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The crystal structure of Thermus aquaticus RNA polymerase holoenzyme (alpha2betabeta'omegasigmaA) complexed with a fork-junction promoter DNA fragment has been determined by fitting high-resolution x-ray structures of individual components into a 6.5-angstrom resolution map. The DNA lies across one face of the holoenzyme, completely outside the RNA(More)
The X-ray crystal structure of Thermus aquaticus core RNA polymerase reveals a "crab claw"-shaped molecule with a 27 A wide internal channel. Located on the back wall of the channel is a Mg2+ ion required for catalytic activity, which is chelated by an absolutely conserved motif from all bacterial and eukaryotic cellular RNA polymerases. The structure(More)
Rifampicin (Rif) is one of the most potent and broad spectrum antibiotics against bacterial pathogens and is a key component of anti-tuberculosis therapy, stemming from its inhibition of the bacterial RNA polymerase (RNAP). We determined the crystal structure of Thermus aquaticus core RNAP complexed with Rif. The inhibitor binds in a pocket of the RNAP beta(More)
To investigate the roles of astroglial cells, we targeted their ablation genetically. Transgenic mice were generated expressing herpes simplex virus thymidine kinase from the mouse glial fibrillary acidic protein (GFAP) promoter. In adult transgenic mice, 2 weeks of subcutaneous treatment with the antiviral agent ganciclovir preferentially ablated(More)
Formation of microtubule architectures, required for cell shape maintenance in yeast, directional cell expansion in plants and cytokinesis in eukaryotes, depends on antiparallel microtubule crosslinking by the conserved MAP65 protein family. Here, we combine structural and single molecule fluorescence methods to examine how PRC1, the human MAP65, crosslinks(More)
Eighteen former and active boxers underwent neurological examination, EEG, computed tomographic scan of the brain, and neuropsychological testing. Eighty-seven percent of the professional boxers had definite evidence of brain damage. All the boxers had abnormal results on at least one of the neuropsychological tests. Brain damage is a frequent result of a(More)
With the development of cognitive models of depression, interest in identifying an enduring cognitive style characteristic of depression-prone individuals has increased. However, empirical evidence for cognitive vulnerability of this kind is as yet sparse. The paper describes the development of a Cognitions Questionnaire (CQ), designed not only to provide(More)
Cell type-specific transcription during Bacillus sporulation is established by sigmaF. SpoIIAB is an anti-sigma that binds and negatively regulates sigmaF, as well as a serine kinase that phosphorylates and inactivates the anti-anti-sigma SpoIIAA. The crystal structure of sigmaF bound to the SpoIIAB dimer in the low-affinity, ADP form has been determined at(More)
The psychiatric state of 483 women was examined antenatally and at 3, 6, and 12 months postpartum. Comprehensive assessments were made of all women antenatally and of subgroups of the full sample postnatally. Psychiatric state was assessed using the General Health Questionnaire, the Present State Examination and the Montgomery and Asberg Depression Rating(More)