Vestigial-like 2 contributes to normal muscle fiber type distribution in mice

Honda, M., Hidaka, K., Fukada, Si. et al. Vestigial-like 2 contributes to normal muscle fiber type distribution in mice. Sci Rep 7, 7168 (2017). https://doi.org/10.1038/s41598-017-07149-

Killing Two Birds with One Stone: Discovery of Dual Inhibitors of Oxygen and Fumarate Respiration in Zoonotic Parasite, Echinococcus multilocularis

Ascofuranone (AF), a meroterpenoid isolated from various filamentous fungi, including Acremonium egyptiacum, has been reported as a potential lead candidate for drug development against parasites and cancer. In this study, we demonstrated that AF and its derivatives are potent anthelminthic agents, particularly against Echinococcus multilocularis, which is the causative agent of alveolar echinococcosis. We measured the inhibitory activities of AF and its derivatives on the mitochondrial aerobic and anaerobic respiratory systems of E. multilocularis larvae. Several derivatives inhibited complex II (succinate:quinone reductase [SQR]; IC50 = 0.037 to 0.135 mM) and also complex I to III (NADH:cytochrome c reductase; IC50 = 0.008 to 0.401 mM), but not complex I (NADH:quinone reductase), indicating that mitochondrial complexes II and III are the targets. In particular, complex II inhibition in the anaerobic pathway was notable because E. multilocularis employs NADH:fumarate reductase (fumarate respiration), in addition to NADH oxidase (oxygen respiration), resulting in complete shutdown of ATP synthesis by oxidative phosphorylation. A structure-activity relationship study of E. multilocularis complex II revealed that the functional groups of AF are essential for inhibition. Binding mode prediction of AF derivatives to complex II indicated potential hydrophobic and hydrogen bond interactions between AF derivatives and amino acid residues within the quinone binding site. Ex vivo culture assays revealed that AF derivatives progressively reduced the viability of protoscoleces under both aerobic and anaerobic conditions. These findings confirm that AF and its derivatives are the first dual inhibitors of fumarate and oxygen respiration in E. multilocularis and are potential lead compounds in the development of anti-echinococcal drugs

Clinical Significance of Measuring Urinary Sulfated Bile Acids in Adult Patients with Hepatobiliary Diseases.

Background/Aims: Measurement of urinary sulfated bile acid (USBA) level is a simple urine test that reflects the degree of cholestasis in newborns. The aim of this study was to clarify the clinical significances of this test for liver diseases in adults. Methodology: We examined the relationship between USBA level in a urine sample by enzymatic assay and clinical parameters and postoperative complications in 27 patients with hepatobiliary diseases who underwent surgical procedures between 2002 and 2007. Results: Mean USBA in all patients before surgery was 39.8 ± 64.0 μmol/L (median value was 6.6). USBA level was increased in patients with cholestasis. USBA level was significantly correlated with serum total bile acid, total bilirubin level and serum hyaluronic acid level (r=0.850, 0.602 and 0.504, respectively) (p<0.05) and, furthermore, tended to be correlated with liver-uptake ratio (LHL15) by technetium-99m galactosyl human serum albumin (99mTc-GSA) scintigraphy and alanine aminotransferase level (r=-0.469 and 0.436, respectively but not significant). USBA level tended to be associated with postoperative uncontrolled ascites (p=0.050, not significant). Postoperative USBA level by day 7 was not changed; however, USBA level in patients with cholestatic diseases was decreased Conclusions: USBA is a simple and sensitive noninvasive test for cholestasis and also useful to predict postoperative uncontrolled ascites after hepatic resections

Mice with Calr mutations homologous to human CALR mutations only exhibit mild thrombocytosis

Shide, K., Kameda, T., Kamiunten, A. et al. Mice with Calr mutations homologous to human CALR mutations only exhibit mild thrombocytosis. Blood Cancer J. 9, 42 (2019). https://doi.org/10.1038/s41408-019-0202-

Integrated genetic and clinical prognostic factors for aggressive adult T-cell leukemia/lymphoma

成人T細胞白血病リンパ腫（ATL）におけるゲノム情報と臨床情報を統合したリスクモデルを確立 --ATLの個別化医療を推進--. 京都大学プレスリリース. 2023-04-10.The prognosis of aggressive adult T-cell leukemia/lymphoma (ATL) is poor, and allogeneic hematopoietic stem-cell transplantation (allo-HSCT) is a curative treatment. To identify favorable prognostic patients after intensive chemotherapy, and who therefore might not require upfront allo-HSCT, we aimed to improve risk stratification of aggressive ATL patients aged <70 years. The clinical risk factors and genetic mutations were incorporated into risk modeling for overall survival (OS). We generated the m7-ATLPI, a clinicogenetic risk model for OS, that included the ATL prognostic index (PI) (ATL-PI) risk category, and non-silent mutations in seven genes, namely TP53, IRF4, RHOA, PRKCB, CARD11, CCR7, and GATA3. In the training cohort of 99 patients, the m7-ATLPI identified a low-, intermediate-, and high-risk group with 2-year OS of 100%, 43%, and 19%, respectively (hazard ratio [HR] 5.46, p < 0.0001). The m7-ATLPI achieved superior risk stratification compared to the current ATL-PI (C-index 0.92 vs. 0.85, respectively). In the validation cohort of 84 patients, the m7-ATLPI defined low-, intermediate-, and high-risk groups with a 2-year OS of 81%, 30%, and 0%, respectively (HR 2.33, p = 0.0094), and the model again outperformed the ATL-PI (C-index 0.72 vs. 0.70, respectively). The simplified m7-ATLPI, which is easier to use in clinical practice, achieved superior risk stratification compared to the ATL-PI, as did the original m7-ATLPI; the simplified version was calculated by summing the following: high-risk ATL-PI category (+10), low-risk ATL-PI category (−4), and non-silent mutations in TP53 (+4), IRF4 (+3), RHOA (+1), PRKCB (+1), CARD11 (+0.5), CCR7 (−2), and GATA3 (−3)

Seasonal variation in fish school spatial distribution and abundance under the Kuroshio regular pattern and the large meander in Suzu coastal waters

The Kuroshio Current can take two paths; usually it follows the regular pattern but occasionally it follows a pattern known as the large meander. In this study, we investigated the abundance of fish that migrate to coastal waters and the spatial distribution of fish schools under both Kuroshio patterns in Suzu district, Kochi prefecture, where the set net is the main fishery industry. We clarified the seasonal variation in the density and distribution of fish schools using a quantitative echo sounder. The effects of the Kuroshio large meander (LM) depended on the season. There was no effect of current pattern in summer or autumn, but in winter and spring the LM altered the marine environment and fish distributions. Cold water masses were formed in the survey area during winter and spring during the LM, and the water temperature dropped significantly compared with during the Kuroshio non-large meander (NLM). This altered the fish species and the distribution of fish schools in the survey area. The catches of Japanese horse mackerels (Trachurus japonicus) and Yellowtails (Seriola quinqueradiata) were much higher during the LM compared with those during the NLM. Unlike these two species, the small-sized pelagic fishes in spring has decreased significantly during the LM