17 research outputs found

    LTP and memory impairment caused by extracellular A\u3b2 and Tau oligomers is APP-dependent

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    The concurrent application of subtoxic doses of soluble oligomeric forms of human amyloid-beta (oA\u3b2) and Tau (oTau) proteins impairs memory and its electrophysiological surrogate long-term potentiation (LTP), effects that may be mediated by intra-neuronal oligomers uptake. Intrigued by these findings, we investigated whether oA\u3b2 and oTau share a common mechanism when they impair memory and LTP in mice. We found that as already shown for oA\u3b2, also oTau can bind to amyloid precursor protein (APP). Moreover, efficient intra-neuronal uptake of oA\u3b2 and oTau requires expression of APP. Finally, the toxic effect of both extracellular oA\u3b2 and oTau on memory and LTP is dependent upon APP since APP-KO mice were resistant to oA\u3b2- and oTau-induced defects in spatial/associative memory and LTP. Thus, APP might serve as a common therapeutic target against Alzheimer's Disease (AD) and a host of other neurodegenerative diseases characterized by abnormal levels of A\u3b2 and/or Tau

    Detection and quantification of mammaglobin in the blood of breast cancer patients: can it be useful as a potential clinical marker? Preliminary results of a GOIM (Gruppo Oncologico dell'Italia Meridionale) prospective study.

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    BACKGROUND: Mammaglobin is expressed mainly in mammary tissue, overexpressed in breast cancer (BC) and rarely in other tissue. The aim of this study was to assess the sensitivity and specificity of transcript MGB1 detection and to evaluate the role of MGB1 as potential clinical marker for the detection of disseminated cancer cells in the blood of BC patients. PATIENTS AND METHODS: A consecutive series of 23 BC tissues, 36 peripheral blood BC samples and 35 healthy peripheral blood samples was prospectively recruited to investigate MGB1 expression by means of a quantitative Real Time RT-PCR assay. RESULTS: MGB1 overexpression in tissue samples of BC patients is significantly associated only with high level of Ki67 (P <0.05). None of the samples from peripheral blood of 35 healthy female individuals were positive for MGB1 transcript. In contrast MGB1 mRNA expression was detected in three of 36 (8%) peripheral blood of BC patients. CONCLUSIONS: Our preliminary results demonstrate that the detection of MGB1 transcript in peripheral blood of BC patients was specific but with low sensitivity. MGB1 overexpression by itself or in combination with Ki67 might be considered an index of BC progression

    High-pressure granulite-facies metamorphism in central Dronning Maud Land (East Antarctica): implications for Gondwana assembly

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    Central Dronning Maud Land (DML; East Antarctica) is located in a key region of the Gondwana supercontinent. The Conradgebirge area (central DML) consists of orthogneisses, derived from both volcanic and plutonic protoliths, and minor metasedimentary rocks, intruded by Cambrian syn- to post-metamorphic plutons and dykes. Mafic-ultramafic boudins in the metavolcanic and metaplutonic gneisses from Conradgebirge consist of amphibolites and high-grade garnet-bearing pyroxene- and amphibole-rich granofels. They occur either as discontinuous levels or as pods boudinaged within highly-strained and strongly-migmatized gneisses. Bulk-rock major and trace-element compositions, together with geochemical discriminant diagrams (e.g., Th/Yb versus Ta/Yb and V versus Ti), suggest derivation from enriched mantle source for the mafic rocks boudinaged in metaplutonic gneisses, whereas a calc-alkaline signature is common for the mafic boudins in metavolcanic rocks. The microstructural study and P–T modelling of an ultramafic metagabbroic rock reveal a prograde metamorphic evolution from amphibolite-facies (ca. 0.5 GPa; 500 °C) up to high-P granulite-facies conditions (ca. 1.5–1.7 GPa; 960–970 °C). Partial melting is testified by “nanogranitoid” inclusions enclosed in garnet. An almost isothermal decompression down to ca. 0.4 GPa and 750–850 °C produced well-developed An + Opx-bearing symplectites around garnet. A final isobaric cooling at nearly 0.4 GPa is testified by Grt coronas around high-T symplectites. The above reconstruction traces a clockwise loading-heating P-T evolution with a peak metamorphism at high-P granulite-facies conditions suggesting crustal thickening at nearly 570 Ma, followed by a tectonically assisted rapid exhumation, and then, by an isobaric cooling. 40Ar-39Ar dating of amphibole and biotite at ~ 505–480 Ma testify mineral re-equilibration at upper crustal level (T &lt; 650 °C) during the isobaric cooling. This tectono-metamorphic scenario seems representative of the evolution resulting from the Neoproterozoic/Early Palaeozoic (600–500 Ma) collision between parts of East- and West-Gondwana blocks that led to the final assembly of Gondwana

    Protracted (~30Ma) eclogite-facies metamorphism in northern Victoria Land (Antarctica): Implications for the geodynamics of the Ross/Delamerian Orogen

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    Northern Victoria Land, Antarctica, plays a key role in any geodynamic reconstructions of the paleo-Pacific margin of Gondwana because it represents the along-strike continuation of Australia in Antarctica and hosts the only Paleozoic eclogites known along the Transantarctic Mountains. The architecture and evolution of the early Cambrian to Early Ordovician Ross–Delamerian Orogen in northern Victoria Land, however, remain controversial. Accurate geodynamic reconstructions have been hindered by a dearth of temporal metamorphic constraints. This study reports laser-ablation split-stream ICP-MS data on zircon in newly recognized eclogite, that preserves a memory of the prograde evolution, and on zircon from its country rock from the Lanterman Range of northern Victoria Land. Geochronological data are supplemented for the eclogite by whole-rock geochemical and petrological constraints, that indicate an E-MORB protolith derived from a depleted mantle source, and P–T conditions for the eclogite-facies stage of ~ 700 °C and 1.7–2.4 GPa. U–Pb ages, trace-element contents, cathodoluminescence imaging and textural/inclusion relationships testify to protracted zircon growth/recrystallization history under eclogite-facies conditions, that also included (re)crystallization during part of the prograde path. Results extend the onset of eclogite-facies metamorphism in northern Victoria Land back to ~ 530 Ma and, together with geochronological evidence for the emplacement of calc-alkaline granitoids at ~ 530–520 Ma, suggest that UHP–HP rocks formed by accretion of material beneath an active continental margin. Regionally, this interpretation implies that burial of mafic rocks and associated siliciclastic sequences to mantle depths commenced significantly earlier than previously believed (~ 500 Ma), thereby contrasting with the common belief that high-pressure metamorphism was linked to arc–continent collision. New and old results reveal the coexistence along the same ridge of two eclogite types: (1) medium-grained, “colder” and undeformed eclogites, that recorded both prograde and peak conditions, and (2) finer-grained, “hotter” and slightly deformed eclogites, that recorded only metamorphic peak conditions with hints of the subsequent retrogression. We propose that “prograde/peak” eclogites formed during an active continental margin stage and “peak” eclogites during the subsequent island arc–continental arc collision

    SHRIMP dating of zircons in eclogite from the Variscan basement in north-eastern Sardinia (Italy)

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    SHRIMP (Sensitive High-Resolution Ion Microprobe) U-Pb ages of zircons from a single sample of mafic eclogite (Punta de li Tulchi, Sardinia, Italy) are reported. The study under cathodoluminescence (CL) reveals two groups of metamorphic zircons and the SHRIMP analyses allow recognition of three ages: 1) 453 ± 14 Ma; 2) 400 ± 10 Ma, and 3) 327 ± 7 Ma. The age of 453 ± 14 Ma could be that of the magmatic protolith and an age of 327 ± 7 Ma can reasonably be attributed to the main Variscan collisional event in Sardinia, which produced Barrovian-type metamorphism, and retrogression of eclogite under amphibolite-facies metamorphism. The intermediate age 400 ± 10 Ma is difficult to interpret and it could represent either the age of the eclogite facies metamorphism or it is a result of Pb-loss during the main Variscan event at 327 ± 7 Ma

    Partial melting of ultramafic granulites from Dronning Maud Land, Antarctica: Constraints from melt inclusions and thermodynamic modeling

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    In the Pan-African belt of the Dronning Maud Land, Antarctica, crystallized melt inclusions (nanogranitoids) occur in garnet from ultramafic granulites. The granulites contain the peak assemblage pargasite+garnet+clinopyroxene with rare relict orthopyroxene and biotite, and retrograde symplectites at contacts between garnet and amphibole. Garnet contains two generations of melt inclusions. Type 1 inclusions, interpreted as primary, are isolated, < 10 mu m in size, and generally have negative crystal shapes. They contain kokchetavite, kumdykolite, and phlogopite, with quartz and zoisite as minor phases, and undevitrified glass was identified in one inclusion. Type 2 inclusions are < 30 mu m in size, secondary, and contain amphibole, feldspars, and zoisite. Type 2 inclusions appear to be the crystallization products of a melt that coexisted with an immiscible CO2-rich fluid. The nanogranitoids were re-homogenized after heating in a piston-cylinder in a series of four experiments to investigate their composition. The conditions ranged between 900 and 950 degrees C at 1.5-2.4 GPa. Type 1 inclusions are trachytic and ultrapotassic, whereas type 2 melts are dacitic to rhyolitic. Thermodynamic modeling of the ultramafic composition in the MnNCKFMASHTO system shows that anatexis occurred at the end of the prograde P-T path, between the solidus (at ca. 860 degrees C-1.4 GPa) and the peak conditions (at ca. 960 degrees C-1.7 GPa). The model melt composition is felsic and similar to that of type 1 inclusions, particularly when the melting degree is low (< 1 mol%), close to the solidus. However the modeling fails to reproduce the highly potassic signature of the melt and its low H2O content. The combination of petrology, melt inclusion study, and thermodynamic modeling supports the interpretation that melt was produced by anatexis of the ultramafic boudins near peak P-T conditions, and that type 1 inclusions contain the anatectic melt that was present during garnet growth. The felsic, ultrapotassic composition of the primary anatectic melts is compatible with low melting degrees in the presence of biotite and amphibole as reactants

    Melt inclusions at MT. Edixon (Antarctica): Chemistry, petrology and implications for the evolution of the Lanterman range

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    The recovery of melt inclusions (MI) in peritectic phases of metamorphic rocks demonstrates their anatectic origin even in the absence of other textural or field evidences, and gives the opportunity to retrieve the chemical composition of primary melts and infermelt entrapment conditions. Herewe report the first recovery of such inclusions in a medium-grade schist from the Edixon Metamorphic Complex (EMC) of the Lanterman Range in northern Victoria Land, Antarctica. This is the first study of melt inclusions from an Al2SiO5-free, graywacketype protolith. Inclusions are hosted in garnet. They are both polycrystalline nanogranitoids, i.e., crystallized former MI, and fluid inclusions (FI) coexisting in the same clusters and displaying frequent negative crystal shape and textures indicative of a primary origin. TheMI contain albite, K-feldspar, quartz,muscovite, biotite\ub1 calcite \ub1siderite\ub1H2O,while the FI are composed by CO2+H2O+N2+CH4\ub1H2S and contain step-daughter calcite. The schist hosting the garnets with melt inclusions contains muscovite, biotite, garnet, plagioclase, K-feldspar, and quartz. Extensive resorption of garnet and replacement by biotite, alongwith composition ofmicas that suggest medium-temperature, subsolidus conditions, indicate that after anatexis the schist was thoroughly recrystallized under retrograde conditions. The MI were remelted in a piston cylinder apparatus at conditions of 740\u2013900 \ub0C at 0.8\u20131.0 GPa with complete remelting taking place at 760\u2013780 \ub0C. The remelted glass is subalkaline, peraluminous (ASI 48 1.3\u20131.5) with CaO 48 1.2\u20132.1 wt% and K2O 48 3.4\u20134.1 wt% and contains 48 4.3\u20135.3wt% of H2O and 400\u20131150 ppmof CO2. The P-T conditions ofmelt entrapmentwere retrieved combining results of experimental remelting with calculated phase equilibria in theMnCNKFMASHTmodel system, and are between 740 and 780 \ub0C and 0.7 to 0.9 GPa. The newand different P-T conditions for a high grade rock of the EMC with respect to other published data, confirm that this metamorphic complex is not homogeneous, and that anatexis may have taken place at different crustal levels during the evolution of the Cambro-Ordovician Ross Orogen
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