PGAP6, a GPI-specific phospholipase A2, has narrow substrate specificity against GPI-anchored proteins

Gun-Hee Lee, Morihisa Fujita, Hideki Nakanishi, Haruhiko Miyata, Masahito Ikawa, Yusuke Maeda, Yoshiko Murakami, Taroh Kinoshita, PGAP6, a GPI-specific phospholipase A2, has narrow substrate specificity against GPI-anchored proteins, Journal of Biological Chemistry, Volume 295, Issue 42, 2020, Pages 14501-14509, ISSN 0021-9258, https://doi.org/10.1074/jbc.RA120.014643

Comparison of short term surgical outcomes of male and female gastrointestinal surgeons in Japan: retrospective cohort study

男女の消化器外科医による手術成績は同等 --女性消化器外科医のさらなる活躍に向けて--. 京都大学プレスリリース. 2022-09-29.Study finds no differences in performance between male and female surgeons. 京都大学プレスリリース. 2022-10-04.[Objective] To compare short term surgical outcomes between male and female gastrointestinal surgeons in Japan. [Design] Retrospective cohort study. [Setting] Data from the Japanese National Clinical Database (includes data on >95% of surgeries performed in Japan) (2013-17) and the Japanese Society of Gastroenterological Surgery. [Participants] Male and female surgeons who performed distal gastrectomy, total gastrectomy, and low anterior resection. [Main outcome measures] Surgical mortality, surgical mortality combined with postoperative complications, pancreatic fistula (distal gastrectomy/total gastrectomy only), and anastomotic leakage (low anterior resection only). The association of surgeons’ gender with surgery related mortality and surgical complications was examined using multivariable logistic regression models adjusted for patient, surgeon, and hospital characteristics. [Results] A total of 149 193 distal gastrectomy surgeries (male surgeons: 140 971 (94.5%); female surgeons: 8222 (5.5%)); 63 417 gastrectomy surgeries (male surgeons: 59 915 (94.5%); female surgeons: 3502 (5.5%)); and 81 593 low anterior resection procedures (male surgeons: 77 864 (95.4%);female surgeons: 3729 (4.6%)) were done. On average, female surgeons had fewer post-registration years, operated on patients at higher risk, and did fewer laparoscopic surgeries than male surgeons. No significant difference was found between male and female surgeons in the adjusted risk for surgical mortality (adjusted odds ratio 0.98 (95% confidence interval 0.74 to 1.29) for distal gastrectomy; 0.83 (0.57 to 1.19) for total gastrectomy; 0.56 (0.30 to 1.05) for low anterior resection), surgical mortality combined with Clavien-Dindo grade ≥3 complications (adjusted odds ratio 1.03 (0.93 to 1.14) for distal gastrectomy; 0.92 (0.81 to 1.05) for total gastrectomy; 1.02 (0.91 to 1.15) for low anterior resection), pancreatic fistula (adjusted odds ratio 1.16 (0.97 to 1.38) for distal gastrectomy; 1.02 (0.84 to 1.23) for total gastrectomy), and anastomotic leakage (adjusted odds ratio 1.04 (0.92 to 1.18) for low anterior resection). [Conclusion] This study found no significant adjusted risk difference in the outcomes of surgeries performed by male versus female gastrointestinal surgeons. Despite disadvantages, female surgeons take on patients at high risk. Greater access to surgical training for female physicians is warranted in Japan

Novel Insights into Conformational Rearrangements of the Bacterial Flagellar Switch Complex

The flagellar motor can spin in both counterclockwise (CCW) and clockwise (CW) directions. The flagellar motor consists of a rotor and multiple stator units, which act as a proton channel. The rotor is composed of the transmembrane MS ring made of FliF and the cytoplasmic C ring consisting of FliG, FliM, and FliN. The C ring is directly involved in rotation and directional switching. The Salmonella FliF-FliG deletion fusion motor missing 56 residues from the C terminus of FliF and 94 residues from the N terminus of FliG keeps a domain responsible for the interaction with the stator intact, but its motor function is reduced significantly. Here, we report the structure and function of the FliF-FliG deletion fusion motor. The FliF-FliG deletion fusion not only resulted in a strong CW switch bias but also affected rotor-stator interactions coupled with proton translocation through the proton channel of the stator unit. The energy coupling efficiency of the deletion fusion motor was the same as that of the wild-type motor. Extragenic suppressor mutations in FliG, FliM, or FliN not only relieved the strong CW switch bias but also increased the motor speed at low load. The FliF-FliG deletion fusion made intersubunit interactions between C ring proteins tighter compared to the wild-type motor, whereas the suppressor mutations affect such tighter intersubunit interactions. We propose that a change of intersubunit interactions between the C ring proteins may be required for high-speed motor rotation as well as direction switching

The Satb1 Protein Directs Hematopoietic Stem Cell Differentiation toward Lymphoid Lineages

SummaryHow hematopoietic stem cells (HSCs) produce particular lineages is insufficiently understood. We searched for key factors that direct HSC to lymphopoiesis. Comparing gene expression profiles for HSCs and early lymphoid progenitors revealed that Satb1, a global chromatin regulator, was markedly induced with lymphoid lineage specification. HSCs from Satb1-deficient mice were defective in lymphopoietic activity in culture and failed to reconstitute T lymphopoiesis in wild-type recipients. Furthermore, Satb1 transduction of HSCs and embryonic stem cells robustly promoted their differentiation toward lymphocytes. Whereas genes that encode Ikaros, E2A, and Notch1 were unaffected, many genes involved in lineage decisions were regulated by Satb1. Satb1 expression was reduced in aged HSCs with compromised lymphopoietic potential, but forced Satb1 expression partly restored that potential. Thus, Satb1 governs the initiating process central to the replenishing of lymphoid lineages. Such activity in lymphoid cell generation may be of clinical importance and useful to overcome immunosenescence

A simplified numerical model for evaluating sediment control by open-type sabo dams in the Joganji River basin

The present study proposes a method to estimate sediment runoff by introducing a dam function of the relationship between inflow sediment and sediment runoff through a slit dam. The model can process rainfall runoff, sediment yield and runoff of a mountainous basin, and the model is applied to the upper reaches of the Joganji River basin, which is known for its huge amount of sediment runoff and intense bed variation because of the sediment yield caused by the earthquake in 1858. The performance of the calculations of sediment control of the slit dam is evaluated by the model. The result indicates that sediment deposition is significantly changed by sediment runoff. The proposed method can be expected to evaluate sediment transport with sabo dams on a basin scale

Efficacy and survival of nivolumab treatment for recurrent/unresectable esophageal squamous-cell carcinoma: real-world clinical data from a large multi-institutional cohort

The version of record of this article, first published in Esophagus, is available online at Publisher’s website: https://doi.org/10.1007/s10388-024-01056-w.Background: Real-world clinical outcomes of and prognostic factors for nivolumab treatment for esophageal squamous-cell carcinoma (ESCC) remain unclear. This study aimed to evaluate real-world outcomes of nivolumab monotherapy in association with relevant clinical parameters in recurrent/unresectable advanced ESCC patients. Methods: This population-based multicenter cohort study included a total of 282 patients from 15 institutions with recurrent/unresectable advanced ESCC who received nivolumab as a second-line or later therapy between 2014 and 2022. Data, including the best overall response, progression-free survival (PFS), and overall survival (OS), were retrospectively collected from these patients. Results: Objective response and disease control rates were 17.0% and 47.9%, respectively. The clinical response to nivolumab treatment significantly correlated with development of overall immune-related adverse events (P <.0001), including rash (P <.0001), hypothyroidism (P =.03), and interstitial pneumonia (P =.004). Organ-specific best response rates were 20.6% in lymph nodes, 17.4% in lungs, 15.4% in pleural dissemination, and 13.6% in primary lesions. In terms of patient survival, the median OS and PFS was 10.9 and 2.4 months, respectively. Univariate analysis of OS revealed that performance status (PS; P <.0001), number of metastatic organs (P =.019), C-reactive protein-to-albumin ratio (CAR; P <.0001), neutrophil–lymphocyte ratio (P =.001), and PMI (P =.024) were significant. Multivariate analysis further identified CAR [hazard ratio (HR) = 1.61, 95% confidence interval (CI) 1.15–2.25, P =.0053)] in addition to PS (HR = 1.65, 95% CI 1.23–2.22, P =.0008) as independent prognostic parameters. Conclusions: CAR and PS before nivolumab treatment are useful in predicting long-term survival in recurrent/unresectable advanced ESCC patients with second-line or later nivolumab treatment