Verapamil Inhibits Ser202/Thr205 Phosphorylation of Tau by Blocking TXNIP/ROS/p38 MAPK Pathway.

PURPOSE: Oxidative stress is a hallmark of Alzheimer's Disease (AD) and promotes tau phosphorylation. Since Thioredoxin Interacting protein (TXNIP), the inhibitor of the anti-oxidant system of Thioredoxin, is up regulated in the hippocampus of AD patients, we investigated whether TXNIP plays a role in promoting tau phosphorylation and whether Verapamil, an inhibitor of TXNIP expression, prevents TXNIP downstream effects. METHODS: We analyzed TXNIP expression and tau phosphorylation in the hippocampus of the 5xFAD mice in the absence and presence of a pharmacological treatment with Verapamil. Using SH-SY5Y cells, we verified the causative role of TXNIP in promoting tau phosphorylation at Ser202/Thr205, by inducing TXNIP silencing. RESULTS: The amyloid beta peptide (Aβ1-42) leads to TXNIP over-expression in SH-SY5Y cells, which in turns induces oxidative stress and the activation of p38 MAPK, promoting tau phosphorylation at Ser202/Thr205. Silencing of TXNIP abolishes Aβ1-42-induced tau phosphorylation, p38 MAPK phosphorylation and subsequent tau phosphorylation. Verapamil prevents TXNIP expression as well as p38 MAPK and tau phosphorylation at Ser202/Thr205 in the hippocampus of the 5xFAD mice. CONCLUSIONS: Our study unveil a novel pathway involved in AD progression that is inhibited by Verapamil, shedding new light on the understanding of the therapeutic potential of Verapamil in AD

Benthic foraminiferal assemblages from three polluted areas in Southern Sardinia (Italy): A review

Previous studies evidence that benthic foraminifera are excellent indicators for monitoring the marine-coastal environments (e.g. Armynot du Châtelet et al., 2004; Coccioni, 2000; Debenay et al., 2000; Geslin et al., 2000, 2002; Murray, 2006; Samir & El-Din, 2001; Scott et al., 2005; Yanko et al., 1994, 1998, 1999; etc.). A detailed study on shallow-water benthic foraminifera of three polluted areas in Sardinia (Portoscuso-Portovesme, Santa Gilla Lagoon and Cagliari Gulf) were carried out in order to get informations on the environmental quality of these areas. Studies of marine sediments collected in Portoscuso-Portovesme (South-west Sardinia) revealed high concentrations of Hg, Cd, Pb and Zn (Cherchi et al., 2009), whereas Santa Gilla lagoon near Cagliari, is particularly affected by a high trace element content, mainly Cr, Cu, Hg, Ni, Pb and Zn. Mercury shows values up to 10 times higher than the background level (Frontalini et al., 2009). On the basis of a preliminary study (work in progress), the spatial distribution of the foraminiferal assemblages and the geochemical data reveal from highly to less heavy metals polluted conditions in the western part of the Cagliari Gulf (industrial area). Biological data and heavy metals contents were analyzed both with bivariate (correlation matrix), multivariate techniques of principal component analysis (PCA) and cluster analysis. The benthic foraminiferal assemblages react to increasing concentrations in heavy metals, often considered as very harmful for the environment. In the studied areas, the statistical analysis shows a possible control of the pollutants both on the taxonomic composition of the benthic foraminiferal assemblages and the development of test abnormalities. The discovery of a very depauperate foraminiferal assemblage and the occurrence of abnormalities, particularly emphasized in the innermost part of the Santa Gilla Lagoon, in Portovesme stations near the industrial complex, and in the western part of the Cagliari Gulf, testify important stress conditions in these areas. Ammonia tepida, Haynesina germanica and bolivinids show tolerance to environmental disturbance and pollution, these species are therefore particularly suitable as bio-indicators in coastal areas

La cartographie de l'interface rural-urbain dans l'amélioration de la prévention et de la préparation aux feux de forêt

International audienceThis presentation shows different situations of the use of interfaces mapping which contribute to improve the Rural Urban Interface (RUI) and Wildland Urban-interface (WUI) knowledge for the forest fire prevention and preparedness for inhabitants, stakeholders and firefighters. The works are based on researches developed by IRSTEA team of Aix-en-Provence, with the collaboration of Spanish team (Tragsatec) and Italian teams from Sardinia (UNISS and CNR) during the European FUME program, on-going works in the FIREXTR project in Portugal and also supported by the French Environment minister programme (bureau of natural and hydrologic risks)

Progranulin expression in brain tissue and cerebrospinal fluid levels in multiple sclerosis.

Background: Progranulin (PGRN) is a fundamental neurotrophic factor, and is also involved in inflammation and wound repair. PGRN may have pro- or anti-inflammatory properties, depending upon proteolysis of the anti-inflammatory parent PGRN protein and the generation of pro-inflammatory granulin peptides. Objectives: Our objectives were as follows: (1) to evaluate the presence and distribution of PGRN in multiple sclerosis (MS) brain tissue, correlating it with demyelination and inflammation; (2) to evaluate cerebrospinal fluid (CSF) PGRN concentrations in patients with MS and controls, in relationship to the clinical features of the disease. Methods: Our study involved the following: (1) neuropathological study of PGRN on post-mortem tissue of 19 MS and six control brains; (2) evaluation of PGRN CSF concentration in 40 MS patients, 15 non-inflammatory controls and five inflammatory controls (viral encephalitis). Results: In active demyelinating lesions, PGRN was expressed on macrophages/microglia. In the normal-appearing white matter (NAWM), expression of PGRN was observed on activated microglia. PGRN was expressed by neurons and microglia in cortical lesions and in normal-appearing cortex. No expression of PGRN was observed in controls, except on neurons. PGRN CSF concentrations were significantly higher in patients with relapsing–remitting MS during relapses and in progressive MS patients, compared with relapsing–remitting MS patients during remissions and with non-inflammatory controls. Conclusions: PGRN is strongly expressed in MS brains, by macrophages/microglia in active lesions, and by activated microglia in the NAWM; PGRN CSF concentrations in MS are correspondingly increased in conditions of enhanced macrophage/microglia activation, such as during relapses and in progressive MS. </jats:p

La cartographie de l'interface rural-urbain dans l'amélioration de la prévention et de la préparation aux feux de forêt

International audienceThis presentation shows different situations of the use of interfaces mapping which contribute to improve the Rural Urban Interface (RUI) and Wildland Urban-interface (WUI) knowledge for the forest fire prevention and preparedness for inhabitants, stakeholders and firefighters. The works are based on researches developed by IRSTEA team of Aix-en-Provence, with the collaboration of Spanish team (Tragsatec) and Italian teams from Sardinia (UNISS and CNR) during the European FUME program, on-going works in the FIREXTR project in Portugal and also supported by the French Environment minister programme (bureau of natural and hydrologic risks)

A tool for mapping rural-urban interfaces on different scales, in Advances in Forest Fire Research

The aim of this paper is to present the methodologies, a software and results developed in the European FUME program to map the rural-urban interfaces (RUI). Three methodologies were set up for RUI mapping: two on the local scale (the community scale) and one on the global scale (the European scale). The first local scale method was developed in a French context by IRSTEA. In this case the RUI is defined by a radius of 100 metres around each house located at a distance inferior to 200 metres from forests or scrublands. The building density was used to create four classes of housing configuration. Then the structure of vegetation was characterized and mapped to emphasize its horizontal continuity with landscape ecology metrics. The RUI map was created by a combination of housing configuration and vegetation characterisation. The second local scale method developed by TRAGSATEC is based on three phases. First a settlement map creation with the union of a land use cover and a vegetation cover defines the housing and the landscape that surrounds them. Then a buffer is created around settlements which are located at a distance inferior to 400 m from the forest; its size depends on the difficulty in protecting the houses against fire. In the final phase the different types of RUI are defined from the type of settlement and vegetation-settlement connection around houses. The global scale method developed by IRSTEA makes possible the comparison of the situations and the importance of RUI in the different European countries. On the global scale, the rural urban interfaces are defined by a radius of 400 metres around houses located atless than 200 metres from forests or shrubland. The global rural urban interface map results from the combination of criteria from the Corine Land Cover database and from the soil sealing database. A major step of the work was the development of a software named RUImap with the three different methods above. The use of the tool could be very advantageous for fire risk analysis on RUI scale, and for local quantification of fuel charge and continuity. This information linked with the direct knowledge of the general context is very important for the local fire risk assessment