Tau phosphorylation at Alzheimer\u27s disease-related Ser356 contributes to tau stabilization when PAR-1/MARK activity is elevated.

Abnormal phosphorylation of the microtubule-associated protein tau is observed in many neurodegenerative diseases, including Alzheimer\u27s disease (AD). AD-related phosphorylation of two tau residues, Ser262 and Ser356, by PAR-1/MARK stabilizes tau in the initial phase of mismetabolism, leading to subsequent phosphorylation events, accumulation, and toxicity. However, the relative contribution of phosphorylation at each of these sites to tau stabilization has not yet been elucidated. In a Drosophila model of human tau toxicity, we found that tau was phosphorylated at Ser262, but not at Ser356, and that blocking Ser262 phosphorylation decreased total tau levels. By contrast, when PAR-1 was co-overexpressed with tau, tau was hyperphosphorylated at both Ser262 and Ser356. Under these conditions, the protein levels of tau were significantly elevated, and prevention of tau phosphorylation at both residues was necessary to completely suppress this elevation. These results suggest that tau phosphorylation at Ser262 plays the predominant role in tau stabilization when PAR-1/MARK activity is normal, whereas Ser356 phosphorylation begins to contribute to this process when PAR-1/MARK activity is abnormally elevated, as in diseased brains

Effects of posture regulation on mood states, heart rate and test performance in children

This experiment aimed to investigate the effects of seated posture regulation on children’s psychological and physiological state and test performance. Thirty-eight boys (mean age: 12.3 ± 0.53 years) participated in both upright and normal posture conditions in a within-participants design. Participants completed a two-dimensional mood scale to measure psychological mood states and performed three tests (calculation, listening comprehension and word memory). Heart rate, as an index of physiological arousal state, was measured. Upright posture resulted in greater vitality and pleasure, as well as increased heart rate, compared with normal posture. Upright posture also led to significantly higher scores for calculation and listening comprehension tests. Moreover, increases in vitality level positively influenced increases in calculation and listening comprehension test scores. This study suggests that adopting an upright posture results in maintaining a positive psychological state and improving test performance of children

Influence of nut shell powder content on the tribological properties of recycled polyolefin composites

The purpose of this study is to investigate the influence of nut shell powder (NSP) content on the tribological properties of recycled polyolefin (R-PO) composites. NSP was previously grinded the dried nut shell by crusher machine cryogenically in liquid nitrogen. NSP/R-PO composites with NSP content of 5, 10 and 20 vol.% were prepared in this study. These composites were extruded by a twin screw extruder and injection-molded. Their tribological properties were measured by a reciprocating type sliding wear tester at constant normal load and sliding speed under dry condition. It was found that NSP is effective for reducing the wear resistance of R-PO, and the influence of NSP content on the tribological properties of NSP/R-PO composites does not remarkably appear, but they are improved with the addition of low content such as 5 vol.%. This may be attributed to the change of wear mechanism according to the filling of NSP. © 2016 Author(s).MEXT, Ministry of Education, Culture, Sports, Science, and Technolog

Preferential Reactivity of Dipeptidyl Peptidase-IV Inhibitor-Associated Bullous Pemphigoid Autoantibodies to the Processed Extracellular Domains of BP180

Bullous pemphigoid (BP) is a common autoimmune blistering disease in which autoantibodies target the hemidesmosomal components BP180 and/or BP230 in basal keratinocytes. In BP, 80 to 90% of autoantibodies target the juxtamembranous extracellular non-collagenous 16th A (NC16A) domain of BP180. Recently, the administration of dipeptidyl peptidase-IV inhibitors (DPP4i), which are widely used as antihyperglycemic drugs, has been recognized to be a causative factor for BP. DPP4i-associated BP (DPP4i-BP) autoantibodies tend to target epitopes on non-NC16A regions of BP180, and the pathomechanism for the development of the unique autoantibodies remains unknown. To address the characteristics of DPP4i-BP autoantibodies in detail, we performed epitope analysis of 18 DPP4i-BP autoantibodies targeting the non-NC16A domains of BP180 using various domain-specific as well as plasmin-digested polypeptides derived from recombinant BP180. Firstly, Western blotting showed that only one DPP4i-BP serum reacted with the epitopes on the intracellular domain of BP180, and no sera reacted with the C-terminal domain of the molecule. In addition, only 2 DPP4i-BP sera reacted with BP230 as determined by enzyme-linked immunosorbent assay. Thus, DPP4i-BP autoantibodies were found to mainly target the non-NC16A mid-portion of the extracellular domain of BP. Interestingly, Western blotting using plasmin-digested BP180 as a substrate revealed that all of the DPP4i-BP sera reacted more intensively with the 97-kDa processed extracellular domain of BP180, which is known as the LABD97 autoantigen, than full-length BP180 did. All of the DPP4i-BP autoantibodies targeting the LABD97 autoantigen were IgG1, and IgG4 was observed to react with the molecule in only 7 cases (38.9%). In summary, the present study suggests that IgG1-class autoantibodies targeting epitopes on the processed extracellular domain of BP180, i.e., LABD97, are the major autoantibodies in DPP4i-BP

Development of a preoperative prediction model for new-onset diabetes mellitus after partial pancreatectomy

ABSTRACT: Pancreatectomy is an invasive surgery that is sometimes associated with complications. New-onset diabetes mellitus sometimes develops after partial pancreatectomy and severely affects the patient's quality of life. This study aimed to develop a preoperative prediction model of new-onset diabetes mellitus after partial pancreatectomy, which will help patients and surgeons to achieve more easily better common decisions on regarding whether to perform partial pancreatectomy. This retrospective cohort study analyzed medical records of patients who underwent partial pancreatectomy (total pancreatectomy excluded) from April 1, 2008, to February 28, 2016, which were available in the database provided by Medical Data Vision Co., Ltd. (Tokyo, Japan). The predictors were preoperative age, body mass index, hemoglobin A1c level, blood glucose level, and indication for partial pancreatectomy. The outcome was the development of new-onset diabetes mellitus at 1 to 12 months after partial pancreatectomy. We used a logistic regression model and calculated the scores of each predictor. To determine test performance, we assessed discrimination ability using the receiver operating characteristic curve and calibration with a calibration plot and the Hosmer-Lemeshow test. We also performed internal validation using the bootstrap method. Of 681 patients, 125 (18.4%) had new-onset diabetes mellitus after partial pancreatectomy. The developed prediction model had a possible range of 0 to 46 points. The median score was 13, and the interquartile range was 9 to 22. The C-statistics of the receiver operating characteristic curve on the score to predict the outcome was .70 (95% confidence interval [CI], .65-.75). Regarding the test performance, the Hosmer-Lemeshow test was not significant (P = .17), and calibration was good. In the bootstrapped cohorts, the C-statistics was .69 (95% CI, .62-.76). We developed a preoperative prediction model for new-onset diabetes mellitus after partial pancreatectomy. This would provide important information for surgeons and patients when deciding whether to perform partial pancreatectomy

Increased Ratio of Non-mercaptalbumin-1 Among Total Plasma Albumin Demonstrates Potential Protein Undernutrition in Adult Rats

The redox state of plasma albumin shifts in response to dietary protein intake in growing rats, and the shift is more sensitive than that of plasma albumin level, a classical marker of protein nutritional status. While it has been suggested that plasma albumin redox state could be useful as a novel marker of protein nutritional status, the above animal model is highly sensitive to dietary protein intake and the observation may not be extrapolated widely to humans. This study aimed to investigate whether albumin redox state also reflects protein nutritional status in adult rats, which have a lower dietary protein requirement and are less responsive to protein intake. Male adult rats were placed on AIN-93M diet (14% casein), or AIN-93M-based low protein diets (10 or 5% casein) ad libitum for 24 weeks. Whereas there was no significant difference in body weight between the groups at the end of the experimental period, the 5% casein diet group had the smallest gastrocnemius muscle weight among the groups, which was significantly lower than that of the 10% casein diet group. Plasma albumin level was also lower in the 5% casein diet group compared with the other groups, but the differences were limited and inconsistent during the experimental period. Among the albumin redox isoforms such as mercaptalbumin, non-mercaptalbumin-1, and non-mercaptalbumin-2, the ratio of non-mercaptalbumin-1 among total albumin was significantly higher in the 5% casein diet group, and the increase remained constant throughout the experimental period. Increased non-mercaptalbumin-1 ratio would thus demonstrate the presence of potential protein undernutrition in adult rats, as manifested only by a decreased gain in a specific type of skeletal muscle; non-mercaptalbumin-1 among total albumin ratio could be useful as a robust marker of protein nutritional status, contributing to prevention of protein undernutrition-related diseases such as frailty and sarcopenia

Results of initial operations in non-small cell lung cancer patients with single-level N2 disease

金沢大学医学部附属病院呼吸器外科Background. There is still debate regarding the use of surgery in the management of non-small cell lung cancer patients with N2 disease. The primary aim of the present study was analysis of the results of initial operations in non-small cell lung cancer patients with single-level N2 disease. Methods. Ninety-four patients with the disease who underwent initial surgery consisting of complete resection of the primary site plus systematic lymphadenectomy were examined. We also immunohistochemically examined lymphatic vessel density and vascular endothelial growth factor-C expression. Results. The overall 5- and 10-year survival rates for the 94 patients were 27.1% and 12.1%, respectively, with a median survival of 22 months. When stratified by skipping status, the 5-year survival rates for the patients in skip-N2 and non-skip-N2 groups were 33.4% and 19.8%, respectively (p = 0.0189). Skip metastasis, T factor, subcarinal lymph node metastasis, and adjuvant chemotherapy were recognized as independent prognostic indicators. In both skip-N2 and non-skip-N2 groups, distant relapse was the dominant pattern of recurrence. Although the peritumoral lymphatic vessel density was associated with vascular endothelial growth factor-C expression in tumors, the lymphangiogenic profile appeared to be different between skip-N2 and non-skip-N2 tumors, suggesting different nodal metastatic process. Conclusions. Lung cancer patients with single-level N2 disease are an oncologically heterogeneous cohort. Although further studies involving randomized comparisons are required, the poor outcomes found here indicate that the initial operation has yet to be validated for patients with this disease. © 2006 by The Society of Thoracic Surgeons

Surgical Results in T2N0M0 Nonsmall Cell Lung Cancer Patients With Large Tumors 5 cm or Greater in Diameter: What Regulates Outcome?

金沢大学医学部附属病院呼吸器外科Background: We assessed the surgical results along with the clinical and biological features of nonsmall-cell lung cancer (NSCLC) patients with localized large tumors. Methods: The study population consisted of 86 NSCLC patients who underwent complete resection of tumors 5 cm or larger in diameter in stage IB (T2N0M0). We immunohistochemically assessed the expression of angiostatin and endostatin. Results: The median tumor size was 6.0 cm (range, 5 to 14 cm). The operative procedures used were lobectomy in 71 cases, bilobectomy in 8 cases, and pneumonectomy in 11 cases. Fifty patients (58.1%) relapsed during the mean follow-up period of 33.6 ± 4.5 months. The median disease-free interval was 9 months. Of 44 recurrent patients whose disease-free interval could be identified, 25 patients (56.8%) relapsed within 12 months after the operation. The overall 5- and 10-year survival rates were 42.0% and 24.2%, respectively. Multivariate analysis showed that the degree of pleural involvement and angiostatin expression within the tumor were independent prognostic indicators. The endostatin expression within tumors also had a weaker relationship with outcome. Conclusions: Long-term surgical results were poor and early relapse was common in this cohort. In addition to pleural involvement, the tumor-induced expression of angiostatin and endostatin merit further investigation to gain possible insights into selection of patients who will benefit from surgery as the first line treatment. © 2006 The Society of Thoracic Surgeons