Neurons dispose of hyperactive kinesin into glial cells for clearance.

Microtubule-based kinesin motor proteins are crucial for intracellular transport, but their hyperactivation can be detrimental for cellular functions. This study investigated the impact of a constitutively active ciliary kinesin mutant, OSM-3CA, on sensory cilia in C. elegans. Surprisingly, we found that OSM-3CA was absent from cilia but underwent disposal through membrane abscission at the tips of aberrant neurites. Neighboring glial cells engulf and eliminate the released OSM-3CA, a process that depends on the engulfment receptor CED-1. Through genetic suppressor screens, we identified intragenic mutations in the OSM-3CA motor domain and mutations inhibiting the ciliary kinase DYF-5, both of which restored normal cilia in OSM-3CA-expressing animals. We showed that conformational changes in OSM-3CA prevent its entry into cilia, and OSM-3CA disposal requires its hyperactivity. Finally, we provide evidence that neurons also dispose of hyperactive kinesin-1 resulting from a clinic variant associated with amyotrophic lateral sclerosis, suggesting a widespread mechanism for regulating hyperactive kinesins.

Transposase-assisted tagmentation: an economical and scalable strategy for single-worm whole-genome sequencing.

AlphaMissense identifies 23 million human missense variants as likely pathogenic, but only 0.1% have been clinically classified. To experimentally validate these predictions, chemical mutagenesis presents a rapid, cost-effective method to produce billions of mutations in model organisms. However, the prohibitive costs and limitations in the throughput of whole-genome sequencing (WGS) technologies, crucial for variant identification, constrain its widespread application. Here, we introduce a Tn5 transposase-assisted tagmentation technique for conducting WGS in Caenorhabditis elegans, Escherichia coli, Saccharomyces cerevisiae, and Chlamydomonas reinhardtii. This method, demands merely 20 min of hands-on time for a single-worm or single-cell clones and incurs a cost below 10 US dollars. It effectively pinpoints causal mutations in mutants defective in cilia or neurotransmitter secretion and in mutants synthetically sterile with a variant analogous to the B-Raf Proto-oncogene, Serine/Threonine Kinase (BRAF) V600E mutation. Integrated with chemical mutagenesis, our approach can generate and identify missense variants economically and efficiently, facilitating experimental investigations of missense variants in diverse species.

Risk factors associated with traffic violations and accident severity in China.

With the recent economic boom in China, vehicle volume and the number of traffic accident fatalities have become the highest in the world. Meanwhile, traffic accidents have become the leading cause of death in China. Systematically analyzing road safety data from different perspectives and applying empirical methods/implementing proper measures to reduce the fatality rate will be an urgent and challenging task for China in the coming years. In this study, we analyze the traffic accident data for the period 2006-2010 in Guangdong Province, China. These data, extracted from the Traffic Management Sector-Specific Incident Case Data Report, are the only officially available and reliable source of traffic accident data (with a sample size>7000 per year). In particular, we focus on two outcome measures: traffic violations and accident severity. Human, vehicle, road and environmental risk factors are considered. First, the results establish the role of traffic violations as one of the major risks threatening road safety. An immediate implication is: if the traffic violation rate could be reduced or controlled successfully, then the rate of serious injuries and fatalities would be reduced accordingly. Second, specific risk factors associated with traffic violations and accident severity are determined. Accordingly, to reduce traffic accident incidence and fatality rates, measures such as traffic regulations and legislation-targeting different vehicle types/driver groups with respect to the various human, vehicle and environment risk factors-are needed. Such measures could include road safety programs for targeted driver groups, focused enforcement of traffic regulations and road/transport facility improvements. Data analysis results arising from this study will shed lights on the development of similar (adjusted) measures to reduce traffic violations and/or accident fatalities and injuries, and to promote road safety in other regions.