Adaptation to G93A superoxide dismutase 1 in a motor neuron cell line model of amyotrophic lateral sclerosis. The role of glutathione

Motor neuron degeneration in amyotrophic lateral sclerosis involves oxidative damage. Glutathione (GSH) is critical as an antioxidant and a redox modulator. We used a motor neuronal cell line (NSC-34) to investigate whether wild-type and familial amyotrophic lateral sclerosis-linked G93A mutant Cu,Zn superoxide dismutase (wt ⁄G93ASOD1) modified the GSH pool and glutamate cysteine ligase (GCL), the rate-limiting enzyme for GSH synthesis. We studied the effect of various G93ASOD1 levels and exposure times. Mutant Cu,Zn superoxide dismutase induced an adaptive process involving the upregulation of GSH synthesis, even at very low expression levels. However, cells with a high level of G93ASOD1 cultured for 10 weeks showed GSH depletion and a decrease in expression of the modulatory subunit of GCL. These cells also had lower levels of GSH and GCL activity was not induced after treatment with the pro-oxidant tertbutylhydroquinone. Cells with a low level of G93ASOD1 maintained higher GSH levels and GCL activity, showing that the exposure time and the level of the mutant protein modulate GSH synthesis. We conclude that failure of the regulation of the GSH pathway caused by G93ASOD1 may contribute to motor neuron vulnerability and we identify this pathway as a target for therapeutic intervention

A demonstrator for bolometric interferometry

Bolometric Interferometry (BI) is one of the most promising techniques for precise measurements of the Cosmic Microwave Background polarization. In this paper, we present the results of DIBO (Demonstrateur d'Interferometrie Bolometrique), a single-baseline demonstrator operating at 90 GHz, built to proof the validity of the BI concept applied to a millimeter-wave interferometer. This instrument has been characterized in the laboratory with a detector at room temperature and with a 4 K bolometer. This allowed us to measure interference patterns in a clean way, both (1) rotating the source and (2) varying with time the phase shift among the two interferometer's arms. Detailed modelisation has also been performed and validated with measurements.Comment: 15 pages, 14 figure

Status and trend of atmospheric deposition chemistry at the CONECOFOR plots, 1998-2005

Ion deposition in the open field and under the canopy was monitored in 13 CONECOFOR plots during 1998-2005. In spite of the remote location of most plots, atmospheric deposition carries considerable amounts of anthropogenic ions (sulphate, nitrate and ammonium). Deposition acidity is buffered by the deposition of base cations, partially due to the long-range transport of Saharan dust. In the study period, sulphate deposition and deposition acidity significantly decreased, because of the decrease in sulphur dioxide emissions in Europe, while nitrate and ammonia deposition did not show a clear temporal pattern

The p50 NF-\u3baB subunit is a prognostic regulator of colorectal cancer-associated inflammation

In most tumors, tumor associated macrophages (TAMs) express an M2-skewed phenotype and are therefore associated with unfavorable prognosis. However, the impact of TAMs in colorectal cancer (CRC) development and outcome is still controversial. We first demonstrate, by parallel studies in colitis-associated cancer (CAC) and in genetically driven ApcMin mouse models, that p50 NF-\u3baB is essential for CRC development by restraining M1-dependent antitumor response. In absence of p50 mice developed fewer and smaller CRC lesions which express enhanced levels of M1/Th1 cytokines/chemokines including IL-12 and CXCL10, whose administration restrained CAC development in vivo. Moreover colons from p50-/- tumor bearers showed a reduced number of TAMs, as opposed to increased NK, NKT, CD8+ T cells and apoptotic cancer cells. Consistently, in CRC patients, high burden of p50+ TAMs was associated with decreased M1/Th1 inflammation and worse outcome indicating p50 as a new candidate for prognostic and target therapeutic intervention

La chimica delle deposizioni atmosferiche e gli inquinanti atmosferici nelle aree del programma CONECOFOR nell\u27anno 2012

Atmospheric deposition was sampled in 13 forest sites in Italy, in the open field, under tree canopy and on stemflow, and analyzed for major ions, dissolved organic carbon and total nitrogen. Ozone concentration was also measured during spring and summer. The results were compared with time series dating back to 1997

La chimica delle deposizioni atmosferiche e gli inquinanti atmosferici nelle aree del programma CONECOFOR nell\u27anno 2011

Atmospheric deposition was sampled in 22 forest sites in Italy, in the open field, under tree canopy and on stemflow, and analyzed for major ions, dissolved organic carbon and total nitrogen. Ozone concentration was also measured during spring and summer. The results were compared with time series dating back to 1997

Characterization of Detergent-Insoluble Proteins in ALS Indicates a Causal Link between Nitrative Stress and Aggregation in Pathogenesis

BACKGROUND:Amyotrophic lateral sclerosis (ALS) is a progressive and fatal motor neuron disease, and protein aggregation has been proposed as a possible pathogenetic mechanism. However, the aggregate protein constituents are poorly characterized so knowledge on the role of aggregation in pathogenesis is limited. METHODOLOGY/PRINCIPAL FINDINGS:We carried out a proteomic analysis of the protein composition of the insoluble fraction, as a model of protein aggregates, from familial ALS (fALS) mouse model at different disease stages. We identified several proteins enriched in the detergent-insoluble fraction already at a preclinical stage, including intermediate filaments, chaperones and mitochondrial proteins. Aconitase, HSC70 and cyclophilin A were also significantly enriched in the insoluble fraction of spinal cords of ALS patients. Moreover, we found that the majority of proteins in mice and HSP90 in patients were tyrosine-nitrated. We therefore investigated the role of nitrative stress in aggregate formation in fALS-like murine motor neuron-neuroblastoma (NSC-34) cell lines. By inhibiting nitric oxide synthesis the amount of insoluble proteins, particularly aconitase, HSC70, cyclophilin A and SOD1 can be substantially reduced. CONCLUSION/SIGNIFICANCE:Analysis of the insoluble fractions from cellular/mouse models and human tissues revealed novel aggregation-prone proteins and suggests that nitrative stress contribute to protein aggregate formation in ALS

Trophic condition of the volcanic Lake Nemi (Central Italy): environmental factors and planktonic communities in a changing environment

Lake Nemi is an interesting case of anthropogenic overexploitation which has caused its progressive environmental deterioration in the past decades. On this lake historical data about the trophic situation are available from 1975 to 1984. The research performed in 2002-03, about ten years after the diversion of urban waste waters, concerned a biological investigation on the phyto- and zooplanktonic communities, integrated with a physico-chemical analysis. The aims of our study are to evaluate the current water quality of the lake and compare it with the water quality observed in 1982-1983, when all biotic and abiotic components indicated a heavily compromised hypereutrophic condition. The water quality data and the comparison with a previous study point out that the biological aspects have partially changed (increased number of Cyanobacteria and phytoplanktonic taxa, particularly Clorophyta and Dinophyta; zooplankton composition changed at a species level, with the appearance of taxa associated to light trophic conditions), and the physico-chemical conditions significantly improved. The mean transparency, dissolved oxygen, nutrients and chlorophyll-a concentrations have all improved. Mean annual temperature at different depths increased, probably due to differences in climatic period and the lowering of the lake surface level (from 32.5 to 27.5 m in 1982 and 2002, respectively). Our results indicate a general improving trend in water quality is taking place since the diversion of waste water discharges. The present abiotic characteristics of the lake allow the phytoplankton to distribute itself in the whole epilimnion, and the zooplankton in the whole water column. A possible further improvement is hypothesized, and the constraints represented by excessive water level lowering and water temperature increasing are also discussed

The Large-Scale Polarization Explorer (LSPE)

The LSPE is a balloon-borne mission aimed at measuring the polarization of the Cosmic Microwave Background (CMB) at large angular scales, and in particular to constrain the curl component of CMB polarization (B-modes) produced by tensor perturbations generated during cosmic inflation, in the very early universe. Its primary target is to improve the limit on the ratio of tensor to scalar perturbations amplitudes down to r = 0.03, at 99.7% confidence. A second target is to produce wide maps of foreground polarization generated in our Galaxy by synchrotron emission and interstellar dust emission. These will be important to map Galactic magnetic fields and to study the properties of ionized gas and of diffuse interstellar dust in our Galaxy. The mission is optimized for large angular scales, with coarse angular resolution (around 1.5 degrees FWHM), and wide sky coverage (25% of the sky). The payload will fly in a circumpolar long duration balloon mission during the polar night. Using the Earth as a giant solar shield, the instrument will spin in azimuth, observing a large fraction of the northern sky. The payload will host two instruments. An array of coherent polarimeters using cryogenic HEMT amplifiers will survey the sky at 43 and 90 GHz. An array of bolometric polarimeters, using large throughput multi-mode bolometers and rotating Half Wave Plates (HWP), will survey the same sky region in three bands at 95, 145 and 245 GHz. The wide frequency coverage will allow optimal control of the polarized foregrounds, with comparable angular resolution at all frequencies.Comment: In press. Copyright 2012 Society of Photo-Optical Instrumentation Engineers. One print or electronic copy may be made for personal use only. Systematic reproduction and distribution, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper are prohibite

Analisi della relazione tra le concentrazione di azoto e la composizione delle comunit? acquatiche

This report presents an analysis of the relationships between environmental variables and organisms belonging to the four biotic communities used to define the lake\u27s ecological quality, according to provisions of the Italian legislation (D.Lgs. 260, November 2010) and the European Water Framework 2000/6. The data analyzed were collected during the sampling surveys carried out within InHabit Project in 13 water bodies, 7 in Piedmont and 6 in Sardinia respectively. In particular, the aim of the study was to evaluate the possible effects of nitrogen on biotic communities. Phytoplankton community shown the clearer responses: according to the result of multivariate analysis, total nitrogen and ammonium nitrogen are among the most significant factors explaining the relationships among phytoplankton orders, species and environmental variables. In particular, cyanobacteria increased considerably with increasing availability of ammonium nitrogen. Conversely, high concentrations of this compound suppress the development of diatoms. Other algal groups show a nonlinear response with respect to nitrogen, with a possible limitation under low levels of nitrogen and an inhibition at higher levels. A comparative analysis, carried out to evaluate the response to the gradient of total phosphorus, shows that this nutrient is not as selective as nitrogen in controlling the structure of the algal assemblage in different environmental conditions. Other biotic communities did not show a clear relationship with nitrogen, but they rather responded to the trophic gradient as a whole: responses by macroinvertebrates seem, especially in the analysis of functional groups, complex and difficult to discriminate, highlighting a possible shifting of the food web towards the presence of large carnivores at high trophic status. Regarding the fish, the results show that nitrogen alone does not seem to be an important controlling factor for the fish communities. However together with the phosphorus, is one of the main elements controlling both biomass and size of the fish fauna, as well as the presence of tolerant, omnivorous or benthofagous species. In conclusion, the results of our analysis highlight the need for a greater emphasis on nitrogen inputs, which, especially in cases of nitrogen carried by atmospheric deposition, may even affect lake ecosystems relatively distant from direct impacts of human activities, thus altering the structure of biotic communities.A partire dai dati raccolti con le campagne di campionamento effettuate nell?ambito del progetto InHabit, questo documento presenta un?analisi delle relazioni tra le variabili ambientali e gli organismi appartenenti alle quattro comunit? biotiche utilizzate per la definizione della qualit? ecologica degli ambienti lacustri, secondo quanto previsto dal D.Lgs. 260 del novembre 2010, che recepisce la Direttiva Europea sulle Acque 2000/60. I campionamenti sono stati condotti in 13 ambienti lacustri, 7 in Piemonte e 6 in Sardegna. In particolare, lo scopo del lavoro ? stato valutare i possibili effetti sulla comunit? biotiche di concentrazioni variabili dei composti azotati inclusi tra le variabili considerate. La comunit? che mostra le risposte pi? chiare ? quella fitoplanctonica: come risulta dall?analisi multivariata, sia azoto ammoniacale che azoto totale compaiono tra le variabili significative per spiegare l?ordinamento di ordini e specie fitoplanctoniche. Tra questi, sono soprattutto i cianobatteri che aumentano sensibilmente all?aumentare della disponibilit? di azoto ammonicale. Al contrario, elevate concentrazioni di questo composto deprimono lo sviluppo delle diatomee. Altri gruppi algali mostrano una risposta non lineare rispetto ai composti azotati, con una possibile limitazione a bassi livelli di azoto ed una inibizione a livelli troppo elevati. L?analisi della risposta rispetto al gradiente di fosforo totale, mostra che questo nutriente non ? selettivo come l?azoto nel controllare la struttura delle associazioni algali in diverse condizioni ambientali. Le altre comunit? non hanno mostrato una relazione evidente con i composti azotati, ma, piuttosto, con il gradiente trofico complessivo: le risposte evidenziate dalla fauna macroinvertebrata, sembrano, soprattutto nell?analisi dei gruppi funzionali, complesse e difficili da discriminare, evidenziando un possibile spostamento degli equilibri della rete trofica verso i carnivori in presenza di elevati livelli trofici. Relativamente alla fauna ittica, i risultati mostrano che da solo l?azoto non sembra essere un fattore di controllo importante per la comunit? ittiche. Tuttavia insieme al fosforo, ? uno degli elementi principali a cui si associano positivamente la biomassa e le dimensioni della fauna ittica, nonch? la presenza di specie tolleranti, onnivore o bentofaghe. In conclusione, i risultati della nostra analisi, sottolineano ulteriormente la necessit? di porre una maggiore attenzione agli apporti di azoto, che, soprattutto nei casi di azoto veicolato da deposizioni atmosferiche, potrebbero interessare anche ecosistemi lacustri relativamente distanti da impatti diretti delle attivit? antropiche, alterandone la struttura delle comunit? biotiche