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排序方式: 共有125条查询结果,搜索用时 15 毫秒
21.
22.
T. Abaffy M. G. Möller D. D. Riemer C. Milikowski R. A. DeFazio 《Metabolomics : Official journal of the Metabolomic Society》2013,9(5):998-1008
The analysis of volatile organic compounds (VOC) as biomarkers of cancer is both promising and challenging. In this pilot study, we used an untargeted approach to compare volatile metabolomic signatures of melanoma and matched control non-neoplastic skin from the same patient. VOC from fresh (non-fixed) biopsied tissue were collected using the headspace solid phase micro extraction method (HS SPME) and analyzed by gas chromatography and mass spectrometry (GCMS). We applied the XCMS analysis platform and MetaboAnalyst software to reveal many differentially expressed metabolic features. Our analysis revealed increased levels of lauric acid (C12:0) and palmitic acid (C16:0) in melanoma. The identity of these compounds was confirmed by comparison with chemical standards. Increased levels of these fatty acids are likely to be a consequence of up-regulated de novo lipid synthesis, a known characteristic of cancer. Increased oxidative stress is likely to cause an additional increase in lauric acid. Implementation of this study design on larger number of cases will be necessary for the future metabolomics biomarker discovery applications. 相似文献
23.
We report the molecular cloning of a full-length cDNA encoding a non-neuronal cytoplasmic intermediate filament (IF) protein of the cephalochordate Branchiostoma lanceolatum. Sequence and structural characteristics of IF-1 reveal a close relation to vertebrate IF proteins: they all lack the extended coil 1b version and the lamin tail homology found in protostomic IF proteins. This implies that divergence of type I to IV IF genes from a common ancestor either coincided with the origin of chordates or occurred at an earlier stage in the evolution of deuterostomes. The structural organization of the cephalochordate gene shows a closer relation to vertebrate type III genes than to type I or II genes. The single gene (approximately 19 kb) is composed of 7 exons and 6 introns which are all located within the sequence encoding the rod domain. The positions and phases of the introns show perfect homology to vertebrate type III genes. In line with the absence of protein sequence similarity of the tail domain, the Branchiostoma gene does not possess the introns interrupting this region in type III genes of vertebrates. 相似文献
24.
A Targeted LC‐MS Strategy for Low‐Abundant HLA Class‐I‐Presented Peptide Detection Identifies Novel Human Papillomavirus T‐Cell Epitopes
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Renata Blatnik Nitya Mohan Maria Bonsack Lasse G. Falkenby Stephanie Hoppe Kathrin Josef Alina Steinbach Sara Becker Wiebke M. Nadler Marijana Rucevic Martin R. Larsen Mogjiborahman Salek Angelika B. Riemer 《Proteomics》2018,18(11)
For rational design of therapeutic vaccines, detailed knowledge about target epitopes that are endogenously processed and truly presented on infected or transformed cells is essential. Many potential target epitopes (viral or mutation‐derived), are presented at low abundance. Therefore, direct detection of these peptides remains a challenge. This study presents a method for the isolation and LC‐MS3‐based targeted detection of low‐abundant human leukocyte antigen (HLA) class‐I‐presented peptides from transformed cells. Human papillomavirus (HPV) was used as a model system, as the HPV oncoproteins E6 and E7 are attractive therapeutic vaccination targets and expressed in all transformed cells, but present at low abundance due to viral immune evasion mechanisms. The presented approach included preselection of target antigen‐derived peptides by in silico predictions and in vitro binding assays. The peptide purification process was tailored to minimize contaminants after immunoprecipitation of HLA‐peptide complexes, while keeping high isolation yields of low‐abundant target peptides. The subsequent targeted LC‐MS3 detection allowed for increased sensitivity, which resulted in successful detection of the known HLA‐A2‐restricted epitope E711–19 and ten additional E7‐derived peptides on the surface of HPV16‐transformed cells. T‐cell reactivity was shown for all the 11 detected peptides in ELISpot assays, which shows that detection by our approach has high predictive value for immunogenicity. The presented strategy is suitable for validating even low‐abundant candidate epitopes to be true immunotherapy targets. 相似文献
25.
The complete cDNA clone for a cytoplasmic intermidiatefilament (IF) protein from the annelid Lumbricus terrestris reported here, shows an extra 42 residues in the coil 1b subdomain of the central rod, as do the IF proteins from nematodes and moluscs. These extra six heptads are also present in all nuclear lamins but not in any known vertebrate cytoplasmic IF protein. Thus, it seems that protostomic metazoa conserve a lamin-like structural element in their cytoplasmic IF proteins, which was lost in the deuterostomic metazoan branch leading to the vertebrates. 相似文献
26.
Miesbauer M Bamme T Riemer C Oidtmann B Winklhofer KF Baier M Tatzelt J 《Biochemical and biophysical research communications》2006,341(1):218-224
A hallmark of prion diseases in mammals is a conformational transition of the cellular prion protein (PrP(C)) into a pathogenic isoform termed PrP(Sc). PrP(C) is highly conserved in mammals, moreover, genes of PrP-related proteins have been recently identified in fish. While there is only little sequence homology to mammalian PrP, PrP-related fish proteins were predicted to be modified with N-linked glycans and a C-terminal glycosylphosphatidylinositol (GPI) anchor. We biochemically characterized two PrP-related proteins from zebrafish in cultured cells and show that both zePrP1 and zeSho2 are imported into the endoplasmic reticulum and are post-translationally modified with complex glycans and a C-terminal GPI anchor. 相似文献
27.
Rambold AS Miesbauer M Olschewski D Seidel R Riemer C Smale L Brumm L Levy M Gazit E Oesterhelt D Baier M Becker CF Engelhard M Winklhofer KF Tatzelt J 《Journal of neurochemistry》2008,107(1):218-229
A hallmark in prion diseases is the conformational transition of the cellular prion protein (PrP(C)) into a pathogenic conformation, designated scrapie prion protein (PrP(Sc)), which is the essential constituent of infectious prions. Here, we show that epigallocatechin gallate (EGCG) and gallocatechin gallate, the main polyphenols in green tea, induce the transition of mature PrP(C) into a detergent-insoluble conformation distinct from PrP(Sc). The PrP conformer induced by EGCG was rapidly internalized from the plasma membrane and degraded in lysosomal compartments. Isothermal titration calorimetry studies revealed that EGCG directly interacts with PrP leading to the destabilizing of the native conformation and the formation of random coil structures. This activity was dependent on the gallate side chain and the three hydroxyl groups of the trihydroxyphenyl side chain. In scrapie-infected cells EGCG treatment was beneficial; formation of PrP(Sc) ceased. However, in uninfected cells EGCG interfered with the stress-protective activity of PrP(C). As a consequence, EGCG-treated cells showed enhanced vulnerability to stress conditions. Our study emphasizes the important role of PrP(C) to protect cells from stress and indicate efficient intracellular pathways to degrade non-native conformations of PrP(C). 相似文献
28.
Gimmon Y Riemer R Oddsson L Melzer I 《Journal of electromyography and kinesiology》2011,21(6):922-928
Objective
Previous studies have demonstrated that ankle muscle fatigue alters postural sway. Our aim was to better understand postural control mechanisms during upright stance following plantar flexor fatigue.Method
Ten healthy young volunteers, 25.7 ± 2.2 years old, were recruited. Foot center-of-pressure (CoP) displacement data were collected during narrow base upright stance and eyes closed (i.e. blindfolded) conditions. Subjects were instructed to stand upright and as still as possible on a force platform under five test conditions: (1) non-fatigue standing on firm surface; (2) non-fatigue standing on foam; (3) ankle plantar flexor fatigue, standing on firm surface; (4) ankle plantar flexor fatigue, standing on foam; and (5) upper limb fatigue, standing on firm surface. An average of the ten 30-s trials in each of five test conditions was calculated to assess the mean differences between the trials. Traditional measures of postural stability and stabilogram-diffusion analysis (SDA) parameters were analyzed.Results
Traditional center of pressure parameters were affected by plantar flexor fatigue, especially in the AP direction. For the SDA parameters, plantar flexor fatigue caused significantly higher short-term diffusion coefficients, and critical displacement in both mediolateral (ML) and anteroposterior (AP) directions. Long-term postural sway was different only in the AP direction.Conclusions
Localized plantar flexor fatigue caused impairment to postural control mainly in the Sagittal plane. The findings indicate that postural corrections, on average, occurred at a higher threshold of sway during plantar flexor fatigue compared to non-fatigue conditions. 相似文献29.
Silja Lucia Salscheider Sarah Gerlich Alfredo CabreraOrefice Esra Peker Robin Alexander Rothemann Lena Maria Murschall Yannik Finger Karolina Szczepanowska Zeinab Alsadat Ahmadi Sergio GuerreroCastillo Alican Erdogan Mark Becker Muna Ali Markus Habich Carmelina Petrungaro Nele Burdina Guenter Schwarz Merlin Klußmann Ines Neundorf David A Stroud Michael T Ryan Aleksandra Trifunovic Ulrich Brandt Jan Riemer 《The EMBO journal》2022,41(17)
The mitochondrial intermembrane space protein AIFM1 has been reported to mediate the import of MIA40/CHCHD4, which forms the import receptor in the mitochondrial disulfide relay. Here, we demonstrate that AIFM1 and MIA40/CHCHD4 cooperate beyond this MIA40/CHCHD4 import. We show that AIFM1 and MIA40/CHCHD4 form a stable long‐lived complex in vitro, in different cell lines, and in tissues. In HEK293 cells lacking AIFM1, levels of MIA40 are unchanged, but the protein is present in the monomeric form. Monomeric MIA40 neither efficiently interacts with nor mediates the import of specific substrates. The import defect is especially severe for NDUFS5, a subunit of complex I of the respiratory chain. As a consequence, NDUFS5 accumulates in the cytosol and undergoes rapid proteasomal degradation. Lack of mitochondrial NDUFS5 in turn results in stalling of complex I assembly. Collectively, we demonstrate that AIFM1 serves two overlapping functions: importing MIA40/CHCHD4 and constituting an integral part of the disulfide relay that ensures efficient interaction of MIA40/CHCHD4 with specific substrates. 相似文献
30.
Klöppel C Michels C Zimmer J Herrmann JM Riemer J 《Biochemical and biophysical research communications》2010,403(1):114-3767
The antioxidative enzyme copper-zinc superoxide dismutase (Sod1) is an important cellular defence system against reactive oxygen species (ROS). While the majority of this enzyme is localized to the cytosol, about 1% of the cellular Sod1 is present in the intermembrane space (IMS) of mitochondria. These amounts of mitochondrial Sod1 are increased for certain Sod1 mutants that are linked to the neurodegenerative disease amyotrophic lateral sclerosis (ALS). To date, only little is known about the physiological function of mitochondrial Sod1. Here, we use the model system Saccharomyces cerevisiae to generate cells in which Sod1 is exclusively localized to the IMS. We find that IMS-localized Sod1 can functionally substitute wild type Sod1 and that it even exceeds the protective capacity of wild type Sod1 under conditions of mitochondrial ROS stress. Moreover, we demonstrate that upon expression in yeast cells the common ALS-linked mutant Sod1G93A becomes enriched in the mitochondrial fraction and provides an increased protection of cells from mitochondrial oxidative stress. Such an effect cannot be observed for the catalytically inactive mutant Sod1G85R. Our observations suggest that the targeting of Sod1 to the mitochondrial IMS provides an increased protection against respiration-derived ROS. 相似文献