Neuroprotective Effects of Physical Activity via the Adaptation of Astrocytes

The multifold benefits of regular physical exercise have been largely demonstrated in human and animal models. Several studies have reported the beneficial effects of physical activity, both in peripheral tissues and in the central nervous system (CNS). Regular exercise improves cognition, brain plasticity, neurogenesis and reduces the symptoms of neurodegenerative diseases, making timeless the principle of "mens sana in corpore sano" (i.e., a healthy mind in a healthy body). Physical exercise promotes morphological and functional changes in the brain, acting not only in neurons but also in astrocytes, which represent the most numerous glial cells in the brain. The multiple effects of exercise on astrocytes comprise the increased number of new astrocytes, the maintenance of basal levels of catecholamine, the increase in glutamate uptake, the major release of trophic factors and better astrocytic coverage of cerebral blood vessels. The purpose of this review is to highlight the effects of exercise on brain function, emphasize the role of astrocytes in the healthy CNS, and provide an update for a better understanding of the effects of physical exercise in the modulation of astrocyte function

SPHERE: Irradiation of sphere-pac fuel of UPuO2−x containing 3% Americium

AbstractAmericium is a strong contributor to the long term radiotoxicity of high activity nuclear waste. Transmutation by irradiation in nuclear reactors of long-lived nuclides like 241Am is therefore an option for the reduction of radiotoxicity of waste packages to be stored in a repository. The SPHERE irradiation experiment is the latest of a series of European experiments on americium transmutation (e.g. EFTTRA-T4, EFTTRA-T4bis, HELIOS, MARIOS) performed in the HFR (High Flux Reactor). The SPHERE experiment is carried out in the framework of the 4-year project FAIRFUELS of the EURATOM 7th Framework Programme (FP7). During the past years of experimental works in the field of transmutation and tests of innovative nuclear fuels, the release or trapping of helium as well as helium induced fuel swelling have been shown to be the key issues for the design of Am-bearing targets. The main objective of the SPHERE experiment is to study the in-pile behaviour of fuel containing 3% of americium and to compare the behaviour of sphere-pac fuel to pellet fuel, in particular the role of microstructure and temperature on fission gas release (mainly He) and on fuel swelling.The SPHERE experiment is being irradiated since September 2013 in the HFR in Petten (The Netherlands) and is expected to be terminated in spring 2015. The experiment has been designed to last up to 18 reactor cycles (corresponding to 18 months) but may reach its target earlier.This paper discusses the rationale and objective of the SPHERE experiment and provides a general description of its design

Parkin isoforms expression in lung adenocarcinoma

PARK2, also known as parkin, is a gene mutated in autosomal recessive juvenile parkinsonism and it has been shown to exhibit E3 ubiquitin ligase activity. However it seems to fulfill also a wide spectrum of protective functions. Recent studies have demonstrated that parkin is an important regulator of process that maintain mitochondrial quality and it is also implicated in proteasomal degradation of toxic substrates. This gene has been also shown to be genetically altered and/or aberrantly expressed in a wide variety of human cancers including lung cancer (Cesari et al., 2003; Veeriah S. et al., 2010). Although many alternatively spliced isoforms have been identified, until now studies have been focused on the full-length isoform (D’Agata and Cavallaro, 2004). To characterize the role of parkin isoforms in lung tumorigenesis we analyzed their expression pattern in human lung adenocarcinomas. These data were correlated to their expression pattern either in human lung epithelial carcinoma (A549) or in human normal bronchial epithelial (BEAS-2B) cell lines. Western blot and immunofluorescence analyses were performed by using two antibodies recognizing different domains of the full length protein. Immunoblots showed that lung adenocarcinomas express parkin isoforms of 50, 37 and 20 kDa. Their expressions were significantly increased in A549 as compared to BEAS-2B, suggesting that parkin isoforms might be involved in cancer progression. In order to characterize some functions of these isoforms, both cell lines were cultured in complete medium or serum starved medium and treated with the proteasome inhibitor MG132 or with carbonyl cyanide 3- clorophenylhydrazone (CCCP), a uncoupling agent that dissipates the mitochondrial membrane. Data obtained revealed that each treatment affects pattern expression of parkin isoforms. These results suggest that some parkin isoforms might be molecular markers of lung adenocarcinoma

Parkin isoforms expression in gliomas

Parkin (PARK2) is one of the largest genes in the human genome encoding for an E3 ubiquitin ligase. Its mutation is the cause of early-onset Parkinson’s disease, but recently it is linked to other pathologies including cancer. Parkin acts as a tumor suppressor. It displays a wide neuroprotective activity by promoting the removal of damaged mitochondria via mitophagy and increasing proteasomal degradation of toxic substrates. PARK2 primary transcript undergoes to an extensive alternative splicing, which enhances transcriptomic diversification and protein diversity in tissues and cells. To date, GenBank lists 26 human PARK2 transcripts corresponding to 21 different alternative splice variants. These transcripts show different expression patterns and encode for proteins with different functions, molecular weight and isoelectric point. Previous studies identified inactivating somatic mutations and frequent intragenic deletions of PARK2 in human cancers including gliomas (Veeriah et al., 2010). Recently, it has been demonstrated that Parkin pathway activation is predictive for the survival outcome of patients with glioma (Yeo et al., 2012). However, these papers focused on the expression of full length Parkin. In the present work we analyzed the expression pattern of Parkin isoforms in astrocytomas of different grade and we investigated their functions in a human glioblastoma multiforme cell line. Immunoblotting analysis by using two specific antibodies revealed that Parkin expression is generally higher in malignant glioblastoma than in less invasive astrocytomas, indicating a correlation between expression pattern of Parkin isoforms and tumor malignancy. Serum deprivation or treatment with a proteosome inhibitor MG132 or with carbonyl cyanide 3-chlorophenylhydrazone (CCCP), an uncoupling agent that dissipates the cells mitochondrial membrane potential, increased expression of 100-55-50 kDa parkin isoforms in glioma cells as compared to controls. These results, consistent with other studies, demonstrated a functional connection between Parkin expression, mitochondrial integrity and endoplasmic reticulum stress (Bouman et al., 2011). Parkin isoforms expression was also confirmed by confocal microscopy analysis. These results suggest that the characterization of some PARK2 isoforms may be usefull clinically to develop a prognostic tool in patients with brain tumor

Health related quality of life in adolescents with idiopathic scoliosis: a cross-cultural comparison between two methods of treatment

he present study aims at evaluating the effects produced on HRQOL by two different methods of physiotherapy in adolescent population with Idiopathic Scoliosis (IS): SEAS, used in Milan (Italia) in ISICO center, and Barcelona Scoliosis Physical Therapy School, in E. Salvá Institut (Spain)

Antibiotics in early life associate with specific gut microbiota signatures in a prospective longitudinal infant cohort

BACKGROUND The effects of antibiotics on infant gut microbiota are unclear. We hypothesized that the use of common antibiotics results in long-term aberration in gut microbiota. METHODS Antibiotic-naive infants were prospectively recruited when hospitalized because of a respiratory syncytial virus infection. Composition of fecal microbiota was compared between those receiving antibiotics during follow-up (prescribed at clinicians' discretion because of complications such as otitis media) and those with no antibiotic exposure. Fecal sampling started on day 1, then continued at 2-day intervals during the hospital stay, and at 1, 3 and 6 months at home. RESULTS One hundred and sixty-three fecal samples from 40 patients (median age 2.3 months at baseline; 22 exposed to antibiotics) were available for microbiota analyses. A single course of amoxicillin or macrolide resulted in aberration of infant microbiota characterized by variation in the abundance of bifidobacteria, enterobacteria and clostridia, lasting for several months. Recovery from the antibiotics was associated with an increase in clostridia. Occasionally, antibiotic use resulted in microbiota profiles associated with inflammatory conditions. CONCLUSIONS Antibiotic use in infants modifies especially bifidobacterial levels. Further studies are warranted whether administration of bifidobacteria will provide health benefits by normalizing the microbiota in infants receiving antibiotics.Peer reviewe

Antimicrobial resistance (AMR) nanomachines: mechanisms for fluoroquinolone and glycopeptide recognition, efflux and/or deactivation

In this review, we discuss mechanisms of resistance identified in bacterial agents Staphylococcus aureus and the enterococci towards two priority classes of antibiotics—the fluoroquinolones and the glycopeptides. Members of both classes interact with a number of components in the cells of these bacteria, so the cellular targets are also considered. Fluoroquinolone resistance mechanisms include efflux pumps (MepA, NorA, NorB, NorC, MdeA, LmrS or SdrM in S. aureus and EfmA or EfrAB in the enterococci) for removal of fluoroquinolone from the intracellular environment of bacterial cells and/or protection of the gyrase and topoisomerase IV target sites in Enterococcus faecalis by Qnr-like proteins. Expression of efflux systems is regulated by GntR-like (S. aureus NorG), MarR-like (MgrA, MepR) regulators or a two-component signal transduction system (TCS) (S. aureus ArlSR). Resistance to the glycopeptide antibiotic teicoplanin occurs via efflux regulated by the TcaR regulator in S. aureus. Resistance to vancomycin occurs through modification of the D-Ala-D-Ala target in the cell wall peptidoglycan and removal of high affinity precursors, or by target protection via cell wall thickening. Of the six Van resistance types (VanA-E, VanG), the VanA resistance type is considered in this review, including its regulation by the VanSR TCS. We describe the recent application of biophysical approaches such as the hydrodynamic technique of analytical ultracentrifugation and circular dichroism spectroscopy to identify the possible molecular effector of the VanS receptor that activates expression of the Van resistance genes; both approaches demonstrated that vancomycin interacts with VanS, suggesting that vancomycin itself (or vancomycin with an accessory factor) may be an effector of vancomycin resistance. With 16 and 19 proteins or protein complexes involved in fluoroquinolone and glycopeptide resistances, respectively, and the complexities of bacterial sensing mechanisms that trigger and regulate a wide variety of possible resistance mechanisms, we propose that these antimicrobial resistance mechanisms might be considered complex ‘nanomachines’ that drive survival of bacterial cells in antibiotic environments