Glutamate induces autophagy via the two-pore channels in neural cells

NAADP (nicotinic acid adenine dinucleotide phosphate) has been proposed as a second messenger for glutamate in neuronal and glial cells via the activation of the lysosomal Ca2+ channels TPC1 and TPC2. However, the activities of glutamate that are mediated by NAADP remain unclear. In this study, we evaluated the effect of glutamate on autophagy in astrocytes at physiological, non-toxic concentration. We found that glutamate induces autophagy at similar extent as NAADP. By contrast, the NAADP antagonist NED-19 or SiRNA-mediated inhibition of TPC1/2 decreases autophagy induced by glutamate, confirming a role for NAADP in this pathway. The involvement of TPC1/2 in glutamate-induced autophagy was also confirmed in SHSY5Y neuroblastoma cells. Finally, we show that glutamate leads to a NAADP-dependent activation of AMPK, which is required for autophagy induction, while mTOR activity is not affected by this treatment. Taken together, our results indicate that glutamate stimulates autophagy via NAADP/TPC/AMPK axis, providing new insights of how Ca2+ signalling glutamate-mediated can control the cell metabolism in the central nervous system

New insights on the relative sea level change during Holocene along the coasts of Tunisia and western Libya from archaeological and geomorphological markers

New data of sea level changes for the Mediterranean region along the coasts of northern Africa are presented. Data are inferred from archaeological sites of Punic-Roman age located along the coast of Tunisia, between Tunis and Jerba island and along the western coast of Libya, between Sabratha and Leptis Magna. Data are based on precise measures of presently submerged archaeological markers that are good indicators of past sea-level elevation. Nineteen selected archaeological sites were studied in Tunisia and four in Libya, all aged between w2.0 and w1.5 ka BP. The functional elevations of significant archaeological markers were measured with respect to the sea level at the time of measurements, applying corrections for tide and atmospheric pressure values. The functional elevations of specific architectural parts of the sites were interpreted, related to sea level at the time of their construction providing data on the relative changes between land and sea. Observations were compared against sea level change predictions derived from the glacio-hydro-isostatic model associated with the Last Glacial cycle. The results indicate that local relative sea level change along the coast of Tunisia and Libya, has increased 0.2 O 0.5 m since the last w2 ka. Besides minor vertical tectonic movements of the land, the observed changes are produced by eustatic and glacio-hydro-isostatic variations acting in the Mediterranean basin since the end of the last glacial maximum

Comparing marine geology and coastal geomorphology vertical tectonic data, a case study between Acquedolci and Patti (Messina).

The study of new data on vertical movements show a complex geologic response in a restricted sector of coastal area between Acquedolci and Patti (north-eastern Sicily). Different surveys allowed to the recognition of morphological, biological and archaeological markers of paleo-sea level. The analysis of these markers and the absolute datings performed, allowed to reconstruct the history of vertical deformation of this sector but only the comparison among coastal geomorphological data and marine geological data of platform-scarp continental system associates, allowed to find the necessary keys words to explain the geologic complexity of this sector

The first experience with a mini-rating scale for the assessment of sexual dysfunction and life-satisfaction in depressed patients in the practice

Even though many scales for the assessment of sexual dysfunction have been recently developed, most of them are suitable rather for the research purpose in clinical trials than to routine interviews in a daily, private practice. We report here the first experience with a simple, semi-quantitative scale for parallel assessment of sexual dysfunction and life-satisfaction (considered to globally reflect the quality of life), which was tested in depressed patients treated in the psychiatric, private practice setting. A combined Sexual Dysfunction(SD-S) and Life-Satisfaction Scale (LS-S), was constructed based on previous interviews with patients. Both consisted of 4-items, assumed to represent core elements of sexual function and individual well-being. The scales were applied to depressed patients treated with any of the SSRIs or with moclobemide, a reversible and selective MAO-A inhibitor. These two treatments were selected for testing the scales because it is known that SSRIs can induce or exacerbate them and moclobemide does not seem to affect them. The selection of treatment modality in this study was, however, entirely at the discretion of the physician. The assessments were done during 3 visits (at baseline, after 2 months and after 4 months). The results of this exploratory trial, testing the applicability, acceptance and utility of a combined mini- SD-S- and LS-S- scale, in 62 depressed patients, showed that the scale: a) was simple to use and well accepted by physicians and patients, b) was a suitable instrument for the practicing physician to control the success of the treatment and c) was sensitively assessing the presence and severity of sexual dysfunction

Resposta de tangerinas e híbridos ao virus da leprose dos citros.

A leprose dos citros é uma das mais importantes viroses da citricultura brasileira. A doença, causada pelo Citrus leprosis virus C (CiLV-C) transmitido por Brevipalpus phoenicis, caracteriza-se pela indução de lesões locais no hospedeiro vegetal. Por ser uma virose não sistêmica, ao contrário da maioria das que ocorrem em plantas, o conhecimento dos mecanismos envolvidos nas interações vírus x planta x vetor se tornam ainda mais importantes, principalmente em relação ao manejo da doença no campo.A leprose tem a sua maior importância econômica no Brasil, embora relatos de sua ocorrência em países das Américas vêm aumentando significativamente nos últimos anos (Bastianel et al., 2010). Por ser um sério problema fitossanitário em pomares de laranjas doces, graças ao plantio em grande escala de variedades altamente suscetíveis, poucos estudos sobre a importância da leprose em outros grupos de citros, como as tangerinas e tangores têm sido relatados. Neste trabalho, estudos foram conduzidos com o objetivo de se ampliar o conhecimento da resposta da doença em variedades de tangerinas e híbridos de importância econômica.pdf 145

Millstones as indicators of relative sea-level changes in northern Sicily and southern Calabria coast lines, Italy

New data are presented for late Holocene relative sea-level changes in two coastal sites of Sicily and Calabria, southern Italy. Reconstructions are based on precise measurements of submerged archaeological remains that are valuable indicators of past sea-level position. The archaeological remains are millstone quarries carved on sandstone coastal rocks and nowadays partially submerged which, to the authors’ knowledge, are used for the first time as sea-level markers. Millstones of similar typology are located on the coast of Capo d’Orlando (northern Sicily) and Capo dell’Armi (southern Calabria). When the archeologically-based sea-level position is compared with the shoreline elevation provided by geological markers (Holocene beachrock, Late Pleistocene marine terraces), a refined understanding of relative sea-level changes and rates of vertical tectonic movements for these coastline locations is gained

Differential role of cyclooxygenase 1 and 2 isoforms in the modulation of colonic neuromuscular function in experimental inflammation

This study examines the role played by cyclooxygenase (COX) isoforms (COX-1 and -2) in the regulation of colonic neuromuscular function in normal rats and after induction of colitis by 2,4-dinitrobenzenesulfonic acid (DNBS). The expression of COX-1 and COX-2 in the colonic neuromuscular layer was assessed by reverse transcription-polymerase chain reaction and immunohistochemistry. The effects of COX inhibitors on in vitro motility were evaluated by studying electrically induced and carbachol-induced contractions of the longitudinal muscle. Both COX isoforms were constitutively expressed in normal colon; COX-2 was up-regulated in the presence of colitis. In normal and inflamed colon, both COX isoforms were mainly localized in neurons of myenteric ganglia. In the normal colon, indomethacin (COX-1/COX-2 inhibitor), SC-560 [5-(4-chloro-phenyl)-1-(4-methoxyphenyl)-3-trifluoromethylpyrazole] (COX-1 inhibitor), or DFU [5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulfonyl)phenyl-2(5H)-furanone] (COX-2 inhibitor) enhanced atropine-sensitive electrically evoked contractions. The most prominent effects were observed with indomethacin or SC-560 plus DFU. In the inflamed colon, SC-560 lost its effect, whereas indomethacin and DFU maintained their enhancing actions. These results were more evident after blockade of noncholinergic pathways. In rats with colitis, in vivo treatment with superoxide dismutase or S-methylisothiourea (inhibitor of inducible nitric-oxide synthase) restored the enhancing motor effect of SC-560. COX inhibitors had no effect on carbachol-induced contractions in normal or DNBS-treated rats. In conclusion, in the normal colon, both COX isoforms act at the neuronal level to modulate the contractile activity driven by excitatory cholinergic pathways. In the presence of inflammation, COX-1 activity is hampered by oxidative stress, and COX-2 seems to play a predominant role in maintaining an inhibitory control of colonic neuromuscular function

High Levels of β-Amyloid, Tau, and Phospho-Tau in Red Blood Cells as Biomarkers of Neuropathology in Senescence-Accelerated Mouse

Alzheimer’s Disease (AD) is the most common Neurodegenerative Disease (ND), primarily characterised by neuroinflammation, neuronal plaques of β-amyloid (Aβ), and neurofibrillary tangles of hyperphosphorylated tau. α-Synuclein (α-syn) and its heteroaggregates with Aβ and tau have been recently included among the neuropathological elements of NDs. These pathological traits are not restricted to the brain, but they reach peripheral fluids as well. In this sense, Red Blood Cells (RBCs) are emerging as a good model to investigate the biochemical alterations of aging and NDs. Herein, the levels of homo- and heteroaggregates of ND-related proteins were analysed at different stages of disease progression. In particular, a validated animal model of AD, the SAMP8 (Senescence-Accelerated Mouse-Prone) and its control strain SAMR1 (Senescence-Accelerated Mouse-Resistant) were used in parallel experiments. The levels of the aforementioned proteins and of the inflammatory marker interleukin-1β (IL-1β) were examined in both brain and RBCs of SAMP8 and SAMR1 at 6 and 8 months. Brain Aβ, tau, and phospho-tau (p-tau) were higher in SAMP8 mice than in control mice and increased with AD progression. Similar accumulation kinetics were found in RBCs, even if slower. By contrast, α-syn and its heterocomplexes (α-syn-Aβ and α-syn-tau) displayed different accumulation kinetics between brain tissue and RBCs. Both brain and peripheral IL-1β levels were higher in SAMP8 mice, but increased sooner in RBCs, suggesting that inflammation might initiate at a peripheral level before affecting the brain. In conclusion, these results confirm RBCs as a valuable model for monitoring neurodegeneration, suggesting peripheral Aβ, tau, and p-tau as potential early biomarkers of AD