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71.
Andrea Gottlieb Hans-Georg Müller Alicia N. Massa Humphrey Wanjugi Karin R. Deal Frank M. You Xiangyang Xu Yong Q. Gu Ming-Cheng Luo Olin D. Anderson Agnes P. Chan Pablo Rabinowicz Katrien M. Devos Jan Dvorak 《PloS one》2013,8(1)
Wheat and maize genes were hypothesized to be clustered into islands but the hypothesis was not statistically tested. The hypothesis is statistically tested here in four grass species differing in genome size, Brachypodium distachyon, Oryza sativa, Sorghum bicolor, and Aegilops tauschii. Density functions obtained under a model where gene locations follow a homogeneous Poisson process and thus are not clustered are compared with a model-free situation quantified through a non-parametric density estimate. A simple homogeneous Poisson model for gene locations is not rejected for the small O. sativa and B. distachyon genomes, indicating that genes are distributed largely uniformly in those species, but is rejected for the larger S. bicolor and Ae. tauschii genomes, providing evidence for clustering of genes into islands. It is proposed to call the gene islands “gene insulae” to distinguish them from other types of gene clustering that have been proposed. An average S. bicolor and Ae. tauschii insula is estimated to contain 3.7 and 3.9 genes with an average intergenic distance within an insula of 2.1 and 16.5 kb, respectively. Inter-insular distances are greater than 8 and 81 kb and average 15.1 and 205 kb, in S. bicolor and Ae. tauschii, respectively. A greater gene density observed in the distal regions of the Ae. tauschii chromosomes is shown to be primarily caused by shortening of inter-insular distances. The comparison of the four grass genomes suggests that gene locations are largely a function of a homogeneous Poisson process in small genomes. Nonrandom insertions of LTR retroelements during genome expansion creates gene insulae, which become less dense and further apart with the increase in genome size. High concordance in relative lengths of orthologous intergenic distances among the investigated genomes including the maize genome suggests functional constraints on gene distribution in the grass genomes. 相似文献
72.
Hermann-Georg Holzhütter Johan Friso Lock Pouria Taheri Sascha Bulik Andrean Goede Martin Stockmann 《PloS one》2013,8(8)
Breath tests based on the administration of a 13C-labeled drug and subsequent monitoring of 13CO2 in the breath (quantified as DOB – delta over baseline) liberated from the drug during hepatic CPY-dependent detoxification are important tools in liver function diagnostics. The capability of such breath tests to reliably indicate hepatic CYP performance is limited by the fact that 13CO2 is not exclusively exhaled but also exchanged with other compartments of the body. In order to assess this bias caused by variations of individual systemic CO2 kinetics we administered intravenously the test drug 13C-methacetin to 25 clinically liver-healthy individuals and monitored progress curves of DOB and the plasma concentration of 13C-methacetin. Applying compartment modelling we estimated for each individual a set of kinetic parameters characterizing the time-dependent exchange of the drug and of CO2 with the liver and non-hepatic body compartments. This analysis revealed that individual variations in the kinetics of CO2 may account for up to 30% deviation of DOB curve parameters from their mean at otherwise identical 13C-methacetin metabolization rates. In order to correct for this bias we introduced a novel detoxification score which ideally should be assessed from the DOB curve of a 2-step test (“2DOB”) which is initialized with the injection of a standard dose of 13C-labeled bicarbonate (in order to provide information on the actual CO2 status of the individual) followed by injection of the 13C-labeled test drug (the common procedure). Computer simulations suggest that the predictive power of the proposed 2DOB breath test to reliably quantity the CYP-specific hepatic detoxification activity should be significantly higher compared to the conventional breath test. 相似文献
73.
Sascha Venturelli Alexander Berger Alexander B?cker Christian Busch Timo Weiland Seema Noor Christian Leischner Sabine Schleicher Mascha Mayer Thomas S. Weiss Stephan C. Bischoff Ulrich M. Lauer Michael Bitzer 《PloS one》2013,8(8)
The polyphenolic alcohol resveratrol has demonstrated promising activities for the prevention and treatment of cancer. Different modes of action have been described for resveratrol including the activation of sirtuins, which represent the class III histone deacetylases (HDACs). However, little is known about the activity of resveratrol on the classical HDACs of class I, II and IV, although these classes are involved in cancer development or progression and inhibitors of HDACs (HDACi) are currently under investigation as promising novel anticancer drugs. We could show by in silico docking studies that resveratrol has the chemical structure to inhibit the activity of different human HDAC enzymes. In vitro analyses of overall HDAC inhibition and a detailed HDAC profiling showed that resveratrol inhibited all eleven human HDACs of class I, II and IV in a dose-dependent manner. Transferring this molecular mechanism into cancer therapy strategies, resveratrol treatment was analyzed on solid tumor cell lines. Despite the fact that hepatocellular carcinoma (HCC) is known to be particularly resistant against conventional chemotherapeutics, treatment of HCC with established HDACi already has shown promising results. Testing of resveratrol on hepatoma cell lines HepG2, Hep3B and HuH7 revealed a dose-dependent antiproliferative effect on all cell lines. Interestingly, only for HepG2 cells a specific inhibition of HDACs and in turn a histone hyperacetylation caused by resveratrol was detected. Additional testing of human blood samples demonstrated a HDACi activity by resveratrol ex vivo. Concluding toxicity studies showed that primary human hepatocytes tolerated resveratrol, whereas in vivo chicken embryotoxicity assays demonstrated severe toxicity at high concentrations. Taken together, this novel pan-HDACi activity opens up a new perspective of resveratrol for cancer therapy alone or in combination with other chemotherapeutics. Moreover, resveratrol may serve as a lead structure for chemical optimization of bioavailability, pharmacology or HDAC inhibition. 相似文献
74.
75.
Spatio-temporal mapping of local soil pH changes induced by roots of lupin and soft-rush 总被引:1,自引:0,他引:1
Nicole Rudolph Sebastian Voss Ahmad B. Moradi Stefan Nagl Sascha E. Oswald 《Plant and Soil》2013,369(1-2):669-680
Aims
The rhizosphere is a dynamic system strongly influenced by root activity. Roots modify the pH of their surrounding soil causing the soil pH to vary as a function of distance from root surface, location along root axes, and root maturity. Non-invasive imaging techniques provide the possibility to capture pH patterns around the roots as they develop.Methods
We developed a novel fluorescence imaging set up and applied to the root system of two lupin (Lupinus albus L., Lupinus angustifolius L.) and one soft-rush (Juncus effusus L.) species. We grew plants in glass containers filled with soil and equipped with fluorescence sensor foils on the container side walls. We gained highly-resolved data on the spatial distribution of H+ around the roots by taking time-lapse images of the samples over the course of several days.Results
We showed how the soil pH in the vicinity of roots developed over time to different values from that of the original bulk soil. The soil pH in the immediate vicinity of the root surface varied greatly along the root length, with the most acidic point being at 0.56–3.36 mm behind the root tip. Indications were also found for temporal soil pH changes due to root maturity.Conclusion
In conclusion, this study shows that this novel optical fluorescence imaging set up is a powerful tool for studying pH developments around roots in situ. 相似文献76.
Sabine S. Neukamm Jennifer Ott Sascha Dammeier Rainer Lehmann Hans-Ulrich H?ring Erwin Schleicher Cora Weigert 《The Journal of biological chemistry》2013,288(23):16403-16415
Insulin receptor substrate (IRS) 2 as intermediate docking platform transduces the insulin/IGF-1 (insulin like growth factor 1) signal to intracellular effector molecules that regulate glucose homeostasis, β-cell growth, and survival. Previously, IRS2 has been identified as a 14-3-3 interaction protein. 14-3-3 proteins can bind their target proteins via phosphorylated serine/threonine residues located within distinct motifs. In this study the binding of 14-3-3 to IRS2 upon stimulation with forskolin or the cAMP analog 8-(4-chlorophenylthio)-cAMP was demonstrated in HEK293 cells. Binding was reduced with PKA inhibitors H89 or Rp-8-Br-cAMPS. Phosphorylation of IRS2 on PKA consensus motifs was induced by forskolin and the PKA activator N6-Phe-cAMP and prevented by both PKA inhibitors. The amino acid region after position 952 on IRS2 was identified as the 14-3-3 binding region by GST-14-3-3 pulldown assays. Mass spectrometric analysis revealed serine 1137 and serine 1138 as cAMP-dependent, potential PKA phosphorylation sites. Mutation of serine 1137/1138 to alanine strongly reduced the cAMP-dependent 14-3-3 binding. Application of cycloheximide revealed that forskolin enhanced IRS2 protein stability in HEK293 cells stably expressing IRS2 as well as in primary hepatocytes. Stimulation with forskolin did not increase protein stability either in the presence of a 14-3-3 antagonist or in the double 1137/1138 alanine mutant. Thus the reduced IRS2 protein degradation was dependent on the interaction with 14-3-3 proteins and the presence of serine 1137/1138. We present serine 1137/1138 as novel cAMP-dependent phosphorylation sites on IRS2 and show their importance in 14-3-3 binding and IRS2 protein stability. 相似文献
77.
“Candidatus Cardinium hertigii” (Bacteroidetes) is a maternally inherited endosymbiont known from several arthropods. Its mechanisms for persistence in host populations are mostly reproductive manipulation, though it has been occasionally reported to improve fitness parameters in several hosts. In Culicoides (Diptera: Ceratopogonidae) biting midges, the prevalence of “Candidatus Cardinium” infection was documented as moderate, with no detectable sex bias. We therefore investigated whether “Candidatus Cardinium” affects important fitness parameters, such as survival and body size, in Culicoides imicola, a dominant vector species. Field-collected midges were trapped and analyzed for survival under different environmental conditions and antibiotic treatment, taking into account “Candidatus Cardinium” infection status and parity status (i.e., parous or nulliparous). Additionally, wing lengths were measured as a proxy parameter for body size and analyzed together with “Candidatus Cardinium” infection data. The findings revealed no difference in survival of Culicoides infected with “Candidatus Cardinium” and that of uninfected midges in both parity states and under all tested conditions: optimal, starvation, heat, and antibiotic treatment. Beyond survival, no wing length difference was found for “Candidatus Cardinium”-infected versus uninfected midges. In aggregate, these findings support our conclusion that “Candidatus Cardinium” does not have an overt effect on the survival and size of adult C. imicola midges. “Candidatus Cardinium” may affect immature stages or may alter adult reproductive performance. 相似文献
78.
Sascha Naomi McKeon Marta Moreno Maria Anise Sallum Marinete Marins Povoa Jan Evelyn Conn 《Memórias do Instituto Oswaldo Cruz》2013,108(5):605-615
To evaluate whether environmental heterogeneity contributes to the
genetic heterogeneity in Anopheles triannulatus, larval habitat
characteristics across the Brazilian states of Roraima and Pará and genetic
sequences were examined. A comparison with Anopheles goeldii
was utilised to determine whether high genetic diversity was unique to
An. triannulatus. Student t test and
analysis of variance found no differences in habitat characteristics between the
species. Analysis of population structure of An. triannulatus
and An. goeldii revealed distinct demographic histories in a
largely overlapping geographic range. Cytochrome oxidase I
sequence parsimony networks found geographic clustering for both species;
however nuclear marker networks depicted An. triannulatus with
a more complex history of fragmentation, secondary contact and recent
divergence. Evidence of Pleistocene expansions suggests both species are more
likely to be genetically structured by geographic and ecological barriers than
demography. We hypothesise that niche partitioning is a driving force for
diversity, particularly in An. triannulatus. 相似文献
79.
Petra Bonova Jozef BurdaViera Danielisova Miroslava NemethovaMiroslav Gottlieb 《Neurochemistry international》2013
In the clinic delayed post-conditioning would represent an attractive strategy for the survival of vulnerable neurons after an ischemic event. In this paper we studied the impact of ischemia and delayed post-conditioning on blood and brain tissue concentrations of glutamate and protein synthesis. We designed two groups of animals for analysis of brain tissues and blood after global ischemia and post-conditioning, and one for analysis of blood glutamate after transient focal ischemia. 相似文献
80.
Petra Bonova Jozef BurdaViera Danielisova Miroslava NemethovaMiroslav Gottlieb 《Neurochemistry international》2013
The period from stroke initiation to the cessation of penumbra damage spread represents a therapeutic window when expansion can be alleviated. In the present work, we studied some biochemical parameters helpful for the estimation of infarct progression and thus for the application of interventions. 相似文献