Deletion of CDKAL1 Affects Mitochondrial ATP Generation and First-Phase Insulin Exocytosis

A variant of the CDKAL1 gene was reported to be associated with type 2 diabetes and reduced insulin release in humans; however, the role of CDKAL1 in β cells is largely unknown. Therefore, to determine the role of CDKAL1 in insulin release from β cells, we studied insulin release profiles in CDKAL1 gene knockout (CDKAL1 KO) mice.Total internal reflection fluorescence imaging of CDKAL1 KO β cells showed that the number of fusion events during first-phase insulin release was reduced. However, there was no significant difference in the number of fusion events during second-phase release or high K(+)-induced release between WT and KO cells. CDKAL1 deletion resulted in a delayed and slow increase in cytosolic free Ca(2+) concentration during high glucose stimulation. Patch-clamp experiments revealed that the responsiveness of ATP-sensitive K(+) (K(ATP)) channels to glucose was blunted in KO cells. In addition, glucose-induced ATP generation was impaired. Although CDKAL1 is homologous to cyclin-dependent kinase 5 (CDK5) regulatory subunit-associated protein 1, there was no difference in the kinase activity of CDK5 between WT and CDKAL1 KO islets.We provide the first report describing the function of CDKAL1 in β cells. Our results indicate that CDKAL1 controls first-phase insulin exocytosis in β cells by facilitating ATP generation, K(ATP) channel responsiveness and the subsequent activity of Ca(2+) channels through pathways other than CDK5-mediated regulation

Generating Lane-Change Trajectories of Individual Drivers

This paper describes a method to generate vehicle trajectories of lane change paths for individual drivers. Although each driver has a consistent preferance in the lane change behavior, lane-changing time and vehicle trajectory are uncertain due to the presence of surrounding vehicles. To model this uncertainty, we propose a statistical driver model. We assume that a driver plans various vehicle trajectories depending on the surrounding vehicles and then selects a safe and comfortable trajectory. Lane change patterns of each driver are modeled with a hidden Markov model (HMM), which is trained using longitudinal vehicle velocity, lateral vehicle position, and their dynamic features. Vehicle trajectories are generated from the HMM in a maximum likelihood criterion at random lane-changing time and state duration. Experimental results show that vehicle trajectories generated from the HMM included a similar trajectory to that of a target driver

Synthesis of All Stereoisomers of 3,3′-Dimethoxy-7,7′-epoxylignane-4,4′-diol and Their Plant Growth Inhibitory Activity

All stereoisomers of 3,3′-dimethoxy-7,7′-epoxylignane-4,4′-diol were synthesized to examine the effect of stereochemistry on their plant growth inhibitory activity using lettuce and Italian ryegrass. The effect of structural modifications such as dehydroxylation, methoxylation and hydroxylation at the 9- and 9′-positions of the lignans on the activity was also studied. Most of the epoxylignanes showed higher plant growth inhibitory potency against ryegrass than against lettuce, and the inhibitory activity varied depending on the configurations of each position of the tetrahydrofuran ring (7-, 7′-, 8-, and 8′-positions of the epoxylignanes). Among the 9,9′-position-modified derivatives, the dehydroxy derivatives showed the highest potency. These results suggested that the plant growth inhibitory activity should be influenced by the structure of the epoxylignanes