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131.
Irena Maus Daniel Wibberg Robbin Stantscheff Katharina Cibis Felix-Gregor Eikmeyer Helmut König Alfred Pühler Andreas Schlüter 《Journal of biotechnology》2013
Methanobacterium sp. Mb1, a hydrogenotrophic methanogenic Archaeon, was isolated from a rural biogas plant producing methane-rich biogas from maize silage and cattle manure in Germany. Here we report the complete genome sequence of the novel methanogenic isolate Methanobacterium sp. Mb1 harboring a 2,029,766 bp circular chromosome featuring a GC content of 39.74%. The genome encodes two rRNA operons, 41 tRNA genes and 2021 coding sequences and represents the smallest genome currently known within the genus Methanobacterium. 相似文献
132.
Martina Bielaszewska Christian Rüter Lisa Kunsmann Lilo Greune Andreas Bauwens Wenlan Zhang Thorsten Kuczius Kwang Sik Kim Alexander Mellmann M. Alexander Schmidt Helge Karch 《PLoS pathogens》2013,9(12)
Enterohemorrhagic Escherichia coli (EHEC) strains cause diarrhea and hemolytic uremic syndrome resulting from toxin-mediated microvascular endothelial injury. EHEC hemolysin (EHEC-Hly), a member of the RTX (repeats-in-toxin) family, is an EHEC virulence factor of increasingly recognized importance. The toxin exists as free EHEC-Hly and as EHEC-Hly associated with outer membrane vesicles (OMVs) released by EHEC during growth. Whereas the free toxin is lytic towards human endothelium, the biological effects of the OMV-associated EHEC-Hly on microvascular endothelial and intestinal epithelial cells, which are the major targets during EHEC infection, are unknown. Using microscopic, biochemical, flow cytometry and functional analyses of human brain microvascular endothelial cells (HBMEC) and Caco-2 cells we demonstrate that OMV-associated EHEC-Hly does not lyse the target cells but triggers their apoptosis. The OMV-associated toxin is internalized by HBMEC and Caco-2 cells via dynamin-dependent endocytosis of OMVs and trafficked with OMVs into endo-lysosomal compartments. Upon endosome acidification and subsequent pH drop, EHEC-Hly is separated from OMVs, escapes from the lysosomes, most probably via its pore-forming activity, and targets mitochondria. This results in decrease of the mitochondrial transmembrane potential and translocation of cytochrome c to the cytosol, indicating EHEC-Hly-mediated permeabilization of the mitochondrial membranes. Subsequent activation of caspase-9 and caspase-3 leads to apoptotic cell death as evidenced by DNA fragmentation and chromatin condensation in the intoxicated cells. The ability of OMV-associated EHEC-Hly to trigger the mitochondrial apoptotic pathway in human microvascular endothelial and intestinal epithelial cells indicates a novel mechanism of EHEC-Hly involvement in the pathogenesis of EHEC diseases. The OMV-mediated intracellular delivery represents a newly recognized mechanism for a bacterial toxin to enter host cells in order to target mitochondria. 相似文献
133.
Marieke?Pingen Ramin?Sarrami-Forooshani Annemarie?MJ?Wensing Petra?van Ham Agata?Drewniak Charles?AB?Boucher Teunis?BH?GeijtenbeekEmail author Monique?NijhuisEmail author 《Retrovirology》2014,11(1):113
Background
Different patterns of drug resistance are observed in treated and therapy naïve HIV-1 infected populations. Especially the NRTI-related M184I/V variants, which are among the most frequently encountered mutations in treated patients, are underrepresented in the antiretroviral naïve population. M184I/V mutations are known to have a profound effect on viral replication and tend to revert over time in the new host. However it is debated whether a diminished transmission efficacy of HIV variants with a reduced replication capacity can also contribute to the observed discrepancy in genotypic patterns.As dendritic cells (DCs) play a pivotal role in HIV-1 transmission, we used a model containing primary human Langerhans cells (LCs) and DCs to compare the transmission efficacy M184 variants (HIV-M184V/I/T) to HIV wild type (HIV-WT). As control, we used HIV harboring the NNRTI mutation K103N (HIV-K103N) which has a minor effect on replication and is found at a similar prevalence in treated and untreated individuals.Results
In comparison to HIV-WT, the HIV-M184 variants were less efficiently transmitted to CCR5+ Jurkat T cells by both LCs and DCs. The transmission rate of HIV-K103N was slightly reduced to HIV-WT in LCs and even higher than HIV-WT in DCs. Replication experiments in CCR5+ Jurkat T cells revealed no apparent differences in replication capacity between the mutant viruses and HIV-WT. However, viral replication in LCs and DCs was in concordance with the transmission results; replication by the HIV-M184 variants was lower than replication by HIV-WT, and the level of replication of HIV-K103N was intermediate for LCs and higher than HIV-WT for DCs.Conclusions
Our data demonstrate that drug resistant M184-variants display a reduced replication capacity in LCs and DCs which directly impairs their transmission efficacy. As such, diminished transmission efficacy may contribute to the lower prevalence of drug resistant variants in therapy naive individuals.134.
Julie Colléter David J. Penman Stéphane Lallement Christian Fauvel Tanja Hanebrekke Renate D. Osvik Hans C. Eilertsen Helena D’Cotta Béatrice Chatain Stefano Peruzzi 《PloS one》2014,9(10)
Androgenesis is a form of uniparental reproduction leading to progenies inheriting only the paternal set of chromosomes. It has been achieved with variable success in a number of freshwater species and can be attained by artificial fertilization of genetically inactivated eggs following exposure to gamma (γ), X-ray or UV irradiation (haploid androgenesis) and by restoration of diploidy by suppression of mitosis using a pressure or thermal shock. The conditions for the genetic inactivation of the maternal genome in the European sea bass (Dicentrarchus labrax L.) were explored using different combinations of UV irradiation levels and durations. UV treatments significantly affected embryo survival and generated a wide range of developmental abnormalities. Despite the wide range of UV doses tested (from 7.2 to 720 mJ.cm−2), only one dose (60 mJ.cm−2.min−1 with 1 min irradiation) resulted in a small percentage (14%) of haploid larvae at hatching in the initial trials as verified by flow cytometry. Microsatellite marker analyses of three further batches of larvae produced by using this UV treatment showed a majority of larvae with variable levels of paternal and maternal contributions and only one larva displaying pure paternal inheritance. The results are discussed also in the context of an assessment of the UV-absorbance characteristics of egg extracts in this species that revealed the presence of gadusol, a compound structurally related to mycosporine-like amino acids (MAAs) with known UV-screening properties. 相似文献
135.
Sziráki I Erdo F Beéry E Molnár PM Fazakas C Wilhelm I Makai I Kis E Herédi-Szabó K Abonyi T Krizbai I Tóth GK Krajcsi P 《Journal of biomolecular screening》2011,16(8):886-894
This study provides evidence that quinidine can be used as a probe substrate for ABCB1 in multiple experimental systems both in vitro and in vivo relevant to the blood-brain barrier (BBB). The combination of quinidine and PSC-833 (valspodar) is an effective tool to assess investigational drugs for interactions on ABCB1. Effects of quinidine and substrate-inhibitor interactions were tested in a membrane assay and in monolayer assays. The authors compared quinidine and digoxin as ABCB1 probes in the in vitro assays and found that quinidine was more potent and at least as specific as digoxin in ATPase and monolayer efflux assays employing MDCKII-MDR1 and the rat brain microcapillary endothelial cell system. Brain exposure to quinidine was tested in dual-/triple-probe microdialysis experiments in rats by assessing levels of quinidine in blood and brain. Comparing quinidine levels in dialysate samples from valspodar-treated and control animals, it is evident that systemic/local administration of the inhibitor diminishes the pumping function of ABCB1 at the BBB, resulting in an increased brain penetration of quinidine. In sum, quinidine is a good probe to study ABCB1 function at the BBB. Moreover, quinidine/PSC-833 is an ABCB1-specific substrate/inhibitor combination applicable to many assay systems both in vitro and in vivo. 相似文献
136.
Chowdhury S Sessions EH Pocas JR Grant W Schröter T Lin L Ruiz C Cameron MD Schürer S LoGrasso P Bannister TD Feng Y 《Bioorganic & medicinal chemistry letters》2011,21(23):7107-7112
Rho kinase (ROCK) inhibitors are potential therapeutic agents to treat disorders such as hypertension, multiple sclerosis, cancers, and glaucoma. Here, we disclose the synthesis, optimization, biological evaluation of potent indole and 7-azaindole based ROCK inhibitors that have high potency on ROCK (IC(50)=1 nM) with 740-fold selectivity over PKA (47). Moreover, 47 showed very good DMPK properties making it a good candidate for further development. Finally, docking studies with a homology model of ROCK-II were performed to rationalize the binding mode of these compounds and showed the compounds bound in both orientations to take advantage to H-bonds with Lys-121 of ROCK-II. 相似文献
137.
The PARAMEDIC-2 trial demonstrated that the use of adrenaline compared with placebo in out-of-hospital cardiac arrest (OHCA) resulted in a small increase in 30-day survival, but was associated with a higher number of survivors with severe neurological impairment. These findings received a lot of attention, and generated a widespread discussion about the role of adrenaline in cardiac arrest. In this point of view, we aim to place the PARAMEDIC-2 results in the right perspective by comparing the relative effect of adrenaline to other determinants of cerebral blood flow.
相似文献138.
An early event of the incompatible plant–pathogen interactions is an oxidative burst. On one hand, the ROS generated during oxidative burst is advantageous. ROS can serve as secondary messengers mediating defence gene activation and establishment of additional defences. On the other hand, the concentration of ROS must be carefully regulated to avoid undesired cellular cytotoxicity. The major water soluble, low molecular weight antioxidant, ascorbic acid plays a crucial role in ROS balancing (scavenging). The regulation of ascorbate level, therefore, can be an important point of the fine-tuning of ROS level during the early phase of plant–pathogen interaction. To evaluate how this interaction affects the biosynthesis, the recycling, and the level of ascorbate, we challenged Arabidopsis thaliana cells with two different harpin proteins (HrpZpto and HrpWpto). HrpZpto and HrpWpto treatments caused a well-defined ROS peak. The expression of the alternative oxidase (AOX1a) and vtc5, one of the paralog genes that encode the rate limiting enzyme of ascorbate biosynthesis, followed the elevation of ROS. Similarly, the activity of ascorbate peroxidase and galactono-1,4-lactone dehydrogenase (EC 1.3.2.3) (GLDH), the enzyme catalysing the ultimate, mitochondria coupled step of ascorbate biosynthesis and the level of ascorbate and glutathione also followed the elevation of ROS due to harpin treatment. The enhanced expression of AOX1a, the elevated activity of GLDH, and the increased level of ascorbate and glutathione all can contribute to the mitigation or absence of programmed cell death. Finally, a new function, the fine-tuning of redox balance during plant–pathogen interaction, can be proposed to vtc5. 相似文献
139.
Capsule Nesting Sky Larks avoided arable fields and the vicinity of farm buildings, and preferred extensive and heterogeneous grassland, where nest success was 30%. 相似文献
140.
Felde Vivian A. Flantua Suzette G. A. Jenks Cathy R. Benito Blas M. de Beaulieu Jacques-Louis Kuneš Petr Magri Donatella Nalepka Dorota Risebrobakken Bjørg ter Braak Cajo J. F. Allen Judy R. M. Granoszewski Wojciech Helmens Karin F. Huntley Brian Kondratienė Ona Kalniņa Laimdota Kupryjanowicz Mirosława Malkiewicz Małgorzata Milner Alice M. Nita Małgorzata Noryśkiewicz Bożena Pidek Irena A. Reille Maurice Salonen J. Sakari Šeirienė Vaida Winter Hanna Tzedakis Polychronis C. Birks H. John B. 《Vegetation History and Archaeobotany》2020,29(1):101-109
Vegetation History and Archaeobotany - The Eemian interglacial represents a natural experiment on how past vegetation with negligible human impact responded to amplified temperature changes... 相似文献