly found as contaminants in products of vegetable origin, particularly in cereal grains, in regions with temperate climate in Europe, America and Asia. Numerous toxic effects are attributed to mycotoxins both in humans and animals, such as mutagenic, cencerogenic and teratogenic properties. Moreover, some of them can alter normal immune responses when they are present in food at levels lower than those necessary to cause the symptoms of mycotoxicosis. In the present work, we evaluated the immunomodulatory effects of four Fusarium toxins (FB1, ZEA, NIV, DON) using two different experimental models: Jurkat cells and porcine lymphocytes. In addition to the activity of single mycotoxins, we evaluated possible interactions between Fusarium toxins to reproduce experimental conditions in vitro as near as possible to field conditions. Our results revealed the immunomodulatory properties of the mycotoxin objects of the current study. They also underline the interest in studying possible interactions among different mycotoxins, particularly among those mainly present in food such as Fusarium mycotoxins, not only regarding their toxicodinamic aspect but also to define tolerable maximum levels of Fusarium toxins in food

Two-to-one resonant multi-modal dynamics of horizontal/inclined cables. Part I : theoretical formulation and model validation

This paper is first of the two papers dealingwith analytical investigation of resonant multimodal dynamics due to 2:1 internal resonances in the finite-amplitude free vibrations of horizontal/inclined cables. Part I deals with theoretical formulation and validation of the general cable model. Approximate nonlinear partial differential equations of 3-D coupled motion of small sagged cables - which account for both spatio-temporal variation of nonlinear dynamic tension and system asymmetry due to inclined sagged configurations - are presented. A multidimensional Galerkin expansion of the solution ofnonplanar/planar motion is performed, yielding a complete set of system quadratic/cubic coefficients. With the aim of parametrically studying the behavior of horizontal/inclined cables in Part II [25], a second-order asymptotic analysis under planar 2:1 resonance is accomplished by the method of multiple scales. On accounting for higher-order effectsof quadratic/cubic nonlinearities, approximate closed form solutions of nonlinear amplitudes, frequencies and dynamic configurations of resonant nonlinear normal modes reveal the dependence of cable response on resonant/nonresonant modal contributions. Depending on simplifying kinematic modeling and assigned system parameters, approximate horizontal/inclined cable models are thoroughly validated by numerically evaluating statics and non-planar/planar linear/non-linear dynamics against those of the exact model. Moreover, the modal coupling role and contribution of system longitudinal dynamics are discussed for horizontal cables, showing some meaningful effects due to kinematic condensation

Grape pomace polyphenols improve insulin response to a standard meal in healthy individuals: A pilot study

Dietary polyphenols have beneficial effects on glucose/lipid metabolism in subjects at high risk to develop type 2 diabetes; however, the underlying mechanisms are not clear. We aimed to evaluate: 1) the acute effects of the consumption of a drink rich in polyphenols from red grape pomace (RGPD) on glucose/insulin and triglyceride responses to a standard meal in healthy individuals, and, 2) the relationship between plasma levels of phenolic metabolites and metabolic parameters

Neuroinflammation, Mast Cells, and Glia: Dangerous Liaisons

The perspective of neuroinflammation as an epiphenomenon following neuron damage is being replaced by the awareness of glia and their importance in neural functions and disorders. Systemic inflammation generates signals that communicate with the brain and leads to changes in metabolism and behavior, with microglia assuming a pro-inflammatory phenotype. Identification of potential peripheral-to-central cellular links is thus a critical step in designing effective therapeutics. Mast cells may fulfill such a role. These resident immune cells are found close to and within peripheral nerves and in brain parenchyma/meninges, where they exercise a key role in orchestrating the inflammatory process from initiation through chronic activation. Mast cells and glia engage in crosstalk that contributes to accelerate disease progression; such interactions become exaggerated with aging and increased cell sensitivity to stress. Emerging evidence for oligodendrocytes, independent of myelin and support of axonal integrity, points to their having strong immune functions, innate immune receptor expression, and production/response to chemokines and cytokines that modulate immune responses in the central nervous system while engaging in crosstalk with microglia and astrocytes. In this review, we summarize the findings related to our understanding of the biology and cellular signaling mechanisms of neuroinflammation, with emphasis on mast cell-glia interactions

Scale-Free model for governing universe dynamics

We investigate the effects of scale-free model on cosmology, providing, in this way, a statistical background in the framework of general relativity. In order to discuss properties and time evolution of some relevant universe dynamical parameters (cosmographic parameters), such as $H(t)$ (Hubble parameter), $q(t)$ (deceleration parameter), $j(t)$ (jerk parameter) and $s(t)$ (snap parameter), which are well re-defined in the framework of scale-free model, we analyze a comparison between WMAP data. Hence the basic purpose of the work is to consider this statistical interpretation of mass distribution of universe, in order to have a mass density $\rho$ dynamics, not inferred from Friedmann equations, via scale factor $a(t)$. This model, indeed, has been used also to explain a possible origin and a viable explanation of cosmological constant, which assumes a statistical interpretation without the presence of extended theories of gravity; hence the problem of dark energy could be revisited in the context of a classical probability distribution of mass, which is, in particular, for the scale-free model, $P(k)\sim k^{-\gamma}$, with $2<\gamma<3$. The $\Lambda$CDM model becomes, with these considerations, a consequence of the particular statistics together with the use of general relativity.Comment: 7 pages, 4 figure

Buckling disappearance via merging/divergence in a nonlinear three-d.o.f. system with linear constitutive law

The phenomenon of buckling disappearance, occurring in a parameter-dependent family of systems admitting a nontrivial fundamental path, is studied. Two different forms of disappearance are detected, namely: (i) the divergence, in which the critical load continuously tends to infinity, and (ii) the merging, in which two critical loads approach each other, coalesce, and then disappear at a finite value of the critical load. It is shown that the two phenomena can be exhibited by the same mechanical system, when a suitable elasto-geometric parameter is varied. More importantly, it is proved that merging continuously changes into divergence when a second parameter is changed. A paradigmatic system is chosen to illustrate the two forms of buckling, i.e., a three degree-of-freedom spherical pendulum, elastically constrained at the ground, loaded by a transverse force and/or a conservative couple, made of two longitudinal potential forces. The springs are taken elastically linear, to stress the fact that divergence not necessarily calls for introducing a nonlinear constitutive law, as also mentioned in literature. Only a linear bifurcation analysis is carried out here, aimed to find the bifurcation points along the nonlinear fundamental path. However, due to the presence of non-negligible prestrains, such a bifurcation problem is governed by nonlinear algebraic equations, whose number of roots cannot be predicted in advance

Solution to the Problem of a Mass Traveling on a Taut String via Integral Equation

The problem of a massive taut string, traveled by a heavy point mass, moving with an assigned law, is formulated in a linear context. Displacements are assumed to be transverse, and the dynamic tension is neglected. The equations governing the moving boundary problem are derived via a variational principle, in which the geometric compatibility between the point mass and the string is enforced via a Lagrange multiplier, having the meaning of transverse reactive force. The equations are rearranged in the form of a unique Volterra integral equation in the reactive force, which is solved numerically. A classical Galerkin solution is implemented for comparison. Numerical results throw light on the physics of the phenomenon and confirm the effectiveness of the algorithm