Calcium depletion destabilises kinetochore fibres by the removal of CENP-F from the kinetochore

Phengchat, R., Takata, H., Uchiyama, S. et al. Calcium depletion destabilises kinetochore fibres by the removal of CENP-F from the kinetochore. Sci Rep 7, 7335 (2017). https://doi.org/10.1038/s41598-017-07777-6

Efficient generation of single domain antibodies with high affinities and enhanced thermal stabilities

Shinozaki, N., Hashimoto, R., Fukui, K. et al. Efficient generation of single domain antibodies with high affinities and enhanced thermal stabilities. Sci Rep 7, 5794 (2017). https://doi.org/10.1038/s41598-017-06277-x

Effects of Syringe Material and Silicone Oil Lubrication on the Stability of Pharmaceutical Proteins

ABSTRACTCurrently, polymer-based prefillable syringes are being promoted to the pharmaceutical market because they provide an increased break resistance relative to traditionally used glass syringes. Despite this significant advantage, the possibility that barrel material can affect the oligomeric state of the protein drug exists. The present study was designed to compare the effect of different syringe materials and silicone oil lubrication on the protein aggregation. The stability of a recombinant fusion protein, abatacept (Orencia), and a fully human recombinant immunoglobulin G1, adalimumab (Humira), was assessed in silicone oil-free (SOF) and silicone oil-lubricated 1-mL glass syringes and polymer-based syringes in accelerated stress study. Samples were subjected to agitation stress, and soluble aggregate levels were evaluated by size-exclusion chromatography and verified with analytical ultracentrifugation. In accordance with current regulatory expectations, the amounts of subvisible particles resulting from agitation stress were estimated using resonant mass measurement and dynamic flow-imaging analyses. The amount of aggregated protein and particle counts were similar between unlubricated polymer-based and glass syringes. The most significant protein loss was observed for lubricated glass syringes. These results suggest that newly developed SOF polymer-based syringes are capable of providing biopharmaceuticals with enhanced physical stability upon shipping and handling. © 2015 The Authors. Journal of Pharmaceutical Sciences published by Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:527–535, 201

Quantitative laser diffraction method for the assessment of protein subvisible particles

Shinichiro Totoki, Gaku Yamamoto, Kouhei Tsumoto, Susumu Uchiyama, Kiichi Fukui. Quantitative Laser Diffraction Method for the Assessment of Protein Subvisible Particles. Journal of Pharmaceutical Sciences, Volume 104, Issue 2, 2015, Pages 618-626. https://doi.org/10.1002/jps.24288

Prediction models for the flux decay profile and initial flux of microfiltration for therapeutic proteins

Inoue K., Masuda Y., Torisu T., et al. Prediction models for the flux decay profile and initial flux of microfiltration for therapeutic proteins. Biotechnology and Bioengineering , (2024); https://doi.org/10.1002/bit.28692.Microfiltration (MF) is an essential step during biopharmaceutical manufacturing. However, unexpected flux decay can occur. Although the flux decay profile and initial flux are important factors determining MF filterability, predicting them accurately is challenging, as the root cause of unexpected flux decay remains elusive. In this study, the methodology for developing a prediction model of flux decay profiles was established. First, the filtration profiles of different monodisperse polystyrene latex and silica beads of various sizes were evaluated. These results revealed that the size and surface electrostatic properties of the beads affect the flux decay profile. Taking the size and surface electrostatic properties of protein aggregates into account, we constructed a predictive model using model bead filtration profiles. We showed that this methodology was applicable to two different MF filters to predict the flux decay profile of therapeutic proteins. Because our proposed prediction model is based on normalized flux, the initial flux is required to predict the overall filtration profile. Then, we applied the Hagen–Poiseuille equation using sample viscosity values to estimate the initial flux. The developed prediction models can be used for effective MF scale-up assessment during the early stages of process development

Appendiceal Mucocele Detected under Treatment of Ulcerative Colitis

A 33-year-old female patient with ulcerative colitis was referred to our outpatient clinic in January 2008 with right lower abdominal pain without bloody diarrhea. Colonoscopy found mild proctosigmoiditis and a submucoal tumor with a maximal diameter of 5 cm in the cecum. Computed tomography revealed a large, hypodense, cystic cylindrical structure extending to the pelvic space. For severe pain, she underwent partial resection of the cecum including the tumor in March 2008. Intraoperatively, the vermiform appendix was swollen like a sausage and compressing the cecum, which accounted for what appeared to be a submucosal tumor like a volcano by endoscopy. Lymphadenectomy was not performed because malignancy was not suspected. In the surgical specimen, the vermiform appendix was spindle-shaped and contained a large quantity of viscous liquid. Postoperative pathological diagnosis was mucinous cystadenoma, and no cancer cells were present in the viscous liquid within the vermiform appendix. The patient left the hospital 7 days postoperatively, and her colitis remains in remission without any complications

Nucleolin functions in nucleolus formation and chromosome congression

Ma N., Matsunaga S., Takata H., et al. Nucleolin functions in nucleolus formation and chromosome congression. Journal of Cell Science, 120, 12, 2091. https://doi.org/10.1242/jcs.008771

H1.X with different properties from other linker histones is required for mitotic progression

AbstractWe report here the characterization of H1.X, a human histone H1 subtype. We demonstrate that H1.X accumulates in the nucleolus during interphase and is distributed at the chromosome periphery during mitosis. In addition, the results of fluorescence recovery after photobleaching indicate that the exchange of H1.X on and off chromatin is faster than that of the other H1 subtypes. Furthermore, RNA interference experiments reveal that H1.X is required for chromosome alignment and segregation. Our results suggest that H1.X has important functions in mitotic progression, which are different from those of the other H1 subtypes

Chromosome Scaffold is a Double-Stranded Assembly of Scaffold Proteins

Poonperm, R., Takata, H., Hamano, T. et al. Chromosome Scaffold is a Double-Stranded Assembly of Scaffold Proteins. Sci Rep 5, 11916 (2015). https://doi.org/10.1038/srep11916

The nuclear scaffold protein SAF-A is required for kinetochore-microtubule attachment and contributes to the targeting of Aurora-A to mitotic spindles

Ma N., Matsunaga S., Morimoto A., et al. The nuclear scaffold protein SAF-A is required for kinetochore-microtubule attachment and contributes to the targeting of Aurora-A to mitotic spindles. Journal of Cell Science, 124, 3, 394. https://doi.org/10.1242/jcs.063347