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排序方式: 共有434条查询结果,搜索用时 843 毫秒
71.
72.
Tafer H Ameres SL Obernosterer G Gebeshuber CA Schroeder R Martinez J Hofacker IL 《Nature biotechnology》2008,26(5):578-583
Small-interfering RNAs (siRNAs) assemble into RISC, the RNA-induced silencing complex, which cleaves complementary mRNAs. Despite their fluctuating efficacy, siRNAs are widely used to assess gene function. Although this limitation could be ascribed, in part, to variations in the assembly and activation of RISC, downstream events in the RNA interference (RNAi) pathway, such as target site accessibility, have so far not been investigated extensively. In this study we present a comprehensive analysis of target RNA structure effects on RNAi by computing the accessibility of the target site for interaction with the siRNA. Based on our observations, we developed a novel siRNA design tool, RNAxs, by combining known siRNA functionality criteria with target site accessibility. We calibrated our method on two data sets comprising 573 siRNAs for 38 genes, and tested it on an independent set of 360 siRNAs targeting four additional genes. Overall, RNAxs proves to be a robust siRNA selection tool that substantially improves the prediction of highly efficient siRNAs. 相似文献
73.
Although proteases represent an estimated 5% to 10% of potential drug targets, inhibitors for metalloproteases (MPs) account for only a small proportion of all approved drugs, failures of which have typically been associated with lack of selectivity. In this study, the authors describe a novel and universal binding assay based on an actinonin derivative and show its binding activities for several MPs and its lack of activity toward all the non-MPs tested. This newly developed assay would allow for the rapid screening for inhibitors of a given MP and for the selectivity profiling of the resulting hits. The assay has successfully enabled for the first time simultaneous profiling of 8 well-known inhibitors against a panel of selected MPs. Previously published activities for these inhibitors were confirmed, and the authors have also discovered new molecular targets for some of them. The authors conclude that their profiling platform provides a generic assay solution for the identification of novel metalloprotease inhibitors as well as their selectivity profiling using a simple and homogeneous assay. 相似文献
74.
There is increasing evidence that oxidative stress may play a role in the pathophysiology of hyperemesis gravidarum. Serum paraoxonase-1 (PON-1) is a high density lipoprotein (HDL)-associated enzyme that prevents oxidative modification of low density lipoprotein. The aim of the study was to measure the serum levels of PON-1 activity in women with hyperemesis gravidarum. Thirty-four women with hyperemesis gravidarum and 31 healthy pregnant women were enrolled in the study. Serum PON-1 activity was measured spectrophotometrically. Lipid hydroperoxide (LOOH) levels were measured by iodometric assay. PON-1 activity was significantly lower and LOOH levels were significantly higher in pregnant women with hyperemesis gravidarum than in healthy pregnant women (P < 0.0001, for all). There were significant correlations between PON-1 and LOOH, triglyceride, total cholesterol, HDL, low density lipoprotein (LDL) and high sensitive C-reactive protein (HSCRP; P < 0.0001, for all). By using multiple regression analysis LDL, HDL, HSCRP and LOOH were independent determinants of serum PON-1 activity in the study. Decreased PON-1 activity might be related to increased oxidative stress and inflammation in pregnant women with hyperemesis gravidarum. Subjects with hyperemesis gravidarum might be more prone to the development of atherogenesis due to low serum PON-1 activity. 相似文献
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76.
Srdjan Ostojic Nicolas Brunel Vincent Hakim 《Journal of computational neuroscience》2009,26(3):369-392
We investigate how synchrony can be generated or induced in networks of electrically coupled integrate-and-fire neurons subject
to noisy and heterogeneous inputs. Using analytical tools, we find that in a network under constant external inputs, synchrony
can appear via a Hopf bifurcation from the asynchronous state to an oscillatory state. In a homogeneous net work, in the oscillatory
state all neurons fire in synchrony, while in a heterogeneous network synchrony is looser, many neurons skipping cycles of
the oscillation. If the transmission of action potentials via the electrical synapses is effectively excitatory, the Hopf
bifurcation is supercritical, while effectively inhibitory transmission due to pronounced hyperpolarization leads to a subcritical
bifurcation. In the latter case, the network exhibits bistability between an asynchronous state and an oscillatory state where
all the neurons fire in synchrony. Finally we show that for time-varying external inputs, electrical coupling enhances the
synchronization in an asynchronous network via a resonance at the firing-rate frequency.
相似文献
Srdjan OstojicEmail: |
77.
Tan-Trung Nguyen Noelya Planchard Jennifer Dahan Nadge Arnal Sandrine Balzergue Abdelilah Benamar Pierre Bertin Vronique Brunaud Cline Dargel-Graffin David Macherel Marie-Laure Martin-Magniette Martine Quadrado Olivier Namy Hakim Mireau 《Molecular biology and evolution》2021,38(8):3445
The high mutational load of mitochondrial genomes combined with their uniparental inheritance and high polyploidy favors the maintenance of deleterious mutations within populations. How cells compose and adapt to the accumulation of disadvantageous mitochondrial alleles remains unclear. Most harmful changes are likely corrected by purifying selection, however, the intimate collaboration between mitochondria- and nuclear-encoded gene products offers theoretical potential for compensatory adaptive changes. In plants, cytoplasmic male sterilities are known examples of nucleo-mitochondrial coadaptation situations in which nuclear-encoded restorer of fertility (Rf) genes evolve to counteract the effect of mitochondria-encoded cytoplasmic male sterility (CMS) genes and restore fertility. Most cloned Rfs belong to a small monophyletic group, comprising 26 pentatricopeptide repeat genes in Arabidopsis, called Rf-like (RFL). In this analysis, we explored the functional diversity of RFL genes in Arabidopsis and found that the RFL8 gene is not related to CMS suppression but essential for plant embryo development. In vitro-rescued rfl8 plantlets are deficient in the production of the mitochondrial heme–lyase complex. A complete ensemble of molecular and genetic analyses allowed us to demonstrate that the RFL8 gene has been selected to permit the translation of the mitochondrial ccmFN2 gene encoding a heme–lyase complex subunit which derives from the split of the ccmFN gene, specifically in Brassicaceae plants. This study represents thus a clear case of nuclear compensation to a lineage-specific mitochondrial genomic rearrangement in plants and demonstrates that RFL genes can be selected in response to other mitochondrial deviancies than CMS suppression. 相似文献
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80.
Steven A. Safren Katie B. Biello Laura Smeaton Matthew J. Mimiaga Ann Walawander Javier R. Lama Aadia Rana Mulinda Nyirenda Virginia M. Kayoyo Wadzanai Samaneka Anjali Joglekar David Celentano Ana Martinez Jocelyn E. Remmert Aspara Nair Umesh G. Lalloo Nagalingeswaran Kumarasamy James Hakim Thomas B. Campbell for the PEARLS Study Team 《PloS one》2014,9(8)