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At least 1,045 records · Page 58Linked to original sources
PubMed2005

Rush hour at the promoter: how the ubiquitin-proteasome pathway polices the traffic flow of nuclear receptor-dependent transcription.

Nuclear receptor-dependent transcription requires the functional activities of many proteins in order to achieve proper gene expression. Progress in understanding transcription mechanisms has revealed the unexpected involvement of the ubiquitin-proteasome pathway in the transcriptional process. In some instances, stabilization of the transcription protein augments the functional role or activation state of that protein, but other evidence supports the hypothesis that degradation of that factor may be required in order for transcription to proceed. Perhaps most peculiar is the observation that several yeast models support the uncoupling of ubiquitylation from concomitant proteasome-mediated degradation, with the former responsible for regulating posttranslational modification of histones and controlling differential recruitment of a transcription factor to distinct promoters. Additionally, the ATPases of the 19S proteasome regulatory cap have been shown to function in transcription elongation, independently of their role in proteolysis. This review summarizes and discusses progress thus far in integrating the disparate fields of ubiquitylation and proteasome-mediated protein degradation with gene transcription.

Animals↗
PubMed2006

Policing the ball: a new potassium channel subunit determines inactivation rate.

Inactivation of potassium currents during maintained firing results in a progressive increase in action potential width and neuronal excitability. In Kv1.1 channels, inactivation has attributed to a beta subunit that blocks the pore of the channel shortly after channel opening. In this issue of Neuron, Shulte and colleagues have identified a novel channel subunit whose interaction with Kv1.1 and the beta subunit prevents such inactivation. Mutations in this subunit lead to temporal lobe epilepsy.

Animals↗
PubMed2006

Myotubularin phosphatases: policing 3-phosphoinositides.

In eukaryotic cells, phosphatidylinositol is subject to differential phosphorylation, resulting in the production of seven distinct phosphatidylinositol phosphates, often referred to as phosphoinositides (PIs). PIs have numerous distinct roles in cellular regulation and membrane trafficking. Recently, myotubularin family PI 3-phosphatases have emerged as key regulators of phosphatidylinositol 3-phosphate and phosphatidylinositol 3,5-bisphosphate, two PIs that regulate traffic within the endosomal-lysosomal pathway. Mutations in several myotubularin genes lead to myotubular myopathy and Charcot-Marie-Tooth peripheral neuropathy. Strikingly, nearly half of the members of the human myotubularin family appear to be catalytically inactive. Several inactive myotubularins have essential functions in mammals. Recent work in mammalian cells and model organisms is shedding light on the roles of myotubularins in membrane traffic.

Animals↗
PubMed1998

Fatalities from non-use of seat belts and helmets in Greece: a nationwide appraisal. Hellenic Road Traffic Police.

It has been established that seat belt use by car occupants and helmet use by motorcycle riders substantially reduces the risk of serious and fatal injuries following accidents. No study, however, has evaluated the motor vehicle deaths that could be prevented in Greece by general use of these devices, even though this country has the highest mortality from motor vehicle accidents in the European Union. We have estimated the odds ratios (OR) for death rather than injury in a motor vehicle accident by seat belt use among occupants of passenger cars or helmet use among motorcycle riders, using a nationwide database in which persons killed or injured in road traffic accidents in 1985 and 1994 were recorded. The study base included 910 dead and 19,511 injured persons for 1985 and 1203 dead and 22,186 injured persons for 1994. The OR and 95% confidence intervals (CI) for death rather than injury was 0.69 (CI: 0.58 to 0.81, p < 10(-5)) for seat belt users versus non-users and 0.64 (CI: 0.51 to 0.81; p < 10(-3)) for helmet users versus non-users. There was evidence that the protective effect of these passive safety devices increased from 1985 to 1994 probably reflecting technological improvements. The proportion of all deaths that could have been avoided if all car occupants used seat belts was estimated to 27%, whereas 38% of motorcycle deaths could have been avoided if all motorcycle riders used helmets. These proportions translate to about 500 deaths per year, mostly deaths among young men.

Accidents, Traffic↗
PubMedDate not supplied

Junction road accidents during cross-flow turns: a sequence analysis of police case files.

In-depth studies of behavioural factors in road accidents using conventional methods are often inconclusive and costly. In a series of studies exploring alternative approaches, 200 cross-flow junction road accidents were sampled from the files of Nottinghamshire Constabulary, UK, coded for computer analysis using a specially devised Traffic Related Action Analysis Language, and then examined using different computational and statistical techniques. For comparison, the same analyses were carried out on 100 descriptions of safe turns, and 100 descriptions of hypothetical accidents provided by experienced drivers. The present study employed a range of sequence analysis techniques to examine the patterns of events preceding accidents of different types. Differences were found between real accidents, hypothetical ones and safe turns; between accidents turning onto and off a road with the right of way; between the accidents of younger and older drivers; between accidents on minor roads and major roads; and between the accident expectations (but not the real accidents) of male and female drivers. Pairs of successive events often provided particularly good cues for discriminating accident types.

Accidents, Traffic↗