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71.
Di Sano F Ferraro E Tufi R Achsel T Piacentini M Cecconi F 《The Journal of biological chemistry》2006,281(5):2693-2700
The endoplasmic reticulum (ER) is the cellular site of polypeptide folding and modification. When these processes are hampered, an unfolded protein response (UPR) is activated. If the damage is too broad, the mammalian UPR launches the apoptotic program. As a consequence, mobilization of ER calcium stores sensitizes mitochondria to direct proapoptotic stimuli. We make use of a mouse Apaf1-deficient cell system of proneural origin to understand the roles played in this context by the apoptosome, the most studied apoptotic machinery along the mitochondrial pathway of death. We show here that in the absence of the apoptosome ER stress induces cytochrome c release from the mitochondria but that apoptosis cannot occur. Under these circumstances, Grp78/BiP and GADD153/CHOP, both hallmarks of UPR, are canonically up-regulated, and calcium is properly released from ER stores. We also demonstrate that caspase 12, a protease until now believed to play a central role in the initiation of ER stress-induced cell death in the mouse system, is dispensable for the mitochondrial pathway of death to take place. 相似文献
72.
Maracchioni A Totaro A Angelini DF Di Penta A Bernardi G Carrì MT Achsel T 《Journal of neurochemistry》2007,100(1):142-153
Mitochondrial damage is linked to many neurodegenerative conditions, such as Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis. These diseases are associated with changes in the splicing pattern of individual mRNAs. Here, we tested the hypothesis that mitochondrial damage modulates alternative splicing, not only of a few mRNAs, but in a general manner. We incubated cultured human neuroblastoma cells with the chemical agent paraquat (a neurotoxin that interferes with mitochondrial function, causing energy deficit and oxidative stress) and analysed the splicing pattern of 13 genes by RT-PCR. For all mRNAs that are alternatively spliced, we observed a dose- and time-dependent increase of the smaller isoforms. In contrast, splicing of all constitutive splicing exons that we monitored did not change. Using other drugs, we show that the modulation of alternative splicing correlates with ATP depletion, not with oxidative stress. Such drastic changes in alternative splicing are not observed in cell lines of non-neuronal origin, suggesting a selective susceptibility of neuronal cells to modulation of splicing. As a significant percentage of all mammalian mRNAs undergo alternative splicing, we predict that mitochondrial failure will unbalance a vast number of isoform equilibriums, which would give an important contribution to neurodegeneration. 相似文献
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74.
We studied wood polymers in their native composite structure using mechanically isolated single spruce (Picea abies [L.] Karst.) fibers. Dichroic infrared spectra of fibers placed in a custom-built microfluidic cuvette were acquired in air, in liquid (heavy) water, and in liquid dimethylacetamide using a novel combination of synchrotron-based Fourier transform infrared microspectroscopy with polarization modulation. Differences were observed in the O-H stretching frequency region of the spruce spectra upon changing the ambient conditions. Analysis of these spectral variations provides information on hydrogen bonding, orientation, and accessibility of structural units of the wood polymers in the spruce cell walls. Our in situ approach contributes to a further understanding of the structural details of wood polymers in their native setting. 相似文献
75.
Meimberg H Abele T Bräuchler C McKay JK Pérez de Paz PL Heubl G 《Molecular phylogenetics and evolution》2006,41(3):566-578
The Canary Islands have been a focus for phylogeographic studies on the colonization and diversification of endemic angiosperm taxa. Based on phylogeographic patterns, both inter island colonization and adaptive radiation seem to be the driving forces for speciation in most taxa. Here, we investigated the diversification of Micromeria on the Canary Islands and Madeira at the inter- and infraspecific level using inter simple sequence repeat PCR (ISSR), the trnK-Intron and the trnT-trnL-spacer of the cpDNA and a low copy nuclear gene. The genus Micromeria (Lamiaceae, Mentheae) includes 16 species and 13 subspecies in Macaronesia. Most taxa are restricted endemics, or grow in similar ecological conditions on two islands. An exception is M. varia, a widespread species inhabits the lowland scrub on each island of the archipelago and could represent an ancestral taxon from which radiation started on the different islands. Our analyses support a split between the "eastern" islands Fuerteventura, Lanzarote and Gran Canaria and the "western" islands Tenerife, La Palma and El Hierro. The colonization of Madeira started from the western Islands, probably from Tenerife as indicated by the sequence data. We identified two lineages of Micromeria on Gomera but all other islands appear to be colonized by a single lineage, supporting adaptive radiation as the major evolutionary force for the diversification of Micromeria. We also discuss the possible role of gene flow between lineages of different Micromeria species on one island after multiple colonizations. 相似文献
76.
Dr. Tilmann Roos 《当今生物学》2015,45(1):28-35
mRNA‐based vaccines Despite substantial improvements in the development of influenza vaccines, the production and availability of these vaccines remain suboptimal. mRNA‐based vaccines provide an alternative because they can be produced in a fast, flexible and scalable manner. This new vaccine format induces B‐ as well as T‐cell responses and generates memory cells. It confers balanced, long lasting and protective immunity against influenza. Even after thermic stress the efficacy of the vaccines remains fully functional and therefore demonstrates the stability of this new class of drug substances. Since these mRNA based‐vaccines elicit long lived, humoral and cellular immune responses, this new vaccine platform is a technology to produce not only prophylactic vaccines against infection diseases but also to develop effective tumor immunotherapeutics. 相似文献
77.
We report on a new approach for studying fragmentation channels in Proton Transfer Reaction-Mass Spectrometry (PTR-MS), which we name primary ion depletion kinetics (PIDK). PTR-MS is a chemical ionization mass spectrometric (CIMS) technique deploying hydronium ions for the chemical ionization. Induced by extremely high concentrations of analyte M, depletion of the primary ions in the drift tube occurs. This is observed as quasi zero concentration of the primary ion H3O+, and constant MH+. Under these non-standard conditions, we find an overall changed fragmentation. We offer two explanations. Either the changed fragmentation pattern is the result of secondary proton transfer reactions. Or, alternatively, the fast depletion of H3O+ leads to reduced heating of H3O+ in the drift field, and consequently changed fragmentation following protonation of the analyte M. In any case, we use the observed changes in fragmentation as a successful new approach to fragmentation studies, and term it primary ion depletion kinetics, PIDK. PIDK easily yields an abundance of continuous data points with little deviation, because they are obtained in one experimental run, even for low abundant fragments. This is an advantage over traditional internal kinetic energy variation studies (electric field per number density (E/N) variation studies). Also, some interpretation on the underlying fragmentation reaction mechanisms can be gleamed. We measure low occurring fragmentation (<2% of MH+) of the compounds dimethyl sulfide, DMS, a compound that reportedly does not fragment, diethyl sulfide DES, and dipropyl sulfide DPS. And we confirm and complement the results with traditional E/N studies. Summing up, the new approach of primary ion depletion kinetics allows for the identification of dehydrogenation [MH+ -H2] and adduct formation (RMH+) as low abundant fragmentation channels in monosulfides. 相似文献
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79.
Windecker S Allemann Y Billinger M Pohl T Hutter D Orsucci T Blaga L Meier B Seiler C 《American journal of physiology. Heart and circulatory physiology》2002,282(6):H2216-H2223
In eight healthy male volunteers (cardiologists; age 36 +/- 5 yr), bicycle spiroergometry, Doppler echocardiography, and quantitative coronary angiography with intracoronary Doppler measurements before and after completion of a physical endurance exercise program of >5 mo duration were performed. Maximum oxygen uptake increased from 46 +/- 6 to 54 +/- 5 ml x kg(-1) x min(-1) (P = 0.04), maximum ergometric workload changed from 3.8 +/- 0.3 to 4.4 +/- 0.3 W/kg (P = 0.001), and left ventricular mass index increased from 82 +/- 18 to 108 +/- 29 g/m(2) (P = 0.001). The right, left main, and left anterior descending coronary artery cross-sectional area increased significantly in response to exercise. Before versus at the end of the exercise program, flow-induced left anterior descending coronary artery cross-sectional area was 10.1 +/- 3.5 and 11.0 +/- 3.9 mm(2), respectively (P = 0.03), nitroglycerin-induced left coronary calibers increased significantly, and coronary flow velocity reserve changed from 3.8 +/- 0.8 to 4.5 +/- 0.7 (P = 0.001). Left coronary artery correlated significantly with ventricular mass and maximum oxygen uptake, and coronary flow velocity reserve was significantly associated with maximum workload. 相似文献
80.
Christian Rausch Ilka Hoof Tilmann Weber Wolfgang Wohlleben Daniel H Huson 《BMC evolutionary biology》2007,7(1):78