12,457 research outputs found
Mitochondria and Reactive Oxygen Species
No full textFascination by the mitochondria, “the colonial posterity of
migrant prokaryocytes, probably primitive bacteria that
swam into ancestral precursors of our eukaryotic cells and
stayed there,”1 stems from the above-mentioned nebulous
endosymbiotic theory of their origin, as well as from the
growing realization of a very special role that they play in the
pathogenesis of diverse diseases.
These organelles generate energy primarily in the form of
the electrochemical proton gradient (H), which fuels
ATP production, ion transport, and metabolism.2 Generation
of this universal energy currency, H, occurs through the
series of oxidative reactions conducted by the respiratory
chain complexes at the ion-impermeable, almost cholesterolfree
inner membrane. Reduced nicotinamide adenine dinucleotide
represents the entry point to the complex I (reduced
nicotinamide adenine dinucleotide:ubiquinone reductase),
whereas the reduced ubiquinol enters the respiratory chain in
the complex III (ubiquinol:cytochrome c [cyt-c] reductase) to
reduce cyt-c, the electron carrier to the complex IV, cyt-c
oxidase. Each of these steps generates H by electrogenic
pumping of protons from the mitochondrial matrix to the
intermembrane space and is coupled to electron flow, thus
generating the electric membrane potential of 180 to 220
mV and a pH gradient of 0.4 to 0.6 U across the inner
mitochondrial membrane resulting in the negatively charged
matrix side of the membrane and alkaline matrix. Ultimately,
accumulated H is converted into the influx of protons
into the matrix driving ATP synthesis or protein transport. In
addition, these end points are necessary for the execution of
2 major enzymatic metabolic pathways within the mitochondrial
matrix: the tricarboxylic acid (TCA) oxidation cycle and
the fatty acid -oxidation pathway. This intricate system
fueling cellular functions is as elegant as it is vulnerable:
practically every component of the system, from the electron
transport chain complexes to the permeability properties of
the membranes, is a target for various noxious stimuli, some
of which can be generated within mitochondria themselves.
The list of these noxious stimuli is too long to be recounted
here, and the interested reader may refer to a recent excellent
review.3 These ancestral oxygen-using proteobacterial invaders
carried with them into eukaryotic cells not only evolutionary
benefits but also potential side reactions, most dangerous
of which are “exothermic oxygen combustion and free
radical emission.” This review is focused on one component
of the noxious mitochondrial pathway: reactive oxygen species
(ROS) from a mitochondrial perspective, which has
previously been extensively reviewed.4 Therefore, we shall
present the most recent findings but periodically offer historical
perspective
Ms. Courtney Chartier, RWWL AUC, August 2011
No full textThis video is a conversation with Ms. Courtney Chartier. Ms. Chartier talks about her work on the "New Georgia Encyclopedia" and "Online Voter Education Project." Andrea Jackson, AUC Woodruff Library, is the interviewer
Ms. Neely Terrell, RWWL AUC, March 2012
No full textThis video is a conversation with Ms. Neely Terrell. Ms. Terrell talks about her book, "Super Singles Activate". Anthony Kinsey and Jahnesta Horney, AUC Woodruff Library, are the interviewers
Ms. Felesha Love, Spelman College, January 2016
No full textThis video is a conversation with Felesha Love. Ms. Love talks about her book, "Brave Leap to Freedom: Integrating Mind, Body, and Spirit to Cultivate Healthy Relationships". Jordan Moore, AUC Woodruff Library, is the interviewer
GLUTAMINE SUPPLEMENTATION AMELIORATES THE PROFILE OF PLASMA METABOLOME AND RESTORES ENDOTHELIAL-MEDIATED VASORELAXATION IN AN IN VIVO MODEL OF ENDOTHELIAL CELL DYSFUNCTION (ED)
No full textÉtude sur le patois de Valbonnais
No full textA lexical and morphologic description of Valbonnais dialect. A 319-page PhD dissertation under the direction of Prof. Antonin DURAFFOUR (Univ. Stendhal, Grenoble, France, 1943)Description lexicale et morphologique du patois de Valbonnais sous la forme d'un manuscrit de 319 pages.Thèse sous la direction du Prof. Antonin DURAFFOUR (Univ. Stendhal, Grenoble, 1943
Chemo-immunotherapy regimen with gemcitabine + FOLFOX 4 (GOLF) followed by subcutaneous (sc) granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-2 (IL-2). Results from a multicenter phase II trial in colon carcinoma patients
No full textWe have recently described a poly-chemotherapy (GOLF) regimen that: A) is active in colon carcinoma patients as second line of therapy; B) induces high levels of necrosis and apoptosis in colon cancer cells; C) up-regulates the expression and release of heat shock proteins (HSP)-70 and -90 and tumour-associated antigens (2,3); and D) down-regulates tumour cell resistance to the death signals of cytotoxic-T-lymphocytes.These effects represented the rationale for projecting GOLFIG regimen. Here we describe the results of a multi-center translational phase II trial designed to evaluate the toxicity, anti-tumour activity of a novel regimen designated as GOLFIG-1, composed by the GOLF poly-chemotherapy followed by the subcutaneous (sc.) administration of GM-CSF and low-dose IL-2 in colorectal carcinoma patients. The study involved 37 patients (21M and 16F, mean age 62.5 years), 24 of whom had received a previous line of treatment, and 24 had liver involvement. All the patients received biweekly chemotherapy with gemcitabine (1g/m2, day 1 and 15), oxaliplatin (85 mg/m2, day 2 and 16), levo-folinic acid (100 mg /m2, day 1, 2, 15, 16) and 5-Fluorouracil (400 mg/m2 as a bolus, and 800 mg/m2 as 24 hour infusion, days 1, 2, 15, 16). These patients also received sc GM-CSF (100 μg, day 3 to 8) followed by sc IL-2 (0.5 X 106 IUs twice a day from day 9 to 14 and from 17 to 29). The treatment was well tolerated and very active in colon carcinoma patients, with high objective response (64.9%) and disease control rates (97.3%), with an average time to progression of 12.94 months (CI 95%: 9.98-15.91). An immunological study confirmed the immunological response to colon carcinoma antigen, a significant reduction in suppressive regulatory T lymphocytes (CD4+CD25+T-reg) and a significant reduction of VEGF levels reported in a previous study. In conclusion, these results suggest that the GOLFIG regimen exerts strong immunological and anti-tumour activity in colorectal cancer patients. A randomized phase III trials aimed to compare the efficacy of GOLFIG-1 with FOLFOX-4 regimen in patients with advanced colorectal carcinoma is presently ongoing
Radar Chart of Citation topic Meso, source: Formulated by author using MS Excel (2016).
No full textRadar Chart of Citation topic Meso, source: Formulated by author using MS Excel (2016).</p
Improving MHC-I ligand identifications from LC-MS/MS data by incorporating allelic peptide motifs
No full textMHC class I (MHC-I)-bound ligands play a pivotal role in CD8 T cell immunity and are hence of major interest in understanding and designing immunotherapies. One of the most commonly utilized approaches for detecting MHC ligands is LC-MS/MS. Unfortunately, the effectiveness of current algorithms to identify MHC ligands from LC-MS/MS data is limited because the search algorithms used were originally developed for proteomics approaches detecting tryptic peptides. Consequently, the analysis often results in inflated false discovery rate (FDR) statistics and an overall decrease in the number of peptides that pass FDR filters. Andreatta et al. describe a new scoring tool (MS-rescue) for peptides from MHC-I immunopeptidome datasets. MS-rescue incorporates the existence of MHC-I peptide motifs to rescore peptides from ligandome data. The tool is demonstrated here using peptides assigned from LC-MS/MS data with PEAKs software but can be deployed on data from any search algorithm. This new approach increased the number of peptides identified by up to 20-30% and promises to aid the discovery of novel MHC-I ligands with immunotherapeutic potential
A comparison of the analytical performance of sodium dodecyl sulfate-polyacrylamide gel electrophoresis, electrospray and matrix-assisted laser desorption/ionization mass spectrometry in the study of the protein extract from bothrops jararaca snake venom
No full textBothrops jararaca Snake venom extract has been analysed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) electrospray mass spectrometry (ESI-MS) and matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) in order to obtain a rapid and accurate characterization. By the SDS-PAGE and MALDI-MS techniques about fourteen components are evidenced; with the latter technique, faster analysis and a more accurate molecular weight determination have been achieved. By ESI-MS the data obtained strongly depend on the operating conditions employed
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