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Myosin phosphatase targeting subunit1 (MYPT1) is a critical subunit of myosin phosphatase (MP), which brings PP1Cδ phosphatase and its substrate together. We previously showed that MYPT1 depletion resulted in oblique chromatid segregation. Therefore, we hypothesized that MYPT1 may control microtubule-dependent motor activity. Dynein, a minus-end microtubule motor, is known to be involved in mitotic spindle assembly. We thus examined whether MYPT1 and dynein may interact. Proximity ligation assay and co-immunoprecipitation revealed that MYPT1 and dynein intermediate chain (DIC) were associated. We found that DIC phosphorylation is increased in MYPT1-depleted cells in vivo, and that MP was able to dephosphorylate DIC in vitro. MYPT1 depletion also altered the localization and motility of Rab7-containing vesicles. MYPT1-depletion dispersed the perinuclear Rab7 localization to the peripheral in interphase cells. The dispersed Rab7 localization was rescued by microinjection of a constitutively active, truncated MYPT1 mutant, supporting that MP is responsible for the altered Rab7 localization. Analyses of Rab7 vesicle trafficking also revealed that minus-end transport was reduced in MYPT1-depleted cells. These results suggest an unexpected role of MP: MP controls dynein activity in both mitotic and interphase cells, possibly by dephosphorylating dynein subunits including DIC., (© 2024 The Authors. Cytoskeleton published by Wiley Periodicals LLC.)

Organic molecules with aromatic groups at the aqueous interfaces play a central role in atmospheric chemistry, green chemistry, and on-water synthesis. Insights into the organization of interfacial organic molecules can be obtained using surface-specific vibrational sum-frequency generation (SFG) spectroscopy. However, the origin of the aromatic C-H stretching mode peak is unknown, prohibiting us from connecting the SFG signal to the interfacial molecular structure. Here, we explore the origin of the aromatic C-H stretching response by heterodyne-detected SFG (HD-SFG) at the liquid/vapor interface of benzene derivatives and find that, irrespective of the molecular orientation, the sign of the aromatic C-H stretching signals is negative for all the studied solvents. Together with density functional theory (DFT) calculations, we reveal that the interfacial quadrupole contribution dominates, even for the symmetry-broken benzene derivatives, although the dipole contribution is non-negligible. We propose a simple evaluation of the molecular orientation based on the aromatic C-H peak area.

Accurate determination of protein structure at interfaces is critical for understanding protein interactions, which is directly relevant to a molecular-level understanding of interfacial proteins in biology and medicine. Vibrational sum frequency generation (VSFG) spectroscopy is often used for probing the protein amide I mode, which reports protein structures at interfaces. Observed peak shifts are attributed to conformational changes and often form the foundation of hypotheses explaining protein working mechanisms. Here, we investigate structurally diverse proteins using conventional and heterodyne-detected VSFG (HD-VSFG) spectroscopy as a function of solution pH. We reveal that blue-shifts of the amide I peak observed in conventional VSFG spectra upon lowering the pH are governed by the drastic change of the nonresonant contribution. Our results highlight that connecting changes in conventional VSFG spectra to conformational changes of interfacial proteins can be arbitrary, and that HD-VSFG measurements are required to draw unambiguous conclusions about structural changes in biomolecules.

In typical aqueous systems, including naturally occurring sweet and salt water and tap water, multiple ion species are co-solvated. At the water-air interface, these ions are known to affect the chemical reactivity, aerosol formation, climate, and water odor. Yet, the composition of ions at the water interface has remained enigmatic. Here, using surface-specific heterodyne-detected sum-frequency generation spectroscopy, we quantify the relative surface activity of two co-solvated ions in solution. We find that more hydrophobic ions are speciated to the interface due to the hydrophilic ions. Quantitative analysis shows that the interfacial hydrophobic ion population increases with decreasing interfacial hydrophilic ion population at the interface. Simulations show that the solvation energy difference between the ions and the intrinsic surface propensity of ions determine the extent of an ion's speciation by other ions. This mechanism provides a unified view of the speciation of monatomic and polyatomic ions at electrolyte solution interfaces.

Triple-negative essential thrombocythemia (ET) is a condition in which mutations in JAK2, CALR and MPL are all negative. Transformation to acute myeloid leukemia may occur during the course of ET, while B-acute lymphoblastic leukemia B-(ALL) is rare. We experienced a case diagnosed as B-ALL during the course of triple-negative ET. Notably, cytoreduction was required for the excessive increase in blood cells during the bone marrow recovery period after chemotherapies. Whole exome sequencing identified 17 somatic mutations: 9 were identified in both ET and B-ALL samples, while 8 were specific to B-ALL, suggesting that these 8 might have caused the transformation.

Background/aim: Operable peritoneal dissemination from distal cholangiocarcinoma after pancreaticoduodenectomy is rare. Furthermore, peritoneal dissemination mimicking liver metastasis has scarcely been reported., Case Report: An 81-year-old woman received pancreaticoduodenectomy for distal cholangiocarcinoma. She was diagnosed with stage IIA (T3a N0 M0) and received curative resection. She did not receive adjuvant chemotherapy. As a result of the examination in our department, she showed two tumors, 20 mm and 8 mm in segments 7/8 and 7, respectively, in the subphrenic liver surface four and half years after the initial pancreaticoduo-denectomy. The larger tumor was slow-growing, and cystic degeneration was inside. Plain computed tomography imaging revealed an isodense tumor with a marginal high ring and weak early enhancement, and prolonged peripheral enhancement was recognized at the marginal portion. Magnetic resonance imaging showed a heterogeneous mass with peripheral hypointensity ring that may be caused by fibrous tissue. Although the smaller tumor was diagnosed only after admission, it presented similar imaging findings to the larger tumor. The preoperative diagnosis was suspected to be liver metastases from DCC or inflammatory pseudotumor. Laparoscopic partial liver resection with diaphragm dissection was performed for both tumors. Pathologically, the tumors were diagnosed as peritoneal dissemination from distal cholangiocarcinoma. In the disseminated cancer cells, the expression of Ki67 was decreased, which was suspected to be one of the reasons for the long recurrence-free interval. The patient is doing well without any recurrence three months after the second operation., Conclusion: Laparoscopic surgery can provide excellent results for diagnosing and treating unknown subphrenic tumors., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Angioimmunoblastic T-cell lymphoma (AITL) is an intractable type of T-cell lymphoma. We and others have identified that the p.Gly17Val RHOA mutation is specifically identified in AITL. We herein report a patient whose condition deteriorated, resulting from massive pericardial effusion one month after undergoing autologous transplantation for AITL. He was diagnosed with cardiac tamponade caused by AITL recurrence in the presence of the p.Gly17Val RHOA mutation as well as T-lineage cells with an aberrant immune-phenotype in the pericardial effusion. This case suggests that a precision medicine approach by detecting the presence of a p.Gly17Val RHOA mutation is useful for the management of AITL.

Toward a comprehensive understanding of the mechanism of glycerol as a moisturizer, studies on the hydrogen-bond (HB) structure of hydration water, which is known to be disordered by glycerol, are insufficient. To this aim, we evaluated the HB configurations based on the HOH bending and OH stretching spectra of the hydration water from those of glycerol/water mixtures by subtracting the contributions of bulk water and glycerol using dielectric relaxation spectroscopy. Analysis of the HOH bending band showed that hydration water-donating HBs lose the intermolecular bending coupling with increasing glycerol by replacing the water-water HBs with water-glycerol HBs. The OH stretching band provided more detailed insight into the HB configuration, indicating that the double-donor double-acceptor and double-donor single-acceptor configurations in bulk water change to a predominantly double-donor single-acceptor configuration in hydration water around glycerol. The formation of more donor HBs than acceptor HBs may be due to the steric constrains by glycerol and/or differences in the partial charge on the oxygen atom between water and glycerol.