Polymorphism of β2-Microglobulin Amyloid Fibrils Manifested by Ultrasonication-enhanced Fibril Formation in Trifluoroethanol

This research was originally published in the Journal of Biological Chemistry. Eri Chatani, Hisashi Yagi, Hironobu Naiki and Yuji Goto. Polymorphism of β2-Microglobulin Amyloid Fibrils Manifested by Ultrasonication-enhanced Fibril Formation in Trifluoroethanol. J. Biol. Chem. 2012; 287, 22827-22837. © the American Society for Biochemistry and Molecular Biolog

Benzalkonium Chloride Accelerates the Formation of the Amyloid Fibrils of Corneal Dystrophy-associated Peptides

This research was originally published in the Journal of Biological Chemistry. Yusuke Kato, Hisashi Yagi, Yuichi Kaji, Tetsuro Oshika and Yuji Goto. Benzalkonium Chloride Accelerates the Formation of the Amyloid Fibrils of Corneal Dystrophy-associated Peptides. J. Biol. Chem. 2013; 288, 25109-25118. © the American Society for Biochemistry and Molecular Biolog

Flow-induced Alignment of Amyloid Protofilaments Revealed by Linear Dichroism

This research was originally published in the Journal of Biological Chemistry. Rumi Adachi, Kei-ichi Yamaguchi, Hisashi Yagi, Kazumasa Sakurai, Hironobu Naiki and Yuji Goto. Flow-induced Alignment of Amyloid Protofilaments Revealed by Linear Dichroism. J. Biol. Chem. 2007; 282, 8978-8983. © the American Society for Biochemistry and Molecular Biolog

Stop-and-go kinetics in amyloid fibrillation

Many human diseases are associated with protein aggregation and fibrillation. Using glucagon as a model system for protein fibrillation we show that fibrils grow in an intermittent fashion, with periods of growth followed by long pauses. Remarkably, even if the intrinsic transition rates vary considerably in each experiment, the probability of being in the growing (stopping) state is very close to 1/4 (3/4), suggesting the presence of 4 independent conformations of the fibril tip. We discuss this possibility in terms of existing structural knowledge

KofamKOALA: KEGG ortholog assignment based on profile HMM and adaptive score threshold

Summary: KofamKOALA is a web server to assign KEGG Orthologs (KOs) to protein sequences by homology search against a database of profile hidden Markov models (KOfam) with pre-computed adaptive score thresholds. KofamKOALA is faster than existing KO assignment tools with its accuracy being comparable to the best performing tools. Function annotation by KofamKOALA helps linking genes to KEGG resources such as the KEGG pathway maps and facilitates molecular network reconstruction. Availability and implementation: KofamKOALA, KofamScan and KOfam are freely available from GenomeNet (https://www.genome.jp/tools/kofamkoala/). Supplementary information: Supplementary data are available at Bioinformatics online

Real-time and Single Fibril Observation of the Formation of Amyloid β Spherulitic Structures

This research was originally published in the Journal of Biological Chemistry. Tadato Ban, Kenichi Morigaki, Hisashi Yagi, Takashi Kawasaki, Atsuko Kobayashi, Shunsuke Yuba, Hironobu Naiki and Yuji Goto. Real-time and Single Fibril Observation of the Formation of Amyloid β Spherulitic Structures. J. Biol. Chem. 2006; 281, 33677–33683. © the American Society for Biochemistry and Molecular Biolog

spERt Technology: A novel strategy to improve productivity through enhanced polyribosome assembly on the endoplasmic reticulum in CHO cells

In cell line development process, it is frequently observed that increased mRNA levels do not always correlate with protein expression levels in CHO cells. In line with this gap, the endoplasmic reticulum (ER) in CHO cells is much less proliferated as compared with that in terminally differentiated (i.e., professional) secretory cells, suggesting that there is still room to improve their specific productivity if translational efficiency on the ER can be up-regulated. Here we present a novel engineering approach (spERt Technology) to improve specific production rates by mimicking the ER translational apparatus of professional secretory cells. In spERt Technology, we exploit the unique factors that are required for translationally active polyribosome formation on the ER to directly enhance the translational efficiency (1, 2). A high antibody (Ab) producing clone generated by a novel screen using flow cytometry (3) was used as a model cell line. The factors were introduced into the high producer and a series of the spERt Technology - introduced cell lines were generated Among these cell lines, we selected one of the best clones (spERt-f9) having stable and high productivity. Polyribosome analysis of these cell lines revealed that enhanced assembly of the ER polyribosomes as expected (1). Consistent with the highly developed polyribosomes, the spERt-introduced cell lines produced higher levels of Ab than that of parental cells, and showed prominent increase of specific production rates. Further optimization of feeding process resulted in remarkable increase of productivity in spERt-f9 cells: Ab titers of 7.6 g/L and 9.5 g/L on day 14 and 17, respectively, were achieved in shake flask fed-batch cultures by using chemically defined media. Importantly, high cell viabilities were maintained in spERt-f9 cells throughout the culture periods. In addition, lower glucose consumption and reduced accumulation of ammonia were observed. Product quality in these cells were analyzed and compared with that in the parental cells. In conclusion, spERt Technology enables to improve productivity of high Ab producers, associated with reduced accumulation of waste metabolites and high cell viabilities

Cardiorespiratory fitness, body mass index, and cancer mortality: a cohort study of Japanese men

Background: The aim of this study is to investigate the independent and joint effects of cardiorespiratory fitness (CRF) and body mass index (BMI) on cancer mortality in a low body mass index population. Methods: We evaluated CRF and BMI in relation to cancer mortality in 8760 Japanese men. The median BMI was 22.6 kg/m2 (IQR: 21.0-24.3). The mean follow-up period was more than 20 years. Hazard ratios and 95% CI were obtained using a Cox proportional hazards model while adjusting for several confounding factors. Results: Using the 2nd tertile of BMI (21.6-23.6 kg/m2) as reference, hazard ratios and 95% CI for the lowest tertile of BMI (18.5-21.5) were 1.26 (0.87–1.81), and 0.92 (0.64–1.34) for the highest tertile (23.7-37.4). Using the lowest tertile of CRF as reference, hazard ratios and 95% CIs for 2nd and highest tertiles of CRF were 0.78 (0.55–1.10) and 0.59 (0.40–0.88). We further calculated hazard ratios according to groups of men cross-tabulated by tertiles of CRF and BMI. Among men in the second tertile of BMI, those belonging to the lowest CRF tertile had a 53% lower risk of cancer mortality compared to those in the lowest CRF tertile (hazard ratio: 0.47, 95% CI: 0.23-0.97). Among those in the highest BMI tertile, the corresponding hazard ratio was 0.54 (0.25-1.17). Conclusion: These results suggest that high CRF is associated with lower cancer mortality in a Japanese population of men with low average BMI

Voluntary Exercise Can Ameliorate Insulin Resistance by Reducing iNOS-Mediated S-Nitrosylation of Akt in the Liver in Obese Rats

Voluntary exercise can ameliorate insulin resistance. The underlying mechanism, however, remains to be elucidated. We previously demonstrated that inducible nitric oxide synthase (iNOS) in the liver plays an important role in hepatic insulin resistance in the setting of obesity. In this study, we tried to verify our hypothesis that voluntary exercise improves insulin resistance by reducing the expression of iNOS and subsequent S-nitrosylation of key molecules of glucose metabolism in the liver. Twenty-one Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of type 2 diabetes mellitus, and 18 non-diabetic control Long-Evans Tokushima Otsuka (LETO) rats were randomly assigned to a sedentary group or exercise group subjected to voluntary wheel running for 20 weeks. The voluntary exercise significantly reduced the fasting blood glucose and HOMA-IR in the OLETF rats. In addition, the exercise decreased the amount of iNOS mRNA in the liver in the OLETF rats. Moreover, exercise reduced the levels of S-nitrosylated Akt in the liver, which were increased in the OLETF rats, to those observed in the LETO rats. These findings support our hypothesis that voluntary exercise improves insulin resistance, at least partly, by suppressing the iNOS expression and subsequent S-nitrosylation of Akt, a key molecule of the signal transduction pathways in glucose metabolism in the liver

Interprofessional education in medical schools in Japan

Interprofessional education (IPE) for medical students is becoming increasingly important, as reflected in the increasing number of medical schools adopting IPE. However, the current status of and barriers to pre-registration IPE implementation in Japanese medical schools remain unknown. The purpose of this study was to clarify the status and barriers of IPE implementation in medical schools in Japan. We conducted a curriculum survey from September to December 2016 of all 81 medical schools in Japan. We mailed the questionnaire and asked the schools’ undergraduate education staff to respond. The survey items were the IPE implementation status and barriers to program implementation. Sixty-four of the 81 schools responded (response rate 79.0%), of which 46 (71.9%) had implemented IPE, 42 (89.1%) as compulsory programs. Half of IPE programs were implemented in the first 2 years, while less than 10% were implemented in the latter years of medical programs. As part of the IPE programs, medical students collaborated with a wide range of professional student groups. The most common learning strategy was lectures. However, one-third of IPE programs used didactic lectures without interaction between multi-professional students. The most common perceived major barrier to implementing IPE was adjustment of the academic calendar and schedule (82.8%), followed by insufficient staff numbers (73.4%). Our findings indicate that IPE is being promoted in undergraduate education at medical schools in Japan. IPE programs differed according to the circumstances of each school. Barriers to IPE may be resolved by improving learning methods, introducing group discussions between multi-professional students in lectures or introducing IPE programs using team-based learning. In summary, we demonstrated the current status and barriers of IPE implementation in Japanese medical schools. Our findings will likely lead to the promotion of IPE programs in Japan