Relationship Between Brain Activity and Real-Road Driving Behavior: A Vector-Based Whole-Brain Functional Near-Infrared Spectroscopy Study

Automobile driving requires multiple brain functions. However, the brain regions related to driving behavior are unknown. Therefore, we measured activity of the frontal, parietal and occipital lobes during driving using functional near-infrared spectroscopy (fNIRS). Cortical activation patterns were examined in relation to driving behaviors, such as steering motion, accelerator pedal motion, and speed control. Six healthy adults participated in the experiment. Cerebral oxygen exchange (COE) was calculated based on the oxyhemoglobin and deoxyhemoglobin concentrations measured by fNIRS. The COE and driving behavior data were collected every 1 m and averaged for all subjects. Functional NIRS data for all 98 channels were extracted using principal component analysis. Similarity between extracted components and driving behaviors were confirmed by |cosine similarity|\u3e0.3. Among the factors with confirmed similarity, we identified brain regions with high principal component loading (|PCL|\u3e0.4). Among the 16 COE factors extracted, COE factor 1 and factor 5 exhibited similarity with steering motion (cosine similarity: factor 1, -0.538; factor 5, 0.551). The PCLs of COE factor 1 and factor 5 were high in the frontal lobe (Brodmann areas [BAs] 9, 8, and 4/3) (PCL\u3e0.8). COE factor 6 exhibited a similarity with accelerator pedal motion (cosine similarity: 0.369), and the PCL of COE factor 6 was highest in the parietal lobe (BA7) (PCL= -0.62). Speed control did not exhibit similarity with any COE factor. These findings will contribute to the selection of brain measurement areas when fNIRS is used for vehicle driving assessment

Frequent Loss of Genome Gap Region in 4p16.3 Subtelomere in Early-Onset Type 2 Diabetes Mellitus

A small portion of Type 2 diabetes mellitus (T2DM) is familial, but the majority occurs as sporadic disease. Although causative genes are found in some rare forms, the genetic basis for sporadic T2DM is largely unknown. We searched for a copy number abnormality in 100 early-onset Japanese T2DM patients (onset age <35 years) by whole-genome screening with a copy number variation BeadChip. Within the 1.3-Mb subtelomeric region on chromosome 4p16.3, we found copy number losses in early-onset T2DM (13 of 100 T2DM versus one of 100 controls). This region surrounds a genome gap, which is rich in multiple low copy repeats. Subsequent region-targeted high-density custom-made oligonucleotide microarray experiments verified the copy number losses and delineated structural changes in the 1.3-Mb region. The results suggested that copy number losses of the genes in the deleted region around the genome gap in 4p16.3 may play significant roles in the etiology of T2DM

Five isoforms of the phosphatidylinositol 3-kinase regulatory subunit exhibit different associations with receptor tyrosine kinases and their tyrosine phosphorylations

AbstractThere are five isoforms of the regulatory subunit for the heterodimeric type of phosphatidylinositol 3-kinase. These five regulatory subunit isoforms were overexpressed using an adenovirus transfection system, and their own tyrosine phosphorylations and associations with various tyrosine kinase receptors were investigated. When overexpressed in CHO-PDGFR cells, the associations of these regulatory subunit isoforms with the platelet-derived growth factor receptor were similar. However, when overexpressed in CHO-IR cells, p55γ exhibited a significantly lower ability to bind with IRS-1 upon insulin stimulation, as compared with other regulatory subunit isoforms. Furthermore, p55α and p55γ were found to be tyrosine-phosphorylated. Finally, interestingly, when overexpressed in CHO-EGFR cells or A431 cells and stimulated with epidermal growth factor (EGF), phosphorylated EGF receptor was detected in p85α, p85β and p50α immunoprecipitates, but not in p55α and p55γ immunoprecipitates. In addition, EGF-induced tyrosine phosphorylation was observed in p85α, p85β, p55α and p55γ, but not in p50α, immunoprecipitates. Thus, each regulatory subunit exhibits specific responses regarding both the association with tyrosine-phosphorylated substrates and its own tyrosine phosphorylation. These results suggest that each isoform possesses specific roles in signal transduction, based on its individual tyrosine kinase receptor

糖尿病モデルラットにおけるシクロスポリンAの腸管吸収

Cyclosporin A (CyA), an immunosuppressant drug, is widely used in the treatment of kidney transplantation in severe diabetic patients. The drug has a clinical problem because of its variable oral bioavailability between patients and even within the same patient. We investigated the effects of diabetic disease models on the absorption of CyA from three parts of small intestine in streptozotocin-induced diabetic (STZ) rats and non-obese spontaneous Goto-Kakizaki (GK) rats. The intestinal absorption rate evaluated by the in situ loop method showed that the remaining rate in the loop was higher in both diabetic model rats, especially in the ileum of STZ rats, than that in control rats. The increased remaining rate was markedly depressed by the addition of verapamil, a well-known specific inhibitor of P-glycoprotein (P-gp). Western blot analysis using monoclonal antibody against P-gp, C219, was carried out : An increased P-gp expression in the intestines was shown in the two diabetic model rats compared with the control rats, being in good agreement with the in situ absorption data. These results suggested the possibility of decreased intestinal absorption of CyA due to the increased expression of P-gp in the diabetic disease