30,837 research outputs found

    Nitric oxide and mitochondrial biogenesis

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    The characteristic structural organization of mitochondria is the product of synthesis of macromolecules within the mitochondria together with the import of proteins and lipids synthesized outside the organelle. Synthetic and import processes are required for mitochondrial proliferation and might also facilitate the growth of pre-existing mitochondria. Recent evidence indicates that these events are regulated in a complex way by several agonists and environmental conditions, through activation of specific signaling pathways and transcription factors. A newly discovered role of this organelle in retrograde intracellular signaling back to the nucleus has also emerged. This is likely to have far-reaching implications in development, aging, disease and environmental adaptation. Generation of nitric oxide (NO) appears to be an important player in these processes, possibly acting as a unifying molecular switch to trigger the whole mitochondrial biogenesis process. High levels of NO acutely inhibit cell respiration by binding to cytochrome c oxidase. Conversely, chronic, smaller increases in NO levels stimulate mitochondrial biogenesis in diverse cell types. NO-induced mitochondrial biogenesis seems to be linked to proliferation and differentiation of normal and tumor cells, as well as in agin

    Dopamine inhibition of neurotensin-induced increase in Ca2+ influx into rat pituitary cells.

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    In this paper, we report that the intracellular mechanism by which neurotensin stimulates prolactin release involves an increase in Ca2+ uptake by pituitary cells rather than an effect on adenylate cyclase system. In addition, dopamine can prevent neurotensin-induced calcium influx by interacting with dopamine D2-receptors which appear to be completely independent of the adenylate cyclase moiety but are coupled to calcium channels

    Sustained quasi-steady turbidity current : outcrop evidence from the Pliocene peri-Adriatic foredeep (Cellino Fm., Central Italy)

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    The aim of this work is to investigate the nature of the numerous, very thick deep-water sheet-sandstones that dominate the lower portion of the Cellino Formation (Central Italy). The studied turbidite system (about 2,500 m thick) represents the Lower Pliocene turbiditic filling of the outer Abruzzo sector of the Periadriatic foredeep. The foredeep was affected by compressional deformation linked to the overall migration of the chain-foredeep system toward the east. Tectonic activity was mostly coeval with the sedimentation and propagated towards the foreland; thrusting became progressively younger from W to E. The Cellino Basin has been intensely explored, being the site of hydrocarbon-bearing sands. The turbidite beds can be distinctively resolved in the well logs and correlated to the measured sedimentary sections on outcrop. Based on well log correlation, tens of individual beds up to 23 m thick have been traced along the axis of the basin over distance in excess of 100 km and, perpendicularly to the basin, over distance of 30-40 km (Carruba et al. in press), with sand volumes on the order of a few 10’s Km3 (10 – 80 Km3). Palaeocurrent data taken from basal flute structures indicates southerly-directed flows, parallel to the depocentral axis of the basin. The thickest beds show a basin-wide extension, onlapping the basin margins without significant thickness variation. The internal organization of the studied megabeds provides evidence for occurrence of long-lived flows and suggests deposition by gradual aggradation from sustained currents (sustained turbidity current; Kneller and Branney, 1995). The following features have been argued to be characteristic for sustained currents: (i) turbidite beds of extraordinary volume and thickness, (ii) very thick massive basal division (0.5 – 6 m thick), (iii) very frequent alternation of structureless and laminated intervals associated to internal scour surfaces, (iv) thick massive mudstone cap (1-10 m) that terminates the vertical organization of the sedimentary structures, (v) crudely developed grain-size profile that is overall upward fining (normally graded), (vi) abundant organic matter, (vii) extensive water-escape features. The very thick massive basal division observed in the studied megabeds can be explained with progressive aggradation and absence of traction at the depositional flow boundary. The very frequent alternation of structureless and laminated intervals observed within the studied deposits, and their internal scour surfaces reflect temporal variation in flow velocity and sediment flux within the same current, as indicated by the discontinuity of the scour surface and the constant grain size above and below the surfaces. The graded upper part of the studied megabeds (a thick massive mud cap terminates the vertical organization of the sedimentary structures) represents the deposits of the waning stage of the current. Assuming a quasi-steady flow scenario we can explain the nature of the numerous very thick megabeds within the Cellino Fm considering that the determining factors of the thickness of the studied deposits are the confinement of the basin and the rate and the duration of deposition, which may proceed as long as the current maintains a flux of grains towards the site of deposition. The origin of these large-volume turbidity currents and their high rate of occurrence can be related to an interaction of many factors and external controls, which are typical of the ancient foredeep basins (Mutti et al., 2003). Our data suggest that the studied megabeds could be originated from catastrophic floods and sediment failures during relative falling- and low-stand stage of sealevel forced by dramatic tectonic uplift of basin margins. Where the mountains fronts are close to shoreline, floods would be able to carry the majority of sediment load directly to the sea; the final depositional area of the ancient fluvial system that probably fed the Cellino basin lies in the deep water, far away from river mouths, and it is recorded by basinal turbidite sandstones and megabeds. Although an understanding of climatic controls is extremely difficult on the basis of available data, high-frequency climatic pulses (that provided the water through which sediments were periodically flushed to the Periadriatic foredeep by flood-related process) could explain the amount of stacked megabeds. In this model, lower-frequency tectonically-forced cycles of uplift/denudation account for sediment availability through time. Consequently, the lower portion of the Cellino Formation could correspond to a stage of a single uplift/denudation cycle. In this stage, the tectonically active Cellino basin reaches its highest instability because the elevation of drainage basins is maximum and its proximity to the shoreline minimum

    Evidence for the existence of two distinct dopamine D-2 receptors in presynaptic nerve terminals from rat corpus striatum

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    1 Radioactive rubidium (86Rb+) efflux was used to measure potassium (K+) permeability in a study designed to assess both the presence and the sensitivity to ions and drugs of the K+ channels in the presynaptic nerve terminals of rat striatum. This method allowed differential measurement of the activity of two distinct components of 86Rb+ efflux, component V (sensitive to voltage and Ca2+-independent) and component C (Ca2+-activated). 2 A series of dopamine D-2 receptor agonists, including quinpirole, bromocriptine and Ru 24213, appeared to affect both components of 86Rb+ efflux. The EC50 values of quinpirole, bromocriptine and Ru 24213 for activating component V of 86Rb+ efflux were 5 pM, 15 pM and 40 pM, respectively. These drugs also stimulated component C of 86Rb+ efflux in the same order, but with lower, potency. 3 The dopaminergic D-2 agonist BHT 920 discriminated between the two components being active on component V (EC50 = 200 pM) and inactive on component C (up to 1 - μM). 4 Activation of voltage-sensitive 86Rb+ efflux by various dopamine D-2 receptor agonists, including BHT 920, were antagonized by 0.1 μM (-)-sulpiride but not by 0.1 μM yohimbine. 5 Lesioning of the nigro-striatal pathway by injection of 6-hydroxydopamine in the substantia nigra caused a reduction of about 60% of the BHT 920-stimulated, voltage-sensitive, Ca2+ independent 86Rb+ efflux (component V). 6 These data indicate that striatal presynaptic nerve terminals contain two distinct dopamine D-2 receptors which can be differentiated both functionally and pharmacologically

    Die Konstruktionen mit verba dicendi und sentiendi

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    Rassegna delle costruzioni sintattiche delle frasi argomentali dell'ittito che riflettono una struttura fortemente implicita legata alla natura nominale di alcune forme verbali infinite che fingono da argomento del verbo della principale. Diversamente dalle altre lingue indoeuropee, le costruzioni completive con kuit (kat. quod), si sviluppano meno e in fase molto tarda

    Childhood obesity, overweight and underweight: a study in primary schools in Milan.

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    The study aims to assess the prevalence of obesity, overweight and underweight in children enrolled in government primary schools (6-11 years of age) in the city of Milan, Italy.One hundred and nine schools were randomly selected for the study. A cross-sectional study was conducted between March and June 2008. A survey was conducted using 16,588 questionnaires completed by parents. Anthropometric data (reported) of both parents and children and information on levels of physical activity and time children spent watching television (TV) were obtained.In the total sample, parents are predominantly (75.0 \%) of normal weight (M: 55.2 \%; F: 79.1 \%), 16.8 \% are overweight (M: 36.9 \%; F: 12.6 \%), 4.0 \% are obese (M: 6.6 \%; F: 3.5 \%) and 4.2 \% are underweight (M: 1.3 \%; F: 4.8 \%). Among children, 68.7 \% are of normal weight (M: 68.2 \%; F: 69.2 \%), 14.7 \% are overweight (M: 15.3 \%; F: 14.2 \%), 4 \% are obese (M: 4.5 \%; F: 3.4 \%), 11.8 \% are underweight (M: 11.2 \%; F: 12.5 \%) and 0.8 \% are severely thin (M: 0.9 \%; F: 0.7 \%). Children practice physical activity once or twice/week (48.3 \%), three to four times/week (38.9 \%) or five to seven times/week (8.9 \%), while 3.9 \% of children do not do any exercise. Most children (85.3 \%) watch TV from 30 min to 2 h/day.Contrary to the reported national average, the study shows the presence of only moderate levels of above-average weight and obesity among children. However, it remains important to monitor this phenomenon to raise awareness and to design programs of prevention throughout the country

    An amino acid-defined diet impairs tumour growth in mice by promoting endoplasmic reticulum stress and mTOR inhibition

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    Objective: Profound metabolic alterations characterize cancer development and, beyond glucose addiction, amino acid (AA) dependency is now recognized as a hallmark of tumour growth. Therefore, targeting the metabolic addiction of tumours by reprogramming their substrate utilization is an attractive therapeutic strategy. We hypothesized that a dietary approach targeted to stimulate oxidative metabolism could reverse the metabolic inflexibility of tumours and represent a proper adjuvant therapy. Methods: We measured tumour development in xenografted mice fed with a designer, casein-deprived diet enriched in free essential amino acids (EAAs; SFA-EAA diet), or two control isocaloric, isolipidic, and isonitrogenous diets, identical to the SFA-EAA diet except for casein presence (SFA diet), or casein replacement by the free AA mixture designed on the AA profile of casein (SFA-CAA diet). Moreover, we investigated the metabolic, biochemical, and molecular effects of two mixtures that reproduce the AA composition of the SFA-EAA diet (i.e., EAAm) and SFA-CAA diet (i.e., CAAm) in diverse cancer and non-cancer cells. Results: The SFA-EAA diet reduced tumour growth in vivo, promoted endoplasmic reticulum (ER) stress, and inhibited mechanistic/mammalian target of rapamycin (mTOR) activity in the tumours. Accordingly, in culture, the EAAm, but not the CAAm, activated apoptotic cell death in cancer cells without affecting the survival and proliferation of non-cancer cells. The EAAm increased branched-chain amino acid (BCAA) oxidation and decreased glycolysis, ATP levels, redox potential, and intracellular content of selective non-essential amino acids (NEAA) in cancer cells. The EAAm-induced NEAA starvation activated the GCN2-ATF4 stress pathway, leading to ER stress, mTOR inactivation, and apoptosis in cancer cells, unlike non-cancer cells. Conclusion: Together, these results confirm the efficacy of specific EAA mixtures in promoting cancer cells’ death and suggest that manipulation of dietary EAA content and profile could be a valuable support to the standard chemotherapy for specific cancers
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