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991.
992.
Structural 3D motifs in RNA play an important role in the RNA stability and function. Previous studies have focused on the characterization and discovery of 3D motifs in RNA secondary and tertiary structures. However, statistical analyses of the distribution of 3D motifs along the RNA appear to be lacking. Herein, we present a novel strategy for evaluating the distribution of 3D motifs along the RNA chain and those motifs whose distributions are significantly non-random are identified. By applying it to the X-ray structure of the large ribosomal subunit from Haloarcula marismortui, helical motifs were found to cluster together along the chain and in the 3D structure, whereas the known tetraloops tend to be sequentially and spatially dispersed. That the distribution of key structural motifs such as tetraloops differ significantly from a random one suggests that our method could also be used to detect novel 3D motifs of any size in sufficiently long/large RNA structures. The motif distribution type can help in the prediction and design of 3D structures of large RNA molecules. 相似文献
993.
Peter L. Roberts Peter Feldman Debbie Crombie Chris Walker Karen Lowery 《Biologicals》2010,38(2):303-310
Virus removal from a high purity factor IX, Replenine®-VF, by filtration using a Planova 15N filter has been investigated. A wide range of relevant and model enveloped and non-enveloped viruses, of various sizes, were effectively removed by this procedure. Virus removal was confirmed to be effective when different batches of filter were challenged with poliovirus-1. It was confirmed that intentionally modified filters that failed the leakage test had completely lost the ability to remove virus, thus confirming that this test demonstrates gross filter failure. In the case of the more sensitive integrity test based on gold particle removal, it was found that a pre-wash step was not essential. Planova filters that had been modified by sodium hydroxide treatment to make them more permeable, and filters manufactured with varying pore-sizes over the range of 15–35 nm, were tested. The integrity test value that resulted in the removal of >4 log10 of poliovirus-1 from the product correlated with that recommended by the filter manufacturer. Virus removal from the product was not influenced by filter load mass, flow-rate or pressure. These studies confirm the robustness of this filtration procedure and allow suitable process limits to be set for this manufacturing step. 相似文献
994.
Hao Wu Courtney Turner Jimmy Gardner Brenda Temple Patrick Brennwald 《Molecular biology of the cell》2010,21(3):430-442
The Rho3 and Cdc42 members of the Rho GTPase family are important regulators of exocytosis in yeast. However, the precise mechanism by which they regulate this process is controversial. Here, we present evidence that the Exo70 component of the exocyst complex is a direct effector of both Rho3 and Cdc42. We identify gain-of-function mutants in EXO70 that potently suppress mutants in RHO3 and CDC42 defective for exocytic function. We show that Exo70 has the biochemical properties expected of a direct effector for both Rho3 and Cdc42. Surprisingly, we find that C-terminal prenylation of these GTPases both promotes the interaction and influences the sites of binding within Exo70. Finally, we demonstrate that the phenotypes associated with novel loss-of-function mutants in EXO70, are entirely consistent with Exo70 as an effector for both Rho3 and Cdc42 function in secretion. These data suggest that interaction with the Exo70 component of the exocyst is a key event in spatial regulation of exocytosis by Rho GTPases. 相似文献
995.
González E Robles Y Govezensky T Bobes RJ Gevorkian G Manoutcharian K 《Journal of biomolecular screening》2010,15(10):1268-1273
In this study, the authors have generated a tapeworm Taenia solium genomic DNA expression library where foreign peptides/proteins were fused to N-termini of M13 cpVIII and expressed at a high copy number on the phage surface, and they showed that this library may be used in bioselection against antipathogen immune sera, allowing the identification of disease-related antigens recognizing antibodies present in clinical samples. They isolated 2 phage clones expressing T. solium-derived antigens specifically reacting with antibodies present in plasma and cerebrospinal fluid samples of neuroimaging-confirmed neurocysticercosis patients. The described antigen discovery strategy may be used for the direct identification of antigens useful for host-pathogen interaction studies as well as for the development of molecular vaccines and diagnostics. 相似文献
996.
Brett M. Macey Matthew J. Jenny Heidi R. Williams Lindy K. Thibodeaux Marion Beal Jonas S. Almeida Charles Cunningham Annalaura Mancia Gregory W. Warr Erin J. Burge A. Fred Holland Paul S. Gross Sonomi Hikima Karen G. Burnett Louis Burnett Robert W. Chapman 《Comparative biochemistry and physiology. Part A, Molecular & integrative physiology》2010,155(3):341-349
Heavy metals, such as copper, zinc and cadmium, represent some of the most common and serious pollutants in coastal estuaries. In the present study, we used a combination of linear and artificial neural network (ANN) modelling to detect and explore interactions among low-dose mixtures of these heavy metals and their impacts on fundamental physiological processes in tissues of the Eastern oyster, Crassostrea virginica. Animals were exposed to Cd (0.001–0.400 μM), Zn (0.001–3.059 μM) or Cu (0.002–0.787 μM), either alone or in combination for 1 to 27 days. We measured indicators of acid–base balance (hemolymph pH and total CO2), gas exchange (Po2), immunocompetence (total hemocyte counts, numbers of invasive bacteria), antioxidant status (glutathione, GSH), oxidative damage (lipid peroxidation; LPx), and metal accumulation in the gill and the hepatopancreas. Linear analysis showed that oxidative membrane damage from tissue accumulation of environmental metals was correlated with impaired acid–base balance in oysters. ANN analysis revealed interactions of metals with hemolymph acid–base chemistry in predicting oxidative damage that were not evident from linear analyses. These results highlight the usefulness of machine learning approaches, such as ANNs, for improving our ability to recognize and understand the effects of sub-acute exposure to contaminant mixtures. 相似文献
997.
Robbins EM Krupp AJ Perez de Arce K Ghosh AK Fogel AI Boucard A Südhof TC Stein V Biederer T 《Neuron》2010,68(5):894-906
Synaptogenesis is required for wiring neuronal circuits in the developing brain and continues to remodel adult networks. However, the molecules organizing synapse development and maintenance in?vivo remain incompletely understood. We now demonstrate that the immunoglobulin adhesion molecule SynCAM 1 dynamically alters synapse number and plasticity. Overexpression of SynCAM 1 in transgenic mice promotes excitatory synapse number, while loss of SynCAM 1 results in fewer excitatory synapses. By turning off SynCAM 1 overexpression in transgenic brains, we show that it maintains the newly induced synapses. SynCAM 1 also functions at mature synapses to alter their plasticity by regulating long-term depression. Consistent with these effects on neuronal connectivity, SynCAM 1 expression affects spatial learning, with knock-out mice learning better. The reciprocal effects of increased SynCAM 1 expression and loss reveal that this adhesion molecule contributes to the regulation of synapse number and plasticity, and impacts how neuronal networks undergo activity-dependent changes. 相似文献
998.
999.
Jinho Kim Daniel J. Amante Jennifer P. Moody Christina K. Edgerly Olivia L. Bordiuk Karen Smith Samantha A. Matson Wayne R. Matson Clemens R. Scherzer H. Diana Rosas Steven M. Hersch Robert J. Ferrante 《生物化学与生物物理学报:疾病的分子基础》2010,1802(7-8):673-681
A major goal of current clinical research in Huntington's disease (HD) has been to identify preclinical and manifest disease biomarkers, as these may improve both diagnosis and the power for therapeutic trials. Although the underlying biochemical alterations and the mechanisms of neuronal degeneration remain unknown, energy metabolism defects in HD have been chronicled for many years. We report that the brain isoenzyme of creatine kinase (CK-BB), an enzyme important in buffering energy stores, was significantly reduced in presymptomatic and manifest disease in brain and blood buffy coat specimens in HD mice and HD patients. Brain CK-BB levels were significantly reduced in R6/2 mice by ~ 18% to ~ 68% from 21 to 91 days of age, while blood CK-BB levels were decreased by ~ 14% to ~ 44% during the same disease duration. Similar findings in CK-BB levels were observed in the 140 CAG mice from 4 to 12 months of age, but not at the earliest time point, 2 months of age. Consistent with the HD mice, there was a grade-dependent loss of brain CK-BB that worsened with disease severity in HD patients from ~ 28% to ~ 63%, as compared to non-diseased control patients. In addition, CK-BB blood buffy coat levels were significantly reduced in both premanifest and symptomatic HD patients by ~ 23% and ~ 39%, respectively. The correlation of CK-BB as a disease biomarker in both CNS and peripheral tissues from HD mice and HD patients may provide a powerful means to assess disease progression and to predict the potential magnitude of therapeutic benefit in this disorder. 相似文献
1000.