bluuebunny/crossref_metadata_2025_split huggingface dataset:
APP substitutions V715F and L720P alter PS1 conformation and differentially affect Aβ and AICD generation
Authors: Tesco Giuseppina , Ginestroni Andrea , Hiltunen Mikko , Kim Minji , Dolios Georgia , Hyman Bradley T. , Wang Rong , Berezovska Oksana , Tanzi Rudolph E. 
Published: September 2005

AbstractThe 37–43 amino acid Aβ peptide is the principal component of β‐amyloid deposits in Alzheimer's disease (AD) brain, and is derived by serial proteolysis of the amyloid precursor protein (APP) by β‐ and γ‐secretase. γ‐Secretase also cleaves APP at Val50 in the Aβ numbering (ε cleavage), resulting in the release of a fragment called APP intracellular domain (AICD). The aim of this study was to determine whether amino acid substitutions in the APP transmembrane domain differentially affect Aβ and AICD generation. We found that the APPV715F substitution, which has been previously shown to dramatically decrease Aβ40 and Aβ42 while increasing Aβ38 levels, does not affect in vitro generation of AICD. Furthermore, we found that the APPL720P substitution, which has been previously shown to prevent in vitro generation of AICD, completely prevents Aβ generation. Using a fluorescence resonance energy transfer (FRET) method, we next found that both the APPV715F and APPL720P substitutions significantly increase the distance between the N‐ and C‐terminus of presenilin 1 (PS1), which has been proposed to contain the catalytic site of γ‐secretase. In conclusion, both APPV715F and APPL720P change PS1 conformation with differential effects on Aβ and AICD production.
Controlled cortical impact injury affects dopaminergic transmission in the rat striatum
Authors: Wagner A. K. , Sokoloski J. E. , Ren D. , Chen X. , Khan A. S. , Zafonte R. D. , Michael A. C. , Dixon C. E. 
Published: September 2005

AbstractThe therapeutic benefits of dopamine (DA) agonists after traumatic brain injury (TBI) imply a role for DA systems in mediating functional deficits post‐TBI. We investigated how experimental TBI affects striatal dopamine systems using fast scan cyclic voltammetry (FSCV), western blot, and d‐amphetamine‐induced rotational behavior. Adult male Sprague–Dawley rats were injured by a controlled cortical impact (CCI) delivered unilaterally to the parietal cortex, or were naïve controls. Amphetamine‐induced rotational behavior was assessed 10 days post‐CCI. Fourteen days post‐CCI, animals were anesthetized and underwent FSCV with bilateral striatal carbon fiber microelectrode placement and stimulating electrode placement in the medial forebrain bundle (MFB). Evoked DA overflow was assessed in the striatum as the MFB was electrically stimulated at 60 Hz for 10 s. In 23% of injured animals, but no naïve animals, rotation was observed with amphetamine administration. Compared with naïves, striatal evoked DA overflow was lower for injured animals in the striatum ipsilateral to injury (p < 0.05). Injured animals exhibited a decrease in Vmax (52% of naïve, p < 0.05) for DA clearance in the hemisphere ipsilateral to injury compared with naïves. Dopamine transporter (DAT) expression was proportionally decreased in the striatum ipsilateral to injury compared with naïve animals (60% of naïve, p < 0.05), despite no injury‐related changes in vesicular monoamine transporter or D2 receptor expression (DRD2) in this region. Collectively, these data appear to confirm that the clinical efficacy of dopamine agonists in the treatment of TBI may be related to disruptions in the activity of subcortical dopamine systems.
Staphylococcus aureus‐derived peptidoglycan induces Cx43 expression and functional gap junction intercellular communication in microglia
Authors: Garg Sarita , Syed Mohsin Md. , Kielian Tammy 
Published: September 2005

AbstractGap junctions serve as intercellular conduits that allow the exchange of small molecular weight molecules (up to 1 kDa) including ions, metabolic precursors and second messengers. Microglia are capable of recognizing peptidoglycan (PGN) derived from the outer cell wall of Staphylococcus aureus, a prevalent CNS pathogen, and respond with the robust elaboration of numerous pro‐inflammatory mediators. Based on recent reports demonstrating the ability of tumor necrosis factor‐α and interferon‐γ to induce gap junction coupling in macrophages and microglia, it is possible that pro‐inflammatory mediators released from PGN‐activated microglia are capable of inducing microglial gap junction communication. In this study, we examined the effects of S. aureus‐derived PGN on Cx43, the major connexin in microglial gap junction channels, and functional gap junction communication using single‐cell microinjections of Lucifer yellow (LY). Exposure of primary mouse microglia to PGN led to a significant increase in Cx43 mRNA and protein expression. LY microinjection studies revealed that PGN‐treated microglia were functionally coupled via gap junctions, the specificity of which was confirmed by the reversal of activation‐induced dye coupling by the gap junction blocker 18‐α‐glycyrrhetinic acid. In contrast to PGN‐activated microglia, unstimulated cells consistently failed to exhibit LY dye coupling. These results indicate that PGN stimulation can induce the formation of a functional microglial syncytium, suggesting that these cells may be capable of influencing neuroinflammatory responses in the context of CNS bacterial infections through gap junction intercellular communication.
Extracellular histidine residues identify common structural determinants in the copper/zinc P2X2 receptor modulation
Authors: Lorca Ramón A. , Coddou Claudio , Gazitúa M. Consuelo , Bull Paulina , Arredondo Cristián , Huidobro‐Toro J. Pablo 
Published: September 2005

AbstractTo assess the mechanism of P2X2 receptor modulation by transition metals, the cDNA for the wild‐type receptor was injected to Xenopus laevis oocytes and examined 48–72 h later by the two‐electrode voltage‐clamp technique. Copper was the most potent of the trace metals examined; at 10 μm it evoked a 25‐fold potentiation of the 10 μm ATP‐gated currents. Zinc, nickel or mercury required 10‐fold larger concentrations to cause comparable potentiations, while palladium, cobalt or cadmium averaged only 12‐ and 3‐fold potentiations, respectively. Platinum was inactive. The non‐additive effect of copper and zinc at 10–100 μm suggests a common site of action; these metals also shifted to the left the ATP concentration–response curves. To define residues necessary for trace metal modulation, alanines were singly substituted for each of the nine histidines in the extracellular domain of the rat P2X2 receptor. The H120A and H213A mutants were resistant to the modulator action of copper, zinc and other metals with the exception of mercury. Mutant H192A showed a reduction but not an abrogation of the copper or zinc potentiation. H245A showed less affinity for copper while this mutant flattened the zinc‐induced potentiation. Mutant H319A reduced the copper but not the zinc‐induced potentiation. In contrast, mutants H125A, H146A, H152A and H174A conserved the wild‐type receptor sensitivity to trace metal modulation. We propose that His120, His192, His213 and His245 form part of a common allosteric metal‐binding site of the P2X2 receptor, which for the specific coordination of copper, but not zinc, additionally involves His319.
JNK inhibitory kinase is up‐regulated in retinal ganglion cells after axotomy and enhances BimEL expression level in neuronal cells
Authors: Wakabayashi Taketoshi , Kosaka Jun , Oshika Tetsuro 
Published: September 2005

AbstractOptic nerve transection results in retinal ganglion cell (RGC) death in adult mammals, after the alteration of gene expression of RGCs. To elucidate the molecular mechanism by which axotomy induces RGC death, we isolated the molecules up‐regulated after optic nerve transection. One of these, axomtomy‐related gene (ARG)357, an 895‐amino‐acid protein containing a complete serine–threonine kinase domain, was isolated from a subtraction library of the rat retina. The sequence showed that this gene was a rat homolog of human c‐Jun N‐terminal kinase (JNK) inhibitory kinase and so belonged to the germinal center kinase‐VIII subfamily of Sterile20s protein kinase. We designated ARG357 as rat JNK inhibitory kinase (JIK). Rat JIK was expressed ubiquitously in various tissues and was highly expressed in the retina, with selective expression in RGCs. After axotomy, BimEL and Hrk, which are BH3‐only proteins, and rat JIK were up‐regulated in RGCs. Overexpression of rat JIK in neuronal cells up‐regulated the expression of BimEL, but not that of Hrk. These results indicate that JIK may contribute to axotomy‐induced RGC death by up‐regulating the expression of BH3‐only protein.
Loss of Usp14 results in reduced levels of ubiquitin in ataxia mice
Authors: Anderson Christopher , Crimmins Stephen , Wilson Julie A. , Korbel Greg A. , Ploegh Hidde L. , Wilson Scott M. 
Published: September 2005

AbstractThe ataxia (axJ) mutation is a spontaneous recessive mutation that results in reduced expression of ubiquitin‐specific protease 14, Usp14. Mice homozygous for the axJ mutation are retarded for growth and exhibit several behavioral disorders, including a resting tremor and hindlimb paralysis. Although pathological defects appear to be limited to the central nervous system, reduction of Usp14 expression was widespread in the axJ mice. Usp14 co‐fractionated with proteasomes isolated from livers and brains of wild‐type mice. Proteasomes isolated from the axJ brains still possessed deubiquitinating activity and were functionally competent to hydrolyze 20S proteasomal substrates in vitro. However, the levels of monomeric ubiquitin were reduced approximately 35% in most of the axJ tissues examined. These results indicate that Usp14 functions to maintain the cellular levels of monomeric ubiquitin in mammalian cells, and that alterations in the levels of ubiquitin may contribute to neurological disease.
Astrocyte–neurone communication following oxygen–glucose deprivation
Authors: Griffin S. , Clark J. B. , Canevari L. 
Published: September 2005

AbstractWe looked at the possible interactions between astrocytes and neurones during reperfusion using an in vitro model of ischaemia–reperfusion injury, as a controlled environment that lends itself easily to manipulation of the numerous variables involved in such an insult. We constructed a chamber in which O2 can be lowered to a concentration of 1 µm and developed a primary cortical neuronal culture that is 99% pure and can survive to at least 10 days in vitro. We also established a novel system for the co‐culture of astrocytes and neurones in order to study the communication between these cells in a manner that allows the complete separation of one cell type from another. Neurone cultures showed profound cell death following an ischaemic period of only 15 min. We co‐cultured neurones that had been subjected to a 15‐min ischaemic insult with either non‐insulted astrocytes or astrocyte‐conditioned medium during the reperfusion stage. Both astrocytes and astrocyte‐conditioned medium enhanced neuronal survival. Our data also suggest that astrocyte‐sourced neuronal glutathione synthesis may play a role in preventing neuronal death.
Role of PKC‐α,γ isoforms in regulation of c‐Fos and TH expression after naloxone‐induced morphine withdrawal in the hypothalamic PVN and medulla oblongata catecholaminergic cell groups
Authors: Benavides Marta , Laorden M. Luisa , Marín M. Teresa , Milanés M. Victoria 
Published: September 2005

AbstractWe previously demonstrated that morphine withdrawal induced hyperactivity of the hypothalamus‐pituitary‐adrenocortical axis by activation of noradrenergic pathways innervating the hypothalamic paraventricular nucleus (PVN), as evaluated by Fos expression and corticosterone release. The present study was designed to investigate the role of protein kinase C (PKC) in this process by estimating changes in PKCα and PKCγ immunoreactivity, and whether pharmacological inhibition of PKC would attenuate morphine withdrawal‐induced c‐Fos expression and changes in tyrosine hydroxylase (TH) immunoreactivity levels in the PVN and nucleus tractus solitarius/ ventrolateral medulla (NTS/VLM). Dependence on morphine was induced in rats by 7 day s.c. implantation of morphine pellets. Morphine withdrawal was induced on day 8 by an injection of naloxone. The protein levels of PKCα and γ were significantly down‐regulated in the PVN and NTS/VLM from the morphine‐withdrawn rats. Morphine withdrawal induced c‐Fos expression in the PVN and NTS/VLM, indicating an activation of neurons in those nuclei. TH immunoreactivity was increased in the NTS/VLM after induction of morphine withdrawal, whereas there was a decrease in TH levels in the PVN. Infusion of calphostin C, a selective protein kinase C inhibitor, produced a reduction in the morphine withdrawal‐induced c‐Fos expression. Additionally, the changes in TH levels in the PVN and NTS/VLM were significantly modified by calphostin C. The present results suggest that activated PKC in the PVN and catecholaminergic brainstem cell groups may be critical for the activation of the hypothalamic‐pituitary adrenocortical axis in response to morphine withdrawal.
Contrasting textural record of two distinct metamorphic events of similar P–T conditions and different durations
Authors: LEXA O. , ŠTÍPSKÁ P. , SCHULMANN K. , BARATOUX L. , KRÖNER A. 
Published: September 2005

AbstractA structural, metamorphic and geochronological study of the Staré Město belt implies the existence of two distinct metamorphic events of similar peak P–T conditions (700–800 °C, 8–10 kbar) during the Cambro‐Ordovician and the Carboniferous tectonometamorphic events. The hypothesis of two distinct periods of metamorphism was suggested on the basis of structural discordance between an undoubtedly Carboniferous granodiorite sill intrusion and earlier Cambro‐Ordovician fabrics of a banded amphibolite complex. The analysis of crystal size distribution (CSD) shows high nucleation density (N0) and low average growth rate (Gt) for Carboniferous mylonitic metagabbros and mylonitic granodiorites. The parameter N0 decreases whereas the quantity Gt increases towards higher temperatures progressively approaching the values obtained from the Cambro‐Ordovician banded amphibolite complex. The spatial distribution of amphibole and plagioclase shows intense mechanical mixing for lower‐temperature mylonitic metagabbros. In high‐temperature mylonites a strong aggregate distribution is developed. Cambro‐Ordovician amphibolites unaffected by Carboniferous deformation show a regular to anticlustered spatial distribution resulting from heterogeneous nucleation of individual phases. This pattern, together with CSD, was subsequently modified by the grain growth and textural equilibration controlled by diffusive mass transfer during Carboniferous metamorphism. The differences between the observed textures of the amphibolites are interpreted to be a consequence of the different durations of the Carboniferous and Cambro‐Ordovician thermal events.
Mineral evolution of a garnet‐pyroxenite nodule within eclogite, eastern Sulu ultrahigh‐pressure metamorphic terrane, East China
Authors: YANG T. N. , ZENG L. , LIOU J. G. 
Published: September 2005

AbstractDetailed microtextural observations and bulk chemical analysis were undertaken on a garnet‐pyroxenite nodule within retrograde eclogites from the NE Sulu ultrahigh‐pressure metamorphic (UHPM) terrane. The results suggest that the protolith was a cumulate from a gabbroic body. The nodule consists primarily of coarse clinopyroxene grains with a very high content of the Ca‐Tschermakite molecule. Microscopic observations and back‐scattered electron images (BSE) demonstrate a complicated intergrowth of clinopyroxene, garnet and ilmenite, which represents the peak metamorphic assemblage. The primary clinopyroxene grains are armoured with a thin garnet corona up to 0.5 mm wide that forms an interconnected network. Within the clinopyroxene grains, four sets of garnet lamellae are distributed along crystallographic planes; locally, a vermicular intergrowth of garnet and diopside is developed. Besides the garnet, parallel arrays of ilmenite blebs are common within the clinopyroxene. Hydrous minerals such as amphibole, zoisite and titanite formed at later stages, and replaced diopside, garnet and ilmenite respectively. The P–T conditions determined for the formation of the garnet lamellae indicate that the garnet pyroxenite experienced UHP metamorphism at the same peak P–T condition as its host eclogite. The very high Ca‐Tschermakite content (31–34 mol.%) of the primary clinopyroxene indicates crystallization at about 9–17 kbar and 1250–1450 °C, and together with the microtextural observations, suggests that the protolith of the garnet pyroxenite was a cumulate from a former gabbroic body, in which case, the host eclogite might represent the gabbroic body.
A new method to calculate end‐member thermodynamic properties of minerals from their constituent polyhedra II: heat capacity, compressibility and thermal expansion
Authors: VAN HINSBERG V. J. , VRIEND S. P. , SCHUMACHER J. C. 
Published: September 2005

AbstractThermodynamic calculations in petrology are generally performed at pressures and temperatures beyond the standard state conditions. Accurate prediction of mineral equilibria therefore requires knowledge of the heat capacity, thermal expansion and compressibility for the minerals involved. Unfortunately, such data are not always available. In this contribution we present a data set to estimate the heat capacity, thermal expansion and compressibility of mineral end‐members from their constituent polyhedra, based on the premise that the thermodynamic properties of minerals can be described by a linear combination of the fractional properties of their constituents. As such, only the crystallography of the phase of interest needs to be known. This approach is especially powerful for hypothetical mineral end‐members and for minerals, for which the experimental determination of their thermodynamic properties is difficult. The data set consists of the properties for 35 polyhedra in the system K–Na–Ca–Li–Be–Mg–Mn–Fe–Co–Ni–Zn–Al–Ti–Si–H, determined by multiple linear regression analysis on a data set of 111 published end‐member thermodynamic properties. The large number of polyhedra determined allows calculation of a much larger variety of phases than was previously possible, and the choice of constituents together with the large number of thermodynamic input data results in estimates with associated uncertainty of generally <5%. The quality of the data appears to be sufficiently accurate for thermodynamic modelling as demonstrated by modelling the stability of margarite in the CASH system and the position of the talc–staurolite–chloritoid–pyrope absent invariant point in the KMASH system. In both cases, our results overlap within error with published equivalents.
A thermodynamic model for Ca–Na clinoamphiboles in Na2O–CaO–FeO–MgO–Al2O3–SiO2–H2O–O for petrological calculations
Authors: DALE J. , POWELL R. , WHITE R. W. , ELMER F. L. , HOLLAND T. J. B. 
Published: September 2005

AbstractA calibration is presented for an activity–composition model for amphiboles in the system Na2O–CaO–FeO–MgO–Al2O3–SiO2–H2O–O (NCFMASHO), formulated in terms of an independent set of six end‐members: tremolite, tschermakite, pargasite, glaucophane, ferroactinolite and ferritschermakite. The model uses mixing‐on‐sites for the ideal‐mixing activities, and for the activity coefficients, a macroscopic multicomponent van Laar model. This formulation involves 15 pairwise interaction energies and six asymmetry parameters. Calibration of the model is based on the geometrical constraints imposed by the size and shape of amphibole solvi inherent in a data set of 71 coexisting amphibole pairs from rocks, formed over 400–600 °C and 2–18 kbar. The model parameters are calibrated by combining these geometric constraints with qualitative consideration of parameter relationships, given that the data are insufficient to allow all the model parameters to be determined from a regression of the data. Use of coexisting amphiboles means that amphibole activity–composition relationships are calibrated independently of the thermodynamic properties of the end‐members. For practical applications, in geothermobarometry and the calculation of phase diagrams, the amphibole activity–composition relationships are placed in the context of the stability of other minerals by evaluating the properties of the end‐members in the independent set that are in internally consistent data sets. This has been performed using an extended natural data set for hornblende–garnet–plagioclase–quartz, giving the small adjustments necessary to the enthalpies of formation of tschermakite, pargasite and glaucophane for working with the Holland and Powell data set.
Ocean‐floor hydrothermal metamorphism in the Limousin ophiolites (western French Massif Central): evidence of a rare preserved Variscan oceanic marker
Authors: BERGER J. , FEMENIAS O. , MERCIER J. C. C. , DEMAIFFE D. 
Published: September 2005

AbstractThe Limousin ophiolite is located at the suture zone between two major thrust sheets in the western French Massif Central. This ophiolitic section comprises mantle‐harzburgite, mantle‐dunite, wehrlites, troctolites and layered gabbros. It has recorded a static metamorphic event transforming the gabbros into undeformed amphibolites and the magmatic ultramafites into serpentinites and/or pargasite‐bearing chloritites. With various thermobarometric methods, it is possible to show that the different varieties of amphibole have registered low‐P (c. 0.2 GPa) conditions with temperature ranging from high‐T, late‐magmatic conditions to greenschist–zeolite metamorphic facies. The abundance of undeformed metamorphic rocks (which is typical of the lower oceanic crust), the occurrence of Ca–Al (–Mg) metasomatism illustrated by the growth of Ca–Al silicates in veins or replacing the primary magmatic minerals, the P–T conditions of the metamorphism and the numerous similarities with oceanic crustal rocks from Ocean Drilling Program and worldwide ophiolites are the main arguments for an ocean‐floor hydrothermal metamorphism in the vicinity of a palaeo‐ridge. Among the West‐European Variscan ophiolites, the Limousin ophiolites constitute an extremely rare occurrence that has not been involved in any HP (subduction‐related) or MP (orogenic) metamorphism as observed in other ophiolite occurrences (i.e. France, Spain and Germany).
Periocular Vitiligo with Onset Around a Congenital Divided Nevus of the Eyelid
Authors: Guerra‐Tapia A. , Isarría María José 
Published: September 2005

Abstract:  Leukoderma in association with congenital melanocytic nevi is a rare phenomenon; nevertheless several reports have been published in the literature. We present a 15‐year‐old boy born with a pigmented lesion on the lower and upper eyelid diagnosed as a congenital divided nevus of the eyelid. At the age of 13, he developed a depigmented area around the nevus and was diagnosed at first as having a halo nevus in a congenital nevus. Over the next two years, an area of depigmentation appeared around the contralateral eye. At the present time, the patient has bilateral periocular depigmentation. Congenital divided nevus of the eyelid is a rare lesion, and no reports have been published to date of depigmentation in association with this lesion. Our patient presented with depigmentation around the nevus as in a halo nevus phenomenon, although at the present time, the depigmented area has a symmetric periocular distribution, and therefore can be labeled as periocular vitiligo associated with a congenital divided nevus.