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排序方式: 共有1006条查询结果,搜索用时 250 毫秒
931.
Jasmin Wellbrock Sara Sheikhzadeh Leticia Oliveira-Ferrer Hauke Stamm Mathias Hillebrand Britta Keyser Marianne Klokow Gabi Vohwinkel Veronika Bonk Benjamin Otto Thomas Streichert Stefan Balabanov Christian Hagel Meike Rybczynski Frank Bentzien Carsten Bokemeyer Yskert von Kodolitsch Walter Fiedler 《PloS one》2014,9(8)
Backgrounds
The Loeys-Dietz syndrome (LDS) is an inherited connective tissue disorder caused by mutations in the transforming growth factor β (TGF-β) receptors TGFBR1 or TGFBR2. Most patients with LDS develop severe aortic aneurysms resulting in early need of surgical intervention. In order to gain further insight into the pathophysiology of the disorder, we investigated circulating outgrowth endothelial cells (OEC) from the peripheral blood of LDS patients from a cohort of 23 patients including 6 patients with novel TGF-β receptor mutations.Methods and Results
We performed gene expression profiling of OECs using microarray analysis followed by quantitative PCR for verification of gene expression. Compared to OECs of age- and sex-matched healthy controls, OECs isolated from three LDS patients displayed altered expression of several genes belonging to the TGF-β pathway, especially those affecting bone morphogenic protein (BMP) signalling including BMP2, BMP4 and BMPR1A. Gene expression of BMP antagonist Gremlin-1 (GREM1) showed the most prominent up-regulation. This increase was confirmed at the protein level by immunoblotting of LDS-OECs. In immunohistochemistry, abundant Gremlin-1 protein expression could be verified in endothelial cells as well as smooth muscle cells within the arterial media. Furthermore, Gremlin-1 plasma levels of LDS patients were significantly elevated compared to healthy control subjects.Conclusions
These findings open new avenues in the understanding of the pathogenesis of Loeys-Dietz syndrome and the development of new diagnostic serological methods for early disease detection. 相似文献932.
Bacillus pumilus Reveals a Remarkably High Resistance to Hydrogen Peroxide Provoked Oxidative Stress
933.
Cyanobacterial HCO3
- transporters BCT1, SbtA and BicA are important components of cyanobacterial CO2-concentration mechanisms. They also show potential in applications aimed at improving photosynthetic rates and yield when expressed in the chloroplasts of C3 crop species. The present study investigated the feasibility of using Escherichia coli to assess function of a range of SbtA and BicA transporters in a heterologous expression system, ultimately for selection of transporters suitable for chloroplast expression. Here, we demonstrate that six β-forms of SbtA are active in E. coli, although other tested bicarbonate transporters were inactive. The sbtA clones were derived from Synechococcus sp. WH5701, Cyanobium sp. PCC7001, Cyanobium sp. PCC6307, Synechococcus elongatus PCC7942, Synechocystis sp. PCC6803, and Synechococcus sp. PCC7002. The six SbtA homologs varied in bicarbonate uptake kinetics and sodium requirements in E. coli. In particular, SbtA from PCC7001 showed the lowest uptake affinity and highest flux rate and was capable of increasing the internal inorganic carbon pool by more than 8 mM relative to controls lacking transporters. Importantly, we were able to show that the SbtB protein (encoded by a companion gene near sbtA) binds to SbtA and suppresses bicarbonate uptake function of SbtA in E. coli, suggesting a role in post-translational regulation of SbtA, possibly as an inhibitor in the dark. This study established E. coli as a heterologous expression and analysis system for HCO3
- transporters from cyanobacteria, and identified several SbtA transporters as useful for expression in the chloroplast inner envelope membranes of higher plants. 相似文献
934.
Rafael Gregorio Mendes Britta Koch Alicja Bachmatiuk Ahmed Aboud El-Gendy Yulia Krupskaya Armin Springer Rüdiger Klingeler Oliver Schmidt Bernd Büchner Samuel Sanchez Mark Hermann Rümmeli 《Biochimica et Biophysica Acta (BBA)/General Subjects》2014
Background
Iron oxide nanoparticles hold great promise for future biomedical applications. To this end numerous studies on iron oxide nanoparticles have been conducted. One aspect these studies reveal is that nanoparticle size and shape can trigger different cellular responses through endocytic pathways, cell viability and early apoptosis. However, systematic studies investigating the size dependence of iron oxide nanoparticles with highly defined diameters across multiple cells lines are not available yet.Methods
Iron oxide nanoparticles with well-defined size distributions were prepared. All samples were thoroughly characterized and the cytotoxicity for four standard cell lines (HeLa Kyoto, human osteosarcoma (U2OS), mouse fibroblasts (NIH 3T3) and mouse macrophages (J7442)) where investigated.Results
Our findings show that small differences in size distribution (ca. 10 nm) of iron oxide nanoparticles do not influence cytotoxicity, while uptake is size dependent. Cytotoxicity is dose-dependent. Broad distributions of nanoparticles are more easily internalized as compared to the narrow distributions for two of the cell lines tested (HeLa Kyoto and mouse macrophages (J7442)).Conclusion
The data indicate that it is not feasible to probe changes in cytotoxicity within a small size range (10 nm). However, TEM investigations of the nanoparticles indicate that cellular uptake is size dependent.General significance
The present work compares narrow and broad distributions for various samples of carbon-coated iron oxide nanoparticles. The data highlights that cells differentiate between nanoparticle sizes as indicated by differences in cellular uptake. This information provides valuable knowledge to better understand the interaction of nanoparticles and cells. 相似文献935.
Frederieke J. Kroon Peter Thorburn Britta Schaffelke Stuart Whitten 《Global Change Biology》2016,22(6):1985-2002
The Great Barrier Reef (GBR) is an iconic coral reef system extending over 2000 km along the north‐east coast of Australia. Global recognition of its Outstanding Universal Value resulted in the listing of the 348 000 km2 GBR World Heritage Area (WHA) by UNESCO in 1981. Despite various levels of national and international protection, the condition of GBR ecosystems has deteriorated over the past decades, with land‐based pollution from the adjacent catchments being a major and ongoing cause for this decline. To reduce land‐based pollution, the Australian and Queensland Governments have implemented a range of policy initiatives since 2003. Here, we evaluate the effectiveness of existing initiatives to reduce discharge of land‐based pollutants into the waters of the GBR. We conclude that recent efforts in the GBR catchments to reduce land‐based pollution are unlikely to be sufficient to protect the GBR ecosystems from declining water quality within the aspired time frames. To support management decisions for desired ecological outcomes for the GBR WHA, we identify potential improvements to current policies and incentives, as well as potential changes to current agricultural land use, based on overseas experiences and Australia's unique potential. The experience in the GBR may provide useful guidance for the management of other marine ecosystems, as reducing land‐based pollution by better managing agricultural sources is a challenge for coastal communities around the world. 相似文献
936.
Mcp3 is a novel mitochondrial outer membrane protein that follows a unique IMP‐dependent biogenesis pathway
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Monika Sinzel Tao Tan Philipp Wendling Hubert Kalbacher Cagakan Özbalci Xenia Chelius Benedikt Westermann Britta Brügger Doron Rapaport Kai Stefan Dimmer 《EMBO reports》2016,17(7):965-981
Mitochondria are separated from the remainder of the eukaryotic cell by the mitochondrial outer membrane (MOM). The MOM plays an important role in different transport processes like lipid trafficking and protein import. In yeast, the ER–mitochondria encounter structure (ERMES) has a central, but poorly defined role in both activities. To understand the functions of the ERMES, we searched for suppressors of the deficiency of one of its components, Mdm10, and identified a novel mitochondrial protein that we named Mdm10 complementing protein 3 (Mcp3). Mcp3 partially rescues a variety of ERMES‐related phenotypes. We further demonstrate that Mcp3 is an integral protein of the MOM that follows a unique import pathway. It is recognized initially by the import receptor Tom70 and then crosses the MOM via the translocase of the outer membrane. Mcp3 is next relayed to the TIM23 translocase at the inner membrane, gets processed by the inner membrane peptidase (IMP) and finally integrates into the MOM. Hence, Mcp3 follows a novel biogenesis route where a MOM protein is processed by a peptidase of the inner membrane. 相似文献
937.
Emma L. Baple Reza Maroofian Barry A. Chioza Maryam Izadi Harold E. Cross Saeed Al-Turki Katy Barwick Anna Skrzypiec Robert Pawlak Karin Wagner Roselyn Coblentz Tala Zainy Michael A. Patton Sahar Mansour Phillip Rich Britta Qualmann Matt E. Hurles Michael M. Kessels Andrew H. Crosby 《American journal of human genetics》2014
938.
Katharina Schneider Eric Seemann Lutz Liebmann Rashmi Ahuja Dennis Koch Martin Westermann Christian A. Hübner Michael M. Kessels Britta Qualmann 《The Journal of cell biology》2014,205(2):197-215
Insights into mechanisms coordinating membrane remodeling, local actin nucleation, and postsynaptic scaffolding during postsynapse formation are important for understanding vertebrate brain function. Gene knockout and RNAi in individual neurons reveal that the F-BAR protein syndapin I is a crucial postsynaptic coordinator in formation of excitatory synapses. Syndapin I deficiency caused significant reductions of synapse and dendritic spine densities. These syndapin I functions reflected direct, SH3 domain–mediated associations and functional interactions with ProSAP1/Shank2. They furthermore required F-BAR domain-mediated membrane binding. Ultra-high-resolution imaging of specifically membrane-associated, endogenous syndapin I at membranes of freeze-fractured neurons revealed that membrane-bound syndapin I preferentially occurred in spines and formed clusters at distinct postsynaptic membrane subareas. Postsynaptic syndapin I deficiency led to reduced frequencies of miniature excitatory postsynaptic currents, i.e., to defects in synaptic transmission phenocopying ProSAP1/Shank2 knockout, and impairments in proper synaptic ProSAP1/Shank2 distribution. Syndapin I–enriched membrane nanodomains thus seem to be important spatial cues and organizing platforms, shaping dendritic membrane areas into synaptic compartments. 相似文献
939.
Regina Waltes Reinhard Kalb Magtouf Gatei Markus Stumm Britta Wieland Raymonda Varon Martin F. Lavin Detlev Schindler Thilo Dörk 《American journal of human genetics》2009,84(5):605-42482
The MRE11/RAD50/NBN (MRN) complex plays a key role in recognizing and signaling DNA double-strand breaks (DSBs). Hypomorphic mutations in NBN (previously known as NBS1) and MRE11A give rise to the autosomal-recessive diseases Nijmegen breakage syndrome (NBS) and ataxia-telangiectasia-like disorder (ATLD), respectively. To date, no disease due to RAD50 deficiency has been described. Here, we report on a patient previously diagnosed as probably having NBS, with microcephaly, mental retardation, ‘bird-like’ face, and short stature. At variance with this diagnosis, she never had severe infections, had normal immunoglobulin levels, and did not develop lymphoid malignancy up to age 23 years. We found that she is compound heterozygous for mutations in the RAD50 gene that give rise to low levels of unstable RAD50 protein. Cells from the patient were characterized by chromosomal instability; radiosensitivity; failure to form DNA damage-induced MRN foci; and impaired radiation-induced activation of and downstream signaling through the ATM protein, which is defective in the human genetic disorder ataxia-telangiectasia. These cells were also impaired in G1/S cell-cycle-checkpoint activation and displayed radioresistant DNA synthesis and G2-phase accumulation. The defective cellular phenotype was rescued by wild-type RAD50. In conclusion, we have identified and characterized a patient with a RAD50 deficiency that results in a clinical phenotype that can be classified as an NBS-like disorder (NBSLD). 相似文献
940.
Joy Armistead Sunita Khatkar Britta Meyer Nehal Patel Gail Coghlan Ryan E. Lamont Shuangbo Liu Peter A. Cattini Peter Koetter Cheryl R. Greenberg Karl-Dieter Entian Barbara Triggs-Raine 《American journal of human genetics》2009,84(6):728-739
Bowen-Conradi syndrome (BCS) is an autosomal-recessive disorder characterized by severely impaired prenatal and postnatal growth, profound psychomotor retardation, and death in early childhood. Nearly all reported BCS cases have been among Hutterites, with an estimated birth prevalence of 1/355. We previously localized the BCS gene to a 1.9 Mbp interval on human chromosome 12p13.3. The 59 genes in this interval were ranked as candidates for BCS, and 35 of these, including all of the best candidates, were sequenced. We identified variant :c.400A→G, p.D86G in the 18S ribosome assembly protein EMG1 as the probable cause of BCS. This mutation segregated with disease, was not found in 414 non-Hutterite alleles, and altered a highly conserved aspartic acid (D) residue. A structural model of human EMG1 suggested that the D86 residue formed a salt bridge with arginine 84 that would be disrupted by the glycine (G) substitution. EMG1 mRNA was detected in all human adult and fetal tissues tested. In BCS patient fibroblasts, EMG1 mRNA levels did not differ from those of normal cells, but EMG1 protein was dramatically reduced in comparison to that of normal controls. In mammalian cells, overexpression of EMG1 harboring the D86G mutation decreased the level of soluble EMG1 protein, and in yeast two-hybrid analysis, the D86G substitution increased interaction between EMG1 subunits. These findings suggested that the D-to-G mutation caused aggregation of EMG1, thereby reducing the level of the protein and causing BCS. NM_006331.6相似文献