Glatiramer Acetate modulates ion channels expression and calcium homeostasis in B cell of patients with relapsing-remitting multiple sclerosis.

To investigate the effects of Glatiramer Acetate (GA) on B cells by an integrated computational and experimental approach. GA is an immunomodulatory drug approved for the treatment of multiple sclerosis (MS). GA effect on B cells is yet to be fully elucidated. We compared transcriptional profiles of B cells from treatment-naïve relapsing remitting MS patients, treated or not with GA for 6 hours in vitro, and of B cells before and after six months of GA administration in vivo. Microarrays were analyzed with two different computational approaches, one for functional analysis of pathways (Gene Set Enrichment Analysis) and one for the identification of new drug targets (Mode-of-action by Network Analysis). GA modulates the expression of genes involved in immune response and apoptosis. A differential expression of genes encoding ion channels, mostly regulating Ca2+ homeostasis in endoplasmic reticulum (ER) was also observed. Microfluorimetric analysis confirmed this finding, showing a specific GA effect on ER Ca2+ concentration. Our findings unveils a GA regulatory effect on the immune response by influencing B cell phenotype and function. In particular, our results highlight a new functional role for GA in modulating Ca2+ homeostasis in these cells.

Recovery of Interdependent Networks.

Recent network research has focused on the cascading failures in a system of interdependent networks and the necessary preconditions for system collapse. An important question that has not been addressed is how to repair a failing system before it suffers total breakdown. Here we introduce a recovery strategy for nodes and develop an analytic and numerical framework for studying the concurrent failure and recovery of a system of interdependent networks based on an efficient and practically reasonable strategy. Our strategy consists of repairing a fraction of failed nodes, with probability of recovery γ, that are neighbors of the largest connected component of each constituent network. We find that, for a given initial failure of a fraction 1 - p of nodes, there is a critical probability of recovery above which the cascade is halted and the system fully restores to its initial state and below which the system abruptly collapses. As a consequence we find in the plane γ - p of the phase diagram three distinct phases. A phase in which the system never collapses without being restored, another phase in which the recovery strategy avoids the breakdown, and a phase in which even the repairing process cannot prevent system collapse.

Heavy metals in human amniotic fluid: a pilot study.

OBJECTIVE: Many heavy metals are essential nutrients for a healthy life. However, significant evidence supports prolonged prenatal exposure as a risk factor for several adverse health effects. The aim of this study is to evaluate the presence of heavy metals in human amniotic fluid (AF) to demonstrate that there is an early fetal in utero exposure. METHODS: The concentrations of a variety of heavy metals, including Be, Ag, Ba, Pb, U, Hg, Sr, Cu, Mn, V, Pd, Sn, Sb, Te, Pt, Sc, Tl, Ni, As, Co, Zn and Se, were measured in 25 AF samples obtained from amniocentesis between 15 and 18 weeks of gestational, after informed consent. RESULTS: Be, Ag, Ba, Pb, U, Cu, Sr, Mn, V, Sn, Te, Pt, As, Tl, Sb, Co, Se and Zn concentrations were detected in measurable amounts in second trimester AF. Mg levels are elevated in all samples. Pd, Ni, Sc and Hg concentrations are below the detection limits in all samples. CONCLUSION: This study demonstrates that heavy metals pass into and accumulate in AF from a very early stage of gestation. Other studies are needed to evaluate the long-term health effects of this early exposure.

Environment and women's reproductive health.

BACKGROUND: There is significant evidence that continuous and prolonged exposure to several endocrine disrupting chemicals (EDC) is a risk factor for reduced fertility and fecundity in women. There is also evidence that ED exposure has trans-generational effects. In this systematic review, we evaluate the evidence for an association between EDC exposure and women's reproductive health. METHODS: Studies were found by searching the PubMed database for articles published up to 2010. Associations between ED exposure and women's reproductive health reported in the PubMed database are summarized and classified as fertility and fecundity, pregnancy outcomes, transgenerational exposure and effects. RESULTS: Epidemiological studies on EDCs are not always consistent, in part due to limitations imposed by practical constraints. In order to make progress in this field, we recommend taking advantage of biomonitoring and biobanks, including the development of appropriate biomarkers, and taking into greater consideration modulating factors such as genetic polymorphisms and dietary habits. Further human studies are warranted with particular focus on impaired fertility/fecundity associated with currently widespread ED (e.g. bisphenol A, phthalates and polybrominated flame retardants). CONCLUSIONS: A detailed appraisal of compounds specifically related to adverse reproductive outcomes is very important for prevention and risk-communication strategies. Besides research needs, the current evidence is sufficient to prompt precautionary actions to protect women's reproductive health.

Conservative model for synchronization problems in complex networks.

In this paper we study the scaling behavior of the interface fluctuations (roughness) for a discrete model with conservative noise on complex networks. Conservative noise is a noise which has no external flux of deposition on the surface and the whole process is due to the diffusion. It was found that in Euclidean lattices the roughness of the steady state W(s) does not depend on the system size. Here, we find that for scale-free networks of N nodes, characterized by a degree distribution P(k) approximately k(-lambda), W(s) is independent of N for any lambda. This behavior is very different than the one found by Pastore y Piontti [Phys. Rev. E 76, 046117 (2007)] for a discrete model with nonconservative noise, which implies an external flux, where W(s) approximately ln N for lambda<3 , and was explained by nonlinear terms in the analytical evolution equation for the interface [La Rocca, Phys. Rev. E 77, 046120 (2008)]. In this work we show that in these processes with conservative noise the nonlinear terms are not relevant to describe the scaling behavior of W(s).

Evolution equation for a model of surface relaxation in complex networks.

In this paper we derive analytically the evolution equation of the interface for a model of surface growth with relaxation to the minimum (SRM) in complex networks. We were inspired by the disagreement between the scaling results of the steady state of the fluctuations between the discrete SRM model and the Edward-Wilkinson process found in scale-free networks with degree distribution P(k) approximately k(-lambda) for lambda<3 [Pastore y Piontti, Phys. Rev. E 76, 046117 (2007)]. Even though for Euclidean lattices the evolution equation is linear, we find that in complex heterogeneous networks nonlinear terms appear due to the heterogeneity and the lack of symmetry of the network; they produce a logarithmic divergency of the saturation roughness with the system size as found by Pastore y Piontti for lambda<3.

PAH content and mutagenicity of marine sediments from the Venice lagoon.

Sediments from the Venice lagoon, a polluted coastal environment in northeastern Italy, were assayed for mutagenicity and content of several toxic microcontaminants, which included selected polycyclic aromatic hydrocarbons (PAHs); the latter are specifically dealt with in this paper. Samples were collected at three lagoon sites with reasonably distinct environmental features--urban, industrial, or agricultural--and at two others considered to be under mixed pollution influences; a sixth sample was obtained from an open sea area to act as background control. The organic matter (EOM) associated with the mineral substrata was extracted; after cleanup, analyte determination was carried out by HRGC-LRMS(SIM) using isotopically labeled compounds as internal standards. Cumulative levels of the selected PAHs were found to be in the range of 0.065 to 0.46 micrograms/g of dry matrix at five sites; a much higher concentration (48 micrograms/g) was detected in the sample from the urban environment. The remarkable PAH level increase at this site was mostly accounted for by the concurrent, apparent increase of EOM contamination as PAH concentration was seen to reach 32 micrograms/mg of EOM from < 1 microgram/mg at the five remaining sites. Mutagenicity assays with Salmonella typhimurium strains TA98 and TA100 of marine sediment organic extracts also highlighted a distinct activity in the sample from the urban site. Further fractionation and analysis of this extract pointed to PAHs as the main mutagenic component present in the sediment matrix, possibly accounting for up to approximately 70-80% of the entire mutagenic potential detected.

Chemical and mutagenic evaluation of sludge from a large wastewater treatment plant.

Digested sludges from a wastewater treatment plant were analyzed to assess their level of contamination by some organic (polychlorobiphenyls (PCBs) and chlorinated pesticides) and inorganic (heavy metals) micropollutants and their mutagenicity features. The heavy metal content in none of the samples exceeded the limits set out in EEC Directive 276/86; as far as PCBs are concerned, the sludges analyzed indicated a level of contamination up to two orders of magnitude higher than some Italian agricultural soils. Mutagenicity assays on either crude or fractionated sludge extracts using Salmonella typhimurium tester strains TA98 and TA100 gave negative results, thus suggesting the absence of genotoxic contaminants in the samples investigated.