102,083 research outputs found
Frataxin deficiency increases cyclooxygenase 2 and prostaglandins in cell and animal models of Friedreich's ataxia
No full text© The Author 2014. Published by Oxford University Press
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.An inherited deficiency of the mitochondrial protein frataxin causes Friedreich's ataxia (FRDA); the mechanism by which this deficiency triggers neuro- and cardio-degeneration is unclear. Microarrays of neural tissue of animal models of the disease showed decreases in antioxidant genes, and increases in inflammatory genes. Cyclooxygenase (COX)-derived oxylipins are important mediators of inflammation. We measured oxylipin levels using tandem mass spectrometry and ELISAs in multiple cell and animal models of FRDA. Mass spectrometry revealed increases in concentrations of prostaglandins, thromboxane B2, 15-HETE and 11-HETE in cerebellar samples of knockin knockout mice. One possible explanation for the elevated oxylipins is that frataxin deficiency results in increased COX activity. While constitutive COX1 was unchanged, inducible COX2 expression was elevated over 1.35-fold (P < 0.05) in two Friedreich's mouse models and Friedreich's lymphocytes. Consistent with higher COX2 expression, its activity was also increased by 58% over controls. COX2 expression is driven by multiple transcription factors, including activator protein 1 and cAMP response element-binding protein, both of which were elevated over 1.52-fold in cerebella. Taken together, the results support the hypothesis that reduced expression of frataxin leads to elevation of COX2-mediated oxylipin synthesis stimulated by increases in transcription factors that respond to increased reactive oxygen species. These findings support a neuroinflammatory mechanism in FRDA, which has both pathomechanistic and therapeutic implications.The study was supported by NIH grants NS077777, EY012245 and AG025532 to G.A.C., and USDA-ARS Intramural Projects 5306-51530-019-00D and 1 U24 DK097154-01 to J.W.N. Funding to pay the Open Access publication charges for this article was provided by the NIH
Short-Term Anxiolytic and Pro-Hypnotic Actvity of a Tryptic Hydrolysate of Bovine Αs1-Casein in Patients with Anxiety Spectrum Disorders
No full textWe conducted a prospective open-label study with 100 outpatients who had sought psychiatric consult in private clinical practice for anxiety/sleep in subthreshold/full blown DSM-IV Anxiety Spectrum Disorders. Clinicians, prescribed for 4 weeks a dietary supplement based on a formulation containing α-casozepine peptide 300 mg/day. The comparison of all rating scales mean scores reported at T0 versus T1 showed a statistically significant decrease (p<0.001). In Clinical Global Impression scale, the 54% of the sample was found to be much improved, 27% minimally improved and 19% showed no change. The 64% of the sample reported an anxiolytic effect, and among the 64 patients with sleep disorders, the 51.5% reported a pro-hypnotic effect. Considering patients in monotherapy with the dietary supplement, an anxiolytic effect was observed in 69.7% while a prohypnotic effect was observed in the 62.5% of the sample. No side-effects were reported during the treatment with no drop-out
High angle faulting in the Carrara marble (NW Tuscany, Italy): fault zone architeture and fluid-rock interaction.
No full textFault zone structure and fluid-rock interaction of a high angle normal fault in Carrara marble (NW Tuscany, Italy)
No full textWe studied the geometry intensity of deformation and fluid-rock interaction of a high angle normal fault within Carrara marble in the Alpi Apuane NW Tuscany Italy The fault is comprised of a core bounded by two major non-parallel slip surfaces The fault core marked by crush breccia and cataclasites asymmetrically grades to the host protolith through a damage zone which is well developed only in the footwall block On the contrary the transition from the fault core to the hangingwall protolith is sharply defined by the upper main slip surface Faulting was associated with fluid-rock interaction as evidenced by kinematically related veins observable in the damage zone and fluid channelling within the fault core where an orange-brownish cataclasite matrix can be observed A chemical and isotopic study of veins and different structural elements of the fault zone (protolith damage zone and fault core) including a mathematical model was performed to document type role and activity of fluid-rock interactions during deformation The results of our studies suggested that deformation pattern was mainly controlled by processes associated with a linking-damage zone at a fault tip development of a fault core localization and channelling of fluids within the fault zone Syn-kinematic microstructural modification of calcite microfabric possibly played a role in confining fluid percolation (C) 2009 Elsevier Ltd All rights reserve
Bibliographie Hilarion G. Petzold 1958 – 2009 mit Anhang als Einführung
No full textDieses Archiv enthält die Gesamtbibliographie der Werke des Autors nebst einiger Texte „Über H. G. Petzold“ im Schlussteil der Bibliographie sowie einen Anhang mit einer Einführung in die Architektur des Werkes in seinem wissenslogischen Aufbau als Ausarbeitung seines „Tree of Science Modells“ (2007).This archive contains the complete bibliography of the author and some texts about H. G. Petzold, moreover an epilogue with an introduction to the architecture of the works in its epistemological structure and composition and as an elaborations of Petzold’s „Tree of Science Modell (2007).https://www.fpi-publikation.de/polyloge/01-2009-petzold-h-g-gesamtbibliographie-h-g-petzold-1958-2009-updating-november2009/peerReviewedpublishedVersio
Dispelling the Myths Behind First-author Citation Counts
No full textWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
Inhibition of mitochondrial function induces an integrated stress response in oligodendroglia.
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